药用植物黄芩的生物学研究进展及展望

doi:10.13560/j.cnki.biotech.bull.1985.2022-0728

摘要/Abstract

摘要：

黄芩为唇形科黄芩属多年生草本植物，在中国具有悠久的药用历史。许多研究表明，黄酮化合物是黄芩的主要活性物质，尤其是根部的黄芩素、汉黄芩素及其苷类，具有抗肿瘤、抗病毒、抗炎、抗氧化、护肝及神经保护等药理活性。本文从化学成分、活性物质的药理、生物技术、组学、代谢生物学和合成生物学研究等方面进行了总结，讨论了黄芩及黄芩属其他植物在现代医学中开发的价值、意义以及存在的问题，以期为其他传统药用植物的开发利用提供借鉴。

关键词: 药用植物, 黄芩, 黄酮

Abstract:

Scutellaria baicalensis Georgi is a perennial herb of Scutellaria L in the Labiaceae, and has been used as medicine for a long history in China. Many studies have shown that flavones are the main bioactive compounds of S. baicalensis, especially baicalein, wogonin and its glycosides in the root, which have anti-tumor, anti-virus, anti-inflammation, anti-oxidation, liver protection and neuroprotection activities. This paper summarized the chemical components, pharmacological mechanisms of active substances, biotechnology, omics, metabolic biology and synthetic biology. Also the paper discussed the potential values, significances and existing issues of S. baicalensis and other plants in Scutellaria genus, aiming to provide reference for the development and utilization of other traditional medicinal plants.

Key words: medicinal plants, Scutellaria baicalensis, flavones

郑敏敏, 柳洁, 赵清. 药用植物黄芩的生物学研究进展及展望[J]. 生物技术通报, 2023, 39(2): 10-23.

ZHENG Min-min, LIU Jie, ZHAO Qing. Research Progress and Prospects of Biological Studies on the Medicinal Plant Scutellaria baicalensis[J]. Biotechnology Bulletin, 2023, 39(2): 10-23.

图/表 6

图1 黄芩植株、黄芩的根和黄芩药材（a）黄芩植株；（b）黄芩的根；（c）黄芩药材

Fig. 1 S. baicalensis plant, S. baicalensis root and S. baicalensis as medicinal material （a）Plant of S. baicalensis.（b）Root of S. baicalensis.（c）S. baicalensis as medical material

表1 《伤寒杂病论》里含有黄芩的复方汤剂

Table 1 Compound decoctions in “Treatise on Febrile and Miscellaneous Diseases” containing S. baicalensis

药方名称 Name of the prescription	配方 Recipe	主治 Mainly for symptoms
干姜黄芩黄连人参汤方 Ganjiang Huangqin Huanglian Renshen decoction	干姜、黄芩、黄连、人参各三两 Dried ginger, root of S. baicalensis, rhizoma coptidis and ginseng 3 Liang（150 g, a Chinese measurement unit, 1 Liang = 50 g）of each	患有寒性腹泻，误用止吐及腹泻的药，导致症状加重，如食物入口即吐，可用干姜黄芩黄连人参汤方主治
葛根黄芩黄连汤方 Gegen Huangqin Huanglian decoction	葛根半斤，甘草二两，黄芩二两，黄连三两 Root of kudzu vine half Jin（250 g, a Chinese measurement unit, 1 Jin = 500 g）, licorice root and root of S. baicalensis 2 Liang, and rhizoma coptidis 3 Liang	头疼、发热、恶寒、出汗、脉浮缓，治疗后反而腹泻不止，且具有气喘出汗等症状，可用葛根黄芩黄连汤方主治
黄芩汤方 Huangqin decoction	黄芩三两，甘草二两，芍药二两，大枣十二枚 Root of S. baicalensis 3 Liang, licorice root and root of Paeonia albiflora 2 Liang each, and 12 jujubes	头疼、脖颈不适、怕冷、口苦、咽干、眼睛昏眩，伴有腹泻的症状，可用黄芩汤方主治
黄芩加半夏生姜汤方 Huangqin Banxia Shengjiang decoction	黄芩三两，芍药二两，甘草二两，大枣十二枚，半夏半升，生姜一两半 Root of S. baicalensis 3 Liang, licorice root and root of Paeonia albiflora 2 Liang each, 12 jujubes, pinellia tuber about half liker, and ginger 1.5 Liang	头疼、脖颈不适、怕冷、口苦、咽干、眼睛昏眩，伴有呕吐的症状，可用黄芩加半夏生姜汤方主治
小柴胡汤方 Xiaochaihu decoction	柴胡半斤，黄芩、人参、甘草、生姜各三两，大枣十二枚，半夏半斤 Bupleurum half Jin, root of S. baicalensis, ginseng, licorice root and ginger 3 Liang of each, 12 jujubes, and pinellia tuber half Jin	冷热交替、食欲不振、内心烦闷、想呕、口苦、咽干、目眩等症状，可用小柴胡汤方主治

