Aloe-emodin is an interferon-inducing agent with antiviral activity against Japanese encephalitis virus and enterovirus 71

Lin, Cheng Wen; Wu, Chia Fang; Hsiao, Nai Wan; Chang, Chia‐Chu; Li, Shih Wein; Wan, Lei; Lin, Ying; Lin, Wei Yong

doi:10.1016/j.ijantimicag.2008.04.018

Cited by 111 publications

(62 citation statements)

References 12 publications

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“…Our prior study proved quercetin an active antienterovirus component of K. gracilis leaf extract, showing IC 50 values above 117 μ M for EV71 and 176 μ M for CoxA16 [14]. Eupafolin was thus suggested as crucially active antienterovirus component in K. gracilis , at the same time showing similar anti-EV71 efficacy and selectivity with identified potential anti-EV71 compounds of natural products like allophycocyanin, aloe-emodin, gallic acid, chrysosplenetin, and penduletin [17–20]. …”

Section: Discussionmentioning

confidence: 92%

Eupafolin and Ethyl Acetate Fraction ofKalanchoe gracilisStem Extract Show Potent Antiviral Activities against Enterovirus 71 and Coxsackievirus A16

Huang

Lai

et al. 2013

Evidence-Based Complementary and Alternative Medicine

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Enterovirus 71 (EV71) and coxsackievirus A16 (CoxA16) are main pathogens of hand-foot-and-mouth disease, occasionally causing aseptic meningitis and encephalitis in tropical and subtropical regions. Kalanchoe gracilis, Da-Huan-Hun, is a Chinese folk medicine for treating pain and inflammation, exhibiting antioxidant and anti-inflammatory activities. Our prior report (2012) cited K. gracilis leaf extract as moderately active against EV71 and CoxA16. This study further rates antienteroviral potential of K. gracilis stem (KGS) extract to identify potent antiviral fractions and components. The extract moderately inhibits viral cytopathicity and virus yield, as well as in vitro replication of EV71 (IC50 = 75.18 μg/mL) and CoxA16 (IC50 = 81.41 μg/mL). Ethyl acetate (EA) fraction of KGS extract showed greater antiviral activity than that of n-butanol or aqueous fraction: IC50 values of 4.21 μg/mL against EV71 and 9.08 μg/mL against CoxA16. HPLC analysis, UV-Vis absorption spectroscopy, and plaque reduction assay indicate that eupafolin is a vital component of EA fraction showing potent activity against EV71 (IC50 = 1.39 μM) and CoxA16 (IC50 = 5.24 μM). Eupafolin specifically lessened virus-induced upregulation of IL-6 and RANTES by inhibiting virus-induced ERK1/2, AP-1, and STAT3 signals. Anti-enteroviral potency of KGS EA fraction and eupafolin shows the clinical potential against EV71 and CoxA16 infection.

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Section: Discussionmentioning

confidence: 92%

Eupafolin and Ethyl Acetate Fraction ofKalanchoe gracilisStem Extract Show Potent Antiviral Activities against Enterovirus 71 and Coxsackievirus A16

Huang

Lai

et al. 2013

Evidence-Based Complementary and Alternative Medicine

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“…Emodin has been previously reported to possess antiviral [16], antiinflammatory [17], antiulcerogenic [18], immunosuppressive [19], and chemopreventive activities [20]. Interestingly, antiproliferative effects of emodin have been observed in many tumor cell lines, including HER2/neuoverexpressing breast cancer [21], lung cancer [22], leukemia [23], HCC [24], and neuroblastoma [25] but not in normal cells, suggesting that emodin may have a significant therapeutic efficacy as an anticancer agent.…”

Section: Introductionmentioning

confidence: 99%

An anthraquinone derivative, emodin sensitizes hepatocellular carcinoma cells to TRAIL induced apoptosis through the induction of death receptors and downregulation of cell survival proteins

