枳实总黄酮通过调控 NF-κB 和 MAPKs 对非酒精性脂肪肝病大鼠的保肝抗炎作用。
Hepatoprotective and anti-inflammatory effects of total flavonoids of Qu Zhi Ke (peel of Citrus changshan-huyou) on non-alcoholic fatty liver disease in rats via modulation of NF-κB and MAPKs.
机构信息
The First Affiliated Hospital, Zhejiang Chinese Medical University, Hangzhou, China; Key Laboratory of Integrative Chinese and Western Medicine for the Diagnosis and Treatment of Circulatory Diseases of Zhejiang Province, Hangzhou, China; Zhejiang You-du Biotech Limited Company, Quzhou, China.
The First Affiliated Hospital, Zhejiang Chinese Medical University, Hangzhou, China.
出版信息
Phytomedicine. 2019 Nov;64:153082. doi: 10.1016/j.phymed.2019.153082. Epub 2019 Sep 3.
BACKGROUND
Citrus flavonoids, consisting of naringin, narirutin, neohesperidine, etc., have therapeutic activities for the treatment of lipometabolic disorders. The peel of Citrus changshan-huyou (Qu Zhi Ke, QZK) is a new source of flavonoids, but attracted little attention so far.
HYPOTHESIS
QZK should possess therapeutic effects against lipometabolic disorders due to the flavonoids it contains.
STUDY DESIGN
In this study, we extracted and purified the flavonoids of QZK (TFCH) and established an obesity-induced non-alcoholic fatty liver disease (NAFLD) model of rats. TFCH was given orally for 8 weeks, and its anti-NAFLD effects and potential mechanism were evaluated.
METHODS
The flavonoid chemoprofile of TFCH was determined by using HPLC. High-fat diet was employed to induce NAFLD model in rats, and six groups were set up: negative control group, reference treatment group, model group, low-dose TFCH (25 mg/kg), intermediate-dose TFCH (50 mg/kg), and high-dose TFCH (100 mg/kg). Serum and liver levels of inflammatory cytokines and NAFLD markers were measured biochemically. The relative mRNA expressions of liver T-bet, GATA3, and TNF-α were tested by real time PCR (qPCR) analysis. The protein expression of p38 and the phosphorylation of NF-κB, ERK1/2, and p38 in liver were tested by Western blot analysis.
RESULTS
The histopathological observation showed that TFCH attenuated hepatic lesions with significantly decreased NAFLD activity scores. The biochemical data showed that TFCH significantly suppressed both systemic and intrahepatic inflammation by inhibiting IL-1β, IL-6, IL-12, TNF-α, and IFN-γ, and the qPCR analysis revealed a Th1/Th2 related anti-inflammatory mechanism of TFCH. Western blot results clarified that TFCH exerted hepatoprotective and anti-inflammatory effects by suppression of phosphorylated NF-κB and MAPKs, indicating a mechanism associated with NF-κB and MAPK signaling pathways.
CONCLUSION
QZK is a new source of Citrus flavonoids for therapeutic use, and TFCH is a promising representative of Citrus flavonoids for anti-NAFLD therapy.
背景
柚皮苷、新橙皮苷、柚皮芸香苷等柑橘类黄酮具有治疗脂代谢紊乱的作用。橘红（Qu Zhi Ke，QZK）的果皮是黄酮类化合物的新来源，但迄今为止受到的关注甚少。
假说
QZK 应该具有治疗脂代谢紊乱的作用，因为它含有类黄酮。
研究设计
本研究从 QZK 中提取和纯化了类黄酮（TFCH），并建立了肥胖诱导的非酒精性脂肪性肝病（NAFLD）大鼠模型。TFCH 经口给予 8 周，评价其抗 NAFLD 作用及其潜在机制。
方法
采用高效液相色谱法（HPLC）测定 TFCH 的类黄酮化学特征。采用高脂肪饮食诱导大鼠 NAFLD 模型，设阴性对照组、阳性药物对照组、模型组、TFCH 低剂量（25mg/kg）组、中剂量（50mg/kg）组和高剂量（100mg/kg）组。用生化方法检测血清和肝脏中炎症细胞因子和 NAFLD 标志物的水平。用实时 PCR（qPCR）分析检测肝脏 T-bet、GATA3 和 TNF-α 的相对 mRNA 表达。用 Western blot 分析检测肝脏中 p38 和 NF-κB、ERK1/2 和 p38 的磷酸化。
结果
组织病理学观察表明，TFCH 可减轻肝损伤，显著降低 NAFLD 活动评分。生化数据显示，TFCH 通过抑制 IL-1β、IL-6、IL-12、TNF-α和 IFN-γ，显著抑制全身和肝内炎症，qPCR 分析揭示了 TFCH 的 Th1/Th2 相关抗炎机制。Western blot 结果表明，TFCH 通过抑制磷酸化 NF-κB 和 MAPKs 发挥肝保护和抗炎作用，表明其作用机制与 NF-κB 和 MAPK 信号通路有关。
结论
QZK 是治疗用柑橘类黄酮的新来源，TFCH 是治疗 NAFLD 的有前途的柑橘类黄酮代表。
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