Exploring the Interplay between Vitamin D, Insulin Resistance, Obesity and Skeletal Health.

Vitamin D (ViD), plays an important role in calcium absorption and bone mineralization, is associated with bone mineral density. Severe deficiency in ViD has long been linked to conditions such as rickets in children and osteomalacia in adults, revealing its substantial role in skeletal health. Additionally, investigations show an existing interconnection between ViD and insulin resistance (Ins-R), especially in patients with type 2 diabetes mellitus (T2DM). Obesity, in conjunction with Ins-R, may augment the risk of osteoporosis and deterioration of skeletal health. This review aims to examine recent studies on the interplay between ViD, Ins-R, obesity, and their impact on skeletal health, to offer insights into potential therapeutic strategies. Cochrane Library, Google Scholar, and Pubmed were searched to investigate relevant studies until December 2023. Current research demonstrates ViD's impact on pancreatic ß-cell function, systemic inflammation, and insulin action regulation. Our findings highlight an intricate association between ViD, Ins-R, obesity, and skeletal health, providing a perspective for the prevention and/or treatment of skeletal disorders in patients with obesity, Ins-R, and T2DM.

Effects of Bee Propolis on FBG, HbA1c, and Insulin Resistance in Healthy Volunteers

Objectives: Bee propolis is a natural substance that is used in traditional medicine due to its versatile pharmacological actions. This study evaluates whether short term use of bee propolis supplementation could have an impact on glycemic control in healthy individuals. Materials and Methods: A single daily dose of 1000 mg of bee propolis was administered orally to a total of 34 healthy individuals for 60 days. Body weight, body mass index (BMI), fasting blood glucose (FBG), glycosylated hemoglobin (HbA1c), and insulin resistance were measured in all participants before and after the use of bee propolis. Results: The results of this study showed that bee propolis was associated with a significant increase in body weight and BMI of healthy volunteers. Bee propolis supplementation decreased FBG and HbA1c, but did not affect insulin resistance. Conclusion: Based on these results, bee propolis supplementation has a potential effect on glycemic control in healthy individuals and this should be considered when using this supplement in medical conditions.

Comparison of Antioxidant Effects of the Proton Pump-Inhibiting Drugs Omeprazole, Esomeprazole, Lansoprazole, Pantoprazole, and Rabeprazole.

INTRODUCTION: Peptic lesions usually develop when there is an imbalance between aggressive drivers and gastro-protective mediators that guard the lining of the gastrointestinal tract. The most crucial of these mediators are antioxidants, whose loss may predispose to oxidative stress, which is believed to be the main aggravator of several diseases including peptic ulcer. Proton pump inhibitors (PPIs) are drugs that are highly effective and widely used for therapeutic management of peptic disorders through inhibition of gastric acid secretion. In spite of this, oxidative damage may continue to be a major issue that can predispose to future lesions. OBJECTIVE: The present study is designed to explore the possible antioxidant capability of different PPIs, including omeprazole, esomeprazole, lansoprazole, pantoprazole, and rabeprazole, in an aim to suggest an agent that, in addition to its acid-suppression properties, can provide antioxidant profit. METHODS: The antioxidant activity of different PPIs was evaluated calorimetrically to test the ability of each drug to quench oxygen free radical, using the well-known stable free radical α,α-diphenyl-ß-picrylhydrazyl (DPPH), and compared to ascorbic acid (AA; vitamin C). The measurements were performed using a spectrophotometer at 517 nm. RESULTS: All the studied drugs reduced DPPH, but to different extents. However, omeprazole and esomeprazole showed the highest ability to scavenge free radicals (50% inhibitory concentrations [IC50s] of the percentage for free radical scavenging activity are 18.7 ± 5.7 and 18.7 ± 5.7, respectively, and the AA equivalents are 83,772 ± 11,887 and 81,732 ± 8,523 mg AA/100 g, respectively). Conversely, lansoprazole, pantoprazole, and rabeprazole might be having no role in this story (IC50s of the percentage for free radical scavenging activity are 49.3 ± 3.1, 49 ± 9.4, and 40.7 ± 7.2, respectively, and the AA equivalents are 30,458 ± 3,884, 32,222 ± 10,377, and 37,876 ± 8,816 mg AA/100 g, respectively). CONCLUSION: Thus, omeprazole and esomeprazole may confer a significant dual action in gastrointestinal protection by providing potent antioxidant properties in addition to their major role as acid-suppression agents. However, further studies are essential to elucidate the mechanism behind the difference between the drugs of the same class.

Sustainable Syntheses of (-)-Jerantinines A & E and Structural Characterisation of the Jerantinine-Tubulin Complex at the Colchicine Binding Site.

The jerantinine family of Aspidosperma indole alkaloids from Tabernaemontana corymbosa are potent microtubule-targeting agents with broad spectrum anticancer activity. The natural supply of these precious metabolites has been significantly disrupted due to the inclusion of T. corymbosa on the endangered list of threatened species by the International Union for Conservation of Nature. This report describes the asymmetric syntheses of (-)-jerantinines A and E from sustainably sourced (-)-tabersonine, using a straight-forward and robust biomimetic approach. Biological investigations of synthetic (-)-jerantinine A, along with molecular modelling and X-ray crystallography studies of the tubulin-(-)-jerantinine B acetate complex, advocate an anticancer mode of action of the jerantinines operating via microtubule disruption resulting from binding at the colchicine site. This work lays the foundation for accessing useful quantities of enantiomerically pure jerantinine alkaloids for future development.

In vitro anticancer properties and biological evaluation of novel natural alkaloid jerantinine B.

Natural products play a pivotal role in medicine especially in the cancer arena. Many drugs that are currently used in cancer chemotherapy originated from or were inspired by nature. Jerantinine B (JB) is one of seven novel Aspidosperma indole alkaloids isolated from the leaf extract of Tabernaemontana corymbosa. Preliminary antiproliferative assays revealed that JB and JB acetate significantly inhibited growth and colony formation, accompanied by time- and dose-dependent apoptosis induction in human cancer cell lines. JB significantly arrested cells at the G2/M cell cycle phase, potently inhibiting tubulin polymerisation. Polo-like kinase 1 (PLK1; an early trigger for the G2/M transition) was also dose-dependently inhibited by JB (IC50 1.5 µM). Furthermore, JB provoked significant increases in reactive oxygen species (ROS). Annexin V+ cell populations, dose-dependent accumulation of cleaved-PARP and caspase 3/7 activation, and reduced Bcl-2 and Mcl-1 expression confirm apoptosis induction. Preclinical in silico biopharmaceutical assessment of JB calculated rapid absorption and bioavailability >70%. Doses of 8-16 mg/kg JB were predicted to maintain unbound plasma concentrations >GI50 values in mice during efficacy studies. These findings advocate continued development of JB as a potential chemotherapeutic agent.