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Fitoterapia. 2016 Jul;112:244-53. doi: 10.1016/j.fitote.2016.06.010. Epub 2016 Jun 23.

Genipin ameliorates hypertension-induced renal damage via the angiotensin II-TLR/MyD88/MAPK pathway.

Author information

1
Department of Cardiology, Yantaishan Hospital, Yantai, Shandong, Province, 264001, China.
2
Department of Cardiology, Yantai Affiliated Hospital of Binzhou Medical College, Yantai, Shandong, Province, 264003, China.
3
Second Department of Internal Medicine, Yantaishan Hospital, Yantai, Shandong, Province, 264001, China.
4
Department of Cardiology, Yantaishan Hospital, Yantai, Shandong, Province, 264001, China. Electronic address: dr.liuwenbo@gmail.com.

Abstract

Genipin is a major active component of Fructus Gardenia, which has been widely used in Traditional Chinese Medicine for the treatment of various cardiovascular diseases. The aim of this study was to investigate the potential effects of genipin on hypertension and the related nephropathy and elucidate the underlying mechanisms of action. We first examined the effects of genipin on blood pressure and renal functions in the Spontaneously Hypertensive (SHR) rats. In the subsequent experiments with human mesangial cells (HMCs), the effects of genipin on angiotensin II (Ang II)-induced HMC proliferation, reactive oxygen species (ROS) generation, and cytokine prodution were examined using the MTT method, 2',7'-dichlorohydrofluorescein (DCFH-DA) staining, and the corresponding enzyme-linked immunosorbent assay (ELISA) kits, respectively. The effects of genipin on Ang II-induced activation of the MAPK pathway and up-regulation of TLR2, TLR4, and MyD88 were detected by real-time PCR and Western blot and further validated in MyD88 siRNA-transfected HMCs. Genipin not only significantly lowered blood pressure in SHR rats after an 8-week treatment, but effectively improved renal functions, evidenced by decreased serum creatinine and blood urea nitrogen (BUN), as well as urinary microalbumin (m-ALB) and N-acetyl-beta-d-glucosaminidase (NAG) upon administration with genipin. Mechanistic studies conducted in Ang II-treated HMCs showed that genipin was able to counteract Ang II-induced cell proliferation, ROS generation, and pro-inflammatory responses. These effects may be mediated through the TLR/MyD88/MAPK signaling pathway. These findings provide new insights into the molecular mechanisms of genipin in the treatment of renal damage in hypertension, which merits a further investigation.

KEYWORDS:

Angiotensin II; Genipin; Human mesangial cells; Hypertension; Toll-like receptors

PMID:
27343367
DOI:
10.1016/j.fitote.2016.06.010
[Indexed for MEDLINE]

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