Medicinal Plants Used in Management and Treatment of Alzheimer’s Disease in Africa: An Insight into Therapeutic Avenues and Possible Development as Future Phytopharmaceuticals

Alzheimer’s disease (AD) is a devastating neurodegenerative disorder which needs adequate studies on effective treatment options. The extracts of plants and their effect on the amelioration of AD symptoms have been extensively studied. This review summarizes the use of medicinal plants in treatments and management of Alzheimers disesase, its mechanisms and active primary metabolite responsible for its mode of action and possible future development of this plant extracts into phytopharmaceuticals.The medicinal plants used in management of Alzheimers disease in Africa particularly in Nigeria includes: Yizhi Jiannao, Moringa oleifera (Drumstick tree), Cassia obtisufolia (Sicklepod), Desmodium gangeticum (Sal Leaved Desmodium), Melissa offiffiffi cinalis (Lemon Balm), and Salvia offiffiffi cinalis (Garden sage, common sage). Keywords: Alzheimer’s disease, Antiamyloid aggregation, Antioxidants, Acetyl choline esterase inhibitor, Plant extracts. DOI: 10.7176/JNSR/10-10-04 Publication date:May 31st 202

An Investigation of the Efficacy of Curcumin for Treatment of Alzheimer\u27s Disease

Curcumin is the primary curcuminoid found in the rhizome of the turmeric plant (Curcuma longa), responsible for the spice’s distinctive yellow color. Research conducted within the past two decades suggests that the compound may be an effective treatment for Alzheimer’s disease, the most prevalent form of dementia affecting nearly 5.2 million Americans. This paper investigates the efficacy of curcumin as treatment for the pathogenesis and symptoms of Alzheimer’s. Research was conducted pertaining to the pathogenesis of Alzheimer’s, the in vitro applications of curcumin, the chemical properties of curcumin, and the in vivo clinical applications of curcumin. The pathogenesis of Alzheimer’s is defined by the aggregation of amyloid-beta plaques, dissociation of tau protein, propagation of reactive oxygen species, and neuroinflammation. Alzheimer’s is also characterized by symptoms of cognitive decline and memory loss. The physiochemical nature of curcumin enables it to interact with multiple biochemical pathways in the central nervous system (CNS), inhibiting the pathogenesis of the disease. In vitro applications of curcumin show much promise to this end. In vivo studies of curcumin on living subjects provide mixed results for the substance’s efficacy on symptoms and pathogenesis. Furthermore, the complex chemical properties of curcumin make drug development very difficult. Curcumin shows much promise in inhibiting the pathogenesis of Alzheimer’s, according to in vitro studies. However, the lack of definitive conclusions from in vivo applications and difficulty in overcoming curcumin’s complex chemical properties for drug development show that the substance cannot yet be designated as an effective treatment for the disease

Evolution of the adaptogenic concept from traditional use to medical systems: Pharmacology of stress- and aging-related diseases

Adaptogens comprise a category of herbal medicinal and nutritional products promoting adaptability, resilience, and survival of living organisms in stress. The aim of this review was to summarize the growing knowledge about common adaptogenic plants used in various traditional medical systems (TMS) and conventional medicine and to provide a modern rationale for their use in the treatment of stress-induced and aging-related disorders. Adaptogens have pharmacologically pleiotropic effects on the neuroendocrine-immune system, which explain their traditional use for the treatment of a wide range of conditions. They exhibit a biphasic dose-effect response: at low doses they function as mild stress-mimetics, which activate the adaptive stress-response signaling pathways to cope with severe stress. That is in line with their traditional use for preventing premature aging and to maintain good health and vitality. However, the potential of adaptogens remains poorly explored. Treatment of stress and aging-related diseases require novel approaches. Some combinations of adaptogenic plants provide unique effects due to their synergistic interactions in organisms not obtainable by any ingredient independently. Further progress in this field needs to focus on discovering new combinations of adaptogens based on traditional medical concepts. Robust and rigorous approaches including network pharmacology and systems pharmacology could help in analyzing potential synergistic effects and, more broadly, future uses of adaptogens. In conclusion, the evolution of the adaptogenic concept has led back to basics of TMS and a new level of understanding of holistic approach. It provides a rationale for their use in stress-induced and aging-related diseases

Nutrition and Prevention of Alzheimer\u27s Dementia

A nutritional approach to prevent, slow, or halt the progression of disease is a promising strategy that has been widely investigated. Much epidemiologic data suggests that nutritional intake may influence the development and progression of Alzheimer’s dementia (AD). Modifiable, environmental causes of AD include potential metabolic derangements caused by dietary insufficiency and or excess that may be corrected by nutritional supplementation and or dietary modification. Many nutritional supplements contain a myriad of health promoting constituents (anti-oxidants, vitamins, trace minerals, flavonoids, lipids, …etc.) that may have novel mechanisms of action affecting cellular health and regeneration, the aging process itself, or may specifically disrupt pathogenic pathways in the development of AD. Nutritional modifications have the advantage of being cost effective, easy to implement, socially acceptable and generally safe and devoid of significant adverse events in most cases. Many nutritional interventions have been studied and continue to be evaluated in hopes of finding a successful agent, combination of agents, or dietary modifications that can be used for the prevention and or treatment of AD. The current review focuses on several key nutritional compounds and dietary modifications that have been studied in humans, and further discusses the rationale underlying their potential utility for the prevention and treatment of AD

