Influence of Amalaki Rasayana on telomerase activity and telomere length in human blood mononuclear cells.

BACKGROUND: Indian traditional medicine practices use defined rasayana preparations to improve the quality of life in aged individuals. Amalaki Rasayana is one such rasayana prepared from the fruits of Phyllanthus emblica and is popularly used to prevent or treat various age related health conditions. Telomerase activity in the cells maintains telomere length and is implicated in ageing and various diseases wherein the shortening of telomere during ageing is controlled chiefly by the telomerase activity. OBJECTIVE: In the present study, we investigated telomerase activity and telomere length in the peripheral blood mononuclear cells of aged individuals administered with Amalaki Rasayana. MATERIALS AND METHODS: Amalaki Rasayana was administered to healthy, aged (45-60 years) volunteers for 45 days after koshta shuddhi procedure. The telomerase activity and telomere length were analyzed on 0, 45th and 90th days of Amalaki Rasayana administration in peripheral blood mononuclear cells from these individuals and compared with age-matched placebo group and young volunteers (22-30 years). The data were compared between the groups. RESULTS: The results indicated an increase in telomerase activity with no discernible change in telomere length in the Amalaki administered participants. The comparison between young and aged participants revealed higher telomerase activity in young participants with no significant differences in telomere length. CONCLUSION: The data indicate that the maintenance of telomere length is facilitated by an increase in telomerase activity upon rasayana administration in aged individuals and Amalaki Rasayana may prevent the erosion of telomeres over a period of time in aged individuals to promote healthy ageing.

Age dependent neuroprotective effects of medhya rasayana prepared from Clitoria ternatea Linn. in stress induced rat brain.

ETHNOPHARMACOLOGICAL RELEVANCE: Indian traditional medicinal system in Ayurveda suggests several preparations, known as medhya rasayanas, of diverse plant origin to enhance the health in general, reduce stress and improve brain function in particular during ageing. These effects in the context of contemporary knowledge and the underlying mechanisms are not clearly understood. Autophagy and DNA damage induced repair are inter-related quintessential pathways and are significantly altered during stress and ageing. Hence, medhya rasayana prepared from Clitoria ternatea (locally known as shankhpushpi) was used to test these effects in Wistar rat model of various age groups upon stereotaxic mediated kainic acid induced brain injury. MATERIALS AND METHODS: The rodent experiments were carried out in one, twelve and eighteen months old male Wistar rats. The rats were orally fed with medhya rasayana prepared from Clitoria ternatea (3g per kg body weight/day) for 60 days. Stereotaxic mediated kainate stress to the hippocampus was performed on day 61. The rats were sacrificed on 66th day and the brain tissues were analyzed histologically and measured for autophagy, base excision repair and antioxidant enzyme activities. In addition, cognitive functions were analyzed by employing novel object recognition task and Morris water maze tests. The gene expression profile of hippocampus was assessed by microarray hybridization and two genes are validated. RESULTS: Our study showed significant decrease of autophagy by medhya rasayana in both 12 and 18 months old rats. The hippocampal CA3 cellularity were increased in stereotaxic mediated stressed rats by medhya rasayana. There were no significant differences in constitutive base excision repair and antioxidant enzyme activities. Medhya rasayana treatment also significantly increased episodic memory in rats. Microarray experiments for pathway specific gene expression analysis showed altered expression of genes of long-term potentiation, axon guidance, neuroactive ligand-receptor interaction, regulation of autophagy, lysosome, homologous recombination and nucleotide excision repair pathways in adult rats by medhya rasayana. CONCLUSIONS: In the present study, we show that reduction in autophagy is crucial for medhya rasayana induced protection of rat hippocampal cells and that artificially enhanced autophagy protects the brain cell damage by maintaining the selective DNA damage repair pathway and removal of reactive oxygen species to inhibit apoptosis. These findings suggest autophagy directed pathways by medhya rasayana prepared from C. ternatea protects the brain cells from stress induced injury.

Effect of Amalaki rasayana on DNA damage and repair in randomized aged human individuals.

ETHNOPHARMACOLOGICAL RELEVANCE: Preparations from Phyllanthus emblica called Amalaki rasayana is used in the Indian traditional medicinal system of Ayurveda for healthy living in elderly. The biological effects and its mechanisms are not fully understood. Since the diminishing DNA repair is the hallmark of ageing, we tested the influence of Amalaki rasayana on recognized DNA repair activities in healthy aged individuals. METHODS: Amalaki rasayana was prepared fresh and healthy aged randomized human volunteers were administrated with either rasayana or placebo for 45 days strictly as per the traditional text. The DNA repair was analyzed in peripheral blood mononuclear cells before and after rasayana administration and after 45 days post-rasayana treatment regimen. UVC-induced DNA strand break repair (DSBR) based on extent of DNA unwinding by fluorometric analysis, nucleotide excision repair (NER) by flow cytometry and constitutive base excision repair (BER) by gap filling method were analyzed. RESULTS: Amalaki rasayana administration stably maintained/enhanced the DSBR in aged individuals. There were no adverse side effects. Further, subjects with different body mass index showed differential DNA strand break repair capacity. No change in unscheduled DNA synthesis during NER and BER was observed between the groups. CONCLUSION: Intake of Amalaki rasayana by aged individuals showed stable maintenance of DNA strand break repair without toxic effects. However, there was no change in nucleotide and base excision repair activities. Results warrant further studies on the effects of Amalaki rasayana on DSBR activities.