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Nepeta angustifolia C. Y. Wu improves renal injury in HFD/STZ-induced diabetic nephropathy and inhibits oxidative stress-induced apoptosis of mesangial cells.
J Ethnopharmacol. 2020 Jun 12; 255:112771.JE

Abstract

ETHNOPHARMACOLOGICAL RELEVANCE

As an important medicinal material constituting a variety of traditional Chinese medicine prescriptions, Nepeta angustifolia C. Y. Wu was used as a folk medicine to treat various vascular-related diseases including apoplexia, and cerebral haemorrhage in Tibet, China. Our previous studies have shown that this plant had a significant protective effect on vascular dysfunction of the intracerebral haemorrhage and diabetic rats. In present study, we aimed to investigate the protective effects and underlying mechanisms of Nepeta angustifolia on diabetic nephropathy (DN), a microvascular complication.

AIM OF THE STUDY

This study is aim to evaluate the protective effect of ethanol extracts of N. angustifolia (NA) on DN, and explore mechanism of action to provide basis for its pharmacological action against DN.

MATERIALS AND METHODS

High-fat diet and low-dose streptozotocin administration (HFD/STZ) induced diabetic rats were randomly divided into 5 groups (n = 8): the diabetic model group, metformin group, and three dose groups of NA (60 mg/kg, 120 mg/kg, 240 mg/kg). After administration of NA for 8 weeks, the blood, urine and renal tissue were collected for subsequent experiments. Biochemical markers (urine protein, Cr, BUN), oxidative stress makers (SOD, GSH-px and MDA) and pro-inflammatory mediators (TNF-α, IL-1β, IL-6 and MCP-1) were evaluated by commercial kit and ELISA, respectively. The effect of NA on DN was further confirmed by evaluation of renal histopathology by using the H&E, PAS and Masson staining. The H2O2-induced HBZY-1 cells (rat glomerular mesangial cells) were also been used to evaluate the renal protective effect of NA (50 μg/mL, 100 μg/mL, 200 μg/mL). The oxidative stress makers were detected by commercial kit. The levels of apoptosis and related proteins (caspase 3, 9) were detected by TUNEL assay and western blot analysis, respectively. The depolarization of mitochondrial membrane potential was detected by JC-1 staining assay.

RESULTS

The administration of NA is helpful to maintain near normal body weight, blood glucose, urine volume, urine protein, kidney index and serum levels of Cr and BUN. NA treatment significantly improve renal dysfunction by the down-regulation of renal oxidative stress and pro-inflammatory mediators in HFD/STZ induced diabetic rats. In vitro experiments, NA has a significant cellular protective effect in H2O2-induced HBZY-1 cells, as well as the regulation in increases of SOD level and the decreases of ROS and MDA levels. Furthermore, NA treatment can significantly inhibit H2O2 induced mesangial cells apoptosis by the increasing mitochondrial potential and suppressing caspases-madiated signaling pathway.

CONCLUSIONS

NA has obvious improvement on renal dysfunction in HFD/STZ induced diabetic rats. NA can protect mesangial cells by inhibiting oxidative stress induced apoptosis, which may be related to its regulation of mitochondrial-caspase apoptosis pathway.

Authors+Show Affiliations

Department of Pharmacy, Qingdao University of Science & Technology, Qingdao, 266042, China.Department of Pharmacy, Qingdao University of Science & Technology, Qingdao, 266042, China.Department of Pharmacy, Baicheng Medical College, Baicheng, 137000, China.Department of Pharmacy, Qingdao University of Science & Technology, Qingdao, 266042, China.Department of Pharmacy, Qingdao University of Science & Technology, Qingdao, 266042, China.Department of Medicament, College of Medicine, Tibet University, Lhasa, 850000, China.Department of Medicament, College of Medicine, Tibet University, Lhasa, 850000, China; Department of Pharmacognosy and Pharmaceutical Botany, Faculty of Pharmaceutical Sciences, Prince of Songkla University, Hat Yai, Songkhla, 90112, Thailand.College of Pharmacy, Chosun University, Dong-gu, Gwangju, 61452, South Korea.Tianjin Key Laboratory of TCM Chemistry and Analysis, Tianjin University of Traditional Chinese Medicine, Tianjin, 300000, China.Department of Pharmacy, Qingdao University of Science & Technology, Qingdao, 266042, China. Electronic address: leebin009@163.com.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

