Evidence and possible mechanism of Scutellaria baicalensis and its bioactive compounds for hepatocellular carcinoma treatment

References

• Maennich D, Marshall L. Hepatocellular carcinoma. Nat Rev Dis Primers. 2021;7(1):1–15.
   PubMed Web of Science ®Google Scholar
• Cao MM, Li H, Sun DQ, et al. Global epidemiological status of liver cancer, 2020. Chine J Cancer Prevent Treat. 2022;29(05):322–15.
   Google Scholar
• Ding X, Cheng YS. Chinese expert consensus on multidisciplinary comprehensive treatment of liver cancer. J Clin Hepatol. 2021;37(02):278–285.
   Google Scholar
• G.O.o.t.N.H. Commission, guidelines for diagnosis and treatment of primary liver cancer. J Clin Hepatol. 2022;38(2):288–303. (2022 edition)
   Google Scholar
• Chen W, Zheng R, Baade PD, et al. Cancer statistics in China, 2015. CA Cancer J Clin. 2016;66(2):115–132. doi: 10.3322/caac.21338.
   PubMed Web of Science ®Google Scholar
• Xiang L, Gao Y, Chen S, et al. Therapeutic potential of SCUTELLARIA baicalensis Georgi in lung cancer therapy. Phytomedicine. 2022;95:153727. doi: 10.1016/j.phymed.2021.153727.
   PubMed Web of Science ®Google Scholar
• Li C, Zhou L, Lin G, et al. Contents of major bioactive flavones in proprietary traditional Chinese medicine products and reference herb of Radix Scutellariae. J Pharm Biomed Anal. 2009;50(3):298–306. doi: 10.1016/j.jpba.2009.04.028.
   PubMed Web of Science ®Google Scholar
• Li-Weber M. New therapeutic aspects of flavones: the anticancer properties of Scutellaria and its main active constituents Wogonin, Baicalein and Baicalin. Cancer Treat Rev. 2009;35(1):57–68. doi: 10.1016/j.ctrv.2008.09.005.
   PubMed Web of Science ®Google Scholar
• Gu YQ, Chen XF, Wang R, et al. Comparative two-dimensional HepG2 and L02/ cell membrane chromatography/ C18/ time-of-flight mass spectrometry for screening selective anti-hepatoma components from Scutellariae Radix. J Pharm Biomed Anal. 2019;164(2019):550–556. doi: 10.1016/j.jpba.2018.10.028.
   PubMedGoogle Scholar
• Li Y, Li Y, Zhang J, et al. Current perspective of traditional chinese medicines and active ingredients in the therapy of hepatocellular carcinoma. J Hepatocell Carcinoma. 2022;9:41–56. doi: 10.2147/JHC.S346047.
   PubMed Web of Science ®Google Scholar
• Zhao Q, Cui MY, Levsh O, et al. Two CYP82D enzymes function as flavone hydroxylases in the biosynthesis of Root-Specific 4’-Deoxyflavones in Scutellaria baicalensis. Mol Plant. 2018;11(1):135–148. doi: 10.1016/j.molp.2017.08.009.
   PubMed Web of Science ®Google Scholar
• Zhao T, Tang H, Xie L, et al. Scutellaria baicalensis Georgi. (Lamiaceae): a review of its traditional uses, botany, phytochemistry, pharmacology and toxicology. J Pharm Pharmacol. 2019;71(9):1353–1369. doi: 10.1111/jphp.13129.
   PubMed Web of Science ®Google Scholar
• Zheng T, Liu H, Hong Y, et al. Promotion of liquid-to-solid phase transition of cGAS by Baicalein suppresses lung tumorigenesis. Signal Transduct Target Ther. 2023;8(1):133.
   PubMed Web of Science ®Google Scholar
• Zhao Q, Zhang Y, Wang G, et al. A specialized flavone biosynthetic pathway has evolved in the medicinal plant, Scutellaria baicalensis. Sci Adv. 2016;2(4):e1501780. doi: 10.1126/sciadv.1501780.
