Molecular targets of Durva Swaras (Cynodon dactylon L. Pers.) in menopause associated deranged hepatic lipid metabolism-non-estrogenic supplementation

AbstractMenopause is frequently associated with hepatic dysfunction and dyslipidemia mainly due to estrogen deficiency. While hormone replacement therapy (HRT) remains the conventional treatment, its long-term use is linked to endometrial hyperplasia and increased cancer risk. Durva Swaras (DS) as Herbal Alternative Therapy (HALT) reported osteoprotective and hepatoprotective effects in ovariectomised rat model of menopause. Moreover, protective role of DS in liver dysfunction is noted in mice liver injury model. In view of substantiating therapeutic benefits of DS, the current investigation monitors impact of DS therapy on gene expression changes in liver to assess lipid metabolism and uterus to evaluate estrogen response along with biochemical markers. Female Sprague-Dawley rats were sorted into sham operated (SHAM), ovariectomised (OVX), OVX with conjugated estrogen treatment (OVX+Std) and OVX with DS treatment (OVX+D). After 60 days of treatment, ovariectomy induced significant increase (p<0.05) in body weights along with elevation of serum lipoproteins compared to SHAM group. Ovariectomy elicited liver function enzymes and expression of hepatic SREBP-1c (Sterol Regulatory Element Binding Transcription Factor-lc), FAS1 (Fatty Acid Synthase-1), and PPAR? (Peroxisome Proliferator Activated Receptor Gamma) (p<0.01) genes besides downregulating PPARa (Peroxisome Proliferator Activated Receptor Alpha) and NRF2 (Nuclear Factor Erythroid 2-related Factor 2) genes. We noted significant decrease (p<0.05) in uteri weight and downregulation of IGF-1 (Insulin-like Growth Factor-1) mRNA in uterus of OVX rats. OVX+Std and OVX+D treatments significantly (p<0.05) lowered triglyceride levels. The liver function enzymes are greatly reduced in treatment groups compared to OVX. DS upregulated hepatic PPAR-a (p=0.1), NRF2 (p<0.05) along with downregulating PPAR? (p<0.01) gene expression. OVX+Std significantly increased (p<0.05) uteri weight and upregulated IGF-1 mRNA compared to OVX group. The ability to modulate key metabolic molecular targets without estrogenic effect on uterus validates DS potential in prevention and management of conditions like fatty liver, dyslipidemia, and oxidative stress during menopause.