表1 《伤寒杂病论》里含有黄芩的复方汤剂

Table 1 Compound decoctions in “Treatise on Febrile and Miscellaneous Diseases” containing S. baicalensis

药方名称 Name of the prescription	配方 Recipe	主治 Mainly for symptoms
干姜黄芩黄连人参汤方 Ganjiang Huangqin Huanglian Renshen decoction	干姜、黄芩、黄连、人参各三两 Dried ginger, root of S. baicalensis, rhizoma coptidis and ginseng 3 Liang（150 g, a Chinese measurement unit, 1 Liang = 50 g）of each	患有寒性腹泻，误用止吐及腹泻的药，导致症状加重，如食物入口即吐，可用干姜黄芩黄连人参汤方主治
葛根黄芩黄连汤方 Gegen Huangqin Huanglian decoction	葛根半斤，甘草二两，黄芩二两，黄连三两 Root of kudzu vine half Jin（250 g, a Chinese measurement unit, 1 Jin = 500 g）, licorice root and root of S. baicalensis 2 Liang, and rhizoma coptidis 3 Liang	头疼、发热、恶寒、出汗、脉浮缓，治疗后反而腹泻不止，且具有气喘出汗等症状，可用葛根黄芩黄连汤方主治
黄芩汤方 Huangqin decoction	黄芩三两，甘草二两，芍药二两，大枣十二枚 Root of S. baicalensis 3 Liang, licorice root and root of Paeonia albiflora 2 Liang each, and 12 jujubes	头疼、脖颈不适、怕冷、口苦、咽干、眼睛昏眩，伴有腹泻的症状，可用黄芩汤方主治
黄芩加半夏生姜汤方 Huangqin Banxia Shengjiang decoction	黄芩三两，芍药二两，甘草二两，大枣十二枚，半夏半升，生姜一两半 Root of S. baicalensis 3 Liang, licorice root and root of Paeonia albiflora 2 Liang each, 12 jujubes, pinellia tuber about half liker, and ginger 1.5 Liang	头疼、脖颈不适、怕冷、口苦、咽干、眼睛昏眩，伴有呕吐的症状，可用黄芩加半夏生姜汤方主治
小柴胡汤方 Xiaochaihu decoction	柴胡半斤，黄芩、人参、甘草、生姜各三两，大枣十二枚，半夏半斤 Bupleurum half Jin, root of S. baicalensis, ginseng, licorice root and ginger 3 Liang of each, 12 jujubes, and pinellia tuber half Jin	冷热交替、食欲不振、内心烦闷、想呕、口苦、咽干、目眩等症状，可用小柴胡汤方主治

图2 黄芩中主要活性黄酮的结构黄芩素上A,B,C及数字为黄酮环编号及碳位点标示

Fig. 2 Structures of main active flavones in S. baicalensis A, B and C and numbers on baicalein are the numbers of flavonoid rings and carbon sites

图3 黄芩的再生植株（a）从叶片外植体诱导愈伤组织；（b）愈伤组织分化得到不定芽；（c）不定芽生根得到小苗

Fig. 3 Regenerated plants of S. baicalensis （a）Callus inducted from leaves. （b）Adventitious buds from callus differentiation.（c）Adventitious buds grow root to young seedlings

图4 不同黄芩外植体诱导的毛状根及转入红色荧光蛋白的毛状根（a）黄芩子叶外植体；（b）黄芩叶片外植体；（c）黄芩下胚轴外植体；（d）子叶外植体诱导的毛状根；（e）叶片外植体诱导的毛状根；（f）明场下的毛状根；（g）激发光下的毛状根，成功转化子可见红色荧光；（h）在液体培养基中培养的黄芩毛状根

Fig. 4 Hairy roots induced by different S. baicalensis expl-ants and hairy roots transferred with dsRed（red fluorescent protein gene）（a）Cotyledon of S. baicalensis;（b）leaf of S. baicalensis;（c）hypocotyl of S. baicalensis;（d）hairy roots induced by cotyledon;（e）hairy roots induced by leaf;（f）hairy roots under bright field; （g）hairy roots under excitation light, red fluorescence can be observed in successful transformant;（h）hairy roots of S. baicalensis cultured in liquid medium

