Protective mechanisms of Leontopodium leontopodioides extracts on lipopolysaccharide-induced acute kidney injury viathe NF-κB/NLRP3 pathway

Xue Bai; Qianqian Ma; Qi Li; Meizhen Yin; Ying Xin; Dong Zhen; Chengxi Wei

doi:10.1016/S1875-5364(23)60384-X

Protective mechanisms of Leontopodium leontopodioides extracts on lipopolysaccharide-induced acute kidney injury viathe NF-κB/NLRP3 pathway

Chin J Nat Med. 2023 Jan;21(1):47-57. doi: 10.1016/S1875-5364(23)60384-X.

Authors

Xue Bai¹, Qianqian Ma², Qi Li², Meizhen Yin², Ying Xin³, Dong Zhen², Chengxi Wei⁴

Affiliations

¹ Inner Mongolia Key Laboratory of Mongolian Medicine Pharmacology for Cardio-Cerebral Vascular System, Inner Mongolia Minzu University, Tongliao 028000, China; College of Preventive Medicine, Medical College, Inner Mongolia Minzu University, Tongliao 028000, China.
² Inner Mongolia Key Laboratory of Mongolian Medicine Pharmacology for Cardio-Cerebral Vascular System, Inner Mongolia Minzu University, Tongliao 028000, China; Institute of Pharmaceutical Chemistry and Pharmacology, Inner Mongolia Minzu University, Tongliao 028000, China.
³ College of Traditional Mongolian Medicine, Inner Mongolia Minzu University, Tongliao 028000, China.
⁴ Inner Mongolia Key Laboratory of Mongolian Medicine Pharmacology for Cardio-Cerebral Vascular System, Inner Mongolia Minzu University, Tongliao 028000, China; Institute of Pharmaceutical Chemistry and Pharmacology, Inner Mongolia Minzu University, Tongliao 028000, China. Electronic address: weichengxi1224@163.com.

PMID: 36641232
DOI: 10.1016/S1875-5364(23)60384-X

Abstract

Sepsis-induced uncontrolled systemic inflammatory response syndrome (SIRS) is a critical cause of multiple organ failure. Acute kidney injury (AKI) is one of the most serious complications associated with an extremely high mortality rate in SIRS, and it lacked simple, safe, and effective treatment strategies. Leontopodium leontopodioides (Willd.) Beauv (LLB) is commonly used in traditional Chinese medicine for the treatment of acute and chronic nephritis. However, it remains unclear whether lipopolysaccharide (LPS) affects LPS-induced AKI. To identify the molecular mechanisms of LLB in LPS-induced HK-2 cells and mice, LLB was prepared by extraction with 70% methanol, while a lipopolysaccharide (LPS)-induced HK-2 cell model and an AKI model were established in this study. Renal histopathology staining was performed to observe the morphology changes. The cell supernatant and kidney tissues were collected for determining the levels of inflammatory factors and protein expression by ELISA, immunofluorescence, and Western blot. The results indicated that LLB significantly reduced the expression of IL-6 and TNF-α in LPS-induced HK-2 cells, as well as the secretion of IL-6, TNF-α, and IL-1β in the supernatant. The same results were observed in LPS-induced AKI serum. Further studies revealed that LLB remarkably improved oxidative stress and apoptosis based on the content of MDA, SOD, and CAT in serum and TUNEL staining results. Notably, LLB significantly reduced the mortality due to LPS infection. Renal histopathology staining results supported these results. Furthermore, immunofluorescence and Western blot results confirmed that LLB significantly reduced the expression of the protein related to the NF-κB signaling pathway and NLRP3, ASC, and Caspase-1 which were significantly increased through LPS stimulation. These findings clearly demonstrated the potential use of LLB in the treatment of AKI and the crucial role of the NF-κB/NLRP3 pathway in the process through which LLB attenuates AKI induced by LPS.

Keywords: Acute kidney injury; Ethnopharmacology; Leontopodium leontopodioides.

MeSH terms

Acute Kidney Injury* / chemically induced
Acute Kidney Injury* / drug therapy
Acute Kidney Injury* / metabolism
Animals
Interleukin-6 / genetics
Interleukin-6 / metabolism
Kidney
Lipopolysaccharides / adverse effects
Mice
NF-kappa B* / genetics
NF-kappa B* / metabolism
NLR Family, Pyrin Domain-Containing 3 Protein / metabolism
Systemic Inflammatory Response Syndrome / metabolism
Systemic Inflammatory Response Syndrome / pathology
Tumor Necrosis Factor-alpha / metabolism

Substances

NF-kappa B
Lipopolysaccharides
NLR Family, Pyrin Domain-Containing 3 Protein
Tumor Necrosis Factor-alpha
Interleukin-6
Nlrp3 protein, mouse