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Chinese medicine Linggui Zhugan formula protects against diabetic kidney disease in close association with inhibition of proteinase 3-mediated podocyte apoptosis in mice.
Yi, Zixuan; Yang, Bei; Wan, Fangyu; Lu, Jing; Liu, Dongyang; Lin, Lin; Xu, Ying; Cen, Zhikang; Fan, Mengqi; Liu, Wei; Lu, Qiuhan; Jiang, Guozhi; Zhang, Yuying; Song, Erfei; Gao, Jie; Ye, Dewei.
Affiliation
  • Yi Z; Key Laboratory of Metabolic Phenotyping in Model Animals, Guangdong Pharmaceutical University, Guangzhou, China; Guangdong Metabolic Disease Research Center of Integrated Chinese and Western Medicine, Guangdong Pharmaceutical University, Guangzhou, China.
  • Yang B; Key Laboratory of Metabolic Phenotyping in Model Animals, Guangdong Pharmaceutical University, Guangzhou, China; Guangdong Metabolic Disease Research Center of Integrated Chinese and Western Medicine, Guangdong Pharmaceutical University, Guangzhou, China.
  • Wan F; Key Laboratory of Metabolic Phenotyping in Model Animals, Guangdong Pharmaceutical University, Guangzhou, China; Guangdong Metabolic Disease Research Center of Integrated Chinese and Western Medicine, Guangdong Pharmaceutical University, Guangzhou, China.
  • Lu J; Key Laboratory of Metabolic Phenotyping in Model Animals, Guangdong Pharmaceutical University, Guangzhou, China; Guangdong Metabolic Disease Research Center of Integrated Chinese and Western Medicine, Guangdong Pharmaceutical University, Guangzhou, China.
  • Liu D; Key Laboratory of Metabolic Phenotyping in Model Animals, Guangdong Pharmaceutical University, Guangzhou, China; Guangdong Metabolic Disease Research Center of Integrated Chinese and Western Medicine, Guangdong Pharmaceutical University, Guangzhou, China.
  • Lin L; Key Laboratory of Metabolic Phenotyping in Model Animals, Guangdong Pharmaceutical University, Guangzhou, China; Guangdong Metabolic Disease Research Center of Integrated Chinese and Western Medicine, Guangdong Pharmaceutical University, Guangzhou, China.
  • Xu Y; School of Chinese Medicine, Guangdong Pharmaceutical University, Guangzhou, China.
  • Cen Z; Key Laboratory of Metabolic Phenotyping in Model Animals, Guangdong Pharmaceutical University, Guangzhou, China; Guangdong Metabolic Disease Research Center of Integrated Chinese and Western Medicine, Guangdong Pharmaceutical University, Guangzhou, China.
  • Fan M; Key Laboratory of Metabolic Phenotyping in Model Animals, Guangdong Pharmaceutical University, Guangzhou, China; Guangdong Metabolic Disease Research Center of Integrated Chinese and Western Medicine, Guangdong Pharmaceutical University, Guangzhou, China.
  • Liu W; The First Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, China.
  • Lu Q; School of Public Health (Shenzhen), Shenzhen Campus of Sun Yat-sen University, Shenzhen, Guangdong, China.
  • Jiang G; School of Public Health (Shenzhen), Shenzhen Campus of Sun Yat-sen University, Shenzhen, Guangdong, China.
  • Zhang Y; Department of Obstetrics, Shenzhen Longhua Maternity and Child Healthcare Hospital, Shenzhen, China.
  • Song E; Department of Metabolic and Bariatric Surgery, The First Affiliated Hospital of Jinan University, Guangzhou, 510630, Guangdong Province, China; Guangdong-Hong Kong-Macao Joint University Laboratory of Metabolic and Molecular Medicine, The University of Hong Kong and Jinan University, Guangzhou, 5106
  • Gao J; The First Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, China. Electronic address: gaojie1769@gzucm.edu.cn.
  • Ye D; Key Laboratory of Metabolic Phenotyping in Model Animals, Guangdong Pharmaceutical University, Guangzhou, China; Guangdong Metabolic Disease Research Center of Integrated Chinese and Western Medicine, Guangdong Pharmaceutical University, Guangzhou, China. Electronic address: deweiye@gdpu.edu.cn.
J Ethnopharmacol ; 335: 118650, 2024 Dec 05.
Article in En | MEDLINE | ID: mdl-39094755
ABSTRACT
ETHNOPHARMACOLOGICAL RELEVANCE Linggui-Zhugan (LGZG) comprises four herbs and is a classic formula in traditional Chinese medicine. There is strong clinical evidence of its pleiotropic effects in the prevention of diabetes and its related complications. Although several classes of drugs are currently available for clinical management of diabetic kidney disease (DKD), tight glycemic and/or hypertension control may not prevent disease progression. This study evaluated the therapeutic effect of the ethnopharmacological agent LGZG on DKD. AIM OF THE STUDY This study aimed to investigate the effects of LGZG formula with standard quality control on experimental DKD and its related metabolic disorders in animal model. Meanwhile, the present study aimed to investigate regulatory effects of LGZG on renal proteinase 3 (PR3) to reveal mechanisms underlying renoprotective benefits of LGZG. MATERIALS AND

METHODS:

LGZG decoction was fingerprinted by high-performance liquid chromatography for quality control. An experimental model of DKD was induced in C57 BL/6J mice by a combination of high-fat diet feeding, uninephrectomy, and intraperitoneal injection of streptozocin. The LGZG decoction was administrated by daily oral gavage.

RESULTS:

Treatment with LGZG formula significantly attenuated DKD-like traits (including severe albuminuria, mesangial matrix expansion, and podocyte loss) and metabolic dysfunction (disordered body composition and dyslipidemia) in mice. RNA sequencing data revealed a close association of LGZG treatment with marked modulation of signaling pathways related to podocyte injury and cell apoptosis. Mechanistically, LGZG suppressed the DKD-triggered increase in renal PR3 and podocyte apoptosis. In-vitro incubation of mouse immortalized podocytes with LGZG-medicated serum attenuated PR3-mediated apoptosis.

CONCLUSION:

Our data demonstrated that the LGZG formula protected against DKD in mice and was closely associated with its inhibitory effects on PR3-mediated podocyte apoptosis.
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Drugs, Chinese Herbal / Apoptosis / Diabetic Nephropathies / Podocytes / Mice, Inbred C57BL Limits: Animals Language: En Journal: J Ethnopharmacol Year: 2024 Document type: Article Affiliation country: Country of publication:
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Drugs, Chinese Herbal / Apoptosis / Diabetic Nephropathies / Podocytes / Mice, Inbred C57BL Limits: Animals Language: En Journal: J Ethnopharmacol Year: 2024 Document type: Article Affiliation country: Country of publication: