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POTENTIAL OF NATURAL SUBSTANCE USAGE IN SOUTH EAST ASIA FOR MEMORY ENHANCEMENT: A REVIEW

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Abstract

The use of natural substance-based supplements and treatments for mental wellness is increasingly gaining attention. Southeast Asia, with its rich heritage of medicinal practices and cultural reliance on natural remedies, presents a unique opportunity to explore such interventions. Delightex is actively collaborating with research partners in Southeast Asia to investigate natural substances that may enhance mental well-being and create enriching experiences. Memory, defined as the capacity to record, retain and recall sensory stimuli, events and information, is a fundamental aspect of mental health. Memory loss and Alzheimer’s Disease (AD) are significant and growing concerns worldwide, particularly due to aging populations. Nootropics are generally well tolerated and typically mild. However, occasional complications can still occur. Hence, it is important to explore more natural alternatives for memory enhancement or treatment of memory loss. In this review, following an initial comprehensive literature search on mental well-being, we focused on memory improvement, identified and summarized 57 natural substances from 31 families with potential memory-enhancing effects. This review highlights their traditional use in Southeast Asia and examines the scientific evidence supporting their efficacy in enhancing memory and potential as nootropics alternatives.

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This calls for alternative and complementary approaches aimed at either preventing or reverting AD-related CI in a curative way without causing adverse events. It is estimated that over 80% of the world’s population utilize herbal medicines for basic healthcare as it is considered safe, affordable, and easily accessible as opposed to conventional healthcare. Various parts of P. thonningii are used in traditional medicine to manage various conditions including CI. However, empirical and scientific data to validate these uses is lacking. In this study, the Morris water maze (MWM) experiment was adopted to evaluate the cognitive-enhancing effects of the studied plant extracts. The malondialdehyde (MDA) profiles in the brains of experimental mice were determined using the thiobarbituric acid reactive substances (TBARS) test. Moreover, qualitative phytochemical profiling of the studied plant extracts was performed using standard procedures. The results showed remarkable cognitive-enhancing activities which were reflected in significantly shorter transfer latencies, navigation distances, longer time spent in platform quadrant, and lower MDA levels compared with those recorded for the negative control mice (). Phytochemical screening of the studied plant extracts revealed the presence of antioxidant phytocompounds, which may have played key roles in the extracts’ potency. Based on the findings herein, P. thonningii extracts, especially the aqueous ones have a promising potential for the management of AD-associated CI. Further studies aimed at isolating and characterizing specific active compounds for CI from P. thonningii are recommended. Additionally, specific mode(s) of action of active principles should be elucidated. Moreover, toxicity studies should be done on the studied plant extracts to ascertain their safety. 1. Introduction Cognitive impairment is the overarching phenomenon referring to a continuum of diseases and mental impairments of the brain tissue, which cause abnormalities in learning, memory, and communicative and intellectual abilities of the affected subject. Cognitive impairment is a complex presentation of continuous degeneration of intellectual functions characterized by a plethora of symptoms caused by diseases/disorders affecting the brain [1, 2]. It is estimated that 35.6 million people are affected with AD and associated cognitive deficits, with over half (58%) living in low- and middle-income countries. Annually, 7.7 million new cases are reported and these figures are expected to almost double every 20 years, to 65.7 million in 2030 and 115.4 million in 2050 [3]. Cognitive impairment is one of the major causes of mental disability and dependency among older people and those suffering from AD and other dementias globally. It is not only debilitating to the affected subjects but also to their caregivers and families. There is often a lack of awareness and understanding of cognitive disorders, resulting in stigmatization and barriers to diagnosis, treatment, and management. The impact of cognitive impairment on caregivers, family, and society in general can be physical and psychological [4]. Recent