Anti-diabetic drug discovery using the bioactive compounds of Momordica charantia by molecular docking and molecular dynamics analysis.

Diabetes mellitus (DM) is a multifactorial life-threatening endocrine disease characterized by abnormalities in glucose metabolism. It is a chronic metabolic disease that involves multiple enzymes such as α-amylase and α-glucosidases. Inhibition of these enzymes has been identified as a promising method for managing diabetes, and researchers are currently focusing on discovering novel α-amylase and α-glucosidase inhibitors for diabetes therapy. Hence, we have selected 12 bioactive compounds from the Momordica charantia (MC) plant and performed a virtual screening and molecular dynamics investigation to identify natural inhibitors of α-amylase and α-glucosidases. Our in silico result revealed that phytocompound Rutin showed the highest binding affinity against α-amylase (1HNY) enzymes at (-11.68 kcal/mol), followed by Karaviloside II (-9.39), Momordicoside F (-9.19), Campesterol (-9.11. While docking against α-glucosidases (4J5T), Rutin again showed the greatest binding affinity (-11.93 kcal/mol), followed by Momordicine (-9.89), and Campesterol (-8.99). Molecular dynamics (MD) simulation research is currently the gold standard for drug design and discovery. Consequently, we conducted simulations of 100 nanoseconds (ns) to assess the stability of protein-ligand complexes based on parameters like RMSD, RMSF, RG, PCA, and FEL. The significance of our findings indicates that rutin from MC might serve as an effective natural therapeutic agent for diabetes management due to its strongest binding affinities with α-amylase and α-glucosidase enzymes. Further research in animals and humans is essential to validate the efficacy of these drug molecules.Communicated by Ramaswamy H. Sarma.

Computational analysis of potential drug-like compounds from Solanum torvum - A promising phytotherapeutics approach for the treatment of diabetes.

Diabetes mellitus (DM) is a global pandemic that is characterized by high blood glucose levels. Conventional treatments have limitations, leading to the search for natural alternatives. This study focused on Solanum torvum (STV), a medicinal plant, to identify potential anti-diabetic compounds using molecular docking and molecular dynamics simulations. We focused on identifying natural inhibitors of two key enzymes involved in glucose metabolism: α-amylase (1HNY) and α-glucosidase (4J5T). In our preliminary docking study, rutin showed the highest binding affinity (-11.58 kcal/mol) to α-amylase, followed by chlorogenin (-7.58 kcal/mol) and myricetin (-5.82 kcal/mol). For α-glucosidase, rutin had the highest binding affinity (-11.78 kcal/mol), followed by chlorogenin (-7.11 kcal/mol) and fisetin (-6.44 kcal/mol). Hence, chlorogenin and rutin were selected for further analysis and compared with acarbose, an FDA-approved antidiabetic drug. Comparative docking revealed that chlorogenin had the highest binding affinity of (-9.9 kcal/mol) > rutin (-8.7 kcal/mol) and > acarbose (-7.7 kcal/mol) for α-amylase. While docking with α-glucosidase, chlorogenin again had the highest binding affinity of (-9.8 kcal/mol) > compared to rutin (-9.5 kcal/mol) and acarbose (-7.9 kcal/mol). Molecular dynamics (MD) simulations were conducted to assess their stability. We simulated 100 nanoseconds (ns) trajectories to analyze their stability on various parameters, including RMSD, RMSF, RG, SASA, H-bond analysis, PCA, FEL, and MM-PBSA on the six docked proteins. In conclusion, our study suggests that chlorogenin and rutin derived from STV may be effective natural therapeutic agents for diabetes management because of their strong binding affinities for the α-amylase and α-glucosidase enzymes.Communicated by Ramaswamy H. Sarma.

Regulation of glucose transporter-4 intervention with S. saman leaves extract in streptozotocin-induced diabetic rats.

Diabetes mellitus is the leading disorder and affects more than millions of people worldwide. Nowadays, the usage of herbal drugs is said to control adiposity and hyperglycemia. The current research investigated the anti-adiposity and antidiabetic activity of S. saman leaf extract and bioactive compounds. Therefore, the results lower the sugar absorption into the blood and reveal the extract's antidiabetic properties. STZ-induced diabetic rats, Samanea saman methanolic extract show improvement in the parameters like fasting blood glucose levels, body weight, other biochemical parameters supported by the histopathological analysis, and an increase in serum levels in the experimental groups. The antioxidant plays a vital role by increasing SOD and catalase activity levels and decreasing lipid peroxidation levels. The methanolic extract protects the tissue from oxidation stress, which is responsible for the glycemic properties. According to the findings, diabetic-treated rats had overnight blood glucose levels lower and near standard biochemical markers. Histopathology of the liver, pancreas, kidneys, and adipose tissues supported the pharmacological observations. Further, we screened and documented S. saman extract used for in vitro and in vivo methods. In terms of effectiveness, the crude extracts exhibit 0.8-fold GLUT4 down-regulation. Consequently, this result contributes to clinical trials and develops antidiabetic therapy as a substitute for synthetic pharmaceuticals.

Polycystic ovary syndrome (PCOS) increases the risk of subsequent gestational diabetes mellitus (GDM): A novel therapeutic perspective.

