Seong-Man Kim1, Hyung Won Ryu2, Ok-Kyoung Kwon3, Daseul Hwang4, Min Gu Kim5, Jae-Hong Min6, Zhiyun Zhang7, Soo-Yong Kim8, Jin-Hyub Paik9, Sei-Ryang Oh10, Kyung-Seop Ahn11, Jae-Won Lee12. 1. Natural Medicine Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB), Chungbuk, 28116, Republic of Korea; College of Pharmacy, Chungnam National University, 99 Daehak-ro, Yuseong-gu, Daejeon, 305-764, Republic of Korea. Electronic address: ksm2906@kribb.re.kr. 2. Natural Medicine Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB), Chungbuk, 28116, Republic of Korea. Electronic address: ryuhw@kribb.re.kr. 3. Natural Medicine Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB), Chungbuk, 28116, Republic of Korea. Electronic address: dooli@kribb.re.kr. 4. Natural Medicine Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB), Chungbuk, 28116, Republic of Korea; College of Pharmacy, Chungbuk National University, Cheongju-si, Chungcheongbuk-do, 28160, Republic of Korea. Electronic address: seul3104@kribb.re.kr. 5. Natural Medicine Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB), Chungbuk, 28116, Republic of Korea; College of Pharmacy, Chungbuk National University, Cheongju-si, Chungcheongbuk-do, 28160, Republic of Korea. Electronic address: alsrn0520@kribb.re.kr. 6. Natural Medicine Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB), Chungbuk, 28116, Republic of Korea; College of Pharmacy, Chungbuk National University, Cheongju-si, Chungcheongbuk-do, 28160, Republic of Korea. Electronic address: 01020835969@kribb.re.kr. 7. State Key Laboratory of Systematic and Evolutionary Botany, Institute of Botany, the Chinese Academy of Sciences, Beijing, 100093, PR China. Electronic address: zhangzy@ibcas.ac.cn. 8. International Biological Material Research Center, Korea Research Institute of Bioscience and Biotechnology, 125 Gwahak-ro, Yuseong-gu, Daejeon, 34141, Republic of Korea. Electronic address: soodole@kribb.re.kr. 9. International Biological Material Research Center, Korea Research Institute of Bioscience and Biotechnology, 125 Gwahak-ro, Yuseong-gu, Daejeon, 34141, Republic of Korea. Electronic address: jpaik@kribb.re.kr. 10. Natural Medicine Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB), Chungbuk, 28116, Republic of Korea. Electronic address: seiryang@kribb.re.kr. 11. Natural Medicine Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB), Chungbuk, 28116, Republic of Korea. Electronic address: ksahn@kribb.re.kr. 12. Natural Medicine Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB), Chungbuk, 28116, Republic of Korea. Electronic address: suc369@kribb.re.kr.
Abstract
ETHNOPHARMACOLOGICAL RELEVANCE: Callicarpa japonica Thunb., as an herbal medicine has been used for the treatment of inflammatory diseases in China and Korea. MATERIALS AND METHODS: Ultra performance liquid chromatography-photodiode array-quadrupole time-of-flight mass spectrometer (UPLC-PDA-QTof MS) was used to detect the major phenylethanoid glycosides in the C. japonica extract. BALB/c mice were intraperitoneally sensitized by ovalbumin (OVA) (on days 0 and 7) and challenged by OVA aerosol (on days 11-13) to induce airway inflammatory response. The mice were also administered with C. japonica Thunb. (CJT) (20 and 40 mg/kg Per oral) on days 9-13. CJT pretreatment was conducted in lipopolysaccharide (LPS)-stimulated RAW264.7 or phorbol 12-myristate 13-acetate (PMA)-stimulated A549 cells. RESULTS: CJT administration significantly reduced the secretion of Th2 cytokines, TNF-α, IL-6, immunoglobulin E (IgE) and histamine, and the recruitment of eosinophils in an OVA-exposed mice. In histological analyses, the amelioration of inflammatory cell influx and mucus secretion were observed with CJT. The OVA-induced airway hyperresponsiveness (AHR), iNOS expression and NF-κB activation were effectively suppressed by CJT administration. In addition, CJT led to the upregulation of HO-1 expression. In an in vitro study, CJT pretreatment suppressed the LPS-induced TNF-α secretion in RAW264.7 cells and attenuated the PMA-induced IL-6, IL-8 and MCP-1 secretion in A549 cells. These effects were accompanied by downregulated NF-κB phosphorylation and by upregulated HO-1 expression. CONCLUSION: These results suggested that CJT has protective activity against OVA-induced airway inflammation via downregulation of NF-κB activation and upregulation of HO-1, suggesting that CJT has preventive potential for the development of allergic asthma.
ETHNOPHARMACOLOGICAL RELEVANCE: Callicarpa japonica Thunb., as an herbal medicine has been used for the treatment of inflammatory diseases in China and Korea. MATERIALS AND METHODS: Ultra performance liquid chromatography-photodiode array-quadrupole time-of-flight mass spectrometer (UPLC-PDA-QTof MS) was used to detect the major phenylethanoidglycosides in the C. japonica extract. BALB/c mice were intraperitoneally sensitized by ovalbumin (OVA) (on days 0 and 7) and challenged by OVA aerosol (on days 11-13) to induce airway inflammatory response. The mice were also administered with C. japonica Thunb. (CJT) (20 and 40 mg/kg Per oral) on days 9-13. CJT pretreatment was conducted in lipopolysaccharide (LPS)-stimulated RAW264.7 or phorbol 12-myristate 13-acetate (PMA)-stimulated A549 cells. RESULTS:CJT administration significantly reduced the secretion of Th2 cytokines, TNF-α, IL-6, immunoglobulin E (IgE) and histamine, and the recruitment of eosinophils in an OVA-exposed mice. In histological analyses, the amelioration of inflammatory cell influx and mucus secretion were observed with CJT. The OVA-induced airway hyperresponsiveness (AHR), iNOS expression and NF-κB activation were effectively suppressed by CJT administration. In addition, CJT led to the upregulation of HO-1 expression. In an in vitro study, CJT pretreatment suppressed the LPS-induced TNF-α secretion in RAW264.7 cells and attenuated the PMA-induced IL-6, IL-8 and MCP-1 secretion in A549 cells. These effects were accompanied by downregulated NF-κB phosphorylation and by upregulated HO-1 expression. CONCLUSION: These results suggested that CJT has protective activity against OVA-induced airway inflammation via downregulation of NF-κB activation and upregulation of HO-1, suggesting that CJT has preventive potential for the development of allergic asthma.