Standardised ido-BR1 Cucumber Extract Improved Parameters Linked to Moderate Osteoarthritis in a Placebo-controlled Study.

BACKGROUND: According to the World Health Organization, osteoarthritis (OA) is one of the 10 most disabling diseases in developed countries, with worldwide estimates of 9.6% prevalence in men and 18.0% in women over 60 years old. Its management is not well established and involves the use of high doses of painkillers coupled with anti-inflammatory agents. OBJECTIVE: In the search for alternatives to manage the disease, previous studies have shown superior properties of Q-ActinTM in managing OA-related pain compared with standard treatments. Qactin is a cucumber extract with the anti-inflammatory iminosugar idoBR1 standardised to over 1%. This study investigated the effects of different doses (20 mg, 100 mg) of Q-Actin in a longitudinal placebo-controlled experiment. METHODS: There were 101 patients with knee OA enrolled for the 180-day study, with 91 patients completing it. Patients were grouped into a placebo group (PLBO), as well as a 20mg dose (Q-Actin 1) and 100 mg dose (Q-Actin 2) groups. The PLBO group received cellulose in capsules identical to the Q-Actin capsules. RESULTS: There was a significant improvement in the pain-related parameters over time that was dose-dependent. CONCLUSION: This study clearly demonstrated the effectiveness of Q-Actin compared to placebo in the management of pain related to moderate osteoarthritis.

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.

Withania somnifera as a potential candidate to ameliorate high fat diet-induced anxiety and neuroinflammation.

BACKGROUND: The epidemic of obesity has reached alarming levels in both developing and developed nations. Excessive calorie intake and sedentary lifestyle due to technological advancements are the main causal factors for overweight and obesity among the human population. Obesity has been associated with a number of co-morbidities such as hypertension, type 2 diabetes mellitus, cardiovascular diseases, and neurodegeneration and dementia. The progression of neurological disorders in obese subjects has been mainly attributed to neuroinflammation. Withania somnifera has been used in numerous Ayurvedic formulations owing to its wide array of health-promoting properties. The current study was designed to test the hypothesis whether dry leaf powder of W. somnifera has anxiolytic and anti-neuroinflammatory potential in diet-induced obesity. METHODS: Young adult female rats were divided into four groups: low fat diet group (LFD) fed with regular chow feed, high fat diet group (HFD) fed with diet containing 30% fat by weight, low fat diet plus extract group (LFDE) fed with regular chow feed supplemented with dry leaf powder of W. somnifera 1 mg/g of body weight (ASH), and high fat diet plus extract group (HFDE) fed with diet containing 30% fat by weight and supplemented with ASH. All the animals were kept on respective feeding regimen for 12 weeks; following which, the animals were tested for their anxiety-like behavior using elevated plus maze test. The animals were sacrificed and used to study various inflammatory markers such as GFAP, Iba1, PPARγ, iNOS, MCP-1, TNFα, IL-1ß, IL-6, and various markers of NF-κB pathway by Western blotting and quantitative real-time PCR. Serum levels of leptin, insulin and pro-inflammatory cytokines were also assayed. RESULTS: ASH treated rats showed less anxiety levels as compared to HFD animals. At molecular level, ASH ameliorated the HFD-induced reactive gliosis and microgliosis and suppressed the expression of inflammatory markers such as PPARγ, iNOS, MCP-1, TNFα, IL-1ß, and IL-6. Further, ASH ameliorated leptin and insulin resistance and prevented HFD-induced apoptosis. CONCLUSIONS: Dry leaf powder of W. somnifera may prove to be a potential therapeutic agent to attenuate neuroinflammation associated with obesity and may prevent its co-morbidities.

Intermittent fasting combined with supplementation with Ayurvedic herbs reduces anxiety in middle aged female rats by anti-inflammatory pathways.

Intermittent fasting-dietary restriction (IF-DR) is an increasingly popular intervention to promote healthy aging and delay age associated decline in brain functions. Also, the use of herbal interventions is gaining attention due to their non-pharmacological approach to treat several abnormalities and promote general health with least side effects. The present study was aimed to investigate the synergistic effects of IF-DR regimen with herbal supplementation on anxiety-like behavior and neuroinflammation in middle aged female rats. We used dried leaf powder of Withania somnifera and dried stem powder of Tinospora cordifolia for our study. The rats were divided into three groups: (1) Control group fed ad libitum (AL); (2) rats deprived of food for full day and fed ad libitum on every alternate day (IF-DR); and (3) IF-DR and herbal extract (DRH) group in which rats were fed ad libitum with herbal extract supplemented diet, every alternate day. Post regimen, the rats were tested for anxiety-like behavior and further used for study of key inflammatory molecules (NFκB, Iba1, TNFα, IL-1ß, IL-6) and glial marker (GFAP) in hippocampus and piriform cortex regions of brain. The study was further extended to explore the effect of DRH regimen on stress response protein (HSP70) and calcium dependent regulators of synaptic plasticity (CaMKIIα, Calcineurin). Our data demonstrated that DRH regimen reduced anxiety-like behavior in middle age female rats and associated neuroinflammation by ameliorating key inflammatory cytokines and modulated stress response. The present data may provide scientific validation for anxiolytic and anti-inflammatory potential of herbal intervention combined with short term IF-DR regimen.

