PUBLICATION

Tanshinone IIA from Salvia miltiorrhiza alleviates follicular maturation arrest symptoms in zebrafish via binding to the human androgen receptors and modulating Tox3 and Dennd1a

Authors
Priyanka, G.C.L., Mahalakshmi, N.C., Almutairi, M.H., Almutairi, B.O., Sudhakaran, G., Premkumar, B., Arockiaraj, J.
ID
ZDB-PUB-240518-7
Date
2024
Source
Tissue & Cell   88: 102404102404 (Journal)
Registered Authors
Keywords
Human androgen receptors, Molecular dynamics, Polycystic ovarian syndrome Tanshinone IIA, Zebrafish
MeSH Terms
  • Protein Binding/drug effects
  • Salvia miltiorrhiza*/chemistry
  • Abietanes*/pharmacology
  • Female
  • Animals
  • Ovarian Follicle*/drug effects
  • Ovarian Follicle*/metabolism
  • Ovarian Follicle*/pathology
  • Receptors, Androgen*/metabolism
  • Zebrafish*
  • Molecular Docking Simulation
  • Humans
  • Signal Transduction/drug effects
  • Polycystic Ovary Syndrome*/drug therapy
  • Polycystic Ovary Syndrome*/metabolism
  • Polycystic Ovary Syndrome*/pathology
  • Zebrafish Proteins/metabolism
PubMed
38759521 Full text @ Tissue Cell
Abstract
Follicular maturation arrest is a prevalent endocrine disorder characterized by hormonal imbalance, ovarian dysfunction, and metabolic disturbances leading to Polycystic ovarian syndrome (PCOS). Tanshinone IIA (TIIA), a bioactive compound derived from Salvia miltiorrhiza, has shown promising therapeutic potential in various diseases, including cardiovascular diseases and cancer. However, its effects on reproductive health and gynecological disorders, particularly PCOS, remain poorly understood. In this study, we investigated the potential therapeutic effects of TIIA on ovarian function. Using a combination of experimental and computational approaches, we elucidated the molecular mechanisms underlying TIIA's pharmacological impact on ovarian function, follicular development, and androgen receptor signaling. Molecular docking and dynamics simulations revealed that TIIA interacts with the human androgen receptor (HAR), modulating its activity and downstream signaling pathways. Our results demonstrate that TIIA treatment alleviates PCOS-like symptoms in a zebrafish model, including improved follicular development, lowered GSI index, improved antioxidant status (SOD, CAT), decreased LDH levels, and enhanced AChE levels by regulating Tox3 and Dennd1a pathway. Our findings suggest that TIIA may hold promise as a novel therapeutic agent for the management of PCOS or ovulation induction.
Genes / Markers
Figures
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Antibodies
Orthology
Engineered Foreign Genes
Mapping