Protective effect of a Chinese Medicine formula He-Ying-Qing-Re Formula on diabetic retinopathy.
BACKGROUND
He-Ying-Qing-Re Formula (HF) is a formula modified from "Si-Miao-Yong-An Decoction", a traditional Chinese medical classic emerged in the Qing dynasty and has been reported for treatment of vascular diseases. HF, containing 8 herbs, has been used in local hospital for decades as a complementary method for diabetic retinopathy (DR) with retinal vascular dysfunction. Clinical reports revealed HF could ameliorate vision defects, microaneurysms, hemorrhages and macular edema. The aim of this study is to investigate the anti-DR action of HF and its underlying mechanism experimentally.


METHODS
Chromatographic fingerprinting of HF and rodent model of DR were established; hypoglycemic effect of HF was measured by fasting, random blood glucose and glucose tolerance test; vascular degeneration was measured by retinal digestion; blood-retina-barrier (BRB) permeability was assessed with Evans Blue leakage assay. Advanced glycation end products (AGEs) were measured in vitro and in vivo level; Migration of retinal vascular endothelial cells were determined by wound healing and transwell chamber assays; permeability of endothelial monolayer was monitored with dextran transport. AGEs-related proteins and signaling were measured with immunoblotting and immunohistochemistry.


RESULTS
Chlorogenic acid, ferulic acid and arctin were identified as major components in HF; HF suppresses retinal vasculature degeneration and BRB permeability damage without significant inhibition on hyperglycemia; HF reduces in vitro and in vivo formation of AGEs and AGEs-induced migration as well as permeability of retinal vascular endothelial cells. Expression of tight junction proteins Zo-1 and Claudin-1 was increased while activation of AGEs receptor and downstream signaling Akt were suppressed upon HF treatment.


CONCLUSIONS
HF exhibits protective effect against diabetic retinopathy, which may be associated with inhibition on AGEs and recovery on endothelial dysfunction via modulation of tight junction and AGEs downstream signaling.
Department of Ophthalmology, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, 725 Southern Wanping Road, Shanghai 200032, China; School of Chinese Medicine, the University of Hong Kong, 10 Sassoon Road, Pokfulam, Hong Kong, China.
Leilei
L
Wang
School of Chinese Medicine, the University of Hong Kong, 10 Sassoon Road, Pokfulam, Hong Kong, China.
Ning
N
Wang
School of Chinese Medicine, the University of Hong Kong, 10 Sassoon Road, Pokfulam, Hong Kong, China.
Hor-yue
HY
Tan
Department of Ophthalmology, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, 725 Southern Wanping Road, Shanghai 200032, China. Electronic address: zhangyinj@126.com.
Yinjian
Y
Zhang
School of Chinese Medicine, the University of Hong Kong, 10 Sassoon Road, Pokfulam, Hong Kong, China. Electronic address: yfeng@hku.hk.
Yibin
Y
Feng
D000818:Animals; D001786:Blood Glucose / Q000187:drug effects; D001813:Blood-Retinal Barrier / Q000187:drug effects; D054443:Cell Migration Assays; D002478:Cells, Cultured; D062445:Claudin-1 / Q000378:metabolism; D003930:Diabetic Retinopathy / Q000097:blood / Q000139:chemically induced / Q000188:drug therapy* / Q000378:metabolism / Q000517:prevention & control*; D004365:Drugs, Chinese Herbal / Q000494:pharmacology* / Q000627:therapeutic use*; D005951:Glucose Tolerance Test; D017127:Glycation End Products, Advanced / Q000097:blood / Q000187:drug effects; D006801:Humans; D007004:Hypoglycemic Agents / Q000494:pharmacology / Q000627:therapeutic use; D008297:Male; D051379:Mice; D010936:Plant Extracts / Q000494:pharmacology / Q000627:therapeutic use; D012162:Retinal Degeneration / Q000188:drug therapy; D013311:Streptozocin
D001786:Blood Glucose; D062445:Claudin-1; D004365:Drugs, Chinese Herbal; D017127:Glycation End Products, Advanced; D007004:Hypoglycemic Agents; D010936:Plant Extracts; C000607032:he-ying-qing-re; D013311:Streptozocin
Advanced glycation end products; Blood-retina-barrier breakdown; Diabetic retinopathy; He-Ying-Qing-Re Formula; Retinal vasculature degeneration