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The effect of D-Limonene on memory and cognitive function in SHRsp rats after stroke. Morris water maze test and novel object recognition test were performed to evaluate memory and cognitive function. The escape latency time (n=8) was presented as (A) an overall value, and at (B) day 2, (C) day 3, (D) day 4 and (E) day 5. (F) Time spent at the target quadrant (n=8). (G) Discrimination-index in the short term memory test (n=8). (H) Discrimination-index in the long term memory test (n=8). * P<0.05, between the groups.
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Stroke is a leading cause of disability and death world-wide and there is currently a lack of effective treatments for acute stroke. D-Limonene is a common natural monocyclic monoterpene possessing various activities. The present study aimed to evaluate the therapeutic efficacy of D-limonene against ischemia-associated cerebral injury in hypertensi...
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... rats after stroke. The function of memory and cogni- tion was evaluated by means of Morris water maze test and novel object recognition test. On the first day, no significant difference was observed in the hidden platform acquisition test among different groups. On the 3-5 days, the escape latency time in SHRsp rats was remarkably longer, compared with the WKY rats ( Fig. 2A-E). Stroke resulted in a significant increase of escape latency time in SHRsp rats ( Fig. 2A-E). The administration of D-Limonene markedly decreased the escape latency time in SHRsp rats after stroke ( Fig. 2A-E). SHRsp rats spent less time in the target quadrant in the probe trial than that in WKY rats (Fig. 2F). Stroke resulted in a significant decrease of time spent in the target quadrant in the probe trial in SHRsp rats (Fig. 2F). The administration of D-Limonene markedly increased the time spent in the target quadrant in the probe trial in SHRsp rats after stroke (Fig. ...
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... rats after stroke. The function of memory and cogni- tion was evaluated by means of Morris water maze test and novel object recognition test. On the first day, no significant difference was observed in the hidden platform acquisition test among different groups. On the 3-5 days, the escape latency time in SHRsp rats was remarkably longer, compared with the WKY rats ( Fig. 2A-E). Stroke resulted in a significant increase of escape latency time in SHRsp rats ( Fig. 2A-E). The administration of D-Limonene markedly decreased the escape latency time in SHRsp rats after stroke ( Fig. 2A-E). SHRsp rats spent less time in the target quadrant in the probe trial than that in WKY rats (Fig. 2F). Stroke resulted in a significant decrease of time spent in the target quadrant in the probe trial in SHRsp rats (Fig. 2F). The administration of D-Limonene markedly increased the time spent in the target quadrant in the probe trial in SHRsp rats after stroke (Fig. ...
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... rats after stroke. The function of memory and cogni- tion was evaluated by means of Morris water maze test and novel object recognition test. On the first day, no significant difference was observed in the hidden platform acquisition test among different groups. On the 3-5 days, the escape latency time in SHRsp rats was remarkably longer, compared with the WKY rats ( Fig. 2A-E). Stroke resulted in a significant increase of escape latency time in SHRsp rats ( Fig. 2A-E). The administration of D-Limonene markedly decreased the escape latency time in SHRsp rats after stroke ( Fig. 2A-E). SHRsp rats spent less time in the target quadrant in the probe trial than that in WKY rats (Fig. 2F). Stroke resulted in a significant decrease of time spent in the target quadrant in the probe trial in SHRsp rats (Fig. 2F). The administration of D-Limonene markedly increased the time spent in the target quadrant in the probe trial in SHRsp rats after stroke (Fig. ...
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... rats after stroke. The function of memory and cogni- tion was evaluated by means of Morris water maze test and novel object recognition test. On the first day, no significant difference was observed in the hidden platform acquisition test among different groups. On the 3-5 days, the escape latency time in SHRsp rats was remarkably longer, compared with the WKY rats ( Fig. 2A-E). Stroke resulted in a significant increase of escape latency time in SHRsp rats ( Fig. 2A-E). The administration of D-Limonene markedly decreased the escape latency time in SHRsp rats after stroke ( Fig. 2A-E). SHRsp rats spent less time in the target quadrant in the probe trial than that in WKY rats (Fig. 2F). Stroke resulted in a significant decrease of time spent in the target quadrant in the probe trial in SHRsp rats (Fig. 2F). The administration of D-Limonene markedly increased the time spent in the target quadrant in the probe trial in SHRsp rats after stroke (Fig. ...
