蜂王浆对长春新碱诱导的大鼠肝毒性的保肝作用：一项生化与分子研究。

Hepatoprotective Effects of Royal Jelly Against Vincristine-Induced Hepatotoxicity in Rats: A Biochemical and Molecular Study.

作者信息

Erzincan Rahime, Caglayan Cuneyt, Kandemir Fatih Mehmet, İzol Ebubekir, Gür Cihan, İleritürk Mustafa

机构信息

Department of Bee and Bee Products, Institute of Science, Bingöl University, Bingöl 12000, Türkiye.

Department of Medical Biochemistry, Faculty of Medicine, Bilecik Seyh Edebali University, Bilecik 11230, Türkiye.

出版信息

Life (Basel). 2025 Mar 14;15(3):459. doi: 10.3390/life15030459.

Vincristine (VCR) is a chemotherapeutic agent classified as a vinca alkaloid. Royal jelly (RJ) is a significant bee product produced by worker bees, characterized by its high protein content. This study aims to investigate the protective effects of RJ against VCR-induced liver damage. VCR was intraperitoneally administered at a dose of 0.1 mg/kg body weight (b.w.) and RJ was orally administered at doses of 150 and 300 mg/kg b.w. Both treatments were applied to the rats on days 1-6 and 9-14. The composition of RJ was analyzed using LC-MS/MS, revealing the presence of 15 different phytochemical compounds with strong antioxidant properties. Serum samples obtained from the rats were analyzed for ALT, ALP, and AST levels. While these enzyme levels were significantly elevated in the VCR group, a notable reduction was observed following RJ administration. Additionally, SOD, CAT, GPx, and GSH antioxidant parameters, along with MDA levels, were evaluated in liver tissue samples. The results indicated a decrease in SOD, CAT, GPx, and GSH activities/levels and an increase in MDA levels in the VCR group. Furthermore, ELISA was used to assess JAK2, STAT3, and mTOR/PI3K/AKT signaling pathways. VCR administration led to a decrease in mTOR/PI3K/AKT levels and an increase in JAK2 and STAT3 levels. In addition, the mRNA transcription levels of inflammation (NF-κB, TNF-α, and IL-1β), endoplasmic reticulum (ER) stress (IRE-1, GRP78, PERK, and ATF-6), and autophagy markers (LC3A and LC3B) were examined. A significant increase in inflammation, ER stress, and autophagy-related markers was observed in the VCR-treated group. Lastly, the protein expression levels of Bax, Bcl-2, Caspase-3, and NF-κB were evaluated. VCR treatment increased Bax, Caspase 3, and NF-κB levels, whereas Bcl-2 levels were decreased. However, following RJ administration, all these parameters were reversed, demonstrating significant improvements. In conclusion, these findings suggest that RJ may exert a protective effect against VCR-induced liver damage.

长春新碱（VCR）是一种被归类为长春花生物碱的化疗药物。蜂王浆（RJ）是工蜂生产的一种重要蜂产品，其特点是蛋白质含量高。本研究旨在探讨蜂王浆对长春新碱诱导的肝损伤的保护作用。长春新碱以0.1毫克/千克体重（b.w.）的剂量腹腔注射，蜂王浆以150和300毫克/千克体重的剂量口服。两种治疗方法均在第1 - 6天和第9 - 14天应用于大鼠。使用液相色谱 - 串联质谱法（LC - MS/MS）分析蜂王浆的成分，发现存在15种具有强抗氧化特性的不同植物化学成分。对从大鼠获得的血清样本进行谷丙转氨酶（ALT）、碱性磷酸酶（ALP）和谷草转氨酶（AST）水平分析。在长春新碱组中，这些酶水平显著升高，而在给予蜂王浆后观察到明显降低。此外，对肝组织样本中的超氧化物歧化酶（SOD）、过氧化氢酶（CAT）、谷胱甘肽过氧化物酶（GPx）和谷胱甘肽（GSH）抗氧化参数以及丙二醛（MDA）水平进行了评估。结果表明，长春新碱组中SOD、CAT、GPx和GSH的活性/水平降低，MDA水平升高。此外，使用酶联免疫吸附测定法（ELISA）评估Janus激酶2（JAK2）、信号转导和转录激活因子3（STAT3）以及雷帕霉素靶蛋白/磷脂酰肌醇3激酶/蛋白激酶B（mTOR/PI3K/AKT）信号通路。给予长春新碱导致mTOR/PI3K/AKT水平降低，JAK2和STAT3水平升高。此外，检测了炎症（核因子κB（NF - κB）、肿瘤坏死因子α（TNF - α）和白细胞介素1β（IL - 1β））、内质网（ER）应激（肌醇需求酶1（IRE - 1）、葡萄糖调节蛋白78（GRP78）、蛋白激酶R样内质网激酶（PERK）和活化转录因子6（ATF - 6））以及自噬标志物（微管相关蛋白1轻链3A（LC3A）和微管相关蛋白1轻链3B（LC3B））的mRNA转录水平。在长春新碱治疗组中观察到炎症、内质网应激和自噬相关标志物显著增加。最后，评估了Bax、Bcl - 2、半胱天冬酶3（Caspase - 3）和NF - κB的蛋白表达水平。长春新碱治疗增加了Bax、Caspase - 3和NF - κB水平，而Bcl - 2水平降低。然而，给予蜂王浆后，所有这些参数都发生了逆转，显示出显著改善。总之，这些发现表明蜂王浆可能对长春新碱诱导的肝损伤发挥保护作用。