Sauropus brevipes ethanol extract negatively regulates inflammatory responses in vivo and in vitro by targeting Src, Syk and IRAK1

• Main Authors: Ji Hye Kim, Jae Gwang Park, Yo Han Hong, Kon Kuk Shin, Jin Kyeong Kim, Young-Dong Kim, Ki Dong Yoon, Kyung-Hee Kim, Byong Chul Yoo, Gi-Ho Sung, Jae Youl Cho
• Format: Article
• Language: English
• Published: Taylor & Francis Group 2021-01-01
• Series: Pharmaceutical Biology
• Subjects: natural product medicine; anti-inflammatory remedy; flavonoids; gastritis; peritonitis
• Online Access: http://dx.doi.org/10.1080/13880209.2020.1866024

Context Sauropus brevipes Müll. Arg. (Phyllanthaceae) has been used as an effective ingredient in a decoction for the treatment of diarrhoea. However, there was no report on its modulatory role in inflammation. Objective This study investigates anti-inflammatory effect of S. brevipes in various inflammation models. Materials and methods The aerial part of S. brevipes was extracted with 95% ethanol to produce Sb-EE. RAW264.7 cells pre-treated with Sb-EE were stimulated by lipopolysaccharide (LPS), and Griess assay and PCR were performed. High-performance liquid chromatography (HPLC) analysis, luciferase assay, Western blotting and kinase assay were employed. C57BL/6 mice (10 mice/group) were orally administered with Sb-EE (200 mg/kg) once a day for five days, and peritonitis was induced by an intraperitoneal injection of LPS (10 mg/kg). ICR mice (four mice/group) were orally administered with Sb-EE (20 or 200 mg/kg) or ranitidine (positive control) twice a day for two days, and EtOH/HCl was orally injected to induce gastritis. Results Sb-EE suppressed nitric oxide (NO) release (IC50=34 µg/mL) without cytotoxicity and contained flavonoids (quercetin, luteolin and kaempferol). Sb-EE (200 µg/mL) reduced the mRNA expression of inducible NO synthase (iNOS). Sb-EE blocked the activities of Syk and Src, while inhibiting interleukin-1 receptor associated kinases (IRAK1) by 68%. Similarly, orally administered Sb-EE (200 mg/kg) suppressed NO production by 78% and phosphorylation of Src and Syk in peritonitis mice. Sb-EE also decreased inflammatory lesions in gastritis mice. Discussion and conclusions This study demonstrates the inhibitory effect of Sb-EE on the inflammatory response, suggesting that Sb-EE can be developed as a potential anti-inflammatory agent.