research has shown that oxidative stress, which is the excessive generation of free radicals or their ineffective attenuation, drives cognitive impairment by damaging brain cells [5]. The high concentration of polyunsaturated fatty acids (PUFAs) in the brain increases its vulnerability to free radicals attack, which, in turn, damage brain cells leading to CI [6, 7]. Lipid peroxidation is thought to be a destructive form of oxidative degradation that impairs cell membranes, thereby generating several secondary products including reactive oxygen metabolites (ROMs) that cause neurotoxicity [8]. An increase in the levels of malondialdehyde (MDA), which is one of the ROMs, has been recognized as an important lipid peroxidation indicator and a marker of oxidative stress [9, 10]. Oxidative damage to proteins causes impairment to endogenous enzymes, which play important roles in proper functioning of the neural and glial cells in the brain. Damage to critical enzymes in the brain may lead to the downregulation of energy metabolism, which in turn triggers cell damage. Moreover, protein oxidation in the central nervous system exacerbates hyperphosphorylation of the tau proteins with aggregations of β-amyloids, which are hallmark features in cognitive-impaired brains of AD-affected patients [11, 12]. Even though pharmacotherapies seem to slow cognitive impairment events, the advantages are mostly marginal and unreliable [13]. Conventional medicines prescribed for the management of cognitive impairment are only palliative and do not cure the disease as they only manage the symptoms and improve quality of life without altering the result of the underlying condition [13, 14]. Furthermore, due to the diverse constellation of neuropsychiatric and behavioral symptoms associated with cognitive impairment, there may be potential undesirable side effects of conventional drugs, where improving one symptom worsens another symptom, thus rendering the management of this condition an uphill task. As a result, there is an urgent need for arsenal therapeutic agents for the management of AD-associated CI, and medicinal plants’ phytocompounds are a potential source [12, 15–17]. Plants have been used since antiquity for the management of cognitive deficits [18–20]. Various plant secondary metabolites that are responsible for their biological activities have been identified [21]. Some of them include terpenoids, phenolic compounds (flavonoids, phenolic acids, quinones, coumarins, lignans, stilbenes, and tannins), nitrogen-containing phytocompounds (alkaloids, amines, and betalains), and carotenoids. Phenolics have been demonstrated to possess the widest spectrum of bioactivity by acting as potent antioxidants [16, 21, 22]. The beneficial properties exerted by these bioactive components of medicinal plants include the inhibition of acetylcholinesterase (AChE), modification of Aβ processing, protection against apoptosis, and attenuation of oxidative stress [12, 15, 16]. Therefore, utilization of antioxidants offers a promising potential in the prevention and treatment of AD-associated cognitive deficits as well as other associated neurologic conditions [5, 8, 23]. Various parts of P. thonningii are used in African traditional medicine for the treatment of diverse conditions and diseases. Briefly, P. thonningii is used for the treatment of malaria, leprosy, ulcers, fever, wounds, arthritis, dizziness, coughs, and dementia and memory enhancement among others [24]. Some of the isolated bioactive compounds from P. thonningii include D-3-O-methylchiroinosital which possess antioxidant, analgesic, antidiabetic, antilipidemic, and antipyretic activities. Additionally, C-methyl flavanols, which have anti-inflammatory and antibacterial activities, have been isolated from this plant [25]. Furthermore, other antioxidant compounds with broad spectra of activities like β-amyrin (7) [25], quercetin (11), and quercitrin (12) [26], among many others (1-6, 8-10, and 13-15), have so far been isolated and identified [25]. Therefore, this study was aimed at investigating in vivo cognitive enhancing, ex-vivo MDA profile lowering and qualitative phytochemical composition of the aqueous and methanolic stem bark extracts of P. thonningii in the quest for better, safe, cost-effective, and potent novel drugs for the treatment of AD-associated cognitive deficits. 