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... rats after stroke. The function of memory and cogni- tion was evaluated by means of Morris water maze test and novel object recognition test. On the first day, no significant difference was observed in the hidden platform acquisition test among different groups. On the 3-5 days, the escape latency time in SHRsp rats was remarkably longer, compared with the WKY rats ( Fig. 2A-E). Stroke resulted in a significant increase of escape latency time in SHRsp rats ( Fig. 2A-E). The administration of D-Limonene markedly decreased the escape latency time in SHRsp rats after stroke ( Fig. 2A-E). SHRsp rats spent less time in the target quadrant in the probe trial than that in WKY rats (Fig. 2F). Stroke resulted in a significant decrease of time spent in the target quadrant in the probe trial in SHRsp rats (Fig. 2F). The administration of D-Limonene markedly increased the time spent in the target quadrant in the probe trial in SHRsp rats after stroke (Fig. ...
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... rats after stroke. The function of memory and cogni- tion was evaluated by means of Morris water maze test and novel object recognition test. On the first day, no significant difference was observed in the hidden platform acquisition test among different groups. On the 3-5 days, the escape latency time in SHRsp rats was remarkably longer, compared with the WKY rats ( Fig. 2A-E). Stroke resulted in a significant increase of escape latency time in SHRsp rats ( Fig. 2A-E). The administration of D-Limonene markedly decreased the escape latency time in SHRsp rats after stroke ( Fig. 2A-E). SHRsp rats spent less time in the target quadrant in the probe trial than that in WKY rats (Fig. 2F). Stroke resulted in a significant decrease of time spent in the target quadrant in the probe trial in SHRsp rats (Fig. 2F). The administration of D-Limonene markedly increased the time spent in the target quadrant in the probe trial in SHRsp rats after stroke (Fig. ...
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... the novel object recognition tests, there was a marked decrease in the capacity to distinguish between familiar objects and novel objects in the SHRsp rats, compared with that in WKY rats (Fig. 2G and H). Stroke resulted in a significant decrease of in the capacity to distinguish between familiar objects and novel objects in the SHRsp rats ( Fig. 2G and H). The administration of D-Limonene markedly increased the capacity to distinguish between familiar objects and novel objects in the SHRsp rats in the short and long term memory tests ( Fig. 2G and ...
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... the novel object recognition tests, there was a marked decrease in the capacity to distinguish between familiar objects and novel objects in the SHRsp rats, compared with that in WKY rats (Fig. 2G and H). Stroke resulted in a significant decrease of in the capacity to distinguish between familiar objects and novel objects in the SHRsp rats ( Fig. 2G and H). The administration of D-Limonene markedly increased the capacity to distinguish between familiar objects and novel objects in the SHRsp rats in the short and long term memory tests ( Fig. 2G and ...
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... the novel object recognition tests, there was a marked decrease in the capacity to distinguish between familiar objects and novel objects in the SHRsp rats, compared with that in WKY rats (Fig. 2G and H). Stroke resulted in a significant decrease of in the capacity to distinguish between familiar objects and novel objects in the SHRsp rats ( Fig. 2G and H). The administration of D-Limonene markedly increased the capacity to distinguish between familiar objects and novel objects in the SHRsp rats in the short and long term memory tests ( Fig. 2G and ...
Citations
... Among plant-derived bioactive compounds, the triterpenoid class of compounds has received enormous attention in recent times. One of the popular triterpenoid compounds, limonene (LMN) has been found to be effective against experimental models of numerous diseases, including neurological disorders such as Alzheimer's disease [16], stroke [17], and cerebral ischemia [18]. LMN exhibits a variety of biological properties, such as antioxidant, anti-inflammatory, anticancer, gastroprotective, neuroprotective [19] properties, and induction of autophagy [20], along with negligible toxicity [21,22]. ...
