Eruberin A, a Natural Flavanol Glycoside, Exerts Anti-Fibrotic Action on Pancreatic Stellate Cells.
BACKGROUND
Eruberin A (2, 3-dehydroflavonoid), a flavanol glycoside isolated from Pronephrium penangianum, has been used as a blood-nourishing folk medicine for centuries; however, it indeed possesses a variety of other health-promoting benefits including anti-fibrotic bioactivity. Activation of pancreatic stellate cells (PSCs) is the key initiating step in pancreatic fibrosis, which is a characteristic feature associated with chronic pancreatitis and pancreatic adenocarcinoma.


METHODS
The anti-fibrotic effect of eruberin A and the underlying mechanisms of its anti-fibrotic action in LTC-14 cells, which retained essential characteristics and morphological features of primary PSCs, were examined by means of real-time polymerase chain reactions, Western blotting and immunostaining.


RESULTS
The application of eruberin A (20 μg/ml) effectively inhibited the expression levels of fibrotic mediators namely alpha-smooth muscle actin, fibronectin and type I-collagen, so as the sonic hedgehog signaling pathway components post transforming growth factor-beta (5 ng/ml) stimulation. Eruberin A treatment also led to a notable decrease in the activation of nuclear factor-kappaB (NF-κB) and the phosphorylation of phosphoinositide 3-kinase (PI3K)/serine-threonine kinase (AKT).


CONCLUSIONS
Our results demonstrated that eruberin A significantly suppressed the expression levels of fibrotic mediators in PSCs, and we suggest that its anti-fibrotic mechanism was associated with an attenuation of the PI3K/AKT/NF-κB signaling pathway.
School of Chinese Medicine, Hong Kong Baptist University, Kowloon Tong, Hong Kong SAR, China.
Siu Wai
SW
Tsang
Hong-Jie
HJ
Zhang
Ye-Gao
YG
Chen
Kathy Ka-Wai
KK
Auyeung
Zhao-Xiang
ZX
Bian
D000818:Animals; D000872:Anthocyanins / Q000737:chemistry / Q000494:pharmacology*; D016923:Cell Death / Q000187:drug effects; D002460:Cell Line; D015536:Down-Regulation / Q000187:drug effects; D005355:Fibrosis; D044948:Flavonols / Q000737:chemistry / Q000494:pharmacology*; D006027:Glycosides / Q000737:chemistry / Q000494:pharmacology*; D053823:Hedgehog Proteins / Q000378:metabolism; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D016328:NF-kappa B / Q000378:metabolism; D058954:Pancreatic Stellate Cells / Q000187:drug effects / Q000473:pathology*; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D051381:Rats; D015398:Signal Transduction / Q000187:drug effects; D016212:Transforming Growth Factor beta / Q000494:pharmacology
D000872:Anthocyanins; D044948:Flavonols; D006027:Glycosides; D053823:Hedgehog Proteins; D016328:NF-kappa B; D016212:Transforming Growth Factor beta; C000607823:eruberin A; D019869:Phosphatidylinositol 3-Kinases