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Huangkui capsule, an extract from Abelmoschus manihot (L.) medic, improves diabetic nephropathy via activating peroxisome proliferator-activated receptor (PPAR)-α/γ and attenuating endoplasmic reticulum stress in rats.
J Ethnopharmacol. 2016 Aug 02; 189:238-49.JE

Abstract

ETHNOPHARMACOLOGICAL RELEVANCE

Abelmoschus manihot (L.) medic (AM) is a natural medicinal plant used for the treatment of chronic kidney disease (CKD) in China. Huangkui capsule (HKC), an extract from AM, has been proved clinically effective in improving renal inflammation and glomerular injury in CKD. However, the mechanisms of HKC are still not fully understood.

AIM OF THE STUDY

Peroxisome proliferator-activated receptor (PPAR)-α/γ dual agonists have the potential to be used as therapeutic agents for the treatment of type 2 diabetes and diabetic nephropathy (DN). This study evaluated the function of Huangkui capsule (HKC), an extract from Abelmoschus manihot (L.) medic (AM), as a dual agonist for PPARα/γ and investigated its anti-DN effects in a DN rat model.

MATERIALS AND METHODS

ChIP and reporter gene assays were performed and the expression of PPARα/γ target genes was monitored to examine the ability of HKC to activate PPARα/γ. DN was induced in male Sprague-Dawley rats via unilateral nephrectomy and intraperitoneal injection of streptozotocin. HKC was administered to the diabetic nephropathy rats at three different doses: high dose HKC (300mg/kg/d); middle dose HKC (175mg/kg/d); and low dose HKC (75mg/kg/d). Irbesartan (4mg/kg/d body weight) was used as a positive control. Following 12 weeks' treatment, we measured general status, renal morphological appearance, proteinuria, blood biochemical parameters, and glomerular morphological changes. The expression of collagen IV, TGFβ, TNFα and IL-6 in renal tissue was evaluated. Endoplasmic reticulum (ER) stress in renal tissue was also analyzed.

RESULTS

HKC enhanced the transcriptional activity of PPARα and PPARγ in cultured cells, livers and kidneys of DN rats, and it reduced serum triglyceride and cholesterol levels and fat in livers of DN rats. Furthermore, HKC reduced the expressions of inflammatory genes in kidneys of DN rats. Strikingly, HKC reduced ER stress and c-Jun NH2-terminal kinase activation in the liver and kidney of DN rats and subsequently improved renal injury.

CONCLUSIONS

Our results show that HKC improved lipid metabolic disorders by activating PPARα/γ and attenuating ER stress. HKC could dose-dependently ameliorate renal inflammation and glomerular injury in DN rats. These results suggest that HKC has potential as an anti-DN agent for the treatment of DN in humans.

Authors+Show Affiliations

Jiangsu Province Hosipital of TCM, Affiliated Hospital of Nanjing University of TCM, Nanjing Hanzhong Road, Nanjing, China.Jiangsu Province Hosipital of TCM, Affiliated Hospital of Nanjing University of TCM, Nanjing Hanzhong Road, Nanjing, China.Jiangsu Province Hosipital of TCM, Affiliated Hospital of Nanjing University of TCM, Nanjing Hanzhong Road, Nanjing, China.Jiangsu Province Hosipital of TCM, Affiliated Hospital of Nanjing University of TCM, Nanjing Hanzhong Road, Nanjing, China. Electronic address: jiangyiyunjcm@sohu.com.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

