Jiang-Zhi-Ning, a traditional Chinese herbal formula for hyperlipidemia: An integrated review of its ethnopharmacology, mechanisms, and clinical potential

Ethnopharmacological Relevance Hyperlipidemia is a complex metabolic disorder and a primary driver of cardiovascular disease. Jiang-Zhi-Ning (JZN), a classical botanical formula in Traditional Chinese Medicine (TCM), has been historically employed to treat syndromes characterized by "phlegm-turbidity" and "blood stasis"—pathological states analogous to modern dyslipidemia and atherogenesis. Composed of hawthorn ( Crataegus pinnatifida Bunge), processed Polygonum multiflorum ( Polygonum multiflorum Thunb.), cassia seeds ( Cassia obtusifolia L . ), and lotus leaf ( Nelumbo nucifera Gaertn.), JZN utilizes a synergistic hierarchical framework (sovereign-minister-assistant-messenger) to achieve holistic metabolic regulation. Aim This review systematically synthesizes recent advancements in JZN research, evaluating its ethnopharmacological rationale, phytochemical profile, molecular mechanisms, and clinical efficacy. Furthermore, it delineates JZN’s multi-target paradigm through a comparative analysis with conventional single-target lipid-lowering pharmacotherapies. Methods A comprehensive literature retrieval was conducted across major electronic databasesc including PubMed, ScienceDirect, Web of Science, CNKI, through January 2026. By synthesizing data from preclinical models, clinical trials, and historical TCM texts, we critically analyzed the pharmacological mechanisms and therapeutic utility of JZN. Results The bioactive constituents of JZN orchestrate a synergistic, multi-pathway response. The formula inhibits exogenous lipid absorption by suppressing pancreatic lipase; recalibrates hepatic lipid metabolism by upregulating low-density lipoprotein receptor (LDL-R), Cytochrome P450 Family 7 Subfamily A Member 1 (CYP7A1), and Adenosine Monophosphate-activated Protein Kinase (AMPK), while simultaneously downregulating 3-Hydroxy-3-Methylglutaryl-Coenzyme A (HMG-CoA) reductase and Sterol Regulatory Element-Binding Protein-1c(SREBP-1c); and mitigates vascular injury by modulating the (NF-κB) inflammatory cascade and bolstering antioxidant defenses. Preclinical and clinical data indicate that JZN correlates with a reduction in total cholesterol, triglycerides, and LDL-C, while elevating high-density lipoprotein cholesterol (HDL-C) and ameliorating atherosclerotic and hepatic lesions with a highly favorable safety profile. Conclusions While JZN exemplifies the convergence of TCM principles and modern molecular pharmacology, its clinical translation remains contingent upon transitioning from isolated in vitro models to high-throughput systems biology platforms and mRNA-centric data. Current findings predominantly reside within the realm of "mechanistic hypotheses," where a significant evidence chain fragment persists between gene transcription and final metabolic phenotypes. To bridge this gap, future research trajectories must pivot from fragmented descriptive studies toward systems pharmacology and robust, multicenter randomized controlled trials. Such a shift is essential to disentangle the complex synergistic networks inherent in this four-herb formula and to validate its long-term clinical efficacy against hard cardiovascular endpoints.