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Anti-acetylcholinesterase and Antioxidant Activities of Inhaled Juniper Oil on Amyloid Beta (1–42)-Induced Oxidative Stress in the Rat Hippocampus
Abstract
Juniper volatile oil is extracted from Juniperus communis L., of the Cupressaceae family, also known as common juniper. Also, in aromatherapy the juniper volatile oil is used against anxiety, nervous tension and stress-related conditions. In the present study, we identified the effects of the juniper volatile oil on amyloid beta (1-42)-induced oxidative stress in the rat hippocampus. Rats received a single intracerebroventricular injection of amyloid beta (1-42) (400 pmol/rat) and then were exposed to juniper volatile oil (200 μl, either 1 or 3 %) for controlled 60 min period, daily, for 21 continuous days. Also, the antioxidant activity in the hippocampus was assessed using superoxide dismutase, glutathione peroxidase and catalase specific activities, the total content of the reduced glutathione, protein carbonyl and malondialdehyde levels. Additionally, the acetylcholinesterase activity in the hippocampus was assessed. The amyloid beta (1-42)-treated rats exhibited the following: increase of the acetylcholinesterase, superoxide dismutase and catalase specific activities, decrease of glutathione peroxidase specific activity and the total content of the reduced glutathione along with an elevation of malondialdehyde and protein carbonyl levels. Inhalation of the juniper volatile oil significantly decreases the acetylcholinesterase activity and exhibited antioxidant potential. These findings suggest that the juniper volatile oil may be a potential candidate for the development of therapeutic agents to manage oxidative stress associated with Alzheimer's disease through decreasing the activity of acetylcholinesterase and anti-oxidative mechanism.
... VOCs have been gaining great interest owing to their remarkable antimicrobial, antioxidant, anti-inflammatory, and anticancer properties, being able to attenuate, or even mitigate, the development of cardiovascular disorders and neuropathologies, and also ameliorate the mental state of individuals [85]. ...
... Since ancient times, J. communis parts have been largely used as antiseptics, contraceptives, and diuretics, and as a remedy to treat colds, chest complaints, rheumatism, headaches, dermatological and respiratory ailments, and kidney and urinary infections [38,39,85]. Given the aforementioned, it is not surprising that this plant is a focus of continuous studies to discover its full potential. ...
... The administration of methanolic extracts of this plant (200 mg/kg) for 21 days on chlorpromazine-induced Parkinson's disease in rats also showed increments in reduced glutathione and decreased levels of TBARS as compared to the untreated group [19]. Furthermore, the inhalation of its oil for 60 min daily for 21 days revealed higher levels of superoxide dismutase and catalase enzymes, and glutathione peroxidase activity on rats' hippocampus subjected to amyloid β (1-42)-induced oxidative stress [85]. ...
Plant-derived products and their extracted compounds have been used in folk medicine since early times. Zimbro or common juniper (Juniperus communis) is traditionally used to treat renal suppression, acute and chronic cystitis, bladder catarrh, albuminuria, leucorrhea, and amenorrhea. These uses are mainly attributed to its bioactive composition, which is very rich in phenolics, terpenoids, organic acids, alkaloids, and volatile compounds. In the last few years, several studies have analyzed the huge potential of this evergreen shrub, describing a wide range of activities with relevance in different biomedical discipline areas, namely antimicrobial potential against human pathogens and foodborne microorganisms, notorious antioxidant and anti-inflammatory activities, antidiabetic, antihypercholesterolemic and antihyperlipidemic effects, and neuroprotective action, as well as antiproliferative ability against cancer cells and the ability to activate inductive hepato-, renal- and gastroprotective mechanisms. Owing to these promising activities, extracts and bioactive compounds of juniper could be useful for the development of new pharmacological applications in the treatment of several acute and chronic human diseases.
... Butyrylcholinesterase inhibition assay. The ability of the investigated extracts to inhibit butyrylcholinesterase was assessed by measuring the absorbance variations at 412 nm for 5 minutes at 25ºC, using acetylthiocholine iodide (0.2 M) as substrate [2,11]. The difference between the initial and last value represented intensity of the inhibitory effect. ...
... Acetylcholinesterase inhibition assay (Ellman's method). Acetylcholinesterase from Electrophorus electrics (0.2 U/mL in phosphate buffer), acetylthiocholine iodide (0.2 M) and diluted samples in DMSO (0.625 mg -20 mg/mL) were used to evaluate the inhibitory capacity of Ajuga extracts [2,11]. The activity value was calculated as a percentage of the difference between the absorbance of the enzyme solution with inhibitor at 412 nm after 5 minutes and the absorbance of the same solution at the initial time. ...
... The pharmacological tests included: Y-maze spontaneous locomotor activity and rotation, radial -arm maze test of working memory and the reference memory, and the working memory and reference memory errors were calculated/group/day. All tests were previously approved by the Ethics Committee, and respected the European guideline of animal bioethics from the Act on Animal Experimentation and Animal Health and Welfare from Romania, and all procedures were in compliance with Directive 2010/63/EU of the European Parliament and of the Council of 22 September 2010 [1,2]. ...
... This mechanism may partially explain the anti-AChE activity observed in the CJRRB-EO. In addition, the α-pinene-rich EO from the berries of Juniperus communis L. (Cupressaceae) exhibits the inhibition of AChE in Aβ(1-42)-treated rats [21]. Hence, the CJRRB-EO may present a sustainable resource for obtaining potent inhibitors of AChE activity. ...
... Moreover, monoterpene-rich EOs, particularly those abundant in α-pinene, from other conifers of the Cupressaceae family, have been shown to enhance the oxidative stress profile in AD rat models [21] and inhibit AChE activity in vitro [31]. Collectively, EOs and EOCs exhibit neuroprotective effects against Aβ-induced toxicity through mechanisms such as anti-amyloid, anti-inflammatory, and antioxidant actions. ...
Alzheimer’s disease (AD), a multifactorial neurodegenerative disorder characterized by severe cognitive impairment, affects millions of people worldwide. However, AD therapy remains limited and mainly symptomatic-focused, with acetylcholinesterase (AChE) inhibitors being the major available drugs. Thus, AD is considered by the WHO as a disorder of public health priority. Among several strategies that have been identified to combat AD, the use of natural multi-target drug ligands (MTDLs) appears to be a promising approach. In this context, we previously found that the essential oils (EOs), obtained via hydrodistillation, from Azorean Cryptomeria japonica sawdust (CJS) and resin-rich bark (CJRRB) were able to exert antioxidant activity via different mechanisms of action. Therefore, in the present work, these EOs were screened for their (i) in vitro anti-AChE and anti-butyrylcholinesterase (BChE) activities, evaluated by a modified Ellman’s assay; (ii) in vitro anti-inflammatory potential, using the albumin denaturation method; and (iii) toxicity against Artemia salina. The CJRRB–EO exhibited both anti-AChE and anti-BChE activities (IC50: 1935 and 600 µg/mL, respectively), whereas the CJS–EO only displayed anti-BChE activity, but it was 3.77-fold higher than that of the CJRRB–EO. Molecular docking suggested that α-pinene and ferruginol compounds contributed to the anti-AChE and anti-BChE activities, respectively. Moreover, the anti-inflammatory activity of the CJS–EO, the CJRRB–EO, and diclofenac was 51%, 70%, and 59% (at a concentration of only 2.21 μg/mL), respectively, with the latter two presenting comparable activity. Concerning the EOs’ potential toxicity, the CJRRB–EO exhibited a lower effect than the CJS–EO (LC50: 313 and 73 µg/mL, respectively). Overall, the EOs from C. japonica biomass residues, chiefly the CJRRB–EO, displayed antioxidant, anticholinesterase, and anti-inflammatory activities in a concentration-dependent manner. These properties demonstrate that these residues may be suitable natural MTDLs for AD complementary therapy when administered through aromatherapy, or, alternatively, could serve as low-cost sources of valuable ingredients, such as α-pinene.
... Similarly, the plant extract was also reported to possess significant neuroprotective effect against chlorpromazine-induced Parkinson like symptoms (Rana and Bais, 2014). The inhalation of volatile oil at the rate of 1% or 3% daily for 21 days improved amyloid-ß induced memory deficits in rat model of Alzheimer disease (Cioanca et al., 2015). The inhalation of volatile oils was found to inhibit Acetylcholinesterase (AChE) activity and prevent oxidative damage in brain of rodents in a dose dependent manner (Cioanca et al., 2015) due to its significant antioxidant potential and ability to inhibit AChE activity involved in the progression of neurological disorders. ...
... The inhalation of volatile oil at the rate of 1% or 3% daily for 21 days improved amyloid-ß induced memory deficits in rat model of Alzheimer disease (Cioanca et al., 2015). The inhalation of volatile oils was found to inhibit Acetylcholinesterase (AChE) activity and prevent oxidative damage in brain of rodents in a dose dependent manner (Cioanca et al., 2015) due to its significant antioxidant potential and ability to inhibit AChE activity involved in the progression of neurological disorders. ...
Plants have been used for thousands of years as medicine for treating variety of diseases and medical complaints by most of the civilizations. Juniperus communis L. is an evergreen aromatic shrub with high therapeutic potential for the treatment of diseases in human and animals. The plant is rich in aromatic oils, invert sugars, resins, catechin, organic acid, terpenic acids, leucoanthocyanidin, alkaloids, flavonoids, tannins, gums, lignins, wax, etc. Juniper berries or extract of the plant has traditionally been used as diuretic, anti-arthritis, anti-diabetes, antiseptic as well as for the treatment of gastrointestinal and autoimmune disorders. The essential oil and extracts of juniper have been experimentally documented to have antioxidant, antibacterial, antiviral and antifungal activities. Recent studies have also found anti-inflammatory, cytotoxic, hypoglycemic and hypolipidemic effects of berries in experimental models. Further, the essential oil incorporation retarded lipid peroxidation in preserved meat due to its high antioxidant effect which not only improved meat product quality but also improved shelf life of the product. Thus natural antioxidant such as juniper can be used in place synthetic antioxidant for the preservation and improving self-life of meat products. New well designed clinical trials in human and animals using well-characterized J. communis extract or oil need to be conducted so that additional information is generated which can support the use of this natural product as a nutraceutical. Keywords: Food science, Chemistry, Juniperus communis, Phytochemical ingredients, Antioxidant, Anti-proliferative, Nutraceutical
... Improved agitation and quality of life indices [54] Clinical trial in AD patients No significant effects [55] Anti-agitation studies Anti-agitation effects [56,57] J. communis ICV Aβ(1-42)-induced AD in rats Reduced memory impairment, antioxidant and anti-cholinesterase potential [59,60] C. nucifera Prospective study in AD patients Improved memory status in AD patients. [62] In vitro neurotoxicity study in rat cortical neurons Neuroprotective effects [63] P. peregrina Scopolamine-induced memory deficits, depression, and anxiety in a rat model of AD Hindered depression, anxiety, and memory deficits. ...
... Juniper oil treated groups showed significantly less memory impairment in both behavioral tests as compared to Aβ(1-42) alone treated group. Later Cioanco et al. [60] demonstrated that antioxidant and anti-AChE potential of juniper volatile oil ameliorates cognitive dysfunction in Aβ(1-42)-induced rat model of AD. ...
Introduction Alzheimerʼs disease (AD) is a multifarious neurodegenerative disease that causes cognitive impairment and gradual memory loss. Senile plaques and neurofibrillary tangles (NFTs) comprised of amyloid β (Aβ) peptides and hyper-phosphorylated tau proteins, respectively, are the classic pathological hallmarks of AD [1]. Several hypotheses have been put forward to reveal the pathobiology of the disorder including cholinergic hypothesis, inflammation hypothesis , oxidative stress, mitochondrial cascade hypothesis, and metabolic hypothesis [2, 3]. According to the World Health Organization , AD is the most common form of dementia and accounts for about 60-70 % of all dementia cases [4]. There is more prevalence for people aged over 65 y [5]. Epigenetic variations on the genetic material of neurons can result in neurodegenerative disorders and these variations in AD genes change from region to region [6]. Familial Alzheimerʼs disease (FAD) and sporadic Alz-heimerʼs disease are the 2 specific types of AD [7]. The combined action of environmental and genetic factors might be culpable for the SAD and FAD types [8]. Depending on the age of onset, AD can be further grouped into early onset (EOAD) and late onset (LOAD) [9]. Mutations in some specific genes like amyloid precursor protein (APP), presenilin I, and presenilin II are responsible for EOAD whereas apolipoprotein E is the only gene identified that causes LOAD [10]. Approximately 5 % of the AD cases is familial early onset type and it develops before 65 y of age, and the remaining 95 % accounts for sporadic late onset type and it develops after 65 y of age [11, 12]. The neuropathophysiology of the neurodegeneration in AD is triggered by anomalous deposition of amyloid plaques and NFTs in varied regions of the brain involved in cognition and memory [13]. Amyloid plaques are protein fragments composed of Aβ
... Improved agitation and quality of life indices [54] Clinical trial in AD patients No significant effects [55] Anti-agitation studies Anti-agitation effects [56,57] J. communis ICV Aβ(1-42)-induced AD in rats Reduced memory impairment, antioxidant and anti-cholinesterase potential [59,60] C. nucifera Prospective study in AD patients Improved memory status in AD patients. [62] In vitro neurotoxicity study in rat cortical neurons Neuroprotective effects [63] P. peregrina Scopolamine-induced memory deficits, depression, and anxiety in a rat model of AD Hindered depression, anxiety, and memory deficits. ...
... Juniper oil treated groups showed significantly less memory impairment in both behavioral tests as compared to Aβ(1-42) alone treated group. Later Cioanco et al. [60] demonstrated that antioxidant and anti-AChE potential of juniper volatile oil ameliorates cognitive dysfunction in Aβ(1-42)-induced rat model of AD. ...
... These ROS propagate from affected cell to other normal cells through gap junctions leading to the development of oxidative stress (Koulakoff et al. 2012;Takeuchi and Suzumura 2014;Yi et al. 2016). Also, there are several reports of the neurotoxicity of these aggregates in in vitro and in vivo studies (Walsh et al. 2002;Ferreira et al. 2007;Selkoe 2008a, b;Mucke and Selkoe 2012;Zussy et al. 2013a, b;Figueiredo et al. 2013;Butterfield et al. 2013;Hritcu et al. 2014;Forny-Germano et al. 2014;Gradinariu et al. 2015;Faucher et al. 2015;Cioanca et al. 2015;Epelbaum et al. 2015;Jin and Selkoe 2015;Leggio et al. 2016). As reported in our previous study, single intracerebroventricular (icv) injection of soluble aggregates of Aβ 42 was able to induce oxidative stress, neurodegeneration, and anxietyrelated behavior in rats (Sharma et al. 2016). ...
... Aβ 42 oligomers are capable of directly inducing the production of free radicals, leading to the formation of oxidative stress. Several experimental models, using Aβ 42 oligomers, have highlighted the increased levels of ROS accompanied with neurodegeneration (Masilamoni et al. 2008;Butterfield and Sultana 2011;Brouillette et al. 2012;Hritcu et al. 2014;Gradinariu et al. 2015;Faucher et al. 2015;Cioanca et al. 2015;Jin and Selkoe 2015;Leggio et al. 2016). Similarly, in the present study, after injecting Aβ 42 oligomers, ROS levels were found to be elevated in different regions of the rat brain. ...
