Processed Buthus martensii Karsch scorpions ameliorate diet-induced NASH in mice by attenuating Kv1.3-mediated macrophage activation.

Autor: Xu E; School of Integrative Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, China; State Key Laboratory on Technologies for Chinese Medicine Pharmaceutical Process Control and Intelligent Manufacture, Nanjing University of Chinese Medicine, Nanjing, Jiangsu, 210023, China; Jiangsu Provincial Medicinal Innovation Center, Affiliated Hospital of Integrated Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing, Jiangsu, 210028, China., Sang M; Jiangsu Provincial Medicinal Innovation Center, Affiliated Hospital of Integrated Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing, Jiangsu, 210028, China., Xu W; State Key Laboratory on Technologies for Chinese Medicine Pharmaceutical Process Control and Intelligent Manufacture, Nanjing University of Chinese Medicine, Nanjing, Jiangsu, 210023, China., Chen Y; State Key Laboratory on Technologies for Chinese Medicine Pharmaceutical Process Control and Intelligent Manufacture, Nanjing University of Chinese Medicine, Nanjing, Jiangsu, 210023, China., Wang Z; State Key Laboratory on Technologies for Chinese Medicine Pharmaceutical Process Control and Intelligent Manufacture, Nanjing University of Chinese Medicine, Nanjing, Jiangsu, 210023, China., Zhang Y; State Key Laboratory on Technologies for Chinese Medicine Pharmaceutical Process Control and Intelligent Manufacture, Nanjing University of Chinese Medicine, Nanjing, Jiangsu, 210023, China., Lu W; Jiangsu Provincial Medicinal Innovation Center, Affiliated Hospital of Integrated Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing, Jiangsu, 210028, China. Electronic address: luwuguang@njucm.edu.cn., Cao P; Quzhou Affiliated Hospital of Wenzhou Medical University, Quzhou People's Hospital, Quzhou, Zhejiang, 324000, China; State Key Laboratory on Technologies for Chinese Medicine Pharmaceutical Process Control and Intelligent Manufacture, Nanjing University of Chinese Medicine, Nanjing, Jiangsu, 210023, China; Jiangsu Provincial Medicinal Innovation Center, Affiliated Hospital of Integrated Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing, Jiangsu, 210028, China; Shandong Academy of Chinese Medicine, Jinan, 250014, China; Animal-Derived Chinese Medicine and Functional Peptides International Collaboration Joint Laboratory, Nanjing University of Chinese Medicine, Nanjing, Jiangsu, 210023, China. Electronic address: cao_peng@njucm.edu.cn.
Jazyk: angličtina
Zdroj: Journal of ethnopharmacology [J Ethnopharmacol] 2025 Jan 30; Vol. 337 (Pt 1), pp. 118794. Date of Electronic Publication: 2024 Sep 05.
DOI: 10.1016/j.jep.2024.118794
Abstrakt: Ethnopharmacological Relevance: Processed Buthus martensii Karsch (BmK) scorpion, also known as Quan-Xie, is a traditional Chinese medicine that is clinically used for the treatment of NAFLD due to its Tong-Luo-San-Jie effects. Our previous study showed that aqueous extract of processed BmK scorpion venom gland (pVg AE) inhibited macrophage inflammation by targeting Kv1.3 and identified the thermostable peptide BmKK2 as a potent Kv1.3 blocker.
Aim of the Study: This study examined the therapeutic effects of processed BmK scorpions on NASH, specifically focusing on the involvement of their anti-inflammatory effects mediated by macrophage-expressed Kv1.3 in NASH.
Materials and Methods: In the present study, the anti-NASH effects of pVg AE were evaluated in high-fat diet (HFD)-induced NASH mouse models. Additionally, the in vitro anti-inflammatory mechanisms of pVg AE and BmKK2 were assessed using a palmitic acid (PA)-induced mouse bone marrow-derived macrophages (BMDMs) inflammation model. Protein and cytokine expression related to the Kv1.3-NF-κB pathway was analyzed by real-time PCR, immunoblotting and ELISA. The effect of pVg AE and BmKK2 on potassium channels was detected by whole-cell voltage-clamp recordings on transfected HEK293T cells or mouse BMDMs. Calcium ion imaging was used to evaluate intracellular calcium signaling. Furthermore, the study utilized Kv1.3 siRNA and a BMDMs and hepatocytes co-culture model to investigate the specific role of Kv1.3 in mediating the anti-NASH effects of pVg AE and BmKK2.
Results: Lipid accumulation upregulated Kv1.3 expression in macrophages in vivo and in vitro. However, pVg AE significantly reduced Kv1.3 expression and Kv1.3-positive macrophage infiltration. Treatment with pVg AE improved obesity, insulin resistance (IR), hepatic steatosis (HS), inflammation, and fibrosis in HFD-fed mice. Mechanistically, pVg AE and BmKK2 inhibited macrophage inflammation by targeting Kv1.3, which reduced PA-induced intracellular Ca 2+ levels, resulting in the inhibition of the NF-κB pathway and TNFα release.
Conclusions: This study demonstrates that Kv1.3-mediated macrophage inflammation is involved in the pathogenesis and treatment of NASH. pVg AE effectively alleviates metabolic stress-induced NASH by inhibiting this inflammation.
Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2024 Elsevier B.V. All rights reserved.)
Databáze: MEDLINE