Tags

Type your tag names separated by a space and hit enter

Huangkui capsule attenuates renal fibrosis in diabetic nephropathy rats through regulating oxidative stress and p38MAPK/Akt pathways, compared to α-lipoic acid.
J Ethnopharmacol. 2015 Sep 15; 173:256-65.JE

Abstract

ETHNOPHARMACOLOGICAL RELEVANCE

In traditional Chinese medicine (TCM), Abelmoschus manihot (L.) medic (AM) is a natural medicinal plant used for the treatment of inflammatory diseases. Recently, Huangkui capsule (HKC), a Chinese patent medicine extracted from AM, has been widely applied to the clinical therapy of renal fibrosis in patients with early diabetic nephropathy (DN). However, the therapeutic mechanisms involved in vivo remain ambiguous. The goal of this study is to expound the mechanism in vivo of HKC in order to deepen the understanding of its clinical effects, by using the approaches of contrasting the dose-effects of HKC on oxidative stress (OS) in the kidney compared to α-lipoic acid (LA), and then demonstrating whether and how anti-oxidative properties of HKC or LA might be beneficial for the treatment of renal fibrosis in vivo.

MATERIALS AND METHODS

Thirty-three rats were divided into 5 groups, a Sham group, a Vehicle group, a L-HKC group, a H-HKC group and a LA group. The different doses of HKC, LA and distilled water were daily administrated for 8 weeks after the induction of DN by the unilateral nephrectomy combined with streptozotocin (STZ) intraperitoneal injections. Rat's general status, biochemical parameters, renal histological changes and OS indicators, as well as the key protein expressions in p38 mitogen-activated protein kinase (p38MAPK)/serine-threonine kinase (Akt) signaling pathways and downstream cytokines including transforming growth factor (TGF)-β1 and tumor necrosis factor (TNF)-α were examined, respectively.

RESULTS

HKC and LA ameliorated body weight, kidney weight, urinary albumin and renal function including blood urea nitrogen and serum uric acid, attenuated renal fibrosis including the cell numbers and extracellular matrix rate in glomerulus, and controlled OS indicators including malondialdehyde, total superoxide dismutase, 8-hydroxy-2'-deoxyguanosine and nicotinamide adenine dinucleotide phosphate oxidase 4, but did not lower blood glucose in DN model rats. Among them, the anti-renal fibrosis effect of H-HKC was better than that of LA. In addition, HKC simultaneously down-regulated the protein expressions of phosphorylated p38MAPK, phosphorylated Akt (p-Akt), TGF-β1 and TNF-α in the kidney of DN model rats, unlike HKC, LA only down-regulated p-Akt and TNF-α protein expressions.

CONCLUSION

We have demonstrated that HKC, similar to LA, is renoprotective via attenuating OS and renal fibrosis in the DN rat model. The potential mechanisms by which HKC and LA exert their therapeutic effects in vivo are respectively through down-regulating the activation of p38MAPK and/or Akt pathways as well as the expressions of TGF-β1 and/or TNF-α in the kidney. Our findings thus provide the useful information about a clinical combination of HKC and LA in early DN patients.

Authors+Show Affiliations

Nanjing Drum Tower Hospital Clinical College of Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjng, China.Department of Traditional Chinese Medicine, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, 321 Zhongshan Road, Nanjing 210008, China.Department of Traditional Chinese Medicine, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, 321 Zhongshan Road, Nanjing 210008, China. Electronic address: wyg68918@sina.com.Department of Nephrology, Jiangsu Provincial Hospital of Chinese Medicine, Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing 210029, China. Electronic address: wyg68918@hotmail.com.Nanjing Drum Tower Hospital Clinical College of Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjng, China.Key Laboratory of New Drug Delivery System of Chinese Meteria Medica, Jiangsu Provincial Academy of Chinese Medicine, Nanjing, China.Nanjing Drum Tower Hospital Clinical College of Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjng, China.Nanjing Drum Tower Hospital Clinical College of Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjng, China.Suzhong Pharmaceutical Group Co., Ltd., Taizhou, China.Suzhong Pharmaceutical Group Co., Ltd., Taizhou, China.

Pub Type(s)

