Neuronutrient impact of Ayurvedic Rasayana therapy
in brain aging Ram Harsh Singh K. Narsimhamurthy Girish Singh Received: 2 April 2008 / Accepted: 26 September 2008 / Published online: 18 October 2008 Springer Science+Business Media B.V. 2008 Abstract Ayurveda is the oldest system of Medi- cine in the world, its antiquity going back to the Vedas. It adapts a unique holistic approach to the entire science of life, health and cure. The areas of special consideration in Ayurveda are geriatrics, rejuvenation, nutrition, immunology, genetics and higher consciousness. The Ayurvedic texts describe a set of rejuvenative measures to impart biological sustenance to the bodily tissues. These remedies are called Rasayana which are claimed to act as micro- nutrients. Some of these Rasayanas are organ and tissue specic. Those specic to brain tissue are called Medhya Rasayana. Such Rasayanas retard brain aging and help in regeneration of neural tissues besides producing antistress, adaptogenic and mem- ory enhancing effect. In addition to the long tradition of textual and experience-based evidence for their efcacy, certain recent studies conducted on these traditional remedies on scientic parameters have shown promising results which have been reviewed in this paper for providing lead for further studies. The popular Medhya Rasayanas are Ashwagandha (Withania somnifera Dunal), Brahmi (Bacopa mon- nieri Linn), Mandukaparni (Centella asiatica Linn) and Sankhapuspi (Convolvulus pluricaulis Chois). Keywords Brain aging Ayurveda Rasayana therapy Neuronutrition Medicinal plants Ayurvedic concept of aging The cause of aging and its exact mechanism is not yet clearly known. However, the process of aging is now known to be controlled largely by genetic, immune and endocrine mechanisms besides many other allied contributing factors with the scope of developing positive interventions. Ayurveda considers aging as the Swabhava or nature of the living being which is considered to be a time-bound entity and it biolog- ically ceases to exist through senescence and death. However, in this school of thought death is limited to physical body only, the subtle energetic body survives death and is claimed to be capable of rebirth. Vagbhatta (300AD) and Sarangdhara (1300AD) describe the time-bound sequential biological human aging in terms of sequential loss of certain biological qualities of life specic to different decades of life as described in the following table (Table 1). If these biolosses are compensated in respective decades by appropriate life-style, nutrition and Ayurvedic R. H. Singh (&) K. Narsimhamurthy Department of Kayachikitsa, Institute of Medical Sciences, Banaras Hindu University, Varanasi 221005, India e-mail: rh_singh2001@yahoo.com G. Singh Department of Community Medicine, Division of Biostatistics, Institute of Medical Sciences, Banaras Hindu University, Varanasi 221005, India 1 3 Biogerontology (2008) 9:369374 DOI 10.1007/s10522-008-9185-z rejuvenative Rasayana remedies described for this purpose, the rate of biological aging may be retarded. Rasayana therapy Since ancient times Ayurveda is practiced through its eight specialized branches namely (1) Kayachikitsa (Internal Medicine), (2) Salya (Surgery), (3) Salakya (Ophthalmology and ENT), (4) Kaumarbhritya (Pedi- atrics), (5) Aagada tantra (Toxicology), (6) Bhuta Vidya (Psychiatry), (7) Rasayana (Rejuvenation) and (8) Bajikarana (Sexology). One of these branches called Rasayana Tantra deals with therapeutic nutri- tion, immuno-enhancing and longevity. The Rasayana remedies of Ayurveda are essentially molecular nutrients and nutrition enhancing agents acting through three basic mechanisms: (1) Rasa enhancing or direct nutrient effect, (2) Agni enhanc- ers or promoters of digestion and metabolism, (3) Srotas purifying agents or promoters of microcircu- lation and tissue perfusion. All these three events singly or jointly lead to