Rotenone (ROT) is a naturally derived pesticide and a well-known environmental neurotoxin associated with induction of Parkinson’s disease (PD). Limonene (LMN), a naturally occurring monoterpene, is found ubiquitously in citrus fruits and peels. There is enormous interest in finding novel therapeutic agents that can cure or halt the progressive degeneration in PD; therefore, the main aim of this study is to investigate the potential neuroprotective effects of LMN employing a rodent model of PD measuring parameters of oxidative stress, neuro-inflammation, and apoptosis to elucidate the underlying mechanisms. PD in experimental rats was induced by intraperitoneal injection of ROT (2.5 mg/kg) five days a week for a total of 28 days. The rats were treated with LMN (50 mg/kg, orally) along with intraperitoneal injection of ROT (2.5 mg/kg) for the same duration as in ROT-administered rats. ROT injections induced a significant loss of dopaminergic (DA) neurons in the substantia nigra pars compacta (SNpc) and DA striatal fibers following activation of glial cells (astrocytes and microglia). ROT treatment enhanced oxidative stress, altered NF-κB/MAPK signaling and motor dysfunction, and enhanced the levels/expressions of inflammatory mediators and proinflammatory cytokines in the brain. There was a concomitant mitochondrial dysfunction followed by the activation of the Hippo signaling and intrinsic pathway of apoptosis as well as altered mTOR signaling in the brain of ROT-injected rats. Oral treatment with LMN corrected the majority of the biochemical, pathological, and molecular parameters altered following ROT injections. Our study findings demonstrate the efficacy of LMN in providing protection against ROT-induced neurodegeneration.
... A number of studies have been shown that non-complexed D-LIM produces significant effects on the cardiovascular system, including arrhythmia and myocardial infarction [11,[15][16][17][18][19][20]. For instance, Nascimento et al. [16] showed that D-LIM produced intense and persistent bradycardia in rats, associated with transient hypotension. ...
d-limonene (D-LIM) is a monoterpene found mainly in the essential oil of citrus fruits. Cardiovascular effects of D-LIM alone have been extensively demonstrated. Despite possessing important pharmacological effects, its chemical properties prevent its clinical application. This study aimed to produce and characterize hydroxypropyl-β-cyclodextrin (HP-β-CD) inclusion complex with D-LIM, and to assess its cardiovascular effects in animal model of arrhythmia. The inclusion complex was prepared by the slurry complexation, and characterized using HPLC, PXRD, DSC, and ¹H NMR. Molecular docking was performed to analyze the interactions between the complex. The antiarrhythmic effect was assessed in an animal model of arrhythmia induced by Bay K 8644. The physicochemical characterization showed that the D-LIM + HP-β-CD complex formation had a complexation efficiency of 79.96 ± 0.24%, which was corroborated with all analysis performed. Docking showed that D-LIM interacts with HP-β-CD through hydrophobic and van der Waals bonds, with binding affinity of −4.2 kcal/mol. D-LIM + HP-β-CD complex (10 mg/kg, i.v.) significantly reduced arrhythmias, reducing arrhythmia score (p < 0.01), duration of arrhythmias (p < 0.05) and prevented tachycardia (p < 0.05). Our results showed an efficient method of complexation of D-LIM + HP-β-CD and improved its cardiovascular effects compared to D-LIM.
... 36 D-limonene greatly mitigated the decrease in cognitive function, memory and behavior and ischemic injury in SHRsp rats, this may be due to inhibition of brain inflammation, vascular remodeling and antioxidant activities (increased activity of superoxide dismutase and catalase, decreased level of malondialdehyde, increased glutathione content). 98 Zingiber officinale (ginger) has been commonly consumed as a spice and herbal medicine for a long time. 99 Its main components are gingerols such as 6-gingerol, 8-gingerol and 10-gingerol). ...
