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Renal protective effect and action mechanism of Huangkui capsule and its main five flavonoids.
J Ethnopharmacol. 2017 Jul 12; 206:152-159.JE

Abstract

ETHNOPHARMACOLOGICAL RELEVANCE

The flower of Abelmoschus manihot (Linn.) Medicus (A. manihot), as a traditional Chinese Herbal medicine, was used widely in China with efficacy of inducing diuresis for treating strangurtia, and subdhing swelling and detoxicating. It has been reported that Huangkui capsule, prepared by the extract of the flower of A. manihot, can reduce the content of urinary protein, serum creatinine and serum urea nitrogen in nephropathy rats and processes renoprotective activity, while the action mechanism need to illuminate deeply.

AIMS OF THE STUDY

In this study, we investigated the protection effect of Huangkui capsule on tubulointerstitial fibrosis in chronic renal failure (CRF) rats and its mechanism against high glucose-induced epithelial to mesenchymal transition (EMT) in renal tubular epithelial cells (HK-2) of its bioactive components.

MATERIALS AND METHODS

The animals were divided into normal group, CRF model group and Huangkui capsule-treated group. Hematoxylin eosin (HE) staining and Masson staining were applied to observe pathological changes in renal tissue of different groups. Biochemical indicators including serum urea nitrogen (BUN), urine protein (UP) and serum creatinine (Scr) were measured according to the manufacturer's instructions of kits. HK-2 cell damaged model was established to access the protection effect and action mechanism of five main flavonoids from Huangkui capsule. The experimental cells were divided into eight groups: control group, model group, positive drug group and five main flavonoids treated groups. The dichlorodihydrofluorescein diacetate (DCFH-DA) assay was used to determine the reactive oxygen species (ROS) in different groups. Western blot was applied to analyze the expression of pathogenesis-related proteins in different groups.

RESULTS

The results stated that Huangkui capsule significantly inhibited the elevation of Scr, BUN, UP, the expression of α-smooth muscle actin (α-SMA), phosphorylation-extracellular signal-regulated kinase (p-ERK1/2), NADPH Oxidase 1, NADPH Oxidase 2 and NADPH Oxidase 4 in adenine-induced CRF rats. The main bioactive components of quercetin (QT), hyperoside (HY), isoquercitrin (IQT), gossypetin-8-O-β-D-glucuronide (GG) and quercetin-3'-O-glucoside (QG) at the dosage of 100µM, like NADPH oxidase inhibitor diphenyleneiodonium, exhibited a significant effect on inhibiting the expression of α-SMA, p-ERK1/2, NADPH Oxidase 1, NADPH Oxidase 2 and NADPH Oxidase 4 in high glucose-induced HK-2 cells, especially GG.

CONCLUSIONS

These results demonstrated that Huangkui capsule and the flavonoids components prevent tubulointerstitial fibrosis in CRF rat involvement in the action mechanism of inhibiting NADPH oxidase/ROS/ERK pathway.

Authors+Show Affiliations

Jiangsu Collaborative Innovation Center of Chinese Medicinal Resources Industrialization, and National and Local Collaborative Engineering Center of Chinese Medicinal Resources Industrialization and Formulae Innovative Medicine, Nanjing University of Chinese Medicine, Nanjing 210023, China. Electronic address: 1021779650@qq.com.Jiangsu Collaborative Innovation Center of Chinese Medicinal Resources Industrialization, and National and Local Collaborative Engineering Center of Chinese Medicinal Resources Industrialization and Formulae Innovative Medicine, Nanjing University of Chinese Medicine, Nanjing 210023, China. Electronic address: sushulan1974@163.com.Jiangsu Collaborative Innovation Center of Chinese Medicinal Resources Industrialization, and National and Local Collaborative Engineering Center of Chinese Medicinal Resources Industrialization and Formulae Innovative Medicine, Nanjing University of Chinese Medicine, Nanjing 210023, China. Electronic address: qiandwnj@126.com.Jiangsu Collaborative Innovation Center of Chinese Medicinal Resources Industrialization, and National and Local Collaborative Engineering Center of Chinese Medicinal Resources Industrialization and Formulae Innovative Medicine, Nanjing University of Chinese Medicine, Nanjing 210023, China. Electronic address: gsh916@163.com.Jiangsu Collaborative Innovation Center of Chinese Medicinal Resources Industrialization, and National and Local Collaborative Engineering Center of Chinese Medicinal Resources Industrialization and Formulae Innovative Medicine, Nanjing University of Chinese Medicine, Nanjing 210023, China; Center for Translational Systems Biology and Neuroscience, Laboratory of Integrative Biomedicine of Brain Diseases, School of Basic Biomedical Science, Nanjing University of Chinese Medicine, Nanjing 210023, China. Electronic address: tw845@163.com.SZYY Group Pharmaceutical Limited, Jiangyan 225500, China.SZYY Group Pharmaceutical Limited, Jiangyan 225500, China. Electronic address: tangrenmao@163.com.Jiangsu Collaborative Innovation Center of Chinese Medicinal Resources Industrialization, and National and Local Collaborative Engineering Center of Chinese Medicinal Resources Industrialization and Formulae Innovative Medicine, Nanjing University of Chinese Medicine, Nanjing 210023, China. Electronic address: duanja@163.com.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

