Aging-related changes in metabolic indicators in female rats and their management with Tinospora cordifolia.

Conflicting reports of HRT necessitates exploration of therapeutic interventions with the least side effects to preserve metabolic homeodynamics in women later in life. The current study was designed to elucidate the cumulative effects of aging and/or high fat diet (HFD) on some metabolic indicators and their management by Tinospora cordifolia stem powder (TCP) using middle-aged acyclic and young adult cyclic female rats as the model system. Animals were fed on either normal chow or HFD supplemented with or without TCP. Blood and liver tissue were collected for biochemical, and histological studies as well as for expression of proteins regulating lipid metabolism. Animals fed with TCP supplemented normal chow feed showed bodyweight management over 12-weeks despite their high feed and calories intake compared to young and age-matched controls as well as HFD-fed animals. TCP dose used was not toxic and rather prevented age-associated liver dysfunctions and ameliorated dyslipidemia and oxidative stress, normalized blood glucose, insulin, leptin, and secretary pro-inflammatory cytokines. Further, bodyweight management effect of TCP was observed to target AMPK signalling pathway as the mediator of lipogenesis, sterol biosynthesis, lipolysis, and ß-oxidation of fatty acids. These findings suggest that TCP supplementation in diet may be a potential interventional strategy to ameliorate aging-associated hepatic and metabolic dysfunctions and to promote healthy aging.

Dietary intervention with Tinospora cordifolia improved aging-related decline in locomotor coordination and cerebellar cell survival and plasticity in female rats.

Reduced bone mineral density, and muscle strength are the hallmark of aging-related motor coordination deficits and related neuropathologies. Since cerebellum regulates motor movements and balance perception of our body, therefore it may be an important target to control the age-related progression of motor dysfunctions. Dry stem powder of Tinospora cordifolia (TCP) was tested as a food supplement to elucidate its activity to attenuate age-associated locomotor dysfunctions. Intact acyclic middle-aged female rats were used in this study as the model system of the transition phase from premenopause to menopause in women along with cycling young adult rats. Normal chow or 30% High Fat Diet (HFD), supplemented with or without TCP was fed to animals for 12 weeks and then tested for locomotor performance on rotarod followed by post-sacrifice protein expression studies. In comparison to young adults, middle-aged animals showed an increase in number of falls and lesser time spent in rotarod performance test, whereas, animals given TCP supplemented feed showed improvement in performance with more pronounced effects observed in normal chow than HFD fed middle-aged rats. Further, due to its multicomponent nature TCP was found to target the expression of various markers of neuroinflammation, apoptosis, cell survival, and synaptic plasticity in the cerebellum region. The current findings suggest that TCP supplementation in the diet may prove to be a potential interventional strategy for the management of frailty and fall-associated morbidities caused by aging-related deterioration of bone mineral density, and muscle strength.

Structural tuning of acridones for developing anticancer agents targeting dihydrofolate reductase.

Targeting dihydrofolate reductase, here, we report the tumor growth inhibitory activity of substituted acridones. The screening of the molecules over 60 cell line panel of human cancer cells identified (S)-oxiran-2-ylmethyl 9-oxo-9,10-dihydroacridine-4-carboxylate (19) with average GI50 0.3 µM. The specificity of the compound to CCRF-CEM, MOLT-4 and SR cell lines of leukemia and SW-620, SF268, LOXIMVI, ACHN and MCF7 cancerous cells exhibiting GI50 in the nM range was observed. C6 Glioma cells treated with compound 19 showed differentiated cell morphology and cell cycle arrest in G2/M phase. The interactions of the compound with dihydrofolate reductase were ascertained with the help of enzyme immunoassays, molecular docking and molecular dynamic studies.

Dietary Supplementation With Tinospora cordifolia Improves Anxiety-Type Behavior and Cognitive Impairments in Middle-Aged Acyclic Female Rats.

