Department of Pharmaceutical Engineering & Biotechnology, Sunmoon University, Chungnam 31460, Korea.
Natural Product Informatics Research Center, KIST Gangneung Institute of Natural Products, Korea Institute of Science and Technology (KIST), 679, Saimdang-ro 25451, Korea.
Molecules. 2019 Oct 30;24(21):3910. doi: 10.3390/molecules24213910.
Biorenovation is a microbial enzyme-catalyzed structural modification of organic compounds with the potential benefits of reduced toxicity and improved biological properties relative to their precursor compounds. In this study, we synthesized a novel compound verified as formononetin 7--phosphate (FMP) from formononetin (FM) using microbial biotransformation. We further compared the anti-inflammatory properties of FMP to FM in lipopolysaccharide (LPS)-treated RAW264.7 macrophage cells. We observed that cell viabilities and inhibitory effects on LPS-induced nitric oxide (NO) production were greater in FMP-treated RAW 264.7 cells than in their FM-treated counterparts. In addition, FMP treatment suppressed the production of proinflammatory cytokines such as prostaglandin-E (PGE), interleukin-6 (IL-6), and interleukin-1β (IL-1β) in a dose-dependent manner and concomitantly decreased the mRNA expression of inducible NO synthase (iNOS) and cyclooxygenase-2 (COX-2). We also found that FMP exerted its anti-inflammatory effects through the downregulation of the extracellular signal-regulated kinase (ERK), c-Jun -terminal kinase (JNK), and nuclear factor kappa B (NF-κB) signaling pathways. In conclusion, we generated a novel anti-inflammatory compound using biorenovation and demonstrated its efficacy in cell-based in vitro assays.
生物翻新是一种微生物酶催化的有机化合物结构修饰,具有降低毒性和改善生物性质的潜力,相对于其前体化合物而言。在这项研究中,我们使用微生物生物转化从芒柄花素(FM)合成了一种新型化合物,经证实为芒柄花素 7--磷酸(FMP)。我们进一步比较了 FMP 和 FM 在脂多糖(LPS)处理的 RAW264.7 巨噬细胞中的抗炎特性。我们观察到,与 LPS 处理的 FM 相比,FMP 处理的 RAW264.7 细胞的细胞活力和对 LPS 诱导的一氧化氮(NO)产生的抑制作用更强。此外,FMP 处理以剂量依赖性方式抑制前列腺素-E(PGE)、白细胞介素-6(IL-6)和白细胞介素-1β(IL-1β)等促炎细胞因子的产生,并同时降低诱导型一氧化氮合酶(iNOS)和环氧化酶-2(COX-2)的 mRNA 表达。我们还发现,FMP 通过下调细胞外信号调节激酶(ERK)、c-Jun 末端激酶(JNK)和核因子 kappa B(NF-κB)信号通路发挥其抗炎作用。总之,我们使用生物翻新生成了一种新型抗炎化合物,并在基于细胞的体外测定中证明了其功效。