图5 黄芩的地上地下两条黄酮合成途径

Fig. 5 Two flavonoid biosynthetic synthesis pathways of S. baicalensis in aerial and root parts

参考文献 86

[1]	中国科学院中国植物志编辑委员会. 中国植物志[M]. 北京: 科学出版社, 1977.
	Editorial Committee of Chinese Flora, Chinese Academy of Sciences. Flora of China[M]. Beijing: Science Press, 1977.
[2]	Shang XF, He XR, He XY, et al. The genus Scutellaria an ethnopharmacological and phytochemical review[J]. J Ethnopharmacol, 2010, 128(2): 279-313. doi: 10.1016/j.jep.2010.01.006 URL
[3]	马继兴. 神农本草经辑注[M]. 北京: 人民卫生出版社, 2013.
	Ma JX. Sheng Nong's herbal classic anthology notes[M]. Beijing: People's Medical Publishing House, 2013.
[4]	中医研究院. 伤寒论语译[M]. 北京: 人民卫生出版社, 1973.
	Academy of traditional Chinese medicine. Annotated treatise on cold damage[M]. Beijing: People's Medical Publishing House, 1973.
[5]	李时珍. 本草纲目[M]. 北京: 华夏出版社, 2012.
	Li SZ. Compendium of Materia Medica[M]. Beijing: Huaxia Publishing House, 2012.
[6]	崔孟颖, 柳洁, 杨蕾, 等. 黄芩, 由古籍里走进现代生活的药用植物[J]. 世界科学技术-中医药现代化, 2016, 18(11): 1921-1928.
	Cui MY, Liu J, Yang L, et al. Huang qin, an medicinal plant recorded in ancient books and used in modern times[J]. Mod Tradit Chin Med Mater Med World Sci Technol, 2016, 18(11): 1921-1928.
[7]	Wang ZL, Wang S, Kuang Y, et al. A comprehensive review on phytochemistry, pharmacology, and flavonoid biosynthesis of Scutellaria baicalensis[J]. Pharm Biol, 2018, 56(1): 465-484. doi: 10.1080/13880209.2018.1492620 URL
[8]	Qiao X, Li R, Song W, et al. A targeted strategy to analyze untargeted mass spectral data: rapid chemical profiling of Scutellaria baicalensis using ultra-high performance liquid chromatography coupled with hybrid quadrupole orbitrap mass spectrometry and key ion filtering[J]. J Chromatogr A, 2016, 1441: 83-95. doi: 10.1016/j.chroma.2016.02.079 pmid: 26952367
[9]	Zhao QY, Chang WW, Chen R, et al. Anti-proliferative effect of wogonin on ovary cancer cells involves activation of apoptosis and cell cycle arrest[J]. Med Sci Monit, 2019, 25: 8465-8471. doi: 10.12659/MSM.917823 URL
[10]	Yan WJ, Ma XC, Zhao XY, et al. Baicalein induces apoptosis and autophagy of breast cancer cells via inhibiting PI3K/AKT pathway in vivo and vitro[J]. Drug Des Devel Ther, 2018, 12: 3961-3972. doi: 10.2147/DDDT.S181939 URL
[11]	Wang CY, Cui CC. Inhibition of lung cancer proliferation by wogonin is associated with activation of apoptosis and generation of reactive oxygen species[J]. Balkan Med J, 2019, 37(1): 29-33. doi: 10.4274/balkanmedj.galenos.2019.2019.7.75 pmid: 31594288
[12]	Hong M, Almutairi MM, Li SY, et al. Wogonin inhibits cell cycle progression by activating the glycogen synthase kinase-3 beta in hepatocellular carcinoma[J]. Phytomedicine, 2020, 68: 153174.
[13]	Polier G, Giaisi M, Köhler R, et al. Targeting CDK9 by wogonin and related natural flavones potentiates the anti-cancer efficacy of the Bcl-2 family inhibitor ABT-263[J]. Int J Cancer, 2015, 136(3): 688-698. doi: 10.1002/ijc.29009 pmid: 24895203
[14]	Yi SJ, Liu GW, Wu Y, et al. Baicalein suppresses the growth of the human thyroid cancer cells by inducing mitotic catastrophe, apoptosis and autophagy via NF-kB signalling pathway[J]. J BUON, 2021, 26(3): 1180.
