Eruberin A, a Natural Flavanol Glycoside, Exerts Anti-Fibrotic Action on Pancreatic Stellate Cells

Abstract

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). Conclusion: 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.

Dihydro‐Resveratrol Ameliorates Lung Injury in Rats with Cerulein‐Induced Acute Pancreatitis

“…Natural products have been shown to provide beneficial effects on various pathological conditions as we reported in previous studies (Tsang and Bian, ; Tsang et al , ). To this end, the pharmacological properties of natural compounds are of our particular interest.…”

Docosahexaenoic Acid Inhibits Expression of Fibrotic Mediators in Mice With Chronic Pancreatitis

“…NF-B has been shown to mediate high fat diet-related pancreatic fibrosis in rats [32]. Furthermore, inhibition of NF-B expression by Eruberin A (2, 3-dehydroflavonoid), a flavanol glycoside isolated from Pronephrium penangianum, has been reported to suppress the expression of fibrotic mediators including -SMA, fibronectin, and type 1-collagen in pancreatic stellate cells [33]. Activation of pancreatic stellate cells is the key commencing step in pancreatic fibrosis, which is a characteristic feature associated with CP.…”

A Comprehensive Review on Pronephrium penangianum

“…In LTC‐14 cells, a cell line retained characteristics and morphological features of PSCs (primary pancreatic stellate cell), eruberin A ( 18 ) can not only effectively inhibit the expression levels of α ‐smooth muscle actin, fibronectin and type I‐collagen (20 μg/ml) as well as the stimulation of post transforming growth factor‐ β in sonic hedgehog signaling pathway (5 ng/ml), but also notably decrease the activation of NF‐κB and the phosphorylation of PI3 K (phosphoinositide 3‐kinase)/Akt (serine‐threonine kinase), which demonstrated that it significantly suppressed the expression levels of fibrotic mediators in PSCs and its anti‐fibrotic mechanism was considered to associate with an attenuation of PI3 K/Akt/NF‐κB signaling way …”