Cancer and inflammation are associated with cachexia. Withania somnifera (W. somnifera) possesses antioxidant and anti-inflammatory potential. We investigated the potential of an aqueous extract of the root of W. somnifera (WRE) to modulate cytokines, antioxidants and apoptosis in leukaemic THP-1 cells and peripheral blood mononuclear cells (PBMC’s). Cytotoxcity of WRE was determined at 24 and 72 h (h). Oxidant scavenging activity of WRE was evaluated (2, 2-diphenyl-1 picrylhydrazyl assay). Glutathione (GSH) levels, caspase (− 8, − 9, − 3/7) activities and adenosine triphosphate (ATP) levels (Luminometry) were thereafter assayed. Tumour necrosis factor-α (TNF-α), interleukin (IL)-6, IL-1β and IL-10 levels were also assessed using enzyme-linked immunosorbant assay. At 24 h, WRE (0.2–0.4 mg/ml) decreased PBMC viability between 20 and 25%, whereas it increased THP-1 viability between 15 and 23% (p < 0.001). At 72 h, WRE increased PBMC viability by 27–39% (0.05, 0.4 mg/ml WRE) whereas decreased THP-1 viability between 9 and 16% (0.05–0.4 mg/ml WRE) (p < 0.001). Oxidant scavenging activity was increased by WRE (0.05–0.4 mg/ml, p < 0.0001). PBMC TNF-α and IL-10 levels were decreased by 0.2–0.4 mg/ml WRE, whereas IL-1β levels were increased by 0.05–0.4 mg/ml WRE (p < 0.0001). In THP-1 cells, WRE (0.05–0.4 mg/ml) decreased TNF-α, IL-1β and IL-6 levels (p < 0.0001). At 24 h, GSH levels were decreased in PBMC’s, whilst increased in THP-1 cells by 0.2–0.4 mg/ml WRE (p < 0.0001). At 72 h, WRE (0.1–0.4 mg/ml) decreased GSH levels in both cell lines (p < 0.0001). At 24 h, WRE (0.2–0.4 mg/ml) increased PBMC caspase (-8, -3/7) activities whereas WRE (0.05, 0.1, 0.4 mg/ml) increased THP-1 caspase (-9, -3/7) activities (p < 0.0001). At 72 h, PBMC caspase (-8, -9, -3/7) activities were increased at 0.05–0.1 mg/ml WRE (p < 0.0001). In THP-1 cells, caspase (-8, -9, -3/7) activities and ATP levels were increased by 0.1–0.2 mg/ml WRE, whereas decreased by 0.05 and 0.4 mg/ml WRE (72 h, p < 0.0001). In PBMC’s and THP-1 cells, WRE proved to effectively modulate antioxidant activity, inflammatory cytokines and cell death. In THP-1 cells, WRE decreased pro-inflammatory cytokine levels, which may alleviate cancer cachexia and excessive leukaemic cell growth.

Ayurveda, the Indian holistic healthcare system encompasses traditional medicines with a principle of creating harmony and maintaining balance within the natural rhythms of the body. Rasayana is one of the branches of Ayurveda frequently used as rejuvenant therapy to overcome many discomforts and prevent diseases. It has been reported that rasayanas have immunomodulatory, antioxidant and antitumor functions. However, the genotoxic potential of many rasayanas remains to be evaluated. The present study was undertaken to assess the role of Brahma rasayana(BR) on genotoxicity in vivo in a mouse test system. The older mice (9 months) were orally fed with rasayana for 8 weeks. The treated groups showed no signs of dose-dependent toxicity at the dosage levels tested. The body weight loss/gain and feed consumption were unaffected at tested doses. Furthermore, sperm abnormalities and chromosomal aberrations were insignificant in the treatment group when compared to controls. However, there was a marginal increase in sperm count in the BR treated animals. These findings clearly indicate that there are no observed adverse genotoxic effects elicited by BR in experimental animals such as mice.

