Development and Characterization of Novel Biopolymer Derived from Abelmoschus esculentus L. Extract and Its Antidiabetic Potential

Abelmoschus esculentus (Okra) is an important vegetable crop, widely cultivated around the world due to its high nutritional significance along with several health benefits. Different parts of okra including its mucilage have been currently studied for its role in various therapeutic applications. Therefore, we aimed to develop and characterize the okra mucilage biopolymer (OMB) for its physicochemical properties as well as to evaluate its in vitro antidiabetic activity. The characterization of OMB using Fourier-transform infrared spectroscopy (FT-IR) revealed that okra mucilage containing polysaccharides lies in the bandwidth of 3279 and 1030 cm⁻¹, which constitutes the fingerprint region of the spectrum. In addition, physicochemical parameters such as percentage yield, percentage solubility, and swelling index were found to be 2.66%, 96.9%, and 5, respectively. A mineral analysis of newly developed biopolymers showed a substantial amount of calcium (412 mg/100 g), potassium (418 mg/100 g), phosphorus (60 mg/100 g), iron (47 mg/100 g), zinc (16 mg/100 g), and sodium (9 mg/100 g). The significant antidiabetic potential of OMB was demonstrated using α-amylase and α-glucosidase enzyme inhibitory assay. Further investigations are required to explore the newly developed biopolymer for its toxicity, efficacy, and its possible utilization in food, nutraceutical, as well as pharmaceutical industries.     

Malformin-A1 (MA1) Sensitizes Chemoresistant Ovarian Cancer Cells to Cisplatin-Induced Apoptosis

High-grade epithelial ovarian cancer is a fatal disease in women frequently associated with drug resistance and poor outcomes. We previously demonstrated that a marine-derived compound MalforminA1 (MA1) was cytotoxic for the breast cancer cell line MCF-7. In this study, we aimed to examine the effect of MA1 on human ovarian cancer cells. The potential cytotoxicity of MA1was tested on cisplatin-sensitive (A2780S) and cisplatin-resistant (A2780CP) ovarian cancer cell lines using AlamarBlue assay, Hoechst dye, flow cytometry, Western blot, and RT-qPCR. MA1 had higher cytotoxic activity on A2780S (IC50 = 0.23 µM) and A2780CP (IC50 = 0.34 µM) cell lines when compared to cisplatin (IC50 = 31.4 µM and 76.9 µM, respectively). Flow cytometry analysis confirmed the cytotoxic effect of MA1. The synergistic effect of the two drugs was obvious, since only 13% of A2780S and 7% of A2780CP cells remained alive after 24 h of treatment with both MA1 and cisplatin. Moreover, we examined the expression of bcl2, p53, caspase3/9 genes at RNA and protein levels using RT-qPCR and Western blot, respectively, to figure out the cell death mechanism induced by MA1. A significant down-regulation in bcl2 and p53 genes was observed in treated cells compared to non-treated cells (p < 0.05), suggesting that MA1 may not follow the canonical pathway to induce apoptosis in ovarian cancer cell lines. MalforminA1 showed promising anticancer activity by inducing cytotoxicity in cisplatin-sensitive and cisplatin-resistant cancer cell lines. Interestingly, a synergistic effect was observed when MA1 was combined with cisplatin, leading to it overcoming its resistance to cisplatin.     

1H-NMR-Based Metabolomics: An Integrated Approach for the Detection of the Adulteration in Chicken,Chevon, Beef and Donkey Meat

Meat is a rich source of energy that provides high-value animal protein, fats, vitamins, minerals and trace amounts of carbohydrates. Globally, different types of meats are consumed to fulfill nutritional requirements. However, the increasing burden on the livestock industry has triggered the mixing of high-price meat species with low-quality/-price meat. This work aimed to differentiate different meat samples on the basis of metabolites. The metabolic difference between various meat samples was investigated through Nuclear Magnetic Resonance spectroscopy coupled with multivariate data analysis approaches like principal component analysis (PCA) and orthogonal partial least square-discriminant analysis (OPLS-DA). In total, 37 metabolites were identified in the gluteal muscle tissues of cow, goat, donkey and chicken using ¹H-NMR spectroscopy. PCA was found unable to completely differentiate between meat types, whereas OPLS-DA showed an apparent separation and successfully differentiated samples from all four types of meat. Lactate, creatine, choline, acetate, leucine, isoleucine, valine, formate, carnitine, glutamate, 3-hydroxybutyrate and α-mannose were found as the major discriminating metabolites between white (chicken) and red meat (chevon, beef and donkey). However, inosine, lactate, uracil, carnosine, format, pyruvate, carnitine, creatine and acetate were found responsible for differentiating chevon, beef and donkey meat. The relative quantification of differentiating metabolites was performed using one-way ANOVA and Tukey test. Our results showed that NMR-based metabolomics is a powerful tool for the identification of novel signatures (potential biomarkers) to characterize meats from different sources and could potentially be used for quality control purposes in order to differentiate different meat types.     

