Shahrekord University of Medical Sciences Journal of Herbmed Pharmacology 2345-5004 15 2 2026 04 01 Lipid-lowering and weight-regulating effects of Triphala aqueous extract in a therapeutic rat model of hypercholesterolemia 239 249 10.34172/jhp.2026.53424 EN Wanlaya Naowaratwattana https://orcid.org/0000-0002-6798-8442 Ladachart Taepongsorat https://orcid.org/0009-0007-0358-5269 Bunleu Sungthong https://orcid.org/0000-0001-8697-0718 Prasob-orn Rinthong https://orcid.org/0000-0002-0359-7936 Journal Article 10.34172/jhp.2026.53424 2025 09 23 2026 02 10 Introduction: Triphala, an Ayurvedic polyherbal formulation composed of Terminalia chebula Retz., Terminalia bellirica (Gaertn.) Roxb., and Phyllanthus emblica L., is associated with metabolic regulation. This study evaluated the lipid-lowering effects of Triphala aqueous extract (TPL) in a therapeutic rat model of hypercholesterolemia and explored a potential mechanism involving 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibition. Methods: Male Wistar rats received cholesterol (2 g/kg, intragastric) in corn oil for 3 weeks to induce hypercholesterolemia. After biochemical confirmation, rats were assigned to six groups (n = 6 each): normal diet, hypercholesterolemic control, atorvastatin (10 mg/kg), or TPL (250, 500, and 1000 mg/kg). Cholesterol administration continued throughout the 6-week treatment period. Serum lipid profiles and body weight were monitored. HMG-CoA reductase inhibition by TPL and individual fruit extracts was assessed. Results: TPL 250 and 500 mg/kg significantly reduced total cholesterol (TC), triglyceride (TG), and low-density lipoprotein cholesterol (LDL-C), whereas TPL 500 mg/kg significantly increased high-density lipoprotein cholesterol (P<0.05). TPL 1000 mg/kg produced lipid-lowering effects comparable to atorvastatin and significantly decreased the atherogenic index of plasma at week 6. In vitro, TPL inhibited HMG-CoA reductase by 36.4±1.5% (5 µg/mL), compared with 82.5 ± 2.4% for pravastatin (0.5 µg/mL). Among individual fruit extracts, P. emblica exhibited the strongest inhibitory activity, followed by T. chebula and T. bellirica, while the combined TPL retained appreciable activity. TPL 1000 mg/kg also attenuated diet-induced body weight gain. Conclusion: TPL exerts significant lipid-lowering and weight-regulating effects under sustained cholesterol challenge, partly mediated by HMG-CoA reductase inhibition, supporting its potential as a natural adjunct for dyslipidemia.