improved nutritional status in the body leading further to the formation of the best qualities of cells and tissues which sustain aging and stressLabhopayo hi shastanam rasadinam Rasayanam (Caraka Cikitsa1). All Rasayanas are nutrition- promoters in general but there are certain organ and tissue specic Rasayanas viz., Medhya Rasayana for brain, Hridya Rasayana for heart, Twacya Rasayana for skin, Caksusya Rasayana for eyes and so on. Similarly, Rasayanas could also be age-specic as they promote nutrition relevant to the natural bio-losses occurring at different phases of life span as depicted in Table 1. The following are some Rasayana remedies which can be used to compensate age-related bio-losses. Brain aging Aging is a generalized systemic involution of the living body, its tissues and cells of which the brain is the most vulnerable component because the neurons are known to be poor in their regenerative capacity. Ayurveda propounds that the Medha, the core cognitive function of brain starts depleting by fourth decade of human life and after the eighth decade the loss of Buddhi or decision making intellect becomes inevitable leading to senile dementia as a normal sequence of events in aging process. Thus, consider- ing optimum span of life of man of Ayurvedic times as 100 years the fourth and ninth decades of life are the major time-sets for brain-aging for which Ayurv- eda introduced rejuvenative Rasayana therapy to help fulll the cherished wish of man to live 100 years with functioning brain and sensesJivem saradah satam, Pasyem saradah satam (Riguveda). The contemporary biosciences also register similar views on brain aging considering it an inevitable phenomenon. Aging is fundamentally the outcome of the overwhelming of the evolutionary processes of the body-mind system by the involutionary events hallmarked with degenerative changes like physio- logical disturbances of neurotransmitter secretions, blunting of dendrites and synapses and formation of Beta Amyloid plaques warranting reparative and rehabilitative care. Many elderly persons become dominantly more handicapped due to the age-related degenerative brain disorders than the actual gross Table 1 Sequential bio-losses during aging described by Sarangdhara (1300AD), a medieval text on Ayurveda and some suggested restorative Rasayanas S.No. Decades Age related bio-losses Restorative Rasayanas 1 010 Loss of corpulence Vacha, Gambhari 2 1120 Loss of growth Amalaki, Bala 3 2130 Loss of lusture Haridra, Kumari, Louha 4 3140 Loss of intellect Sankhapuspi,Brahmi 5 4150 Loss of skin glow Kumari, Somaraji 6 5160 Loss of vision Triphala, Jyotismati 7 6170 Loss of virility Kapikacchu, Aswagandha 8 7180 Loss of strength Amalaki, Bala 9 8190 Loss of cognitive power Brahmi, Mandukaparni 10 91100 Loss of locomotive ability Amalaki, Bala, Aswagandha 370 Biogerontology (2008) 9:369374 1 3 somatic aging. Therefore brain aging is a matter of great concern in geriatric health care which has already emerged as a major task in global health care program because of rapid population-aging. Most of the developing countries of the world are already in the grip of high proportion of elderly persons in their population displaying signicant negative impact on socioeconomic and health-care planning of the pres- ent society. Most demographers world over believe that population aging is going to remain the most signicant demographic trend of the 21st Century which will inuence a wide range of public issues of our times (Preston et al. 1989). The following table shows the trend of population aging in major regions of the world. (Table 2). Neuronutrient Medhya Rasayanas Rasayana Tantra, one of the eight specialty branches of Ayurveda was designed in ancient times to take nutritive care, immuno-enhancing and longevity. A large number of herbal and herbomineral Rasayana remedies are in vogue in the hands of Ayurvedic practitioners in India