Memory and learning is negatively affected by many factors. Alzheimer's disease is a progressive and irreversible neurological disorder that occurs gradually, a sickness that is increasingly common, and multiple scientific articles suggest that essential oils improve memory and learning and are useful in the treatment of various neurodegenerative diseases, including Alzheimer's disease. This review aims to conduct a critical collection of current information on research into both memory and learning impairment, as well as essential oils that are able to avoid this neurodegenerative disease. Currently, different animal models have been useful for the study of neurodegenerative problems that alter memory and learning, experimental pharmacological, genetic and toxicological models that can simulate specific cognitive deficit syndromes. In addition, research in this review show several essential oil compounds that present positive results in animal studies, but still lack human clinical trials. Therefore, the assessment of the safety and efficacy of these phytochemical compounds in diseases that cause memory impairment and learning, remain a promising area for future research.
... D-limonene also enhanced the activity of SOD and catalase, increased GSH content and reduced the MDA level, as well as dihydroethidium staining in SHRsp rats after stroke. The blockage of cerebral inflammation and vascular remodeling in addition to the antioxidant potentiality of D-limonene is thought to be responsible for its protective effects against ischemic damage in SHRsp rats [109]. ...
Limonene is a monoterpene confined to the family of Rutaceae, showing several biological properties such as antioxidant, anti-inflammatory, anticancer, antinociceptive and gastroprotective characteristics. Recently, there is notable interest in investigating the pharmacological effects of limonene in various chronic diseases due to its mitigating effect on oxidative stress and inflammation and regulating apoptotic cell death. There are several available studies demonstrating the neuroprotective role of limonene in neurodegenerative diseases, including Alzheimer’s disease, multiple sclerosis, epilepsy, anxiety, and stroke. The high abundance of limonene in nature, its safety profile, and various mechanisms of action make this monoterpene a favorable molecule to be developed as a nutraceutical for preventive purposes and as an alternative agent or adjuvant to modern therapeutic drugs in curbing the onset and progression of neurodegenerative diseases. This manuscript presents a comprehensive review of the available scientific literature discussing the pharmacological activities of limonene or plant products containing limonene which attribute to the protective and therapeutic ability in neurodegenerative disorders. This review has been compiled based on the existing published articles confined to limonene or limonene-containing natural products investigated for their neurotherapeutic or neuroprotective potential. All the articles available in English or the abstract in English were extracted from different databases that offer an access to diverse journals. These databases are PubMed, Scopus, Google Scholar, and Science Direct. Collectively, this review emphasizes the neuroprotective potential of limonene against neurodegenerative and other neuroinflammatory diseases. The available data are indicative of the nutritional use of products containing limonene and the pharmacological actions and mechanisms of limonene and may direct future preclinical and clinical studies for the development of limonene as an alternative or complementary phytomedicine. The pharmacophore can also provide a blueprint for further drug discovery using numerous drug discovery tools.
... Numerous studies indicated that the plant parts like seeds, leaves, stem, flowers and phytochemi are of natural origin promotes health benefits against various diseases in humans especially CNS disorders including brain stroke. The phytochemicals like naringin, Shikonin, curcumin, rutin, ginseng tea, limonene, punicalagin [31][32][33][34][35][36] showed neur due to their antioxidant mechanisms. ...