   PubMed Web of Science ®Google Scholar
• Lam W, Jiang Z, Guan F, et al. PHY906(KD018), an adjuvant based on a 1800-year-old Chinese medicine, enhanced the anti-tumor activity of Sorafenib by changing the tumor microenvironment. Sci Rep. 2015;5(1):9384. doi: 10.1038/srep09384.
   PubMedGoogle Scholar
• Tan HY, Wang N, Man K, et al. Autophagy-induced RelB/p52 activation mediates tumour-associated macrophage repolarisation and suppression of hepatocellular carcinoma by natural compound baicalin. Cell Death Dis. 2015;6(10):e1942–e1942. doi: 10.1038/cddis.2015.271.
   PubMedGoogle Scholar
• Eun HS, Min KS, Jeong LH, et al. Scutellarein induces fas-mediated extrinsic apoptosis and G2/M cell cycle arrest in Hep3B hepatocellular carcinoma cells. Nutrients. 2019;11(2):263. doi: 10.3390/nu11020263.
   PubMed Web of Science ®Google Scholar
• Cen Y, Xia M, Jia W, et al. Baicalein inhibits the biological behavior of hepatocellular carcinoma stem cells by downregulation of Decoy receptor 3 expression. Chin J Tissue Eng Res. 2020;24(7):1023–1029.
   Google Scholar
• Page MJ, Mckenzie JE, Bossuyt PM, et al. The PRISMA 2020 statement: an updated guideline for reporting systematic reviews. BMJ. 2021;372:71.
   PubMed Web of Science ®Google Scholar
• Cheng C-W, Wu T-X, Shang H-C, et al. CONSORT extension for Chinese herbal medicine formulas 2017: recommendations, explanation, and elaboration (simplified Chinese version). Ann Intern Med. 2017;167(2):112–121. doi: 10.7326/M16-2977.
   PubMed Web of Science ®Google Scholar
• Brown A. Meta-Analysis, decision analysis, and cost-effectiveness analysis: methods for quantitative synthesis in medicine. Gastroenterology. 2002;123(2):650–651. doi: 10.1016/S0016-5085(02)70041-3.
   Google Scholar
• Korevaar DA, Hooft L, Riet GT. Systematic reviews and meta-analyses of preclinical studies: publication bias in laboratory animal experiments. Lab Anim. 2011;45(4):225–230. doi: 10.1258/la.2011.010121.
   PubMedGoogle Scholar
• Higgins JPT, Thompson SG, Deeks JJ, et al. Measuring inconsistency in meta-analyses. BMJ. 2003;327(7414):557–560. doi: 10.1136/bmj.327.7414.557.
   PubMed Web of Science ®Google Scholar
• Higgins J, Green SR. Cochrane collaboration. Cochrane handbook for systematic reviews of interventions. England: Chichester; 2011.
   Google Scholar
• Yuan X, Li LT, Wang Q. Effectiveness evaluation of animal tests based on existing antitumor Chinese medicine Addie. Chin J Exp Formulat. 2013;19(10):349–354.
   Google Scholar
• Liu X, You JL, Zhang BN. 32 Cases of primary hepatocellular carcinoma were treated by combined intervention with fine-tuning formula No. 2. ShanXI J Trad Chin Med. 2013;34(05):518–520.
   Google Scholar
• Wang GT, Yang XW, Wang Q, et al. Curative effect of baicalin capsule combined with transcatheter arterial chemoembolization on primary hepatocellular carcinoma. Chin J Integrated Trad Western Medicine Liver Diseas. 2016;26(6):369–370.
   Google Scholar
• Zhang C, Lian SF, Zhao T, et al. Efficacy of nourishing Qi and nourishing yin combined with TACE in the treatment of patients with advanced liver cancer. World Chin Med. 2018;13(06):1461–1463.
   Google Scholar
• Li Y, Guo P, Tian YY. Effect of Huangqin decoction combined with sequential transcatheter arterial chemoembolization on nuclear factor-κB and hypoxia-inducible factor-1α in patients with primary hepatocellular carcinoma. China J Trad Chin Med Pharm. 2019;34(8):3870–3873.
   Google Scholar
• Wang XD, Zhu X, Li DY. Effects of Huangqin decoction combined with sequential transcatheter arterial chemoembolization on serum NF-κB, HIF-1α, AFP levels and liver function in patients with primary liver cancer. J Changchun University Chin Med. 2022;38(2):175–178.