The characteristic feature of Alzheimer’s disease (AD) is the deposition of amyloid beta inside the brain mainly consisting of Aβ 40 and 42 aggregates. Soluble aggregates of Aβ 42 are reported to be more toxic and exert their neurotoxicity by the induction of oxidative damage and cognitive deficits such as anxiety-like behavior. These alterations emerge due to the induction of gap junction communication through increased activity and expression of connexins such as connexin43 (Cx43) leading to the release of small neurotoxic molecules. In the present study, single intracerebroventricular (icv) injection of Aβ 42 oligomers (10 μl/rat) was used to induce oxidative damage and anxiety-related behavior in rats. Carbenoxolone (Cbx), a gap junction blocker, was tested (20 mg/kg body weight, i.p., for 6 weeks) against these alterations. Cbx supplementation reversed the Aβ 42 oligomer–induced alterations in the antioxidant defense system. The levels ROS, lipid peroxidation, and protein carbonyls were normalized with Cbx co-treatment leading to the decreased DNA fragmentation and pyknosis in different regions of the rat brain. Cbx induced the anxiolytic behavior and ameliorated the cognitive decline in rats post Aβ 42 oligomer injection. The increased expression of Cx43 post Aβ 42 oligomer injection was also reduced with Cbx supplementation, which might have inhibited the release of small neurotoxic molecules. Our results showed that Cbx prevents the Aβ 42 oligomer–induced oxidative damage and anxiety-like behavior partly by blocking the gap junction communication, which suggests that the therapeutic potential of Cbx may be explored in the progression of AD.
... Improved agitation and quality of life indices [54] Clinical trial in AD patients No significant effects [55] Anti-agitation studies Anti-agitation effects [56,57] J. communis ICV Aβ(1-42)-induced AD in rats Reduced memory impairment, antioxidant and anti-cholinesterase potential [59,60] C. nucifera Prospective study in AD patients Improved memory status in AD patients. [62] In vitro neurotoxicity study in rat cortical neurons Neuroprotective effects [63] P. peregrina Scopolamine-induced memory deficits, depression, and anxiety in a rat model of AD Hindered depression, anxiety, and memory deficits. ...
... Juniper oil treated groups showed significantly less memory impairment in both behavioral tests as compared to Aβ(1-42) alone treated group. Later Cioanco et al. [60] demonstrated that antioxidant and anti-AChE potential of juniper volatile oil ameliorates cognitive dysfunction in Aβ(1-42)-induced rat model of AD. ...
Alzheimerʼs disease is a multifarious neurodegenerative disease that causes cognitive impairment and gradual memory loss. Several hypotheses have been put forward to postulate its pathophysiology. Currently, few drugs are available for the management of Alzheimerʼs disease and the treatment provides only symptomatic relief. Our aim is to review the relevant in vitro, in vivo, and clinical studies focused toward the potential uses of essential oils in the treatment of Alzheimerʼs disease. Scientific databases such as PubMed, ScienceDirect, Scopus, and Google Scholar from April 1998 to June 2018 were explored to collect data. We have conducted wide search on various essential oils used in different models of Alzheimerʼs disease. Out of 55 essential oils identified for Alzheimerʼs intervention, 28 have been included in the present review. A short description of in vivo studies of 13 essential oils together with clinical trial data of Salvia officinalis, Salvia lavandulifolia, Melissa officinalis, Lavandula angustifolia, and Rosmarinus officinalis have been highlighted. In vitro studies of remaining essential oils that possess antioxidant and anticholinesterase potential are also mentioned. Our literary survey revealed encouraging results regarding the various essential oils being studied in preclinical and clinical studies of Alzheimerʼs disease with significant effects in modulating the pathology through anti-amyloid, antioxidants, anticholinesterase, and memory-enhancement activity.
... Previous studies support the vulnerability of the central nervous system (CNS) to oxidative stress possibly due to large rate of oxygen consumption, the richness of iron, high level of polyunsaturated fatty acids, and low levels of antioxidants (Butterfield et al., 2001;Paula et al., 2005). Recent studies have highlighted the importance of oxidative processes in the pathogenesis of AD (Cioanca et al., 2015;E Abdel Moneim, 2015). Although the initiating events are still unknown, it has been proposed that oxidative damage is involved in the initiation of AD and is the first apparent sign in progression of AD (Arimon et al., 2015;Wang et al., 2014). ...
... Central injection of Aβ 1-42 provokes several impairments including oxidative stress (Bagheri et al., 2011), cholinergic dysfunction (Olariu et al., 2001), and neuronal apoptosis (Ivins et al., 1999;Ruan et al., 2010) possibly through induction of protein oxidation and lipid peroxidation. In line with other studies, our results demonstrated that Aβ 1-42 increased oxidative stress in the hippocampus which was confirmed by diminished enzymatic antioxidant defense and increased MDA levels, end product of lipid peroxidation (Butterfield and Boyd-Kimball, 2004;Cioanca et al., 2013Cioanca et al., , 2015Turunc Bayrakdar et al., 2014). Nevertheless, we found that administration of troxerutin (300 mg/kg) could significantly reverse MDA levels and enhance enzymatic antioxidant defense against Aβ 1-42 in the hippocampus. ...
Alzheimer’s disease (AD) is an age-related neurodegenerative disease linked with increased production and/or deposition of amyloid-beta (Aβ) in the brain. The aim of the present study was to investigate the possible neuroprotective effect of troxerutin on an animal model of Alzheimer’s disease. Alzheimer model was induced by a single dose intracerebroventricular (ICV) injection of Aβ 1-42 (5 nmol/5 µl). Thereafter, troxerutin (300 mg/kg) was gavaged for 14 days. The hippocampal malondialdehyde (MDA) levels and enzymatic activities of superoxide dismutase (SOD), glutathione peroxidase (GPx), and acetylcholinesterase (AChE) were measured using enzymelinked immunosorbent assay (ELISA) method. In addition, the number of apoptotic cells in the dentate gyrus (DG) was assessed by TUNEL kit. The results showed that ICV microinjection of Aβ 1-42 increased MDA levels, reduced SOD and GPx, and increased AChE activities in the hippocampus. Chronic administration of troxerutin significantly attenuated MDA levels and AChE activity and increased SOD and GPx activities in the hippocampus. Moreover, the number of apoptotic cells was decreased by troxerutin treatment. Taken together, our study demonstrated that troxerutin could increase the resistance of hippocampal neurons against apoptosis, at least in part, by diminishing the activity of AChE and oxidative stress. Therefore, troxerutin may have beneficial effects in the management of Alzheimer’s disease. © 2017, Leibniz Research Centre for Working Environment and Human Factors. All rights reserved.
... Any variation in the content of the secondary metabolites is very important, especially in plants of commercial significance, where the chemical composition clearly affects the quality of consumer products. Recently, the effects of juniper berry oil inhalation on anxiety and depression levels in a beta-amyloid (1e42) rat model have been examined (Hritcu et al., 2016), and it has been hypothesized that the oils could be used to reduce nervous tension and ameliorate stress-related conditions (Cioanca et al., 2015). In the last few years, the biocide action of plant essential oils has also been evaluated and, in terms of pest prevention, they can be considered as an alternative to the synthetic chemical pesticides (Angioni et al., 2003;Sacchetti et al., 2005). ...
... Beta-caryophyllene, although a sesquiterpene, can selectively bind the type-2 cannabinoid receptor with a significant anti-inflammatory activity without any psychotomimetic effects (Klauke et al., 2014) and may ameliorate the symptoms of anxiety and depressive disorders in a rat model (Hritcu et al., 2016). The inhalation of the juniper volatile oil could protect the brain from oxidative stress (Cioanca et al., 2015) and may improve memory deficits in a rat model of Alzheimer's disease (Cioanca et al., 2014). Beta-caryophyllene is usually found in high concentrations in many plants and spices, such as oregano, rosemary, thyme, cinnamon, and black pepper, and the United States Food and Drug Administration (USFDA) has approved it as food additive (approval reference no. ...
Juniperus communis L., also known as the common juniper, is a dioecious aromatic evergreen shrub and has been traditionally used in many countries as a diuretic, antiseptic, and digestive and as a flavor to aromatize certain alcoholic beverages. We analyzed the chemical variability in the volatile profiles from berries of J. communis, harvested in one of the oldest European parks, the National Park of Abruzzo, Lazio, and Molise (PNALM, Central Italy). We examined the berries in different phases of the biological cycle for 1 year (at six ripening stages). Hydrodistilled essential oils from the fresh berries were analyzed by gas chromatography–flame ionization detection (GC-FID), gas chromatography–mass spectrometry (GC-MS) and principal component analysis (PCA). A total of 90 components were detected, and remarkable qualitative and quantitative differences were observed in the chemical components during the ripening stages, from the green unripe berries to the bluish-black berries harvested at full maturity. The essential oils were an α-pinene (13.43–32.34%) chemotype. The monoterpene hydrocarbons decreased during the ripening with a progressive increase in sesquiterpenes such as germacrene D (12.29–17.59%) and β-caryophyllene (7.71–8.51%), which are the major components in ripe berry essential oils. The sesquiterpene hydrocarbon fraction (65.3–47.9%) also contained α-humulene, germacrene B, δ-cadinene, bicyclogermacrene, and eudesma 4(14),11 diene. Germacrene D and β-caryophyllene in high concentrations may be considered as marker components of the genus Juniperus from the Molise region. This particular chemical composition has been reported for the first time. It is interesting to note the presence of β-caryophyllene (7–11%), whose inhalation has been reported to affect anxiety and depression in a rat model. An in vitro antifungal assay showed that the essential oil from green and ripe berries inhibits the growth of Sclerotium rolfsii, a phytopathogen fungus that causes post-harvest diseases in many fruits and vegetables.
... The synthetic drug tacrine (Cognex®) (1) was the first AChE inhibitor to be licensed, but its routine use has been restricted by associated hepatotoxic effects. The use of tacrine (1) has been eclipsed by the newer AChE inhibitors such as donepezil (Aricept®) (2), rivastigmine (3) and galantamine (4) [8]. ...
... However, despite great potential, concerns regarding the juniper volatile oil safety have been raised and need to be properly addressed. It has been reported a little toxicity of the juniper volatile oil extracted from multiple juniper species in animals [8]. .90 ...
Background:
The use of aromatic plants to relief different illness is not a new therapy. Actually aromatic plants have been used for many centuries by different cultures around the world [25]. Pharmacological studies provide scientific support to the traditional use of aromatic medicinal plants and aromatherapy; nevertheless, more clinical trials are required regarding to their effectiveness in order to establish a guidance for their use in routine healthcare. Moreover, modern medicine in studies about olfactory function has attained great achievements and got Nobel Prize in 2004. These new searches have obviously fueled interest in the essential oils and volatile compounds of natural origin. Several reviews on the newly discovered AChEi obtained from plants, fungus and marine organisms have also been published over the last years. The majority of these AChEi belong to the alkaloid group, including indole, isoquinoline, quinolizidine, piperidine and steroidal alkaloids.
Results:
Probably the interest in the essential oils and volatile compounds will be fueled from the new available scientific data about receptor on olfactory mucosa of nasal cavity. It can receive and distinguish different odor molecules, which produce nerve impulse and transmit into olfactory bulb via olfactory nerves. The nerve cells in the olfactory bulb transmit the signals into hippocampus. Because hippocampus is closely related with learning and memory functions, the volatile compounds can be potential drugs in AD therapies.
... Екстракт квіток ромашки (Chamomilae flores -2,0 мг) має потужну антимікробну та протизапальну дію. Це забезпечується підвищеним вмістом природніх хінонів та антиоксидантів (оксидоредуктаза, супероксиддисмутаза, каталаза), що забезпечує інгибіцію циклооксигенази ЦОГ-2 та простагландіну Е 2 у макрофагах [43][44][45]. ...
INTRODUCTION. The article demonstrates the experience of use the FLAVIA multicomponent plant complex in the treatment of acute cystitis in women. MATERIALS AND METHODS. The work evaluated the effectiveness and safety of the multicomponent FLAVIA plant complex in the treatment of acute cystitis in women. Compared with the use of standard antibacterial therapy. 80 patients with acute cystitis, aged from 20 to 40 years, took part in the study: 1 group (clinical): 40 patients took the multicomponent herbal complex FLAVIA (1 capsule twice a day, regardless of food intake, for 30 days) together with antibacterial therapy (phosphomycin — 3 g once); Group 2 (control): 40 patients received only antibacterial therapy (phosphomycin — 3 g once). Control visits took place after 7 (to determine the immediate results of treatment) and after 14 and 30 days after the start of therapy. To study the speed of elimination of symptoms and the dynamics of the disease’s impact on quality of life, patients were asked to fill out ACSS and VAS pain questionnaires. Studies of the general analysis of urine and bacteriological analysis of urine were carried out three times. The effectiveness of therapy was evaluated by the final result after antibiotic therapy. One of the main indicators of the effectiveness of treatment was the percentage of relapses and repeated diseases within 3 months. The following research methods were used: examination, ultrasound of the organs of the abdominal cavity, kidneys and bladder; general laboratory studies; bacteriological examination of urine; assessment of acute cystitis symptoms (ACSS questionnaire); pain assessment by visual analog scale (VAS). RESULTS AND THEIR DISCUSSION. As a result of the course of therapy, all patients noted a significant improvement in their state. The effectiveness of therapy in eliminating dysuric symptoms was 97.4% in the first group, and 88.9% in the 2nd group (р<0.05). For the longest time, the patients were bothered by symptoms of burning during urination — in all patients of group 1, it was eliminated on the 7th day, and in 3 patients of group 2, this symptom bothered them even a month after therapy. The feeling of not completely emptying the bladder in all patients of group 1 was eliminated on the 3rd day, and in 1 person from group 2, this symptom also appeared a month after therapy. The average duration of symptoms of acute cystitis in the studied control group was 1.6–2.2 times longer than in the comparison group according to various symptoms. All patients of the clinical group noted a decrease in dysuric phenomena on the 3rd day of treatment, and 76.3% noted the absence of dysuric manifestations. In the control group, only on the 14th day of treatment, the level of absence of dysuria was similar (77.8%). Analyzing the data of the general analysis of urine, it should be noted that leukocyturia before therapy was 100% characteristic of all patients, and on the 14th day it remained in 4 (10.5%) patients of 1 group and in 12 (33.3%) patients of 2 group (p<0.01). On the 30th day, leukocyturia was not noted in any patient who took the multicomponent herbal complex FLAVIYA, but in 4 (11.1%) cases among the patients of the 2nd group, a relapse of the disease was noted. Erythrocyturia was eliminated in all 17 patients of 1 group who had it at the beginning of the study on the 7th day of therapy, and in all 15 patients with such a symptom of 2 group — only on the 14th day. Changes in the peripheral blood — leukocytosis, an increase in ESR of more than 15 mm/h and an increase in the level of C-reactive protein were eliminated in patients of both groups by the 7th day of therapy. Subfebrile temperature disappeared as a result of treatment up to 3 days in both groups. The research data indicate a high overall therapeutic efficiency of complex therapy using FLAVIA (97.4%), in contrast to the control group (88.9%). As a result of the analysis of the data of the ACSS questionnaire, it was found that the average total score of the ACSS questionnaire for typical symptoms before therapy was 9.9±2.4 points, and for the quality of life section — 5.4±1.2 points in patients of group 1 and 9.2±2.1 points and 5.1±1.0 points in patients of group 2. This testified to the high expressiveness of the symptoms of acute cystitis. In terms of dynamics, we compared the average scores of the ACSS-typical domain between the 1st and 30th day of therapy, and on the 30th day the indicator was 2.2±0.3 in the clinical group; and in the control 4.1±0.8 points. From this, it can be concluded that the use of the multicomponent herbal complex FLAVIA in the treatment of acute cystitis had a greater dynamics of eliminating the symptoms of the disease according to the ACSS questionnaire, compared to the therapy in patients without the use of FLAVIYA. As a result of the analysis of pain syndrome intensity data according to the VAS scale, the average score before therapy was 8.3±1.3 points in patients of group 1 and 8.6±1.4 points in patients of group 2. The pain syndrome was characterized by pain of varying intensity and was most often localized in the lower abdomen. It was diagnosed in 32 (84.2%) patients of group 1 and in 29 (80.6%) of group 2. After the start of treatment, the pain syndrome was eliminated in all patients of group 1 on the 5th day, and in patients of group 2, it was eliminated only after 14 days of therapy. From the data it can be concluded that the use of FLAVIA in the treatment of acute cystitis probably accelerates the elimination of pain sensations both in terms of presence and intensity of pain in comparison with the treatment of patients without the use of FLAVIA. Good tolerability of the drug was noted. Adverse reactions as a result of taking the multicomponent herbal complex FLAVIA have not been detected. CONCLUSIONS. According to the obtained results and literature data, we can say about the potentiation of the effect of antibiotics by the FLAVIA multicomponent plant complex, which is manifested in the high therapeutic efficiency of the treatment of women with acute cystitis, which is already 97.4% on the 14th day, compared to the effectiveness of the control group on this time, which was 77.8% (p<0.01). Similar results of the therapy were obtained according to the ACSS questionnaire, where the average score for 30 days was 2.2±0.3 and 4.1±0.8 (p<0.01) in the clinical and control groups, respectively, indicating better dynamics elimination of symptoms of the disease in the clinical group in comparison with therapy in patients without use of FLAVIA. The multicomponent plant complex FLAVIYA has a anti-inflammatory effect, which is manifested in the reduction of pain syndrome and dysuric phenomena already on the 3rd day of treatment, which decreased significantly more and were eliminated faster than in the control group. Along with the clinical effectiveness, evidence of the bacteriological effectiveness of the multicomponent herbal complex was obtained, which, together with the absence of side effects, confirms the feasibility of wide clinical use of FLAVIA for the complex treatment of women with acute cystitis or exacerbation of chronic cystitis.
