Scutellaria baicalensis is a traditional Chinese medicinal material that has attracted much attention for its anticancer potential due to its rich content of bioactive flavonoids such as baicalein, baicalin, and wogonin. This review synthesizes the available evidence and elucidates the multiple mechanisms by which these compounds exert their antitumor effects, including induction of apoptosis, cell cycle arrest, epigenetic regulation, metabolic reprogramming, and tumor microenvironment remodeling. Flavonoids in Scutellaria baicalensis target key oncogenic pathways, thereby inhibiting cancer cell proliferation, metastasis, and angiogenesis while enhancing immune surveillance. Notably, they are able to reverse drug resistance by inhibiting efflux transporters, restoring chemosensitivity, and impairing DNA repair mechanisms, highlighting their therapeutic versatility. Preclinical studies have highlighted the synergistic effects of Scutellaria baicalensis derivatives in combination with conventional chemotherapy or radiotherapy. Scutellaria baicalensis provides a holistic approach to address tumor heterogeneity and therapeutic resistance by combining traditional phytomedicine with modern pharmacological strategies, making it a valuable adjunct in next-generation cancer therapy.
1. Crucitta S, Cucchiara F, Mathijssen R, Mateo J, Jager A, Joosse A, et al. Treatment-driven tumour heterogeneity and drug resistance: Lessons from solid tumours. Cancer treatment reviews. 2022;104:102340.
2. Phung CD, Le TG, Nguyen VH, Vu TT, Nguyen HQ, Kim JO, et al. PEGylated-paclitaxel and dihydroartemisinin nanoparticles for simultaneously delivering paclitaxel and dihydroartemisinin to colorectal cancer. Pharmaceutical Research. 2020;37:1-11.
3. Zhao T, Tang H, Xie L, Zheng Y, Ma Z, Sun Q, et al. Scutellaria baicalensis Georgi.(Lamiaceae): a review of its traditional uses, botany, phytochemistry, pharmacology and toxicology. Journal of Pharmacy and Pharmacology. 2019;71(9):1353-69.
4. Pei T, Yan M, Huang Y, Wei Y, Martin C, Zhao Q. Specific flavonoids and their biosynthetic pathway in Scutellaria baicalensis. Frontiers in plant science. 2022;13:866282.
5. Wen Y, Wang Y, Zhao C, Zhao B, Wang J. The pharmacological efficacy of baicalin in inflammatory diseases. International journal of molecular sciences. 2023;24(11):9317.
6. Rahmani AH, Almatroudi A, Khan AA, Babiker AY, Alanezi M, Allemailem KS. The multifaceted role of baicalein in cancer management through modulation of cell signalling pathways. Molecules. 2022;27(22):8023.
7. Chan EWC, Wong SK, Tangah J, Inoue T, Chan HT. A synopsis on flavonoids from the roots of Scutellaria baicalensis with some insights on baicalein and its anti-cancer properties. Journal of Chinese Pharmaceutical Sciences. 2019;28(4):217.
8. Chen M, Ren X, Sun S, Wang X, Xu X, Li X, et al. Structure, biological activities and metabolism of flavonoid glucuronides. Mini Reviews in Medicinal Chemistry. 2022;22(2):322-54.
9. Hu Z, Guan Y, Hu W, Xu Z, Ishfaq M. An overview of pharmacological activities of baicalin and its aglycone baicalein: New insights into molecular mechanisms and signaling pathways. Iranian Journal of Basic Medical Sciences. 2022;25(1):14.
10. Tang S, Wang B, Liu X, Xi W, Yue Y, Tan X, et al. Structural insights and biological activities of flavonoids: Implications for novel applications. Food Frontiers. 2025;6(1):218-47.
11. Morshed AH, Paul S, Hossain A, Basak T, Hossain MS, Hasan MM, et al. Baicalein as promising anticancer agent: a comprehensive analysis on molecular mechanisms and therapeutic perspectives. Cancers. 2023;15(7):2128.
12. Banik K, Khatoon E, Harsha C, Rana V, Parama D, Thakur KK, et al. Wogonin and its analogs for the prevention and treatment of cancer: A systematic review. Phytotherapy Research. 2022;36(5):1854-83.
13. Olennikov D, Chirikova N. New Flavonoids of the Genus Scutellaria. II. Baicalein and Wogonin Glycosides from S. baicalensis. Chemistry of Natural Compounds. 2024;60(2):229-34.