   Google Scholar
• Wang XF, Wu T. Effect of Huangqin decoction on the levels of NF-κB and HIF-1α in patients with primary liver cancer. J Mathemat Med Pharm. 2022;35(2):281–283.
   Google Scholar
• Liang X, Hu XY. Effect of wenshen prescription on clinical efficacy and Th17/Treg balance in patients with advanced primary hepatocellular carcinoma associated with hepatitis B. Shizhen J Tradit Chin Med Res. 2020;31(07):1649–1651.
   Google Scholar
• Yan JG. Effect of qinggan huayu decoction on immune function of primary hepatocellular carcinoma model rats. Beijing: Beijing University of Chinese Medicine; 2010.
   Google Scholar
• Cheng XY, Zhang Y, Lu HM. Experimental study on the immunogenicity of HSP70 induced by baicalaria, a heat-clearing and detoxifying chinese herb, in mouse hepatocellular carcinoma H22 cells. J Guangdong Med University. 2018;(6):629–631.
   Google Scholar
• Cui K, Fan GR, Ji SJ, et al. Inhibitory effect of baicalein on hepatocellular carcinoma H22 tumor bearing mice. J Chin Pharm. 2012;23(31):2897–2899.
   Google Scholar
• Cui XS. Experimental study on molecular mechanism of antitumor effect of baicalin. Yanbian: Yanbian University; 2008. p. 1–77.
   Google Scholar
• Huang QS, Li HZ, Bao W, et al. Inhibitory effect and mechanism of baicalein on ascites hepatocellular carcinoma in mice. Shandong Med. 2013;53(28):31–33.
   Google Scholar
• Lu XM, Guo Y, Yu Y, et al. Effect of baicalin on the expression of PI3K, AKT and mTOR in H22 hepatocellular carcinoma tumor tissues. J Lanzhou University. 2020;46(5):21–27.
   Google Scholar
• Lu XM, Yu Y, Guo Y, et al. Effect of baicalin on the expression of HMGB1, MMP2 and MMP9 in tumor tissues of H22 hepatocellular carcinoma mice. Health Vocat Educ. 2020;38(11):107–109.
   Google Scholar
• Dong M, Hou JM, Gao MH, et al. Inhibitory effect of baicalin on tumor growth of SMMC-7721 xenograft in nude mice and its mechanism. J Modern Oncol. 2014;22(2):256–258.
   Google Scholar
• Feng JJ. The mechanism and clinical significance of baicalein on human hepatocellular carcinoma cell line SMMC-7721 transplanted tumor in nude mice. Luzhou: Southwest Medical University; 2012. p. 1–54.
   Google Scholar
• Li R. Effect of Qinggan Huayu Granule on tumor inhibition, immune function and RAF/MEK/ERK pathway in S180 and H22 tumor-bearing mice. Beijing: Beijing University of Chinese Medicine; 2016. p. 1–76.
   Google Scholar
• Zheng YH, Yin LH, Grahn TH, et al. Anticancer effects of baicalein on hepatocellular carcinoma cells. Phytother Res. 2014;28(9):1342–1348. doi: 10.1002/ptr.5135.
   PubMed Web of Science ®Google Scholar
• Yang XC, Lam W, Jiang Z, et al. YIV-906 potentiated anti-PD1 action against hepatocellular carcinoma by enhancing adaptive and innate immunity in the tumor microenvironment. Sci Rep. 2021;11(1):13482. doi: 10.1038/s41598-021-91623-3.
   PubMed Web of Science ®Google Scholar
• Du ZL, Cui DJ, Wang LP. Inhibition effect and mechanisms of baicalein on the growth of HepG2 hepatocellular carcinoma cells xenograft model in nude mice and its mechanism. Chin J Cancer Prevent Treat. 2020;27(11):848–854.
   Google Scholar
• Hong M, Almutairi MM, Li S, et al. Wogonin inhibits cell cycle progression by activating the glycogen synthase kinase-3 beta in hepatocellular carcinoma. Phytomedicine. 2020;68:153174. doi: 10.1016/j.phymed.2020.153174.
