Mechanisms and Intervention of Prebiotic Foods in Musculoskeletal Health.

The review focuses primarily on collating and analyzing the mechanistic research data that discusses the function of prebiotics to halt the frailty of musculoskeletal system. Musculoskeletal diseases (MSDs) are frequently reported to co-occur within their own categories of conditions, such as osteoarthritis, rheumatoid arthritis, gouty arthritis, and psoriatic arthritis owing to their overlapping pathogenesis. Consequently, the same drugs are often used to manage the complications of most types. A few recent studies have addressed the therapeutic functions of gut microbes toward those commonly shared MSD pathway targets. Improving microbial diversity and enriching their population in the gut would promote the regeneration and recovery of the musculoskeletal system. Prebiotics are usually nondigestible substrates that are selectively used or digested by the gut microbes conferring health promotion. The microbial fermentation of prebiotics generates numerous host-beneficial therapeutic molecules. This study inspects the presumptive functions of plant-derived prebiotics for the growth and restoration of intestinal microbiota and the consequent improvement of skeletal health. The review also highlights the discrete functions of prebiotics against inflammation, autoimmunity, infection, physiologic overloading mechanism, and aging-associated loss of metabolism in MSD.

Ethnomedical, phytochemical and pharmacological insights on an Indian medicinal plant: The balloon vine (Cardiospermum halicacabum Linn.).

ETHNOPHARMACOLOGICAL RELEVANCE: Cardiospermum halicacabum Linn. (C. halicacabum) is one of the well-known leafy green vegetables in India. It is an herbaceous climber from the Sapindaceae family which is found in almost every Continent and Oceania. In the traditional Indian medicine systems, this plant is used for the treatment of rheumatism, abdominal pain, orchitis, dropsy, lumbago, skin diseases, cough, nervous disorders, and hyperthermia. AIM OF THE REVIEW: This review presents the current information about ethnomedical uses and progress on geographical distribution, pharmacological activities, phytochemistry, micropropagation, and toxicity of C. halicacabum. Also, critically summarizes the relationship between the reported pharmacological activities and the traditional usages along with the future perspectives for research on this medicinal plant. MATERIALS AND METHODS: The data on C. halicacabum were collected using multiple internet sources such as Google Scholar, Science Direct, Taylor & Francis, PubMed, Web of Science, Springer Link, Wiley online, and plant databases. RESULTS: Chemical characterization using LC-MS/MS, HPLC, and NMR exposed the presence of chlorogenic acid, caffeic acid, coumaric acid, luteolin-7-o-glucuronide, apigenin-7-o-glucuronide, and chrysoeriol in different parts of C. halicacabum. Based on the outcomes of this review, the main bioactive compounds found in C. halicacabum include phenols, phenolic acids, flavonoids, flavonoid glycosides, and flavonoid glucuronides. Besides the above-mentioned constituents, palmitic acid, oleic acid, stearic acid, linolenic acid, eicosenoic acid, and arachidic acid are the compounds that constitute the fatty acid profile of C. halicacabum seeds. Specifically, Cardiospermin, a bioactive compound isolated from the root extract of C. halicacabum has been recognized for its anxiolytic activity. Moreover, C. halicacabum showed a broad spectrum of pharmacological activities including anti-inflammatory, anti-arthritic, anti-diabetic, anxiolytic activity, antiulcer, apoptotic activity, antibacterial, antiviral, anti-diarrheal, antioxidant, hepatoprotective, and nephroprotective properties. However, the bioactive compounds responsible for most of the above therapeutic properties have not been elucidated till now. CONCLUSION: Phytochemicals from C. halicacabum showed noticeable pharmacological effects against plethora of health disorders. Some of the traditional applications were supported by modern scientific studies, however, more pharmacological evaluations should be conducted to validate other traditional uses of C. halicacabum. Despite C. halicacabum's vast pharmacological activity, additional human clinical trials are needed to determine the potent and safe dosages for the treatment of various health abnormalities. Besides, bioassay-guided isolation of active constituents, pharmacokinetic evaluations and identification of their mode of action are recommended for future investigations on C. halicacabum to unveil its therapeutic drug leads. Overall, this review suggests that C. halicacabum could be a new source of functional foods.

Brassica juncea (L.) Czern. leaves alleviate adjuvant-induced rheumatoid arthritis in rats via modulating the finest disease targets - IL2RA, IL18 and VEGFA.

