Ameliorative effects of Ayurvedic Latakaranja vati on dehydroepiandrosterone-induced polycystic ovarian syndrome in rats via inhibition of pro-inflammatory cytokines and oxidative stress
10.1016/j.dcmed.2026.02.011
- Author:
Mandlik Deepa
;
Ghaisas Mahesh
;
Vaidya Anuja
;
Ukey Samee
;
Deshpande Manasi
;
Sathiyanarayanan Arulmozhi
- Publication Type:Journal Article
- Keywords:
Latakaranja vati;
Polycystic ovarian syndrome;
Dehydroepiandrosterone;
Network pharmacology;
Hormonal analysis
- From:
Digital Chinese Medicine
2026;9(1):144-160
- CountryChina
- Language:English
-
Abstract:
Objective:To evaluate the therapeutic potential and underlying mechanism of Latakaranja vati (LV) in dehydroepiandrosterone (DHEA)-induced polycystic ovarian syndrome (PCOS) in female Wistar rats through integrated network pharmacology, molecular docking, and experimental validation.
Methods:Bioactive constituents in LV tablets were identified using liquid chromatography-mass spectrometry (LC-MS). Network pharmacology analysis was performed to predict LV-related targets and PCOS-associated genes using BindingDB, Super-PRED, GeneCards, and DisGeNET databases. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses were conducted to clarify biological processes and signaling pathways. Molecular docking simulations evaluated binding affinities between LV phytoconstituents and key predicted targets. For in vivo validation, PCOS was induced in 36 female Wistar rats by daily subcutaneous administration of DHEA (60 mg/kg) for 21 d, and after successful model establishment, rats were randomly divided into DHEA, metformin (MET), clomiphene citrate (CC), and LV low-dose (LV-L, 51.5 mg/kg), medium-dose (LV-M, 103 mg/kg), and high-dose (LV-H, 206 mg/kg) groups (n = 6 each), which were orally administered for 21 d, respectively. Additional 6 rats were kept as normal control (NC) group, which did not receive any DHEA treatment. Estrous cyclicity, body weight, ovarian weight and diameter, fasting blood glucose (FBG), serum hormones [testosterone, progesterone, estrogen, follicle-stimulating hormone (FSH), luteinizing hormone (LH), and anti-Müllerian hormone (AMH)], insulin resistance [homeostatic model assessment for insulin resistance (HOMA-IR)], lipid profile [total cholesterol (TC), triglycerides (TG), high-density lipoprotein (HDL), and low-density lipoprotein (LDL)], inflammatory cytokines [tumor necrosis factor (TNF)-α and interleukin (IL)-6], oxidative stress markers [superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), malondialdehyde (MDA), and nitric oxide (NO)], myeloperoxidase (MPO), and ovarian histopathology were evaluated.
Results:LC-MS analysis identified eight major phytoconstituents in LV: sitosterol, citrulline, bonducellin, oleic acid, δ-caesalpin, heptocosane, palmitic acid, and stearic acid. Network pharmacology revealed 36 overlapping targets between LV and PCOS, with key targets including estrogen receptor 1 (ESR1), nuclear receptor subfamily 3 group C member 1 (NR3C1), signal transducer and activator of transcription 3 (STAT3), and epidermal growth factor receptor (EGFR). GO and KEGG enrichment analyses indicated involvement in lipid metabolism regulation, steroid hormone receptor activity, prolactin signaling pathway, hypoxia-inducible factor (HIF)-1 signaling pathway, and insulin resistance pathways. Molecular docking demonstrated strong binding affinities between LV phytoconstituents and predicted targets, with sitosterol showing the strongest binding to EGFR (− 9.9 kcal/mol) and ESR1 (− 8.3 kcal/mol). In vivo experiments confirmed that LV treatment restored normal estrous cyclicity and significantly reduced body weight, ovarian weight, and ovarian diameter compared with DHEA group (P < 0.05, P < 0.01, or P < 0.001). LV dose-dependently restored FBG, insulin, and HOMA-IR levels (P < 0.01 or P < 0.001), and improved lipid profile, including reduced TC, TG, and LDL, and increased HDL (P < 0.05, P < 0.01, or P < 0.001). Hormonal abnormalities were corrected with testosterone, LH, and AMH decreased and progesterone, estrogen, and FSH increased (P < 0.05, P < 0.01, or P < 0.001). Furthermore, LV enhanced activities of antioxidant enzymes (SOD, CAT, and GPx), and reduced oxidative stress markers (MDA and NO) (P < 0.05, P < 0.01, or P < 0.001). Pro-inflammatory cytokines TNF-α and IL-6 were significantly suppressed, and MPO activity decreased compared with DHEA group (P < 0.05, P < 0.01, or P < 0.001). Histopathological examination showed that after LV treatment, ovarian morphology recovered with cystic follicles decreased and corpus luteum increased. Among the three LV-treated groups, LV-H group exhibited the most pronounced improvements across all parameters, indicating a clear dose-dependent therapeutic effects.
Conclusion:LV showed protective effects against DHEA-induced pcos by restoring endocrine balance and mitigating metabolic, oxidative, and inflammatory disturbances. The involvement of key regulatory targets, including ESR1, NR3C1, STAT3, and EGFR, supports its multi-target therapeutic potential. These findings highlight LV as a promising herbal candidate for polycystic ovarian syndrome management.
