Pharmacological and Neuroprotective Natural Products in the Treatment of Alzheimer's Disease (original) (raw)
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Current vs Emerging Natural Compounds-Based Treatments for Alzheimer’s Disease
2021
Alzheimer’s disease is a progressive and irreversible neurodegenerative disease that affects millions of people globally. Presently, AD is considered a serious health concern, a social and economic burden. There is still no medically accepted cure for AD. Current therapeutics that are marketed for AD treatment only attenuate the symptoms and have several side effects. To avoid the side effects associated with synthetic drugs, natural compounds have gained huge attention in the last 20 years, since they have been part of our common diet and have shown neuroprotective effects. This chapter presents a brief review on the existing medication and ongoing research on natural compounds in clinical trials for AD treatment. However, natural compounds alone have low permeability through the Blood Brain Barrier (BBB) and have low bioavailability. Therefore, a combination of natural compounds with nanocarriers could be a potential therapeutic strategy for AD.
Frontiers in Pharmacology, 2019
Editorial on the Research Topic Natural Products-Based Drugs: Potential Therapeutics Against Alzheimer's Disease and Other Neurological Disorders Alzheimer's disease (AD) and dementia are disorders of the aging population and becoming major health care burden worldwide due to unavailability of complete therapy. AD is the most frequent cause of dementia among 60% to 80% patients and has effected 45 million people globally which is estimated to triple by 2050 (Alzheimer's, 2015). AD is a progressive, neurodegenerative disorder, characterized by behavioral turbulence, cognitive dysfunctions, imperfection in routine life activities, thus putting a huge socioeconomic burden on the health care system (Ahmad et al., 2015; Ali et al., 2017; Ayaz et al., 2017b). Among the pathophysiological hallmarks of the disease are the deficiency of vital neurotransmitter acetylcholine (ACh), deposition of amyloid plaques (Aβ), highly phosphorylated tau proteins, and imbalance in gluatamatergic system (Ayaz et al., 2017a; Khalil et al., 2018; Ovais et al., 2018a). Only five drugs are clinically approved for use, among which tacrine, galantamine, donepezil, and rivastigmine are cholinesterase inhibitors whereas the fifth one memantine is glutamatergic system modulator (Ayaz et al., 2015; Kamal et al., 2015). These drugs have limited efficacy and are associated with side effects like tacrine is hepatotoxic (Watkins et al., 1994). Currently, results from clinical trials performed in mild to moderate AD dementia have directed researchers to find more effective yet safe alternatives from natural sources (Yiannopoulou and Papageorgiou, 2013; Cummings et al., 2014; Ovais et al., 2018b). The plant kingdom consists of a huge number of species with tremendous diversity of bioactive metabolites with different chemical scaffold (Ramawat et al., 2009; Ahmad et al., 2016; Mir et al., 2019). According to reports, only 6% and 15% of medicinal plants have been systematically investigated for pharmacological and phytochemical potentials respectively (Choudhary, 2001). Since, natural products are synthesized by living organisms, they have naturally optimized properties for various biological functions including binding to specific bimolecules or target proteins. Comparison of the structural features of natural and compounds synthetic revealed that the major difference between the two sources originates from starting points which makes synthesis more easy. For instance, separation of chiral compounds is a big challenge, so usually molecules with less number of chiral centers is synthesized and favored (Jan et al., 2019; Hussain et al., 2019). Besides the less number of chiral centers, synthetic molecules have low molecular weight, high chain lengths, less number of Lipinski type H-bond receptors and donors, less oxygen, and more halogen, nitrogen and sulfer.
International Journal of Molecular Sciences
Alzheimer’s Disease (AD) is a neurodegenerative disorder related with the increase of age and it is the main cause of dementia in the world. AD affects cognitive functions, such as memory, with an intensity that leads to several functional losses. The continuous increase of AD incidence demands for an urgent development of effective therapeutic strategies. Despite the extensive research on this disease, only a few drugs able to delay the progression of the disease are currently available. In the last years, several compounds with pharmacological activities isolated from plants, animals and microorganisms, revealed to have beneficial effects for the treatment of AD, targeting different pathological mechanisms. Thus, a wide range of natural compounds may play a relevant role in the prevention of AD and have proven to be efficient in different preclinical and clinical studies. This work aims to review the natural compounds that until this date were described as having significant benef...
Perspectives for treating Alzheimer's disease: a review on promising pharmacological substances
Sao Paulo Medical Journal, 2016
CONTEXT AND OBJECTIVE: Dementia is a syndrome characterized by functional and cognitive decline. Alzheimer's disease (AD) is one of the most common causes of dementia and has high prevalence among the elderly. It is known that there is no drug capable of interfering with the course of the disease. Research on treatments for AD has been marked by the appearance of new drugs and their abandonment. This study aimed to describe drugs that have been studied with regard to treating AD and which are capable of influencing the course of the disease. DESIGN AND SETTING: Narrative review on original articles published worldwide. METHODS: A systematized search was conducted in the PubMed/MEDLINE, Cochrane Library/Cochrane and SciELO/Bireme databases. The descriptors "Molecular Mechanisms of Pharmacological Action" and "Drug Therapy" were each combined with the descriptor "Alzheimer disease". All of these can be found in MeSH and DeCS. These descriptors were us...
