Polypeptide from Moschus Suppresses Lipopolysaccharide-Induced Inflammation by Inhibiting NF-κ B-ROS/NLRP3 Pathway.
10.1007/s11655-023-3598-z
- Author:
Jing YI
1
;
Li LI
2
;
Zhu-Jun YIN
2
;
Yun-Yun QUAN
2
;
Rui-Rong TAN
2
;
Shi-Long CHEN
2
;
Ji-Rui LANG
2
;
Jiao LI
2
;
Jin ZENG
2
;
Yong LI
3
;
Zi-Jian SUN
4
;
Jun-Ning ZHAO
5
Author Information
1. Department of Pharmacology, Southwest Medical University, Luzhou, Sichuan Province, 646000, China.
2. Sichuan Institute for Translational Chinese Medicine, Translational Chinese Medicine Key Laboratory of Sichuan Province, Sichuan Academy of Chinese Medicine Sciences, Chengdu, 610000, China.
3. Sichuan Fengchun Pharmaceutical Co., Ltd., Deyang, Sichuan Province, 618100, China.
4. Sichuan Ant Recommendation Biotechnology Co., Ltd., Chengdu, 610000, China.
5. Department of Pharmacology, Southwest Medical University, Luzhou, Sichuan Province, 646000, China. zarmy@189.cn.
- Publication Type:Journal Article
- Keywords:
Chinese medicine;
Moschus;
NLRP3 inflammasome;
inflammation;
nuclear factor κB;
polypeptide;
thioredoxin interacting protein
- From:
Chinese journal of integrative medicine
2023;29(10):895-904
- CountryChina
- Language:English
-
Abstract:
OBJECTIVE:To examine the anti-inflammatory effects and potential mechanisms of polypeptide from Moschus (PPM) in lipopolysaccharide (LPS)-induced THP-1 macrophages and BALB/c mice.
METHODS:The polypeptide was extracted from Moschus and analyzed by high-performance liquid chromatography and sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE). Subsequently, LPS was used to induce inflammation in THP-1 macrophages and BALB/c mice. In LPS-treated or untreated THP-1 macrophages, cell viability was observed by cell counting kit 8 and lactate dehydrogenase release assays; the proinflammatory cytokines and reactive oxygen species (ROS) were measured by enzyme-linked immunosorbent assay and flow cytometry, respectively; and protein and mRNA levels were measured by Western blot and real-time quantitative polymerase chain reaction (qRT-PCR), respectively. In LPS-induced BALB/c mice, the proinflammatory cytokines were measured, and lung histology and cytokines were observed by hematoxylin and eosin (HE) and immunohistochemical (IHC) staining, respectively.
RESULTS:The SDS-PAGE results suggested that the molecular weight of purified PPM was in the range of 10-26 kD. In vitro, PPM reduced the production of interleukin 1β (IL-1β), IL-18, tumor necrosis factor α (TNF-α), IL-6 and ROS in LPS-induced THP-1 macrophages (P<0.01). Western blot analysis demonstrated that PPM inhibited LPS-induced nuclear factor κB (NF-κB) pathway and thioredoxin interacting protein (TXNIP)/nucleotide-binding oligomerization domain, leucine-rich repeat and pyrin domain containing 3 (NLRP3) inflammasome pathway by reducing protein expression of phospho-NF-κB p65, phospho-inhibitors of NF-κB (Iκ Bs) kinase α/β (IKKα/β), TXNIP, NLRP3, apoptosis-associated speck-like protein containing a caspase recruitment domain (ASC), and pro-caspase-1 (P<0.05 or P<0.01). In addition, qRT-PCR revealed the inhibitory effects of PPM on the mRNA levels of TXNIP, NLRP3, ASC, and caspase-1 (P<0.05 or P<0.01). Furthermore, in LPS-induced BALB/c mice, PPM reduced TNF-α and IL-6 levels in serum (P<0.05 or P<0.01), decreased IL-1β and IL-18 levels in the lungs (P<0.01) and alleviated pathological injury to the lungs.
CONCLUSION:PPM could attenuate LPS-induced inflammation by inhibiting the NF-κB-ROS/NLRP3 pathway, and may be a novel potential candidate drug for treating inflammation and inflammation-related diseases.
