CYP3A4 mediated pharmacokinetics drug interaction potential of Maha-Yogaraj Gugglu and E, Z guggulsterone

Abstract

Maha yogaraja guggulu (MYG) is a classical herbomineral polyherbal formulation being widely used since centuries. The aim of this study was to investigate the effect of MYG formulation and its major constituents E & Z guggulsterone on CYP3A4 mediated metabolism. In vitro inhibition of MYG and Guggulsterone isomers on CYP3A4 was evaluated by high throughput fluorometric assay. Eighteen Adult male Sprague–Dawley rats (200 ± 25 g body weight) were randomly divided into three groups. Group A, Group B and Group C were treated with placebo, MYG and Standard E & Z guggulsterone for 14 days respectively by oral route. On 15th day, midazolam (5 mg/kg) was administered orally to all rats in each group. Blood samples (0.3 mL) were collected from the retro orbital vein at 0.25, 0.5, 0.75, 1, 2, 4, 6, 12 and 24 h of each rat were collected. The findings from the in vitro & in vivo study proposed that the MYG tablets and its guggulsterone isomers have drug interaction potential when consumed along with conventional drugs which are CYP3A4 substrates. In vivo pharmacokinetic drug interaction study of midazolam pointed out that the MYG tablets and guggulsterone isomers showed an inhibitory activity towards CYP3A4 which may have leads to clinically significant interactions.

Alpinetin suppresses CYP3A4, 2C9, and 2E1 activity in vitro

“…For instance, the inhibitory effect of Maha yogaraja guggulu and its major ingredients ( E -guggulsterone and Z -guggulsterone) on CYP3A4 led to its interaction with conventional CYP3A4 substrates (Sabarathinam et al. 2021 ). Moreover, due the anti-breast cancer activity of alpinetin, its co-adminsitration with other antitumor drugs should draw special attention.…”

Standardization and validation of phytometabolites by UHPLC and high‐performance thin layer chromatography for rapid quality assessment of ancient ayurvedic medicine, Mahayograj Guggul

“…These obtained F I G U R E 3 3D UV-Visible spectra of (A) reference standard-mix and (B) Mahayograj Guggul (MYG). Ten target analytes, (1) gallic acid, (2) protocatechuic acid, (3) vanillic acid, (4) ferulic acid, (5) ellagic acid, (6) picroside I, (7) cinnamic Acid, (8) piperine, (9) guggulsterone-E, and (10) guggulsterone-Z, were scanned with respect to time (x-axis), wavelength (y-axis), and signal intensity (z-axis). UHPLC fingerprint of reference standard-mix and detected analytes of MYG were found similar high recoveries confirm that the proposed method is validated in terms of the accuracy (Table 3).…”

“…The Guggul, core ingredient of MYG medicine, is a resin obtained from Commiphora mukul [8]. Phytochemically, the resin is composed of minerals, terpenes, essential oil, sterols, sterones (guggulsterone ‐E,‐ Z, ‐M and dehydro‐guggulsterone‐M), ferrulates, lignans, and flavanones, which are responsible for its capabilities against various chronic diseases [9,10]. Collected evidence suggest that guggulsterone‐E and ‐Z have potent lipid lowering, cardio‐protective, and anti‐inflammatory capabilities [11].…”

In Silico Studies Comparing the Adjuvant Therapies Approved for Parkinson’s disease

“…The ADMET parameters of the chosen drugs were assessed using the pKCSM online server 9,10,11,12 . Various properties like the factors concerning the absorption, distribution, metabolism, excretion and toxicity were collected from the server.…”