2. Academic Validation
  3. Bavachin enhances NLRP3 inflammasome activation induced by ATP or nigericin and causes idiosyncratic hepatotoxicity

Bavachin enhances NLRP3 inflammasome activation induced by ATP or nigericin and causes idiosyncratic hepatotoxicity

  • Front Med. 2021 Aug;15(4):594-607. doi: 10.1007/s11684-020-0809-2.
Nan Qin  # 1 2,  Guang Xu  # 1,  Yan Wang  # 1 3,  Xiaoyan Zhan 1,  Yuan Gao 4,  Zhilei Wang 1,  Shubin Fu 1,  Wei Shi 1,  Xiaorong Hou 1,  Chunyu Wang 1,  Ruisheng Li 5,  Yan Liu 5,  Jiabo Wang 1,  Haiping Zhao 6,  Xiaohe Xiao 7 8,  Zhaofang Bai 9
Affiliations

Affiliations

  • 1 China Military Institute of Chinese Materia, the Fifth Medical Centre, Chinese PLA General Hospital, Beijing, 100039, China.
  • 2 Department of Pharmacy, Nantong Hospital of Traditional Chinese Medicine, Nantong, 226300, China.
  • 3 School of Pharmacy, Henan University of Chinese Medicine, Zhengzhou, 450046, China.
  • 4 School of Traditional Chinese Medicine, Capital Medical University, Beijing, 100069, China.
  • 5 Research Center for Clinical and Translational Medicine, the Fifth Medical Centre, Chinese PLA General Hospital, Beijing, 100039, China.
  • 6 School of Traditional Chinese Medicine, Jiangxi University of Traditional Chinese Medicine, Nanchang, 330004, China. cdzhp3690098@163.com.
  • 7 China Military Institute of Chinese Materia, the Fifth Medical Centre, Chinese PLA General Hospital, Beijing, 100039, China. pharmacy_302@126.com.
  • 8 Integrative Medical Centre, the Fifth Medical Centre, Chinese PLA General Hospital, Beijing, 100039, China. pharmacy_302@126.com.
  • 9 China Military Institute of Chinese Materia, the Fifth Medical Centre, Chinese PLA General Hospital, Beijing, 100039, China. baizf2008@hotmail.com.
  • # Contributed equally.
PMID: 33909257 DOI: 10.1007/s11684-020-0809-2
Abstract

Psoraleae Fructus (PF) is a well-known traditional herbal medicine in China, and it is widely used for osteoporosis, vitiligo, and Other Diseases in clinical settings. However, liver injury caused by PF and its preparations has been frequently reported in recent years. Our previous studies have demonstrated that PF could cause idiosyncratic drug-induced liver injury (IDILI), but the mechanism underlying its hepatotoxicity remains unclear. This paper reports that bavachin isolated from PF enhances the specific stimuli-induced activation of the NLRP3 inflammasome and leads to hepatotoxicity. Bavachin boosts the secretion of IL-1β and Caspase-1 caused by ATP or nigericin but not those induced by poly(I:C), monosodium urate crystal, or intracellular lipopolysaccharide. Bavachin does not affect AIM2 or NLRC4 inflammasome activation. Mechanistically, bavachin specifically increases the production of nigericin-induced mitochondrial Reactive Oxygen Species among the most important upstream events in the activation of the NLRP3 inflammasome. Bavachin increases the levels of aspartate transaminase and alanine aminotransferase in serum and hepatocyte injury accompanied by the secretion of IL-1β via a mouse model of lipopolysaccharide-mediated susceptibility to IDILI. These results suggest that bavachin specifically enhances the ATP- or nigericin-induced activation of the NLRP3 inflammasome. Bavachin also potentially contributes to PF-induced idiosyncratic hepatotoxicity. Moreover, bavachin and PF should be evaded among patients with diseases linked to the ATP- or nigericin-mediated activation of the NLRP3 inflammasome, which may be a dangerous factor for liver injury.

Keywords

IL-1β; NLRP3 inflammasome; Psoraleae Fructus; bavachin; caspase-1; idiosyncratic drug-induced liver injury.

Figures
Products
嗨！很高兴为您提供帮助！

尊敬的 MCE 客户您好，
请您选择所在区域，我们将转接对应客服为您服务！

热门区域

A

B

C

F

G

H

J

L

N

Q

S

T

X

Y

Z

热 A B C F G H J L N Q S T X Y Z