Comparative Study
Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

26226437

Citation

Mao, Zhi-Min, et al. "Huangkui Capsule Attenuates Renal Fibrosis in Diabetic Nephropathy Rats Through Regulating Oxidative Stress and p38MAPK/Akt Pathways, Compared to Α-lipoic Acid." Journal of Ethnopharmacology, vol. 173, 2015, pp. 256-65.
Mao ZM, Shen SM, Wan YG, et al. Huangkui capsule attenuates renal fibrosis in diabetic nephropathy rats through regulating oxidative stress and p38MAPK/Akt pathways, compared to α-lipoic acid. J Ethnopharmacol. 2015;173:256-65.
Mao, Z. M., Shen, S. M., Wan, Y. G., Sun, W., Chen, H. L., Huang, M. M., Yang, J. J., Wu, W., Tang, H. T., & Tang, R. M. (2015). Huangkui capsule attenuates renal fibrosis in diabetic nephropathy rats through regulating oxidative stress and p38MAPK/Akt pathways, compared to α-lipoic acid. Journal of Ethnopharmacology, 173, 256-65. https://doi.org/10.1016/j.jep.2015.07.036
Mao ZM, et al. Huangkui Capsule Attenuates Renal Fibrosis in Diabetic Nephropathy Rats Through Regulating Oxidative Stress and p38MAPK/Akt Pathways, Compared to Α-lipoic Acid. J Ethnopharmacol. 2015 Sep 15;173:256-65. PubMed PMID: 26226437.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Huangkui capsule attenuates renal fibrosis in diabetic nephropathy rats through regulating oxidative stress and p38MAPK/Akt pathways, compared to α-lipoic acid. AU - Mao,Zhi-Min, AU - Shen,Shan-Mei, AU - Wan,Yi-Gang, AU - Sun,Wei, AU - Chen,Hao-Li, AU - Huang,Meng-Meng, AU - Yang,Jing-Jing, AU - Wu,Wei, AU - Tang,Hai-Tao, AU - Tang,Ren-Mao, Y1 - 2015/07/28/ PY - 2015/02/04/received PY - 2015/06/13/revised PY - 2015/07/25/accepted PY - 2015/7/31/entrez PY - 2015/8/1/pubmed PY - 2016/8/9/medline KW - Akt signaling pathway KW - Diabetic nephropathy KW - Huangkui capsule KW - Oxidative stress KW - Renal fibrosis KW - p38MAPK signaling pathway SP - 256 EP - 65 JF - Journal of ethnopharmacology JO - J Ethnopharmacol VL - 173 N2 - ETHNOPHARMACOLOGICAL RELEVANCE: In traditional Chinese medicine (TCM), Abelmoschus manihot (L.) medic (AM) is a natural medicinal plant used for the treatment of inflammatory diseases. Recently, Huangkui capsule (HKC), a Chinese patent medicine extracted from AM, has been widely applied to the clinical therapy of renal fibrosis in patients with early diabetic nephropathy (DN). However, the therapeutic mechanisms involved in vivo remain ambiguous. The goal of this study is to expound the mechanism in vivo of HKC in order to deepen the understanding of its clinical effects, by using the approaches of contrasting the dose-effects of HKC on oxidative stress (OS) in the kidney compared to α-lipoic acid (LA), and then demonstrating whether and how anti-oxidative properties of HKC or LA might be beneficial for the treatment of renal fibrosis in vivo. MATERIALS AND METHODS: Thirty-three rats were divided into 5 groups, a Sham group, a Vehicle group, a L-HKC group, a H-HKC group and a LA group. The different doses of HKC, LA and distilled water were daily administrated for 8 weeks after the induction of DN by the unilateral nephrectomy combined with streptozotocin (STZ) intraperitoneal injections. Rat's general status, biochemical parameters, renal histological changes and OS indicators, as well as the key protein expressions in p38 mitogen-activated protein kinase (p38MAPK)/serine-threonine kinase (Akt) signaling pathways and downstream cytokines including transforming growth factor (TGF)-β1 and tumor necrosis factor (TNF)-α were examined, respectively. RESULTS: HKC and LA ameliorated body weight, kidney weight, urinary albumin and renal function including blood urea nitrogen and serum uric acid, attenuated renal fibrosis including the cell numbers and extracellular matrix rate in glomerulus, and controlled OS indicators including malondialdehyde, total superoxide dismutase, 8-hydroxy-2'-deoxyguanosine and nicotinamide adenine dinucleotide phosphate oxidase 4, but did not lower blood glucose in DN model rats. Among them, the anti-renal fibrosis effect of H-HKC was better than that of LA. In addition, HKC simultaneously down-regulated the protein expressions of phosphorylated p38MAPK, phosphorylated Akt (p-Akt), TGF-β1 and TNF-α in the kidney of DN model rats, unlike HKC, LA only down-regulated p-Akt and TNF-α protein expressions. CONCLUSION: We have demonstrated that HKC, similar to LA, is renoprotective via attenuating OS and renal fibrosis in the DN rat model. The potential mechanisms by which HKC and LA exert their therapeutic effects in vivo are respectively through down-regulating the activation of p38MAPK and/or Akt pathways as well as the expressions of TGF-β1 and/or TNF-α in the kidney. Our findings thus provide the useful information about a clinical combination of HKC and LA in early DN patients. SN - 1872-7573 UR - https://www.unboundmedicine.com/medline/citation/26226437/Huangkui_capsule_attenuates_renal_fibrosis_in_diabetic_nephropathy_rats_through_regulating_oxidative_stress_and_p38MAPK/Akt_pathways_compared_to_α_lipoic_acid_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0378-8741(15)30053-2 DB - PRIME DP - Unbound Medicine ER -