Effects of combined epigallocatechin gallate and chlorogenic acid on metabolic parameters and pulmonary remodeling in a metabolic syndrome model: A preclinical study

Abstract

Metabolic syndrome (MetS) may contribute to pulmonary fibrotic remodeling through metabolic dysregulation, oxidative stress, and inflammatory signaling. Epigallocatechin gallate (EGCG) and chlorogenic acid (CGA) have antioxidant, anti-inflammatory, and metabolic regulatory properties, but their combined effects on systemic and pulmonary peroxisome proliferator-activated receptor gamma (PPARγ) levels and pulmonary fibrosis in MetS remain insufficiently characterized. The aim of this study was to evaluate the effects of combined EGCG and CGA administration on metabolic parameters, plasma and lung tissue PPARγ levels, and histological pulmonary fibrosis severity, as well as to examine the relationships between PPARγ levels and fibrosis severity in a rat model of MetS. This experimental study included 30 male Sprague-Dawley rats randomly allocated to healthy control, untreated MetS, and MetS treated with combined EGCG-CGA groups (n=10 each). MetS was induced using a high-fat, high-sucrose diet and intraperitoneal streptozotocin. Treated rats received EGCG 300 mg/kg/day and CGA 200 mg/kg/day by oral gavage for nine weeks. Metabolic parameters, plasma and lung tissue PPARγ levels, and pulmonary fibrosis severity assessed using the modified Ashcroft score were evaluated. Compared with controls, untreated MetS rats had higher body weight, fasting blood glucose, triglyceride levels, and Ashcroft scores, but lower high-density lipoprotein (HDL) cholesterol and plasma and lung PPARγ levels (all p<0.001). Compared with untreated MetS rats, EGCG-CGA-treated rats had a more favorable metabolic profile and lower Ashcroft scores (p=0.012). Plasma and lung PPARγ levels were higher in EGCG-CGA-treated rats than in untreated MetS rats (64.4±35.1 vs 17.0±4.9 ng/mL and 46.0±7.2 vs 27.9±4.9 ng/mg protein, respectively; both p<0.001). Plasma and lung PPARγ were positively correlated (r=0.805; p<0.001), whereas both were negatively correlated with Ashcroft score (r=-0.749 and r=-0.912, respectively; both p<0.001). In conclusion, combined EGCG-CGA was associated with improved metabolic profiles, increased systemic and pulmonary PPARγ levels, and lower histological pulmonary fibrosis severity in MetS rats.