27224243

Citation

Ge, Jing, et al. "Huangkui Capsule, an Extract From Abelmoschus Manihot (L.) Medic, Improves Diabetic Nephropathy Via Activating Peroxisome Proliferator-activated Receptor (PPAR)-α/γ and Attenuating Endoplasmic Reticulum Stress in Rats." Journal of Ethnopharmacology, vol. 189, 2016, pp. 238-49.
Ge J, Miao JJ, Sun XY, et al. Huangkui capsule, an extract from Abelmoschus manihot (L.) medic, improves diabetic nephropathy via activating peroxisome proliferator-activated receptor (PPAR)-α/γ and attenuating endoplasmic reticulum stress in rats. J Ethnopharmacol. 2016;189:238-49.
Ge, J., Miao, J. J., Sun, X. Y., & Yu, J. Y. (2016). Huangkui capsule, an extract from Abelmoschus manihot (L.) medic, improves diabetic nephropathy via activating peroxisome proliferator-activated receptor (PPAR)-α/γ and attenuating endoplasmic reticulum stress in rats. Journal of Ethnopharmacology, 189, 238-49. https://doi.org/10.1016/j.jep.2016.05.033
Ge J, et al. Huangkui Capsule, an Extract From Abelmoschus Manihot (L.) Medic, Improves Diabetic Nephropathy Via Activating Peroxisome Proliferator-activated Receptor (PPAR)-α/γ and Attenuating Endoplasmic Reticulum Stress in Rats. J Ethnopharmacol. 2016 Aug 2;189:238-49. PubMed PMID: 27224243.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Huangkui capsule, an extract from Abelmoschus manihot (L.) medic, improves diabetic nephropathy via activating peroxisome proliferator-activated receptor (PPAR)-α/γ and attenuating endoplasmic reticulum stress in rats. AU - Ge,Jing, AU - Miao,Jun-Jun, AU - Sun,Xin-Yi, AU - Yu,Jiang-Yi, Y1 - 2016/05/17/ PY - 2015/12/06/received PY - 2016/04/29/revised PY - 2016/05/14/accepted PY - 2016/5/26/entrez PY - 2016/5/26/pubmed PY - 2017/4/21/medline KW - Diabetic nephropathy KW - Endoplasmic reticulum stress KW - Fenofibrate (PubChem CID: 3339) KW - Huangkui capsule KW - Irbesartan (PubChem CID: 3749) KW - PPARα/γ KW - Streptozocin (PubChem CID: 29327) KW - Thapsigargin (PubChem CID: 446378) KW - Troglitazone (PubChem CID: 5591) SP - 238 EP - 49 JF - Journal of ethnopharmacology JO - J Ethnopharmacol VL - 189 N2 - ETHNOPHARMACOLOGICAL RELEVANCE: Abelmoschus manihot (L.) medic (AM) is a natural medicinal plant used for the treatment of chronic kidney disease (CKD) in China. Huangkui capsule (HKC), an extract from AM, has been proved clinically effective in improving renal inflammation and glomerular injury in CKD. However, the mechanisms of HKC are still not fully understood. AIM OF THE STUDY: Peroxisome proliferator-activated receptor (PPAR)-α/γ dual agonists have the potential to be used as therapeutic agents for the treatment of type 2 diabetes and diabetic nephropathy (DN). This study evaluated the function of Huangkui capsule (HKC), an extract from Abelmoschus manihot (L.) medic (AM), as a dual agonist for PPARα/γ and investigated its anti-DN effects in a DN rat model. MATERIALS AND METHODS: ChIP and reporter gene assays were performed and the expression of PPARα/γ target genes was monitored to examine the ability of HKC to activate PPARα/γ. DN was induced in male Sprague-Dawley rats via unilateral nephrectomy and intraperitoneal injection of streptozotocin. HKC was administered to the diabetic nephropathy rats at three different doses: high dose HKC (300mg/kg/d); middle dose HKC (175mg/kg/d); and low dose HKC (75mg/kg/d). Irbesartan (4mg/kg/d body weight) was used as a positive control. Following 12 weeks' treatment, we measured general status, renal morphological appearance, proteinuria, blood biochemical parameters, and glomerular morphological changes. The expression of collagen IV, TGFβ, TNFα and IL-6 in renal tissue was evaluated. Endoplasmic reticulum (ER) stress in renal tissue was also analyzed. RESULTS: HKC enhanced the transcriptional activity of PPARα and PPARγ in cultured cells, livers and kidneys of DN rats, and it reduced serum triglyceride and cholesterol levels and fat in livers of DN rats. Furthermore, HKC reduced the expressions of inflammatory genes in kidneys of DN rats. Strikingly, HKC reduced ER stress and c-Jun NH2-terminal kinase activation in the liver and kidney of DN rats and subsequently improved renal injury. CONCLUSIONS: Our results show that HKC improved lipid metabolic disorders by activating PPARα/γ and attenuating ER stress. HKC could dose-dependently ameliorate renal inflammation and glomerular injury in DN rats. These results suggest that HKC has potential as an anti-DN agent for the treatment of DN in humans. SN - 1872-7573 UR - https://www.unboundmedicine.com/medline/citation/27224243/Huangkui_capsule_an_extract_from_Abelmoschus_manihot__L___medic_improves_diabetic_nephropathy_via_activating_peroxisome_proliferator_activated_receptor__PPAR__α/γ_and_attenuating_endoplasmic_reticulum_stress_in_rats_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0378-8741(16)30305-1 DB - PRIME DP - Unbound Medicine ER -