Multi-Targeted Molecular Docking,Pharmacokinetics, and Drug-Likeness Evaluation of Okra-Derived Ligand Abscisic Acid Targeting Signaling Proteins Involved in the Development of Diabetes

Diabetes mellitus is a global threat affecting millions of people of different age groups. In recent years, the development of naturally derived anti-diabetic agents has gained popularity. Okra is a common vegetable containing important bioactive components such as abscisic acid (ABA). ABA, a phytohormone, has been shown to elicit potent anti-diabetic effects in mouse models. Keeping its anti-diabetic potential in mind, in silico study was performed to explore its role in inhibiting proteins relevant to diabetes mellitus- 11β-hydroxysteroid dehydrogenase (11β-HSD1), aldose reductase, glucokinase, glutamine-fructose-6-phosphate amidotransferase (GFAT), peroxisome proliferator-activated receptor-gamma (PPAR-gamma), and Sirtuin family of NAD(+)-dependent protein deacetylases 6 (SIRT6). A comparative study of the ABA-protein docked complex with already known inhibitors of these proteins relevant to diabetes was compared to explore the inhibitory potential. Calculation of molecular binding energy (ΔG), inhibition constant (pKi), and prediction of pharmacokinetics and pharmacodynamics properties were performed. The molecular docking investigation of ABA with 11-HSD1, GFAT, PPAR-gamma, and SIRT6 revealed considerably low binding energy (ΔG from −8.1 to −7.3 Kcal/mol) and predicted inhibition constant (pKi from 6.01 to 5.21 µM). The ADMET study revealed that ABA is a promising drug candidate without any hazardous effect following all current drug-likeness guidelines such as Lipinski, Ghose, Veber, Egan, and Muegge.     

Multicomponent access to novel proline/cyclized cysteine tethered monastrol conjugates as potential anticancer agents

The versatility of multicomponent Biginelli’s reaction is exploited in the development of proline and cyclized cysteine tethered conjugates of monastrol, a kinesin Eg5 inhibitor. Ten new conjugates are synthesized focusing on structural replacement of the ester moiety (C-5 position) of the monastrol backbone with amino acid based amide moieties. On cytotoxic evaluation, conjugate 24 has shown promising in vitro cytotoxic activity against leukemia. Molecular docking studies revealed that the conjugates 19 and 24 exhibit better interaction at kinesin Eg5 receptor compared to monastrol. Moreover, computational calculations and predictions of important molecular properties suggest that these new amino acid based conjugates could be further improved to provide potential anticancer agents.     

CuSO4/sodium ascorbate catalysed synthesis of benzosuberone and 1,2,3-triazole conjugates: Design,synthesis and in vitro anti-proliferative activity

A novel series of conjugates of benzosuberone and 1,2,3-triazole i.e. 3-(4-phenyl-1H-1,2,3-triazol-1-yl)propyl-9-chloro-2,3-dimethyl-6,7-dihydro-5H-benzo[7]annulene-8-carboxylic acids (8a-j) were synthesized in good to excellent yields catalysed by CuSO₄ under milder reaction conditions and evaluated for their anti-proliferative activity. The structural elucidation of the prepared compounds was carried out using IR, ¹H NMR, ¹³C NMR and Mass spectral analysis. The newly synthesized derivatives (8a-j) were evaluated for their anti-proliferative activity against four human cell lines and the novel derivatives showed moderate to excellent activity. The obtained results suggest that these compounds can be considered as new hits for anti-proliferative drug development programme and further SAR studies can help obtain better anticancer agents.     

Geographical traceability of wheat and its products using multielement light stable isotopes coupled with chemometrics

The present study was aimed to investigate the variation of stable isotopic ratios of carbon, nitrogen, hydrogen, and oxygen in wheat kernel along with different processed fractions from three geographical origins across 5 years using isotope ratio mass spectrometry (IRMS). Multiway ANOVA revealed significant differences among region, harvest year, processing, and their interactions for all isotopes. The region contributed the major variability in the δ¹³C ‰, δ²H ‰, δ¹⁵N ‰, and δ¹⁸O‰ values of wheat. Variation of δ¹³C ‰, δ¹⁵N ‰, and δ¹⁸O ‰ between wheat whole kernel and its products (break, reduction, noodles, and cooked noodles) were ?0.7‰, and no significant difference was observed, suggesting the reliability of these isotope fingerprints in geographical traceability of wheat‐processed fractions and foods. A significant influence of wheat processing was observed for δ²H values. By applying linear discriminant analysis (LDA) to the whole dataset, the generated model correctly classified over 91% of the samples according to the geographical origin. The application of these parameters will assist in the development of an analytical control procedure that can be utilized to control the mislabeling regarding geographical origin of wheat kernel and its products.