Teruna Hilwan Yuda, Rullah Kamal, Hendra Rudi, Utami Rahayu, Islami Deri, Mohd Faudzi Siti Munirah, Mohd Aluwi Mohd Fadhlizil Fasihi, Lam Kok Wai
Department of Chemistry, Faculty Mathematics and Natural Sciences, Universitas Riau, Pekanbaru 28293, Indonesia.
Department of Pharmaceutical Chemistry, Kulliyyah of Pharmacy, International Islamic University Malaysia 25200, Kuantan, Pahang, Malaysia.
Adv Pharmacol Pharm Sci. 2024 Oct 30;2024:8811022. doi: 10.1155/2024/8811022. eCollection 2024.
Pinocembrin (PCB), a flavonoid known for its anti-inflammatory properties, has been approved for various clinical trial applications. To evaluate deeper into the anti-inflammatory potential of the specific enantiomer of natural PCB, we conducted the first investigation into the efficacy of the pure enantiomer (2)-PCB in modulating inflammatory mediators induced by lipopolysaccharide (LPS) in both murine RAW 264.7 and human U937 macrophage cell lines. This particular compound was isolated from (Annonaceae), a native plant of Indonesia. This plant has been used traditionally as an herbal medicine to alleviate inflammation. (2)-PCB was isolated from the stem bark of by defatting with -hexane followed by maceration with methanol. Purification was performed using several chromatographic techniques. The absolute configuration was determined using electronic circular dichroism (ECD) spectroscopy. This compound was then tested for its inhibitory activity on prostaglandin E (PGE) and subjected to docking simulations. The results indicated that (2)-PCB significantly suppressed the production of PGE induced by LPS in both RAW 264.7 and U937 cell lines. The docking simulations revealed that (2)-PCB reduced PGE levels by suppressing mitogen-activated protein kinase (MAPK) activation through inhibiting p38 and extracellular signal-regulated kinases (ERK). These findings suggest that the compound may prevent worsening of septic shock caused by bacterial infection.
匹诺塞林(PCB)是一种以其抗炎特性而闻名的黄酮类化合物,已被批准用于各种临床试验应用。为了更深入地评估天然PCB特定对映体的抗炎潜力,我们首次研究了纯对映体(2)-PCB在调节小鼠RAW 264.7和人U937巨噬细胞系中脂多糖(LPS)诱导的炎症介质方面的功效。这种特殊的化合物是从印度尼西亚本土植物番荔枝科植物中分离出来的。这种植物传统上被用作草药来减轻炎症。(2)-PCB是通过用正己烷脱脂,然后用甲醇浸渍从该植物的茎皮中分离出来的。使用几种色谱技术进行纯化。使用电子圆二色性(ECD)光谱确定绝对构型。然后测试该化合物对前列腺素E(PGE)的抑制活性并进行对接模拟。结果表明,(2)-PCB在RAW 264.7和U937细胞系中均显著抑制LPS诱导的PGE产生。对接模拟显示,(2)-PCB通过抑制p38和细胞外信号调节激酶(ERK)来抑制丝裂原活化蛋白激酶(MAPK)的激活,从而降低PGE水平。这些发现表明该化合物可能预防由细菌感染引起的心源性休克恶化。