2. Academic Validation
  3. (-)-Asarinin alleviates gastric precancerous lesions by promoting mitochondrial ROS accumulation and inhibiting the STAT3 signaling pathway

(-)-Asarinin alleviates gastric precancerous lesions by promoting mitochondrial ROS accumulation and inhibiting the STAT3 signaling pathway

  • Phytomedicine. 2024 Apr:126:155348. doi: 10.1016/j.phymed.2024.155348.
Maoyuan Zhao 1,  Yueqiang Wen 2,  Yi Yang 3,  Huafeng Pan 4,  Shunkai Xie 5,  Caifei Shen 6,  Wenhao Liao 3,  Nianzhi Chen 3,  Qiao Zheng 3,  Gang Zhang 3,  Yuchen Li 3,  Daoyin Gong 7,  Jianyuan Tang 8,  Ziyi Zhao 9,  Jinhao Zeng 10
Affiliations

Affiliations

  • 1 TCM Regulating Metabolic Diseases Key Laboratory of Sichuan Province, Hospital of Chengdu University of Traditional Chinese Medicine, 39 Shi-er-Qiao Road, Chengdu, Sichuan 610072, China; School of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing 100029, China.
  • 2 School of Basic Medicine, Chengdu University of Traditional Chinese Medicine, Chengdu 611137, China.
  • 3 TCM Regulating Metabolic Diseases Key Laboratory of Sichuan Province, Hospital of Chengdu University of Traditional Chinese Medicine, 39 Shi-er-Qiao Road, Chengdu, Sichuan 610072, China.
  • 4 Science and Technology Innovation Center, Guangzhou University of Chinese Medicine, Guangzhou 510405, China.
  • 5 Acupuncture and Tuina School, Chengdu University of Traditional Chinese Medicine, Chengdu 610075, China.
  • 6 Department of Endoscopy Center, Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu 610072, China.
  • 7 Department of Pathology, Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu 610072, China.
  • 8 TCM Regulating Metabolic Diseases Key Laboratory of Sichuan Province, Hospital of Chengdu University of Traditional Chinese Medicine, 39 Shi-er-Qiao Road, Chengdu, Sichuan 610072, China. Electronic address: tangjy@cdutcm.edu.cn.
  • 9 TCM Regulating Metabolic Diseases Key Laboratory of Sichuan Province, Hospital of Chengdu University of Traditional Chinese Medicine, 39 Shi-er-Qiao Road, Chengdu, Sichuan 610072, China. Electronic address: zhaoziyi@cdutcm.edu.cn.
  • 10 TCM Regulating Metabolic Diseases Key Laboratory of Sichuan Province, Hospital of Chengdu University of Traditional Chinese Medicine, 39 Shi-er-Qiao Road, Chengdu, Sichuan 610072, China; Department of Gastroenterology, Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu 610072, China. Electronic address: zengjinhao@cdutcm.edu.cn.
PMID: 38335913 DOI: 10.1016/j.phymed.2024.155348
Abstract

Background: (-)-Asarinin (Asarinin) is the primary component in the extract of the herb Asarum sieboldii Miq. It possesses various functions, including pain relief, anti-viral and anti-tuberculous bacilli effects, and inhibition of tumor growth. Gastric precancerous lesion (GPL) is a common but potentially carcinogenic chronic gastrointestinal disease, and its progression can lead to gastric dysfunction and Cancer development. However, the protective effects of asarinin against GPL and the underlying mechanisms remain unexplored.

Methods: A premalignant cell model (methylnitronitrosoguanidine-induced malignant transformation of human gastric epithelial cell strain, MC cells) and a GPL animal model were established and then were treated with asarinin. The cytotoxic effect of asarinin was assessed using a CCK8 assay. Detection of intracellular Reactive Oxygen Species (ROS) using DCFH-DA. Apoptosis in MC cells was evaluated using an annexin V-FITC/PI assay. We performed western blot analysis and immunohistochemistry (IHC) to analyze relevant markers, investigating the in vitro and in vivo therapeutic effects of asarinin on GPL and its intrinsic mechanisms.

Results: Our findings showed that asarinin inhibited MC cell proliferation, enhanced intracellular ROS levels, and induced cell Apoptosis. Further investigations revealed that the pharmacological effects of asarinin on MC cells were blocked by the ROS scavenger N-acetylcysteine. IHC revealed a significant upregulation of phospho-signal transducer and activator of transcription 3 (p-STAT3) protein expression in human GPL tissues. In vitro, asarinin exerted its pro-apoptotic effects in MC cells by modulating the STAT3 signaling pathway. Agonists of STAT3 were able to abolish the effects of asarinin on MC cells. In vivo, asarinin induced ROS accumulation and inhibited the STAT3 pathway in gastric mucosa of mice, thereby halting and even reversing the development of GPL.

Conclusion: Asarinin induces Apoptosis and delays the progression of GPL by promoting mitochondrial ROS production, decreasing mitochondrial membrane potential (MMP), and inhibiting the STAT3 pathway.

Keywords

(-)-Asarinin; Gastric precancerous lesions; Mitochondria; ROS; STAT3.

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