14. Xiang L, Gao Y, Chen S, Sun J, Wu J, Meng X. Therapeutic potential of Scutellaria baicalensis Georgi in lung cancer therapy. Phytomedicine. 2022;95:153727.
15. Wang Y, Chen S, Sun S, Liu G, Chen L, Xia Y, et al. Wogonin induces apoptosis and reverses sunitinib resistance of renal cell carcinoma cells via inhibiting CDK4-RB pathway. Frontiers in Pharmacology. 2020;11:1152.
16. Saraei R, Marofi F, Naimi A, Talebi M, Ghaebi M, Javan N, et al. Leukemia therapy by flavonoids: Future and involved mechanisms. Journal of cellular physiology. 2019;234(6):8203-20.
17. Wei Q, Zhang Y-h. Flavonoids with anti-angiogenesis function in cancer. Molecules. 2024;29(7):1570.
18. Wang L, Ni B, Wang J, Zhou J, Wang J, Jiang J, et al. Research Progress of Scutellaria baicalensis in the Treatment of Gastrointestinal Cancer. Integrative Cancer Therapies. 2024;23:15347354241302049.
19. Pourhanifeh MH, Farrokhi-Kebria H, Mostanadi P, Farkhondeh T, Samarghandian S. Anticancer Properties of Baicalin against Breast Cancer and other Gynecological Cancers: Therapeutic Opportunities based on Underlying Mechanisms. Current Molecular Pharmacology. 2024;17(1):e18761429263063.
20. Li J, Yan L, Luo J, Tong L, Gao Y, Feng W, et al. Baicalein suppresses growth of non-small cell lung carcinoma by targeting MAP4K3. Biomedicine & Pharmacotherapy. 2021;133:110965.
21. Yang B, Bai H, Sa Y, Zhu P, Liu P. Inhibiting EMT, stemness and cell cycle involved in baicalin-induced growth inhibition and apoptosis in colorectal cancer cells. Journal of Cancer. 2020;11(8):2303.
22. Zhang Q, Guo S, Ge H, Wang H. The protective role of baicalin regulation of autophagy in cancers. Cytotechnology. 2025;77(1):33.
23. Ke P-Y, Chang C-W, Hsiao Y-C. Baicalein activates parkin-dependent mitophagy through NDP52 and OPTN. Cells. 2022;11(7):1132.
24. Guo J, Jin G, Hu Y, Zhao Z, Nan F, Hu X, et al. Wogonin restrains the malignant progression of lung cancer through modulating MMP1 and PI3K/AKT signaling pathway. Protein and Peptide Letters. 2023;30(1):25-34.
25. Wang H, Jiang Y, Zhu M, Li H, Chen H, Wang H, et al. LW-213, a derivative of wogonin, triggers reticulophagy-mediated cell death in NSCLC via lysosomal damage combined with NPC1 inhibition. Phytomedicine. 2024;134:155958.
26. Lee J, Roh J-L. Targeting Nrf2 for ferroptosis-based therapy: Implications for overcoming ferroptosis evasion and therapy resistance in cancer. Biochimica et Biophysica Acta (BBA)-Molecular Basis of Disease. 2023;1869(7):166788.
27. Sun Q, Liu Q, Zhou X, Wang X, Li H, Zhang W, et al. Flavonoids regulate tumor-associated macrophages–from structure-activity relationship to clinical potential. Pharmacological Research. 2022;184:106419.
28. Tian-Tian C, Sha-Li D, Shi-Jun W, Li W, Lu Y. Dahuang Zhechong pills inhibit liver cancer growth in a mouse model by reversing Treg/Th1 balance. Chinese Journal of Natural Medicines. 2022;20(2):102-10.
29. Huang D-N, Wang S, Sooranna SR, Miao J-H. The efficacy of natural bioactive compounds for the treatment of nasopharyngeal carcinoma. Mini Reviews in Medicinal Chemistry. 2021;21(13):1679-91.
30. He G, Huang X, Dong Y, Chen K, He X, Pan M, et al. Preliminary investigation on the mechanism of baicalein regulating the effects of Nischarin on invasion and apoptosis of human breast cancer cells MCF-7 through Wnt3α/β-catenin pathway. International Immunopharmacology. 2024;143:113262.
31. Chen Y, Chen L, Hong D, Chen Z, Zhang J, Fu L, et al. Baicalein inhibits fibronectin-induced epithelial–mesenchymal transition by decreasing activation and upregulation of calpain-2. Cell Death & Disease. 2019;10(5):341.
32. Yan C, Wang G. Advances in research on flavonoids in tumor immunotherapy. Molecular Medicine Reports. 2025;31(6):150.
33. Song L, Zhu S, Liu C, Zhang Q, Liang X. Baicalin triggers apoptosis, inhibits migration, and enhances anti‐tumor immunity in colorectal cancer via TLR4/NF‐κB signaling pathway. Journal of food biochemistry. 2022;46(3):e13703.
34. Cui Y, Liu J, Wang X, Wu Y, Chang Y, Hu X, et al. Baicalin attenuates the immune escape of oral squamous cell carcinoma by reducing lactate accumulation in tumor microenvironment. Journal of Advanced Research. 2025.
35. Yu X, Li H, Hu P, Qing Y, Wang X, Zhu M, et al. Natural HDAC‐1/8 inhibitor baicalein exerts therapeutic effect in CBF‐AML. Clinical and translational medicine. 2020;10(4):e154.
36. Qi J, Li J, Bie B, Shi M, Zhu M, Tian J, et al. Baicalein Attenuates Hepatocellular Carcinoma Cell Survival and Induces Apoptosis Through the miR‑3178/HDAC10 pathway. 2021.
37. Dong Y, He G, Chen K, He X, Pan M, Huang X, et al. Baicalein promotes KDM4E to induce BICD1 and inhibit triple‐negative breast cancer progression by blocking PAR1 signaling. Molecular Carcinogenesis. 2024;63(7):1288-302.
38. Yang D, Guo Q, Liang Y, Zhao Y, Tian X, Ye Y, et al. Wogonin induces cellular senescence in breast cancer via suppressing TXNRD2 expression. Archives of Toxicology. 2020;94:3433-47.
39. Jiang H, Yao Q, An Y, Fan L, Wang J, Li H. Baicalin suppresses the progression of Type 2 diabetes-induced liver tumor through regulating METTL3/m6A/HKDC1 axis and downstream p-JAK2/STAT1/clevaged Capase3 pathway. Phytomedicine. 2022;94:153823.
40. Yang SY, Jhang JS, Huang WL, Tsai LH, Tsai MC, Chan CP, et al. Wogonin Inhibits Ovarian Cancer by Activating the AMPK‐TET2‐5hmC Axis. Molecular Carcinogenesis. 2025;64(3):440-9.
41. Huang L, Peng B, Nayak Y, Wang C, Si F, Liu X, et al. Baicalein and baicalin promote melanoma apoptosis and senescence via metabolic inhibition. Frontiers in cell and developmental biology. 2020;8:836.
42. Li J, Zhang D, Wang S, Yu P, Sun J, Zhang Y, et al. Baicalein induces apoptosis by inhibiting the glutamine-mTOR metabolic pathway in lung cancer. Journal of Advanced Research. 2025;68:341-57.
43. Sui X, Han X, Chen P, Wu Q, Feng J, Duan T, et al. Baicalin induces apoptosis and suppresses the cell cycle progression of lung cancer cells through downregulating Akt/mTOR signaling pathway. Frontiers in Molecular Biosciences. 2021;7:602282.
44. Sun Y, Guo W, Guo Y, Lin Z, Wang D, Guo Q, et al. 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 and chemical toxicology. 2022;169:113450.
45. Li L, Ji Y, Zhang L, Cai H, Ji Z, Gu L, et al. Wogonin inhibits the growth of HT144 melanoma via regulating hedgehog signaling-mediated inflammation and glycolysis. International Immunopharmacology. 2021;101:108222.
46. Wang X, Chang Y, Gao M, Zhang F. Wogonoside Attenuates Cutaneous Squamous Cell Carcinoma by Reducing Epithelial–Mesenchymal Transition/Invasion and Cancer Stem-Like Cell Property. OncoTargets and therapy. 2020:10097-109.
47. Chen Y, Zhang J, Zhang M, Song Y, Zhang Y, Fan S, et al. Baicalein resensitizes tamoxifen‐resistant breast cancer cells by reducing aerobic glycolysis and reversing mitochondrial dysfunction via inhibition of hypoxia‐inducible factor‐1α. Clinical and Translational Medicine. 2021;11(11):e577.