Polycystic ovary syndrome (PCOS) is a multifactorial disorder that harms both the reproductive as well as metabolic health of women. In addition, PCOS is a leading symptom of infertility in women. Nevertheless, PCOS-afflicted women who are fortunate enough to become pregnant unfortunately have an increased risk of pregnancy complications, such as gestational diabetes mellitus (GDM), preterm birth, etc. Many people believe GDM disappears after childbirth, despite the fact that GDM is a warning symptom of type 2 diabetes mellitus (T2DM), metabolic syndrome, and cardiovascular disease (CVD). According to growing evidence, GDM complicates 40 % of PCOS pregnancies, suggesting that PCOS is a risk factor for GDM. Hence, PCOS is a lifelong disorder that can eventually lead to various long-term health complications, including chronic menstrual irregularity, infertility, endometrial hyperplasia, and endometrial cancer. Thus, it's an undeniable scientific fact that both PCOS and GDM are significantly associated with each other. However, most studies on the risk of GDM in PCOS patients are retrospective, hence inconclusive evidence exists as to whether PCOS per se is a risk factor for GDM or any other factor associated. Henceforth, we intend to get a better therapeutic perspective of the maternal health complications associated with PCOS and GDM.

Evaluation of the anti-diabetic effect of biogenic silver nanoparticles and intervention in PPARγ gene regulation.

The current study demonstrated a green, friendly, low-cost biosynthesis of silver nanoparticles (AgNPs) from Kigelia africana leaves (Lam.) Benth. extract (KAE) as both a major capping and reducing agent. The produced AgNPs were characterized using a variety of analytical methods, like the X-ray powder diffraction (XRD), HRTEM, Fourier transforms infrared (FTIR), and UV-Vis spectrophotometer. The formation of AgNPs with maximum absorbance at max = 435 nm was endorsed by surface plasmon resonance. FTIR analysis revealed that biological macromolecules of KAE were involved in the stabilization and synthesis of AgNPs. At the same time, HRTEM images revealed that the average particle size of the spherical AgNPs ranged from about 25 nm to 35 nm. Further, cytotoxicity assessment of AgNPs was done using the RINm5F insulinoma cell line with an MTT assay. Followed by, the RINm5F insulinoma cells treated with AgNPs and KAE, the expression of the Peroxisome proliferator-activated receptor gamma (PPARγ) gene was accessed. The results showed gene expression was upregulated in the RINm5F insulinoma cell line thus confirming AgNPs and KAE anti-diabetic efficacy. Furthermore, the findings show that nanotechnology has enhanced the effectiveness of current methodologies in gene expression and regulation which has contributed to the emergence of different forms of advanced regulatory systems.

Gestational diabetes mellitus - A metabolic and reproductive disorder.

Maternal health associated with Gestational Diabetes Mellitus (GDM) has been gaining significant research attention due to its severe risk and adverse health effects. GDM is the leading health disease in pregnant women. It is the most common metabolic disease and it can affect up to 25% of women during pregnancy. Pregnancy is a sensitive period that impacts both pregnant women and their unborn children's long-term health. It is a well-known fact that the leading causes of disease and mortality worldwide are diabetes mellitus and cancer, and specifically, women with diabetes mellitus are at a higher risk of developing breast cancer (BC). Women who have diabetes are equally vulnerable to reproductive diseases. Reproductive dysfunctions with diabetes are mainly attributed to coexisting polycystic ovarian syndrome (PCOS), obesity, and hyperinsulinemia, etc. Moreover, India has long been recognized as the world's diabetic capital, and it is widely acknowledged that particularly pregnant and lactating women are among the most affected by diabetes. In India, one-third (33%) of women with GDM had a history of maternal diabetes. Nevertheless, the latest research suggests that gestational diabetes is also a risk factor for cardiometabolic diseases of the mother and offspring. Therefore, in the 21st century, GDM imposes a major challenge for healthcare professionals. We intend to explore the role of diabetes on female reproductive function throughout various stages of life in the perspective of the changing prognosis, prevalence, and prevention of GDM.

Quorum sensing intervened bacterial signaling: Pursuit of its cognizance and repression.

Bacteria communicate within a system by means of a density dependent mechanism known as quorum sensing which regulate the metabolic and behavioral activities of a bacterial community. This sort of interaction occurs through a dialect of chemical signals called as autoinducers synthesized by bacteria. Bacterial quorum sensing occurs through various complex pathways depending upon specious diversity. Therefore the cognizance of quorum sensing mechanism will enable the regulation and thereby constrain bacterial communication. Inhibition strategies of quorum sensing are collectively called as quorum quenching; through which bacteria are incapacitated of its interaction with each other. Many virulence mechanism such as sporulation, biofilm formation, toxin production can be blocked by quorum quenching. Usually quorum quenching mechanisms can be broadly classified into enzymatic methods and non-enzymatic methods. Substantial understanding of bacterial communication and its inhibition enhances the development of novel antibacterial therapeutic drugs. In this review we have discussed the types and mechanisms of quorum sensing and various methods to inhibit and regulate density dependent bacterial communication.

Optimization of quorum quenching mediated bacterial attenuation of Solanum torvum root extract by response surface modelling through Box-Behnken approach.

The present study was intended to optimize the quorum sensing inhibitory action of Solanum torvum root extract against Chromobacterium violaceum. Factors such as bacterial density, frequency of administration and concentration of extract were analysed. Plant samples were collected from Thrissur District, Kerala, India. Response surface modelling of factors by Box-Behnken approach was employed for optimizing quorum quenching activity of extract. The adequacy of mathematical model was verified by ANOVA and Cook's distance table. Results revealed that quorum quenching property of Solanum torvum root extract is highly influenced by variables studied whereas maximum activity was found during administration of 300 µg/ml extract thrice in a day. It was also understood that extract does not possess any bactericidal activity wherein it only silence its quorum sensing mediated functions. This observations can be further used in quorum quenching studies.