[15]	Huynh DL, Sharma N, Kumar Singh A, et al. Anti-tumor activity of wogonin, an extract from Scutellaria baicalensis, through regulating different signaling pathways[J]. Chin J Nat Med, 2017, 15(1): 15-40.
[16]	Huynh DL, Ngau TH, Nguyen NH, et al. Potential therapeutic and pharmacological effects of Wogonin: an updated review[J]. Mol Biol Rep, 2020, 47(12): 9779-9789. doi: 10.1007/s11033-020-05972-9 pmid: 33165817
[17]	Tang Q, Ji FL, Sun WH, et al. Combination of baicalein and 10-hydroxy camptothecin exerts remarkable synergetic anti-cancer effects[J]. Phytomedicine, 2016, 23(14): 1778-1786. doi: S0944-7113(16)30191-X pmid: 27912880
[18]	Xing F, Sun C, Luo N, et al. Wogonin increases cisplatin sensitivity in ovarian cancer cells through inhibition of the phosphatidylinositol 3-kinase(PI3K)/Akt pathway[J]. Med Sci Monit, 2019, 25: 6007-6014. doi: 10.12659/MSM.913829 URL
[19]	Yu ML, Qi BQ, Wu XX, et al. Baicalein increases cisplatin sensitivity of A549 lung adenocarcinoma cells via PI3K/Akt/NF-κB pathway[J]. Biomed Pharmacother, 2017, 90: 677-685. doi: S0753-3322(17)30370-0 pmid: 28415048
[20]	Banik K, Khatoon E, Harsha C, et al. Wogonin and its analogs for the prevention and treatment of cancer: a systematic review[J]. Phytother Res, 2022, 36(5): 1854-1883. doi: 10.1002/ptr.7386 pmid: 35102626
[21]	Chen CH, Huang TS, Wong CH, et al. Synergistic anti-cancer effect of baicalein and silymarin on human hepatoma HepG2 Cells[J]. Food Chem Toxicol, 2009, 47(3): 638-644. doi: 10.1016/j.fct.2008.12.024 URL
[22]	Park CH, Han SE, Nam-Goong IS, et al. Combined effects of baicalein and docetaxel on apoptosis in 8505c anaplastic thyroid cancer cells via downregulation of the ERK and Akt/mTOR pathways[J]. Endocrinol Metab(Seoul), 2018, 33(1): 121-132.
[23]	Kuo YT, Liu CH, Wong SH, et al. Small molecules baicalein and cinnamaldehyde are potentiators of measles virus-induced breast cancer oncolysis[J]. Phytomedicine, 2021, 89: 153611. doi: 10.1016/j.phymed.2021.153611 URL
[24]	Huang YF, Bai C, He F, et al. Review on the potential action mechanisms of Chinese medicines in treating Coronavirus Disease 2019(COVID-19)[J]. Pharmacol Res, 2020, 158: 104939. doi: 10.1016/j.phrs.2020.104939 URL
[25]	李玉丽, 谭周进, 袁振仪. 中医“三药三方”防治新型冠状病毒肺炎研究进展[J]. 时珍国医国药, 2021, 32(5): 1251-1253.
	Li YL, Tan ZJ, Yuan ZY. Research progress of “three drugs and three parties” in prevention and treatment of COVID-19 in Traditional Chinese medicine[J]. Lishizhen Med Mater Med Res, 2021, 32(5): 1251-1253.
[26]	吉米丽汗·司马依, 买买提明·努尔买买提, 艾尼瓦尔·吾买尔, 等. 基于网络药理学及分子对接探索金花清感颗粒辅助治疗新型冠状病毒肺炎(COVID-19)活性成分研究[J]. 中药材, 2020, 43(5): 1271-1279.
	Simayi J, Noormaimaiti M, Wumaire A, et al. Study on the active components in the adjuvant treatment of novel coronavirus pneumonia(COVID-19)with Jinhua qinggan granules based on network pharmacology and molecular docking[J]. J Chin Med Mater, 2020, 43(5): 1271-1279.
[27]	Xia QD, Xun Y, Lu JL, et al. Network pharmacology and molecular docking analyses on Lianhua Qingwen capsule indicate Akt1 is a potential target to treat and prevent COVID-19[J]. Cell Prolif, 2020, 53(12): e12949.
[28]	孙逊, 陶嘉磊, 许少菊, 等. 基于网络药理学探究化湿败毒方治疗新型冠状病毒肺炎的分子机制[J]. 中药材, 2020, 43(8): 2047-2052.
