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.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.