Tian-Qi Xuan1, Guohua Gong2, Huanhuan Du3, Chunyan Liu4, Yun Wu5, Guilan Bao6, Qianqian Ma7, Dong Zhen8. 1. Institute of Pharmaceutical Chemistry and Pharmacology, Inner Mongolia Minzu University, Tongliao, 028000, Inner Mongolia Autonomous Region, PR China; Inner Mongolia Key Laboratory of Mongolian Medicine Pharmacology for Cardio-Cerebral Vascular System, Tongliao, 028000, Inner Mongolia Autonomous Region, PR China. Electronic address: 1543505206@qq.com. 2. Inner Mongolia Key Laboratory of Mongolian Medicine Pharmacology for Cardio-Cerebral Vascular System, Tongliao, 028000, Inner Mongolia Autonomous Region, PR China; Affiliated Hospital of Inner Mongolia Minzu University, Tongliao, 028000, Inner Mongolia Autonomous Region, PR China. Electronic address: gonggguohua0211@163.com. 3. Institute of Pharmaceutical Chemistry and Pharmacology, Inner Mongolia Minzu University, Tongliao, 028000, Inner Mongolia Autonomous Region, PR China; Inner Mongolia Key Laboratory of Mongolian Medicine Pharmacology for Cardio-Cerebral Vascular System, Tongliao, 028000, Inner Mongolia Autonomous Region, PR China. Electronic address: joycetu@126.com. 4. Institute of Pharmaceutical Chemistry and Pharmacology, Inner Mongolia Minzu University, Tongliao, 028000, Inner Mongolia Autonomous Region, PR China; Inner Mongolia Key Laboratory of Mongolian Medicine Pharmacology for Cardio-Cerebral Vascular System, Tongliao, 028000, Inner Mongolia Autonomous Region, PR China. Electronic address: 76526971@qq.com. 5. Affiliated Hospital of Inner Mongolia Minzu University, Tongliao, 028000, Inner Mongolia Autonomous Region, PR China. Electronic address: wuyun1214@126.com. 6. Institute of Pharmaceutical Chemistry and Pharmacology, Inner Mongolia Minzu University, Tongliao, 028000, Inner Mongolia Autonomous Region, PR China; Inner Mongolia Key Laboratory of Mongolian Medicine Pharmacology for Cardio-Cerebral Vascular System, Tongliao, 028000, Inner Mongolia Autonomous Region, PR China. Electronic address: bgl-6891@163.com. 7. Institute of Pharmaceutical Chemistry and Pharmacology, Inner Mongolia Minzu University, Tongliao, 028000, Inner Mongolia Autonomous Region, PR China; Inner Mongolia Key Laboratory of Mongolian Medicine Pharmacology for Cardio-Cerebral Vascular System, Tongliao, 028000, Inner Mongolia Autonomous Region, PR China. Electronic address: maqq2020@126.com. 8. Institute of Pharmaceutical Chemistry and Pharmacology, Inner Mongolia Minzu University, Tongliao, 028000, Inner Mongolia Autonomous Region, PR China; Inner Mongolia Key Laboratory of Mongolian Medicine Pharmacology for Cardio-Cerebral Vascular System, Tongliao, 028000, Inner Mongolia Autonomous Region, PR China. Electronic address: dongzhen@imun.edu.cn.