	Sun X, Tao JL, Xu SJ, et al. The molecular mechanism of treating COVID-19 with Huashi Baidu formula based on network pharmacology[J]. J Chin Med Mater, 2020, 43(8): 2047-2052.
[29]	刘畅, 孙磊, 聂晶, 等. 基于网络药理学和分子对接法的化湿败毒方对抗新型冠状病毒肺炎(COVID-19)分子机制初步研究[J]. 辽宁中医药大学学报, 2021, 23(11): 56-63.
	Liu C, Sun L, Nie J, et al. Mechanism of Huashi Baidu decoction for treatment of Corona virus disease 2019 based on network pharmacology and molecular docking[J]. J Liaoning Univ Tradit Chin Med, 2021, 23(11): 56-63.
[30]	Zhao J, Tian SS, Lu D, et al. Systems pharmacological study illustrates the immune regulation, anti-infection, anti-inflammation, and multi-organ protection mechanism of Qing-Fei-Pai-Du Decoction in the treatment of COVID-19[J]. Phytomedicine, 2021, 85: 153315. doi: 10.1016/j.phymed.2020.153315 URL
[31]	Wu JA, Attele AS, Zhang L, et al. Anti-HIV activity of medicinal herbs: usage and potential development[J]. Am J Chin Med, 2001, 29(1): 69-81. doi: 10.1142/S0192415X01000083 URL
[32]	Ma SC, Du J, But PPH, et al. Antiviral Chinese medicinal herbs against respiratory syncytial virus[J]. J Ethnopharmacol, 2002, 79(2): 205-211. doi: 10.1016/S0378-8741(01)00389-0 URL
[33]	Oo A, Teoh BT, Sam SS, et al. Baicalein and baicalin as zika virus inhibitors[J]. Arch Virol, 2019, 164(2): 585-593. doi: 10.1007/s00705-018-4083-4 pmid: 30392049
[34]	Zandi K, Teoh BT, Sam SS, et al. Novel antiviral activity of baicalein against dengue virus[J]. BMC Complement Altern Med, 2012, 12: 214. doi: 10.1186/1472-6882-12-214 URL
[35]	Lalani SS, Anasir MI, Poh CL. Antiviral activity of silymarin in comparison with baicalein against EV-A71[J]. BMC Complement Med Ther, 2020, 20(1): 97. doi: 10.1186/s12906-020-2880-2 pmid: 32293397
[36]	Lani R, Hassandarvish P, Shu MH, et al. Antiviral activity of selected flavonoids against Chikungunya virus[J]. Antiviral Res, 2016, 133: 50-61. doi: 10.1016/j.antiviral.2016.07.009 URL
[37]	Liao HF, Ye J, Gao LL, et al. The main bioactive compounds of Scutellaria baicalensis Georgi. for alleviation of inflammatory cytokines: a comprehensive review[J]. Biomed Pharmacother, 2021, 133: 110917. doi: 10.1016/j.biopha.2020.110917 URL
[38]	Huang YQ, Sun MY, Yang XF, et al. Baicalin relieves inflammation stimulated by lipopolysaccharide via upregulating TUG1 in liver cells[J]. J Physiol Biochem, 2019, 75(4): 463-473. doi: 10.1007/s13105-019-00698-0 pmid: 31396818
[39]	Xin LY, Gao JL, Lin HC, et al. Regulatory mechanisms of baicalin in cardiovascular diseases: a review[J]. Front Pharmacol, 2020, 11: 583200. doi: 10.3389/fphar.2020.583200 URL
[40]	Ge JL, Yang HH, Zeng YF, et al. Protective effects of wogonin on lipopolysaccharide-induced inflammation and apoptosis of lung epithelial cells and its possible mechanisms[J]. Biomed Eng Online, 2021, 20(1): 125. doi: 10.1186/s12938-021-00965-6 pmid: 34906140
[41]	Bui TT, Piao CH, Song CH, et al. Baicalein, wogonin, and Scutellaria baicalensis ethanol extract alleviate ovalbumin-induced allergic airway inflammation and mast cell-mediated anaphylactic shock by regulation of Th1/Th2 imbalance and histamine release[J]. Anat Cell Biol, 2017, 50(2): 124-134. doi: 10.5115/acb.2017.50.2.124 URL