   PubMed Web of Science ®Google Scholar
• Xu M, Lu N, Zhang HW, et al. Wogonin induced cytotoxicity in human hepatocellular carcinoma cells by activation of unfolded protein response and inactivation of AKT. Hepatol Res. 2013;43(8):890–905. doi: 10.1111/hepr.12036.
   PubMed Web of Science ®Google Scholar
• Chiu YW, Lin TH, Huang WS, et al. Baicalein inhibits the migration and invasive properties of human hepatoma cells. Toxicol Appl Pharmacol. 2011;255(3):316–326. doi: 10.1016/j.taap.2011.07.008.
   PubMed Web of Science ®Google Scholar
• Lam W, Yang XC, Jiang Z, et al. YIV906 (PHY906) enhanced the antitumor activity of immune checkpoint blockade therapy: anti-PD1 against liver cancer. Cancer Res. 2018;78(13_Supplement):2724–2724. doi: 10.1158/1538-7445.AM2018-2724.
   Google Scholar
• Liu X, Tian S, Liu M, et al. Wogonin inhibits the proliferation and invasion, and induces the apoptosis of HepG2 and Bel7402 HCC cells through NFB/Bcl-2, EGFR and EGFR downstream ERK/AKT signaling. Int J Mol Med. 2016;38(4):1250–1256. doi: 10.3892/ijmm.2016.2700.
   PubMed Web of Science ®Google Scholar
• Kuo HM, Tsai HC, Lin YL, et al. Mitochondrial-dependent caspase activation pathway is involved in baicalein-induced apoptosis in human hepatoma J5 cells. Int J Oncol. 2009;35(4):717–724. doi: 10.3892/ijo_00000384.
   PubMed Web of Science ®Google Scholar
• Liang RR, Zhang S, Qi JAN, et al. Preferential inhibition of hepatocellular carcinoma by the flavonoid Baicalein through blocking MEK-ERK signaling. Int J Oncol. 2012;41(3):969–978. doi: 10.3892/ijo.2012.1510.
   PubMed Web of Science ®Google Scholar
• Park HS, Park KI, Hong GE, et al. Korean Scutellaria baicalensis Georgi methanol extracts inhibits metastasis via the Forkhead Box M1 activity in hepatocellular carcinoma cells. J Ethnopharmacol. 2014;155(1):847–851. doi: 10.1016/j.jep.2014.05.053.
   PubMed Web of Science ®Google Scholar
• Xiao X, Wang X, Pu X, et al. Effect of baicalein on the in vitro migration and invasion of human hepatocellular carcinoma cell line SMMC-7721. Chin J Clin Oncol. 2012;39(6):305–309.
   Google Scholar
• Hepatocellular Carcinoma. New Eng J Med. 2019;381(1):e2.
   PubMedGoogle Scholar
• Innes H, Nahon P. Statistical perspectives on using hepatocellular carcinoma risk models to inform surveillance decisions. J Hepatol. 2023;79(5):1332–1337.
   PubMed Web of Science ®Google Scholar
• Yang C, Zhang H, Zhang L, et al. Evolving therapeutic landscape of advanced hepatocellular carcinoma. Nat Rev Gastroenterol Hepatol. 2023;20(4):203–222. doi: 10.1038/s41575-022-00704-9.
   PubMed Web of Science ®Google Scholar
• Liu SH, Cheng YC. Old formula, new Rx: the journey of PHY906 as cancer adjuvant therapy. J Ethnopharmacol. 2012;140(3):614–623. doi: 10.1016/j.jep.2012.01.047.
   PubMed Web of Science ®Google Scholar
• Liu SH, Foo A, Jiang Z, et al. PHY906 as a broad-spectrum enhancer in cancer therapy: clinical and preclinical results in hepatocellular carcinoma. Proc Am Assoc Cancer Res. 2006;47:(abstr 2142).
   Google Scholar
• Yun Y, So S, Rose M, et al. Phase I/II study of PHY906/capecitabine in advanced hepatocellular carcinoma. Anticancer Res. 2009;29(10):4083.
