Towards the development of phytoextract based healthy ageing cognitive booster formulation, explored through Caenorhabditis elegans model.

The positive effect of herbal supplements on aging and age-related disorders has led to the evolution of natural curatives for remedial neurodegenerative diseases in humans. The advancement in aging is exceedingly linked to oxidative stress. Enhanced oxidative stress interrupts health of humans in various ways, necessitating to find stress alleviating herbal resources. Currently, minimal scientifically validated health and cognitive booster resources are available. Therefore, we explored the impact of plant extracts in different combinations on oxidative stress, life span and cognition using the multicellular transgenic humanized C. elegans, and further validated the same in Mus musculus, besides testing their safety and toxicity. In our investigations, the final product-the HACBF (healthy ageing cognitive booster formulation) thus developed was found to reduce major aging biomarkers like lipofuscin, protein carbonyl, lipid levels and enhanced activity of antioxidant enzymes. Further confirmation was done using transgenic worms and RT-PCR. The cognitive boosting activities analyzed in C. elegans and M. musculus model system were found to be at par with donepezil and L-dopa, the two drugs which are commonly used to treat Parkinson's and Alzheimer's diseases. In the transgenic C. elegans model system, the HACBF exhibited reduced aggregation of misfolded disease proteins α-synuclein and increased the health of nicotinic acetylcholine receptor, levels of Acetylcholine and Dopamine contents respectively, the major neurotransmitters responsible for memory, language, learning behavior and movement. Molecular studies clearly indicate that HACBF upregulated major genes responsible for healthy aging and cognitive booster activities in C. elegans and as well as in M. musculus. As such, the present herbal product thus developed may be quite useful for healthy aging and cognitive boosting activities, and more so during this covid-19 pandemic. Supplementary Information: The online version contains supplementary material available at 10.1007/s13237-022-00407-1.

The underlying pathophysiology and therapeutic approaches for osteoporosis.

With an increase in the ageing population worldwide, the prevalence of osteoporosis increases at an alarming rate in both male and female irrespective of their ethnicity. At present, the currently available therapeutic options are mostly limited to either bone resorptive or bone forming efficacies and both approaches are associated with serious side effects. Despite these options, there is still need for newer therapeutics to treat osteoporosis, which can offer beneficial effects for maintaining balanced dynamics between bone formation and bone resorption, devoid of any side effect. The proper understanding of pathophysiology of the disease is essential for designing or investigating an effective and safe anti-osteoporotic agent. This review represents a discussion around the molecular targets with their implications in disease progression, available therapeutic options, the emerging targets, and the importance of designing an effective anti-osteoporotic agent.

Antioxidant and Hepatoprotective Potential of Swaras and Hima Extracts of Tinospora cordifolia and Boerhavia diffusa in Swiss albino Mice.

BACKGROUND: In Ayurveda, five basic extraction procedures are mentioned in order of their decreasing potency. Swaras is considered as the most potent followed by, kalka, kwatha, fanta and hima. OBJECTIVE: Present study was carried out to investigate the antioxidant and hepatoprotective potential of swaras and hima extracts of T.cordifolia and B. diffusa. MATERIALS AND METHODS: Swaras and hima extracts of T. cordifolia and B. diffusa were prepared. Phytochemical screening and in vitro antioxidant activities was carried out using standard methods. Hepatoprotective efficacy of extracts were carried out in Swiss albino mice using paracetamol induced hepatotoxicity. Animals were administered with swaras and hima extracts of both plants at 200 mg/kg BW dose for 7 days and on 8th day hepatotoxicity was induced by intraperitoneal injection of paracetamol at 500 mg/kg BW. The degree of liver protection was determined by measuring the levels of liver enzymes followed by histopathology. RESULTS AND DISCUSSION: The results of phytochemical, antioxidant and hepatoprotective activities showed that there were no significant difference between swaras and hima extracts. Both the extract of T. cordifolia were equally potent in reducing SGOT (P < 0.01) and ALP level (P < 0.001). Similar effects were observed with the Swaras and hima extracts of B. diffusa. Both the extracts reduced SGOT and ALP (P < 0.01). Histopathological findings among all the extracts were also more or less similar in lowering the paracetamol mitigated necrosis. CONCLUSION: The present study suggested that T. cordifolia and B. diffusa possess potential hepatoprotective activity irrespective of the extraction procedure. SUMMARY: Aqueous extracts of Tinospora cordifolia and Boerhavia diffusa exhibited significant antioxidant and hepatoprotective activitiesAqueous extracts of both the plants were extracted using different extraction procedures mentioned in AyurvedaSwaras and hima extracts of both the plants significantly reduced the deleterious effects of paracetamol, suggesting that both the plant extracts are equipotentAcute toxicity of both the plant extracts did not produce any toxic effects. Abbreviations used: TC swaras: T. cordifolia swaras; TC hima: T. cordifolia hima; BD swaras: B. diffusa swaras; BD hima: B. diffusa hima; BW: Body weight; LDL: Low-density lipoprotein; HDL: High-density lipoprotein; SGOT: Serum glutamate oxaloacetate transminase; SGPT: Serum glutamate pyruvate transminase; ALP: Alkaline phosphatase; I.P: Intraperitoneal; TAC: Total antioxidant capacity; DPPH: 2,2-diphenyl-1-picrylhydrazyl; TCA: Trichloro acetic acid; NO: Nitric oxide; TPC: Total phenolic content; NAPQI: N-acetyl-p-benzoquinone imine; PCM: Paracetamol.