Brassica juncea (BJ) is a familiar edible crop, which has been used as a dietary ingredient and to prepare anti-inflammatory/anti-arthritic formulations in Ayurveda. But, the scientific validation or confirmation of its therapeutic properties is very limited. This study was performed to determine the efficiency of BJ leaves for the treatment of Rheumatoid arthritis using in vivo and in silico systems. Standard in vitro procedures was followed to study the total phenolic, flavonoid contents and free radical scavenging ability of the extracts of BJ. The effective extract was screened and the presence of bioactive chemicals was studied using HPLC. Further, the possible therapeutic actions of the BJ active principles against the disease targets were studied using PPI networking and docking analysis. IL2RA, IL18 and VEGFA are found to be the potential RA target and the compounds detected from BJ extract have shown great binding efficiency towards the target from molecular docking study. The resulting complexes were then subject to 100 ns molecular dynamics simulation studies with the GROMACS package to analyze the stability of docked protein-ligand complexes and to assess the fluctuation and conformational changes during protein-ligand interactions. To confirm the anti-arthritic activity of BJ, the extract was tested in CFA-induced arthritic Wistar rats. The test groups administered with BJ extract showed retrieval of altered hematological parameters and substantial recovery from inflammation and degeneration of rat hind paw.Communicated by Ramaswamy H. Sarma.

Fortification of raw rice and rice flour using Cissus quadrangularis L. (veldt grape) stem powder to overcome osteoporosis and its associated skeletal complication through staple diet.

This study aimed to prepare the fortified rice/flour with Cissus quadrangularis (CQ) stem powder to eliminate nutritional deficiency and improve bone health. Mineral analysis by atomic absorption spectroscopy revealed that the CQ stem has adequate quantities of calcium, magnesium, and a moderate amount of phosphorous to meet the Recommended Dietary Allowance (RDA). Thus, the rice and flour were fortified with freeze-dried CQ stem powder to improve its nutraceutical contents. The fortification was done using standard vacuum impregnation and blending process. Furthermore, the recuperative activity of prepared fortified rice (CQFR) and flour (CQFF) was tested in chemically induced osteoporosis and osteoarthritis animal models. The efficiency of CQ fortified diet against these complications was confirmed by hematology, radiology, and histopathological analysis. The rat groups fed with CQFF/CQFR diet showed significant improvement from calcium deficiency and its allied physiological damage. Thus, this study confirms that the CQ fortified rice would provide recovery from skeletal complications associated with calcium deficiency through fixing both homeostasis and bio-accessibility of the calcium. PRACTICAL APPLICATIONS: Micronutrient and mineral deficiency is relatively higher in the regions where rice/rice products are consumed as a staple diet. Dietary intake of calcium and some essential minerals have major influences on bone and joint health. Cissus quadrangularis (CQ) is a familiar herb, conventionally used in India to fix broken bones and strengthen the skeletal system. The Atomic absorption spectroscopy data from this study showed that the CQ stem holds a high amount of calcium and other essential minerals to promote skeletal health. Preparation of fortified rice and flour with CQ stem would be a beneficial source of the essential minerals/ bioactive principles to promote and sustain skeletal health in the underprivileged population. These study data substantiated the practical application of producing the CQ fortified nutraceutical staple diet, especially to the people who are afflicted with morbid skeletal complications.

Attenuation of protein glycation by functional polyphenolics of dragon fruit (Hylocereus polyrhizus); an in vitro and in silico evaluation.

Chronic hyperglycemia and oxidative stress promote non-enzymatic glycation that leads to the production of advanced glycation end products (AGEs). AGEs casue significant damage to physiological proteins which result in several complications. The scenario also corresponds to the chronic consumption of a diet rich in AGEs. Despite understanding these mechanisms at the molecular level, the discovery of new drugs for these complications is under progress. Natural compounds might have great therapeutic potential for treating glycative consequences. In view of this, the study aimed to evaluate fruit extracts of Hylocereus polyrhizus towards determining its phenolics and flavonoid contents, as well as assessing it's in vitro antiglycative potential through the use of multistage glycation markers (early, intermediate and end stage products of ß-aggregation) in sugar-protein model. In vitro hypoglycemic activity of H. polyrhizus extracts was evaluated through α-amylase and α glucosidase inhibitory activities. In vitro antioxidant potential of the fruit extracts was also examined against different free radical types including DPPH and ABTS. Among the different in vitro assays performed, methanolic and acetone extracts of the fruit, with higher phenolics and flavonoid content, have exerted significant antiglycation and antioxidant activities than other extracts namely aqueous, ethanol, hydro-ethanol, hydro-methanol, and petroleum ether. Ultra-Performance Liquid Chromatography coupled with Electrospray Ionization Mass Spectrometry (UPLC-ESI-MS/MS) analysis was employed to identify active polyphenolics that may be responsible for the antiglycative potential of H. polyrhizus. The analysis revealed some high-profile compounds that have well documented for their therapeutic benefits. Additionally, In silico analysis also showed the possible connection between identified compounds and mechanisms of action. 4- Prenylresveratrol, Vicenin, and Luteolin had observed as effectively interact with target protein in molecular docking analysis. This suggests H. polyrhizus as a good source of anti-glycation and antioxidants that may have potential applications for the treatment and prevention of glycation associated diabetic and aging complications.