... Juniper species of various parts showed incredible potential to work on memory and hinder the movement of certain catalysts related to the movement of neurological pathologies, for example, Alzheimer's and Parkinson's illness as indicated by a few articles [11,45,46]. Bais et al. [11] detailed that the day-to-day organization of 200 mg/kg of J. Communis methanolic separates for 21 d in rodents with actuated Parkin-child's sickness by chlorpromazine can diminish engine dysfunctions, including catalepsy and muscle unbending nature, and increment locomotor action when contrasted with the untreated gathering. ...
Juniper species belonging to the family Cupressaceae are evergreen shrubs or trees that thrive in dry, rocky, or sandy soils. There are roughly 67 species in the genus, all indigenous to the northern hemisphere. Several species of this genus have been reported to have a variety of pharmacological activities, including diuretic, anti-inflammatory, anti-fungal, hepatoprotective, antidiabetic, and anti-hyperlipidemic properties. Additionally, some species have been shown to have antioxidant, antimicrobial, and neuroprotective properties in Parkinson's disease patients. The majority of these activities are caused by the phytochemical constituents found in these species. This article covers most of the constituents of plants of the genus juniper reported from 2010 to 2023. Furthermore, the biological activities of plants of the genus juniper are presented.
... EOs components including linalool, (E)-cinnamaldehyde and (E)-cinnamyl acetate have been also shown to suppress Aβ aggregation [10,11]. Given that acetylcholinesterase has a pro-aggregating effect on Aβ (reviewed in [12]), it is noteworthy that several EOs or their components have anticholinesterase activity [8,10,[13][14][15][16][17][18]. Additionally, there are EOs that can also inhibit tau phosphorylation [19,20]. ...
Essential oils exhibit numerous medicinal properties, including antimicrobial, anti-inflammatory and antioxidant effects. Recent studies also indicate that certain essential oils demonstrate anti-amyloidogenic activity against β-amyloid, the protein implicated in Alzheimer’s disease. To investigate whether the anti-aggregating properties of essential oils extend to α-synuclein, the protein involved in Parkinson’s disease, we constructed and employed a whole-cell biosensor based on the split-luciferase complementation assay. We validated our biosensor by using baicalein, a known inhibitor of α-synuclein aggregation, and subsequently we tested eight essential oils commonly used in food and the hygienic industry. Two of them, citron and sage, along with their primary components, pure linalool (the main constituent in citron essential oil) and pure eucalyptol (1,8-cineole, the main constituent in sage essential oil), were able to reduce α-syn aggregation. These findings suggest that both essential oils and their main constituents could be regarded as potential components in functional foods or incorporated into complementary Parkinson’s disease therapies.
... Scopolamine-induced AD model in rats Improved spatial and working memory, antidepressant, anxiolytic, anti-alzheimer [33] 17. Zataria Oil ICV Aβ (25-35)-induced AD in rats Reversed Aβ-induced learning deficits, antioxidant, anti-inflammatory, anti-cholinesterase activities [34] 18. Juniper Oil ICV Aβ (1-42)-induced AD in rats Reduced memory impairment, antioxidant, anticholinesterase activities [35] 19. Paeonia Oil Scopolamine-induced memory deficits, depression and anxiety in rat model of AD Hindered depression, anxiety and memory deficits [36] 20. ...
Alzheimer’s disease is a complex neurodegenerative disorder characterised by cognitive decline and progressive memory deterioration. Multiple hypotheses have been proposed to elucidate the pathophysiology of the phenomenon in question. At present, there exists a limited number of pharmaceutical interventions for the management of Alzheimer’s disease, with the treatment options primarily focused on alleviating symptoms rather than addressing the underlying causes of the condition. The objective of this study is to conduct a comprehensive review of the pertinent in vitro, in vivo, and clinical research pertaining to the potential therapeutic applications of essential oils in the management of Alzheimer’s disease. Data was collected by conducting a search in scientific databases, including google scholar, Scopus, ScienceDirect and PubMed. A comprehensive investigation was undertaken to explore the utilisation of diverse essential oils in various models of Alzheimer’s disease. The findings of our literary investigation indicate promising outcomes concerning the diverse essential oils that have been examined in research on Alzheimer’s disease. These oils have demonstrated notable effects in regulating the disease’s pathology through their anti-amyloid, antioxidant, anticholinesterase, and memory-enhancement properties.
... 56 It is, thus, a major contributor to pathophysiology of neurodegenerative disorders, including AD. 57 Therefore, antioxidant substances are a promising target for reducing rate of AD development and progression. 58 In this study, ketamine treated mice exhibited increased oxidative stress in their brains. On the other hand, A. dubius extract reduced oxidative stress in cognitively damaged mice. ...
Amaranthus dubius is a vegetable consumed for its nutritional content in Kenya. In herbal medicine, A. dubius is utilized to relief fever, anemia and hemorrhage. Additionally, it is utilized to manage cognitive dysfunction and is considered to augment brain function, but there is no empirical evidence to support this claim. The contemporary study investigated cognitive enhancing potential of A. dubius in mice model of Alzheimer's disease (AD)-like dementia induced with ketamine. Cognitively damaged mice were treated with aqueous extract of A. dubius leaf upon which passive avoidance task (PAT) was used to assess the cognitive performance. At the end of passive avoidance test, brains of the mice were dissected to evaluate the possibility of the extract to inhibit hallmarks that propagate AD namely oxidative stress and acetylcholinesterase activity. Additionally, characterization of secondary metabolites was done using liquid chromatograph- mass spectrometry analysis. During PAT test, extract-treated mice showed significantly increased step-through latencies than AD mice, depicting ability of A. dubius to reverse ketamine-induced cognitive decline. Further, the extract remarkably lowered malondialdehyde levels to normal levels and effectively inhibited acetylcholinesterase enzyme. The study showed that A. dubius extract is endowed with phytoconstituents that possess anti-oxidant and anticholinesterase activities. Thus, this study confirmed promising therapeutic effects of 200, 300 and 400 mg/kg bw of A. dubius extract with potential to alleviate cognitive disarray observed in AD.
... Juniper berries are rich in various products of secondary metabolism, the most important of which is the essential oil. Previous research has shown that the essential oil of juniper berries has a very pronounced biological activity, including antimicrobial (Angioni et al., 2003), antioxidant (Miceli et al., 2009), and also memory-enhancing effects (Cioanca et al., 2015). The Food and Drug Administration has characterized essential oils as safe for use in diet, further, they are very important natural products that ensure the extension of the shelf life of food products (Feng et al., 2019;Silvestre et al., 2019). ...
... 48 Clove oil is a mind stimulant used in the treatment of anxiety, insomnia, and depression, 49 was also comfirmed by using SOD, GSH-Px, and CAT activities, the total content of the reduced glutathione and protein carbonyl levels. 51 Of concern is that the safety of juniper volatile oil need to be properly addressed. It has been reported a little toxicity of the juniper volatile oil extracted from multiple juniper species in animals. ...
Aims
The aim of this review is to outline recent advancements in the application and mechanistic studies of aromatic plant extracts in Alzhermer`s disease (AD) to demonstrate their value in the management of this disease.
Background
AD is a neurodegenerative disease with a complex pathogenesis characterized by severe cognitive impairment. Currently, there are very few drugs available for the treatment of AD, and treatments are primarily focused on symptom relief. Aromatherapy is a traditional complementary alternative therapy that focuses on the prevention and treatment of the disease through the inhalation or transdermal administration of aromatic plant extracts. Over the past few years, studies on the use of aromatic plant extracts for the treatment of AD have been increasing and have demonstrated a definitive therapeutic effect.
Methods
We systematically summarized in vitro, in vivo, and clinical studies focusing on the potential use of aromatic plant extracts in the treatment of AD in PubMed, ScienceDirect, Google Scholar, and the Chinese National Knowledge Infrastructure from 2000 to 2022.
Results
Our literature survey indicates that aromatic plant extracts exert anti‐AD effects by modulating pathological changes through anti‐amyloid, anti‐tau phosphorylation, anti‐cholinesterase, anti‐inflammation, and anti‐oxidative stress mechanisms (Figure 1).
Conclusion
This review provides a future strategy for the research of novel anti‐AD drugs from aromatic plant extracts.
... The effects of inhaled juniper volatile oil (1% and 3%, daily, for 21 days) on spatial memory performance were assessed in an Aβ(1-42) rat model of Alzheimer's disease. The Aβ(1-42)-treated rats exhibited decrease of spontaneous alternations percentage within Y-maze task and increase of working memory and reference memory errors within radial arm maze task [138][139]. ...
Alzheimer's disease is the most common cause of dementia, accounting for an estimated 60% to 80% of cases. The
treatment of Alzheimer's disease remains challenging. Many medicinal plants possessed beneficial therapeutic effect inAlzheimer’s disease and memory deficits, by their anti-inflammatory, antioxidant, neuroprotective, NF-κB inhibition, phosphodiesterase inhibition, anti-amyloidogenic, and anticholinesterase activities. In the current article, the medicinal plants with beneficial effects in Alzheimer’s disease and memory deficits were discussed. This article considers not only
the therapeutic effect of medicinal plants in AD and memory deficits, but also discussed the mechanisms of their beneficial effects.
... The effects of inhaled juniper volatile oil (1% and 3%, daily, for 21 days) on spatial memory performance were assessed in an Aβ(1-42) rat model of Alzheimer's disease. The Aβ(1-42)-treated rats exhibited decrease of spontaneous alternations percentage within Y-maze task and increase of working memory and reference memory errors within radial arm maze task [138][139]. ...
Alzheimer's disease is the most common cause of dementia, accounting for an estimated 60% to 80% of cases. The treatment of Alzheimer's disease remains challenging. Many medicinal plants possessed beneficial therapeutic effect inAlzheimer’s disease and memory deficits, by their anti-inflammatory, antioxidant, neuroprotective, NF-κB inhibition, phosphodiesterase inhibition, anti-amyloidogenic, and anticholinesterase activities. In the current article, the medicinal plants with beneficial effects in Alzheimer’s disease and memory deficits were discussed. This article considers not only
the therapeutic effect of medicinal plants in AD and memory deficits, but also discussed the mechanisms of their beneficial effects.
... The effects of inhaled juniper volatile oil (1% and 3%, daily, for 21 days) on spatial memory performance were assessed in an Aβ(1-42) rat model of Alzheimer's disease. The Aβ(1-42)-treated rats exhibited decrease of spontaneous alternations percentage within Y-maze task and increase of working memory and reference memory errors within radial arm maze task [138][139]. ...
Alzheimer's disease is the most common cause of dementia, accounting for an estimated 60% to 80% of cases. The treatment of Alzheimer's disease remains challenging. Many medicinal plants possessed beneficial therapeutic effect inAlzheimer’s disease and memory deficits, by their anti-inflammatory, antioxidant, neuroprotective, NF-κB inhibition, phosphodiesterase inhibition, anti-amyloidogenic, and anticholinesterase activities. In the current article, the medicinal plants with beneficial effects in Alzheimer’s disease and memory deficits were discussed. This article considers not only the therapeutic effect of medicinal plants in AD and memory deficits, but also discussed the mechanisms of their beneficial effects.
... Besides, in vivo anticholinesterase activities of bioactive components have been largely investigated (Ahirwar et al. 2012). For example, the essential oils of Salvia lavandulifolia Vahl, Pinus nigra J.F.Arnold, Pinus halepensis Mill., Juniperus communis L., Dennettia tripetala Baker f. and Citrus limon (L.) Osbeck were found to inhibit the cholineesterase in the rat brain (Perry et al. 2002;Cioanca et al. 2015;Oyemitan et al. 2019;Postu et al. 2019;Liu et al. 2020). Moreover, the leaf extracts of Rosmarinus officinalis L. demonstrated significant AChE inhibition leading to improved long-term memory in rats (Ozarowski et al. 2013). ...
Elaeoselinum thapsioides is an Algerian medicinal plant used in traditional medicine to treat different diseases. The essential oil obtained by hydrodistillation from the aerial parts of Elaeoselinum thapsioides (Desf.) Maire (Apiaceae) growing wild in Algeria, was analyzed by GC-MS for the first time. Forty-five compounds were detected, accounting for 93.8% of the total oil, which was characterized by a high content of hydrocarbons derivatives of monoterpenes (75.9%). Myrcene (61.0%) was the principal constituent of the essential oil, followed by germacrene D (10.3%), α-pinene (6.5%) and β-pinene (2.9%). In vitro anticholinesterase activity of the essential oil was investigated by the Ellman method that evidenced a low acetylcholinesterase and butyrylcholinesterase inhibitory effect.
... Ефективність наведеного вище фармпрепарату зумовлена високим рівнем у нього так званого терпенового компоненту. Згідно результатів проведеного мета аналізу (MEDLINE, EMBASE, OVID, Science Direct, Proquest, Google scholar, Cochrane Library), використання комплексних препаратів із тер пеновими сполуками (екстракти олії сосни, олії ялівцю) сприяє руйнації конкрементів й виділенню їхніх фрагментів та продуктів запалення (слиз, частки фібрину) в осіб різних вікових груп [22]. ...
