Antiviral activity of aloe-emodin against influenza A virus via galectin-3 up-regulation

Li, Shih Wen; Yang, Tsuey Ching; Lai, Chien‐Chen; Huang, Su; Liao, Jun Ming; Wan, Lei; Lin, Ying; Lin, Cheng Wen

doi:10.1016/j.ejphar.2014.05.028

Cited by 138 publications

(97 citation statements)

References 27 publications

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“…1) is an anthraquinone polyphenol and a naturally active ingredient of Chinese herbs such as Cassia occidentalis , Rheum palmatum L. and Polygonum multiflorum Thunb, which are used as traditional medicines in many countries [10-12]. Recent studies have demonstrated that aloe-emodin possesses a wide range of biological and pharmacological activities, such as anticancer [13-15], antiviral [16], antimicrobial [17], and anti-inflammatory effects [18]. Previous studies have revealed that aloe-emodin exhibits therapeutic effects via regulation of the expressions of protein kinase C (PKC), bcl-2, caspases and members of the mitogen-activated protein kinase (MAPK) family [19, 20].…”

Section: Introductionmentioning

confidence: 99%

Induction of Apoptosis in HepaRG Cell Line by Aloe-Emodin through Generation of Reactive Oxygen Species and the Mitochondrial Pathway

Dong

Yin

et al. 2017

Cell Physiol Biochem

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Background/Aims: Aloe-emodin (1,8-dihydroxy-3-hydroxymethyl-anthraquinone), an anthraquinone active compounds, is isolated from some traditional medicinal plants such as Rheum palmatum L. and Cassia occidentalis, which induce hepatotoxicity in rats. The aim of this study was to determine potential cytotoxic effects of aloe-emodin on HepaRG cells and to define the underlying mechanism. Methods: MTT was used to evaluate cell viability. Apoptotic cell death was analyzed via Annexin V-FITC/PI double staining. Intracellular reactive oxygen species (ROS) and mitochondrial membrane potential (MMP) were determined by flow cytometry, while the expression of apoptosis-related proteins was determined by Western blot analysis. Results: Treatment with aloe-emodin significantly reduced cell viability and induced apoptosis in HepaRG cells in a dose- and time-dependent manner. It provoked ROS generation and depolarization of MMP in HepaRG cells when compared with controls. Aloe-emodin dose-dependently increased release of mitochondrial cytochrome c, and levels of Fas, p53, p21, Bax/Bcl-2 ratio, as well as activation of caspase-3, caspase-8, caspase-9, and subsequent cleavage of poly(ADP-ribose)polymerase (PARP). It also induced S-phase cell cycle arrest by increasing the expression of p21 and cyclin E proteins while significantly decreasing the expression of cyclin A and CDK2. Conclusion: These results suggest that aloe-emodin inhibits cell proliferation and induces apoptosis in HepaRG cells, most probably through a mechanism involving both Fas death pathway and the mitochondrial pathway by generation of ROS. These findings underscore the need for risk assessment of human exposure to aloe-emodin.

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Section: Introductionmentioning

confidence: 99%

Induction of Apoptosis in HepaRG Cell Line by Aloe-Emodin through Generation of Reactive Oxygen Species and the Mitochondrial Pathway

Dong

Yin

et al. 2017

Cell Physiol Biochem

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“…Aloe-emodin, an anthraquinone constituent in Aloe barbadensis MILLER, Rheum palmatum L., Cassia obtusifolia L. and C. angustifolia VAHL, etc. (Peng et al, 2014;Shia et al, 2009a;Wu et al, 2013;Xu et al, 2012), has shown a wide range of beneficial activities including anticancer Guo et al, 2007;Mulakayala et al, 2013), antivirus (Li et al, 2014), anti-inflammation Park et al, 2009) and antiangiogenesis (Cardenas et al, 2006). However, most of the bioactivities of aloe-emodin were demonstrated by in vitro studies.…”

Section: Introductionmentioning

confidence: 99%

Analysis of the pharmacokinetics and metabolism of aloe‐emodin following intravenous and oral administrations in rats

