Computational Investigation of Isoquinoline Alkaloid from the Stems of Tinospora Cordifolia against Polycystic Ovarian Syndrome

Abstract

Polycystic Ovarian Syndrome (PCOS)is a global, substantial, metabolic, and endocrine health concern affecting one in every five women of progenitive aged (reproductive) women. Despite the fact that systematic screening and early diagnosis have improved the conception rate in recent decades, infertility still claims ~4%-20% of reproductive-aged women across the globe. In contemporary drug development, in-silico techniques are predominantly employed to investigate interactions between drugs and receptors, as well as quantum chemical properties. A computational approach was used in the current study to conform the quantum chemical properties, Density-functional theory (DFT) analysis, ADMET drug-likeness of the Isoquinoline, alkaloid [Berberine (BER), Palmatine (PAL), Jatrorrhizine (JAT), &Magnoflorine (MAG)], isolated from Tinospora cordifolia stem, and the four receptors were selected from PDB database.Methods Docking studies were carried out withHuman Androgen Receptor(1E3G),Insulin receptor(3EKK), Estrogen Receptor beta(1U3S),and Human steroidogenic cytochromeP450 17A1(6WR0)by using AutoDockVina with a pliable ligand docking approach. ADMET prediction and toxicological predictions were performed using SwissADME. DFT analysis was used to predict the optimized structures and molecular electrostatic potential surfaces of the isolated compounds, GROMACS for Molecular Dynamic (MD) Simulation Studies.Results and Discussion BER and PALshown better docking scores against the1E3Ghuman androgen receptor.The absorption of molecules through the skin was measured in cm/s by the skin permeability value (Kp). Higher negative values of MAG (-6.44), JAT (-5.9), PAL (-5.79), and BER (-5.78) resulted in lower skin permeation (log Kp, cm/s). CYP17A1 has a remarkable binding affinity for all four Isoquinoline alkaloids [BER (-5.46), JAT (-5.26), MAG (-6.13), and PAL (-6.01). Isoquinoline alkaloids (BER& PAL) have potential roles against various diseases, and in specific PCOS, scientific evaluation has been put forth based on virtual screening.

Regulation of Insulin Resistance, Lipid Profile and Glucose Metabolism Associated with Polycystic Ovary Syndrome by Tinospora cordifolia

“…Isoquinoline alkaloids (such as berberine and palmatine) play significant roles in warding off a wide range of illnesses. Virtual screening has been used to evaluate the efficacy of an alkaloid extracted from TC stems for the treatment of PCOS [ 14 ]. Berberine improved IR and blood hormone levels in PCOS.…”

“…When docked against the human androgen receptor 1E3G, BER and PAL performed better than other compounds. Isoquinoline alkaloids (BER and PAL) may have functions against a variety of disorders; for example, virtual screening of an alkaloid from the stems of TC against PCOS led to a scientific evaluation [ 14 ]. Furthermore, BER effectively restored serum hormone levels and reduced insulin resistance.…”

Therapeutic Effect of Tinospora cordifolia (Willd) Extracts on Letrozole-Induced Polycystic Ovarian Syndrome and its Complications in Murine Model

“…Isoquinoline alkaloids are of tremendous interest due to their many therapeutic applications. The plant TC is said to be particularly high in isoquinoline alkaloids such as berberine, magnoflorine, palmatine and jatrorrhizine 19 and in another study berberine, isoquinoline alkaloids reversed ovarian apoptosis and morphological damage. Ber’s effects on ovarian granulosa cell proliferation and death were decreased by blocking the PI3K/AKT pathway.…”