... The inhalation of volatile oil at the rate of 1% or 3% daily for 21 days also to improve amyloid ß induced memory deficits in rat model of Alzheimer disease and was found Acetylcholine inhibition (AChE) activity involved in the progression of neurolog-esterase activity and prevent oxidative damage in brain of rodents in a dose dependent manner due to its significant antioxidant potential and ability to inhibit AChE activity involved in the progression of neurological disorders. 24 In another study neuroprotective activity of methanolic extract of J. communis (MEJC) was evaluated in chlorpromazine (CPZ) induced Parkinson's model in rats. Various behavior parameters like catalepsy (bar test), muscle rigidity (rota rod test), locomotor activity (actophotometer) and its effect on biochemical parameters (TBARS, GSH, nitrite, and total protein) in rats brain was observed in which Methnolic extract of J. communis showed a significant ( < 0.001) neuroprotective effect. ...
Abhal (Juniperus communis L.) belonging to the family Cupressaceae is an evergreen, aromatic shrub, native to Europe, South Asia, and North America and used as medicine since 70 AD when Dioscorides introduced It first. The blackish red berry like fruits are known as Abhal in Unani System of Medicine. It is mainly used as diuretic, lithotriptic, anti-inflammatory, emmenagogue, demulcent, mild astringent, and anthelmintic. Juniperus communis L. contains volatile oils, acids, flavonoids, tannins and many more compounds. The diuretic effect of juniper is thought to be due to sesquiterpene hydrocarbons present in it. Various pharmacological studies on Juniperus communis L. exhibit e.g. diuretic, carminative, stimulant and abortifacient properties as well as direct effect on smooth muscle contraction.
... Inversely, mitochondrial damage, diminished levels of antioxidants, elevated levels of oxidative stress and their markers, and other abnormalities lead to the risk of Alzheimer's disease. 8,9 These abnormalities can appear either on account of primarily pathogenesis of the disease or other related factors such as vitamin deficiencies and lead to a decrease in energy levels which in-turn leads to the neuronal death and sustain Alzheimer's disease progression. 4,10,11 The disorders like hypertension, obesity, diabetes, etc. were identified with an imbalance of diet. ...
Background: Alzheimer’s disease is known as one of the fastest growing lethal diseases worldwide where we have limited and undesired ways for regulating its pathological progress. Now-a-days, nutritional compounds have been using to treat several brain disorders and one of them; vitamins were strongly reported to combat cognition and memory deterioration in neurodegenerative diseases including Alzheimer’s disease.
Objective: Here, the author tried to find the precise physiological roles, status, and worth of vitamins in the brain and how exactly these nutrients modulate progression of Alzheimer’s disease.
Results & Discussion: After a comprehensive and systematic literature review, the author reports that vitamins have various targets in Alzheimer’s disease pathogenesis by which they act to avert the neuronal dysfunction in the disease. Several Alzheimer’s disease associated neurological deficits have reported regulating by vitamin intake but the beneficial effects identified mostly in combinatorial and long-term studies.
Conclusion: In this way, the author suggests that it might be better to test vitamins with other components over single vitamin approach for a compatible and synergistic effect as well as using a combination of vitamin with other compounds can target multiple pathways. This strategy may help in deteriorating memory dysfunction and cognition impairment in Alzheimer’s disease pathophysiology.
... Acetylcholinesterase from Electrophorus electrics (0.2 U/mL in phosphate buffer), acetylthiocholine iodide (0.2 M) and various concentrations of chamomile, parsley and celery extracts diluted in DMSO were employed for the analysis. The ability of the investigated extracts to inhibit acetylcholinesterase was assessed by Ellman's method by measuring the absorbance variations at 412 for 5 minutes [19,20]. The activity value was calculated as a percentage of the difference between the absorbance values (enzyme solution with inhibitor at after 5 minutes and the absorbance of the same solution at the initial time). ...
Background
This study was designed as a continuation of a complex investigation about the phytochemical composition and biological activity of chamomile, parsley and celery extracts against A375 human melanoma and dendritic cells.
Objective
The main aim was the evaluation of the antimicrobial potential of selected extracts as well as the in vitro anticancer activity against MCF7 human breast cancer cells.
Methods
In order to complete the picture regarding the phytochemical composition molecular fingerprint was sketched out by the help of FTIR spectroscopy The activity of two enzymes (acetylcholinesterase and butyrylcholinesterase) after incubation with the three extracts was spectrophotometrically assessed. The antimicrobial potential was evaluated by disk diffusion method. The in vitro anti-cancer potential against MCF7 human breast cancer cells was appraised by MTT, LDH, wound healing, cell cycle, DAPI, Annexin-V-PI assays.
Results
Results showed variations between the investigated extracts in terms of inhibitory activity against enzymes such as acetyl- and butyrilcholinesterase. Chamomile and parsley extracts were active only against tested Gram-positive cocci, while all tested extracts displayed antifungal effects. Among the screened samples at the highest tested concentration, namely 60 µg/mL parsley was the most active extract in terms of reducing the viability of MCF7 - human breast adenocarcinoma cell line and inducing the release of lactate dehydrogenase. On the other hand chamomile and celery extracts manifested potent anti-migratory effects. Furthermore, celery extract was the most active in terms of total apoptotic events, while chamomile extract induced the highest necrosis rate.
Conclusion
The screened samples containing phytochemicals belonging in majority to the class of flavonoids and polyphenols can represent candidates for antimicrobial and anticancer agents.
... But some of the recent studies have reported that the soluble amyloid-beta (Ab) oligomers are mainly responsible to induce the synaptic loss and cognitive decline in the initial stages of AD. In the last decade, a lot of studies have suggested a strong correlation between the neurotoxicity and oligomeric Ab levels (Mucke and Selkoe, 2012;Walsh and Teplow, 2012;Zussy et al., 2013;Cioanca et al., 2015;Epelbaum et al., 2015;Faucher et al., 2015;Gradinariu et al., 2015;Jin and Selkoe, 2015;Leggio et al., 2016;Sharma et al., 2016). These oligomeric Ab aggregates are formed by the aggregation of the different Ab peptide species. ...
The equilibrium between cerebral production and clearance of Aβ is maintained either by the active removal through blood-brain barrier or by the uptake and degradation through ubiquitin-proteasome system (UPS) and autophagy. The dysfunction of UPS and dysregulation of molecular chaperones such as heat shock proteins (HSPs) is well correlated with the progression of Alzheimer's disease (AD). Therefore, the restoration of heat shock system and UPS appears to be an effective approach to maintain the Aβ homeostasis. The alteration in the Aβ homeostasis was induced by a single bilateral intrahippocampal injection of Aβ 42 oligomers (10 μl/rat) into the dorsal hippocampus of the rat brain. Cbx (carbenoxolone), a HSP inducer and Aβ 42 aggregation inhibitor, was tested (20 mg/kg body weight, i.p. for six-weeks) against the altered Aβ homeostasis in the rat brain. Aβ 42 oligomers downregulated the expression of HSPs and co-treatment with Cbx prevented this decline. Cbx was able to restore the UPS function post Aβ 42 oligomer injection. Aβ 42 oligomers induced upregulation of the expression levels of APP, BACE-1 and Tau was also normalized after the co-treatment with Cbx. A significant decrease in the thioflavin-T and Aβ positive deposits in different regions of the rat brain was observed after Cbx co-treatment. Thus, the present study projects Cbx as a potential candidate for the maintenance of Aβ homeostasis through inhibition of amyloid aggregation and restoration of the functioning of molecular chaperones and UPS system in the progression of AD.
... MDA is one of the products of lipid peroxidation, whose level increased in hippocampal neurons of Aβ treated rats (43). In the present study, homogenate level of MDA in Aβ-injected rats' hippocampus increased significantly (p < 0.001), compared with healthy control values (Fig. 7a). ...
PurposeThe current drugs for Alzheimer’s disease (AD) are only used to slow or delay the progression of the pathology. So using a novel technology is a necessity to synthesize more effective medications to control this most common cause of dementia. In this study, using nanochelating technology, ALZc3 was synthesized and its therapeutic effects were evaluated in comparison with memantine on a well-known rat model of AD, which is based on Amyloid-βeta (Aβ) injection into the brain.Materials and MethodsAβ (1–42) was injected bilaterally into the CA1 area of the hippocampus of male rats and then animals were treated daily by oral administration of Alz-C3, memantine or their vehicles. Activities of antioxidant enzymes catalase and superoxide dismutase (SOD), glutathione (GSH) and malondialdehyde (MDA) levels, as well as Bax/Bcl-2 ratio, caspase-3 activation, and TNF-α expression were evaluated 7 days after Aβ injection. Finally, learning and memory of the rats were assessed by Morris water maze test.ResultsALZc3 and memantine improved memory impairment and antioxidant activity and reduced TNF-α expression, caspase-3 activity and Bax/Bcl-2 ratio in the rat’s hippocampus. The results showed a superiority of ALZC3 compared to memantine in reducing caspase-3, increasing CAT activity in Aβ (1–42)-injected groups and improving apoptosis factor in healthy mice.Conclusion
These results indicated that ALZc3 could significantly prevent the memory impairment and Aβ (1–42) toxicity. Thus, ALZc3 could be a promising novel anti-AD agent.
... EO, [8] Lavandula stoechas L. EO, [9] Coriandrum sativum L. volatile oil [10] or Juniperus communis L. oil. [11] Videira et al. isolated an individual compound, 2,3,4,4tetramethyl-5-methylenecyclopent-2-enone, from Lavandula × losae Sánchez-Gómez, Alcaraz & García Vall EO, which exerted beneficial effects in cellular and mouse models of Alzheimer's disease. [12] The review article presents the most important and well-studied monoterpenes which can play significant role in pharmacy and medicine. ...
Terpenes are a widespread group of secondary metabolites that can be found in various family plants such as the Lamiaceae. In view of their numerous valuable biological activities, the industrial production of concrete terpenes and essential oils rich in the substances is intensively studied. Monoterpenes constitute a significant part of the whole group of the aforementioned secondary metabolites. This is due to their numerous biological activities and their ability to permeate the skin. Despite the fact that these substances have gain popularity, they are not comprehensive characterized. The presented review is based on studies of the biological activities of the most important monoterpenes and the essential oils rich in these compounds. The authors focused attention on antioxidant activity, inhibition towards acetyl‐ and butyrylcholinesterase, and α‐amylase and α‐glucosidase, antifungal, hepatoprotective, sedative properties, and their skin permeation enhancement.
... Terpenoids are mixture of naturally occuring, volatile compounds which are synthesized by plants in the form of secondary metabolites. The essential oils (EOs) obtained from certain plants such as juniper oil from common juniper (Juniperus communis L) (19) and clove oil obtained from clove buds (Eugenia caryophyllus) (20) are reported to have anticholinesterase activity (8,21,22). So, essential oils may show their neuroprotective effect by down-regulation of AChE and up-regulation of BDNF in the brain. ...
Acetylcholinesterase (AChE) is an enzyme involved in the progression of Alzheimer's disease (AD). Cardamom oil (CO) has been reported to have acetylcholinesterase inhibitory, antioxidant and anti-anxiety effects. Hence, we studied the effect of cardamom oil in aluminum chloride induced neurotoxicity in rats. AD like symptoms were induced in Wistar rats with aluminum chloride (100 mg/kg, p.o.). Cardamom oil was administered concomitantly by oral route at doses of 100 and 200 mg/kg for 42 days. Behavioral parameters like Morris water maze, elevated plus maze, passive avoidance test and locomotor activity were evaluated on day 21 and 42. AChE activity, oxidative stress parameters, histopathological studies and immunohistochemistry studies were carried out in hippocampus and cortex. Cardamom oil treatment showed significant improvement in behavioral parameters, inhibition of AChE activity (p < 0.001) and reduction in oxidative stress in the brain. Histopathological studies of hippocampus and cortex by hematoxylin & eosin (H. & E.) and congo red stain showed inhibition of neuronal damage and amyloid β plaque formation with cardamom oil treatment. Immunohistochemistry showed, CO treatment inhibited amyloid β expression and upregulated brain-derived neurotrophic factor (BDNF). The present study showed that, cardamom oil has neuroprotective effect in aluminum chloride induced neurotoxicity linked with inhibition of AChE activity and reduction in oxidative damage. This effect of cardamom oil may be useful in management of Alzheimer's disease.
... Aqueous-methanolic extract [20] Juniperus sp Acetylcholinesterase Inhibitory effect Phenolic fraction of leaves [21,22] Thymus vulgaris Acetylcholinesterase Inhibitory effect Essential oil [23,24] Peganum harmala. L. Cerebroprotective effect Acetylcholinesterase Inhibitory effect ...
Background:
Dementia is a chronic neurodegenerative disease causing progressive and gradual impairment of different brain's cognitive functions. The prevalence of dementia is about 3 to 7% in different parts of the world.
Objective:
The aim of this study was to determine the etiologies of dementia according to the Traditional Persian Medicine scientists' viewpoint and introduce their recommended herbal remedies for this disease.
Method:
The authors explored six main Traditional Persian Medicine textbooks for the disease of dementia, its etiologies and related recommended herbal treatments. Two main keywords of "Lisarghes" and" Nesyan" were searched for this purpose. Medical databases, including PubMed, Scopus, Google Scholar, and Science Direct were searched for related articles published between 1966 and 2016 to review the pharmacological components and active ingredients of suggested herbal medicines.
Results:
According to the Traditional Persian Medicine, dementia is resulted from brain dystemperament, a condition caused by cold and moist or cold and dry tempers. To treat this disease, Traditional Persian scientists recommended various herbal remedies. Current studies have demonstrated that some of these medicinal plants have beneficial effects for the aforementioned disease, including acetyl cholinesterase inhibitory function, neuroprotective effects, and memory enhancing role.
Conclusion:
The Traditional Persian Medicine literature suggested different herbal remedies for treating dementia. Modern studies support the usefulness of some of these medicines. However, the effect of a large number of these remedies has remained unexamined, a matter which need to be investigated in future researches.
... The presence of phenolics, flavonoids and a significant antioxidant activity in methanolic extracts of different plant materials of Jordanian J. phoenicea were confirmed by the results of the current investigation. This is in accord with similar reports for juniper species from other regions (Elmastaş et al., 2006;Moein et al., 2010;Emami et al., 2011;Höferl et al., 2014;Cioanca et al., 2015;Elmhdwi et al., 2015). However, antioxidant activity as reported in this study did not correlate with the total content of phenolics and flavonoids, except for extracts obtained from cuttings of small seedlings, which shared the highest antioxidant activity with that of C2-type callus and in vitro shoots. ...