Shia

Lin

et al. 2016

Biomedical Chromatography

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Aloe-emodin, a natural polyphenolic anthraquinone, has shown various beneficial bioactivities in vitro. The aim of this study was to investigate the pharmacokinetics and metabolism of aloe-emodin. Aloe-emodin was intravenously and orally administered to rats. The concentrations of aloe-emodin and rhein, a metabolite of aloe-emodin, were determined by HPLC method prior to and after hydrolysis with β-glucuronidase and sulfatase/β-glucuronidase. The results showed that the systemic exposures of aloe-emodin and its metabolites were ranked as aloe-emodin glucuronides (G) > rhein sulfates (S) > aloe-emodin > rhein and rhein G when aloe-emodin was given intravenously. In contrast, when aloe-emodin was administered orally, the parent form of aloe-emodin was not absorbed per se, and the systemic exposures of its metabolites were ranked as aloe-emodin G > rhein G > rhein. In conclusion, the metabolites of aloe-emodin are more important than the parent form for the bioactivities in vivo. Copyright © 2016 John Wiley & Sons, Ltd.

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“…A purified sample of aloe‐emodin prepared from aloin was previously shown to block the infectivity of HSV, VZV, SuHV, influenza virus, adenovirus, and rhinovirus (Sydiskis et al, ). Aloe‐emodin isolated from AV has been previously reported for antiviral activities against HSV, poliovirus, and influenza A virus (Bernard et al, ; Cohen et al, ; Li, Yang, & Lai, ; Semple, Pyke, Reynolds, & Flower, ). In the present study, AV‐derived aloe‐emodin for the first time, demonstrated a very high anti‐HBV activity; that is, inhibitions of HBs/HBeAg expression (~83%) in HepG2.2.15 cells close to Lamivudine (~86%).…”

Section: Discussionmentioning

confidence: 99%

The anti‐hepatitis B virus therapeutic potential of anthraquinones derived from Aloe vera

Parvez

Al‐Dosari

Alam

et al. 2019

Phytotherapy Research

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Although the approved hepatitis B virus (HBV)‐polymerase inhibitors (e.g., lamivudine) often lead to drug‐resistance, several natural products have shown promising efficacies. Though Aloe vera (AV) gel and its constituents are shown inhibitors of many viruses, their anti‐HBV activity still remains elusive. We therefore, tested the anti‐HBV potential of AV extract and its anthraquinones in hepatoma cells, including molecular docking, high‐performance thin layer chromatography (HPTLC), and cytochrome P450 (CYP3A4) activation analyses. Our anti‐HBV assays (HBsAg/HBeAg Elisa) showed maximal inhibition of viral antigens production by aloe‐emodin (~83%) > chrysophanol (~62%) > aloin B (~61%) > AV extract (~37%) in HepG2.2.15 cells. Interestingly, the effect of aloe‐emodin was comparable with lamivudine (~86%). Moreover, sequential treatment with lamivudine (pulse) followed by aloe‐emodin (chase) enhanced the efficacy of monotherapy by ~12%. Docking (AutoDock Vina) of the anthraquinones indicated strong interactions with HBV‐polymerase residues that formed stable complexes with high Gibbs's free energy. Further, identification of aloe‐emodin and aloin B by validated HPTLC in AV extract strongly endorsed its anti‐HBV potential. In addition, our luciferase‐reporter gene assay of transfected HepG2 cells showed moderate induction of CYP3A4 by aloe‐emodin. In conclusion, this is the first report on anti‐HBV potential of AV–derived anthraquinones, possibly via HBV‐polymerase inhibition. Of these, although aloin B exhibits novel antiviral effect, aloe‐emodin appears as the most promising anti‐HBV natural drug with CYP3A4 activating property towards its enhanced therapeutic efficacy.

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Antiviral activity of aloe-emodin against influenza A virus via galectin-3 up-regulation

Cited by 138 publications

References 27 publications

Induction of Apoptosis in HepaRG Cell Line by Aloe-Emodin through Generation of Reactive Oxygen Species and the Mitochondrial Pathway

Induction of Apoptosis in HepaRG Cell Line by Aloe-Emodin through Generation of Reactive Oxygen Species and the Mitochondrial Pathway

Analysis of the pharmacokinetics and metabolism of aloe‐emodin following intravenous and oral administrations in rats

The anti‐hepatitis B virus therapeutic potential of anthraquinones derived from Aloe vera

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