et al. 2013

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Recombinant tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is currently under clinical trials for cancer, however many tumor cells, including hepatocellular carcinoma (HCC) develop resistance to TRAIL-induced apoptosis. Hence, novel agents that can alleviate TRAIL-induced resistance are urgently needed. In the present report, we investigated the potential of emodin to enhance apoptosis induced by TRAIL in HCC cells. As observed by MTT cytotoxicity assay and the externalization of the membrane phospholipid phosphatidylserine, we found that emodin can significantly potentiate TRAIL-induced apoptosis in HCC cells. When investigated for the mechanism(s), we observed that emodin can downregulate the expression of various cell survival proteins, and induce the cell surface expression of both TRAIL receptors, death receptors (DR) 4 as well as 5. In addition, emodin increased the expression of C/EBP homologous protein (CHOP) in a time-dependent manner. Knockdown of CHOP by siRNA decreased the induction of emodin-induced DR5 expression and apoptosis. Emodin-induced induction of DR5 was mediated through the generation of reactive oxygen species (ROS), as N-acetylcysteine blocked the induction of DR5 and the induction of apoptosis. Also, the knockdown of X-linked inhibitor of apoptosis protein by siRNA significantly reduced the sensitization effect of emodin on TRAILinduced apoptosis. Overall, our experimental results clearly indicate that emodin can indeed potentiate TRAIL-induced Aruljothi Subramaniam and Ser Yue Loo contributed equally to this work.

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“…Studies have demonstrated the antiviral activity of type I IFNs against EV71 infection in vitro and in vivo (25,26). Furthermore, treatment with an IFN-inducing agent (27) and synergistic inhibition of EV71 replication by IFN-␣ and rupintrivir (28) have been identified as effective treatment regimens. However, during EV71 infection, several immune escape strategies are elicited by EV71 to attenuate the type I IFN response.…”

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confidence: 99%

Enterovirus 71 Proteins 2A and 3D Antagonize the Antiviral Activity of Gamma Interferon via Signaling Attenuation

Wang

Chen

Chang

et al. 2015

J Virol

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Enterovirus 71 (EV71) infection causes severe mortality involving multiple possible mechanisms, including cytokine storm, brain stem encephalitis, and fulminant pulmonary edema. Gamma interferon (IFN-␥) may confer anti-EV71 activity; however, the claim that disease severity is highly correlated to an increase in IFN-␥ is controversial and would indicate an immune escape initiated by EV71. This study, investigating the role of IFN-␥ in EV71 infection using a murine model, showed that IFN-␥ was elevated. Moreover, IFN-␥ receptor-deficient mice showed higher mortality rates and more severe disease progression with slower viral clearance than wild-type mice. E nterovirus 71 (EV71) is a single-stranded RNA virus in the Picornaviridae family. The EV71 genome encodes four structural proteins, VP1 to VP4, and seven nonstructural proteins, 2A to 2C and 3A to 3D (1). Numerous studies have investigated the functions of viral proteins in viral replication and virulence (2). During EV71 infection, capsid VP proteins mediate virus entry by binding to cellular receptors, human scavenger receptor class B and P-selectin glycoprotein ligand 1 (3). Additionally, VP proteins participate in the assembly of viral particles (4). The 3C protein, a chymotrypsin-like protease, reduces host cell transcription dramatically by inhibiting cell polyadenylation (5) and induces caspase-regulated neural cell apoptosis (6). To develop specific anti-EV71 drugs, a number of small molecules targeting viral proteins have been designed, such as the 3C inhibitor rupintrivir and the 3D inhibitor aurintricarboxylic acid (ATA) (7-9).EV71 infection typically causes mild, self-limiting hand-footand-mouth disease; however, patients sometimes have significant morbidity and mortality resulting from hemorrhagic pulmonary edema following acute central nervous system-related cardiopulmonary failure and brain stem encephalitis (2,10,11). In addition to the direct cytotoxicity caused by EV71 infection (12-16) and the resultant virulence factors (6, 17), host factors such as the aberrant production of cytokines that is detected during EV71-associated pulmonary edema can also lead to disease. In infected

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Aloe-emodin is an interferon-inducing agent with antiviral activity against Japanese encephalitis virus and enterovirus 71

Cited by 111 publications

References 12 publications

Eupafolin and Ethyl Acetate Fraction ofKalanchoe gracilisStem Extract Show Potent Antiviral Activities against Enterovirus 71 and Coxsackievirus A16

Eupafolin and Ethyl Acetate Fraction ofKalanchoe gracilisStem Extract Show Potent Antiviral Activities against Enterovirus 71 and Coxsackievirus A16

An anthraquinone derivative, emodin sensitizes hepatocellular carcinoma cells to TRAIL induced apoptosis through the induction of death receptors and downregulation of cell survival proteins

Enterovirus 71 Proteins 2A and 3D Antagonize the Antiviral Activity of Gamma Interferon via Signaling Attenuation

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