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J Ethnopharmacol. 2016 Jun 5;185:162-70. doi: 10.1016/j.jep.2016.03.026. Epub 2016 Mar 15.

Protection of tauroursodeoxycholic acid on high glucose-induced human retinal microvascular endothelial cells dysfunction and streptozotocin-induced diabetic retinopathy rats.

Author information

1
Key Laboratory of New Drug Delivery System of Chinese Materia Medica, Jiangsu Provincial Academy of Chinese Medicine, Jiangsu, Nanjing 210028, PR China; School of Pharmacy, Anhui University of Chinese Medicine, Anhui, Hefei 230012, PR China.
2
Key Laboratory of New Drug Delivery System of Chinese Materia Medica, Jiangsu Provincial Academy of Chinese Medicine, Jiangsu, Nanjing 210028, PR China.
3
Department of Pediatrics, Jiangsu Integrative Hospital of Chinese Traditional and Western Medicine, Jiangsu, Nanjing 210028, PR China.
4
Jumpcan Pharmaceutical Co., Ltd, Taixing 225400, PR China.
5
Key Laboratory of New Drug Delivery System of Chinese Materia Medica, Jiangsu Provincial Academy of Chinese Medicine, Jiangsu, Nanjing 210028, PR China; School of Pharmacy, Anhui University of Chinese Medicine, Anhui, Hefei 230012, PR China. Electronic address: wenmoxiushi@163.com.
6
Key Laboratory of New Drug Delivery System of Chinese Materia Medica, Jiangsu Provincial Academy of Chinese Medicine, Jiangsu, Nanjing 210028, PR China; School of Pharmacy, Anhui University of Chinese Medicine, Anhui, Hefei 230012, PR China. Electronic address: jxiaobin2005@hotmail.com.

Abstract

ETHNOPHARMACOLOGICAL RELEVANCE:

Tauroursodeoxycholic acid (TUDCA), one of the main ingredients from bear gall which hold "Clearing heat and detoxification, Removing liver fire for improving eyesight" functions, is formed by the conjugation of ursodeoxycholic acid (UDCA) with taurine. However, the limited information of TUDCA on protecting diabetic retinopathy (DR) has been known. The present study was conducted to evaluate the protection of TUDCA on high glucose-induced human retinal microvascular endothelial cells (HRMECs) dysfunction and streptozotocin (STZ)-induced diabetic retinopathy (DR) rats and the possible mechanism underlying was also explored.

MATERIALS AND METHODS:

The proliferation of high glucose-induced HRMECs was determined by MTT assay. DR rats' model was established by an administration of high-glucose-fat diet and an intraperitoneal injection of STZ (30mg/kg). The cell supernatant and rats' serum were collected for the assays of NO content by ELISA kits. Retinas were stained with hematoxylin and eosin (HE) to observe pathological changes. Immunohistochemical assay was applied to examine the protein expression of ICAM-1, NOS, NF-κB p65 and VEGF in rat retinas. Furthermore, western blot analysis was carried out to examine the protein expression of ICAM-1, NOS, NF-κB p65 and VEGF in high glucose-induced HRMECs.

RESULTS:

After treating with TUDCA, high glucose-induced HRMECs proliferation could be significantly inhibited. TUDCA (5.0μM, 25.0μM and 125.0μM) could decrease NO content in high glucose-induced HRMECs. Furthermore, TUDCA (500mg/kg/d and 250mg/kg/d) also decrease NO content in serum of DR rats. Additionally, both immunocytochemistry analysis and western blot analysis showed that the over-expression of ICAM-1, NOS, NF-κB p65 and VEGF were significantly decreased by TUDCA.

CONCLUSION:

The data indicated that TUDCA could ameliorate DR by decreasing NO content and down-regulating the protein expression of ICAM-1, NOS, NF-κB p65 and VEGF. Thus, our experimental results suggested that TUDCA might be a potential drug for the prevention and treatment of DR.

KEYWORDS:

Calcium Dobesilate (PubChem CID: 29963); Diabetic retinopathy; HRMECs; Streptozotocin (PubChem CID: 5300); Tauroursodeoxycholic acid; Tauroursodeoxycholic acid (PubChem CID: 9848818); Ursodeoxycholic acid (PubChem CID: 31401)

PMID:
26988565
DOI:
10.1016/j.jep.2016.03.026
[Indexed for MEDLINE]

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