Natural Therapeutics for Alzheimer’s Disease
Functional Food and Human Health, 2018
Alzheimer's disease (AD) is a neurodegenerative disease which is serious, persistent and progressive and is linked with deterioration of memory and cognition. Commonly, Alzheimer's is the reason to cause dementia in aged people. The pathogenesis of this disease is linked with the buildup of amyloid beta (Aβ) plaques and neurofibrillary tangles (NFTs) in brain tissues, and also the tau protein gets hyper-phosphorylated in neurons. The generation of reactive oxygen species (ROS) as a result of oxidative stress is regarded as the main cause of AD. The present treatment offers only symptomatic relief which turns down the rate of cognitive destruction related with AD. Inhibition of the enzyme acetylcholinesterase (AChE) is believed as one of the key therapeutic approach contributing only symptomatic relief and modest disease modifying result. None of the drugs currently available could delay or halt the progression of AD. Several compounds showed positive results in preclinical studies but failed in clinical trials as they had limited targeting because of their inability to cross blood-brain barrier (BBB). Several problems exist in the development of new therapeutics. Medicinal plants have been reported for promising anti-AD action in many preclinical and clinical trials. Natural compounds provide various structural characteristics and biological activities and therefore are an attractive source for developing compounds against AD. Advance in extraction and separation method leads to the generation of natural products as potential therapeutics. Various medicinal plants also in their basic structure or as secluded compounds have demonstrated to lessen the pathological characteristics related with AD. In this chapter an effort has been made to focus on natural substances having role in anti-Alzheimer's therapy with their source, mechanism of action and limitations.
Pharmacognostical Sources of Popular Medicine To Treat Alzheimer's Disease
The open medicinal chemistry journal, 2018
A large number of classical and recently discovered plants are indicated in preventing and/or treating Alzheimer's disease (AD). Name of plants with their anti-AD effects are important for their further use and investigation. A short overview of AD is given; anti-Alzheimer plants are given in a Table. Various medicinal plants are listed here as sources of popular medicines to be used in cases when patients are afraid of developing and/or suffer from AD. Some of these plants have been used for centuries. The major sources in the literature, over one hundred of references are given for plants that show beneficial effect on the progress of AD. Plant extracts are widely used addition to the synthetic drugs approved by various administrative authorities to stop/slow down the progress of symptoms of AD.
The Role of Natural Products in Pharmacotherapy of Alzheimer�s Disease
Ethnobotanical Leaflets, 2005
Alzheimer's disease is characterized by forgetfulness, disturbance in memory and loss of mental abilities. The final outcome of the disease is loss of personality and intellectual functions. Alzheimer's disease is common cause of dementia particularly after the age of 70 years. Cholinesterase inhibitors are used for the treatment of Alzheimer's dementia, but due to unpleasant side effect; these groups of drugs can not be used for long term treatment. Phyto drugs are being investigated for possible cure of Alzheimer's disease. A number of constituents like Galanthamine, Huperzine, Hyperforin, & Desoxy-peganine have shown promising result. Some Ayurvedic herbs like Bacopa monneria (Bacosides) have recently gained attention because of memory enhancing activity. The article deals with latest findings in phytotherapy of Alzheimer's disease.
Pathophysiology of Alzheimer Disease: Current Drug Therapy
Alzheimer's disease (AD) is a neurodegenerative age related disease in which patients of age 65 or more suffer from memory impairment problems. This disease is related to the nervous system degradation and various pathophysiological conditions have been identified such as formation of β-amyloid and plaques, nerve degeneration, neurotransmitter depletion, accumulation of toxins, oxidative stress and inflammation. Local RAS system in the brain is different from vascular RAS and play an important role in pathophysiology of AD. RAS system modulates inflammatory processes, neurotransmitter activity and amyloid and plaque formation. Angiotensin II, a vasoconstriction peptide of RAS system also induces neuronal cell loss by the process of cell senescence. Genetic polymorphism is also an important factor for pathophysiology and treatment of AD. No treatment is available which can eradicate AD completely; only prophylactic treatments are available which gives only prophylactic relief. Treatments are given which improve the pathophysiological condition of the disease and restore the brain cells activity. Treatment approach includes prevention of β amyloid and plaque formation, restoration of neurotransmitter system, prevention of oxidative stress and inflammation. Other than allopathic medicines, traditional system of medicines also have number of herbs and plants which have the property of learning and memory improvement via different mechanism of actions.