Houttuyniacordata extracts and constituents inhibit the infectivity of dengue virus type 2 in vitro

OBJECTIVE Dengue virus belongs to the Flaviviridaefamily,and causes dengue fever and its related complications.Currently,there are no antiviral agents or licensed vaccines against dengue in humans.Houttuyniacordata Thunb.(Saururaceae)is documented to possess antiviral activity against several medically important viruses.METHODS The in vitro activities of the total ethyl acetate(EA)extracts of two batches of H.cordata,five EA fractions,and four of its constituent polyphenols(chlorogenic acid,hyperoside,quercetin,and quercitrin)against the new guinea C strain of dengue-2 virus were investigated.RESULTS Using the plaque reduction test,the total EA extracts of H.cordatainhibited viral infectivity when pre-incubated with virus before the viral adsorption stage,but exhibited no dose-dependent response when added to the cells at 6h post-infection.The 50% inhibitory concentration(IC50)of total EA extracts from two batches of H.cordata added before the viral adsorption stage were 0.24±3.1μg·mL-1 and 0.04±4.6μg·mL-1.However,only one out of five tested EA fractions showed considerably- weaker IC50 of 333μg·mL1.The pure polyphenol compounds displayed some anti-dengue activity,with their combinations yielding greater antiviral effects,especially the combination of chlorogenic acid and hyperoside with a high selectivity index.However,the enhanced efficacy of the polyphenol combinations was still less than that of the total EA extracts which revealed absence of cytotoxicity.Therefore,there may be other compounds in H.cordatathat contribute to the superior efficacy of the EA extracts.CONCLUSION We conclude that H.cordata possesses anti-dengue-2 virus activity,and harbors potential for the development of antiviral agents against dengue.

Non-typeable haemophilus influenzae-induced exacerbation on a cigarette smoke lung injury model:Protective effect of andrographolide

OBJECTIVE To develop a 2-week cigarette smoke(CS)acute lung injury model exacerbated by haemophilus influenzae(NTHi)and study the protective effect of andrographolide in this COPD model.METHODS Female BALB/c mice,6-8-week-old,were exposed to 4% 3R4 FCS delivered using aperistaltic pump daily for 2 weeks to induce an acute lung injury model.After 2 weeks of smoking,mice were inoculated intratracheally with NTHi to induce exacerbation on the model.Mice were sacrificed 48 h after last bacteria challenge and lung samples were collected for various analyses.RESULTS After developing a 2-week CS acute lung injury model exacerbated by NTHi,the CS+NTHi group was shown to have a higher inflammatory response,higher bacterial clearance,an upregulation of MMP12 mRNA levels and decrease in TIMP1 mRNA levels in the lungs.Administration of Andrographolide suppressed BALF lung cellular infiltrates,TNF-α,CXCL1/KC,IL-1βand 8-OHdG protein levels,together with increased HO-1 and GR mRNA levels and decreased MMP-8 and MMP-9 mRNA levels.Andrographolide was able to ameliorate lung histopathology as observed with H&E staining and inflammation scoring.Andrographolide was also shown to reduce Keap-1 level in lungs without affecting DJ-1 level.CONCLUSION This study demonstrates the protective effect of andrographolide in a novel 2-week CS acute lung injury model exacerbated by NTHi and presents it as a potential therapeutic for COPD.