2. Academic Validation
  3. BmKK2, a thermostable Kv1.3 blocker from Buthus martensii Karsch (BmK) scorpion, inhibits the activation of macrophages via Kv1.3-NF-κB- NLPR3 axis

BmKK2, a thermostable Kv1.3 blocker from Buthus martensii Karsch (BmK) scorpion, inhibits the activation of macrophages via Kv1.3-NF-κB- NLPR3 axis

  • J Ethnopharmacol. 2023 May 12;116624. doi: 10.1016/j.jep.2023.116624.
Zhiheng Wang 1,  Ming Sang 1,  Yuxin Zhang 2,  Shengjun Chen 3,  Song Li 3,  Yonggen Chen 2,  Erjin Xu 1,  Qian Zhou 1,  Wenhao Xu 2,  Chenglei Zhao 1,  Dawei Wang 1,  Wuguang Lu 4,  Peng Cao 5
Affiliations

Affiliations

  • 1 Jiangsu Provincial Medical Innovation Center, Affiliated Hospital of Integrated Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing, Jiangsu, 210028, China.
  • 2 School of Pharmacy, Nanjing University of Chinese Medicine, Nanjing, Jiangsu, 210023, China.
  • 3 Tianjiang Phamarceutical Co., Ltd, China.
  • 4 Jiangsu Provincial Medical Innovation Center, Affiliated Hospital of Integrated Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing, Jiangsu, 210028, China; School of Pharmacy, Nanjing University of Chinese Medicine, Nanjing, Jiangsu, 210023, China. Electronic address: [email protected].
  • 5 Jiangsu Provincial Medical Innovation Center, Affiliated Hospital of Integrated Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing, Jiangsu, 210028, China; School of Pharmacy, Nanjing University of Chinese Medicine, Nanjing, Jiangsu, 210023, China. Electronic address: [email protected].
PMID: 37182676 DOI: 10.1016/j.jep.2023.116624
Abstract

Ethnopharmacological relevance: Inflammation plays pivotal role in the development of chronic diseases. Reducing chronic inflammation is an important strategy for preventing and managing many chronic diseases. In traditional Chinese medicine, the processed Buthus martensii Karsch (BmK) scorpion(also called "Quanxie") has been used to treat chronic inflammatory arthritis and spondylitis for hundreds of years suggests that "Quanxie" could potentially be utilized as a resource for identifying new anti-inflammatory compounds. However, the molecular basis and the underline mechanism for the anti-inflammatory effect of processed BmK scorpion are still unclear.

Aim of the study: The study aims to determine the potential involvement of macrophage-expressed Kv1.3 in the anti-inflammatory effect of processed BmK scorpion venom, as well as to identify new Kv1.3 blockers derived from processed BmK scorpion.

Materials and methods: In this study, the in vivo and in vitro anti-inflammatory activities were determined using carrageenan-induced paw edema, LPS-induced sepsis mouse models and LPS-induced macrophage activation model respectively. The effect of processed BmK scorpion water extract, processed BmK venom and BmKK2 on different potassium channels were detected by whole-cell voltage-clamp recordings on transfected HEK293 cells or mouse BMDMs. The cytokines were detected using RT-PCR and competitive enzyme-linked immunosorbent assay. High performance liquid chromatography, SDS-PAGE and peptide Mass Spectrometry analysis were used to isolate and identify the BmKK2. SiRNA, western blotting and flow cytometry were used to analysis the anti-inflammatory mechanism of BmKK2.

Results: Here we demonstrate that BmKK2, a thermostable toxin targeting Kv1.3 is the critical anti-inflammatory component in the processed BmK scorpion. BmKK2 inhibits inflammation by targeting and inhibiting the activity of macrophage Kv1.3, thereby inhibiting the activation of NF-kB-NLPR3 pathway and the subsequent release of inflammatory factors.

Conclusions: These findings provide new insights into the molecular basis of the anti-inflammatory effects of "Quanxie" and highlight the importance of targeting Kv1.3 expressed on macrophages as an anti-inflammatory approach.

Keywords

Anti-inflammatory; BmKK2; Kv1.3-NF-κB-NLRP3 axis; Scorpion.

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