2. Academic Validation
  3. Saikosaponin A inhibits the activation of pancreatic stellate cells by suppressing autophagy and the NLRP3 inflammasome via the AMPK/mTOR pathway

Saikosaponin A inhibits the activation of pancreatic stellate cells by suppressing autophagy and the NLRP3 inflammasome via the AMPK/mTOR pathway

  • Biomed Pharmacother. 2020 Aug;128:110216. doi: 10.1016/j.biopha.2020.110216.
Lihua Cui 1,  Caixia Li 1,  Yuzhen Zhuo 1,  Lei Yang 1,  Naiqiang Cui 2,  Yuhong Li 3,  Shukun Zhang 4
Affiliations

Affiliations

  • 1 Tianjin Key Laboratory of Acute Abdomen Disease Associated Organ Injury and ITCWM Repair, Institute of Acute Abdominal Diseases of Integrated Traditional Chinese and Western Medicine, Tianjin Nankai Hospital, Tianjin 300100, China; Nankai Clinical College, Tianjin Medical University, Tianjin 300107, China.
  • 2 Department of Hepatobiliary and Pancreatic Surgery, Tianjin Nankai Hospital, Tianjin 300100, China; Nankai Clinical College, Tianjin Medical University, Tianjin 300107, China.
  • 3 Institute of TCM, Tianjin University of Traditional Chinese Medicine, Tianjin 301617, China. Electronic address: liyuhong@tjutcm.edu.cn.
  • 4 Tianjin Key Laboratory of Acute Abdomen Disease Associated Organ Injury and ITCWM Repair, Institute of Acute Abdominal Diseases of Integrated Traditional Chinese and Western Medicine, Tianjin Nankai Hospital, Tianjin 300100, China; Nankai Clinical College, Tianjin Medical University, Tianjin 300107, China. Electronic address: shu1971@163.com.
PMID: 32497863 DOI: 10.1016/j.biopha.2020.110216
Abstract

Pancreatic stellate cells (PSCs) are the main effector cells in the development of pancreatic fibrosis. Finding substances that inhibit PSC activation is an important approach to inhibiting pancreatic fibrosis. Saikosaponin A (SSa) has numerous pharmacological activities, but its effect on PSCs remains unknown. This study was conducted to explore the effects of SSa on PSC activation in cultured rat PSCs. Cell viability, proliferation, migration and Apoptosis were evaluated by MTT assays, the iCELLigence System, Transwell assays and flow cytometry. Markers of PSC activation, Autophagy and the NLRP3 inflammasome were measured by Real-Time PCR, immunofluorescence and western blotting. Rapamycin and phenformin hydrochloride were used to determine the effect of SSa via the AMPK/mTOR pathway. The results showed that SSa suppressed PSC viability, proliferation, and migration and promoted Apoptosis. SSa inhibited PSC activation, restrained PSC Autophagy and suppressed the NLRP3 inflammasome. In addition, there was interaction between Autophagy and the NLRP3 inflammasome during SSa inhibition of PSCs. Moreover, promotion of p-AMPK increased Autophagy and the NLRP3 inflammasome. Inhibition of p-mTOR increased Autophagy and decreased the NLRP3 inflammasome. Our results indicated that SSa inhibited PSC activation by inhibiting PSC Autophagy and the NLRP3 inflammasome via the AMPK/mTOR pathway. These findings provide a theoretical basis for the use of SSa to treat pancreatic fibrosis and further suggest that targeting Autophagy and the NLRP3 inflammasome may provide new strategies for the treatment of pancreatic fibrosis.

Keywords

AMPK/mTOR; Autophagy; NLRP3; Pancreatic stellate cells; Saikosaponin A.

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