Deltan polyherbal formula offers multifaceted protection against cardiometabolic syndrome via metabolic and microbiome rebalancing

Objective: Cardiometabolic syndrome (CMS) increases risks for type 2 diabetes and cardiovascular disease. Although individual herbal extracts such as Panax ginseng, Panax notoginseng, and Salvia miltiorrhiza have demonstrated metabolic and cardiovascular benefits, their combined synergistic actions have not been comprehensively evaluated within an integrated preclinical framework. This study aimed to evaluate the efficacy of Deltan, a polyherbal formulation of Panax ginseng, Panax notoginseng, and Salvia miltiorrhiza, in mitigating CMS by modulating oxidative stress, lipid metabolism, inflammation, and gut microbiota. Methods: A multi-tiered approach was employed, including UHPLC–HRMS metabolomic profiling, in silico molecular docking, in vitro antioxidant, lipase-inhibitory, and cardiomyoblast viability assays, and an eight-week randomized, controlled preclinical trial in Wistar rats fed a cholesterol- and fat-enriched diet. Evaluations included biochemical parameters, inflammatory mediators, and gut microbiota analysis via 16S rRNA sequencing. Results: Deltan demonstrated potent antioxidant (IC₅₀ = 45.2 ± 2.3 μg/mL for DPPH scavenging) and lipaseinhibitory activities (IC₅₀ = 38.7 ± 1.9 μg/mL), effectively preserving H9c2 cardiomyoblast viability (89.6 ±3.4 % at 100 μg/mL) and reducing PCSK9 (↓ 31 %) and Galectin-3 (↓ 27 %) secretion, comparable to simvastatin (↓ 35 % and ↓ 29 %, respectively). In vivo, Deltan prevented diet-induced weight gain (􀀀 18.4 % vs. CFED control), normalized serum lipids (total cholesterol ↓ 29 %, triglycerides ↓ 24 %, HDL ↑ 18 %) and glucose (↓ 22 %), attenuated hepatic stress markers (ALT and AST ↓ ~30 %), and regulated inflammatory and lipid-regulatory biomarkers including TNF-α (↓ 33 %), PCSK9 (↓ 36 %), ANGPTL3 (↓ 28 %), and PLA2G7 (↓ 25 %). Conclusion: Deltan effectively targets multiple aspects of CMS through antioxidative, anti-inflammatory, lipidregulatory, and microbiota-modulating mechanisms. These preclinical findings highlight its potential as a safe, multi-target phytotherapeutic intervention for CMS. Future studies should isolate active phytochemicals, elucidate detailed molecular pathways, and validate efficacy through clinical trials.