Research Progress of Coptis chinensis Franch. in the Intervention of Type 2 Diabetes Mellitus: A Perspective from Chemical Constituents and Signaling Pathways

Tianjin University of Traditional Chinese Medicine, College of Pharmaceutical Engineering of Traditional Chinese Medicine, Jinghai District, Tianjin, 301617, China

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Abstract

In recent years, the mechanism of action of Coptis chinensis Franch. (Huanglian) and its main active components (represented by berberine) in the prevention and treatment of type 2 diabetes mellitus (T2DM) has been extensively studied. Coptis chinensis Franch. regulates energy metabolism, antioxidant responses, and immunoinflammatory processes through multiple targets and pathways, thereby improving insulin sensitivity and protecting β-cell function. Emerging evidence indicates that Coptis chinensis Franch. exerts metabolic and anti-inflammatory effects not only via classical signalling pathways (e.g., PI3K/AKT, AMPK/Nrf2, NF-κB, mTOR) but also by intervening in various forms of regulated cell death (RCD), including autophagy, apoptosis, pyroptosis, and ferroptosis. Based on these findings, this review proposes the concept of the "Multidimensional Cell Death Network (MCDN)": under the pathological context of chronic metabolic stress induced by hyperglycaemia and hyperlipidaemia, various cell death pathways are interconnected and convertible, forming a "death network hub" centred on key molecules such as AMPK/mTOR, Nrf2, and NF-κB. Coptis chinensis Franch. achieves therapeutic effects from single-target inhibition to network homeostasis reconstruction through synergistic interventions at multiple nodes of this network (e.g., inhibiting the NLRP3-GSDMD proptosis axis, activating Nrf2/GPX4 to suppress ferroptosis, and promoting mitophagy via AMPK). This article systematically summarizes the chemical constituents, signalling pathways, and MCDN-related mechanisms of Coptis chinensis Franch. in T2DM intervention, and proposes future verification strategies based on multiomics and network pharmacology. It is expected to provide theoretical support for the clinical translation of Coptis chinensis Franch. and the modernization of traditional Chinese medicine (TCM).