Chinese native medicine Scutellaria baicalensis Georgi, also referred to as Chinese skullcap or Huang-Qin, is frequently used to treat cancer, viral infections, and seizures. This plant’s abundance of flavones (wogonoside) and their related aglycones (wogonin) is responsible for many of its pharmacologic effects. A significant ingredient in S. baicalensis that has been the subject of the most research is wogonin. Numerous preclinical investigations revealed that wogonin suppresses tumor growth by cell cycle arrest, stimulating cell death and preventing metastasis. This review focuses on a complete overview of published reports that suggest chemopreventive action of wogonin and the mechanistic insights behind these neoplastic activities. It also emphasizes the synergistic improvements made by wogonin in chemoprevention. The factual data in this mini-review stimulate additional research on chemistry and toxicological profile of wogonin to confirm its safety issues. This review will encourage researchers to generalize the merits of wogonin to be used as potential compound for cancer treatment.
SungHFerlayJSiegelRLLaversanneMSoerjomataramIJemalABrayF. Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries.CA Cancer J Clin2021;71:209–49
2.
ThunMJDeLanceyJOCenterMMJemalAWardEM. The global burden of cancer: priorities for prevention.Carcinogenesis2010;31:100–10
3.
SrivastavaSDubeyAKMadaanRBalaRGuptaYDhimanBSKumarS. Emergence of nutrigenomics and dietary components as a complementary therapy in cancer prevention.Environ Sci Pollut Res Int2022;29:89853–73
4.
Castro-EspinCAgudoA. The role of diet in prognosis among cancer survivors: a systematic review and meta-analysis of dietary patterns and diet interventions.Nutrients2022;14:348
5.
GanesanKDuBChenJ. Effects and mechanisms of dietary bioactive compounds on breast cancer prevention.Pharmacol Res2022;178:105974
6.
BanikKKhatoonEHarshaCRanaVParamaDThakurKKBishayeeAKunnumakkaraAB. Wogonin and its analogs for the prevention and treatment of cancer: a systematic review.Phytother Res2022;36:1854–83
7.
WangJGeRQiuXXuXWeiLLiZBianJ. Discovery and synthesis of novel Wogonin derivatives with potent antitumor activity in vitro.Eur J Med Chem2017;140:421–34
8.
ZhaoZNianMQiaoHYangXWuSZhengX. Review of bioactivity and structure-activity relationship on baicalein (5,6,7-trihydroxyflavone) and wogonin (5,7-dihydroxy-8-methoxyflavone) derivatives: structural modifications inspired from flavonoids in Scutellaria baicalensis.Eur J Med Chem2022;243:114733
9.
GharariZHanachiPWalkerTR. Green synthesized Ag-nanoparticles using Scutellaria multicaulis stem extract and their selective cytotoxicity against breast cancer.Anal Biochem2022;653:114786
10.
Sharifi-RadJHerrera-BravoJSalazarLAShaheenSAbdulmajid AyatollahiSKobarfardFImranMImranACustódioLDolores LópezMSchoebitzMMartorellMKumarMAnsar Rasul SuleriaHChoWC. The therapeutic potential of wogonin observed in preclinical studies.Evid Based Complement Alternat Med2021;2021:9935451
11.
HuangBLiuHHuangDMaoXHuXJiangCPuMZhangGZengX. Apoptosis induction and imaging of cadmium-telluride quantum dots with wogonin in multidrug-resistant leukemia K562/A02 cell.J Nanosci Nanotechnol2016;16:2499–503
12.
QiXXuHZhangPChenGChenZFangCLinL. Investigating the mechanism of Scutellariae barbata herba in the treatment of colorectal cancer by network pharmacology and molecular docking.Evid Based Complement Alternat Med2021;2021:3905367
13.
TanHLiXYangWHKangY. A flavone, Wogonin from Scutellaria baicalensis inhibits the proliferation of human colorectal cancer cells by inducing of autophagy, apoptosis and G2/M cell cycle arrest via modulating the PI3K/AKT and STAT3 signalling pathways.J BUON2019;24:1143–9
14.
HeLLuNDaiQZhaoYZhaoLWangHLiZYouQGuoQ. Wogonin induced G1 cell cycle arrest by regulating Wnt/β-catenin signaling pathway and inactivating CDK8 in human colorectal cancer carcinoma cells.Toxicology2013;312:36–47
15.
ButtGOzbeyUMalikDAttarRYoussefLFarooqiAA. Regulation of cell signaling pathways by Wogonin in different cancers: mechanistic review.Cell Mol Biol2021;67:1–7
16.