2. Materials and Methods 2.1. Plant Material and Processing Fresh stem barks of P. thonningii were collected from Cianyi village, Muchomoke sublocation, Gitiburi location, Siakago division, Mbeere North Subcounty in Embu County, Kenya, where the plant grew naturally. This plant was chosen for this study based on its ethnomedical information and use among the locals. The plant was identified primarily by its local name (“Mukuura”) and diseases it treats by the help of a reputable local herbalist. Voucher specimen was prepared, identified, and authenticated (GM001/2017) by a taxonomist at the Department of Plant Sciences, Kenyatta University, and the specimen was deposited for future reference. The collected barks of the plant were then cut into small pieces and spread evenly to dry under shade at room temperature for a period of 14 days. Regular grabbling was done to ensure uniform drying. The dried material was then ground into a coarse powder with the help of an electric plant mill and stored in a well-labeled khaki envelope awaiting extraction. 2.2. Preparation of Methanolic and Aqueous Extracts Approximately 200 grams of the powdered material- of P. thonningii barks were macerated in 750 ml of methanol (AR grade) in 1-liter conical flask, with regular shaking for 48 hours. The methanolic mixture was carefully decanted and filtered through Whatman No. 1 filter paper. The filtrates were concentrated in vacuo with the help of a rotary evaporator set at 50°C, transferred into preweighed, clean, dry, and labeled universal glass bottles. They were then kept in a hot-air oven set at 35°C for 5 days to allow for complete drying. The aqueous extract was obtained by boiling 50 g of powdered P. thonningii bark in distilled water for five minutes. The extracts were then cooled to room temperature, filtered, and transferred into clean freeze-drying flasks. The flasks were then fitted into a freeze dryer for lyophilization for a period of 48 hours. The dry and lyophilized extracts were transferred into clean, dry, preweighed, and labeled universal glass bottles. The actual weights of the extracts were calculated by subtracting the weight of the empty bottle from that of the bottle containing the extract. The percentage yields of respective extracts were calculated using the formula described by Harborne (1976) and modified by Afolayan et al. [25] and Truong et al. [27]. The respective extracts were then sealed and stored in a refrigerator at 4°C awaiting biological and chemical assays. 2.3. Determination of In Vivo Cognitive-Enhancing Effects 2.3.1. Experimental Animals In this study, Swiss-Albino mice (white) aged 4-5 weeks with an average weight of were obtained from the animal breeding house of Kenya Medical Research Institute (KEMRI) Nairobi, Kenya. The mice were kept in standard conditions and housed in polypropylene rectangular cages measuring with soft wood shavings as bedding material. They were randomly selected and housed in groups of 3 males and 2 females in separate home cages, provided with standard laboratory animal food (rodent pellets) and tap water ad libitum. They were maintained at a natural 12-hour-day/12-hour-night cycle in a room maintained at , 360 lux lighting, and 65% humidity. They were acclimatized for 72 hours before experimentation. Humane handling and standard protocols/guidelines for laboratory animal care and use were followed in this study according to the National Research Council [25], after Kenyatta University ethical approval and National Commission for Science, Technology and Innovation authorization (NACOSTI/P/19/2080). 2.3.2. Preparation of Drugs and Administration The methanolic and aqueous stem bark extracts of P. thonningii for administration at dose levels of 200 mg/kg bw, 100 mg/kg bw, and 50 mg/kg bw were prepared freshly each day in normal saline according to the guidelines described by [26]. The positive control (Donepezil) was also prepared at a dose level of 1 mg/kg bw in normal saline using the same guidelines. All the drugs were orally administered (p.o) to respective experimental groups of mice at 0900 hrs during the experimentation period. Hyoscine hydrobromide (scopolamine) was prepared in normal saline at a dose of 1 mg/kg bw in the same manner as for extracts and Donepezil. It was administered intraperitoneally (i.p) during the experiment. 2.3.3. Morris Water Maze Setup The Morris water maze method described by Morris [27–29] was used in this study for determination of in vivo cognitive-enhancing effects of the two medicinal plant extracts. The water maze comprised a white circular tank that formed a pool measuring 110 cm in diameter and 45 cm in height with a featureless inner surface. The circular pool was filled with water, in which 750 g of powdered fat-free milk was mixed, to a height of 30 cm to make the pool opaque. The temperature of the maze was monitored using a calibrated mercury bulb thermometer and maintained at . A white escape platform measuring 10 cm in diameter and 29 cm in height was centered in the northwest (NW) quadrant of the pool. The water level was adjusted to 1 cm below the top surface of the escape platform and later to 1 cm above the escape platform. On the walls of the maze, manila papers of blue, green, pink, and yellow colors were mounted to the west (W), north (N), south (S), and east (E) quadrants, respectively, as local visual cues before introducing the mice. The continuous location of each swimming mouse, from the start position to the top of the platform, was monitored with the help of a digital Sony video camera that was mounted 1.5 meters above the maze linked to Any-Maze tracking software version 6.05 installed in Windows 10 Pro PC [27–29]. 