Aims: The purpose of the present study was targeted to explore the possible role of thymol against global cerebral ischemia-reperfusion injury in albino rats. Study Design: Healthy Albino Wistar rats (200–250 gm) were divided randomly into 5 groups (n=6). Group I and II were considered as normal control and sham control, received 2% tween 80 orally, group III was ischemic- reperfusion (disease control) and received 2% tween 80 orally and Group IV and V received thymol at doses of 50 mg/kg, per oral and 100 mg/kg, per oral. respectively. Place and Duration of Study: Department of Pharmacology, Sri Padmavathi School of pharmacy, Tiruchanur, Tirupati in between Sept 2019 to March 2020. Methodology: Group I and II were considered as normal control and sham control, received 2% tween 80 orally, group III was ischemic- reperfusion (disease control) and received 2% tween 80 orally and Group IV and V received thymol at doses of 50 mg/kg, per oral (p.o) and 100 mg/kg, per oral (p.o). respectively. After pretreatment with thymol for 2 weeks, rats were subjected to bilateral common carotid artery occlusion for 1 hour accompanied by 22 hours reperfusion (I/R). After 22 hrs of reperfusion, motor coordination, hanging wire test, despair swim tests were studied. Antioxidant levels of reduced glutathione (GSH), superoxide dismutase (SOD), catalase (CAT) and pro-oxidant level of Malondialdehyde (MDA) were analyzed in brain tissue homogenate. Changes in cerebral infarct size and histopathology were studied. Results: Pretreated groups of thymol (50 and 100 mg/kg p.o) showed significant improvement in neurobehavioral changes and attenuated oxidative damage as indicated by reduced LPO, restored GSH, SOD and CAT levels and decreased infract size when compared to ischemic reperfusion group. Conclusion: This study suggests that thymol may have a beneficial role against global ischemia reperfusion induced damage caused by excessive free radicals and behavioral alterations in rats.
... Limonene, a common monoterpene found as major component of the active complex of the genus Citrus [15], has been shown to exert anxiolytic, antinociceptive, antioxidant, and anti-inflammatory activity [16][17][18][19][20], as well as to display a protective effect against metabolic syndromes and gastrointestinal and respiratory tract diseases [21,22]. Interestingly, limonene has been suggested to act on the central nervous system, affecting the expression of adenylate cyclase 1 [15], which has been demonstrated to regulate cAMP levels. ...
Many natural-derived compounds, including the essential oils from plants, are investigated to find new potential protective agents in several neurodegenerative disorders such as Alzheimer’s disease (AD). In the present study, we tested the neuroprotective effect of limonene, one of the main components of the genus Citrus, against the neurotoxicity elicited by Aβ1-42 oligomers, currently considered a triggering factor in AD. To this aim, we assessed the acetylcholinesterase activity by Ellman’s colorimetric method, the mitochondrial dehydrogenase activity by MTT assay, the nuclear morphology by Hoechst 33258, the generation of reactive oxygen species (ROS) by DCFH-DA fluorescent dye, and the electrophysiological activity of KV3.4 potassium channel subunits by patch-clamp electrophysiology. Interestingly, the monoterpene limonene showed a specific activity against acetylcholinesterase with an IC50 almost comparable to that of galantamine, used as positive control. Moreover, at the concentration of 10 µg/mL, limonene counteracted the increase of ROS production triggered by Aβ1-42 oligomers, thus preventing the upregulation of KV3.4 activity. This, in turn, prevented cell death in primary cortical neurons, showing an interesting neuroprotective profile against Aβ1-42-induced toxicity. Collectively, the present results showed that the antioxidant properties of the main component of the genus Citrus, limonene, may be useful to prevent neuronal suffering induced by Aβ1-42 oligomers preventing the hyperactivity of KV3.4.
... Conversely, D-lim treatment was able to antagonize these alterations, but the increment in serum activities of SOD and CAT and decrease in serum MDA concentrations were not statistically significant. Our results are in accordance with former studies [21,[24][25][26]59], which indicated the protective effects of D-lim against various oxidative stress conditions, and support the hypothesis that D-lim ameliorates GM-induced oxidative stress. These antioxidative protective effects of D-lim might be associated with its abilities to scavenge ROS [25,60] and/or induce the gene expression of antioxidant enzymes. ...