Abstract
ETHNOPHARMACOLOGICAL RELEVANCE: Peucedanum praeruptorum seed root is a common medicinal herb with antipyretic, expectorant, antitussive, and therapeutic effects against bronchitis and furuncle. The roots of this herb contain many coumarin compounds, including pteryxin. AIM OF THIS STUDY: To investigate whether pteryxin can alleviate the LPS-induced lung injury and the mechanism involved. MATERIAL AND METHODS: Male BALB/C mice were orally given sodium carboxymethylcellulose (CMC-Na) (0.5%, 1mL/100g) and pteryxin (suspended in CMC-Na; 0.5%) at 5, 10, 25 mg/kg once daily for 7 days. Subsequently, the mice received a single intratracheal instillation of 5 mg/kg LPS or saline as the control. After 8 hours, the mice were sacrificed to collect bronchoalveolar lavage fluid (BALF) and lung tissues. These samples were used to determine the lung W/D (wet/dry) weight ratio, total protein (TP) levels, inflammatory cytokines (IL-6, TNF-α, and IL-1β) and expression of protein involved in MAPK/NF-κB pathway and NLRP3 inflammasome. H&E staining was carried out on tissue sections to explore the pathological alterations induced by LPS. The protein expression of F4/80 and NLRP3 in lung tissues was analyzed using immunohistochemical staining. The binding of pteryxin to target proteins (MAPK, NF-κB and NLRP3) was determined based on molecular docking tests. RESULTS: Treatment with pteryxin reduced the lung W/D weight ratio, total protein (TP) level and levels of inflammatory cytokines (TNFα, IL-6 and IL-1 β) significantly. Therefore, it ameliorated LPS-induced inflammatory response in BALB/C mice. Moreover, pteryxin suppressed LPS-induced upregulation of proteins involved in MAPK/NF-κB signaling pathway and NLRP3 inflammasome activation. The expression level of F4/80 and NLRP3 was also downregulated by pteryxin pretreatment in lung tissues. Docking analysis revealed that pteryxin bound to target proteins (MAPK, NF- κB and NLRP3) with a fit-well pattern . CONCLUSION: Pteryxin may attenuate LPS-induced acute lung injury by dampening MAPK/NF-κB signaling and NLRP 3 inflammasome activation.
ETHNOPHARMACOLOGICAL RELEVANCE: Peucedanum praeruptorum seed root is a common medicinal herb with antipyretic, expectorant, antitussive, and therapeutic effects against bronchitis and furuncle. The roots of this herb contain many coumarin compounds, including pteryxin. AIM OF THIS STUDY: To investigate whether pteryxin can alleviate the LPS-induced lung injury and the mechanism involved. MATERIAL AND METHODS: Male BALB/C mice were orally given sodium carboxymethylcellulose (CMC-Na) (0.5%, 1mL/100g) and pteryxin (suspended in CMC-Na; 0.5%) at 5, 10, 25 mg/kg once daily for 7 days. Subsequently, the mice received a single intratracheal instillation of 5 mg/kg LPS or saline as the control. After 8 hours, the mice were sacrificed to collect bronchoalveolar lavage fluid (BALF) and lung tissues. These samples were used to determine the lung W/D (wet/dry) weight ratio, total protein (TP) levels, inflammatory cytokines (IL-6, TNF-α, and IL-1β) and expression of protein involved in MAPK/NF-κB pathway and NLRP3 inflammasome. H&E staining was carried out on tissue sections to explore the pathological alterations induced by LPS. The protein expression of F4/80 and NLRP3 in lung tissues was analyzed using immunohistochemical staining. The binding of pteryxin to target proteins (MAPK, NF-κB and NLRP3) was determined based on molecular docking tests. RESULTS: Treatment with pteryxin reduced the lung W/D weight ratio, total protein (TP) level and levels of inflammatory cytokines (TNFα, IL-6 and IL-1 β) significantly. Therefore, it ameliorated LPS-induced inflammatory response in BALB/C mice. Moreover, pteryxin suppressed LPS-induced upregulation of proteins involved in MAPK/NF-κB signaling pathway and NLRP3 inflammasome activation. The expression level of F4/80 and NLRP3 was also downregulated by pteryxin pretreatment in lung tissues. Docking analysis revealed that pteryxin bound to target proteins (MAPK, NF- κB and NLRP3) with a fit-well pattern . CONCLUSION: Pteryxin may attenuate LPS-induced acute lung injury by dampening MAPK/NF-κB signaling and NLRP 3 inflammasome activation.