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

Lihua Cui; Caixia Li; Yuzhen Zhuo; Lei Yang; Naiqiang Cui; Yuhong Li; Shukun Zhang

Biomedicine & Pharmacotherapy (Aug 2020)

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

Lihua Cui,
Caixia Li,
Yuzhen Zhuo,
Lei Yang,
Naiqiang Cui,
Yuhong Li,
Shukun Zhang

Affiliations

Lihua Cui: 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
Caixia Li: 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
Yuzhen Zhuo: 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
Lei Yang: 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
Naiqiang Cui: Department of Hepatobiliary and Pancreatic Surgery, Tianjin Nankai Hospital, Tianjin 300100, China; Nankai Clinical College, Tianjin Medical University, Tianjin 300107, China
Yuhong Li: Institute of TCM, Tianjin University of Traditional Chinese Medicine, Tianjin 301617, China; Corresponding author at: Institute of TCM, Tianjin University of Traditional Chinese Medicine, 10 Poyang Lake Road, Tianjin 301617, China.
Shukun Zhang: 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; Corresponding author at: Institute of Acute Abdominal Diseases of Integrated Traditional Chinese and Western Medicine, Tianjin Nankai Hospital, 6 Changjiang Road, Tianjin 300100, China.

Journal volume & issue: Vol. 128
p. 110216

Abstract

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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.

Published in Biomedicine & Pharmacotherapy

ISSN: 0753-3322 (Print); 1950-6007 (Online)
Publisher: Elsevier
Country of publisher: France
LCC subjects: Medicine: Therapeutics. Pharmacology
Website: https://www.journals.elsevier.com/biomedicine-and-pharmacotherapy

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