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Protective effect of ginsenoside metabolite compound K against diabetic nephropathy by inhibiting NLRP3 inflammasome activation and NF-κB/p38 signaling pathway in high-fat diet/streptozotocin-induced diabetic mice.
Int Immunopharmacol. 2018 Oct; 63:227-238.II

Abstract

Though the antidiabetic effect of ginsenoside compound K (CK) has been well studied, the effect of CK on diabetic nephropathy (DN) is not clear. Whether CK would have a protective effect against DN and it could exert the protective effect by inhibiting the oxidative stress, NLRP3 inflammasome and NF-κB/p38 signaling pathway were investigated in this study. Here, the HFD (high fat diet)/STZ (streptozotocin)-induced DN mice model was established to assess the CK effect in vivo. Parallel experiments uncovering the molecular mechanism by which CK prevents from DN was performed in rat glomerular mesangial cell line HBZY-1 exposed to high glucose. CK (10, 20, 40 mg/kg/day) were intragastrically administered for 8 weeks, the general status, biochemical parameters, renal pathological changes and oxidative stress-parameters were observed, and the NLRP3 inflammasome and NF-κB/p38 signaling pathway were evaluated. The results showed that the elevated fasting blood glucose, serum creatinine, blood urea nitrogen and 24-hour urine protein of the DN mice were significantly decreased, and the proliferation of glomerular mesangial matrix was alleviated by CK. In addition, the generation of ROS in the kidney was significantly decreased, and the expression of Nox1 and Nox4 proteins were down-regulated. Further, the expression of NLRP3 inflammasome components (NLRP3, ASC and Caspase-1) and the inflammatory cytokines IL-1β and IL-18 were also significantly down-regulated in vivo and in vitro. The phosphorylation of renal p38 MAPK was also inhibited by CK. MCC950 (an inhibitor of NLRP3 inflammasome) and VX-765 (a Caspase-1 Inhibitor) showed significant interaction with CK on the decrease of IL-1β concentration in HBZY-1 cells. In conclusion, our study provided evidence that the protective effect of CK on diabetes-induced renal injury is associated with down-regulating the expression of NADHP oxidase, and inhibition of ROS-mediated activation of NLRP3 inflammasome and NF-κB/p38 signaling pathway, suggesting its therapeutic implication for renal inflammation.

Authors+Show Affiliations

Department of Pharmacology, College of Basic Medicine, Changchun University of Chinese Medicine, Changchun 130117, China.Department of Pharmacology, College of Basic Medicine, Changchun University of Chinese Medicine, Changchun 130117, China.Department of Pharmacology, College of Basic Medicine, Changchun University of Chinese Medicine, Changchun 130117, China.Department of Pathology, The First Hospital of Jilin University, Changchun 130000, China.Department of Pharmacology, College of Basic Medicine, Changchun University of Chinese Medicine, Changchun 130117, China. Electronic address: jiangshuang_2000@163.com.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

30107367

Citation

Song, Wu, et al. "Protective Effect of Ginsenoside Metabolite Compound K Against Diabetic Nephropathy By Inhibiting NLRP3 Inflammasome Activation and NF-κB/p38 Signaling Pathway in High-fat Diet/streptozotocin-induced Diabetic Mice." International Immunopharmacology, vol. 63, 2018, pp. 227-238.
Song W, Wei L, Du Y, et al. Protective effect of ginsenoside metabolite compound K against diabetic nephropathy by inhibiting NLRP3 inflammasome activation and NF-κB/p38 signaling pathway in high-fat diet/streptozotocin-induced diabetic mice. Int Immunopharmacol. 2018;63:227-238.
Song, W., Wei, L., Du, Y., Wang, Y., & Jiang, S. (2018). Protective effect of ginsenoside metabolite compound K against diabetic nephropathy by inhibiting NLRP3 inflammasome activation and NF-κB/p38 signaling pathway in high-fat diet/streptozotocin-induced diabetic mice. International Immunopharmacology, 63, 227-238. https://doi.org/10.1016/j.intimp.2018.07.027
Song W, et al. Protective Effect of Ginsenoside Metabolite Compound K Against Diabetic Nephropathy By Inhibiting NLRP3 Inflammasome Activation and NF-κB/p38 Signaling Pathway in High-fat Diet/streptozotocin-induced Diabetic Mice. Int Immunopharmacol. 2018;63:227-238. PubMed PMID: 30107367.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Protective effect of ginsenoside metabolite compound K against diabetic nephropathy by inhibiting NLRP3 inflammasome activation and NF-κB/p38 signaling pathway in high-fat diet/streptozotocin-induced diabetic mice. AU - Song,Wu, AU - Wei,Lin, AU - Du,Yanwei, AU - Wang,Yimei, AU - Jiang,Shuang, Y1 - 2018/08/11/ PY - 2018/02/17/received PY - 2018/07/01/revised PY - 2018/07/24/accepted PY - 2018/8/15/pubmed PY - 2018/12/12/medline PY - 2018/8/15/entrez KW - Compound K KW - Diabetic nephropathy KW - NLRP3 KW - Nox1 KW - TXNIP KW - p38 SP - 227 EP - 238 JF - International immunopharmacology JO - Int Immunopharmacol VL - 63 N2 - Though the antidiabetic effect of ginsenoside compound K (CK) has been well studied, the effect of CK on diabetic nephropathy (DN) is not clear. Whether CK would have a protective effect against DN and it could exert the protective effect by inhibiting the oxidative stress, NLRP3 inflammasome and NF-κB/p38 signaling pathway were investigated in this study. Here, the HFD (high fat diet)/STZ (streptozotocin)-induced DN mice model was established to assess the CK effect in vivo. Parallel experiments uncovering the molecular mechanism by which CK prevents from DN was performed in rat glomerular mesangial cell line HBZY-1 exposed to high glucose. CK (10, 20, 40 mg/kg/day) were intragastrically administered for 8 weeks, the general status, biochemical parameters, renal pathological changes and oxidative stress-parameters were observed, and the NLRP3 inflammasome and NF-κB/p38 signaling pathway were evaluated. The results showed that the elevated fasting blood glucose, serum creatinine, blood urea nitrogen and 24-hour urine protein of the DN mice were significantly decreased, and the proliferation of glomerular mesangial matrix was alleviated by CK. In addition, the generation of ROS in the kidney was significantly decreased, and the expression of Nox1 and Nox4 proteins were down-regulated. Further, the expression of NLRP3 inflammasome components (NLRP3, ASC and Caspase-1) and the inflammatory cytokines IL-1β and IL-18 were also significantly down-regulated in vivo and in vitro. The phosphorylation of renal p38 MAPK was also inhibited by CK. MCC950 (an inhibitor of NLRP3 inflammasome) and VX-765 (a Caspase-1 Inhibitor) showed significant interaction with CK on the decrease of IL-1β concentration in HBZY-1 cells. In conclusion, our study provided evidence that the protective effect of CK on diabetes-induced renal injury is associated with down-regulating the expression of NADHP oxidase, and inhibition of ROS-mediated activation of NLRP3 inflammasome and NF-κB/p38 signaling pathway, suggesting its therapeutic implication for renal inflammation. SN - 1878-1705 UR - https://www.unboundmedicine.com/medline/citation/30107367/Protective_effect_of_ginsenoside_metabolite_compound_K_against_diabetic_nephropathy_by_inhibiting_NLRP3_inflammasome_activation_and_NF_κB/p38_signaling_pathway_in_high_fat_diet/streptozotocin_induced_diabetic_mice_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S1567-5769(18)30356-4 DB - PRIME DP - Unbound Medicine ER -