| In vitro: |
| Antiviral Res. 2014 Sep;109:30-41. | | Apigenin inhibits enterovirus 71 replication through suppressing viral IRES activity and modulating cellular JNK pathway.[Pubmed: 24971492] | Enterovirus 71 (EV71) is a member of genus Enterovirus in Picornaviridae family, which is one of the major causative agents for hand, foot and mouth disease (HFMD), and sometimes associated with severe central nervous system diseases in children. Currently there are no effective therapeutic medicines or vaccines for the disease.
METHODS AND RESULTS:
In this report, we found that apigenin and luteolin, two flavones that differ only in the number of hydroxyl groups could inhibit EV71-mediated cytopathogenic effect (CPE) and EV71 replication with low cytotoxicity. Both molecules also showed inhibitory effect on the viral polyprotein expression. They prevented EV71-induced cell apoptosis, intracellular reactive oxygen species (ROS) generation and cytokines up-regulation. Time-of-drug addition study demonstrated that apigenin and luteolin acted after viral entry. We examined the effect of apigenin and luteolin on 2A(pro) and 3C(pro) activity, two viral proteases responsible for viral polyprotein processing, and found that they showed less inhibitory activity on 2A(pro) or 3C(pro). Further studies demonstrated that apigenin, but not luteolin could interfere with viral IRES activity. Also, apigenin inhibited EV71-induced c-Jun N-terminal kinase (JNK) activation which is critical for viral replication, in contrast to luteolin that did not.
CONCLUSIONS:
This study demonstrated that apigenin may inhibit EV71 replication through suppressing viral IRES activity and modulating cellular JNK pathway. It also provided evidence that one hydroxyl group difference in the B ring between apigenin and luteolin resulted in the distinct antiviral mechanisms. This study will provide the basis for better drug development and further identification of potential drug targets. |
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| In vivo: |
| Br J Nutr. 2015 Feb 28;113(4):618-26. | | Intestinal anti-inflammatory activity of apigenin K in two rat colitis models induced by trinitrobenzenesulfonic acid and dextran sulphate sodium.[Pubmed: 25654996] | Flavonoids are polyphenolic compounds that are widespread in nature, and consumed as part of the human diet in significant amounts. The aim of the present study was to test the intestinal anti-inflammatory activity of apigenin K, a soluble form of apigenin, in two models of rat colitis, namely the trinitrobenzenesulfonic acid (TNBS) model and the dextran sulphate sodium (DSS) model.
METHODS AND RESULTS:
Apigenin K (1, 3 and 10 mg/kg; by the oral route; n 4-6 per group) was administered as a pre-treatment to rats with TNBS and DSS colitis, and colonic status was checked by macroscopic and biochemical examination. Apigenin K pre-treatment resulted in the amelioration of morphological signs and biochemical markers in the TNBS model. The results demonstrated a reduction in the inflamed area, as well as lower values of score and colonic weight:length ratio compared with the TNBS group. Myeloperoxidase (MPO) activity was reduced by 30 % (P< 0·05). Moreover, apigenin K pre-treatment ameliorated morphological signs and biochemical markers in the DSS model. Thus, macroscopic damage was significantly reduced and the colonic weight:length ratio was lowered by approximately 10 %, while colonic MPO and alkaline phosphatase activities were decreased by 35 and 21 %, respectively (P< 0·05). Apigenin K pre-treatment also tended to normalise the expression of a number of colonic inflammatory markers (e.g. TNF-α, transforming growth factor-β, IL-6, intercellular adhesion molecule 1 or chemokine (C-C motif) ligand 2).
CONCLUSIONS:
In conclusion, apigenin K is found to have anti-inflammatory effects in two preclinical models of inflammatory bowel disease. | | Evid Based Complement Alternat Med . 2017;2017:2590676. | | Apigenin Attenuates Adriamycin-Induced Cardiomyocyte Apoptosis via the PI3K/AKT/mTOR Pathway[Pubmed: 28684964] | | Treatment with Adriamycin (ADR) is one of the major causes of chemotherapy-induced cardiotoxicity and therefore is the principal limiting factor in the effectiveness of chemotherapy for cancer patients. Apigenin (API) has been shown to play a cardioprotective role. The present study examined the effect of API on ADR-induced cardiotoxicity in mice. Sixty male Kunming mice were randomly divided into 4 groups: a control group, ADR model group, low-dose API treatment group (125 mg·kg-1), and high-dose API treatment group (250 mg·kg-1). Blood samples were taken to evaluate a spectrum of myocardial enzymes. Cardiomyocyte apoptosis was measured using a TUNEL assay, and cardiomyocyte autophagy was observed using electron microscopy. Moreover, apoptosis-related proteins, such as Bax and Bcl-2, autophagy-related proteins, including Beclin1 and LC3B, and PI3K/AKT/mTOR pathway-related proteins were examined with western blot. Our results demonstrate that ADR caused an increase in the serum levels of cardiac injury markers and enhanced cardiomyocyte apoptosis and autophagy. API administration prevented the effects associated with ADR-induced cardiotoxicity in mice and inhibited ADR-induced apoptosis and autophagy. API also promoted PI3K/AKT/mTOR pathway activity in ADR-treated mice. In conclusion, API may have a protective effect against ADR-induced cardiotoxicity by inhibiting apoptosis and autophagy via activation of the PI3K/AKT/mTOR pathway. |
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