Review Article

Dihydromyricetin Acts as a Potential Redox Balance Mediator in Cancer Chemoprevention

Table 3

Anti-inflammatory activities and mechanisms of the action of DHM.

Treatment methodsMode of administrationDose and duration timeMechanism of action/activities/effects showedReference

LPS-induced inflammation50, 100, and 150 μg/mL for 2 hShowed anti-inflammatory activity by inhibiting interconnected ROS/Akt/IKK/NF-κB signaling pathways. Significantly inhibited the release of nitric oxide (NO) and proinflammatory cytokines such as IL-1β, IL-6, and TNF-α in a dose-dependent mannerShimei et al. (2012)
LPS-induced inflammation in RAW264.7 cells0.4, 0.8,1.5, 3, 6.2, 12.5, 25, 50, and 100 μM for 24 hShowed anti-inflammatory effects through the inhibition of the release of nitric oxide (NO) in RAW macrophagesYuemei et al. (2019)
A549 cells were stimulated with TLR3 agonist poly(I : C)25, 50, and 100 μM for 3 daysAttenuated inflammation through TLR3 pathwayYuanxin et al. (2020)
TNF-α-induced inflammation in HUVECs5, 10, 25, 50, 75, and 100 𝜇M for 24 hAttenuated endothelial dysfunction induced by TNF-α in a miR-21-dependent mannerDafeng et al. (2018)
TNF-α-induced inflammation50–200 μM for 24 hoursShowed anti-inflammatory activity via suppression of TNF-α-induced NF-κB activationNina et al. (2016)
LPS-induced cardiomyocyte inflammation25, 50, and 100 μM for 12 hExhibited anti-inflammatory activity in cardiomyocytes by reducing TNF-α and IL-6 levels via inhibition of the TLR4/NF-κB signaling pathwaysMeng-qiao et al. (2017)
LPS-induced inflammation in BV-2 cells10, 25, and 50 μM for 24 hDHM significantly reduced LPS-induced NO, IL-6, and TNF-α production and levels of iNOS and COX-2 in BV-2 cellsYafei et al. (2017)
LPS-induced inflammation in BV-2 cells20, 40, 80, or 100 mg/L for 48 hDHM exhibited the anti-inflammatory effect on LPS-induced BV-2 microglial cells through the TRL4/NF-κB signaling pathway and suppressed the levels of IL-6, IL-1β, and TNF-α, and inhibited the protein expression of iNOS and COX-2Nianshui et al. (2019)
TPA-induced acute inflammation/LPS-induced RAW 264.7 macrophage cellsTopical application2.3 and 4.6 mg per ear for 5 h/37.5, 75, 150, and 300 μM for 2 hShowed anti-inflammatory activity through suppressing the activation of NF-κB and the phosphorylation of p38 and JNK. Inhibited the levels of proinflammatory cytokines such as TNF-α, IL-1β, and IL-6 as well as increased the level of the anti-inflammatory cytokine IL-10 in LPS-treated mice. Reduced the protein expression of iNOS, TNF-α, and COX-2 in RAW cellsHou et al. (2015)
LPS-induced inflammationAmp was dissolved in dimethylsulfoxide (DMSO), and dilutions were made in DMEM0.5 μg/mL for 24 hReduced the phosphorylation levels of JAK2-STAT3 and STAT3 nuclear translocation and suppressed LPS-induced activation of the IκB/NF-κB inflammation pathway. Decreased the production of NO and PGE2 and suppressed the expression of iNOS and COX-2 and reduced proinflammatory cytokines such as IL-1β, IL-6, and TNF-αLeihua et al. (2017)
Ovalbumin- (OVA-) induced inflammation in C57BL/6 mouseAdministered intraperitoneally10 mg/kg BW for 14 daysDHM exhibited anti-inflammatory activity by reducing the levels of IL-4, IL-5, and IL-13 in the bronchoalveolar lavage fluid in an OVA-induced asthma modelBin et al. (2017)
Doxorubicin- (DOX-) induced cardiotoxicity rat model and DOX-induced H9C2 cellsAdministered intragastrically100 mg/kg/day or 200 mg/kg/day for 6 weeksDHM protected against DOX-induced cardiotoxicity by inhibiting NLRP3 inflammasome activation via stimulation of the SIRT1 pathway and suppressed IL-1β and IL-18 release, and upregulated SIRT1 protein levels in vivo and in vitroZhenzhu et al. (2020)
