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.

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.

Regulatory mechanisms of heme regulatory protein BACH1: a potential therapeutic target for cancer.

A limited number of overexpressed transcription factors are associated with cancer progression in many types of cancer. BTB and CNC homology 1 (BACH1) is the first mammalian heme-binding transcription factor that belongs to the basic region leucine zipper (bZIP) family and a member of CNC (cap 'n' collar). It forms heterodimers with the small musculoaponeurotic fibrosarcoma (MAF) proteins and stimulates or suppresses the expression of target genes under a very low intracellular heme concentration. It possesses a significant regulatory role in heme homeostasis, oxidative stress, cell cycle, apoptosis, angiogenesis, and cancer metastasis progression. This review discusses the current knowledge about how BACH1 regulates cancer metastasis in various types of cancer and other carcinogenic associated factors such as oxidative stress, cell cycle regulation, apoptosis, and angiogenesis. Overall, from the reported studies and outcomes, it could be realized that BACH1 is a potential pharmacological target for discovering new therapeutic anticancer drugs.

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.

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.