Juniperus phoenicea is an ornamental shrub that is also used to flavor food and to supply medicines and timber. Its micropropagation is of industrial concern and can occur by axillary shoot multiplication. Microcuttings of J. phoenicia were established in vitro on Murashige and Skoog (MS) and Rugini Olive (OM) media in glass tubes (25 mm x 150 mm). Factors studied were explant length (0.5 or 1.5 cm) and orientation (horizontal or vertical), media strength (OM, ½OM, MS, ½MS) and the following growth regulators: the anti-auxin 2,3,5-triiodobenzoic acid (TIBA), the cytokinins 6-benzyladenine (BA) and thidiazuron (TDZ), and the growth retardant daminozide (DM). Microcuttings placed vertically on the surface of OM, ½OM and ½MS media without hormones exhibited axillary bud differentiation, but they were swollen and turned brown one month later when placed horizontally on the medium surface. The number of shoots, averaged across OM, ½OM and ½MS media, was significantly higher from longer (1.5 cm) than shorter (0.5 cm) microcuttings (4.11 versus 1.57 shoots microcutting-1) after 60 days of culture. TIBA or DM at 0.1 mg l-1 included in OM medium enhanced leaf differentiation, callus induction and formation of adventitious shoots over three months from 0.5 cm long microcuttings taken from in vitro shoots. The formation of adventitious shoots was sporadic and occurred at a rate of 1 shoot microcutting-1 in the presence of 0.1 mg l-1 DM. OM supplemented with 0.1 mg l-1 TIBA resulted in significantly the highest leaf differentiation (55 leaves microcutting-1), with a rooting rate of 40%. Contents of phenols, flavonoids and antioxidants were compared for cuttings from young seedlings, callus, in vitro shoots, and seeds. Antioxidant activity was significantly the highest for shoots grown on hormone-free OM medium and callus maintained on OM medium containing 0.1 mg l-1 2,4-D (94.7 and 94.3% inhibition of DPPH free radicals, respectively). Thus, different routes for in vitro regeneration of J. phoenicea can be of potential use for many biotechnological, pharmaceutical and food industry applications.
... Isolated fractions from all the six Juniperus species were reported as potential source of natural antioxidants for treatment and prevention of diseases in which oxidative stress takes place [13]. Antioxidant potential has also been reported for essential oils of Juniper berries of different species of Junipers [33,34]. ...
Alzheimer's disease, a type of dementia, poses serious challenges to patients, especially older people, and no definitive treatment is available for this disease, with drug treatments having many side effects. As essential oils of plants deserve particular attention in the treatment of diseases, this study aimed to review the potential therapeutic effects of essential oils on treatment of psychosomatic aspects of Alzheimer's disease. To collect information, we searched different databases, including MagIran, SID, IranDoc and IranMedex, Embase, Science Direct, PubMed, Google Scholar, Scopus and Web of Science using the keywords of essential oil, Alzheimer, acetylcholinesterase, memory, forgetfulness, aromatherapy, medicinal plant, herbal drugs, and their Persian equivalents from January 2010 to June 2022; the search included both single and multiple keywords. We retrieved 233 articles, reviewed the titles, abstracts, and full texts of the articles, and then included 25 related articles in this review (11 in vitro studies and 14 in vivo studies). The study results of in vitro and in vivo studies showed the effectiveness of different essential oils such as salvia family, tangerine and lemon oils, Juniperus communis , Anthriscus nemorosa , olibanum, inhaled coriander, Schisandra chinensis , lavender, rose essential oil, Nepeta cataria , Cinnamomum zeylanicum and Lippia origanoides , on memory and learning, enzymes, oxidative stress and inflammation, behavioural and cognitive symptoms in Alzheimer's disease. These findings suggest that essential oils can serve as complementary therapies for neurodegenerative diseases like Alzheimer's and for addressing memory impairments, although further research, especially human clinical trials, is needed to validate these findings, determine optimal dosages, and explore the long‐term safety of essential oils in clinical settings.
Juniperus rigida Sieb. et Zucc. has been long used as a traditional medicine in China, Korea, and Japan. Diseases like neuralgia, dropsy, gout, brucellosis, dermatitis, nephritis, and rheumatoid arthritis have been treated by J. rigida. According to most studies of the plant, these uses above are mainly attributed to its phytochemical composition, which turns out rich in phenolics, terpenoids, organic acids, alkaloids, and volatile compounds. In recent years, more and more reports are pointing out the bioactive potential of this evergreen shrub in a wide range of different biomedical fields, namely antioxidant, anti-wrinkling, anti-bacterial, anti-inflammatory, cytotoxic, anti-cancer, anti-tumor, anti-mutagenicity, anti-obesity, anti-cholinesterase, anti-fungal activities. Despite these promising results, more in vivo and in vitro studies are needed to provide more evidence and methods for its application in cosmetics and pharmacology. Therefore, we conducted the first review on J. rigida, a recalcitrant plant and a promising source of bioactive compounds and medical outcomes, to outline and summarize all the bioactive compounds and biomedical activities reported so far.
All over the world, wild edible plants are an essential source of chemical components that justify their use in folk medicine. The aim of this review is to document and summarize the knowledge of ten wild plants analyzed in a previous study for their ethnomedical significance. Achillea millefolium, Borago officinalis, Foeniculum vulgare, Gentiana lutea, Juniperus communis, Laurus nobilis, Malva sylvestris, Satureja montana, Silybum marianum and Urtica dioica were the subjects of our study. They are commonly found in the central Italian Apennines and the Mediterranean basin. Phytochemicals contained in wild plants, such as phenols, polyphenols, flavonoids, condensed tannins, carotenoids, etc., are receiving increasing attention, as they exert a wide range of biological activities with resulting benefits for human health. Based on the 353 studies we reviewed, we focused our study on the following: (a) the ethnobotanical practices and bioactive phytochemicals; (b) the composition of polyphenols and their role as antioxidants; (c) the methodologies commonly used to assess antioxidant activity; (d) the most advanced spectroscopic and spectrometric techniques used to visualize and characterize all components (metabolomic fingerprinting). The potential of pure compounds and extracts to be used as nutraceuticals has also been highlighted through a supposed mechanism of action.
Numerous studies have demonstrated essential oils’ diverse chemical compositions and pharmacological properties encompassing antinociceptive, anxiolytic-like, and anticonvulsant activities, among other notable effects. The utilization of essential oils, whether inhaled, orally ingested, or applied topically, has commonly been employed as adjunctive therapy for individuals experiencing anxiety, insomnia, convulsions, pain, and cognitive impairment. The utilization of synthetic medications in the treatment of various disorders and symptoms is associated with a wide array of negative consequences. Consequently, numerous research groups across the globe have been prompted to explore the efficacy of natural alternatives such as essential oils. This review provides a comprehensive overview of the existing literature on the pharmacological properties of essential oils and their derived compounds and the underlying mechanisms responsible for these observed effects. The primary emphasis is on essential oils and their constituents, specifically targeting the nervous system and exhibiting significant potential in treating neurodegenerative disorders. The current state of research in this field is characterized by its preliminary nature, highlighting the necessity for a more comprehensive overlook of the therapeutic advantages of essential oils and their components. Integrating essential oils into conventional therapies can enhance the effectiveness of comprehensive treatment regimens for neurodegenerative diseases, offering a more holistic approach to addressing the multifaceted nature of these conditions
Alzheimer's disease (AD) is a neurodegenerative disease that affects several elderly people per years. AD is a pathology of multifactorial etiology, resulting from multiple environmental and genetic determinants. However, there is no effective pharmacological alternative for the treatment of this illness. In this sense, the purpose of current study was to characterize the mechanisms by which Aβ1-42 injection via intracerebroventricular induces neurobehavioral changes in a time-course curve. In addition, suberoylanilide hydroxamic acid (SAHA) inhibitor of histone deacetylase (HDAC) was used to investigate the involvement of epigenetic modifications Aβ1-42-caused in aged female mice. In general manner, Aβ1-42 injection induced a major neurochemical disturbance in hippocampus and prefrontal cortex of animals and a serious impairment of memory. Overall, SAHA treatment attenuated neurobehavioral changes caused by Aβ1-42 injection in aged female mice. The subchronic effects presented of SAHA were through modulation of HDAC activity, regulation of brain-derived neurotrophic factor (BDNF) levels and expression of BDNF mRNA, accompanied by unlocking cAMP/PKA/pCREB pathway in hippocampus and prefrontal cortex of animals.
Giriş
Ardıçlar özellikle kuzey yarımkürede geniş yayılış gösterirler. Toplam tür sayısı ise her kaynakta farklılıklar göstermektedir. Türkiye’de yakın zamana kadar yayılış gösteren tür sayısı 7 olarak kabul edilmekteydi: Juniperus drupacea (andız), J. oxycedrus (katran ardıcı), J. communis (adi ardıç), J. excelsa (boylu ardıç), J. foetidissima (kokulu ardıç), J. sabina (sabin ardıcı), J. phoenicea (Finike ardıcı). Ancak artan saha araştırmaları ve genetik bilimdeki ilerlemeler bu sayının daha yüksek olduğunu işaret etmektedir.
Geçmişte katran ardıcının alttürü olarak tanımlanmış olan büyük kozalaklı katran ardıcının (J. oxycedrus subsp. macrocarpa) günümüzde J. macrocarpa adıyla ayrı bir tür olduğu benimsenmiştir (Yaltırık ve Akkemik, 2011). Diğer yandan ülkemizde yaygın olarak gözlenen katran ardıcının (J. oxycedrus) gerçekte J. deltoides olduğunu öne süren kaynaklar bulunmaktadır. Adams 2004 yılında J. oxycedrus’un Buzul Çağı kaynaklı coğrafik izolasyon neticesinde Akdeniz havzasının batısında yetişen bir tür olduğunu, daha önceki bilgilere göre Akdeniz havzasının tümünde, Kafkasya, İran, Kırım ve Türkiye’de yayılış gösteren J. oxycedrus subsp. oxycedrus olarak bilinen türün de J. deltoides türü olduğunu belirtmiştir. Ancak bu konuda çok örneklemeli ve detaylı bir çalışma yapılıncaya kadar ülkemizdeki türün J. oxycedrus subsp. oxycedrus olarak değerlendirilmesi kabul görmüştür (Yaltırık ve Akkemik, 2011).
Yine ülkemizde boylu ardıcın bir alttürü olarak bilinen J. excelsa subsp. polycarpos, 2004 yılında Adams tarafından yapılan genetik araştırmaların ardından J. polycarpos adıyla ayrı bir tür olarak kabul edilmiştir. Kırsal Çevre ve Ormancılık Sorunları Araştırma Derneği, Davis’in 1965 yılında yayınladığı ve Hakkari, Zap Geçidi, Kalolan yakınlarında bulunan J. excelsa bireylerinden alınan örnekler üzerinde yaptığı morfolojik incelemelerde belirgin farklılıklar bulmuş, ancak bu farklılıkların ayrı bir tür tanımını destekleyebilecek yeterlilikte olmadığı sonucuna varmıştır.
İleride yapılacak kimyasal ve moleküler araştırmaların bu bireylerin ayrı bir tür olarak kabul edilmesine fırsat vermesi olasıdır, ancak bugünkü mevcut veriler değerlendirilerek bu yayında J. excelsa subsp. polycarpos ayrı bir tür olarak kabul edilmemiş, J. excelsa altında bir alttür olarak ele alınmıştır.
Doğal ve egzotik ardıç türleri ülkemizde yaygın olarak park ve bahçelerin düzenlenmesinde kullanılmaktadır. Kitapta, Türkiye’de doğal olarak yetişen ardıç türlerinin yanı sıra, şehirlerde sıkça gözlenebilen egzotik türlerden J.chinensis ile J. virginiana da ayrı başlıklar şeklinde ele alınacaktır.
Türkiye’nin ardıçları üzerine hazırlanmış en kapsamlı yayın özelliğindeki bu
kitap ardıçların evriminden jeolojik devirlerde Anadolu’daki ardıç varlığına,
ardıç türlerinden ardıç ormanlarına, ardıçlar ile ilişkili mantar ve likenlerden
tarihî yapılarda ardıç kullanımına kadar ardıçlara dair hemen hemen her
konuyu içinde barındırmakla kalmayıp başlı başına bir kitap konusu olabilecek
Anadolu kültüründe ardıçlar, anıtsal ardıçlar gibi bölümleri de içermektedir.
Essential oils or volatile oils are natural products that have a large series of uses in the food and cosmetic sectors. According to their intended use, essential oils are subjected to various European guidelines that aim to protect the health and safety of consumers. Volatile oils present important biological activities, some of the most known being their antimicrobial properties, but other potential therapeutic indications for such products have been more recently suggested, as well. However, they are not necessarily harmless and can present an important sensitizing potential. Essential oils have been administered through different routes, including inhalations and skin applications, in the treatment of stress and anxiety. Regardless of the route of administration, aromatherapy deeply relies on the sense of smell and its connection with the limbic system. Nevertheless, outside of the principles of aromatherapy, numerous scientific studies have revealed their potential beneficial implications in Alzheimer’s and other neurological disorders. © 2020, Romanian Society for Pharmaceutical Sciences. All rights reserved.
This ethnobotanical survey was carried out in Caspoggio (Valmalenco, SO, Italy) with the purpose of investigating the traditional uses of medicinal plants. Moreover, a bibliographic research meant to validate or refute the uses, focusing on the potentially responsible compounds, was performed. Fifty-nine species, attributable to 30 families (Asteraceae, Pinaceae, Malvaceae, and Lamiaceae the most cited), were mentioned. Arnica montana, anti-inflammatory for traumas and musculoskeletal pains; Pinus mugo, expectorant; Malva sylvestris, anti-inflammatory and soothing; Achillea moschata, digestive. The compounds, responsible for the therapeutic activities, are often polyphenols and terpenoids: helenanin in A. montana, α-pinene, δ-3-carene, and limonene in P. mugo, gossypin and malvin in M. sylvestris, luteolin and apigenin in A. moschata. Scientific evidence for at least one of the traditional activities described was found for 50 species but only in 26 out of 196 works consulted, it is possible to make a comparison between investigated extracts and traditional preparations. This study is thus a stimulus to new phytochemical investigations, mimicking as much as possible the traditional preparations. This work is part of the European Interreg Italy-Switzerland B-ICE project, aimed at creating a management model for the ongoing climate change and searching for new sources of territory valorization as attractions for tourists.
Alzheimer’s disease (AD) is a neurodegenerative disorder characterized by a clinically and progressive loss of cognitive function, neuropsychiatric and behavioral disorders. Some studies showed that chrysin has antioxidant and anti-inflammatory properties. However, your bioavailability is relatively low. Therefore, the present study was designed to investigate the effects of chrysin loaded lipid-core nanocapsules (LNCs) on neurochemical and behavioral changes in a model of AD induced by β-amyloid1-42 (Aβ1−42) peptide in aged female mice. For this purpose, aged female mice received free chrysin (FC) (5 mg/kg, per oral, p.o.) or chrysin loaded LNCs (C1-LNC and C5-LNC) (1 or 5 mg/kg, p.o.) for 14 days after Aβ1-42 administration (400 pmol, i.c.v.). Aβ1-42 induced significant impairments on memory and learning (morris water maze task, object recognition and step-down-type passive avoidance), also caused oxidative stress, reduced the levels of brain-derived neurotrophic factor (BDNF), increased neuroinflammation in prefrontal cortex and hippocampus of aged animals. Thus, C1-LNC and C5-LNC displayed significant effect against Aβ₁−₄2, via attenuation of oxidative stress and neuroinflammation, modulation of neurochemical and behavioral changes in a model of AD. These results point to chrysin loaded LNCs (mainly C5-LNC) can be a promising biomedical tool and a new therapeutic approach for treatment and prevention of AD.
