Decrease in Dengue virus-2 infection and reduction of cytokine/chemokine production by Uncaria guianensis in human hepatocyte cell line Huh-7

Abstract

BACKGROUND Dengue fever may present hemorrhages and cavitary effusions as result of exacerbated immune responses. We investigated hydro-alcoholic extracts from leaves (UGL) and bark (UGB) of the medicinal species Uncaria guinanensis with respect to antiviral effects in Dengue virus (DENV) infection and in immunological parameters associated with in vivo physiopathological features.METHODS Chemical profiles from UGB or UGL were compared in thin layer chromatography and 1H nuclear magnetic resonance using flavonoid compounds and a pentacyclic oxindole alkaloid-enriched fraction as references. DENV-2-infected hepatocytes (Huh-7) were treated with extracts. Cell viability, DENV antigens and immunological factors were detected by enzyme-linked immunosorbent assay (ELISA) or flow cytometry.FINDINGS The UGL mainly differed from UGB by selectively containing the flavonoid kaempferitrin. UGB and UGL improved hepatocyte viability. Both extracts reduced intracellular viral antigen and inhibited the secretion of viral non-structural protein (NS1), which is indicative of viral replication. Reduction in secretion of macrophage migration inhibitory factor was achieved by UGB, of interleukin-6 by UGL, and of interleukin-8 by both UGB and UGL. MAINCONCLUSIONS The U. guianensis extracts presented, antiviral and immunomodulatory effects for DENV and possibly a hepatocyte-protective activity. Further studies may be performed to consider these products as potential candidates for the development of an herbal product for the future treatment of dengue.

Research Progress of the Antiviral Bioactivities of Natural Flavonoids

“…Studies have displayed that flavonols are more active than flavones against herpes simplex virus type 1, and the activity order from strong to weak was found to be galangin, kaempferol, and quercetin. Zandi et al studied the anti-dengue virus properties of quercetin, hesperetin, naringin, and daidzein at different stages of DENV-2 (dengue virus type-2) infection and replication cycle [41]. Quercetin was found to be most effective against DENV-2 in cells.…”

“…Another feature of flavonoids is a reduction in the release of peroxidase. This reduction inhibits the production of reactive oxygen species by neutrophils by interfering with 1-antitrypsin activation and the metabolism of arachidonic acid [41,43].…”

Antiviral Activity of Faramea hyacinthina and Faramea truncata Leaves on Dengue Virus Type‐2 and Their Major Compounds

“…[14 -16] Some hepatocyte-derived cell lines have been used as targets for in vitro DENV infection models. [16 -18] Continuing our search, the antiviral and immunomodulatory effects in DENV-2-infected hepatocyte cell line (Huh-7) of the species U. guianensis have been described [19] as well as the anti-DENV activity of extracts from other Rubiaceae species when screened in hepatocarcinoma cell lineage (HepG2) revealing the significant antiviral effect of the MeOH extract of Faramea bahiensis leaves. The chemical study of this extract led to the isolation, among other, of the new antiviral flavanone apiofuranoside (1).…”

Immortalized stem cell-derived hepatocyte-like cells: An alternative model for studying dengue pathogenesis and therapy

“…A cytokine storm is a pathogenic factor that contributes to severe dengue infections [ 41 ]. Since hepatocytes are primary target cells for DENV replication in vivo [ 15 , 42 ] and are known for their ability to produce cytokines in response to flavivirus infections [ 43 , 44 ], the kinetics of cytokine gene and protein expression after DENV infection were evaluated and compared among the hepatic cell lines and PHHs ( Fig 5 ). Productive infection of PHHs from two donors was confirmed prior to the assessment of cytokine expression patterns ( S4 Fig ).…”