Potential of Ayurvedic Drugs in Differentiating Neuronal Stem Cells from Human Breast Milk: A Review

Recently, Stem cell therapy has revolutionized excellent clinical therapy with the potential of stem cells to differentiate into various cell types and it may help to replace different cell lines of an organism. Frequent, clinical trials are carried out to merge the new scientific stem cell information and techniques with traditional knowledge and plant extracts that may result in less toxic, affordable, and highly available natural alternative therapeutics. Ayurveda, the traditional Indian system of medicine has given great emphasis to the promotion of health. Ayurveda therapies are based on the restoration of body balance and nourishment of dhatus. Rasayana concept of Ayurveda explains tissue regeneration and cell renewal. Rasayana drugs and therapies provide research opportunities for the biology of regeneration. Specific Medhya Rasayana stimulates and nourishes respective Medha (Dhi, Driti, and Smriti) dhatus. Interpretation of this description offers clues for specific differentiation of neuronal stem cells from human breast milk (HBM) in the presence of some herbal extracts. The previous studies suggest that neuronal stem cells differentiate from Human Breast Milk (Human mesenchymal stem cell) more effectively with Madhya Rasayana drugs. The present review highlights the potential of Ayurveda and its possible contributions in regenerative medicine

Donepezil combined with traditional Chinese medicine has promising efficacy on mild cognitive impairment: a systematic review and meta-analysis

ObjectivePrior research has shown mixed results regarding the effectiveness of combining donepezil and traditional Chinese medicine (TCM) to treat mild cognitive impairment (MCI). In light of this, our study aims to examine the efficacy and safety of this treatment approach for patients with MCI.MethodsWe conducted a comprehensive search of various databases, including Medline (via PubMed), Cochrane, Embase, Web of Science, Chinese National Knowledge Infrastructure, Chinese Biomedical Literature Database, Chinese Scientific Journal Database, and Wanfang Database from their inception to November 16, 2022. The selection of studies, risk of bias assessment, and data extraction were carried out independently by two authors. The statistical analysis was performed using STATA.ResultsOur meta-analysis included a total of 35 studies with 2,833 patients, published between 2008 and 2022, with intervention durations ranging from 4 weeks to 12 months. However, most of the studies had a high risk of detection bias. Our findings indicated that the combination of donepezil and TCM significantly improved the Montreal Cognitive Assessment (MoCA) score (weighted mean difference [WMD] = 2.79, 95% confidence interval [CI]: 1.82 to 3.75) and the Barthel Index score (WMD = 9.20, 95% CI: 5.39 to 13.00) compared to donepezil alone. However, subgroup analyses showed that the MoCA score did not increase significantly in patients with MCI resulting from cerebrovascular disease (WMD = 1.47, 95% CI: −0.02 to 2.96).ConclusionThe combination of donepezil and TCM may have a more positive effect on cognitive function and activities of daily living in patients with MCI compared to the use of donepezil alone. However, due to the limited quality of the studies included in our analysis, these findings should be interpreted with caution

Evaluation of the efficacy, safety and tolerability of herbal medicine for management of the behavioural and psychological symptoms of dementia

