Xie Zhang1, Chao-Yue Sun2, Yong-Bin Zhang3, Hui-Zhen Guo4, Xue-Xuan Feng5, Shao-Zhong Peng6, Jie Yuan7, Rong-Bo Zheng8, Wei-Ping Chen9, Zi-Ren Su10, Xiao-Dan Huang11. 1. School of Chinese Materia Medica, Guangzhou University of Chinese Medicine, Guangzhou 510006, PR China; Guangdong Provincial Key Laboratory of New Chinese Medicinal Development and Research, Guangzhou 510006, PR China. Electronic address: 985958620@qq.com. 2. School of Chinese Materia Medica, Guangzhou University of Chinese Medicine, Guangzhou 510006, PR China; Guangdong Provincial Key Laboratory of New Chinese Medicinal Development and Research, Guangzhou 510006, PR China. Electronic address: 936316352@qq.com. 3. School of Chinese Materia Medica, Guangzhou University of Chinese Medicine, Guangzhou 510006, PR China. Electronic address: yongbinzhang@gzucm.edu.cn. 4. State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou, Guangdong 510060, PR China. Electronic address: 604041882@qq.com. 5. Guangdong Medical Laboratory Animal Center, Foshan 528248, PR China. Electronic address: 345375526@qq.com. 6. Guangzhou Wanglaoji Pharmaceutical Company Limited, Guangzhou 510450, PR China. Electronic address: 691789232@qq.com. 7. School of Chinese Materia Medica, Guangzhou University of Chinese Medicine, Guangzhou 510006, PR China; Guangdong Provincial Key Laboratory of New Chinese Medicinal Development and Research, Guangzhou 510006, PR China. Electronic address: 466754442@qq.com. 8. Guangzhou Wanglaoji Pharmaceutical Company Limited, Guangzhou 510450, PR China. Electronic address: zrbb0819@sina.com. 9. Guangzhou Wanglaoji Pharmaceutical Company Limited, Guangzhou 510450, PR China. Electronic address: Chenwp@gpc.com.cn. 10. School of Chinese Materia Medica, Guangzhou University of Chinese Medicine, Guangzhou 510006, PR China; Guangdong Provincial Key Laboratory of New Chinese Medicinal Development and Research, Guangzhou 510006, PR China. Electronic address: suziren@gzucm.edu.cn. 11. Guangzhou Wanglaoji Pharmaceutical Company Limited, Guangzhou 510450, PR China. Electronic address: xiaodanhuang@126.com.
Abstract
ETHNOPHARMACOLOGICAL RELEVANCE: Kegan Liyan oral liquid (KGLY), a Chinese prescription modified from classic formulas Yin-Qiao-San (from TCM classic Wenbing Tiaobian) and Shen-Jie-San (first mentioned in Shanghan Wenyi Tiaobian), has been reported to exert heat-clearing and detoxifying effects and used extensively for the treatment of severe pulmonary diseases in clinics including influenza, cough and pneumonia. AIM OF THIS STUDY: The purpose of this study was to investigate the protective effect of KGLY on lipopolysaccharide (LPS) induced acute lung injury (ALI) in mice and to illuminate the underlying mechanisms. MATERIALS AND METHODS: Mice were orally administrated with KGLY (50, 100 and 150mg/kg) before intratracheal instillation of LPS. 24h post LPS challenge, lung tissues and the bronchoalveolar lavage fluid (BALF) were collected for lung wet/dry (W/D) weight ratio, histopathological examinations and biochemical analyses. The cell counts, protein concentration, interleukin-1β (IL-1β), interleukin-6 (IL-6), necrosis factor-α (TNF-α), macrophage inflammatory protein-2 (MIP-2) in BALF, superoxide dismutase (SOD), glutathione (GSH), myeloperoxidase (MPO) and malondialdehyde (MDA) levels were detected. Meanwhile, the activation of toll-like receptor 4 (TLR4), nuclear factor kappa B (NF-κB), as well as matrix metalloproteinases 9 (MMP-9) were determined by western blot assay. RESULTS: KGLY significantly prolonged mice survival time and ameliorated LPS-induced edema, thickening of alveolar septa and inflammatory cell infiltration in a dose-dependent manner. Additionally, KGLY markedly attenuated LPS-induced acute pulmonary inflammation via decreasing the expressions of cytokines and chemokines (IL-1β, IL-6, TNF-α, and MIP-2), enhanced the activities of anti-oxidative indicators (SOD and GSH), suppressed the levels of MPO and MDA, and down-regulated the expressions of TLR4, NF-κB and MMP9. CONCLUSIONS: The results suggested that the relieving effect of KGLY against LPS-induced ALI might be partially due to suppression of oxidative stress and inflammatory response, inhibition of TLR4-mediated NF-κB activation, and down-regulation of MMP9 expression, indicating it may be a potential therapeutic agent for ALI.
ETHNOPHARMACOLOGICAL RELEVANCE: Kegan Liyan oral liquid (KGLY), a Chinese prescription modified from classic formulas Yin-Qiao-San (from TCM classic Wenbing Tiaobian) and Shen-Jie-San (first mentioned in Shanghan Wenyi Tiaobian), has been reported to exert heat-clearing and detoxifying effects and used extensively for the treatment of severe pulmonary diseases in clinics including influenza, cough and pneumonia. AIM OF THIS STUDY: The purpose of this study was to investigate the protective effect of KGLY on lipopolysaccharide (LPS) induced acute lung injury (ALI) in mice and to illuminate the underlying mechanisms. MATERIALS AND METHODS:Mice were orally administrated with KGLY (50, 100 and 150mg/kg) before intratracheal instillation of LPS. 24h post LPS challenge, lung tissues and the bronchoalveolar lavage fluid (BALF) were collected for lung wet/dry (W/D) weight ratio, histopathological examinations and biochemical analyses. The cell counts, protein concentration, interleukin-1β (IL-1β), interleukin-6 (IL-6), necrosis factor-α (TNF-α), macrophage inflammatory protein-2 (MIP-2) in BALF, superoxide dismutase (SOD), glutathione (GSH), myeloperoxidase (MPO) and malondialdehyde (MDA) levels were detected. Meanwhile, the activation of toll-like receptor 4 (TLR4), nuclear factor kappa B (NF-κB), as well as matrix metalloproteinases 9 (MMP-9) were determined by western blot assay. RESULTS: KGLY significantly prolonged mice survival time and ameliorated LPS-induced edema, thickening of alveolar septa and inflammatory cell infiltration in a dose-dependent manner. Additionally, KGLY markedly attenuated LPS-induced acute pulmonary inflammation via decreasing the expressions of cytokines and chemokines (IL-1β, IL-6, TNF-α, and MIP-2), enhanced the activities of anti-oxidative indicators (SOD and GSH), suppressed the levels of MPO and MDA, and down-regulated the expressions of TLR4, NF-κB and MMP9. CONCLUSIONS: The results suggested that the relieving effect of KGLY against LPS-induced ALI might be partially due to suppression of oxidative stress and inflammatory response, inhibition of TLR4-mediated NF-κB activation, and down-regulation of MMP9 expression, indicating it may be a potential therapeutic agent for ALI.