Coptisine

Insulin resistance (IR) is a central pathological feature of type 2 diabetes mellitus and metabolic syndrome, with dysregulated glycolytic metabolism in adipose tissue playing a critical role. Coptisine (Cop), a natural alkaloid, has been shown to exhibit anti-inflammatory and glucose-lowering properties; however, its mechanism in IR remains unclear.c Using both high-fat diet (HFD)-induced IR mice and tumor necrosis factor-α (TNF-α)-stimulated adipocytes, this study systematically evaluated the effects of Cop on insulin sensitivity and glycolytic metabolism. Techniques including glucose tolerance tests (GTTs), insulin tolerance tests (ITTs), Seahorse metabolic analysis, quantitative polymerase chain reaction (qPCR), Western blotting, and immunohistochemistry were employed to investigate the underlying mechanisms and the involvement of the key molecular target SMARCE1. Cop markedly improved IR in HFD-fed mice, reducing serum insulin levels, enhancing insulin sensitivity, and ameliorating adipose tissue architecture. In adipocyte models, Cop decreased levels of glycolytic metabolites lactate and pyruvate, expression of key glycolytic enzymes, includinng hexokinase 2 (HK2), lactate dehydrogenase A (LDHA), and pyruvate kinase M2 (PKM2), as well as extracellular acidification rate (ECAR). Further experiments revealed that Cop significantly inhibited SMARCE1 expression under IR conditions, while SMARCE1 overexpression reversed its inhibitory effects on glycolysis. In vivo studies confirmed that SMARCE1 overexpression exacerbated IR and up-regulated glycolytic enzyme expression in mice. Cop ameliorates IR by targeting SMARCE1-mediated suppression of glycolytic flux. These findings elucidate both the mechanistic basis and therapeutic potential of Cop for the treatment of metabolic disorders.

Helicobacter pylori remain a major global health challenge due to rising antibiotic resistance, persistent biofilm formation, and oxidative stress-mediated gastric pathogenesis. Innovative therapeutic approaches are urgently required to overcome the limitations of conventional antibiotic regimens.

We engineered a novel mucoadhesive nanocarrier (COP-LIG@LIPSNCs) by synergistically integrating biofilm-disrupting lignin nanoparticles with biocompatible liposomal vesicles to encapsulate the bioactive isoquinoline alkaloid coptisine. The formulations were comprehensively characterized using DLS, FTIR, XRD, and TEM. Antibacterial and antibiofilm were evaluated through MIC/MBC assays, time-kill kinetics, confocal bioimaging, and electron microscopy. Cytocompatibility was assessed using L929 fibroblasts, while in vivo mucoadhesion and therapeutic efficacy were investigated in a murine model.

COP-LIG@LIPSNCs exhibited a stable nanoscale size (∼197 nm; PDI 0.152; ζ-potential -31.4 mV, EE% 89.2 ± 1.4 % and LE% 2.1 ± 0.08 %). COP-LIG@LIPSNCs displayed sustained behaviour, releasing 42.28 ± 4.2 % in SGF and 58.17 ± 4.1 % in SIF after 48 h, with strong mucoadhesion. Antibacterial studies demonstrated potent activity against H. pylori (MIC 32 μg/mL; MBC 64 μg/mL), achieving >92 % eradication of planktonic cells and ∼ 89 % disruption of established biofilms within 24 h. CLSM and SEM confirmed nanocarrier penetration, membrane disruption, and biofilm dispersion. Surprisingly, the H. pylori burden of the COP@LIG@LIP group was significantly lower at 1.38 × 10⁴ CFU/g compared to negative control, indicating the effective treatment effect of killing H. pylori in vivo.

COP-LIG@LIPSNCs represent a novel and multifunctional nanoplatform that synergistically combines antimicrobial, antibiofilm, and antioxidant actions. This study pioneers a sustainable strategy using lignin to create an advanced therapeutic alternative, showing significant promise for managing drug-resistant H. pylori infections.