Dementia involves a gradual loss of memory and cognitive skills. Over 50% of people with dementia also suffer from the behavioural and psychological symptoms of dementia (BPSD). BPSD refer to disturbed perception, thought content and mood associated with dementia, and include psychosis, agitation, aggression, irritability, depression, anxiety and abnormal motor activity. BPSD can have a negative impact on the progression of Alzheimer’s disease and related disorders and are associated with a greater level of caregiver distress. Currently recommended pharmacological treatments for dementia, including acetylcholinesterase inhibitors and memantine, focus on relieving cognitive symptoms, while BPSD are managed according to the presenting symptoms. Guidelines recommend non-pharmacological approaches for BPSD but selective serotonin reuptake inhibitors, analgesics and second generation antipsychotics may be used when other approaches fail. Pharmacological treatments for BPSD have limited benefit and safe prescribing is difficult as some may produce severe adverse effects and may worsen cognitive symptoms. Consequently, there is a pressing need for new approaches to BPSD management. Multiple clinical studies have reported that herbal medicines (HMs), such as Ginkgo biloba leaf extract, can alleviate BPSD as well as improve cognition in dementia. The present project aimed to determine the current state of evidence for HMs and propose future directions for the development of plant-based therapeutics for managing BPSD. Both historical use and contemporary clinical trials provide evidence for the use of herbs for management of memory impairment, cognitive symptoms of dementia and BPSD. Based on these findings, there is potential for identifying effective herbal interventions that could be fast-tracked into clinical use for this unmet need. Identification of useful compounds and their possible mechanisms of action may contribute to development of new therapeutic approaches and/or drug discovery. Notably, the acetylcholinesterase inhibitors galantamine and rivastigmine were discovered from plant-derived compounds. The objectives of this project were to assess the current state of evidence and its limitations regarding the efficacy, safety and tolerability of HMs for BPSD by systematically reviewing and analysing the results of clinical trials and the classical Chinese medicine literature on BPSD; identify any HMs that show potential benefit for BPSD; based on the best available evidence, select a herbal intervention suitable for further clinical investigation; and design a rigorous randomised controlled trial (RCT) to test the intervention that addresses the limitations of previous clinical studies. The comprehensive systematic review and meta-analysis included 31 controlled clinical trials testing 19 different HMs. Meta-analysis of well-designed, placebo-controlled studies indicated that the G. biloba leaf extract EGb 761® was safe and well-tolerated. Significant and clinically meaningful improvements in BPSD and cognition were detected at 24 weeks. However, independently funded studies of G. biloba leaf extract are needed to confirm these findings. Meta-analysis of randomised, comparative effectiveness studies of the Japanese multi-herb formula Yokukansan (Chinese: Yi gan san) showed no significant differences on BPSD outcomes when compared to standard pharmacotherapies used in Japan for BPSD management and superiority to no treatment. However, the only placebo-controlled study of Yokukansan for BPSD did not find any difference in BPSD outcomes at the end of four weeks treatment. Important limitations were identified in this trial which could have resulted in a false negative. These included its short duration, relatively small sample size, large improvement in the placebo group, and the use of a simplified outcome measure which could be less likely to detect changes in symptoms. Overall, the clinical evidence for Yokukansan suggested improvements in BPSD, notably in the clinically important symptoms of irritability/lability and agitation/aggression. An issue identified with Yokukansan was the increased risk of liquorice-induced hypokalaemia, which requires monitoring. Lack of replication and methodological issues in the studies testing other HMs precluded any conclusions for these other interventions. The classical Chinese medical literature was evaluated using the Zhong Hua Yi Dian database, using similar methods to a previous study which evaluated the herbs used for treatment of the cognitive symptoms of dementia. No specific term in the literature corresponded with BPSD, although terms for specific symptoms such as anxiety, depression and agitation were frequently mentioned in conjunction with terms for memory impairment. Some of the HMs described in the classical Chinese medical literature for treatment of memory impairments with mood and behavioural symptoms had also been tested in the clinical trial literature, including Glycyrrhiza uralensis, Poria cocos and Angelica species, which are ingredients of Yokukansan, but the most frequently cited herbs in the classical literature were generally not the same as the frequently tested HMs in clinical trials. The in vitro and in vivo literature showed evidence of relevance to treatment of BPSD for G. biloba, Yokukansan and their constituent compounds. For both these HMs, animal studies have reported anti-aggression-like, antidepressant-like, anxiolytic-like effects as well as benefits on abnormal motor activities and reduction in cognitive impairments and mental stress. Important activities of G. biloba leaf and Yokukansan of relevance to BPSD include modulation of neurotransmission, neuroendocrine regulation and antioxidant effects. The issue of wide variation in placebo effect sizes in BPSD studies was explored through meta-analysis of placebo data. Results showed that placebo effect sizes for BPSD have increased over time. Proposed new studies may therefore require larger sample sizes in order to be adequately powered. Based on the available evidence, it appears that EGb 761® provides small improvements in cognitive symptoms and reduces BPSD while Yokukansan can improve BPSD but not cognition, although it does not appear to have any negative effect on cognition. Both HMs are available commercially, are well characterised and are in widespread use but their combination has not been tested in a clinical trial. Notably, most studies of EGb 761® were conducted in Europe or Russia while Yokukansan was tested in Japan. Therefore, it was proposed that the combination of EGb 761® and Yokukansan at conservative dosages should be tested through an adequately powered, randomised, placebo-controlled clinical trial. A clinical trial protocol was designed which utilised validated diagnostic criteria and assessments relevant to an older population with BPSD, including assessments of caregiver distress associated with BPSD. Issues relating to informed consent from participants and their caregivers were addressed. Safety was an important consideration and was addressed through inclusion and exclusion criteria, careful monitoring of adverse events and strategies to reduce the risk of liquorice-induced hypokalaemia. The results of the RCT would provide useful data on the safety, tolerability and efficacy of this combined intervention in an Australian population with BPSD. The results would assist with clinical decision-making in the management of BPSD