Clinical application of gentamicin (GM) is well known to be associated with the development of acute kidney injury (AKI). This study was the first to investigate the possible protective effects of D-limonene (D-lim) on AKI following GM administration in rats. 32 rats arranged in four groups (n=8): (1) the control group received saline intraperitoneally (0.5 ml/day) and orally (0.5 ml/day), (2) the D-lim group received D-lim (100 mg/kg) orally and saline (0.5 ml/day) intraperitoneally, (3) the GM group received GM (100 mg/kg/day) intraperitoneally and saline (0.5 ml/day) orally, and (4) the treated group received intraperitoneal GM (100 mg/kg) and oral D-lim (100 mg/kg). All treatments were performed daily for 12 consecutive days. Results revealed that D-lim ameliorated GM-induced AKI, oxidative stress, mitochondrial apoptosis, and inflammation. D-lim showed nephroprotective effects as reflected by the decrease in serum urea and creatinine and improvement of renal histopathological changes. D-lim alleviated GM-induced oxidative stress by increasing the activities of renal catalase, serum and renal glutathione peroxidase, and renal superoxide dismutase and decreasing renal malondialdehyde and serum nitric oxide levels. Intriguingly, D-lim suppressed mitochondrial apoptosis by considerably downregulating Bax and caspase-3 (Casp-3) mRNA and protein expressions and markedly enhancing Bcl2 mRNA and protein expressions. Furthermore, D-lim significantly decreases GM-induced inflammatory response through downregulation of NF-κB, IL-6, and TNF-α mRNA and/or protein expressions and decrease in renal myeloperoxidase activity. Finally, D-lim remarkably downregulated PCNA protein expression in the treated group compared with the GM group. In brief, this study showed that D-lim alleviated AKI following GM administration in rats, partially through its antioxidant, anti-inflammatory, and antiapoptotic activities as well as downregulation of PCNA expression.
... 43) It has also been reported that limonene (+) causes neuronal differentiation, inhibits inflammation associated with AD, and has strong antioxidant properties. [44][45][46] Based on these findings, it is not surprising that limonene (+) has a neuroprotective effect on Aβ42 toxicity. ...
Forest bathing is suggested to have beneficial effects on various aspects of human health. Terpenes, isoprene based-phytochemicals emitted from trees, are largely responsible for these beneficial effects of forest bathing. Although the therapeutic effects of terpenes on various diseases have been revealed, their effects on neuronal health have not yet been studied in detail. Here, we screened 16 terpenes that are the main components of Korean forests using Drosophila Alzheimer’s disease (AD) models to identify which terpenes have neuroprotective effects. Six out of the 16 terpenes, ρ-cymene, limonene (+), limonene (-), linalool, α-pinene (+), and β-pinene (-), partially suppressed the beta amyloid 42 (Aβ42)-induced rough eye phenotype when fed to Aβ42-expressing flies. Among them, limonene (+) restored the decreased survival of flies expressing Aβ42 in neurons during development. Limonene (+) treatment did not affect Aβ42 accumulation and aggregation, but did cause to decrease cell death, reactive oxygen species levels, extracellular signal-regulated kinase phosphorylation, and inflammation in the brains or the eye imaginal discs of Aβ42-expressing flies. This neuroprotective effect of limonene (+) was not associated with autophagic activity. Our results suggest that limonene (+) has a neuroprotective function against the neurotoxicity of Aβ42 and, thus, is a possible therapeutic reagent for AD.
... Another important constituent, linalool, was studied, free and β-cyclodextrin complexed, in both normotensive and hypertensive rats demonstrating antihypertensive effects associated to a direct action on the vascular smooth muscle leading to vasodilation, to increased vasodilator responsiveness and reduced sensitivity to the sympathetic agonist phenylephrine (Anjos et al., 2013;Camargo et al., 2018). For limonene, the blood pressure attenuation was imputed to antioxidant activity, lipid lowering and promotion of vascular remodelling (Santiago et al., 2010;Wang et al., 2018). Direct effect on the vascular smooth muscle leading to vasodilation was suggested for citronellol (Bastos et al., 2009;Ribeiro-Filho et al., 2016), while β-pinene was suggested to induce endothelium-independent vasorelaxation caused by the inhibition of the Ca 2+ influx through L-type Ca 2+ channel associated to a decrease in calcium sensitivity (Moreira et al., 2016). ...