Alzheimer's disease (AD) is a progressive neurodegenerative disease and the most common form of dementia, representing about 60-70% of cases. Curcumin is a natural compound extracted from Curcuma longa Linn, widely used in cooking, presenting several biological activities, including neuroprotection. However, it has low solubility and consequently its bioavailability is limited. In recent years, researchers have focused their attention on delivery systems based on nanotechnology because of their promising potential and advantages over conventional approaches. This study investigated the neuroprotective effects of curcumin loaded lipid-core nanocapsules (LNC) in a model of Alzheimer's disease (AD) induced by intracerebroventricular injections of β-amyloid1-42 (Aβ1-42) peptide in aged female mice, and compared these effects with those from free curcumin. Aged female mice received curcumin, free (50 mg/kg, p.o.) or loaded nanocapsules (10 or 1 mg/kg, p.o.) for 14 days after Aβ1-42 administration. Aβ1-42 induced significant cognitive deficit (Morris Water Maze test), as well as caused increased the levels of inflammatory cytokines in prefrontal cortex, hippocampus and serum of mice. LNC displayed significant neuroprotection against Aβ1-42-induced behavioral and neurochemical changes in a model of AD. These results provide insights into the neuroprotective actions of curcumin and its nanoencapsulation as a promising approach for application as an neuroprotective agent in the prevention of AD.
An increasing body of evidence indicates that the activation of indoleamine-2,3-dyoxigenase (IDO), a first and rate-limiting enzyme in the kynurenine (KYN) pathway, is involved in Aβ1-42-neurotoxicity and AD pathogenesis. We have reported for the first time that brain IDO activation is related to Aβ1-42 exposure in young mice. Because aging is characterized by a brain dyshomeostasis and because it remains the most dominant risk factor for AD, the purpose of this study was to determine whether aging is associated with a higher sensitivity to behavioural and neurochemical alterations elicited by an intracerebroventricular (i.c.v.) injection of Aβ1-42 (400 pmol/mice), and whether KYN pathway is involved in these effects. We confirmed that aged mice displayed higher cognitive deficit in the object recognition test and higher anxiety-like behaviour in the elevated plus-maze and open field tests after the Aβ1-42 administration. Aged mice also responded to Aβ1-42 with a higher deficiency of brain-derived neurotrophic factor, glutathione levels and total radical-trapping antioxidant capacity, a higher IDO activity, and a higher KYN and KYN/tryptophan ratio in the prefrontal cortex and hippocampus. These effects of Aβ1-42 were associated with a higher proinflammatory status, as measured by higher levels of interleukin-6, lower levels of interleukin-10 and higher expression of glial fibrillary acidic protein (GFAP) and allograft inflammatory factor 1 (Iba1) in the brain of aged mice. These results represent primary evidence suggesting that age-associated inflammatory signature and down-regulation of neuroprotectants in the brain render aged mice more vulnerable to Aβ1-42-induced memory loss, anxiety symptoms and KYN pathway dysregulation.
We investigated the neuropharmacological effects of the methanolic extract from Lactuca capensis Thunb. leaves (100 and 200 mg/kg) for 21 days on memory impairment in an Alzheimer's disease (AD) rat model produced by direct intraventricular delivery of amyloid-β1-42 (Aβ1-42). Behavioural assays such as Y-maze and radial arm maze test were used for assessing memory performance. Aβ1-42 decreased cognitive performance in the behavioural tests which were ameliorated by pre-treatment with the methanolic extract. Acetylcholinesterase activity and oxidant–antioxidant balance in the rat hippocampus were abnormally altered by Aβ1-42 treatment while these deficits were recovered by pre-treatment with the methanolic extract. In addition, rats were given Aβ1-42 exhibited in the hippocampus decreased brain-derived neurotrophic factor (BDNF) mRNA copy number and increased IL-1β mRNA copy number which was reversed by the methanolic extract administration. These findings suggest that the methanolic extract could be a potent neuropharmacological agent against dementia via modulating cholinergic activity, increasing of BDNF levels and promoting antioxidant action in the rat hippocampus.
Anaesthetic properties and potential genotoxicity of six essential oils extracted from the medicinal plants Origanum vulgare, Eugenia aromatica, Aloysia triphylla, Melaleuca alternifolia, Juniperus communis, Cinnamomum zeylanicum, are presently assessed in gilthead seabream. Essential oils are an alternative option for fish anaesthesia, which is necessary in order to ensure welfare under intensively reared conditions. Their anaesthetic efficacy was assessed in comparison with chemical agents, by monitoring fish behavior throughout the anaesthesia and recovery stages, while the post-treatment mortality rate was also recorded. Genotoxicity was evaluated using the single cell gel comet assay in vitro and in vivo. DNA migration (tail moment) and the percentage of cells with increased level of DNA damage in hepatocytes were assessed. All essential oils proved to qualify as anaesthetic agents achieving deep narcosis and behavioural recovery. Essential oils indicated higher efficiency compared to chemicals, mitigating the side-effects that are often associated with synthetic substances. E. aromatic, O. vulgare and A. triphylla induced genotoxic effects at applied doses. However, as genotoxicity is dose dependent and most essential oils usually devoid of long-term genotoxic risk, lower anaesthetic doses have to be tested in order to be proposed for commercial use in aquaculture species. M. alternifolia and J. communis did not induced genotoxicity, maintaining DNA damage at control group level. Finally, C. zeylanicum was evaluated as equal competent anaesthetic agent satisfying the criteria of the ideal anaesthetic, reducing DNA strand breakage and indicating anti-stress, anti-genotoxic and geno-protective effect.
Alzheimer’s disease (AD) is a neurodegenerative disorder that is characterized by a progressive cognitive decline along with various neuropsychiatric symptoms, including depression and anxiety. Increasing evidence has been proposed the activation of the tryptophan-degrading indoleamine-2,3-dyoxigenase (IDO), the rate-limiting enzyme of kynurerine pathway (KP), as a pathogenic factor of amyloid-beta (Aβ)-related inflammation in AD. In the current study, the effects of an intracerebroventricular (i.c.v.) injection of Aβ1-42 peptide (400 pmol/mice; 3μl/site) on the regulation of KP biomarkers (IDO activity, tryptophan and kynurerine levels) and the impact of Aβ1-42 on neurotrophic factors levels were investigated as potential mechanisms linking neuroinflammation to cognitive/emotional disturbances in mice. Our results demonstrated that Aβ1-42 induced memory impairment in the object recognition test. Aβ1-42 also induced emotional alterations, such as depressive and anxiety-like behaviors, as evaluated in the tail suspension and elevated-plus maze tests, respectively. We observed an increase in levels of proinflammatory cytokines in the Aβ1-42-treated mice, which led to an increase in IDO activity in the prefrontal cortex (PFC) and the hippocampus (HC). The IDO activation subsequently increased kynurerine production and the kynurenine/tryptophan ratio and decreased the levels of neurotrophic factors in the PFC and HC, which contributed to Aβ-associated behavioral disturbances. The inhibition of IDO activation by IDO inhibitor 1-methyltryptophan (1-MT), prevented the development of behavioral and neurochemical alterations. These data demonstrate that brain IDO activation plays a key role in mediating the memory and emotional disturbances in an experimental model based on Aβ-induced neuroinflammation.
Juniper volatile oil is extracted from Juniperus communis L., of the Cupressaceae family, also known as common juniper. The therapeutic properties of juniper oil are antiseptic, antirheumatic, antispasmodic, astringent, carminative, depurative, diuretic, rubefacient, stimulating, stomachic, sudorific and tonic. In traditional medicine, juniper oil was used to relieve anxiety, nervous tension and mental exhaustion. In the present study, the effects of inhaled juniper volatile oil (1% and 3%, daily, for 21 days) extracted from J. communis L. on spatial memory performance were assessed in an Aβ(1-42) rat model of Alzheimer's disease. The Aβ(1-42)-treated rats exhibited the following: decrease of spontaneous alternations percentage within Y-maze task and increase of working memory and reference memory errors within radial arm maze task. Exposure to juniper volatile oil significantly improved these parameters, suggesting positive effects on spatial memory formation. Therefore, juniper volatile oil could be a potential candidate for further preclinical study aimed at the treatment of cognitive deficits in Alzheimer's disease.
As a kind of medicine which can also be used as food, Alpinia oxyphylla Miq. has a long clinical history in China. A variety of studies demonstrated the significant neuroprotective activity effects of chloroform (CF) extract from the fruits of Alpinia oxyphylla. In order to further elucidate the possible mechanisms of CF extract which mainly contains sesquiterpenes with neuroprotection on the cognitive ability, mice were injected with Aβ 1-42 and later with CF in this study. The results showed that the long-term treatment of CF enhanced the cognitive performances in behavior tests, increased activities of glutathione peroxidase (GSH-px) and decreased the level of malondialdehyde (MDA), acetylcholinesterase (AChE), and amyloid-β (Aβ), and reversed the activation of microglia, degeneration of neuronal acidophilia, and nuclear condensation in the cortex and hippocampus. These results demonstrate that CF ameliorates learning and memory deficits by attenuating oxidative stress and regulating the activation of microglia and degeneration of neuronal acidophilia to reinforce cholinergic functions.
The present study analyzed the possible anxiolytic, antidepressant and antioxidant proprieties of inhaled coriander volatile oil extracted from Coriandrum sativum var. microcarpum in beta-amyloid (1–42) rat model of Alzheimer's disease. The anxiolytic- and antidepressant-like effects of inhaled coriander volatile oil were studied by means of in vivo (elevated plus-maze and forced swimming tests) approaches. Also, the antioxidant activity in the hippocampus was assessed using catalase specific activity and the total content of the reduced glutathione. The beta-amyloid (1–42)-treated rats exhibited the following: decrease of the locomotor activity, the percentage of the time spent and the number of entries in the open arm within elevated plus-maze test and decrease of swimming and immobility times within forced swimming test. Exposure to coriander volatile oil significantly improved these parameters, suggesting anxiolytic- and antidepressant-like effects. Moreover, coriander volatile oil decreased catalase activity and increased glutathione level in the hippocampus.
Our results suggest that multiple exposures to coriander volatile oil can be useful as a mean to counteract anxiety, depression and oxidative stress in Alzheimer's disease conditions.
For decades, a link between increased levels of iron and areas of Alzheimer's disease (AD) pathology has been recognized, including AD lesions comprised of the peptide β-amyloid (Aβ). Despite many observations of this association, the relationship between Aβ and iron is poorly understood. Using X-ray microspectroscopy, X-ray absorption spectroscopy, electron microscopy and spectrophotometric iron(II) quantification techniques, we examine the interaction between Aβ(1-42) and synthetic iron(III), reminiscent of ferric iron stores in the brain. We report Aβ to be capable of accumulating iron(III) within amyloid aggregates, with this process resulting in Aβ-mediated reduction of iron(III) to a redox-active iron(II) phase. Additionally, we show that the presence of aluminium increases the reductive capacity of Aβ, enabling the redox cycling of the iron. These results demonstrate the ability of Aβ to accumulate iron, offering an explanation for previously observed local increases in iron concentration associated with AD lesions. Furthermore, the ability of iron to form redox-active iron phases from ferric precursors provides an origin both for the redox-active iron previously witnessed in AD tissue, and the increased levels of oxidative stress characteristic of AD. These interactions between Aβ and iron deliver valuable insights into the process of AD progression, which may ultimately provide targets for disease therapies.
Inhibition of Acetylcholinesterase (AChE) is still considered as the main therapeutic strategy against Alzheimer's disease (AD). Many plant derived phytochemicals have shown AChE inhibitory activity in addition to the currently approved drugs for AD. In the present study, methanolic extracts of 20 plants used in Indian Ayurvedic system of medicine for improving cognitive function were screened for acetylcholinesterase inhibitory activity by Ellman's microplate colorimetric method. Out of 20 extracts, Emblica officinalis, Nardostachys jatamansi, Nelumbo nucifera, Punica granatum and Raulfia Serpentina showed IC50 values <100 µg/ml for acetylcholinesterase inhibitory activity. Antioxidant activities of these plants were assessed by DPPH scavenging assay. Among the extracts used, antioxidant activity was highest for Terminalia chebula and Emblica officinalis with IC50 values <10 µg/ml. Considering the complex multifactorial etiology of AD, these plant extracts will be safer and better candidates for the future disease modifying therapies against this devastating disease.
Abstract The underlying mechanisms of Alzheimer's Disease (AD) are still unclear. It's suggested that poly(ADP-ribose) polymerase-1 (PARP-1) overactivation can cause neuroinflammation and cell death. In this study we searched the effects of nicotinamide (NA), endogenous PARP-1 inhibitor, on oxidative stress, apoptosis, and the regulation of PARP-1 and nuclear factor kappa B (NF-κB) in amyloid beta peptide (1-42) (Aβ(1-42)) induced neurodegeneration. Sprague-Dawley rats were divided into four groups as control, Aβ(1-42), Aβ(1-42)+NA(100 and 500 mg/kg). All groups were stereotaxically injected bilaterally into the hippocampus with Aβ(1-42) or saline. After surgery NA administrations were made intraperitoneally (ip) for seven days. In order to investigate the effects of Aβ(1-42) and NA, protein carbonyls, lipid peroxidation, reactive oxygen species (ROS) production, glutathione (GSH) levels, activities of antioxidant enzymes (catalase, superoxide dismutase, glutathione peroxidase), mitochondrial function, mRNA and protein levels of PARP-1, NF-κB, p53, Bax and Bcl-2 were measured in specific brain regions as cortex and hippocampus. Aβ(1-42) treatment only increased the oxidative stress parameters and caused decline in antioxidant enzyme activities, mitochondrial function and GSH levels. Also, overexpression of PARP-1, NF-κB, p53, Bax and the decreased levels of Bcl-2 were observed in Aβ(1-42) treated group. NA treatments against Aβ(1-42) upregulated Bcl-2 and downregulated PARP-1, NF-κB, p53, Bax levels. NA treatments also decreased the oxidative stress parameters and elevated antioxidant enzyme activities, GSH levels and mitochondrial function against Aβ(1-42) treatment. These data suggest that NA may have a therapeutic potential in neurodegenerative processes due to the decreased levels of oxidative stress, apoptosis, and PARP-1 activity.
Coriandrum sativum L., commonly known as coriander and belonging to the Apiaceae family is cultivated throughout the world for its nutritional value. In traditional medicine, coriander is recommended for the relief of pain, anxiety, flatulence, loss of appetite and convulsions. In the present study, the effects of inhaled coriander volatile oil (1% and 3%, daily, for 21days) extracted from Coriandrum sativum var. microcarpum on spatial memory performance were assessed in an Aβ(1-42) rat model of Alzheimer's disease. The Aβ(1-42)-treated rats exhibited the following: decrease of spontaneous alternations percentage within Y-maze task and increase of working memory errors, reference memory errors and time taken to consume all five baits within radial arm maze task. Exposure to coriander volatile oil significantly improved these parameters, suggesting positive effects on spatial memory formation. Assessments of oxidative stress markers in the hippocampal tissue of Aβ(1-42)-treated rats showed a significant increase of superoxide dismutase (SOD), lactate dehydrogenase (LDH) and a decrease of glutathione peroxidase (GPX) specific activities along with an elevation of malondialdehyde (MDA) level. Coriander volatile oil significantly decreased SOD and LDH specific activities, increased GPX specific activity and attenuated the increased MDA level. Also, DNA cleavage patterns were absent in the coriander rats, thus suggesting antiapoptotic activity of the volatile oil. Therefore, our results suggest that exposure to coriander volatile oil ameliorates Aβ(1-42)-induced spatial memory impairment by attenuation of the oxidative stress in the rat hippocampus.