An antidiabetic polyherbal phytomedicine confers stress resistance and extends lifespan in Caenorhabditis elegans.

An Ayurvedic polyherbal extract (PHE) comprising six herbs viz. Berberis aristata, Cyperus rotundus, Cedrus deodara, Emblica officinalis, Terminalia chebula and Terminalia bellirica is mentioned as an effective anti-hyperglycemic agent in 'Charaka Samhita', the classical text of Ayurveda. Previously, antidiabetic drug metformin was found to elicit antiaging effects and PHE was also found to exhibit antidiabetic effects in humans. Therefore, we screened it for its in vivo antioxidant antiaging effect on stress and lifespan using human homologous Caenorhabditis elegans model system. The effect on aging is evaluated by studying effect of PHE on mean survival in worms. The stress modulatory potential was assessed by quantification of intracellular ROS level, autofluorescent age pigment lipofuscin, oxidative and thermal stress assays. Additionally, stress response was quantified using gene reporter assays. The 0.01 µg/ml dose of PHE was able to enhance mean lifespan by 16.09% (P < 0.0001) in C. elegans. Furthermore, PHE treated worms demonstrated oxidative stress resistance in both wild type and stress hypersensitive mev-1 mutant along with upregulation of stress response genes sod-3 and gst-4. The delayed aging under stress can be attributed to its direct reactive oxygen species-scavenging activity and regulation of some age associated genes like daf-2, daf-16, skn-1, sod-3 and gst-4 in wild-type worms. Additonally, PHE delayed age related paralysis phenotype in CL4176 transgenic worms. Altogether, our results suggest PHE significantly improves the oxidative stress and life span in C. elegans. Overall the present study suggests this polyherbal formulation might play important role in regultaing aging and related complications like diabetes.

Protective effect of Triphala Rasayana against paracetamol-induced hepato-renal toxicity in mice.

BACKGROUND: Paracetamol, a widely used analgesic and antipyretic, is known to cause liver and renal injury in humans when administered in higher and repeated doses that cause acute liver injury. Triphala is a well-known Ayurvedic Rasayana formulation that is prescribed for balancing of Vata, Pitta and Kapha. Traditionally, it is used for the treatment of liver and kidney diseases. OBJECTIVE: The present study was undertaken to examine the protective effect of Triphala extract against paracetamol-induced hepato-renal injury in Swiss albino mice. MATERIALS AND METHODS: Swiss albino mice (weight 20-25 g) were used in this study. The mice were divided into five groups of six animals each. The aqueous extract of Triphala was given orally at two different doses (100 and 300 mg/kg body weight) for seven consecutive days, followed by a single intraperitoneal injection of paracetamol (500 mg/kg body weight) to induce hepato-renal toxicity. Serum levels of liver enzymes, aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), bilirubin, creatinine, urea and uric acid were measured as indices of liver and renal injury. All the statistical analyses were performed with the help of one-way analysis of variance (ANOVA) followed by Student-Newman-Keuls test as post hoc test. Results were considered statistically significant when P < 0.05. RESULTS: Pre-treatment with Triphala extract at 100 mg/kg and 300 mg/kg body weight exhibited a significant (P < 0.01) hepatoprotective activity. The protective effect of Triphala extract at 300 mg/kg body weight appears more effective than 100 mg/kg body weight. CONCLUSION: The present study gives an evidence of the protective role of Triphala extract against paracetamol-induced hepato-renal toxicity and validates its traditional claim in the Ayurveda system.

