Study On The Protective Effect Of Rabdosia Japonica Var. Glaucocalyx (Maxim.) Hara. And Eupatorium Lindleyanum DC. On Lipopolysaccharide-induced Acute Lung Injury In Mice

This paper aimed to study on the protective effect of Rabdosia japonica var.glaucocalyx (Maxim.) Hara. and Eupatorium lindleyanum DC. onlipopolysaccharide-induced (LPS-induced) acute lung injury (ALI) in mice and todetermined the active fraction of those two plants, respectively. The protective effectmechanisms of those two plants were explored in terms of inflammatory cytokines,complement levels, anti-oxidation.Part I: Study on the protective effect of Rabdosia japonica var. glaucocalyx (Maxim.) Hara.on LPS-induced ALI in mice.Rabdosia japonica var. glaucocalyx (Maxim.) Hara. is widely used as a traditionalChinese folk medicine, shows anti-bacterial, anti-inflammatory and anti-tumor activities.The plant is used for the treatment of hepatitis, gastritis, mastitis and tonsillitis.Anti-complementary activity test in vitro indicated that the EtOH extracts of Rabdosiajaponica var. glaucocalyx (Maxim.) Hara.(RJ) and the flavonoids fraction of RJ (RJFs)showed the inhibitions on the complement system towards the classical pathway. AsUHPLC-Q-TOF/MS analysis showed, RJ mainly contains terpenes and flavonoids; RJFsmainly contains diterpenes and flavonoids. HPLC analysis showed that the contents ofglaucocalyxin A, quercetin and luteolin in RJFs were2.90%,0.308%and0.291%,respectively. Pretreatment with RJ and RJFs could significantly decrease lung wet-to-dry weight(W/D) ratio, nitric oxide (NO) and protein concentration in bronchoalveolar lavage fluid(BALF), which was exhibited together with the lowered myeloperoxidase (MPO) activity,the increased superoxide dismutase (SOD) activity and down-regulation the level of tumornecrosis factor-α (TNF-α), interleukin-6(IL-6) and interleukin-1β (IL-1β) in ALI model.Additionally, RJFs attenuated lung histopathological changes and significantly reducedcomplement3c deposition. Furthermore, RJFs decreased the level of C3in serum.In summary, RJ and RJFs significantly attenuate LPS-induced ALI via reducingproductions of pro-inflammatory mediators, decreasing the level of complement andreducing radicals.Part II: Study on the protective effect of Eupatorium lindleyanum DC. on LPS-inducedALI in mice.Eupatorium lindleyanum DC.(EUP) is widely used as a traditional Chinese medicinefor the treatment of colds, tonsillitis, chronic bronchitis and bronchitis.Anti-complementary activity test in vitro showed that the sesquiterpene, diterpene,flavonoid as well as sesquiterpene, diterpene, flavonoid enrichment fractions isolated fromEUP showed the inhibitions on the complement system towards the classical pathway. Thethree fractions showed the inhibitions on the complement system towards the alternativepathway. As UHPLC-Q-TOF/MS analysis showed, EUP mainly contains sesquiterpenes,diterpenes, sterols and flavonoids. HPLC analysis showed that the contents of eupalinolideF, eupalinolide G, eupalinolide H eupalinolide I and eupalinolide K in the sesquiterpenesfraction of EUP (EUP-SQT) were3.8%,31.4%,6.6%,3.3%and46.3%, respectively; thecontents of nepetin and jaceosidin in the flavonoids fraction of EUP (EUP-FLA) were25.2%and65.7%.Pretreatment with the EtOH extracts of EUP (EUP-EtOH), the water extract of EUP(EUP-H2O), EUP-SQT and EUP-FLA could significantly decrease lung W/D ratio, NO andprotein concentration in BALF, which was exhibited together with the lowered MPOactivity, the increased SOD activity and down-regulation the level of TNF-α, IL-6and IL-1β in ALI model. Additionally, they attenuated lung histopathological changes andsignificantly reduced complement3c deposition with decreasing the level of C3in serum.Furthermore, EUP-SQT and EUP-FLA decreased the level of C3c in serumIn summary, EUP significantly attenuate LPS-induced ALI via reducing productionsof pro-inflammatory mediators, decreasing the level of complement and reducing radicals.EUP-SQT and EUP-FLA might play the major protective role in ALI.