Pharmacist at Central Administration for Pharmaceutical Affairs, Ministry of Health, Cairo, Egypt.
Pharmacology & Toxicology Department, Faculty of Pharmacy, Ain Shams University, Cairo, Egypt.
Ann Hepatol. 2018 Mar 1;17(2):307-317. doi: 10.5604/01.3001.0010.8661.
The present study aimed to elucidate the potential antifibrotic effects of pinocembrin (PIN), a flavanone found abundantly in honey and propolis, by studying its effect on different oxidative stress, inflammatory and fibrosis markers in an experimental model of CCl4-induced liver fibrosis.
PIN (20 mg/kg) was given orally 3 times/week for 6 consecutive weeks alternating with CCl4 (0.5 mL/kg, 1:1 mixture with corn oil, i. p.) twice weekly. Different hepatotoxicity indices, oxidative stress, inflammatory and liver fibrosis markers were assessed.
PIN significantly restored liver transaminases and total cholesterol to normal levels. Also, PIN ameliorated oxidative stress injury evoked by CCl4 as evidenced by inhibition of reduced glutathione depletion and lipid peroxidation as well as elevation of antioxidant enzyme superoxide dismutase (SOD). Further, PIN upregulated the nuclear factor erythroid 2 (NF-E2)-related factor 2 (Nrf2), thereby inducing the expression and activity of the cytoprotective enzyme hemeoxygenase-1 (HO-1). Moreover, PIN alleviated pro-inflammatory cytokines such as TNF-α via inhibiting nuclear factor-κB (NF-κB) activation. As markers of fibrosis, collagen and α-SMA expression increased markedly in the CCl4 group and PIN prevented these alterations. In addition, PIN down-regulated TGFβ1 and p-Smad2/3, thereby inhibiting TGFβ1/Smad signaling pathway.
These results suggest that PIN possess potent antifibrotic effects that can be explained on its antioxidant properties. It ameliorates oxidative stress and inflammation during induction of fibrogenesis via its ability to augment celular antioxidant defenses, activating Nrf2-mediated HO-1 expression and modulating NF-κB and TGF-β1/Smad signaling pathway.
本研究旨在探讨白杨素（PIN）的潜在抗纤维化作用，白杨素是一种在蜂蜜和蜂胶中含量丰富的黄烷酮，通过研究其对 CCl4 诱导的肝纤维化实验模型中不同氧化应激、炎症和纤维化标志物的影响来阐明这一作用。
PIN（20mg/kg）每周口服 3 次，连续 6 周，与 CCl4（0.5mL/kg，与玉米油 1:1 混合，ip）交替使用，每周 2 次。评估了不同的肝毒性指数、氧化应激、炎症和肝纤维化标志物。
PIN 可使肝转氨酶和总胆固醇恢复正常水平。此外，PIN 通过抑制还原型谷胱甘肽耗竭和脂质过氧化以及提高抗氧化酶超氧化物歧化酶（SOD）来改善 CCl4 引起的氧化应激损伤。此外，PIN 上调核因子红细胞 2（NF-E2）相关因子 2（Nrf2），从而诱导保护性酶血红素加氧酶-1（HO-1）的表达和活性。此外，PIN 通过抑制核因子-κB（NF-κB）的激活来减轻 TNF-α等促炎细胞因子。作为纤维化标志物，胶原和α-SMA 的表达在 CCl4 组中显著增加，而 PIN 可防止这些改变。此外，PIN 下调 TGFβ1 和 p-Smad2/3，从而抑制 TGFβ1/Smad 信号通路。
这些结果表明，PIN 具有强大的抗纤维化作用，其抗氧化特性可以解释这一作用。它通过增强细胞抗氧化防御能力、激活 Nrf2 介导的 HO-1 表达以及调节 NF-κB 和 TGF-β1/Smad 信号通路，在诱导纤维化过程中改善氧化应激和炎症。
