Luo Zhujun, He Hao, Tang Tiantian, Zhou Jun, Li Huifang, Seeram Navindra P, Li Dongli, Zhang Kun, Ma Hang, Wu Panpan
School of Biotechnology and Health Sciences, Wuyi University, Jiangmen, China.
International Healthcare Innovation Institute, Jiangmen, China.
Front Chem. 2022 May 4;10:892554. doi: 10.3389/fchem.2022.892554. eCollection 2022.
We previously reported that the structural modifications of pentacyclic triterpenoids including oleanolic acid resulted in enhanced hyaluronidase inhibitory activity but whether this applies to other pentacyclic triterpenoids such as betulinic acid (BA) is unknown. Herein, we synthesized BA derivatives with an α,β-unsaturated ketene moiety and evaluated for their: 1) hyaluronidase inhibitory activity and, 2) anti-inflammatory effects against lipopolysaccharides (LPS) induced inflammation. Compared to BA, the BA derivatives exerted improved anti-hyaluronidase activity (26.3%-72.8% vs. 22.6%) and anti-inflammatory effects by reducing nitrite production in BV2 cells (3.9%-46.8% vs. 3.4%) and RAW264.7 cells (22.7%-49.2% vs. 20.4%). BA derivatives inhibited LPS-induced production of pro-inflammatory cytokines in THP-1 cells (15.2%-22.4%). BA derivatives also exerted promising anti-inflammatory effects against hyaluronic acid fragment induced nitrite production (8.6%-35.6%) in THP-1 cells. BA derivatives showed augmented anti-hyaluronidase and anti-inflammatory effects but further biological evaluations using models are warranted to confirm their efficacy.
我们之前报道过，包括齐墩果酸在内的五环三萜类化合物的结构修饰导致透明质酸酶抑制活性增强，但这是否适用于其他五环三萜类化合物，如桦木酸（BA）尚不清楚。在此，我们合成了具有α,β-不饱和烯酮部分的BA衍生物，并对其进行了评估：1）透明质酸酶抑制活性，以及2）对脂多糖（LPS）诱导的炎症的抗炎作用。与BA相比，BA衍生物通过降低BV2细胞（3.9%-46.8%对3.4%）和RAW264.7细胞（22.7%-49.2%对20.4%）中的亚硝酸盐生成，发挥了更好的抗透明质酸酶活性（26.3%-72.8%对22.6%）和抗炎作用。BA衍生物抑制了LPS诱导的THP-1细胞中促炎细胞因子的产生（15.2%-22.4%）。BA衍生物对THP-1细胞中透明质酸片段诱导的亚硝酸盐生成（8.6%-35.6%）也具有显著的抗炎作用。BA衍生物显示出增强的抗透明质酸酶和抗炎作用，但需要使用模型进行进一步的生物学评估以确认其疗效。
