Minamisaka Keita, Fujii Airi, Li Cheng, Nishidono Yuto, Shirako Saki, Kawamura Teruhisa, Ikeya Yukinobu, Nishizawa Mikio
Department of Medical Biosciences, Faculty of Life Sciences, Ritsumeikan University, Kusatsu 525-8577, Shiga, Japan.
College of Pharmaceutical Sciences, Ritsumeikan University, Kusatsu 525-8577, Shiga, Japan.
Molecules. 2025 Jul 16;30(14):2996. doi: 10.3390/molecules30142996.
The capitula of Linné or Ramatuelle ( in Japanese) are included in several formulae of Kampo medicines (traditional Japanese medicines), such as , which is used for headache and dizziness. Luteolin, the principal constituent of , has antioxidant and anti-inflammatory activities. However, the effects of other flavonoids on this crude drug have not yet been thoroughly investigated. To evaluate and compare anti-inflammatory effects, we used primary cultured rat hepatocytes, which produce proinflammatory mediators, such as nitric oxide (NO) and proinflammatory cytokines, in response to interleukin (IL)-1β. Eight derivatives of 5,7-dihydroxyflavone were purified and identified in the ethyl acetate-soluble fraction of a capitulum extract: luteolin (Compound ), apigenin (), diosmetin (), 5,7-dihydroxy-3',4',5'-trimethoxyflavone (), acacetin (), eupatilin (), jaceosidin (), and 6-methoxytricin (). Luteolin is the most abundant compound in this fraction. All compounds significantly suppressed NO production in hepatocytes, with apigenin and acacetin showing the greatest efficacy. The comparison of the IC values of the inhibition of NO production suggests that substitutions by hydroxyl and methoxy groups at the C-3' and C-4' positions of 5,7-dihydroxyflavone may be at least essential for the suppression of NO production. In hepatocytes, acacetin and luteolin decreased the levels of mRNAs encoding inducible nitric oxide synthase (iNOS), proinflammatory cytokines, including tumor necrosis factor, IL-6, and type 1 IL-1 receptor, which regulates inflammatory responses. Based on the comparison of the IC values and the content, luteolin, jaceosidin, and diosmetin may be responsible for the anti-inflammatory effects of capitula.
林奈或拉马图勒（日语）的头状花序被包含在多种汉方药（传统日本药）配方中，比如用于治疗头痛和头晕的 。木犀草素是 的主要成分，具有抗氧化和抗炎活性。然而，其他黄酮类化合物对这种生药的作用尚未得到充分研究。为了评估和比较抗炎效果，我们使用了原代培养的大鼠肝细胞，这些细胞在受到白细胞介素（IL）-1β刺激时会产生促炎介质，如一氧化氮（NO）和促炎细胞因子。从一个头状花序提取物的乙酸乙酯可溶部分中纯化并鉴定出了8种5,7-二羟基黄酮衍生物：木犀草素（化合物 ）、芹菜素（ ）、香叶木素（ ）、5,7-二羟基-3',4',5'-三甲氧基黄酮（ ）、刺槐素（ ）、泽兰黄酮（ ）、南茼蒿素（ ）和6-甲氧基小麦黄素（ ）。木犀草素是该部分中含量最丰富的化合物。所有化合物均显著抑制肝细胞中NO的产生，芹菜素和刺槐素的效果最为显著。抑制NO产生的IC值比较表明，5,7-二羟基黄酮在C-3'和C-4'位被羟基和甲氧基取代可能至少是抑制NO产生所必需的。在肝细胞中，刺槐素和木犀草素降低了编码诱导型一氧化氮合酶（iNOS）、促炎细胞因子（包括肿瘤坏死因子、IL-6和调节炎症反应的1型IL-1受体）的mRNA水平。基于IC值和含量的比较，木犀草素、南茼蒿素和香叶木素可能对头状花序的抗炎作用负责。