Hypertension has become the leading risk factor for worldwide cardiovascular diseases. Conventional pharmacological treatment, after both dietary and lifestyle changes, is generally proposed. In this review, we present the antihypertensive properties of phytocomplexes from thirteen plants, long ago widely employed in ethnomedicines and, in recent years, increasingly evaluated for their activity in vitro and in vivo, also in humans, in comparison with synthetic drugs acting on the same systems. Here, we focus on the demonstrated or proposed mechanisms of action of such phytocomplexes and of their constituents proven to exert cardiovascular effects. Almost seventy phytochemicals are described and scientifically sound pertinent literature, published up to now, is summarized. The review emphasizes the therapeutic potential of these natural substances in the treatment of the 'high normal blood pressure' or 'stage 1 hypertension', so-named according to the most recent European and U.S. guidelines, and as a supplementation in more advanced stages of hypertension, however needing further validation by clinical trial intensification.
... In a vascular dementia rat model study, Lou et al. [82] reported that β-caryophyllene-hydroxypropyl-β-cyclodextrin inclusion complex could alleviate cognitive deficits by increasing the expression of CB2 in the brain, along with the expression levels of phosphoinositide 3-kinase (PI3K) and protein kinase B (Akt). β-Caryophyllene also acted as agonist for CB2 and PPAR-α receptors in an animal hypoperfusion-reperfusion model of oxidative stress, and modulated activation of the endocannabinoid system and lipoperoxidation as well ▶ ↑Percentage of open arm entries and stay in these arms ↓ Stress-induced damage in CA1 pyramidal neurons [98] Transient cerebral ischemia in stroke-prone spontaneously hypertensive rats ↓ Cerebral infarct size ↓ mRNA expression of IL-1β, MCP-1, and COX-2 ↑ mRNA expression of VEGF in the brain ↑ SOD, CAT ↑ Glutathione ↓ MDA Improvement of behavior [99] Scopolamine-induced dementia Improvement of associative and non-associative memory ↑ Dopamine ↓ AChE activity [100] cont. ...
... Moreover, impairment in cognitive and memory functions following cerebral ischemia was reversed by D-limonene in rats. It decreased the cerebral infarct size following stroke, along with decreasing mRNA expression of IL-1β, monocyte chemoattractant protein-1 (MCP-1), and COX-2, and increasing the activities of antioxidant enzymes in rats following stroke [99]. In another in vivo study, administration of s-limonene attenuated the memory deficits resulting from scopolamine. ...
Neuroprotective agents are able to defend the central nervous system against acute or chronic neuronal injuries. Even with the progress made over the last decades, most of the medications prescribed for the management of neurodegenerative diseases can only reduce their symptoms and slow down their progression. Based on natural product research, there are potential effective medicinal plants and phytochemicals for modulating neuronal functions and protecting against neurodegeneration. Plants in the genus Pistacia are also among valuable natural resources for neuroprotection research based on experiences in traditional medicine. Studies have supported the value of bioactive compounds of the genus Pistacia for central nervous system disorders such as Alzheimerʼs, Parkinsonʼs, multiple sclerosis, cerebral ischemia, depression, and anxiety. Related literature has also revealed that most of the evidence on neuroprotection in the genus Pistacia is in the form of preliminary studies, mainly including models of behavior, motor function, and memory impairments in animals, neural toxicity, cerebral ischemia and seizure models, evaluation of their effects on antioxidant and inflammatory biomarkers, amyloid β aggregation, and acetylcholinesterase as well as investigations into some cellular pathways. Along with the phytonutrients in kernels such as pistachios, various phytochemicals, mostly terpenes, and phenolic compounds have also been identified in different plant parts, in particular their oleoresins, of species in the genus Pistacia. In this review, the pharmacology of neurological effects and related molecular mechanisms of the plants belonging to the genus Pistacia and its active constituents, as well as pharmacokinetics aspects, are discussed.