28408246

Citation

Cai, Hong-Die, et al. "Renal Protective Effect and Action Mechanism of Huangkui Capsule and Its Main Five Flavonoids." Journal of Ethnopharmacology, vol. 206, 2017, pp. 152-159.
Cai HD, Su SL, Qian DW, et al. Renal protective effect and action mechanism of Huangkui capsule and its main five flavonoids. J Ethnopharmacol. 2017;206:152-159.
Cai, H. D., Su, S. L., Qian, D. W., Guo, S., Tao, W. W., Cong, X. D., Tang, R., & Duan, J. A. (2017). Renal protective effect and action mechanism of Huangkui capsule and its main five flavonoids. Journal of Ethnopharmacology, 206, 152-159. https://doi.org/10.1016/j.jep.2017.02.046
Cai HD, et al. Renal Protective Effect and Action Mechanism of Huangkui Capsule and Its Main Five Flavonoids. J Ethnopharmacol. 2017 Jul 12;206:152-159. PubMed PMID: 28408246.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Renal protective effect and action mechanism of Huangkui capsule and its main five flavonoids. AU - Cai,Hong-Die, AU - Su,Shu-Lan, AU - Qian,Da-Wei, AU - Guo,Sheng, AU - Tao,Wei-Wei, AU - Cong,Xu Dong, AU - Tang,Renmao, AU - Duan,Jin-Ao, Y1 - 2017/04/10/ PY - 2016/09/22/received PY - 2017/02/12/revised PY - 2017/02/20/accepted PY - 2017/4/15/pubmed PY - 2018/4/18/medline PY - 2017/4/15/entrez KW - Chronic renal failure KW - Flavonoids KW - HK2 cells KW - Huangkui capsule KW - NADPH oxidase/ROS/ERK pathway KW - gossypetin-8-O-β- D-glucuronide (PubChem CID: 5490334) KW - hyperoside (PubChem CID: 5281643) KW - isoquercitrin (PubChem CID: 5280804) KW - myricetin (PubChem CID: 5281672) KW - myricetin-3-O-β-D-glucoside (PubChem CID: 5318606) KW - quercetin-3′-O-β-D-glucoside (PubChem CID: 44259229) SP - 152 EP - 159 JF - Journal of ethnopharmacology JO - J Ethnopharmacol VL - 206 N2 - ETHNOPHARMACOLOGICAL RELEVANCE: The flower of Abelmoschus manihot (Linn.) Medicus (A. manihot), as a traditional Chinese Herbal medicine, was used widely in China with efficacy of inducing diuresis for treating strangurtia, and subdhing swelling and detoxicating. It has been reported that Huangkui capsule, prepared by the extract of the flower of A. manihot, can reduce the content of urinary protein, serum creatinine and serum urea nitrogen in nephropathy rats and processes renoprotective activity, while the action mechanism need to illuminate deeply. AIMS OF THE STUDY: In this study, we investigated the protection effect of Huangkui capsule on tubulointerstitial fibrosis in chronic renal failure (CRF) rats and its mechanism against high glucose-induced epithelial to mesenchymal transition (EMT) in renal tubular epithelial cells (HK-2) of its bioactive components. MATERIALS AND METHODS: The animals were divided into normal group, CRF model group and Huangkui capsule-treated group. Hematoxylin eosin (HE) staining and Masson staining were applied to observe pathological changes in renal tissue of different groups. Biochemical indicators including serum urea nitrogen (BUN), urine protein (UP) and serum creatinine (Scr) were measured according to the manufacturer's instructions of kits. HK-2 cell damaged model was established to access the protection effect and action mechanism of five main flavonoids from Huangkui capsule. The experimental cells were divided into eight groups: control group, model group, positive drug group and five main flavonoids treated groups. The dichlorodihydrofluorescein diacetate (DCFH-DA) assay was used to determine the reactive oxygen species (ROS) in different groups. Western blot was applied to analyze the expression of pathogenesis-related proteins in different groups. RESULTS: The results stated that Huangkui capsule significantly inhibited the elevation of Scr, BUN, UP, the expression of α-smooth muscle actin (α-SMA), phosphorylation-extracellular signal-regulated kinase (p-ERK1/2), NADPH Oxidase 1, NADPH Oxidase 2 and NADPH Oxidase 4 in adenine-induced CRF rats. The main bioactive components of quercetin (QT), hyperoside (HY), isoquercitrin (IQT), gossypetin-8-O-β-D-glucuronide (GG) and quercetin-3'-O-glucoside (QG) at the dosage of 100µM, like NADPH oxidase inhibitor diphenyleneiodonium, exhibited a significant effect on inhibiting the expression of α-SMA, p-ERK1/2, NADPH Oxidase 1, NADPH Oxidase 2 and NADPH Oxidase 4 in high glucose-induced HK-2 cells, especially GG. CONCLUSIONS: These results demonstrated that Huangkui capsule and the flavonoids components prevent tubulointerstitial fibrosis in CRF rat involvement in the action mechanism of inhibiting NADPH oxidase/ROS/ERK pathway. SN - 1872-7573 UR - https://www.unboundmedicine.com/medline/citation/28408246/Renal_protective_effect_and_action_mechanism_of_Huangkui_capsule_and_its_main_five_flavonoids_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0378-8741(16)30956-4 DB - PRIME DP - Unbound Medicine ER -