ShaoWZhangCLiKLuZZhaoZGaoKLvC. Wogonin inhibits inflammation and apoptosis through STAT3 signal pathway to promote the recovery of spinal cord injury.Brain Res2022;1782:147843
17.
WuKTengMZhouWLuFZhouYZengJYangJLiuXZhangYDingYShenW. Wogonin induces cell cycle arrest and apoptosis of hepatocellular carcinoma cells by activating hippo signaling.Anticancer Agents Med Chem2022;22:1551–60
18.
ZhaoQChangWChenRLiuY. Anti-proliferative effect of wogonin on ovary cancer cells involves activation of apoptosis and cell cycle arrest.Med Sci Monit2019;25:8465–71
19.
TaiMCTsangSYChangLYFXueH. Therapeutic potential of wogonin: a naturally occurring flavonoid.CNS Drug Rev2005;11:141–50
20.
HassaninMTolbaMTadrosMElmazarMSingabAN. Wogonin a promising component of Scutellaria baicalensis: a review on its chemistry, pharmacokinetics and biological activities.Arch Pharm Sci Ain Shams Univ2019;3:170–9
21.
LiTWengTWangJWeiZZhaoLLiZ. A practical and efficient approach to the preparation of bioactive natural product wogonin.Org Process Res Dev2017;21:171–6
22.
QiQPengJLiuWYouQYangYLuNWangGGuoQ. Toxicological studies of wogonin in experimental animals.Phytother Res2009;23:417–22
23.
TalbiAZhaoDLiuQLiJFanAYangWHanXChenX. Pharmacokinetics, tissue distribution, excretion and plasma protein binding studies of wogonin in rats.Molecules2014;19:5538–49
24.
JangJHyunPKParkH. Structure and antiinflammatory activity relationships of wogonin derivatives.Arch Pharm Res2005;28:877–84
25.
SunYGuoWGuoYLinZWangDGuoQZhouY. Apoptosis induction in human prostate cancer cells related to the fatty acid metabolism by wogonin-mediated regulation of the AKT-SREBP1-FASN signaling network.Food Chem Toxicol2022;169:113450
26.
GuoJHuYJinGZhaoZNanFHuXHuYHanQ. Wogonin restrains the malignant progression of lung cancer through modulating MMP1 and PI3K/AKT signaling pathway.Protein Pept Lett2023;30:25–34
27.
WangCCuiC. Inhibition of lung cancer proliferation by wogonin is associated with activation of apoptosis and generation of reactive oxygen species.Balkan Med J2019;37:29–33
28.
FengQWangHPangJJiLHanJWangYQiXLiuZLuL. Prevention of wogonin on colorectal cancer tumorigenesis by regulating p53 nuclear translocation.Front Pharmacol2018;9:1356
29.
ZhaoYZhangLWuYDaiQZhouYLiZYangLGuoQLuN. Selective anti-tumor activity of wogonin targeting the Warburg effect through stablizing p53.Pharmacol Res2018;135:49–59
30.
QingYWangXWangHHuPLiHYuXZhuMWangZZhuYXuJGuoQHuiH. Pharmacologic targeting of the P-TEFb complex as a therapeutic strategy for chronic myeloid leukemia.Cell Commun Signal2021;19:83
31.
HuangKFZhangGDHuangYQDiaoY. Wogonin induces apoptosis and down-regulates survivin in human breast cancer MCF-7 cells by modulating PI3K-AKT pathway.Int Immunopharmacol2012;12:334–41
32.
HuCXuMQinRChenWXuX. Wogonin induces apoptosis and endoplasmic reticulum stress in HL-60 leukemia cells through inhibition of the PI3K-AKT signaling pathway.Oncol Rep2015;33:3146–54
33.
HongMAlmutairiMMLiSLiJ. Wogonin inhibits cell cycle progression by activating the glycogen synthase kinase-3 beta in hepatocellular carcinoma.Phytomedicine2020;68:153174
34.
WangYZhangYQianCCaiMLiYLiZYouQWangQHuRGuoQ. GSK3β/β-catenin signaling is correlated with the differentiation of glioma cells induced by wogonin.Toxicol Lett2013;222:212–23
35.
RajabiMMousaSA. The role of angiogenesis in cancer treatment.Biomedicines2017;5:34
36.
LuganoRRamachandranMDimbergA. Tumor angiogenesis: causes, consequences, challenges and opportunities.Cell Mol Life Sci2020;77:1745–70
37.
KimuraYSumiyoshiM. Anti-tumor and anti-metastatic actions of wogonin isolated from Scutellaria baicalensis roots through anti-lymphangiogenesis.Phytomedicine2013;20:328–36
38.
DongPZhangYGuJWuWLiMYangJZhangLLuJMuJChenLLiSWangJLiuY. Wogonin, an active ingredient of Chinese herb medicine Scutellaria baicalensis, inhibits the mobility and invasion of human gallbladder carcinoma GBC-SD cells by inducing the expression of maspin.J Ethnopharmacol2011;137:1373–80
39.
HuynhDLSharmaNKumar SinghASingh SodhiSZhangJJMongreRKGhoshMKimNHo ParkYKee JeongD. Anti-tumor activity of wogonin, an extract from Scutellaria baicalensis, through regulating different signaling pathways.Chin J Nat Med2017;15:15–40
40.
HongMChengHSongLWangWWangQXuDXingW. Wogonin suppresses the activity of matrix metalloproteinase-9 and inhibits migration and invasion in human hepatocellular carcinoma.Molecules2018;23:3020384
41.
YouWDiAZhangLZhaoG. Effects of wogonin on the growth and metastasis of colon cancer through the Hippo signaling pathway.Bioengineered2022;13:2586–97
42.
CoussensLMWerbZ. Inflammation and cancer.Nature2002;420:860–67
43.
LiLJiYZhangLCaiHJiZGuLYangS. Wogonin inhibits the growth of HT144 melanoma via regulating hedgehog signaling-mediated inflammation and glycolysis.Int Immunopharmacol2021;101:108222
44.
ChiYSLimHParkHKimHP. Effects of wogonin, a plant flavone from Scutellaria radix, on skin inflammation: in vivo regulation of inflammation-associated gene expression.Biochem Pharmacol2003;66:1271–8
45.
ChenLGHungLYTsaiKWPanYSTsaiYDLiYZLiuYW. Wogonin, a bioactive flavonoid in herbal tea, inhibits inflammatory cyclooxygenase-2 gene expression in human lung epithelial cancer cells.Mol Nutr Food Res2008;52:1349–57
46.
YaoJZhaoLZhaoQZhaoYSunYZhangYMiaoHYouQDHuRGuoQL. NF-κB and Nrf2 signaling pathways contribute to wogonin-mediated inhibition of inflammation-associated colorectal carcinogenesis.Cell Death Dis2014;5:e1283
47.
BadawyAMEl-NagaRNGadAMTadrosMGFawzyHM. Wogonin pre-treatment attenuates cisplatin-induced nephrotoxicity in rats: impact on PPAR-γ, inflammation, apoptosis and Wnt/β-catenin pathway.Chem Biol Interact2019;308:137–46
48.
HuynhDLNgauTHNguyenNHTranGBNguyenCT. Potential therapeutic and pharmacological effects of Wogonin: an updated review.Mol Biol Rep2020;47:9779–89
49.
Sharifi-RadJHerrera-BravoJSalazarLAShaheenSAyatollahiSAKobarfardFImranMImranACustódioLLópezMDSchoebitzMMartorellMKumarMSuleriaHARChoWC. The therapeutic potential of wogonin observed in preclinical studies.Evid Based Complement Alternat Med2021;2021:9935451
50.
WuJYChenLGHuCWChiuKCLinWHoPCWengBBC. Immunotoxicity and anti-inflammatory characterizations of prenylated flavonoids – the lipophilic 7-O-terpenylated wogonin.Life2022;12:2116
51.
KumarRHarilalSParambiDGTNarayananSEUddinMSMarathakamAJoseJMathewGEMathewB. Fascinating chemopreventive story of wogonin: a chance to hit on the head in cancer treatment.Curr Pharm Des2021;27:467–78
52.
TuliHSKashyapDSharmaAKSandhuSS. Molecular aspects of melatonin (MLT)-mediated therapeutic effects.Life Sci2015;135:147–57
53.
AggarwalVTuliHSKaurJAggarwalDParasharGParasharNCKulkarniSKaurGSakKKumarMAhnKS. Garcinol exhibits anti-neoplastic effects by targeting diverse oncogenic factors in tumor cells.Biomedicines2020;8:103
54.
HeFWangQZhengXLYanJQYangLSunHHuLNLinYWangX. Wogonin potentiates cisplatin-induced cancer cell apoptosis through accumulation of intracellular reactive oxygen species.Oncol Rep2012;28:601–5
55.
LeeEEnomotoRSuzukiCOhnoMOhashiTMiyauchiATanimotoEMaedaKHiranoHYokoiTSugaharaC. Wogonin, a plant flavone, potentiates etoposide-induced apoptosis in cancer cells.Ann N Y Acad Sci2007;1095:521–6
56.
EnomotoRKoshibaCSuzukiCLeeE. Wogonin potentiates the antitumor action of etoposide and ameliorates its adverse effects.Cancer Chemother Pharmacol2011;67:1063–72
57.
LeeEEnomotoRKoshibaCHiranoH. Inhibition of P-glycoprotein by wogonin is involved with the potentiation of etoposide-induced apoptosis in cancer cells.Ann N Y Acad Sci2009;1171:132–6
58.
PolierGGiaisiMKöhlerRMüllerWWLutzCBussECKrammerPHLi-WeberM. Targeting CDK9 by wogonin and related natural flavones potentiates the anti-cancer efficacy of the Bcl-2 family inhibitor ABT-263.Int J Cancer2015;136:688–98
59.
WangTGaoJYuJShenL. Synergistic inhibitory effect of wogonin and low-dose paclitaxel on gastric cancer cells and tumor xenografts.Chin J Cancer Res2013;25:505–13
60.
DingKJiangWJiaHLeiM. Synergistically anti-multiple myeloma effects: flavonoid, non-flavonoid polyphenols, and bortezomib.Biomolecules2022;12:1647
61.
YangLWangQLiDZhouYZhengXSunHYanJZhangLLinYWangX. Wogonin enhances antitumor activity of tumor necrosis factor-related apoptosis-inducing ligand in vivo through ROS-mediated downregulation of cFLIPL and IAP proteins.Apoptosis2013;18:618–26
62.
RushworthSAMicheauO. Molecular crosstalk between TRAIL and natural antioxidants in the treatment of cancer.Br J Pharmacol2009;157:1186–8
63.
LeeDHRheeJGLeeYJ. Reactive oxygen species up-regulate p53 and Puma; a possible mechanism for apoptosis during combined treatment with TRAIL and wogonin.Br J Pharmacol2009;157:1189–202
64.
GuoYYangLGuoWWeiLZhouY. FV-429 enhances the efficacy of paclitaxel in NSCLC by reprogramming HIF-1α-modulated FattyAcid metabolism.Chem Biol Interact2021;350:109702
65.
GuoQLuLLiaoYWangXZhangYLiuYHuangSSunHLiZZhaoL. Influence of c-Src on hypoxic resistance to paclitaxel in human ovarian cancer cells and reversal of FV-429.Cell Death Dis2018;9:e3178
66.
ZhaoLShaYYZhaoQYaoJZhuBBLuZJYouQDGuoQL. Enhanced 5-fluorouracil cytotoxicity in high COX-2 expressing hepatocellular carcinoma cells by wogonin via the PI3K/Akt pathway.Biochem Cell Biol2013;91:221–9
67.
HuangSTWangCYYangRCChuCJWuHTPangJHS. Wogonin, an active compound in Scutellaria baicalensis, induces apoptosis and reduces telomerase activity in the HL-60 leukemia cells.Phytomedicine2010;1:47–54
68.
TsaiCFYehWLHuangSMTanTWLuDY. Wogonin induces reactive oxygen species production and cell apoptosis in human glioma cancer cells.Int J Mol Sci2012;13:9877–92
69.
GeWYinQXianH. Wogonin induced mitochondrial dysfunction and endoplasmic reticulum stress in human malignant neuroblastoma cells via IRE1α-dependent pathway.J Mol Neurosci2015;56:652–62
70.
WangSJZhaoJKRenSSunWWZhangWJZhangJN. Wogonin affects proliferation and the energy metabolism of SGC-7901 and A549 cells.Exp Ther Med2019;17:911–8
71.
YangDGuoQLiangYZhaoYTianXYeYTianJWuTLuN. Wogonin induces cellular senescence in breast cancer via suppressing TXNRD2 expression.Arch Toxicol2020;94:3433–47
72.
GoJHWeiJDParkJIAhnKSKimJH. Wogonin suppresses the LPS-enhanced invasiveness of MDA-MB-231 breast cancer cells by inhibiting the 5-LO/BLT2 cascade.Int J Mol Med2018;42:1899–1908
73.
YuJSKimAK. Wogonin induces apoptosis by activation of ERK and p38 MAPKs signaling pathways and generation of reactive oxygen species in human breast cancer cells.Mol Cells2011;31:327–35
74.
ZhangTLiuMLiuQXiaoGG. Wogonin increases gemcitabine sensitivity in pancreatic cancer by inhibiting Akt pathway.Front Pharmacol2022;13:1068855
75.
XingFSunCLuoNHeYChenMDingSLiuCFengLChengZ. Wogonin increases cisplatin sensitivity in ovarian cancer cells through inhibition of the phosphatidylinositol 3-kinase (PI3K)/Akt pathway.Med Sci Monit2019;25:6007–14
76.
RuibinJBoJDanyingWChihongZJianguoFLinhuiG. Therapy effects of wogonin on ovarian cancer cells.Biomed Res Int2017;2017:9381513