in geriatric care. These remedies in principles are expected to produce their positive health impact through molecular nutritive effect, immuno-enhancing and longevity promotion. The Medhya Rasayanas are a special class of Ayurvedic nutraceuticals which are specic to brain and nervous system. They are claimed to promote cognitive functions of the brain as related to brain aging. There is a bulk of scriptural and experience- based evidence for their efcacy besides a number of recent scientic studies substantiating the ancient claim (Singh 2007). Some such observations are reviewed here under to provide a lead for further studies. Some observations Ashwagandha (Withania somnifera Dunal.) is a pop- ular Indian medicinal plant. Its roots are used as a nervine tonic and adaptogen for centuries. Dwivedi and Singh (1997) studied the effect of this plant drug on mental and physical health of elderly volunteers measuring the impact through a standardized biolog- ical age scale (BAS), brief psychiatric rating scale for mental health (BPRS) and immediate memory span test using ne powder of Ashwagandha roots in the dose of 5 g twice a day for 6 months orally in elderly persons ([60 years). BAS and BPRS contained rated items related to the features of biological aging and mental state, respectively, administered in the form of standardized questionnaires. Singh et al (1987) studied the antistress effect in normal and stressed rats using total alcoholic extract of the dry roots of the Ashwa- gandha in standardized doses and reported signicant activity, being twice more effective than P. gensin in terms of Ed 50. Archana and Namashivayam (1999)studied further the humoral basis of the anti- stress and anti inammatory activities of this drug. Singh and Malaviya (1978) and Bhattacharya et al. (1997) reported anxiolytic activity in the Glycowit- hanolides from Withania somnifera (Tables 35). More recently Kuboyama et al. (2005) reported neuritic regeneration and synaptic reconstruction induced by Withanolide-A isolated from Ashwagan- dha. It was also shown to prevent the formation of Beta Amyloid plaques. Brahmi (Bacopa monnieri Linn.) is another Medhya herbal plant in extensive medicinal use in India as a memory enhancer and brain tonic. Singh and Singh (1978) reported memory enhancing effect in this plant (Table 6) which has been substantiated by many subsequent studies (Singh and Dhawan 1997; Stough et al. 2001). Holcomb et al. (2006) reported that this Table 2 Observed and forecasted percentages of the elderly (65 ? years) in the population (Kinsella and Victoria 2001) Countries/Regions Year 1950 Year 2000 Year 2050 World 5.0 6.9 19.3 China 4.5 6.9 22.7 India 3.3 5.0 14.8 Japan 4.9 17.2 36.4 Europe 8.2 14.7 29.2 USA 8.3 14.7 29.2 Table 3 Effect of Ashwagandha (Withania somnifera) in elderly persons in terms of certain indices of Biological and Mental Aging (BAS and BPRS) after Dwivedi and Singh 1997 Variables Before treatt. Mean S.D After six months treatt. Mean S.D P BAS total score 19.33 4.57 14.95 4.53 \0.01 Immediate memory score 4.55 0.86 4.85 1.00 \0.01 BPRS total score 32.40 5.22 22.93 2.86 \0.01 Biogerontology (2008) 9:369374 371 1 3 drug reduces amyloid levels in PSAPP. This drug has signicant neurotransmittral balancing effect (Singh et al. 1979a, b, c; Pathak and Singh 1986). Mandukaparni (Centella asiatica) was reported to possess anxiolytic and memory enhancing effect by Mishra and Singh (1980) which has been reconrmed by Wigneweera (2006, personal communication). Agrawal and Singh (1998) conducted an open trial of Mandukaparni in cases of educable mental retar- dation indicating signicant improvement in performance IQ, Social Quotient, immediate memory span and reaction time. The psychomotor and cog- nitive functions were measured using (1) Bhatia Battery for performance test of intelligence and memory, (2) Vineland Social Maturity Scale for behavioral and social