Vito Anggarino Damay, Juan Leonardo, Axel Brahmantyo Maynardo Nugroho, Vincent Lau, Arditya Damarkusuma, Dante Saksono Harbuwono, Sidartawan Soegondo, Happy Kurnia Permatasari, Ratna Karuna, Nurpudji Astuti Taslim, Raymond Rubianto Tjandrawinata, Hilman Zulkifli Amin, Antonello Santini, Sergio Vencio, Rony Abdi Syahputra, Fahrul Nurkolis
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 lipase-inhibitory 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, lipid-regulatory, 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. © 2025 The Author(s)
Department of Cardiovascular Medicine, Universitas Pelita Harapan, Banten, Tangerang, 15811, Indonesia; Citra Deli Kreasitama Ltd, Banten, 15124, Indonesia; Cardiac, Thoracic, and Vascular Surgery Study Program, Faculty of Medicine, University of Indonesia, Jakarta, 10430, Indonesia; Faculty of Medicine, Universitas Indonesia, Jakarta Pusat, 10430, Indonesia; Department of Cardiology and Vascular Medicine, Faculty of Medicine, Public Health, and Nursing, Universitas Gadjah Mada-RS Sardjito, Yogyakarta, Indonesia; Division of Endocrinology, Metabolism, and Diabetes, Department of Internal Medicine, Faculty of Medicine Universitas Indonesia, Dr. Cipto Mangunkusumo National Referral Hospital, Jakarta, 10430, Indonesia; Department of Biochemistry and Biomolecular, Faculty of Medicine, Universitas Brawijaya, Malang, Indonesia; Universitas Kristen Petra, Surabaya, 60236, Indonesia; Division of Clinical Nutrition, Department of Nutrition, Faculty of Medicine, Hasanuddin University, Makassar, Indonesia; Center for Pharmaceutical and Nutraceutical Research and Policy, Faculty of Biotechnology, Atma Jaya Catholic University of Indonesia, Jakarta, 12930, Indonesia; Department of Cardiovascular Medicine, National Cerebral and Cardiovascular Center, Osaka, Japan; Faculty of Medicine, Universitas Indonesia, Jalan Salemba Raya No 6, Central Jakarta, 10430, Indonesia; Department of Pharmacy, University of Napoli Federico II, Via Domenico Montesano, 49 – 80131, Napoli, Italy; Institute of Pharmaceutical Sciences, GO, Goiania, Brazil; Department of Pharmacology, Faculty of Pharmacy, Universitas Sumatera Utara, Medan, 20155, Indonesia; Master of Basic Medical Science, Faculty of Medicine, Universitas Airlangga, Surabaya, Indonesia; State Islamic University of Sunan Kalijaga (UIN Sunan Kalijaga), Yogyakarta, 55281, Indonesia; Medical Research Center of Indonesia, Surabaya, Indonesia