   PubMed Web of Science ®Google Scholar
• Zhang F, Chen B, Wu TN, et al. Clinical study on Huangqin decoction in Sorafenib-induced diarrhea. J Hunan University Chin Med. 2019;39(9):1148–1152.
   Google Scholar
• Wang YF, Li T, Tang ZH, et al. Baicalein triggers autophagy and inhibits the protein kinase B/mammalian target of rapamycin pathway in hepatocellular carcinoma HepG2 cells. Phytother Res. 2015;29(5):674–679. doi: 10.1002/ptr.5298.
   PubMed Web of Science ®Google Scholar
• Guo Y, Li J, Li Z, et al. Baicalein regulates hepatocellular carcinoma cell proliferation and chemosensitivity via mir-181a-5p-mediated regulation of notch2-c-Myc-Cyclin A2/CDK2 signaling. Hepatology. 2018;68:1253A.
   Web of Science ®Google Scholar
• Du ZL, Cui DJ, Wang LP. Baicalein inhibits the growth of HepG2 hepatocellular carcinoma xenograft in nude mice and its mechanism. Chin J Cancer Prevent Treatment. 2020;27(11):848–854.
   Google Scholar
• Chang WH, Chen CH, Gau RJ, et al. Effect of baicalein on apoptosis of the human Hep G2 cell line was induced by mitochondrial dysfunction. Planta Med. 2002;68(4):302–306. doi: 10.1055/s-2002-26760.
   PubMed Web of Science ®Google Scholar
• Li YS, Tu M, Cheng C, et al. Wogonoside induces apoptosis in Bel-7402, a hepatocellular carcinoma cell line, by regulating Bax/Bcl-2. Oncol Lett. 2015;10(3):1831–1835. doi: 10.3892/ol.2015.3408.
   PubMed Web of Science ®Google Scholar
• Wang W, Guo Q, You Q, et al. Involvement of bax/bcl-2 in wogonin-induced apoptosis of human hepatoma cell line SMMC-7721. Anticancer Drugs. 2006;17(7):797–805. doi: 10.1097/01.cad.0000217431.64118.3f.
   PubMed Web of Science ®Google Scholar
• Yu JQ, Liu HB, Tian DZ, et al. Changes in mitochondrial membrane potential and reactive oxygen species during wogonin-induced cell death in human hepatoma cells. Hepatol Res. 2007;37(1):68–76. doi: 10.1111/j.1872-034X.2007.00003.x.
   PubMed Web of Science ®Google Scholar
• Wang ZX, Jiang CP, Chen WB, et al. Baicalein induces apoptosis and autophagy via endoplasmic reticulum stress in hepatocellular carcinoma cells. Biomed Res Int. 2014;2014:732516. doi: 10.1155/2014/732516.
   PubMed Web of Science ®Google Scholar
• Zhang XJ, Tang X, Liu HQ, et al. Autophagy induced by baicalin involves downregulation of CD147 in SMMC-7721 cells in vitro. Oncol Rep. 2012;27(4):1128–1134. doi: 10.3892/or.2011.1599.
   PubMed Web of Science ®Google Scholar
• Yu Z, Luo X, Wang C, et al. Baicalin promoted site-2 protease and not site-1 protease in endoplasmic reticulum stress-induced apoptosis of human hepatocellular carcinoma cells. FEBS Open Bio. 2016;6(11):1093–1101. doi: 10.1002/2211-5463.12130.
   PubMed Web of Science ®Google Scholar
• Guo Y, Wang N, Gao YM, et al. Treatment with baicalin up-regulates the expression of connexion 26 and connexion 43 in human hepatocellular carcinoma cell line SMMC-7721. World Chin J Digestol. 2012;20(33):3197–3202. doi: 10.11569/wcjd.v20.i33.3197.
   Google Scholar
• Harding JJ, Abou-Alfa GK, Shi Y, et al. A phase II randomized placebo controlled study investigating the combination of yiv-906 and sorafenib (SORA) in HBV (+) patients (Pts) with advanced hepatocellular carcinoma (HCC. J Clin Oncol. 2020;38(4_suppl):TPS601–TPS601. doi: 10.1200/JCO.2020.38.4_suppl.TPS601.
   Web of Science ®Google Scholar