Cecal ligation and puncture- (CLP-) induced lung injury modelOrally administered50, 100, 150 mg/kg/day for 3 daysDHM treatment significantly inhibited the CLP-induced NLRP3 inflammasome pathway, IL-1β, and IL-18Yu-Chang et al. (2019)
LPS-mediated inflammationDiet supplemented with ampelopsin100 and 400 mg/kg BW for 28 daysShowed the anti-inflammatory activity through the reduction of activation of AKT and STAT3 phosphorylation and suppressed the DNA-binding activity of NF-κB. Decreased the proinflammatory mediators such as TNF-α, IL-1β, IL-6, and COX-2Xiang et al. (2017)
Double-blind clinical trialOrally administeredFour 150 mg capsules daily for 12 weeksExhibited anti-inflammatory activity by decreasing the serum levels of TNF-α, cytokeratin-18 fragment, and fibroblast growth factor 21Shihui et al. (2015)
APP/PS1 double transgenic miceInjected intraperitoneally1 mg/kg BW for 2 and 4 weeksDHM reduced activation of NLRP3 inflammasomes and reduced expression of NLRP3 inflammasome components and decreased IL-1β in transgenic miceJie et al. (2018)
Collagen-induced inflammationIntraperitoneally5, 25, and 50 mg/kg BW every other day for 5 weeksAlleviated inflammation in rats by attenuating IL-1β production via suppression of NF-κB signalingJing et al. (2019)
Lead- (Pb-) stimulated inflammationOral gavage administration125 and 250 mg/kg/BW for 3 monthsInhibited Pb-induced inflammation by regulating the AMPK, Aβ, TLR4, MyD88, p38, and GSK-3β pathwaysChan-Min et al. (2018)
Caerulin-induced inflammation in mice and BMDMsIntraperitoneallySingle dose of 25/100 mg/kgInhibited production of proinflammatory cytokines IL-1β, TNF-α, and IL-17 in mice and BMDMsRongrong et al. (2018)
LPS-induced inflammation in chickensFeeding in the diet0.025, 0.05, and 0.1 mg/kg for 14 daysDHM reduced inflammation by inhibiting NLRP3 inflammasome and TLR4/NF-κB signaling pathway in ileum in chickensYicong et al. (2020)
Mice transplanted with Colo-205 cellsIntragastric administration25, 50, and 100 mg/kg for 21 daysDecreased the levels of IL-1β, IL-6, IL-8, and TNF-α as well as reduced the expression of COX-2 and iNOSJun et al. 2019
LPS-induced inflammation in lung tissueOral gavage administration500 mg/kg BW for 4 daysExhibited anti-inflammatory effects by inhibiting the MAPK signaling pathway as well as TNF-α, IL-1𝛽, and IL-6 levelsBo et al. (2018)
A rat model of inflammation induced by collagenIntraperitoneally5, 25, and 50 mg/kg for 5 weeksExhibited anti-inflammatory effects by inhibiting NF-κB signaling pathwayJing et al. (2020)
Carrageenan-induced paw edema in rat and LPS-induced inflammation in RAW264.7 modelIntraperitoneal injection50, 100, and 250 mg/kg for 7 daysDHM significantly reduced rat paw edema induced by carrageenan and noticeably inhibited NO secretion, iNOS, and COX-2 protein expression and decreased p65 phosphorylation via suppression of IKK-β activity and IKK-α/β phosphorylationRui et al. (2016)
Complete Freund’s Adjuvant- (CFA-) induced inflammation in rheumatoid arthritis modelGavage administration20 and 50 mg/kg per day for 25 daysDHM inhibited the expressions of proinflammatory cytokines IL-1β, IL-6, TNF-α, and COX-2 via activating the Nrf2 pathwayJianguo et al. (2018)
Streptozotocin-induced diabetic inflammationIntragastrically given100 mg/kg/day for 14 weeksDHM reduced the levels of proinflammatory factors such as IL-6 and TNF-αBin et al. (2017a)
Alcohol-induced inflammation in C57BL/6 miceIncorporated in the diet75 and 150 mg/kg BW for 6 weeksDHM considerably alleviated the hepatic IL-1β and IL-6 levelsPing et al. (2017)