Momordica cymbalaria improves reproductive parameters in alloxan-induced male diabetic rats.

Male reproductive dysfunction is one of the common complications of diabetes mellitus that causes infertility. This study was designed to investigate the protective effect of Momordica cymbalaria (M. cymbalaria) extracts on diabetes mediated reproductive toxicity in male Wistar rats. The induction of diabetes was performed using a single intraperitoneal injection of alloxan (120 mg/kg). Skin and seed extracts (250 and 500 mg/kg) of M. cymbalaria were orally administered to alloxan-induced diabetic male rats for 28 days. Postprandial blood glucose (PBG) levels were recorded at 7-day interval for four weeks. The effects of the treatment on blood glucose, weight of reproductive organs, sperm count, testosterone levels, antioxidant capacity, and histomorphology were evaluated. Treatment with the above extracts of M. cymbalaria significantly (p < 0.05) improved the reproductive parameters as well as the antioxidant levels superoxide dismutase (SOD) and glutathione-s-transferase (GST) in the diabetic rats. Also, oral treatment with M. cymbalaria extracts significantly reduced the PBG and malondialdehyde (MDA) levels. Further, it revived the histomorphology of reproductive organs in diabetic rats. Interestingly, skin extract at a dose of 500 mg/kg was found to be more efficient in elevating the level of testosterone and sperm count in the diabetic rats. Based on the results, it is clear that M. cymbalaria not only regulates the postprandial blood glucose levels but also improves the reproductive health in the diabetic state.

Cissus quadrangularis (veldt grape) attenuates disease progression and anatomical changes in mono sodium iodoacetate (MIA)-induced knee osteoarthritis in the rat model.

The Cissus quadrangularis (CQ) stem has interesting nutritional and pharmacological properties to promote the health of the skeletal system. It is a well-recognized plant in the conventional system of medicine in India for treating bone and joint-associated complications. This study focuses on identifying the active constituents from the stem and root extracts of CQ and validating its anti-osteoarthritic activity by the in vivo model. Notable levels of phenolics and flavonoids were found in the ethanol extracts of both CQ stem (CQSE) and root (CQRE), among other solvent fractions. UPLC-MS/MS analysis of these selective extracts resulted in different classes of active compounds from both positive and negative ionization modes. By analyzing their mass spectra and fragmentation pattern, 25 active compounds were identified. The CQSE and CQRE extracts, along with the standard drug (naproxen), were further tested in mono-sodium iodoacetate-induced experimental OA animals. The modulatory effects of the test extracts were assessed by haematology, synovial and cartilage marker profiling, radiology and histopathological analysis. The in vivo findings from the biochemical and physiological studies have led to the conclusion that the CQSE extract is a good choice for the management of OA. The results were substantially better than CQ root extract and naproxen drug-treated groups. Thus, CQS has bioactive constituents, which could facilitate recovery from joint tissue damage, cellular metabolism and associated risk factors attributable to dysfunctions in OA incidence and progression.

Antidiabetic and hypolipidemic efficacy of skin and seed extracts of Momordica cymbalaria on alloxan induced diabetic model in rats.