Cell-based screening of bioactive compounds has served as an important gateway in drug discovery. In the present report, using human neuroblastoma cells and enrolling an extensive three-step screening of 57 phytochemicals, we have identified caffeic acid phenethyl ester (CAPE) as a potent neurodifferentiating natural compound. Analyses of control and CAPE-induced neurodifferentiated cells revealed: (i) modulation of several key proteins (NF200, MAP-2, NeuN, PSD95, Tuj1, GAP43, and GFAP) involved in neurodifferentiation process; and (ii) attenuation of neuronal stemness (HOXD13, WNT3, and Msh-2) and proliferation-promoting (CDC-20, CDK-7, and BubR1) proteins. We anticipated that the neurodifferentiation potential of CAPE may be beneficial for the treatment of neurodegenerative diseases and tested it using the Drosophila model of Alzheimer’s disease (AD) and mice model of amnesia/loss of memory. In both models, CAPE exhibited improved disease symptoms and activation of physiological functions. Remarkably, CAPE-treated mice showed increased levels of neurotrophin-BDNF, neural progenitor marker-Nestin, and differentiation marker-NeuN, both in the cerebral cortex and hippocampus. Taken together, we demonstrate the differentiation-inducing and therapeutic potential of CAPE for neurodegenerative diseases.

Background: Ayurveda, the traditional Indian system of medicine has given great emphasis to the promotion of health. Rasayana is one of the eight branches of Ayurveda which refers to rejuvenant therapy. It has been reported that rasayanas have immuno-modulatory, antioxidant and antitumor functions, however, the genotoxic potential and modulation of DNA repair of many rasayanas have not been evaluated. Methods: The present study assessed the role of Brahmarasayana (BR) on Ethyl methanesulfonate (EMS)-and Methyl methanesulfonate (MMS)-induced genotoxicity and DNA repair in in vivo mouse test system. The mice were orally fed with BR (5 g or 8 mg / day) for two months and 24 h later EMS or MMS was given intraperitoneally. The genotoxicity was analyzed by chromosomal aberrations, sperm count, and sperm abnormalities. Results: The results have revealed that BR did not induce significant chromosomal aberrations when compared to that of the control animals (p >0.05). On the other hand, the frequencies of chromosomal aberrations induced by EMS (240 mg / kg body weight) or MMS (125 mg / kg body weight) were significantly higher (p<0.05) to that of the control group. The treatment of BR for 60 days and single dose of EMS or MMS on day 61, resulted in significant (p <0.05) reduction in the frequency of chromosomal aberrations in comparison to EMS or MMS treatment alone, indicating a protective effect of BR. Constitutive base excision repair capacity was also increased in BR treated animals. Conclusion: The effect of BR, as it relates to antioxidant activity was not evident in liver tissue however rasayana treatment was observed to increase constitutive DNA base excision repair and reduce clastogenicity. Whilst, the molecular mechanisms of such repair need further exploration, this is the first report to demonstrate these effects and provides further evidence for the role of brahmarasayana in the possible improvement of quality of life.

Alzheimer's disease (AD) is the leading cause of dementia around the globe. The disease's genesis is multifaceted, and its pathophysiology is complicated. Malfunction of mitochondria has been regarded as one of the intracellular events that are substantially damaged in the onset of AD and are likely a common trait of other neurodegenerative illnesses. Several mitochondrial characteristics begin to diminish with age, eventually reaching a state of significant functional failure concurrent with the beginning of neurodegenerative diseases, however, the exact timing of these processes is unknown. Mitochondrial malfunction has a multitude of negative repercussions, including reduced calcium buffering and secondary excitotoxicity contributing to synaptic dysfunction, also free radical production, and activation of the mitochondrial permeability transition. Hence mitochondria are considered a therapeutic target in neurodegenerative disorders such as Alzheimer's. Traditional medicinal systems practiced in different countries employing various medicinal plants postulated to have potent role in the therapy and management of memory impairment including amnesia, dementia as well as AD. Although, the chemical assessment and clinical studies using these medicinal plants or plant products have demonstrated the therapeutic efficacy for AD, the precise mechanism of action is still obscure. Therefore, this review discusses the contribution of mitochondria towards AD pathogenesis and considering phytotherapeutics as a potential therapeutic strategy.