32201300

Citation

Huang, Shan, et al. "Nepeta Angustifolia C. Y. Wu Improves Renal Injury in HFD/STZ-induced Diabetic Nephropathy and Inhibits Oxidative Stress-induced Apoptosis of Mesangial Cells." Journal of Ethnopharmacology, vol. 255, 2020, p. 112771.
Huang S, Tan M, Guo F, et al. Nepeta angustifolia C. Y. Wu improves renal injury in HFD/STZ-induced diabetic nephropathy and inhibits oxidative stress-induced apoptosis of mesangial cells. J Ethnopharmacol. 2020;255:112771.
Huang, S., Tan, M., Guo, F., Dong, L., Liu, Z., Yuan, R., Dongzhi, Z., Lee, D. S., Wang, Y., & Li, B. (2020). Nepeta angustifolia C. Y. Wu improves renal injury in HFD/STZ-induced diabetic nephropathy and inhibits oxidative stress-induced apoptosis of mesangial cells. Journal of Ethnopharmacology, 255, 112771. https://doi.org/10.1016/j.jep.2020.112771
Huang S, et al. Nepeta Angustifolia C. Y. Wu Improves Renal Injury in HFD/STZ-induced Diabetic Nephropathy and Inhibits Oxidative Stress-induced Apoptosis of Mesangial Cells. J Ethnopharmacol. 2020 Jun 12;255:112771. PubMed PMID: 32201300.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Nepeta angustifolia C. Y. Wu improves renal injury in HFD/STZ-induced diabetic nephropathy and inhibits oxidative stress-induced apoptosis of mesangial cells. AU - Huang,Shan, AU - Tan,Meng, AU - Guo,Feng, AU - Dong,Linsha, AU - Liu,Zhiming, AU - Yuan,Ruiying, AU - Dongzhi,Zhuoma, AU - Lee,Dong-Sung, AU - Wang,Yuefei, AU - Li,Bin, Y1 - 2020/03/19/ PY - 2019/12/23/received PY - 2020/03/03/revised PY - 2020/03/14/accepted PY - 2020/3/24/pubmed PY - 2021/1/14/medline PY - 2020/3/24/entrez KW - Apoptosis KW - Caspase 3/9 KW - Diabetic nephropathy KW - HBZY-1 KW - Nepeta angustifolia C. Y. Wu SP - 112771 EP - 112771 JF - Journal of ethnopharmacology JO - J Ethnopharmacol VL - 255 N2 - ETHNOPHARMACOLOGICAL RELEVANCE: As an important medicinal material constituting a variety of traditional Chinese medicine prescriptions, Nepeta angustifolia C. Y. Wu was used as a folk medicine to treat various vascular-related diseases including apoplexia, and cerebral haemorrhage in Tibet, China. Our previous studies have shown that this plant had a significant protective effect on vascular dysfunction of the intracerebral haemorrhage and diabetic rats. In present study, we aimed to investigate the protective effects and underlying mechanisms of Nepeta angustifolia on diabetic nephropathy (DN), a microvascular complication. AIM OF THE STUDY: This study is aim to evaluate the protective effect of ethanol extracts of N. angustifolia (NA) on DN, and explore mechanism of action to provide basis for its pharmacological action against DN. MATERIALS AND METHODS: High-fat diet and low-dose streptozotocin administration (HFD/STZ) induced diabetic rats were randomly divided into 5 groups (n = 8): the diabetic model group, metformin group, and three dose groups of NA (60 mg/kg, 120 mg/kg, 240 mg/kg). After administration of NA for 8 weeks, the blood, urine and renal tissue were collected for subsequent experiments. Biochemical markers (urine protein, Cr, BUN), oxidative stress makers (SOD, GSH-px and MDA) and pro-inflammatory mediators (TNF-α, IL-1β, IL-6 and MCP-1) were evaluated by commercial kit and ELISA, respectively. The effect of NA on DN was further confirmed by evaluation of renal histopathology by using the H&E, PAS and Masson staining. The H2O2-induced HBZY-1 cells (rat glomerular mesangial cells) were also been used to evaluate the renal protective effect of NA (50 μg/mL, 100 μg/mL, 200 μg/mL). The oxidative stress makers were detected by commercial kit. The levels of apoptosis and related proteins (caspase 3, 9) were detected by TUNEL assay and western blot analysis, respectively. The depolarization of mitochondrial membrane potential was detected by JC-1 staining assay. RESULTS: The administration of NA is helpful to maintain near normal body weight, blood glucose, urine volume, urine protein, kidney index and serum levels of Cr and BUN. NA treatment significantly improve renal dysfunction by the down-regulation of renal oxidative stress and pro-inflammatory mediators in HFD/STZ induced diabetic rats. In vitro experiments, NA has a significant cellular protective effect in H2O2-induced HBZY-1 cells, as well as the regulation in increases of SOD level and the decreases of ROS and MDA levels. Furthermore, NA treatment can significantly inhibit H2O2 induced mesangial cells apoptosis by the increasing mitochondrial potential and suppressing caspases-madiated signaling pathway. CONCLUSIONS: NA has obvious improvement on renal dysfunction in HFD/STZ induced diabetic rats. NA can protect mesangial cells by inhibiting oxidative stress induced apoptosis, which may be related to its regulation of mitochondrial-caspase apoptosis pathway. SN - 1872-7573 UR - https://www.unboundmedicine.com/medline/citation/32201300/Nepeta_angustifolia_C__Y__Wu_improves_renal_injury_in_HFD/STZ_induced_diabetic_nephropathy_and_inhibits_oxidative_stress_induced_apoptosis_of_mesangial_cells_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0378-8741(19)35075-5 DB - PRIME DP - Unbound Medicine ER -