2.3.4. Swim Training In this study, the day prior to the experimentation day was dedicated to training each of the experimental mice to swim for 60 seconds in the presence of the visible escape platform followed by another training session in the absence of the escape platform, with an intertraining break of 20 minutes to allow the mice to rest and recover. This was followed by another training session with the invisible platform in the same manner as the preceding trainings, where each mouse could explore the maze, searching for the hidden platform so as to help it create a spatial map of the surroundings and for proper orientation. The location of the escape platform was in the northwest (NW) quadrant and remained unchanged throughout the training session. The specific starting points were predetermined (the boundaries of each quadrant) as north (N), south (S), east (E), and west (W), respectively, and were changed in every trial and session of experiment. 2.3.5. Acquisition In the acquisition days, the water level in the maze was adjusted to 1 cm above the escape platform, which was centered in the northwest (NW) quadrant to make it invisible at water level. Mice were subjected to three sessions each day for three consecutive days with an intertrial break of 20 minutes. The starting points were predetermined in the same manner as during the training session and were alternated throughout the experiment. During each trial, mice were held and gently placed in the water maze facing the wall away from the escape platform. Each mouse could explore the pool, searching for the hidden escape platform for a maximum period of 60 seconds. Once the mouse located the platform, it could remain on it for 10 seconds for further examination of the surroundings. If the mouse did not locate the platform within 60 seconds, it was gently guided to the platform and allowed to rest there for 15 seconds as it explored the surroundings. It was then gently removed from the pool and placed in a holding cage that contained paper towels to dry. This parameter was averaged for each session of trials and for each experimental mouse. Transfer latency (time taken to search for and locate the hidden platform with 60 s cutoff) and the navigation distance (distance covered during the MWM task) for each experimental mouse were recorded by a digital video recorder. 2.3.6. Probe Trial To assess learning and memory retention, the experimental mice were subjected to a single probe trial on the last day of experimentation (Day 4) by introducing each of them into the maze without the escape platform. This helped assess whether the experimental mice had learnt the task and if they were able to remember the location of the hidden escape platform. They were allowed to explore and search for the escape platform as during the acquisition phase, and the respective times spent in the NW quadrant for each mouse were recorded. 2.3.7. Induction of Cognitive Impairment Cognitive impairment was induced during the last day of experimentation (Day 4) by an intraperitoneal (i.p) injection of 200 μl of hyoscine hydrobromide (scopolamine) at a dose of 1 mg/kg bw to all the experimental mice except for the normal control mice, to which 200 μl of normal saline was administered intraperitoneally. 2.3.8. Experimental Design A controlled randomized, laboratory-based study design was adopted, from which an experimental design was drawn. For each of the studied plant extracts, thirty (30) experimental mice were randomly assigned to six treatment groups each consisting of five mice (3 males and 2 females). The grouping protocol was as presented in Table 1. Treatment groups Treatment I Normal control Normal saline only (10 ml/kg bw; i.p) II Negative control Normal saline+scopolamine (1 mg/kg bw; i.p) III Positive control Donepezil (1 mg/kg bw; p.o)+scopolamine (1 mg/kg bw; i.p) IV Experimental group 1 Extract (50 mg/kg bw; p.o)+scopolamine (1 mg/kg bw; i.p) V Experimental group 2 Extract (100 mg/kg bw; p.o)+scopolamine (1 mg/kg bw; i.p) VI Experimental group 3 Extract (200 mg/kg bw; p.o)+scopolamine (1 mg/kg bw) All the administered drugs were prepared in normal saline (0.9% NaCl). Extract: aqueous/methanolic stem bark extracts of P. thonningii; p.o: oral administration; i.p: intraperitoneal administration.
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Polygala japonica Houtt. (PJ) has been reported have positive effect on the nerves system including depression, but the underlying mechanism is needed to be understood. Here we show that PJ counteracts behavioral effects induced by chronic restraint, a model of depression mimicking exposure to stress, through adult hippocampal neurogenesis (AHN) enhancement. Chronic stress increased the immobility time in the tail suspension test (TST) and forced swim test (FST) and decreased the time in the center of elevated plus maze (EPM) relative to controls. Moreover, chronic stress also induced the cognitive deficit in novel object recognition test, object location test and barnes maze. These behavioral alterations were accompanied by the decreased AHN. Treatment with PJ reversed the behavioral and AHN alterations. We also found that PJ had no significant effect on cell proliferation and neuronal differentiation in dentate gyrus (DG) of the hippocampus, but it inhibited the apoptosis of the newborn neurons by activation of bcl-2 and phopho-erk1/2 and increased the number of the newborn neurons. Our results demonstrate that administration of PJ to chronic stress mice alleviates depression-like behaviors and normalizes the deficit in hippocampal neurogenesis with inhibiting newborn neuron apoptosis.
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In this study, the effects of Nigella Sativa (NS) hydro-alcoholic extract on lipopolysaccharide (LPS)-induced learning and memory impairments, hippocampal cytokine levels, and brain tissues oxidative damage were investigated in rats. The rats were grouped and treated: (1) control (saline), (2) LPS (1 mg/kg i.p.), and (3–5) 100, 200, or 400 mg/kg NS hydro-alcoholic extract 30 min before LPS injection. The treatment was started since 6 days before the behavioral experiments and continued during the behavioral tests (LPS injection 2 h before each behavioral experiment). Finally, the brains were removed for biochemical assessments. In Morris water maze (MWM) test, LPS increased the escape latency and traveled path compared to control group, whereas all doses of NS hydro-alcoholic extract decreased them compared to LPS group. In passive avoidance (PA) test, the latency to enter the dark compartment in LPS group was shorter than control group while in all treated groups it was longer than LPS group. LPS increased tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), malondialdehyde (MDA), and nitric oxide (NO) metabolites, and decreased thiol content, superoxide dismutase (SOD), and catalase (CAT) in the hippocampal tissues compared to control group while NS hydro-alcoholic extract decreased MDA and NO metabolites and increased thiol content, SOD, and CAT compared to LPS group. Findings of the current study indicated that the hydro-alcoholic extract of NS improved the LPS-induced learning and memory impairments induced by LPS in rats by improving hippocampal cytokine levels and brain tissues oxidative damage.
Article
Objective To evaluate the effects of oral rosemary on memory performance, anxiety, depression, and sleep quality in university students. Methods In this double-blinded randomized controlled trial, the 68 participating students randomly received 500 mg rosemary and placebo twice daily for one month. Prospective and retrospective memory performance, depression, anxiety and sleep quality of the students were measured using Prospective and Retrospective Memory Questionnaire, Hospital Anxiety and Depression Scale, and Pittsburgh Sleep Quality Inventory at baseline and after one month. Results The scores of all the scales and subscales except the sleep latency and sleep duration components of Pittsburgh Sleep Quality Inventory were significantly decreased in the rosemary group in comparison with the control group after one month. Conclusions Rosemary as a traditional herb could be used to boost prospective and retrospective memory, reduce anxiety and depression, and improve sleep quality in university students.
