Title:Panax notoginseng Saponins Alleviate LPS-induced Fibrosis of HK-2 Cells
by Inhibiting the Activation of NLRP3 Inflammasome and Pyroptosis
Volume: 25
Issue: 1
Author(s): Jing Xie, Xin Ma, Xueying Li, Nan Mao, Sichong Ren*Junming Fan*
Affiliation:
- Department of
Nephrology, The First Affiliated Hospital of Chengdu Medical College, Chengdu, 610500, China
- School of Clinical
Medicine, Chengdu Medical College, Chengdu, 610083, China
- Department of
Nephrology, The First Affiliated Hospital of Chengdu Medical College, Chengdu, 610500, China
- School of Clinical
Medicine, Chengdu Medical College, Chengdu, 610083, China
Keywords:
Panax notoginseng, saponins, renal fibrosis, HK-2 cells, NLRP3 inflammasome, pyroptosis.
Abstract:
Background: Renal fibrosis is related to impaired kidney function and can eventually
lead to end-stage renal disease, for which no effective treatment is available. Panax notoginseng
saponins (PNS), as a commonly used traditional Chinese medicine, is considered a possible alternative
for the treatment of fibrosis.
Objective: The purpose of the present study was to investigate the effects and possible mechanisms
of PNS on renal fibrosis.
Methods: HK-2 cells were used to induce renal fibrosis cell model by lipopolysaccharide (LPS),
and the cytotoxicity of PNS on HK-2 cells was investigated. Cell damage, pyroptosis, and fibrosis
were analyzed to investigate the effects of PNS on LPS-induced HK-2 cells. NLRP3 agonist Nigericin
was used further to explore the inhibitory effect of PNS on LPS-induced pyroptosis so as
to clarify the possible mechanism of PNS on renal fibrosis.
Results: PNS had no cytotoxicity on HK-2 cells, and could reduce the apoptosis and the release of
lactate dehydrogenase (LDH) and inflammatory cytokines of LPS-induced HK-2 cells, showing an
alleviating effect on cell damage. PNS also reduced the expression of pyroptosis proteins NLRP3,
IL-1β, IL-18, and Caspase-1, as well as fibrosis proteins α-SMA, collagen Ⅰ and p-Smad3/Smad3,
which showed an inhibitory effect on LPS-induced pyroptosis and fibrosis. In addition, LPSinduced
cell damage, pyroptosis, and fibrosis were aggravated after Nigericin treatment, while
PNS alleviated the aggravation caused by Nigericin.
Conclusion: PNS inhibited pyroptosis by inhibiting the activation of NLRP3 inflammasome in
LPS-induced HK-2 cells, which ultimately alleviated renal fibrosis and played a good role in the
treatment of kidney diseases.