ETHNOPHARMACOLOGICAL RELEVANCE: Momordica cymbalaria, a wild vegetable belongs to the Cucurbitaceae family, has long been used as a food and a remedy for diabetes mellitus in the Asian native medicinal system. AIM OF THE STUDY: This study aims to evaluate the efficacy of ethanolic extract of skin (EESK) and methanolic extract of seed (MESE) of M. cymbalaria (MC), for their hypoglycemic and hypolipidemic effects in alloxan induced diabetic rats. MATERIALS AND METHODS: The diabetes induced rats were given skin and seed extracts at doses 250 and 500 mg/kg b.w. p.o. for 28 days. Alloxan monohydrate (120 mg/kg) was used to induce diabetes mellitus. Daily food and water intake were assessed. Blood glucose levels and body weights were measured every 7 days throughout the experiment. Antioxidant assays, different biochemical and glycemic parameters were evaluated. Histopathological studies on pancreas, liver and kidney were also studied. RESULTS: Treatment of EESK and MESE showed dose significant decrease in fasting blood glucose level (FBG) in experimental diabetic animals with significant reduction in food and water intake and increase in body weight. Findings confirmed the hypoglycemic and hypolipidemic effects of EESK and MESE in the experimental groups. The impaired glucose tolerance and altered activities of the hepatic enzymes such as AST, ALT and ALP levels of diabetic rats were significantly improved by the administration of EESK and MESE. Oral treatment with MC extract for 28 days demonstrated significant protective effects on the lipid profile, biochemical parameters and antioxidant levels. Besides, biochemical findings were supported by histopathological investigations. CONCLUSION: These results suggest that the treatment with EESK and MESE of MC at a dose of 500 mg/kg b.w. have better protective effects against hyperglycemia, hyperlipidemia and oxidative stress generated during diabetes justifying the use of the plant in traditional systems of medicine.

Food advanced glycation end products as potential endocrine disruptors: An emerging threat to contemporary and future generation.

Mankind exposure to chemicals in the past century has increased dramatically throughout environment. There is no question that chemicals interfere with the physiology of biological system. Abundance of chemicals is documented to be detrimental to human and wildlife. The mammalian endocrine system is comprised of many interacting tissues mediate themselves through hormones that are essential for metabolism, growth and development. Humans secrete over fifty different hormones to orchestrate major physiological functions however; these vital functions can be intervened by huge number of internal and external chemical stressors that are identified as endocrine disruptors. Advanced glycation end products (AGEs), familiarly known as Maillard products, formed through non-enzymatic glycation whose production is augmented on aging as well as environmental stressors. Processed foods have become very popular today due to their taste, convenience, and inexpensiveness. Manufacture of these day-to-day foods involves extreme temperatures on processing results in the formation of AGEs could independently promote oxidative stress, aging, diabetes, cancer, degenerative diseases, more fascinatingly hormonal disruption is the subject of interest of this review. Based on some substantial observations documented till time, we discuss the emergence of dietary AGEs as potential endocrine disruptors by emphasizing their occurrence, mechanisms and participation in endocrine interruption. Both economically and in terms of human life, AGEs may represent an enormous cost for the future society. Therefore, by explicating their novel role in endocrine diseases, the review strives to make an impact on AGEs and their exposure among public as well as scientific communities.

Evaluation of antidiabetic activity of bud and flower of Avaram Senna (Cassia auriculata L.) In high fat diet and streptozotocin induced diabetic rats.

Type 2 Diabetes Mellitus (T2DM) is very common metabolic disorder affecting people of all age groups. The change in life style and environmental factors are the considerable factors which are involved in the development of the disorder. The different parts of medicinal plants vary in their composition of bioactive compounds. There are reports on antidiabetic activity of C. auriculata L. flower and leaves. Traditionally bud of C. auriculata L. is used to treat diabetes rather than flower. This study aims to explore the antidiabetic efficiency of bud and flower and to identify the differential composition of phycompounds present in bud and flower parts of C. auriculata L. The compounds present in the bud and flower parts were identified using LC-ESI/MS analysis. Antidiabetic activity of C. auriculata L. bud and flower parts was studied in high fat diet (HFD) and streptozotocin (STZ) induced diabetic rats. During which parameters such as feed intake, water intake, and body weight were monitored. After 21 days of the study, blood parameters like insulin, glucose, lipid profile, hepatic function test, renal function test and oxidative stress markers were analysed. Real time PCR was done to monitor the expression of IRS2 and GRIA2 genes. The LC-ESI/MS analysis showed the presence of various phenolics and flavonoid compounds specific to bud and flower parts. The antidiabetic activity results showed that the animal treated with C. auriculata L. bud ethanol extract (CABE500) could better reverse and control the progression of the disease compared to the flower ethanol extract. The gene expression studies revealed that regulation of IRS2 gene occurred in bud but not in flower extract treated animal livers and no differential expression of GRIA2 gene in all the experimental groups. C. auriculata L. bud extract can potentially better control the diabetes compared to the flower extract.