title: Protective Effect of Astragaloside IV Against Paraquat-Induced Lung Injury in Mice by Suppressing Rho Signaling.
abstract: The purpose of the present study was to evaluate the protective effects of astragaloside IV (AS IV) against paraquat (PQ)-induced pulmonary injury in vivo. Fifty BALB/C mice were randomized into five groups: (1) control, (2) PQ, (3) PQ + dexamethasone (Dex, 5 mg/kg), (4) PQ + AS IV (50 mg/kg), and (5) PQ + AS IV (100 mg/kg). A single dose of PQ (50 mg/kg, i.p.) was intraperitoneally given to induced acute lung injury. Then, mice were treated with AS IV (50 and 100 mg/kg/day, orally) for 5 days. At the end of the experiment, animals were euthanized; then, the bronchoalveolar lavage fluid (BALF) and lung tissues were collected for histological observation, biochemical assay, and Western blot analysis. Malondialdehyde (MDA), myeloperoxidase (MPO), catalase (CAT), superoxide dismutase (SOD), glutathione peroxidase (GSH-Px) in lung tissues, and interleukin-6 (IL-6), IL-1β, tumor necrosis factor-α (TNF-α) levels in BALF were determined. Histological examination indicated that AS IV attenuated lung damage caused by PQ. Biochemical results showed that AS IV treatment significantly reduced the levels of MDA, MPO, and inflammatory cytokines while increased the levels of SOD, CAT, and GSH-Px compared with those in PQ group. Western blot results revealed that AS IV attenuated the Txnip/Trx expressions and inhibited Rho/ROCK/nuclear factor kappaB (NF-κB) signaling pathway in PQ-challenged mice. These findings suggested the protective effect of AS IV as a natural product on PQ-induced pulmonary injury.
authors.affiliation: State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing, 210009, China.
authors.forename: Tong
authors.initials: T
authors.lastname: Chen
authors.affiliation: State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing, 210009, China.
authors.forename: Ruoning
authors.initials: R
authors.lastname: Wang
authors.affiliation: State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing, 210009, China.
authors.forename: Wenjiao
authors.initials: W
authors.lastname: Jiang
authors.affiliation: School of Pharmacy, China Pharmaceutical University, Nanjing, 210009, China.
authors.forename: Huimin
authors.initials: H
authors.lastname: Wang
authors.affiliation: State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing, 210009, China.
authors.forename: Ang
authors.initials: A
authors.lastname: Xu
authors.affiliation: State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing, 210009, China.
authors.forename: Guo
authors.initials: G
authors.lastname: Lu
authors.affiliation: State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing, 210009, China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Ren
authors.affiliation: State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing, 210009, China.
authors.forename: Yangmei
authors.initials: Y
authors.lastname: Xu
authors.affiliation: State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing, 210009, China.
authors.forename: Yangyang
authors.initials: Y
authors.lastname: Song
authors.affiliation: School of Pharmacy, China Pharmaceutical University, Nanjing, 210009, China.
authors.forename: Shoulei
authors.initials: S
authors.lastname: Yong
authors.affiliation: State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing, 210009, China. huijicpu@163.com.
authors.forename: Hui
authors.initials: H
authors.lastname: Ji
authors.affiliation: State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing, 210009, China. mazhanqiangnanjing@126.com.|Department of Pharmacology of Chinese Materia Medica, China Pharmaceutical University, Nanjing, 210009, China. mazhanqiangnanjing@126.com.
authors.forename: Zhanqiang
authors.initials: Z
authors.lastname: Ma
mesh_terms: D055371:Acute Lung Injury / Q000139:chemically induced / Q000188:drug therapy / Q000517:prevention & control*; D000818:Animals; D000975:Antioxidants / Q000627:therapeutic use*; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry; D002374:Catalase / Q000378:metabolism; D004365:Drugs, Chinese Herbal; D004789:Enzyme Activation / Q000187:drug effects; D005979:Glutathione Peroxidase / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D008168:Lung / Q000473:pathology; D008315:Malondialdehyde / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D016328:NF-kappa B / Q000378:metabolism*; D018384:Oxidative Stress / Q000187:drug effects; D010269:Paraquat / Q000494:pharmacology*; D009195:Peroxidase / Q000378:metabolism; D011897:Random Allocation; D012503:Saponins / Q000627:therapeutic use*; D015398:Signal Transduction; D013482:Superoxide Dismutase / Q000378:metabolism; D013879:Thioredoxins / Q000378:metabolism; D014315:Triterpenes / Q000627:therapeutic use*; D014409:Tumor Necrosis Factor-alpha; D020741:rho GTP-Binding Proteins / Q000378:metabolism*; D054460:rho-Associated Kinases / Q000378:metabolism*
chemical_list: D000975:Antioxidants; D004365:Drugs, Chinese Herbal; D015850:Interleukin-6; D016328:NF-kappa B; D012503:Saponins; D014315:Triterpenes; D014409:Tumor Necrosis Factor-alpha; C515559:Txn1 protein, mouse; C052064:astragaloside A; D008315:Malondialdehyde; D013879:Thioredoxins; D002374:Catalase; D009195:Peroxidase; D005979:Glutathione Peroxidase; D013482:Superoxide Dismutase; D054460:rho-Associated Kinases; D020741:rho GTP-Binding Proteins; D010269:Paraquat
keywords: Rho; Txnip/Trx; astragaloside IV; lung injury; paraquat