image: (A) TG levels in HepG2 cells treated with vehicle (BSA), Bv (20 μg/mL), or 23 isolated compounds (20 μg/mL) for 24 h in the presence of PA. (B) Structure of P19 (BmK Tx-2). (C) Schematic of the experimental procedure used to investigate the effects of BmK Tx-2 on GAN diet-induced MASH in mice. The mice were intraperitoneally administered saline or BmK Tx-2 (75 or 150 nmol/kg) on alternate days for 8 weeks starting at week 16; n = 8-9 mice per group. (D) Serum levels of lipids (TGs and TC) in the mice. (E) LW/BW values of the mice. (F) Liver lipid content (TGs). (G) H&E staining and NASs of mouse liver sections. Scale bar, 50 µm. (H) Immunohistochemical staining and quantification of CD11b+ cells in mouse liver sections. Scale bar, 50 µm. (I) Serum ALT and AST levels in the mice. (J) PSR staining and statistical analysis of PSR-stained mouse liver sections. Scale bar, 50 µm. (K-L) mRNA levels of proinflammatory markers (Il-1β, Il6, and Tnf-α), chemokines (Ccl2 and Cxcl10) and MASH-related profibrotic molecules (Col1α1, α-Sma, Ctgf, and Tgfβ) in the mouse liver. (M) Schematic of the experimental procedure used to investigate the role of BmK Tx-2 in CD-HFD diet-induced MASH in mice. The mice were intraperitoneally administered saline, BmK Tx-2 (150 nmol/kg) or Resmetirom (3 mg/kg) for 6 weeks starting at week 3; n = 6 mice per group. (N) Serum ALT and AST levels in the mice. (O) H&E staining and NASs of mouse liver sections. Scale bar, 50 µm. (P) PSR staining and statistical analysis of PSR stained mouse liver sections. Scale bar, 50 µm. (Q) mRNA levels of proinflammatory markers (Il-1β, Il6, and Tnf-α), chemokines (Ccl2 and Cxcl10), and MASH-related profibrotic molecules (Col1α1, α-Sma, Ctgf, and Tgfβ) in the mouse liver. The data are presented as the means ± SEMs. Significance was assessed via one-way ANOVA (A, D, E, F, G, H, I, J, K, L, N, O, P and Q). # indicates a significant difference compared with the NCD group. ##p < 0.01. * indicates a significant difference compared with the GAN group or CD-HFD group. *p < 0.05, **p < 0.01.
Credit: Erjin Xu, Wuguang Lu, Yonggen Chen, Ming Sang, Jiao Chen, Xueting Cai, Wenhao Xu, Yuxin Zhang, Zhiheng Wang, Feng Zhang, Peng Cao
Researchers have identified a peptide from the venom of the Buthus martensii Karsch scorpion that can penetrate liver cells and disrupt a protein interaction implicated in fatty liver disease. The peptide, named BmK Tx-2, binds to a heat shock protein (HSP90β) that normally suppresses a fat-burning transcription factor (PPARα). By blocking this interaction, BmK Tx-2 promotes PPARα activity, enhances fatty acid oxidation, and reduces liver fat, inflammation, and fibrosis in diet-induced mouse models of MASLD. The study, published in iMetaMed, highlights a new mechanistic approach for treating metabolic liver diseases by targeting protein–protein interactions within cells.
Article Title
A cell-penetrating scorpion venom peptide disrupts the HSP90β–PPARα interaction to ameliorate metabolic dysfunction-associated steatotic liver disease
Article Publication Date
23-Dec-2025
COI Statement
The authors declare no conflicts of interest.