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The present study aimed at isolation of endophytic basidiomycetous fungi and evaluation of their in-vitro and in-vivo antidiabetic potential. Preliminary screening for in-vitro activity was carried out using α-glucosidase inhibition assay. An endophytic isolate Sch1 (isolated from Aloe vera), identified to be Schizophyllum commune Fr. on molecular basis, exhibiting more than 90% α-glucosidase inhibitiory activity was selected for further studies. Detailed in-vivo investigations for antidiabetic potential of ethyl acetate extract of S. commune (Sch1), at two different doses, were carried out in streptozotocin induced diabetic Wistar rats. Treatment of diabetic rats with S. commune extract caused significant decrease in blood glucose level and increase in body weight after 14 days experimental period. It significantly restored renal parameters including creatinine, blood urea nitrogen, fractional excretion of sodium, and potassium level in diabetic rats. Improvement in lipid profile and level of antioxidant parameters viz. reduced glutathione, thiobarbituric acid reactive species, and superoxide anion generation was also observed after treatment. Liver enzymes (serum glutamic pyruvic transaminase, serum glutamic-oxaloacetic transaminases, and alkaline phosphatase) homeostasis was found to be markedly improved in diabetic rats administered with S. commune extract. The effects were more pronounced at higher concentration and comparable to acarbose which was used as positive control. Phytochemical analysis revealed the presence of phenolics and terpenoids in the ethyl acetate extract. This is the first report highlighting the therapeutic potential of an endophytic S. commune in the management of diabetes.

The current investigation was aimed at in vivo MAOA inhibitory activity of coumarins angelicin, bergapten, and scopoletin isolated from the roots of Angelica archangelica. The isolated compounds were screened for MAOA (pdb ID 2Z5y) binding through molecular docking studies. The molecular docking results displayed that bergapten has a maximum affinity for MAOA, followed by angelicin and scopoletin. In silico prediction of physicochemical parameters indicated that maximum blood–brain barrier (BBB) permeability was observed with angelicin (2.3), followed by bergapten (2.0) and least with scopoletin (0.644). In consonance to the results of molecular docking studies, appreciable in vivo antidepressant activity of angelicin and bergaptan was observed over the mouse model of reserpine-induced depression. The modulation of MAOA in the antidepressant effect of extract and its isolated fractions was also determined. Biochemical examination of the brain tissue indicated that bergapten has maximum MAOA inhibitory activity while scopoletin fails to inhibit brain MAOA.

Beyond the conventional mode of working of anti-inflammatory agents through enzyme inhibition, herein, COX-2 was provided with an alternate substrate. A proline-centered pentapeptide isoconformational to arachidonic acid, which exhibited appreciable selectivity for COX-2, overcoming acetic acid- and formalin-induced pain in rats to almost 80%, was treated as a substrate by the enzyme. Remarkably, COX-2 metabolized the pentapeptide into small fragments consisting mainly of di- and tripeptides that ensured the safe breakdown of the peptide under in vivo conditions. The kinetic parameter K cat/K m for COX-2-mediated metabolism of the peptide (6.3 × 105 M–1 s–1) was quite similar to 9.5 × 105 M–1 s–1 for arachidonic acid. Evidenced by the molecular dynamic studies and the use of Y385F COX-2, it was observed that the breakage of the pentapeptide has probably been taken place through H-bond activation of the peptide bond by the side chains of Y385 and S530.