adaptability (Table 7). The drug was administered in the form of whole plant ne powder in the dose of 2.5 gm twice a day orally for six months. Sankhapuspi (Convolvulus pluricaulis), another Medhya plant is reported to possess anxiolytic and memory enhancing and mood elevating effect and is claimed to retard brain aging (Singh and Mehta 1977; Koirala and Singh 1992; Dhingra et al. 2007). Kapikacchu (Mucuna pruriens) is a Rasayana- Bajikarana plant drug. It is frequently used for the treatment of Parkinsons disease and depressive illness in elderly persons. On Phytochemical studies Mucuna pruriens seeds have been shown to contain signicant quantity of L-Dopa which could be the basis for its anti- Parkinsonism effect. This drug is also used as an aphrodisiac in polpular Ayurvedic practice (Singh 2001, 2003). Comments Brain aging and its manifestations form the most important component of aging process as it may lead Table 4 Showing the humoral basis of the antistress activity of the extracts of Ashwagandha roots in normal and stressed rats (Archana and Namashivayam 1999) Observation Mean SD Normal Control Swimming Stress Swimming Stress ? Ashwagandha Plasma corticosteron mg/dl 98.95 0.51 107.2 0.38 P\0.05 99.77 0.14 P\0.05 Phagocytic index 68.50 0.56 78.0 0.58 P\0.05 68.83 1.20 P\0.05 Total swim time 5.30 0.24 8.90 0.50 P\0.05 Table 5 Antistress effect of the extract of some Rasayana drugs in terms of Ed 50 in almino rats (Singh N et al. 1987) Plant drugs screened Prevention of increase of adrenal wt. Prevention of adrenal ascorbic acid Prevention of increase of adrenal cortisol Prevention of restraint induced ulcer Antistress unit activity as Ed. 50 1. Tulasi (O. sanctum) 12.0 1.6 13.0 1.5 13.4 2.0 15.3 1.2 13.7 1.3 2. Ashwagandha (W. somnifera) 13.0 1.4 14.5 1.5 16.0 1.8 15.9 1.8 14.9 1.5 3. P. gensin 15.0 1.8 24.1 2.1 24.7 2.2 18.0 1.6 25.2 2.3 Table 6 Effect of Brahmi (Bacopa monnieri) on certain mental health indices in human subjects after Singh and Singh 1978 Observations (n = 22) Mean Scores SD P Before Treatt. After Treatt. Immediate memory span 5.94 1.18 6.37 1.17 \0.01 Mental fatigue index 1. Work output/5 M 711.15 270.15 855.85 233.55 \0.01 2. Error score/5 M 7.85 12.65 1.15 2.49 \0.05 372 Biogerontology (2008) 9:369374 1 3 to more crippling impact than gross somatic aging warranting specialized care. The conventional system of Medicine does not offer much in this direction. Ayurveda, the ancient Indian system of Medicine in its Rasayana tantra/Rejuvenation Therapy offers a range of anti-aging remedies in general and specic remedies for brain-aging such as Ashwagandha, Brahmi, Mandukaparni, Sankhapuspi, Kapikacchu and several other such herbal and herbomineral drugs. Besides textual and experience-based evidence for their efcacy now several new scientic studies have been conducted showing interesting results as reviewed in this paper as a lead for further studies. Conceptually it is held that all Rasayana drugs produce their effect by acting through nutrition dynamics (Rasa, Agni, Srotas) at molecular level. They may not possess sharp pharmaceutical activities if used in holistic form and hence as such they may be treated as soft and safe medications which are the popular professional demand in present times. The evidence-base for the efcacy of these med- ications is three-fold viz., (1) Literary and conceptual evidence, (2) Experience-based evidence and long tradition of use and (3) New scientic evidence which is being attempted now to be generated with the help of selected clinical and experimental studies which are obviously not adequate at present but it is worthwhile to project such evidences to provide lead for further studies. References Agrawal SC, Singh RH (1998) Effect of Medhya Rasayana drug, Mandukaparni (Centella asiatica) on cognitive functions and social adaptability in mental retardation. J Res Ayu Siddha 18(34):97107 Archana R, Namashivayam A (1999) Antistress effect of Withania somnifera. J Ethnopharmacol 64:9193 Bhattacharya SK et al (1997) Anxiolytic activity of Glyco- withanolides from Withania somnifera. J Exp Biol 35:236 Choudhary MI et al (2004) Cholinesterase inhibiting Withan- olides from Withania somnifera. Chem Pharm Bull (Tokyo) 52(2):13581361 Dhingra D et al (2007) Evaluation of the antidepressant-like activity in Convolvulus pluricaulis Chois in mouse forced to swim and tail suspension tests. Med Sci Monit 13(7):151165 Dwivedi KK, Singh RH (1997) A study on psychiatric symp- toms of geriatric patients and response of Ayurvedic Rasayana therapy. Ph.D thesis Kayachikitsa, Banaras Hindu University, Varanasi, India Holcomb L et al (2006) Bacopa monnieri extract reduces Amyloid levels in PSAPP mice. J Alzheimers Dis 9(3):251 Kinsella K, Victoria AV (2001) An Aging world: 2001. U.S. Census Bureau Series P 94/011, Washington DC Koirala RR, Singh RH (1992) Clinical and behavioral study of Medhya drugs on brain function. MD thesis Kayachikitsa, Banaras Hindu University, Varanasi, India Kuboyama T et al (2005) Neuritic regeneration and synaptic reconstruction induced by Withanolide-A. Brit J Phar- macol 144(7):961971 Mishra BK, Singh RH (1980) Clinical and Experimental evaluation of Medhya Rasayana effect of Mandukaparni (Centella asiatica) MD thesis, Kayachikitsa, Banaras Hindu University, Varanasi, India Narsimhamurthy K, Singh RH (2005) Mental state examina- tion. Adv Ayurvedic Med 04:1131 Pathak SR, Singh RH (1986) Study on inuence of some plant products on brain function. Ph.D. Thesis (Ayu-Zoology), Banaras Hindu University, Varanasi, India Preston SH, Christine H, Mitchell E (1989) Demographic conditions responsible for population aging. Demography 26:291704 Singh HK, Dhawan BN (1997) Neuropsychopharmacological studies on Brahmi. Ind J Pharmacol 29:53595365 Singh L, Singh RH (1978) Study on psychotropic effect of Brahmi (Bacopa monnieri) M.D. Ay. Thesis, Banaras Hindu University, Varanasi, India Singh N et al. (1987) Study of antistress effect of plant drugs. Ann Natl Acad Ind Med 01(01) Singh RH, Mehta AK (1977) Studies on Psychotropic effect of Medhya Rasayana drug, Sankhapuspi (Convolvulus plu- ricaulis Chois.) Part 13. J Res Ind Med 12:03 Singh RH, Malaviya PC (1978) Studies on the effect of Rasayana drug Aswagandha (Withania somnifera). J Res Ind Med 13/01:1524 Singh RH et al (1979a) Studies on the effect of Aswagandha (Withania somnifera Dunal.) Part-2. J Res Ind Med 14(01):4954 Table 7 Pattern of mental performance in cases of educable mental retardation after treatment with Mandukaparni (Centella asiatica) after Agrawal and Singh 1998 Observations Mean SD Before treatment After treatment P Performance I.Q. 56.395 04.65 60.385 05.931 P\0.05 Immediate memory span 3.00 0.87 3.66 0.88 P\0.01 Social quotient 59.03 14.56 66.20 14.04 P\0.01 Biogerontology (2008) 9:369374 373 1 3 Singh RH, Singh L, Sen SP (1979b) Antianxiety effect of Medhya Rasayana drug Brahni (Bacopa monnieri Linn). J Res Ind Med 14(03):0106 Singh RH, Sinha BN et al (1979c) Comparative biochemical studies on the effect of four Medhya Rasayana drugs on brain in rats. J Res Ind Med 14(03):0714 Singh RH (2001) The holistic principles of ayurvedic medi- cinerejuvenation therapy. Choukhamba Surbharti, New Delhi Singh RH (2003) Psychiatric disorders in ayurveda. In: Mishra LC (ed) Scientic basis of ayurvedic therapies. CRC Press, Boca Raton, pp 439451 Singh RH (2007) Brain Aging and AyurvedaSpecial Refer- ence to Rasayana Therapy. Ann Neurosci 14(Suppl.): 1516 Stough C et al (2001) The chronic effect of Bacopa monnieri (Brahmi) on cognitive functions on healthy human sub- jects. Psychopharmacology 156(4):481484 Sarangdhara (1300AD) Sarangdhara Samhita Part-2/6. Cho- ukhamba, Varanasi Vagbhatta (300 AD) Astanga Hridaya. Choukhamba, Varanasi 374 Biogerontology (2008) 9:369374 1 3
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