Antihyperglycemic Potential of Quercetin-3-glucoside Isolated from Leucaena leucocephala Seedpods via the SIRT1/AMPK/GLUT4 Signaling Cascade.

Leucaena leucocephala. (Lam.) de Wit, a traditional medicinal plant, has been reported among the ethnic communities of Mexico, Indonesia, China, and India for the treatment of diabetes, obesity, and related complications. This study investigates the antihyperglycemic activity of the plant and its isolated active compound quercetin-3-glucoside. Further, bioactivity guided marker assisted development of an enriched bioactive fraction toward enhancing insulin sensitization was carried out. The enriched fraction was also found to contain 397.96 mg/g of quercetin-3-glucoside along with three other marker compounds, which were also isolated and identified. Quercetin-3-glucoside, out of the four isolated marker compounds from the plant, showed the most significant bioactivity when tested in palmitate-induced insulin-resistant C2C12 myotubes. The compound also showed significant upregulation of sirtuin1 (SIRT1) followed by enhancement of insulin-dependent signaling molecules SIRT1/AMPK/PGC1-α and GLUT4 translocation. Molecular dynamics studies showed the compound having stable interactions with the SIRT1 protein. SIRT1 upregulation has been associated with enhanced insulin sensitivity in skeletal muscle, increasing the glucose uptake by muscle cells. The prepared enriched fraction also modulated the SIRT1/AMPK/GLUT4 pathway. The findings of the present study may find future application toward the development of botanical or phytopharmaceutical drugs from the traditionally important plant L. leucocephala against type II diabetes.

Therapeutic Potential of Bioactive Compounds from Edible Mushrooms to Attenuate SARS-CoV-2 Infection and Some Complications of Coronavirus Disease (COVID-19).

The novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), a highly infectious positive RNA virus, has spread from its epicenter to other countries with increased mortality and morbidity. Its expansion has hampered humankind's social, economic, and health realms to a large extent. Globally, investigations are underway to understand the complex pathophysiology of coronavirus disease (COVID-19) induced by SARS-CoV-2. Though numerous therapeutic strategies have been introduced to combat COVID-19, none are fully proven or comprehensive, as several key issues and challenges remain unresolved. At present, natural products have gained significant momentum in treating metabolic disorders. Mushrooms have often proved to be the precursor of various therapeutic molecules or drug prototypes. The plentiful bioactive macromolecules in edible mushrooms, like polysaccharides, proteins, and other secondary metabolites (such as flavonoids, polyphenols, etc.), have been used to treat multiple diseases, including viral infections, by traditional healers and the medical fraternity. Some edible mushrooms with a high proportion of therapeutic molecules are known as medicinal mushrooms. In this review, an attempt has been made to highlight the exploration of bioactive molecules in mushrooms to combat the various pathophysiological complications of COVID-19. This review presents an in-depth and critical analysis of the current therapies against COVID-19 versus the potential of natural anti-infective, antiviral, anti-inflammatory, and antithrombotic products derived from a wide range of easily sourced mushrooms and their bioactive molecules.

Enhanced delivery of quercetin and doxorubicin using ß-cyclodextrin polymer to overcome P-glycoprotein mediated multidrug resistance.

In this study, we prepared a ß-cyclodextrin polymer (ß-CDP) co-loaded quercetin (QCT) and doxorubicin (DOX) nanocarrier (ß-CDP/QD NCs) by freeze-dried method to combat P-glycoprotein (P-gp) mediated multidrug resistance (MDR) in KB-ChR 8-5 cancer cells. Various microscopic and spectroscopic techniques were employed to characterize the prepared nanocarrier. The molecular docking studies confirm the effective binding interactions of QCT and DOX with the synthesized ß-CD polymer. The in vitro drug release study illustrates the sustainable release of DOX and QCT from the ß-CDP nanocarrier. Further, we noticed that the QCT released from the ß-CDP nanocarrier improved the intracellular availability of DOX via modulating P-gp drug efflux function in KB-ChR 8-5 cells and MCF-7/DOX cancer cells. Cell uptake results confirmed the successful internalization of DOX in KB-ChR 8-5 cells compared with free DOX. Cell-based assays such as nuclear condensation, alteration in the mitochondrial membrane potential (MMP), and apoptosis morphological changes confirmed the enhanced anticancer effect of ß-CDP/QD NCs in the resistant cancer cells. Hence, QCT and DOX co-loaded ß-CDP may be considered effective in achieving maximum cell death in the P-gp overexpressing MDR cancer cells.

Endophytic fungi occurring in Ipomoea carnea tissues and their antimicrobial potentials

The aim of this work was to study the endophytic fungi associated with the tissues of Ipomoea carnea, a common invasive plant of India. A total of 69 isolates belonging to ten taxa comprising 1.45% Zygomycetes, 10.14% Coelomycetes, 62.32% Hypomycetes, 18.84% sterile mycelia and 7.25% unidentified species were obtained. Species of Curvularia, Aspergillus, Fusarium, Colletotrichum and sterile fungus were isolated as dominant endophytes. Colonization frequency of Curvularia (7.25%) was highest which was isolated from all the tissues. The samples collected during the monsoon harbored more endophytes and showed higher species richness than the samples obtained in summer season. Of the total isolates, 15 isolates (21.74%) displayed antimicrobial activity, inhibiting at least one of the test microorganisms that comprised of pathogenic bacteria (Staphylococcus aureus, Bacillus subtilis, Escherichia coli, Salmonella typhi, Pseudomonas fluorescens, Shigella dysentriae) and fungi (Trichophyton rubrum, Aspergillus fumigatus, Trichophyton sp). The results provided promising baseline information on the endophytic fungal diversity associated with I. carnea tissues and their potential exploitation as antimicrobial agents.