In order to examine antioxidant properties of methanol extracts of cones and needles of the unexplored Juniperus sibirica Burgsdorf. (Cupressaceae) species, various assays which measure free radical scavenging ability were carried out: DPPH, hydroxyl, superoxide anion and nitric oxide radical scavenger capacity test and reducing power (FRAP) assay. In all of the tests the extracts showed a potent antioxidant effect compared with BHT, a well-known synthetic antioxidant. In addition, the anti-inflammatory activity considering inhibitory potency toward COX-1 and 12-LOX was observed. Both extracts showed markedly anti-inflammatory activity, with needles having somewhat higher potency concerning both assays, reaching IC50 at 1.29 mg/mL towards COX-1 and IC50 at 1.34 mg/mL towards 12-LOX. Besides, in the extracts examined the total phenolic and flavonoid amounts were also determined, together with presence and content of the selected flavonoids: luteolin-7-O-glucoside, apigenin-7-O-glucoside, luteolin, apigenin, rutin and quercetin, which were studied using LC–MS/MS technique. LC–MS/MS analysis showed a noticeable content of natural products according to which the examined J. sibirica Burgsdorf. species could well be regarded as a promising new source of bioactive natural compounds, which can be used both as a food supplement and a remedy.
The commercial essential oils of Citrus aurantium L., Cupressus sempervirens L., Eucalyptus globulus Labill., Foeniculum vulgare Mill. and Thymus vulgaris L., isolated by steam distillation by a company of Morocco were evaluated in terms of in vitro antioxidant activity through several methods. In vitro acetylcholinesterase inhibitory activity was also determined. Citrus limon (L.) Burm. f. oil was also studied, but it was obtained by peel expression. The best antioxidant was T. vulgaris oil, independent of the method used, mainly due to the presence of the phenolic monoterpenes thymol and carvacrol, which when studied as single compounds also presented the best activities. Concerning the acetylcholinesterase inhibition activity, E. globulus was the most effective. Nevertheless its main components 1,8-cineole and limonene were not the most active, a feature that corresponded to δ-3-carene.
Protein carbonyl content is widely used as both a marker for oxidative stress and a measure of oxidative damage. Widely used methods for determination of protein carbonylation utilize the reaction of carbonyl groups with 2,4-dinitrophenylhydrazine (DNPH) to form protein-bound 2,4-dinitrophenylhydrazones. Hydrazones can be quantitated spectrophotometrically or, for greater sensitivity, detected immunochemically with anti-dinitrophenyl antibodies. Attention to methodology is important to avoid artifactual elevation in protein carbonyl measurements. We studied extracts of Escherichia coli to identify and eliminate such effects. Nucleic acid contamination caused serious artifactual increases in the protein carbonyl content determined by spectrophotometric techniques. Both in vitro synthesized DNA oligonucleotides and purified chromosomal DNA reacted strongly with 2,4-DNPH. Treatment of cell extracts with DNase+RNase or with streptomycin sulfate to precipitate nucleic acids dramatically reduced the apparent carbonyl, while exposure to proteinase K did not. The commercial kit for immunochemical detection of protein carbonylation (OxyBlot from Chemicon/Millipore) recommends a high concentration of thiol in the homogenizing buffer. We found this recommendation leads to an artifactual doubling of the protein carbonyl, perhaps due to a thiol-stimulated Fenton reaction. Avoiding oxidizing conditions, removal of nucleic acids, and prompt assay of samples can prevent artifactual effects on protein carbonyl measurements.
We have previously described the oxidative inactivation of several key metabolic enzymes by a variety of mixed function oxidation systems. Because many of the enzymes which are inactivated have been shown by others to accumulate as inactive or less active forms during cellular aging, we have examined the levels of oxidatively modified proteins in two model systems used for studies on aging. The results show that levels of oxidatively modified proteins increase with age in circulating erythrocytes, and this change is correlated with the loss of marker enzyme activity. Our studies also show that in cultured fibroblasts from normal donors the levels of oxidatively modified proteins increase only after the age of 60. However, the levels of oxidatively modified proteins in fibroblasts from individuals with progeria or Werner's syndrome are significantly higher than age-matched controls. Moreover, treatment of glucose-6-phosphate dehydrogenase with a mixed function oxidation system leads to oxidative modification and increased heat lability of the enzyme. Taken together these results suggest that loss of functional enzyme activity and increased heat lability of enzymes during aging may be due in part to oxidative modification by mixed function oxidation systems.
Evidence from postmortem analysis implicates the involvement of microglia in the neurodegenerative process of several degenerative neurological diseases, including Alzheimer's disease and Parkinson's disease. It remains to be determined, however, whether microglial activation plays a role in the initiation stage of disease progression or occurs merely as a response to neuronal death. Activated microglia secrete a variety of proinflammatory and neurotoxic factors that are believed to induce and/or exacerbate neurodegeneration. In this article, we summarize recent advances on the study of the role of microglia based on findings from animal and cell culture models in the pathogenesis of neurodegenerative diseases, with particular emphasis on Parkinson's disease. In addition, we also discuss novel approaches to potential therapeutic strategies.
Increasing evidence suggests that oxidative stress is intimately associated with Alzheimer disease pathophysiology. Nucleic acids (nuclear DNA, mitochondrial DNA, and RNA) are one of the several cellular macromolecules damaged by reactive oxygen species, particularly the hydroxyl radical. Because neurons are irreplaceable and survive as long as the organism does, they need elaborate defense mechanisms to ensure their longevity. In Alzheimer disease, however, an accumulation of nucleic acid oxidation is observed, indicating an increased level of oxidative stress and/or a decreased capacity to repair the nucleic acid damage. In this review, we present data supporting the notion that mitochondrial and metal abnormalities are key sources of oxidative stress in Alzheimer disease. Furthermore, we outline the mechanisms of nucleic acid oxidation and repair. Finally, evidence showing the occurrence of nucleic acid oxidation in Alzheimer disease will be discussed.
The nephrotoxicity of juniper oil (CAS 73049-62-4), a phytomedicine with diuretic resp. aquaretic activity, was evaluated in male Sprague-Dawley rats after oral administration. Two chemically slightly different oil batches were tested for 28 days with 100, 333 or 1000 mg (series 1, batch 1) resp. 100, 300 or 900 mg (series 2, batch 2) juniper oil/kg. Additionally terpinene-4- ol, a compound with postulated aquaretic activity, which can be found in essential juniper oil up to an amount of 10 mg% was tested in a dosage of 400 mg/kg. Neither of the tested substances induced changes in function or morphology of the kidneys at the tested doses, and they were revealed to be nontoxic.
Alzheimer’s disease (AD) a progressive, age-related neurodegenerative disorder that affects memory, cognition, and speech, is present in more than 4 million persons. The number of cases of AD will significantly elevate, because the mean population in the United States is increasing [1]. AD is characterized pathologically by the presence of extracellular senile plaques, intracellular neurofibrillary tangles, and synapse loss. Senile plaques are composed of an amyloid beta-peptide (Aβ) core surrounded by dystrophic neurites.
83 5.1 Introduction Alzheimer's disease (AD) a progressive, age-related neurodegenerative disorder that affects memory, cognition, and speech, is present in more than 4 mil-lion persons. The number of cases of AD will sig-nificantly elevate, because the mean population in the United States is increasing [1]. AD is character-ized pathologically by the presence of extracellular senile plaques, intracellular neurofibrillary tangles, and synapse loss. Senile plaques are composed of an amyloid beta-peptide (Aβ) core surrounded by dystrophic neurites. Amyloid precursor protein (APP) is a transmem-brane glycoprotein of unknown function that is pres-ent in many cells. The protease α-secretase cleaves APP between residues 16 and 17 of Aβ(1-42) to release soluble APP and form a C-terminal fragment of APP. β-secretase proteolytically cleaves APP at the N-terminal side of Aβ(1-42), while γ-secretase cleaves APP on the carboxy-terminus of this sequence. γ-Secretase cleavage takes place at differ-ent residues near the carboxy terminus of Aβ result-ing principally in the 40-mer and 42-mer, Aβ(1-40) and Aβ(1-42), respectively. These two peptides comprise most of the brain-resident peptide. The more toxic of the two peptides, Aβ(1-42), aggre-gates more quickly than Aβ(1-40). Aβ(1-42) plays a central role in the pathogenesis of AD, mostly evi-denced by the observation of mutations in the genes for APP or presenilin-1 and presenilin-2, all of which result in familial AD and increased produc-tion of Aβ(1-42) [2]. We and others have also demonstrated that the AD brain is under extensive oxidative stress as indexed by protein oxidation and lipid peroxidation [3–7]. Moreover, Aβ(1-42) induces protein oxidation and lipid peroxidation both in vitro and in vivo [3–6, 8–11]. Thus, Aβ(1-42), central to the pathogenesis of AD, is likely also to be central to the oxidative stress under which the AD brain exists. We developed a unifying model for the pathogen-esis of AD based on the central role of Aβ(1-42) as a mediator of free radical–induced oxidative stress in AD brain [4, 12–14]. In this model, Aβ(1-42) inserts into the lipid bilayer as a small aggregate resulting in lipid peroxidation and oxidative modifi-cation of proteins [3, 15], both of which are inhibited by vitamin E [16]. In addition, the AD-related peptide Aβ(1-42) causes an influx of Ca 2+ into the neuron, resulting in loss of intracellular Ca 2+ home-ostasis, mitochondrial dysfunction, and ultimately cell death [17, 18]. In this review, the role of Aβ(1-42)-induced lipid peroxidation and protein oxidation in the patho-genesis of AD is discussed. Additionally, we point out the importance of the single methionine of Aβ(1-42) (residue 35 of this 42-mer) to the oxida-tive stress and neurotoxic properties of Aβ(1-42).
Significance:
Alzheimer disease (AD) is an age-related neurodegenerative disease. AD is characterized by progressive cognitive impairment. One of the main histopathological hallmarks of AD brain is the presence of senile plaques (SPs) and another is elevated oxidative stress. The main component of SPs is amyloid beta-peptide (Aβ) that is derived from the proteolytic cleavage of amyloid precursor protein.
Recent advances:
Recent studies are consistent with the notion that methionine present at 35 position of Aβ is critical to Aβ-induced oxidative stress and neurotoxicity. Further, we also discuss the signatures of oxidatively modified brain proteins, identified using redox proteomics approaches, during the progression of AD.
Critical issues:
The exact relationships of the specifically oxidatively modified proteins in AD pathogenesis require additional investigation.
Future directions:
Further studies are needed to address whether the therapies directed toward brain oxidative stress and oxidatively modified key brain proteins might help delay or prevent the progression of AD.
A photometric method for determining acetylcholinesterase activity of tissue extracts, homogenates, cell suspensions, etc., has been described. The enzyme activity is measured by following the increase of yellow color produced from thiocholine when it reacts with dithiobisnitrobenzoate ion. It is based on coupling of these reactions: The latter reaction is rapid and the assay is sensitive (i.e. a 10 μ1 sample of blood is adequate). The use of a recorder has been most helpful, but is not essential. The method has been used to study the enzyme in human erythrocytes and homogenates of rat brain, kidney, lungs, liver and muscle tissue. Kinetic constants determined by this system for erythrocyte eholinesterase are presented. The data obtained with acetylthiocholine as substrate are similar to those with acetylcholine.
Juniperus L. (Cupressaceae) species are mostly spread out in the Northern Hemisphere of the world, and some of them are used as folkloric medicines. The fruits of some species are eaten. Since oxidative stress is one of the reasons for neurodegeneration and is associated with the Alzheimer's disease (AD), the extracts prepared from the fruits of six Juniperus species were screened for their antioxidant activity. Therefore, the extracts were also evaluated against acetylcholinesterase (AChE) and butyrylcholinesterase (BChE), which are chief enzymes in the pathogenesis of AD. In addition, antimicrobial activity was also evaluated.
In the β-carotene-linoleic acid assay, acetone extracts of J. oxycedrus subsp. oxycedrus, J. sabina and J. excelsa, and methanol extracts of J. phoenicea and J. sabina, effectively inhibited oxidation of linoleic acid. The hexane extracts of J. oxycedrus subsp. oxycedrus, J. foetidissima and J. phoenicea showed remarkable inhibitory effect against AChE and BChE.
Because of their high antioxidant activity, J. excelsa, J. oxycedrus subsp. oxycedrus, J. sabina and J. phoenicia might be used in the food industry as preservative agents or extension of the shelf-life of raw and processed foods. Since the hexane extracts of J. oxycedrus subsp. oxycedrus and J. foetidissima demonstrated significant anticholinesterase activity they should be considered as a potential source for anticholinesterase agents.
The present study was designed to define and compare the flavonoid composition and the biological potential of berries methanol extracts of Juniperus communis L. var. communis (Jcc) and Juniperus communis L. var. saxatilis. Pall. (Jcs) from Turkey. Total polyphenols (Folin-Ciocalteau method) were 3-fold higher in Jcc (59.17 +/- 1.65 mg GAE/g extract) than in Jcs (17.64 +/- 0.09 mg GAE/g extract). Flavonoid and biflavonoid content, evaluated by HPLC-DAD-ESI-MS analysis, was higher in Jcc (25947 +/- 0.86 and 4346 +/- 3.95 microg/g extract) than in Jcs (5387 +/- 34.88 and 1944 +/- 26.88 microg/g extract). The HPLC analysis of Jcc allowed the separation of 16 flavonoids; hypolaetin-7-pentoside and quercetin-hexoside are the main compounds. Moreover, gossypetin-hexoside-pentoside and gossypetin-hexoside were identified for the first time in Jcc berries. In Jcs eight flavonoids were identified: quercetin-hexoside and isoscutellarein-8-O-hexoside are the most abundant compounds. The in vitro antioxidant activity was determined using different methods; Jcc was found to be more active than Jcs in the DPPH test (IC(50) of 0.63 +/- 0.09 mg/mL and 1.84 +/- 0.10 mg/mL) in reducing power assay (12.82 +/- 0.10 ASE/mL and 64.14 +/- 1.20 ASE/mL), and in TBA assay (IC(50) of 4.44 +/- 0.70 microg/mL and 120.07 +/- 3.60 microg/mL). By contrast, Jcs exhibited more elevated Fe(2+) chelating ability than Jcc. The extracts were also studied for their antimicrobial potential, displaying antimicrobial capacity only against Gram-positive bacteria.
Accumulated evidence suggests that oxidative stress is involved in amyloid beta (Abeta)-induced cognitive dysfunction. Silibinin (silybin), a flavonoid derived from the herb milk thistle (Silybum marianum), has been shown to have antioxidative properties; however, it remains unclear whether silibinin improves Abeta-induced neurotoxicity. In the present study, we examined the effect of silibinin on the memory impairment and accumulation of oxidative stress induced by Abeta(25-35) in mice.
Aggregated Abeta(25-35) (3 nmol) was intracerebroventricularly administered to mice. Treatment with silibinin (2, 20 and 200 mg.kg(-1), once a day, p.o.) was started immediately after the injection of Abeta(25-35). Locomotor activity was evaluated 6 days after the Abeta(25-35) treatment, and cognitive function was evaluated in a Y-maze and novel object recognition tests 6-11 days after the Abeta(25-35) treatment. The levels of lipid peroxidation (malondialdehyde) and antioxidant (glutathione) in the hippocampus were measured 7 days after the Abeta(25-35) injection.
Silibinin prevented the memory impairment induced by Abeta(25-35) in the Y-maze and novel object recognition tests. Repeated treatment with silibinin attenuated the Abeta(25-35)-induced accumulation of malondialdehyde and depletion of glutathione in the hippocampus.