48. Zhang Y, Zhang M, Hu G, Zhang Z, Song R. Elevated system exposures of baicalin after combinatory oral administration of rhein and baicalin: Mainly related to breast cancer resistance protein (ABCG2), not UDP-glucuronosyltransferases. Journal of Ethnopharmacology. 2020;250:112528.
49. Liu W, Wang Y, Xia L, Li J. Research progress of plant-derived natural products against drug-resistant cancer. Nutrients. 2024;16(6):797.
50. Mazurakova A, Koklesova L, Csizmár SH, Samec M, Brockmueller A, Šudomová M, et al. Significance of flavonoids targeting PI3K/Akt/HIF-1α signaling pathway in therapy-resistant cancer cells–a potential contribution to the predictive, preventive, and personalized medicine. Journal of Advanced Research. 2024;55:103-18.
51. Xu X, Ji S, Chen Y, Xia S, Li Y, Chen L, et al. Induction of DNMT1-dependent demethylation of SHP-1 by the natural flavonoid compound Baicalein overcame Imatinib-resistance in CML CD34+ cells. Cell Communication and Signaling. 2023;21(1):47.
52. Zhang T, Liu M, Liu Q, Xiao GG. Wogonin increases gemcitabine sensitivity in pancreatic cancer by inhibiting Akt pathway. Frontiers in Pharmacology. 2022;13:1068855.
53. Li C, Wang Y, Zhang W, Yang X, Wang Y, Hou G, et al. The antitumor mechanisms of glabridin and drug delivery strategies for enhancing its bioavailability. Frontiers in Oncology. 2024;14:1506588.
54. Butt G, Ozbey U, Attar R, Youssef L, Farooqi AA. Regulation of cell signaling pathways by Wogonin in different cancers: Mechanistic review. Cellular and Molecular Biology. 2021;67(2):1-7.
55. Li P, Hu J, Shi B, Tie J. Baicalein enhanced cisplatin sensitivity of gastric cancer cells by inducing cell apoptosis and autophagy via Akt/mTOR and Nrf2/Keap 1 pathway. Biochemical and Biophysical Research Communications. 2020;531(3):320-7.
56. Liu H, Liu H, Zhou Z, Chung J, Zhang G, Chang J, et al. Scutellaria baicalensis enhances 5-fluorouracil-based chemotherapy via inhibition of proliferative signaling pathways. Cell Communication and Signaling. 2023;21(1):147.
57. Limbach KE, Wen W, Xing Q, Yan J, Yim JH. Baicalein activates 5’adenosine monophosphate-activated protein kinase, inhibits the mammalian target of rapamycin, and exhibits antiproliferative effects in pancreatic neuroendocrine tumors in vitro and in vivo. Surgery. 2023;173(1):12-8.
58. Zhou H, Hu D, Zhao X, Qin S, Nong Q, Tian Y, et al. An optimal combination of four active components in Huangqin decoction for the synergistic sensitization of irinotecan against colorectal cancer. Chinese Medicine. 2024;19(1):94.
59. Zieniuk B, Uğur Ş. The Therapeutic Potential of Baicalin and Baicalein in Breast Cancer: A Systematic Review of Mechanisms and Efficacy. Current Issues in Molecular Biology. 2025;47(3):181.
60. Li M, Duan F, Pan Z, Liu X, Lu W, Liang C, et al. Astragalus polysaccharide promotes doxorubicin-induced apoptosis by reducing O-GlcNAcylation in hepatocellular carcinoma. Cells. 2023;12(6):866.
61. Hao Q, Wu Y, Vadgama JV, Wang P. Phytochemicals in inhibition of prostate cancer: evidence from molecular mechanisms studies. Biomolecules. 2022;12(9):1306.
62. Qiao K, Mo J, Pan Y, Zhang S, Jiang C, Lyu M, et al. Gold nanoparticle doped Cuhemin nanosheets with a remodeling tumor microenvironment for multiple radiotherapy sensitization. Journal of Materials Chemistry B. 2023;11(18):4095-101.
63. Xu X, Qian Y, Zhu S, Tian H, Zhai P, Zhu S, et al. Wogonin inhibits radiation-induced DNA damage repair in hepatocellular carcinoma cells by upregulating p21. The Korean journal of physiology & pharmacology: official journal of the Korean Physiological Society and the Korean Society of Pharmacology.
