2. Academic Validation
  3. Vicenin-2 in Suhuang antitussive capsule attenuates mitophagy-dependent ferroptosis via LRP1 for treating post-infectious cough

Vicenin-2 in Suhuang antitussive capsule attenuates mitophagy-dependent ferroptosis via LRP1 for treating post-infectious cough

  • J Ethnopharmacol. 2025 Jun 12:349:119880. doi: 10.1016/j.jep.2025.119880.
Qimeng Tian 1,  Hong Jiang 1,  Yajun Luan 2,  Jingge Sun 1,  Yihang Sui 1,  Ling Chen 1,  Yongxiang Wang 3,  Ninghua Tan 4
Affiliations

Affiliations

  • 1 Department of TCMs Pharmaceuticals, School of Traditional Chinese Pharmacy, China Pharmaceutical University, Nanjing, 211198, PR China.
  • 2 Beijing Haiyan Pharmaceutical Co., Ltd., Yangzijiang Pharmaceutical Group, Beijing, 102206, PR China.
  • 3 Key Laboratory for Quality Control of Traditional Chinese Medicine of National Administration of Traditional Chinese Medicine, Institute of Chinese Medicine, Jiangsu Longfengtang Chinese Medicine Co., Ltd., Yangzijiang Pharmaceutical Group, Taizhou, 225321, PR China. Electronic address: wangyongxiang@yangzijiang.com.
  • 4 Department of TCMs Pharmaceuticals, School of Traditional Chinese Pharmacy, China Pharmaceutical University, Nanjing, 211198, PR China. Electronic address: nhtan@cpu.edu.cn.
PMID: 40288661 DOI: 10.1016/j.jep.2025.119880
Abstract

Ethnopharmacological relevance: Suhuang antitussive capsule (SH) is the only clinically approved traditional Chinese patent medicine for the treatment of post-infectious cough (PIC). During the past decade, our lab has conducted intensive researches on SH, including its efficacy and mechanism on PIC, and determined that SH has favorable anti-inflammatory, antitussive, expectorant, and anti-asthmatic pharmacological effects. Recently, we found that vicenin-2 (VIC-2) could be detected in SH and showed activity in vitro primary screening on PIC.

Aim of the study: To investigate the therapeutic effects of VIC-2 on PIC and its potential mechanisms, and want to elucidate VIC-2 as one of the efficacious components of SH.

Materials and methods: The PIC mouse model was established with lipopolysaccharide (LPS)-induced combined cigarette smoke (CS)-exposed ICR mice, while the in vitro assay was constructed to induce BEAS-2B cells with cigarette smoke extract (CSE). The therapeutic effects of VIC-2 on PIC in vitro and in vivo were assessed by pathological sections, cough assay, immune cell counting, and quantitative-polymerase chain reaction (Q-PCR). The mechanisms of VIC-2 on Ferroptosis and Mitophagy in PIC were further explored by cell viability assay, Prussian blue staining, lipid peroxidation assessment, confocal laser scanning microscopy, and western blotting. Subsequently, virtual docking, cellular thermal shift assay (CETSA), and drug affinity responsive target stability (DARTS) verified the target relationship between VIC-2 and LDL receptor-related protein 1 (LRP1). In addition, the link between LRP1 and mitophagy-dependent Ferroptosis was explored by knocking down LRP1.

Results: VIC-2 significantly improved lung inflammation, oxidative stress, and airway remodeling in PIC and inhibited mitophagy-dependent Ferroptosis, confirming that it is one of the antitussive components of SH for the treatment of PIC. LRP1 is one of the pharmacological targets of VIC-2, in which VIC-2 exerted the above effects through up-regulating LRP1 by influencing the LRP1-Parkin interaction. The blockade of LRP1 reversed the both in vitro and in vivo pharmacological activities of VIC-2. Furthermore, our results showed for the first time that defects in LRP1 lead to Ferroptosis.

Conclusion: This study demonstrates that VIC-2 inhibits mitophagy-dependent Ferroptosis via LRP1 for the treatment of PIC, constituting one of the antitussive components of SH.

Keywords

Ferroptosis; LDL receptor-related protein 1; Mitophagy; Post-infectious cough; Suhuang antitussive capsule; Vicenin-2.

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