The midlife transition period in women marks the progressive flattening of neurological health along with increased adiposity, dyslipidemia, frailty, and inflammatory responses mainly attributed to the gradual decline in estrogen levels. Conflicting reports of hormone replacement therapy (HRT) necessitate the exploration of novel therapeutic interventions using bioactive natural products having the least toxicity and a holistic mode of action for the preservation of metabolic homeodynamics with aging in women. The present study was planned to investigate the effects of aging and/or a high-fat diet (HFD) on cognitive impairments and anxiety and further their management by dietary supplement with the Tinospora cordifolia stem powder (TCP). Acyclic female rats were included in this study as the model system of the perimenopause phase of women along with young 3-4 months old rats as controls. Rats were fed on with and without TCP supplemented normal chow or HFD for 12 weeks. Animals fed on a TCP supplemented normal chow showed consistent management of body weight over a 12-week regimen although their calorie intake was much higher in comparison to their age-matched controls. Post-regimen, neurobehavioral tests, such as novel object recognition and elevated plus maze, performed on these animals showed improvement in their learning and memory abilities as well as the anxiety-like behavior. Furthermore, due to the presence of multiple components, TCP was observed to modulate the expression of key marker proteins to ameliorate neuroinflammation and apoptosis and promote cell survival and synaptic plasticity in the hippocampus and the prefrontal cortex (PFC) regions of the brain. These findings suggest that TCP supplementation in diet during the midlife transition period in women may be a potential interventional strategy for the management of menopause-associated anxiety and cognitive impairments and healthy aging.

Tinospora cordifolia ameliorates brain functions impairments associated with high fat diet induced obesity.

Obesity is a rapidly growing health problem worldwide and its prevalence has increased markedly in both the developing and developed nations. It is associated with a range of co-morbidities such as cardiovascular disease, type 2 diabetes mellitus, and cognitive dysfunctions. Therefore, the need for a safe and effective treatment has led to the exploration of natural products for the management of obesity. In the present study, we tested the anxiolytic, anti-apoptotic, and anti-neuroinflammatory potential of Tinospora cordifolia in a high fat diet-induced obesity rat model system. Young female Wistar albino rats were divided into three groups: (1) Low fat diet (LFD), fed on normal chow feed; (2) High fat diet (HFD), fed on diet containing 30% fat by weight; and (3) High fat diet containing extract (HFDE), fed on high fat diet supplemented with the stem powder of T. cordifolia (TCP). The rats from each group were kept on their respective feeding regimen for 12 weeks. The body weight and calorie intake were recorded weekly. The elevated plus maze test and rotarod performance test were performed to evaluate the anxiety-like behavior and locomotor coordination, respectively. The levels of serum cytokines (IL-6 and TNF-α) were estimated and various markers for inflammation, synaptic plasticity, apoptosis, and energy homeostasis were studied by western blotting. The HFDE rats showed reduced anxiety-like behavior and improved locomotor behavior as compared to HFD-induced obese rats. The TCP supplementation in high fat diet suppressed the expression of inflammatory molecules, including serum cytokines (IL-6 and TNF-α), and modulated apoptosis and synaptic plasticity. TCP was found to be effective in managing body weight in HFD-fed rats by maintaining energy metabolism and cellular homeostasis. T. cordifolia may be recommended as a potential therapeutic agent to prevent the adverse effects of obesity and obesity-associated brain dysfunctions.

From ayurvedic folk medicine to preclinical neurotherapeutic role of a miraculous herb, Tinospora cordifolia.

In Ayurveda, the age-old Indian traditional system of medicine, health is considered to be achieved as equilibrium of physical and mental wellbeing and brain related ailments are recognized as 'Vatavyadi'. Rasayana herbs were mainly used for pharmacological treatment of neurological diseases and Tinospora cordifolia is one of the popular Rasayana herbs of Ayurveda. The traditional claims of therapeutic activity of this herb for treatment of fever, diabetes, anxiety, immunodeficiency, memory deficit and psychological problems have been explored by different research groups using reverse pharmacology and advance technological approaches. The aim of current review is to compile and discuss the neurotherapeutic potential of T. cordifolia in the light of various preclinical and clinical studies from literature. This review summarizes the information about different extracts of this herb and decoctions used for various neuro-related problems such as neurodegenerative diseases, neuroinflammation, sleep disorders, neural cancers, memory and cognition deficits and psychological problems besides other potential activities. The review also provides the knowledge of underlying therapeutic mechanism of T. cordifolia and its active phytoconstituents.