Medical Research Center-Globalization of Herbal Formulation, College of Korean Medicine, Daegu Haany University, Gyeongsan 38610, Republic of Korea.
Department of Biological Sciences, College of Biomedical Sciences and Engineering, Inje University, Gimhae 621-749, Republic of Korea.
Int J Mol Med. 2018 May;41(5):2771-2783. doi: 10.3892/ijmm.2018.3465. Epub 2018 Feb 6.
Socheongryong-Tang (SCRT) is a natural medicine prescription that has been mainly used in East Asia for the treatment of inflammatory disorders, including asthma and allergic rhinitis. The present study evaluated the anti-inflammatory effects of SCRT on lipopolysaccharide (LPS)-stimulated RAW 264.7 cells and in a rat model of carrageenan (CA)-induced paw edema. Levels of tumor necrosis factor-α (TNF-α), interleukin (IL)-1β, IL-6 and prostaglandin E2 (PGE2) in the culture supernatant were quantified and nitric oxide (NO) production was monitored. In addition, the effect of SCRT on the protein expression of nuclear factor-κB (NF-κB), mitogen-activated protein kinases (MAPKs), inducible NO synthase (iNOS) and cyclooxygenase-2 (COX-2) was assessed by western blot analysis. Furthermore, the effects of SCRT on acute inflammation in vivo and changes in the histomorphometry and histopathology of paw skin were observed using CA-treated rats. SCRT (1 mg/ml) inhibited the LPS-induced changes in the protein expression of NF-κB, JNK, ERK1/2, iNOS and COX-2, as well as the production of NO, PGE2 and cytokines. In the rat paw edema assay, administration of 1 g/kg of lyophilized powder obtained from the aqueous extracts of SCRT for 3 consecutive days inhibited the CA-induced increases in skin thickness, mast cell degranulation, and infiltration of inflammatory cells in the ventral and dorsal pedis skin within 4 h. These results demonstrated that SCRT exerts its anti-inflammatory activities in LPS-stimulated RAW 264.7 cells through decreasing the production of inflammatory mediators, including PGE2, NO and cytokines, via suppression of the NF-κB and JNK and ERK1/2 signaling pathways. In addition, the data of the CA-induced paw edema indicated an anti-edema effect of SCRT. SCRT (1 g/kg) reduced acute edematous inflammation through inhibition of mast cell degranulation and infiltration of inflammatory cells. Therefore, the present study provided scientific evidence for the anti-inflammatory activities of SCRT as well as the underlying mechanisms.
芍甘汤(SCRT)是一种天然药物配方,主要在东亚用于治疗炎症性疾病,包括哮喘和过敏性鼻炎。本研究评估了 SCRT 对脂多糖(LPS)刺激的 RAW 264.7 细胞和角叉菜胶(CA)诱导的爪肿胀大鼠模型的抗炎作用。定量测定培养上清液中肿瘤坏死因子-α(TNF-α)、白细胞介素(IL)-1β、IL-6 和前列腺素 E2(PGE2)的水平,并监测一氧化氮(NO)的产生。此外,通过 Western blot 分析评估 SCRT 对核因子-κB(NF-κB)、丝裂原活化蛋白激酶(MAPKs)、诱导型一氧化氮合酶(iNOS)和环氧化酶-2(COX-2)的蛋白表达的影响。此外,通过 CA 处理的大鼠观察 SCRT 对体内急性炎症的影响以及爪皮肤的组织形态和组织病理学变化。SCRT(1mg/ml)抑制 LPS 诱导的 NF-κB、JNK、ERK1/2、iNOS 和 COX-2 蛋白表达的变化,以及 NO、PGE2 和细胞因子的产生。在大鼠爪肿胀试验中,连续 3 天给予 1g/kg 的从 SCRT 水提物中冻干的粉末抑制 CA 诱导的皮肤厚度增加、肥大细胞脱颗粒以及背侧和腹侧足底皮肤中炎症细胞的浸润在 4 小时内。这些结果表明,SCRT 通过抑制 NF-κB 和 JNK 和 ERK1/2 信号通路,降低 PGE2、NO 和细胞因子等炎症介质的产生,从而发挥其在 LPS 刺激的 RAW 264.7 细胞中的抗炎活性。此外,CA 诱导的爪肿胀数据表明 SCRT 具有抗水肿作用。SCRT(1g/kg)通过抑制肥大细胞脱颗粒和炎症细胞浸润来减轻急性水肿性炎症。因此,本研究为 SCRT 的抗炎活性及其潜在机制提供了科学依据。