Silibinin prevents memory impairment and oxidative damage induced by Abeta(25-35) and may be a potential therapeutic agent for Alzheimer's disease.
Juniperus L. (Cupressaceae) species have been used to various inflammatory and infectious diseases such as bronchitis, colds, cough, fungal infections, hemorrhoids, gynecological diseases, and wounds in Turkish folk medicine.
To evaluate this traditional information, anti-inflammatory and antinociceptive activities of the methanolic and aqueous extracts prepared from different parts (stem, fruit and leaves) of the five Turkish taxa under Juniperus section of the gender; J. drupacea, J. communis var. communis, J. communis var. saxatilis, J. oxycedrus subsp. oxycedrus, and J. oxycedrus subsp. macrocarpa growing were investigated.
For the anti-inflammatory activity, carrageenan-induced and PGE(2)-induced hind paw edema models, and for the antinociceptive activity p-benzoquinone-induced writhing and hot plate tests in mice were employed.
The methanolic extracts of fruit and leaves from J. oxycedrus subsp. oxycedrus and J. communis var. saxatilis exhibited notable inhibition in carrageenan-induced edema model at a dose of 100mg/kg. The same extracts also displayed significant activity against PGE(2)-induced edema model. While, the remaining extracts were found inactive against these edema models. A similar activity pattern was observed against p-benzoquinone-induced abdominal constriction test without inducing any gastric damage or apparent acute toxicity, whereas all extracts were inactive in hot plate test.
The experimental data demonstrated that J. oxycedrus subsp. oxycedrus and J. communis var. saxatilis displayed remarkable anti-inflammatory and antinociceptive activities; however, further studies are warranted to define and isolate the active anti-inflammatory and antinociceptive components from these active species which may yield safe and effective agents to be used in the treatment of inflammatory disorders.
Linalool is a monoterpene often found as a major component of essential oils obtained from aromatic plant species, many of which are used in traditional medical systems as hypno-sedatives. Psychopharmacological evaluations of linalool (i.p. and i.c.v.) revealed marked sedative and anticonvulsant central effects in various mouse models. Considering this profile and alleged effects of inhaled lavender essential oil, the purpose of this study was to examine the sedative effects of inhaled linalool in mice. Mice were placed in an inhalation chamber during 60 min, in an atmosphere saturated with 1% or 3% linalool. Immediately after inhalation, animals were evaluated regarding locomotion, barbiturate-induced sleeping time, body temperature and motor coordination (rota-rod test). The 1% and 3% linalool increased (p<0.01) pentobarbital sleeping time and reduced (p<0.01) body temperature. The 3% linalool decreased (p<0.01) locomotion. Motor coordination was not affected. Hence, linalool inhaled for 1h seems to induce sedation without significant impairment in motor abilities, a side effect shared by most psycholeptic drugs.
The reaction of lipid peroxides in animal tissues with thiobarbituric acid was dependent on pH of the reaction mixture as was the case for linoleic acid hydroperoxide. The optimum pH was found to be 3.5. Taking this fact into consideration, a standard procedure for the assay of lipid peroxide level in animal tissues by their reaction with thiobarbituric acid was developed as follows. Ten percent ( tissue homogenate was mixed with sodium dodecyl sulfate, acetate buffer (pH 3.5), and aqueous solution of thiobarbituric acid. After heating at 95°C for 60 min, the red pigment produced was extracted with n-butanol-pyridine mixture and estimated by the absorbance at 532nm. As an external standard, tetramethoxy-propane was used, and lipid peroxide level was expressed in terms of nmol malondialdehyde. Using this method, the liped peroxide level in the liver of rats suffering from carbon tetrachloride intoxication was investigated. The results were in good agreement with previously reported data obtained by measuring diene content.
A method is described for the estimation of red cell superoxide dismutase (erythrocuprein) and a normal range of activity established. It is likely that this enzyme is essential to the red cell for the detoxification of superoxide radicals, and plays a protective role similar to that of the glutathione-glutathione peroxidase system. It is suggested that superoxide dismutase deficiency may be an unrecognized cause of Heinz body hemolytic anemia. The separation of superoxide dismutase from hemoglobin by polyacrylamide gel electrophoresis is also described. Normal superoxide dismutase activity was measured in one case of Wilson's disease.
Red cell superoxide dismutase activity was determined on cord blood samples. The normal range of activity in neonates, measured per gram of haemoglobin, was lower than that obtained for adults, with the mean value for neonates being approximately two-thirds of the adult level. When activity was measured on a per cell basis it was still lower than the adult level. Adult levels are reached at approximately three months postnatal age. No correlation was found between low superoxide dismutase activity and prematurity, low birthweight. Apgar, respiratory distress syndrome, or sex.
A number of systems that generate oxygen free radicals catalyze the oxidative modification of proteins. Such modifications
mark enzymes for degradation by cytosolic neutral alkaline proteases. Protein oxidation contributes to the pool of damaged
enzymes, which increases in size during aging and in various pathological states. The age-related increase in amounts of oxidized
protein may reflect the age-dependent accumulation of unrepaired DNA damage that, in a random manner, affects the concentrations
or activities of numerous factors that govern the rates of protein oxidation and the degradation of oxidized protein.
Bicinchoninic acid, sodium salt, is a stable, water-soluble compound capable of forming an intense purple complex with cuprous ion (Cu1+) in an alkaline environment. This reagent forms the basis of an analytical method capable of monitoring cuprous ion produced in the reaction of protein with alkaline Cu2+ (biuret reaction). The color produced from this reaction is stable and increases in a proportional fashion over a broad range of increasing protein concentrations. When compared to the method of Lowry et al., the results reported here demonstrate a greater tolerance of the bicinchoninate reagent toward such commonly encountered interferences as nonionic detergents and simple buffer salts. The stability of the reagent and resulting chromophore also allows for a simplified, one-step analysis and an enhanced flexibility in protocol selection. This new method maintains the high sensitivity and low protein-to-protein variation associated with the Lowry technique.
A simple colorimetric assay for catalase activity has been described using K2Cr2O7/acetic acid reagent. Kat. f values of different enzyme sources were determined by the colorimetric method and compared with the values obtained by titrimetric methods.
Methanol and dichloromethanol extracts of leaves and stems of Juniperus oxycedrus have been tested for their toxicity, analgesic, antiinflammatory and central effects. Both extracts showed low acute toxicity and decreased spontaneous motility. The methanol extract exhibited an analgesic effect in models of chemical, mechanical and thermal stimulation whereas dichloromethanol extract showed only a significant effect in models of pain induced by chemical stimulation. Both extracts showed a significant antiinflammatory activity and inhibition of the rat paw oedema induced by carrageenin.
It has been more than 10 years since it was first proposed that the neurodegeneration in Alzheimer's disease (AD) may be caused
by deposition of amyloid ??-peptide (A??) in plaques in brain tissue. According to the amyloid hypothesis, accumulation of A??
in the brain is the primary influence driving AD pathogenesis. The rest of the disease process, including formation of neurofibrillary
tangles containing tau protein, is proposed to result from an imbalance between A?? production and A?? clearance.
We have recently shown free radical generation is associated with cognitive impairment in intracerebroventricular (ICV) streptozotocin (STZ) model of sporadic dementia of Alzheimer's type in rats. Trans resveratrol is a polyphenolic compound and is known to have antioxidant activity. In the present study, the effect of trans resveratrol was investigated on ICV STZ induced cognitive impairment and oxidative stress in rats. Adult male Wistar rats were injected with ICV STZ bilaterally, on day 1 and day 3. The learning and memory behavior was assessed using passive avoidance paradigms, elevated plus maze and the closed field activity test while the parameters of oxidative stress assessed were malondialdehyde [MDA] and glutathione. The rats were treated with trans resveratrol chronically at doses of 10 and 20 mg/kg,i.p. for 21 days starting from day 1 of STZ injection. Trans resveratrol treatment significantly prevented ICV STZ induced cognitive impairment. There was a rise in brain glutathione and an insignificant increase in brain MDA in trans resveratrol treated ICV STZ rats as compared to significantly elevated brain MDA levels in the vehicle treated ICV STZ animals. The study demonstrates the effectiveness of trans resveratrol in preventing the cognitive deficits as well as the oxidative stress caused by ICV STZ in rats and it's potential in the treatment of neurodegenerative diseases such as Alzheimer's disease.
We have demonstrated that oxidative stress is involved, at least in part, in beta-amyloid protein (Abeta)-induced neurotoxicity in vivo [Eur. J. Neurosci. 1999;11:83-90; Neuroscience 2003;119:399-419]. However, mechanistic links between oxidative stress and memory loss in response to Abeta remain elusive. In the present study, we examined whether oxidative stress contributes to the memory deficits induced by intracerebroventricular injection of Abeta (1-42) in mice. Abeta (1-42)-induced memory impairments were observed, as measured by the water maze and passive avoidance tests, although these impairments were not found in Abeta (40-1)-treated mice. Treatment with antioxidant alpha-tocopherol significantly prevented memory impairment induced by Abeta (1-42). Increased activities of the cytosolic Cu,Zn-superoxide dismutase (Cu,Zn-SOD) and mitochondrial Mn-superoxide dismutase (Mn-SOD) were observed in the hippocampus and cerebral cortex of Abeta (1-42)-treated animals, as compared with Abeta (40-1)-treated mice. The induction of Cu,Zn-SOD was more pronounced than that of Mn-SOD after Abeta (1-42) insult. However, the concomitant induction of glutathione peroxidase (GPX) in response to significant increases in SOD activity was not seen in animals treated with Abeta (1-42). Furthermore, glutathione reductase (GRX) activity was only increased at 2h after Abeta (1-42) injection. Production of malondialdehyde (lipid peroxidation) and protein carbonyl (protein oxidation) remained elevated at 10 days post-Abeta (1-42), but the antioxidant alpha-tocopherol significantly prevented these oxidative stresses. Therefore, our results suggest that the oxidative stress contributes to the Abeta (1-42)-induced learning and memory deficits in mice.
In this study the antinociceptive and the gastroprotective effects of orally administered or inhaled Lavandula hybrida Reverchon "Grosso" essential oil, and its principal constituents linalool and linalyl acetate were evaluated in rodents. Either when orally administered (100 mg/kg) or inhaled for 60 min lavender essential oil significantly reduced the acetic acid-writhing response in a naloxone-sensitive manner. In the hot plate test, analgesic activity observed after oil inhalation was inhibited by naloxone, atropine, mecamylamine pretreatment suggesting the involvement of opioidergic as well as cholinergic pathways. Regardless of the administration route and the experimental model used both linalool and linalyl acetate did not produce significant analgesic response. Oral or inhalatory treatment with analgesic doses of essential oil did not affect mice spontaneous locomotor activity. Concerning the gastric effects, lavender oil, linalool and linalyl acetate oral administration protected against acute ethanol-induced gastric ulcers but did not prevent indomethacin-induced lesions indicating no interference with arachidonic acid metabolic cascade. In conclusion, besides this gastroprotection, lavender oil reveals an interesting analgesic activity mainly relevant after inhalation, at doses devoid of sedative side effect, suggesting the interest for potential application of this oil in aromatherapy.
Oxidative stress is extensive in Alzheimer disease (AD) brain. Amyloid beta-peptide (1-42) has been shown to induce oxidative stress and neurotoxicity in vitro and in vivo. Genetic mutations that result in increased production of Abeta1-42 from amyloid precursor protein are associated with an early onset and accelerated pathology of AD. Consequently, Abeta1-42 has been proposed to play a central role in the pathogenesis of AD as a mediator of oxidative stress. In this review, we discuss the role of Abeta1-42 in the lipid peroxidation and protein oxidation evident in AD brain and the implications of such oxidative stress for the function of various proteins that we have identified as specifically oxidized in AD brain compared to control, using proteomics methods. Additionally, we discuss the critical role of methionine 35 in the oxidative stress and neurotoxic properties exhibited by Abeta1-42.
Organisms are constantly exposed to various forms of reactive oxygen species (ROS) that lead to oxidation of proteins, nucleic acids, and lipids. Protein oxidation can involve cleavage of the polypeptide chain, modification of amino acid side chains, and conversion of the protein to derivatives that are highly sensitive to proteolytic degradation. Unlike other types of modification (except cysteine oxidation), oxidation of methionine residues to methionine sulfoxide is reversible; thus, cyclic oxidation and reduction of methionine residues leads to consumption of ROS and thereby increases the resistance of proteins to oxidation. The importance of protein oxidation in aging is supported by the observation that levels of oxidized proteins increase with animal age. The age-related accumulation of oxidized proteins may reflect age-related increases in rates of ROS generation, decreases in antioxidant activities, or losses in the capacity to degrade oxidized proteins.
Oxidative stress has been implicated to play a crucial role in the pathogenesis of a number of diseases, including neurodegenerative disorders, cancer, and ischemia, just to name a few. Alzheimer disease (AD) is an age-related neurodegenerative disorder that is recognized as the most common form of dementia. AD is histopathologically characterized by the presence of extracellular amyloid plaques, intracellular neurofibrillary tangles, the presence of oligomers of amyloid beta-peptide (Abeta), and synapse loss. In this review we discuss the role of Abeta in the pathogenesis of AD and also the use of redox proteomics to identify oxidatively modified brain proteins in AD and mild cognitive impairment. In addition, redox proteomics studies in in vivo models of AD centered around human Abeta(1-42) are discussed.
Fuzhisan (FZS), a Chinese herbal complex prescription, has been used in the treatment of Alzheimer's disease (AD) for more than 15 years. Previous studies showed that FZS enhanced the cognitive ability in AD patients and AD model rats. FZS modulated the impaired cellular functions, and attenuated the damage caused by beta-amyloid protein, dose-dependently regulated and ameliorated the cholinergic functions of the Abeta(25-35)-induced AD-model mice. The SPECT imaging revealed that FZS improved the blood flow of the frontal and temporal lobes and the callosal gyrus in AD patients. However, little investigation of the effects of FZS on the naturally aged rats was reported. The underlying mechanism also remains to be explored. Recently we investigated the effects of the aqueous extract of FZS on the cognitive functions of the aged rats and the pharmacological basis for its therapeutic efficacy. The results showed a significant improvement made by FZS (0.3, 0.6, and 1.2 g/kg/d) for impaired cognitive functions of the aged rats. The rats manifested a shortened latency in Morris water maze test after intra-gavage administration (ig) of FZS for 30 consecutive days. The micro-positron emission tomography (microPET) using (18)F-2-fluoro-2-deoxy-D-glucose ((18)F-FDG) as the tracer demonstrated that FZS promoted the glucose metabolism in the whole brains especially the temporal and parietal regions in the aged rats. The spectrophotometry and Western blot showed that FZS obviously increased the activity and the production of choline O-acetyltransferase (ChAT, EC 2.3.1.6) and the acetylcholine (ACh) contents in the hippocampus, thus regulated and ameliorated the impaired cholinergic functions of the aged rats. The therapeutical effects of FZS on the learning and memory of the aged rats were dose-dependent. The mechanism of action of FZS in ameliorating the memory dysfunction of the aged rats is ascribed to the reinforcement of the function of the cholinergic system and the enhancement of the glucose metabolism in the brains. The results of this study, together with a survey of the findings in the clinical treatment with FZS suggest that FZS may not merely alleviate the symptoms of the dementia, but may also augment the production of the neurotransmitter ACh and the energy supply in the brain to build up fitness of the patients. FZS may be beneficial for the treatment of Alzheimer's disease or cognitive impairment in old people.