Book
This book introduces readers to nearly 600 common weeds. In addition to essential information, each chapter includes photos for a specific type of weed to show its morphology in different growth periods, such as seedling, root, flower, fruit, and mature plant. The book also discusses control measures, including agricultural, chemical, physical, biological, and comprehensive methods. The Volume2 mainly focuses on fern and 216 species of weeds of magnoliids or dicotyledoneae. With the development of society and economics, weeds have become a recurring problem. In particular, the exotic, invasive, and quarantine weeds have spread dramatically and rapidly. On the other hand, many people, even those who are engaged in weed control, do not (or cannot) distinguish between weeds. Thus there is significant demand for illustrations of weed morphologies, as well as information on their control measures. This book offers a valuable, practical guide for all those working in the fields of crop cultivation, plant protection and quarantine management.
Article
Introduction The “nootropic” or simplified as a “smart drug”, is a common term that will tag along with the compound responsible for the enhancement of mental performance. Certain individuals with a history of mental or substance use disorders might be particularly vulnerable to its adverse effects. Methodology A review was conducted aiming to clarify the mechanisms associated of how these drugs increase mental functions including memory, motivation, concentration, and attention; and which kind of individuals are at risk of developing adverse effects when taking these drugs. The literature search was conducted in PubMed data reviewing articles dating between 2015 and 2016. Results – Glutaminergic Signalling, Cholinergic System, Amyloid Precursor Protein and Secondary Messenger may be related to the cognitive enhancement achieved by Nootropics. Others, like insulin and angiotensin receptor may involved too. – Some of them, like Ginkgo biloba, seem to have neuroprotective effects observed in human and animal models, acting as antioxidant and antiapoptotic, also inducing inhibition effects against caspase-3 activation and amyloid-aggregation toward Alzheimer's disease. – Synthetic nootropics, a lab created compound such as piracetam, especially in people with history of drug abuse, may be associated with psychiatric exacerbations of some patients. Conclusions Young adults all over Europe, especially university students, are starting to use nootropic drugs to improve their academic results. Some of them seem to have beneficial effects over mental health but others are sometimes related with sudden and unexplained exacerbations in stable psychiatric patients. It is important to early identify symptoms and to treat them properly.
Article
The objective of the present study was to evaluate the memory enhancing activity of Lawsonia inermis Linn. leaves against scopolamine induced amnesia by elevated plus maze and Y-maze test. The Powdered leaf materials were extracted with 95% ethanol. The dried extract was subjected to phytochemical analysis and free radical scavenging activity. Acute oral toxicity was performed as per OECD guidelines 425. A dose level 200 mg/kg and 400 mg/kg were selected for pharmacological screening. Swiss albino mice of male sex were divided into ten groups of six animals each. Five groups were subjected to evaluation by elevated plus maze and remaining by Y-maze model. Immediately after evaluation, the whole brain of each animal was subjected to determination of acetyl cholinesterase (AChE), malondialdehyde (MDA), glutathione (GSH), catalase (CAT) and superoxide dismutase (SOD) activity. Extract at dose levels of 200 mg/kg and 400 mg/kg showed a significant increase in inflexion ratio in elevated plus maze and increase in percentage alternation in Y-maze model compared to negative control animals in respective models. A significant decrease in brain AChE and MDA with a significant increase in GSH, CAT and SOD levels were noted in animals treated with extract in both models. The preliminary analysis of extract showed the presence of phenolics, tannins, flavonoids and a potent invitro free radical scavenging activity. These findings suggest that, the memory enhancing effect of Lawsonia inermis leaves might be due to enhancement of cholinergic neurotransmission through inhibition of AChE activity and by stabilizing the antioxidant system.