Role Of Indian Traditional Medicines For Alzheimer’s Disease Management

<p>Dementia, a common problem in elderly, is rising worldwide including India. Alzheimer&rsquo;s disease is the main aetiology for dementia. Currently anticholinesterases, N-methyl-D-aspartate receptor antagonists, disease modifying agents form the mainstay of treatment of Alzheimer&rsquo;s disease (AD). However, recent breakthroughs in Alzheimer&rsquo;s disease research have given multiple new treatment targets. The newer agents include molecules targeting &tau;-protein like modulators of &tau;-kinases or phosphatases, kinase inhibitors, &tau;-aggregation inhibitors. It also includes molecules, which targets amyloid plaques like inhibitors or modulators of the secretases, amyloid-&beta; aggregation inhibitors and amyloid-plaque degradation enhancers. Role of nootropics, statins and antipsychotics in the management of Alzheimer&rsquo;s disease is limited and lacks conclusive evidence. Studies with vaccines have shown reduced amyloid-&beta; and &tau;- pathology, neutralized soluble amyloid beta oligomers. But search for the appropriate vaccine for Alzheimer&rsquo;s disease is still on. Antioxidants, metal chelators, metal-protein attenuating compounds, metal complexes have also shown some potential. Traditional medicines like huperzine A and galantamine have been used for management of Alzheimer&rsquo;s disease. Traditional medicinal system in India particularly Ayurveda mentions neuroprotective actions of plant drugs like <em>Brahmi</em>, <em>Shankhapushpi</em>, <em>Amla</em>, <em>Guduchi</em>, <em>Tulsi</em>, <em>Ashwagandha </em>and <em>Haritaki</em>, which can help in improving the treatment armamentarium for Alzheimer&rsquo;s disease. The understanding of Alzheimer&rsquo;s disease neurobiology is improving now and the search for better treatment options is still on. This provides an opportunity for more research on integrated approach using existing therapies, traditional and alternative medicines with newer treatments and potential candidates for management of Alzheimer&rsquo;s disease.</p><p>Ancient system of medicine in India, the <em>Ayurveda</em> described various herbal formulations named <em>Medhya Rasayana </em>for the management of neurological disorders including AD. <em>Brahmi </em>(<em>Bacopa monnieri</em>) has been used to improve intelligence and memory and this use is studied clinically. It has also been found to be effective in rat model of AD as a potential cognitive enhancer and neuroprotector. A meta-analysis of RCTs on <em>Brahmi </em>extracts for their cognitive effects showed its potential to improve cognition, particularly speed of attention. However, its role in management of AD is questionable due to lack of clinical evidence. Various Ayurvedic herbs like <em>Amla </em>(<em>Phyllanthus emblica</em>), <em>Guduchi (Tinospora cordifolia</em>), <em>Shankhapushpi </em>(<em>Convolvulus pluricaulis</em>), <em>Ashwagandha </em>(<em>Withania somnifera</em>), <em>Tulsi </em>(<em>Ocimum sanctum</em>), <em>Mandukaparni </em>(<em>Centella asiatica</em>) and <em>Haritaki </em>(<em>Terminalia chebula</em>) have been used in the treatment of memory disorders effectively. In a proof of concept study done by us in rodents, a combination of <em>Phyllanthus </em><em>emblica</em> and <em>Tinospora</em><em> cordifolia</em> with <em>Bhavana Samskara</em> (of <em>Ocimum </em>sanctum) showed better results than modern agents like rivastigmine or piracetam on learning and memory parameters. These drugs are the potential candidates for management of dementia including that of AD though the exact actions of these plants drugs are yet to be explored in clinical studies. <em>Curcumin</em> has been known for ages and used commonly in India as an ingredient of food and cosmetic products. It has antioxidant, anti-inflammatory, and platelet aggregation inhibiting properties. It has also been found to have effect on A&beta; aggregation in AD and currently being investigated in clinical studies. Resveratrol, a polyphenol from various herbs and red wine with neuroprotective actions has been studied as a potential candidate for the management of AD in pre-clinical studies however; its bioavailability appeared to be a limiting factor. Marine-derived drugs like homotaurine, bryostatin, cytarabine, trabectedin, eribulin, and ziconotide have shown beneficial effects in neurodegenerative diseases that included AD. Some of these drugs have entered clinical studies. Currently clinical trials evaluating the role of Bry-1 (bryostatin) and</p><p>homotaurine in management of AD have been in progress</p><p>Integrated approach for management of AD could be helpful considering the limitations of available treatment options. Dietary or nutritional supplements, yoga, meditation, acupuncture have been reported to benefit in such patients and also used as preventive measures for dementia. Household spices such as ginger, turmeric, rosemary, sage, cinnamon, salvia herbs are also known to prevent neurodegeneration with the phytochemicals available in them. However, the exact mechanisms and overall therapeutic benefits are still unclear and thus no evidence based recommendations exists for their use.</p><p><em>Ayurveda</em> have some promising agents to be evaluated in clinical trials for the management of AD. Evidence with alternate therapies is limited and robust clinical data is lacking. Thus, further research is needed to evaluate if integrated approach of combining the existing therapies, traditional medicines and newer treatments can improve the care for patients with AD. Considering the global disease burden, the clinicians need a specific guidance on the management strategies for AD.</p><p>&nbsp;</p>
KR Expert - Harshad Malve

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