Effects of a standardized Ayurvedic formulation on diabetes control in newly diagnosed Type-2 diabetics; a randomized active controlled clinical study.

OBJECTIVES: The purpose of this study was to investigate the efficacy of a standardized polyherbal formulation consists of aqueous extracts from six herbs, in patients with Type-2 diabetes mellitus. DESIGN: Randomized, active control study. INTERVENTIONS: 93 patients, newly diagnosed with Type-2 diabetes mellitus were randomly allocated to group 1 (received polyherbal capsules 500 mg/day, up titrated weekly to a maximum of 3 g/day) and group 2 (received Metformin 500 mg/day, up titrated weekly to a maximum of 2 g/day). MAIN OUTCOME MEASURES: The primary endpoint was effect on the change from baseline in blood glucose (Fasting blood Glucose and Postprandial blood glucose), and glycosylated hemoglobin (HbA1c). The secondary outcome includes the effect on lipid levels, liver enzymes and renal function test. RESULTS: After 24 weeks, mean laboratory measured fasting and post prandial blood glucose showed a decrease of 25.52% and 24.22% in polyherbal formulation (PHF) treated group, compared to 31.46% and 24% decrease in Metformin treated group (estimated treatment difference -10.8; 95% CI -22.63 to 1.03 and -0.36; -12.1 to 11.38, respectively). Reduction in HbA1c was also similar for PHF and Metformin (estimated treatment difference 0.01; 95% CI -0.51 to 0.53). However, the decrease in the mean total cholesterol level was more pronounced in PHF treated group (estimated mean difference 61.3; 95% CI 55.32 to 67.28) than Metformin treated group (estimated mean difference 41.12; 95% CI 34.92 to 47.32). Also, there was statistical significance between the treatment groups in total cholesterol level at the end of six months treatment (estimated treatment difference 20.18; 95% CI 12.34 to 28.02). CONCLUSION: The study demonstrated that daily intake of this PHF decreased the glycemic level and improved lipid homeostasis, while maintaining the other serum biochemical levels to the normal, and therefore it may be useful for the patients with Type-2 diabetes. This trial is registered in the Clinical Trials Registry - India (CTRI) (CTRI/2014/03/004490).

Hepatoprotective Effect of A Polyherbal Extract Containing Andrographis Paniculata, Tinospora Cordifolia and Solanum Nigrum Against Paracetamol Induced Hepatotoxicity.

