Biotechnological Engineering Center for Pharmaceutical Research and Development, Jiangxi Agricultural University, Nanchang 330045, China.
Laboratory of Natural Medicine and Microbiological Drug, College of Bioscience and Bioengineering, Jiangxi Agricultural University, Nanchang 330045, China.
Molecules. 2023 Jun 24;28(13):4972. doi: 10.3390/molecules28134972.
Plant flavonoids have attracted increasing attention as new antimicrobial agents or adjuvants. In our previous work, it was confirmed that the cell membrane is the major site of plant flavonoids acting on the Gram-positive bacteria, which likely involves the inhibition of the respiratory chain. Inspired by the similar structural and antioxidant characters of plant flavonoids to hydro-menaquinone (MKH), we deduced that the quinone pool is probably a key target of plant flavonoids inhibiting Gram-positive bacteria. To verify this, twelve plant flavonoids with six structural subtypes were preliminarily selected, and their minimum inhibitory concentrations (MICs) against Gram-positive bacteria were predicted from the antimicrobial quantitative relationship of plant flavonoids to Gram-positive bacteria. The results showed they have different antimicrobial activities. After their MICs against were determined using the broth microdilution method, nine compounds with MICs ranging from 2 to 4096 μg/mL or more than 1024 μg/mL were eventually selected, and then their MICs against were determined interfered with different concentrations of menaquinone-4 (MK-4) and the MKs extracted from . The results showed that the greater the antibacterial activities of plant flavonoids were, the more greatly their antibacterial activities decreased along with the increase in the interfering concentrations of MK-4 (from 2 to 256 μg/mL) and the MK extract (from 4 to 512 μg/mL), while those with the MICs equal to or more than 512 μg/mL decreased a little or remained unchanged. In particular, under the interference of MK-4 (256 μg/mL) and the MK extract (512 μg/mL), the MICs of -mangostin, a compound with the greatest inhibitory activity to out of these twelve plant flavonoids, increased by 16 times and 8 to 16 times, respectively. Based on the above, it was proposed that the quinone pool is a key target of plant flavonoids inhibiting Gram-positive bacteria, and which likely involves multiple mechanisms including some enzyme and non-enzyme inhibitions.
植物类黄酮作为新型抗菌剂或佐剂越来越受到关注。在我们之前的工作中，已经证实细胞膜是植物类黄酮作用于革兰氏阳性菌的主要部位，这可能涉及到呼吸链的抑制。受植物类黄酮与氢泛醌（MKH）相似的结构和抗氧化特性的启发，我们推断醌库可能是植物类黄酮抑制革兰氏阳性菌的关键靶标。为了验证这一点，初步选择了 12 种具有 6 种结构亚型的植物类黄酮，并根据植物类黄酮对革兰氏阳性菌的抗菌定量关系预测了它们对革兰氏阳性菌的最小抑菌浓度（MIC）。结果表明它们具有不同的抗菌活性。用肉汤微量稀释法测定它们对的 MIC 后，最终选择了 9 种 MIC 范围在 2 至 4096 μg/mL 或大于 1024 μg/mL 的化合物，然后用不同浓度的 MK-4（menaquinone-4）和从 中提取的 MKs 干扰测定它们对的 MIC。结果表明，植物类黄酮的抗菌活性越强，随着 MK-4（浓度从 2 至 256 μg/mL）和 MK 提取物（浓度从 4 至 512 μg/mL）干扰浓度的增加，其抗菌活性降低得越大，而 MIC 等于或大于 512 μg/mL 的化合物降低得较小或保持不变。特别是在 MK-4（256 μg/mL）和 MK 提取物（512 μg/mL）的干扰下，这 12 种植物类黄酮中对抑制作用最强的化合物 - 密蒙花素对的 MIC 分别增加了 16 倍和 8 至 16 倍。基于以上结果，提出了醌库是植物类黄酮抑制革兰氏阳性菌的关键靶标，这可能涉及到多种机制，包括一些酶和非酶抑制。
