Wu Yu-Lin, Chen Jin-Fen, Jiang Lin-Yun, Wu Xiao-Li, Liu Yu-Hong, Gao Chang-Jun, Wu Yan, Yi Xiao-Qing, Su Zi-Ren, Cai Jian, Chen Jian-Nan
Guangdong Provincial Key Laboratory of New Drug Development and Research of Chinese Medicine, School of Pharmaceutical Sciences, Guangzhou University of Chinese Medicine, Guangzhou, China.
The First Affiliated Hospital of Chinese Medicine, Guangzhou University of Chinese Medicine, Guangzhou, China.
Front Pharmacol. 2021 Aug 16;12:698219. doi: 10.3389/fphar.2021.698219. eCollection 2021.
Buch-Ham., an exotic mangrove species with antidiabetic, antibacterial, and antioxidant capacities, mainly distributes in the southeast coastal areas in China. The present work investigated the protective effects of leaves and branches extraction (SAL) on hyperuricemia (HUA) in mice. Potassium oxonate (PO) and hypoxanthine (HX) were used to establish the HUA model by challenge for consecutive 7 days. Results revealed that SAL inhibited the increases in kidney weight and index compared to the vehicle group. Meanwhile, SAL significantly decreased the levels of uric acid (UA), creatinine (CRE), and blood urea nitrogen (BUN) in serum. Additionally, SAL inhibited the activity of xanthine oxidase (XOD) in the liver. SAL ameliorated PO- and HX-induced histopathological changes. Moreover, it regulated oxidative stress markers including malondialdehyde (MDA), catalase (CAT), superoxide dismutase (SOD) activity, and glutathione (GSH) content. Also, SAL inhibited the increases in renal levels of interleukin-6 (IL-6), interleukin-18 (IL-18), interleukin-1β (IL-1β), tumor necrosis factor (TNF-α), monocyte chemotactic protein 1 (MCP-1), and transforming growth factor-β (TGF-β). SAL remarkably reduced suppressor of cytokine signaling 3 (SOCS3), Janus kinase 2 (JAK2), and subsequent phosphorylation of signal transducer and activator of transcription 3 (STAT3) expression. In addition, SAL inhibited the activation of nuclear factor kappa-B (NF-κB) in the kidney. Furthermore, SAL protected against HUA by regulating renal UA transporters of organic anion transporter (OAT1), urate reabsorption transporter 1 (URAT1), and glucose transporter 9 (GLUT9). These findings suggested that SAL ameliorated HUA by inhibiting the production of uric acid and enhancing renal urate excretion, which are related to oxidative stress and inflammation, and the possible molecular mechanisms include its ability to inhibit the JAK/STAT signaling pathway. Thus, SAL might be developed into a promising agent for HUA treatments.
布氏海桑是一种具有抗糖尿病、抗菌和抗氧化能力的外来红树林物种，主要分布在中国东南沿海地区。本研究调查了布氏海桑叶和枝提取物（SAL）对小鼠高尿酸血症（HUA）的保护作用。连续7天用氧嗪酸钾（PO）和次黄嘌呤（HX）诱导建立HUA模型。结果显示，与溶剂对照组相比，SAL抑制了肾脏重量和肾指数的增加。同时，SAL显著降低了血清中尿酸（UA）、肌酐（CRE）和血尿素氮（BUN）的水平。此外，SAL抑制了肝脏中黄嘌呤氧化酶（XOD）的活性。SAL改善了PO和HX诱导的组织病理学变化。此外，它调节了氧化应激标志物，包括丙二醛（MDA）、过氧化氢酶（CAT）、超氧化物歧化酶（SOD）活性和谷胱甘肽（GSH）含量。此外，SAL抑制了肾脏中白细胞介素-6（IL-6）、白细胞介素-18（IL-18）、白细胞介素-1β（IL-1β）、肿瘤坏死因子（TNF-α）、单核细胞趋化蛋白1（MCP-1）和转化生长因子-β（TGF-β）水平的升高。SAL显著降低了细胞因子信号转导抑制因子3（SOCS3）、Janus激酶2（JAK2）以及随后信号转导和转录激活因子3（STAT3）的磷酸化表达。此外，SAL抑制了肾脏中核因子κB（NF-κB）的激活。此外，SAL通过调节肾脏中有机阴离子转运体（OAT1）、尿酸重吸收转运体1（URAT1）和葡萄糖转运体9（GLUT9）的尿酸转运蛋白来预防HUA。这些发现表明，SAL通过抑制尿酸生成和增强肾脏尿酸排泄来改善HUA，这与氧化应激和炎症有关，其可能的分子机制包括抑制JAK/STAT信号通路的能力。因此，SAL可能会被开发成为一种有前景的HUA治疗药物。