BACKGROUND: Traditionally, a number of medicinal plants are used to treat various types of hepatic disorders but few of them were pharmacologically evaluated for their safety and efficacy. The combination of Andrographis paniculata (Kalmegha), Tinospora cordifolia (Guduchi), and Solanum nigrum (Kakmachi) was traditionally used in Indian System of Medicine (Ayurveda) for the treatment of various liver-related disorders. OBJECTIVE: In the present study, an attempt was made to substantiate the ethnopharmacological use of a traditional formulation in hepatoprotection against paracetamol-induced hepatotoxicity. SUBJECTS AND METHODS: Swiss albino mice (weight 20-25 g) were used for this study. Intraperitoneal injection of paracetamol (500 mg/kg body weight) was used to induce hepatotoxicity. Serum levels of alanine transaminase, aspartate aminotransferase, bilirubin, alkaline phosphatase, were used as indices of liver injury. In addition total cholesterol, triglyceride, low-density lipoprotein, high-density lipoprotein and creatinine were also assayed using the standard procedure. RESULTS: Among the two different doses, pretreatment with Polyherbal extract at 500 mg/kg body weight exhibited a significant (P < 0.05) hepatoprotective activity as compared to paracetamol group. CONCLUSION: The polyherbal extract exhibits a significant hepatoprotective effect in vivo. The study contributes to its use in traditional Ayurveda system for the management of liver diseases. SUMMARY: Traditionally, a number of medicinal plants are used to treat various types of liver disorders but few of them were pharmacologically evaluated for their safety and efficacy. Combination of Andrographis paniculata (Kalmegha), Tinospora cordifolia (Guduchi), and Solanum nigrum (Kakmachi) was traditionally used in Ayurveda for the treatment of various liver related disorders. In the present study an attempt was made to validate the ethnopharmacological use of a traditional formulation in hepatoprotection against paracetamol induced hepatotoxicity. Swiss albino mice (weight 20-25 g) were used for this study. Intraperitoneal injection (IP) of paracetamol (500 mg/kg body weight) was used to induce hepatotoxicity. Serum levels of Alanine transaminase (ALT), Aspartate Aminotransferase (AST), Bilirubin, Alkaline phosphatase (ALP),. were used as indices of liver injury. In addition total cholesterol, triglyceride, Low density lipoprotein (LDL), High density lipoprotein (HDL) and creatinine were also assayed using standard procedure. Among the two different doses, pre-treatment with Polyherbal extract at 500 mg/kg body weight exhibited a significant (P < 0.05) hepatoprotective activity as compared to paracetamol group. The polyherbal extract exhibits significant hepatoprotective effect in vivo. The study contributes to its use in traditional Ayurveda system for the management of liver diseases.

Scientific validation of polyherbal hepatoprotective formulation against paracetamol induced toxicity

Objective: This polyherbal formulation has been traditionally used in the Indian system of medicine as a chief formulation for the treatment of hepatic diseases as hepatoprotective. The aim of the study was to study hepatoprotective activity which will be scientific validation of traditional knowledge claimed about this polyherbal formulation. Methods: Hepatotoxicity was induced by administration of paracetamol (300mg/kg) to the animals. The levels of liver enzymes (SGOT, SGPT, Alkaline phosphatase, Serum Bilirubin), lipid profiles (triglyceride, cholesterol, HDL, LDL), creatinine, urea levels and histopathological parameters were measured in order to evaluate hepatoprotective activity of polyherbal formulation. Results: The polyherbal formulation produced a significant hepatoprotective activity of the decoction of polyherbal formulation. The polyherbal formulation (PHF = 1) shows good hepatoprotective activity by lowering the levels of SGOT, alkaline phosphatase, bilirubin parameters (P<0.05), lipid profiles - cholesterol, triglyceride, LDL and histopathological evaluations shows that PHF = 1 and PHF = 3 formulations have significantly hepatoprotective activity (P<0.05). Conclusions: The study validates that polyherbal formulation has a good hepatoprotective activity. Further standardization processes may be performed in order to make it a beneficial hepatoprotective formulation.

Safety evaluation of Trikatu, a generic Ayurvedic medicine in Charles Foster rats.

Chemical characterization and acute and sub-acute toxicity study of Trikatu, a generic herbal formulation of Indian system of medicine, was carried out in Charles Foster (CF) rats for safety profiling. In acute toxicity experiment, Trikatu at 2,000 mg/kg body weight once orally was well tolerated by the experimental animals (both male and female) and no changes were observed in mortality, morbidity, gross pathology, gain in weight, vital organ weight, hematological (total white blood cells (WBC) and red blood cells (RBC) count), biochemical parameters such as serum creatinine, serum glutamate oxaloacetate transaminase (SGOT), serum glutamate pyruvate transaminase (SGPT), serum lipid profile and tissue biochemical parameters such as reduced glutathione and malonaldehyde content as oxidative stress markers. In sub-acute experiment, Trikatu was administered at 5, 50 and 300 mg/kg body weight once daily for 28 days in female CF rats, and non-significant changes were found in most of the parameters studied such as acute experiment except significant increase in low density lipoprotein (LDL) cholesterol level at 50 and 300 mg/kg body weight, decrease in high density lipoprotein (HDL) cholesterol level at 300 mg/kg body weight, increase in SGPT activity at 50 mg/kg body weight and decrease in WBC count at 300 mg/kg body weight on 28(th) day post treatment.