Aqueous Leaf Extract of Withania somnifera as a Potential Neuroprotective Agent in Sleep-deprived Rats: a Mechanistic Study.

Modern lifestyle and sustained stress of professional commitments in the current societal set up often disrupts the normal sleep cycle and duration which is known to lead to cognitive impairments. In the present study, we report whether leaf extract of Withania somnifera (Ashwagandha) has potential neuroprotective role in acute stress of sleep deprivation. Experiments were performed on three groups of adult Wistar rats: group 1 (vehicle treated-undisturbed sleep [VUD]), group 2 (vehicle treated-sleep deprived [VSD]), and group 3 (ASH-WEX treated-sleep deprived [WSD]). Groups 1 and 2 received single oral feeding of vehicle and group 3 received ASH-WEX orally (140 mg/kg or 1 ml/250 g of body weight) for 15 consecutive days. Immediately after this regimen, animals from group 1 were allowed undisturbed sleep (between 6 a.m. and 6 p.m.), whereas rats of groups 2 and 3 were deprived of sleep during this period. We observed that WSD rats showed significant improvement in their performance in behavioral tests as compared to VSD group. At the molecular level, VSD rats showed acute change in the expression of proteins involved in synaptic plasticity, cell survival, and apoptosis in the hippocampus region of brain, which was suppressed by ASH-WEX treatment thus indicating decreased cellular stress and apoptosis in WSD group. This data suggest that Ashwagandha may be a potential agent to suppress the acute effects of sleep loss on learning and memory impairments and may emerge as a novel supplement to control SD-induced cognitive impairments.

Withania somnifera as a potential anxiolytic and immunomodulatory agent in acute sleep deprived female Wistar rats.

Sleep is a profound regulator of cellular immunity, and the curtailment of sleep in present day lifestyle leads to disruption of neuro-immune-endocrine interactions. No therapeutic remedy is yet known for the amelioration of detrimental effects caused by sleep deprivation (SD). The current study was aimed to elucidate the effects of acute SD on immune function and its modulation by water extract from leaves of Withania somnifera (ASH-WEX). Three groups of animals, i.e. Vehicle-Undisturbed sleep (VUD), Vehicle-Sleep deprived (VSD) and ASH-WEX fed sleep deprived (WSD) rats were tested for their anxiety-like behaviour and further used for the study of inflammatory and apoptotic markers expression in piriform cortex and hippocampus regions of the brain. VSD animals showed high level of anxiety in elevated plus maze test, which was ameliorated in WSD group. The stress induced expression of inflammatory and immune response markers GFAP, TNFα, IL-6, OX-18 and OX-42 in VSD animals was found to be modulated by ASH-WEX. Further, the stress induced apoptosis was suppressed in WSD group as indicated by expression of NF-κB, AP-1, Bcl-xL and Cytochrome c. This study provides scientific validation to the anxiolytic, anti-inflammatory and anti-apoptotic properties of ASH-WEX, which may serve as an effective dietary supplement for management of SD induced stress and associated functional impairments.

Tinospora cordifolia ameliorates anxiety-like behavior and improves cognitive functions in acute sleep deprived rats.

Sleep deprivation (SD) leads to the spectrum of mood disorders like anxiety, cognitive dysfunctions and motor coordination impairment in many individuals. However, there is no effective pharmacological remedy to negate the effects of SD. The current study examined whether 50% ethanolic extract of Tinospora cordifolia (TCE) can attenuate these negative effects of SD. Three groups of adult Wistar female rats - (1) vehicle treated-sleep undisturbed (VUD), (2) vehicle treated-sleep deprived (VSD) and (3) TCE treated-sleep deprived (TSD) animals were tested behaviorally for cognitive functions, anxiety and motor coordination. TSD animals showed improved behavioral response in EPM and NOR tests for anxiety and cognitive functions, respectively as compared to VSD animals. TCE pretreatment modulated the stress induced-expression of plasticity markers PSA-NCAM, NCAM and GAP-43 along with proteins involved in the maintenance of LTP i.e., CamKII-α and calcineurin (CaN) in hippocampus and PC regions of the brain. Interestingly, contrary to VSD animals, TSD animals showed downregulated expression of inflammatory markers such as CD11b/c, MHC-1 and cytokines along with inhibition of apoptotic markers. This data suggests that TCE alone or in combination with other memory enhancing agents may help in managing sleep deprivation associated stress and improving cognitive functions.