Novel Anti-Hepatitis B Virus Activity of Euphorbia schimperi and Its Quercetin and Kaempferol Derivatives

Abstract

Natural or plant products, because of their structural diversity, are a potential source for identifying new anti-hepatitis B virus (HBV) agents. Here, we report the anti-HBV activity of Euphorbia schimperi and its quercetin (QRC) and kaempferol derivatives. The anti-HBV-active methanol fraction of E. schimperi was subjected to chromatographic techniques, leading to isolation of three flavonols, following their structure determination by 1 H and 13 C NMR spectroscopies. Their cytotoxicity and anti-HBV potential were assessed using HBV reporter HepG2.2.15 cells, and their modes of action were delineated by molecular docking. The isolated compounds identified as quercetin-3-O-glucuronide (Q3G), quercetin-3-O-rhamnoside (Q3R), and kaempferol-3-O-glucuronide (K3G) were non-cytotoxic to HepG2.2.15 cells. The viral HBsAg/ HBeAg production on day 5 was significantly inhibited by K3G (∼70.2/∼73.4%), Q3G (∼67.8/∼72.1%), and Q3R (∼63.2%/ ∼68.2%) as compared to QRC (∼70.3/∼74.8%) and lamivudine (∼76.5/∼84.5%) used as standards. The observed in vitro anti-HBV potential was strongly supported by in silico analysis, which suggested their structure-based activity via interfering with viral Pol/RT and core proteins. In conclusion, this is the first report on the anti-HBV activity of E. schimperi-derived quercitrin-3-Oglucuronide, quercitrin-3-O-rhamnoside, and kaempferol-3-O-glucuronide, most likely through interfering with HBV proteins.

The anti‑hepatitis B virus activity of sea buckthorn is attributed to quercetin, kaempferol and isorhamnetin

“…In previous studies, while sea buckthorn leaf extract was reported for anti-DNV activity (32), the isolated compound, hiporamin, was found to exert potent antiviral effects against influenza virus, HSV and HIV (34). Of the three antiviral flavonoids identified in its leaves (34), quercetin and kaempferol, as well as their derivatives have been demonstrated to have marked HBsAg and HBeAg inhibitory potentials in HepG2.2.15 cells (27)(28)(29)(30). Notably, although the broad antiviral potential of isorhamnetin remains unexplored, a previous study reported its in vitro activity against the influenza virus (37).…”

“…Notably, quercetin and kaempferol, as well as their glucoside and rhamnoside derivatives have been shown to possess enhanced antiviral activities against human immunodeficiency virus (HIV) and herpes simplex virus (HSV), genetically close to HBV (21). In line with this finding, the authors have recently reported quercetin and kaempferol, including their derivatives, as well as anthraquinones and catechins with promising anti-HBV activities in cell-culture model (26)(27)(28)(29)(30)(31)(32).…”

The anti-hepatitis B virus and anti-hepatotoxic efficacies of solanopubamine, a rare alkaloid from Solanum schimperianum

“…These activities are suggested via direct inhibition of viral products, enhancement of host-immunity or anti-inflammation as well as hepatoprotection from oxidative or apoptotic damages. We have recently demonstrated several plant extracts and bioactive phytoconstituents with promising anti-oxidative, hepatoprotective and anti-HBV activities ( Arbab et al, 2017 , Parvez et al, 2018a , Parvez et al, 2018b , Parvez et al, 2019a , Parvez et al, 2019b , Parvez et al, 2020 , Parvez et al, 2021 ). Natural alkaloids containing nitrogen in a heterocyclic ring have a range of therapeutic salutations, including anti-HBV activities in vitro and in vivo .…”

The Dietary Flavonol Kaempferol Inhibits Epstein–Barr Virus Reactivation in Nasopharyngeal Carcinoma Cells

“…EBV lytic reactivation-based therapy is a prevalent treatment for EBV-associated malignancies [ 22 , 38 ]. Two opposing strategies have been applied: one is to induce lytic reactivation of tumor-resident EBV to cytolytic tumor cells [ 39 ], and the other is to prohibit EBV reactivation to relieve cancer progression [ 40 ]. Compared with the former strategy, the latter has the following advantages: (1) inhibition of the EBV lytic cycle decreases the opportunity for EBV reactivation-induced tumorigenesis, (2) blocking EBV lytic production avoids virion transmission to other cells, (3) suppressing EBV reactivation reduces the secretion of oncogenic endocrine factors from EBV-positive tumor cells, and (4) Decreasing lytic protein expression can attenuate the immune evasion of lytic EBV.…”