School of Chemistry and Physics, University of KwaZulu-Natal, Westville Campus, Private Bag X54001, Durban 4000, South Africa.
School of Life Sciences, University of KwaZulu-Natal, Westville Campus, Private Bag X54001, Durban 4000, South Africa.
J Ethnopharmacol. 2018 Apr 24;216:134-146. doi: 10.1016/j.jep.2018.01.031. Epub 2018 Feb 1.
Senegalia nigrescens is used in traditional medicine for the treatment of dysentery and convulsions.
This study was aimed at identifying bioactive compounds from S. nigrescens and carrying out in vitro and in silico anti-quorum sensing studies on the compounds.
Extracts of S. nigrescens were chromatographed repeatedly. The isolated compounds were characterised using NMR spectroscopy and mass spectrometry. The anti-quorum sensing potential of S. nigrescens crude extracts and selected phytochemicals was quantified using Chromobacterium violaceum quorum sensing-controlled violacein inhibition assays. Qualitative modulation of quorum sensing activity and signal synthesis was investigated using agar diffusion double ring assays and C. violaceum. Molecular docking was conducted to explore the binding conformations of ent-kaurene diterpenes and flavonoids into the binding sites of quorum sensing regulator proteins, CviR and CviR'.
Phytochemical investigation of S. nigrescens resulted in the isolation of a new ent-kaurene diterpenoid (ent-kaur-15-en-18,20-diol) alongside ent-kaur-15-en-18-ol, being isolated for the first time from a plant species. Other compounds isolated included 30-hydroxylup-20(29)-en-3β-ol, 3β-hydroxy-20(29)-en-lupan-30-al, lupeol, stigmasterol, a long chain alcohol (tetracosan-1-ol) and three flavonoids (melanoxetin, quercetin and quercetin-3-O-methyl ether). Structures of isolated compounds were elucidated using different spectroscopic techniques including 1D and 2D NMR. Inhibition of violacein production was concentration-dependent, with 56.52% inhibition being obtained with 200 µg of quercetin-3-O-methyl ether, while 53.38% inhibition was obtained with 600 µg of quercetin. Agar diffusion double ring assays indicated CviI synthase/CviR receptor modulation by S. nigrescens phytochemicals, suggesting that quorum signal synthesis was down-regulated and/or targeting binding of signal to the receptor. The computed binding energy data suggested that the flavonoids had a stronger tendency to inhibit both CviR and CviR' with varying binding affinities.
S. nigrescens crude extracts together with the novel ent-kaurenoids and flavonoids demonstrated potential anti-quorum sensing activity. S. nigrescens may thus represent a source of anti-quorum sensing therapeutic candidates for the control of existing and emerging infectious diseases.
Senegalia nigrescens 被用于传统医学中，用于治疗痢疾和惊厥。
本研究旨在从 S. nigrescens 中鉴定出生物活性化合物，并对这些化合物进行体外和计算机模拟的抗群体感应研究。
反复对 S. nigrescens 提取物进行色谱分离。通过 NMR 光谱和质谱对分离出的化合物进行表征。使用 Chromobacterium violaceum 群体感应控制的紫色素抑制试验定量测定 S. nigrescens 粗提取物和选定植物化学物质的抗群体感应潜力。使用琼脂扩散双环试验和 C. violaceum 研究定性调节群体感应活性和信号合成。进行分子对接以探索 ent-kaurene 二萜和类黄酮进入群体感应调节蛋白 CviR 和 CviR'结合位点的结合构象。
对 S. nigrescens 的植物化学研究导致分离出一种新的 ent-kaurene 二萜（ent-kaur-15-en-18,20-二醇）以及 ent-kaur-15-en-18-醇，这是首次从植物物种中分离出来的。分离出的其他化合物包括 30-羟基乳香-20(29)-烯-3β-醇、3β-羟基-20(29)-烯-羊毛甾烷-30-醇、羽扇豆醇、豆甾醇、长链醇（二十四烷-1-醇）和三种类黄酮（melanoxetin、槲皮素和槲皮素-3-O-甲基醚）。使用包括 1D 和 2D NMR 在内的不同光谱技术阐明了分离化合物的结构。紫色素产生的抑制作用呈浓度依赖性，200μg 的槲皮素-3-O-甲基醚可获得 56.52%的抑制作用，而 600μg 的槲皮素可获得 53.38%的抑制作用。琼脂扩散双环试验表明 S. nigrescens 植物化学物质对 CviI 合酶/CviR 受体的调节，表明群体信号合成被下调和/或靶向信号与受体的结合。计算的结合能数据表明，类黄酮对 CviR 和 CviR'具有更强的抑制作用，结合亲和力不同。
S. nigrescens 粗提取物以及新的 ent-kaurenoids 和类黄酮表现出潜在的抗群体感应活性。因此，S. nigrescens 可能代表用于控制现有和新兴传染病的抗群体感应治疗候选物的来源。
