Tehran University of Medical Sciences Traditional and Integrative Medicine 2476-5104 11 1 2026 03 21 2279 2279 EN Anang Triadi Faculty of Medicine, Universitas Wijaya Kusuma Surabaya, Surabaya, Indonesia Johanes Aprilius Kristijanto Faculty of Medicine, Universitas Wijaya Kusuma Surabaya, Surabaya, Indonesia Muzaijadah Arimbi Department of Internal Medicine, Faculty of Medicine, Universitas Wijaya Kusuma Surabaya, Surabaya, Indonesia Nur Khamidah Department of Public Health, Faculty of Medicine, Universitas Wijaya Kusuma Surabaya, Surabaya, Indonesia Farida Soetedjo Department of Internal Medicine, Faculty of Medicine, Universitas Wijaya Kusuma Surabaya, Surabaya, Indonesia 2025 07 31 2025 11 08 Secondhand smoke (SHS) exposure is a major environmental risk factor that contributes to dyslipidemia and cardiovascular diseases by disrupting hepatic lipid metabolism. Peperomia pellucida (L.) Kunth, a medicinal herb rich in polyphenols and flavonoids, has demonstrated potential lipid-regulating properties, but its efficacy against SHS-induced metabolic disturbances remains underexplored. This study investigated the therapeutic effects of ethanolic extract of P. pellucida on SHS-induced dyslipidemia in male Wistar rats by integrating biochemical, molecular, and translational endpoints. Rats were divided into five groups: normal control (NC), P. pellucida-only (PP), SHS-exposed control (SHS), SHS + atorvastatin (SHS+ATV), and SHS + P. pellucida (SHS+PP). SHS exposure was performed for 4 weeks using a standardized sidestream smoke chamber, followed by 4 weeks of oral treatment. Serum lipid profiles (TC, TG, LDL-C, HDL-C, VLDL-C) and atherogenic index (TC/HDL-C) were measured enzymatically. Hepatic mRNA expression of SREBP-1c, PPAR-α, and LDLR was assessed via RT-qPCR, and corresponding protein levels were quantified using rat-specific ELISA kits. Total phenolic and flavonoid content of the extract were determined spectrophotometrically. SHS exposure induced significant dyslipidemia and upregulated hepatic SREBP-1c while downregulating PPAR-α and LDLR at both mRNA and protein levels (p < 0.05). Treatment with P. pellucida significantly (p < 0.05) restored lipid parameters and normalized gene and protein expression profiles, with comparable efficacy to atorvastatin. The extract showed high phenolic and flavonoid content, supporting its bioactivity. In conclusion, P. pellucida ameliorates SHS-induced dyslipidemia through modulation of key hepatic lipid metabolism regulators at transcriptional and translational levels, highlighting its potential as a phytotherapeutic candidate for environmentally triggered metabolic disorders. https://jtim.tums.ac.ir/index.php/jtim/article/view/2279