[42]	Jin X, Liu MY, Zhang DF, et al. Baicalin mitigates cognitive impairment and protects neurons from microglia-mediated neuroinflammation via suppressing NLRP3 inflammasomes and TLR4/NF-κB signaling pathway[J]. CNS Neurosci Ther, 2019, 25(5): 575-590. doi: 10.1111/cns.13086 pmid: 30676698
[43]	Piao HZ, Jin SA, Chun HS, et al. Neuroprotective effect of wogonin: potential roles of inflammatory cytokines[J]. Arch Pharm Res, 2004, 27(9): 930-936. pmid: 15473663
[44]	Wang CZ, Zhang CF, Luo Y, et al. Baicalein, an enteric microbial metabolite, suppresses gut inflammation and cancer progression in Apc^Min/+ mice[J]. Clin Transl Oncol, 2020, 22(7): 1013-1022. doi: 10.1007/s12094-019-02225-5 pmid: 31650468
[45]	Dinda B, Dinda S, DasSharma S, et al. Therapeutic potentials of baicalin and its aglycone, baicalein against inflammatory disorders[J]. Eur J Med Chem, 2017, 131: 68-80. doi: S0223-5234(17)30153-8 pmid: 28288320
[46]	王斌, 张腾霄, 孟祥才. 黄芩组织培养技术及研究进展[J]. 中药材, 2017, 40(9): 2233-2236.
	Wang B, Zhang TX, Meng XC. Tissue culture technology and research progress of Scutellaria baicalensis[J]. J Chin Med Mater, 2017, 40(9): 2233-2236.
[47]	刘建霞, 温日宇, 李慧, 等. 黄芩离体再生体系的建立[J]. 陕西农业科学, 2018, 64(6): 25-27, 64.
	Liu JX, Wen RY, Li H, et al. Establishment of regeneration in vitro system in Scutellaria baicalensis[J]. Shaanxi J Agric Sci, 2018, 64(6): 25-27, 64.
[48]	韩淑兰. 黄芩细胞悬浮培养体系的建立及降低再生苗玻璃化的研究[D]. 哈尔滨: 东北林业大学, 2016.
	Han SL. The research of establishing cell suspension culture system and reducing hyperhydricity in regenerated shoots of Scutellaria baicalensis Georgi[D]. Harbin: Northeast Forestry University, 2016.
[49]	李富雄, 张东向, 李善文. 黄芩同源四倍体的诱导及细胞形态学观察[J]. 北方园艺, 2009(3): 119-121.
	Li FX, Zhang DX, Li SW. The inducing of autotetraploid of Scutellaria baicalensis Georgi[J]. North Hortic, 2009(3): 119-121.
[50]	于辉, 高赛男, 任亚超, 等. HPLC法测定四倍体黄芩中黄芩苷和汉黄芩苷的含量[J]. 现代中药研究与实践, 2013, 27(1): 15-16.
	Yu H, Gao SN, Ren YC, et al. Determination of baicalein and wogonin in tetraploid Scutellaria baicalensis by HPLC[J]. Res Pract Chin Med, 2013, 27(1): 15-16.
[51]	Zhou ML, Zhu XM, Shao JR, et al. Production and metabolic engineering of bioactive substances in plant hairy root culture[J]. Appl Microbiol Biotechnol, 2011, 90(4): 1229-1239. doi: 10.1007/s00253-011-3228-0 URL
[52]	Shi M, Liao P, Nile SH, et al. Biotechnological exploration of transformed root culture for value-added products[J]. Trends Biotechnol, 2021, 39(2): 137-149. doi: 10.1016/j.tibtech.2020.06.012 pmid: 32690221
[53]	Kim YS, Kim YB, Kim Y, et al. Overexpression of cinnamate 4-hydroxylase and 4-coumaroyl CoA ligase prompted flavone accumulation in Scutellaria baicalensis hairy roots[J]. Nat Prod Commun, 2014, 9(6): 803-807.
[54]	Park NI, Xu H, Li XH, et al. Enhancement of flavone levels through overexpression of Chalcone isomerase in hairy root cultures of Scutellaria baicalensis[J]. Funct Integr Genomics, 2011, 11(3): 491-496. doi: 10.1007/s10142-011-0229-0 URL
[55]	Park CH, Xu H, Yeo HJ, et al. Enhancement of the flavone contents of Scutellaria baicalensis hairy roots via metabolic engineering using maize Lc and Arabidopsis PAP1 transcription factors[J]. Metab Eng, 2021, 64: 64-73. doi: 10.1016/j.ymben.2021.01.003 URL
[56]	Zhao Q, Yang J, Cui MY, et al. The reference genome sequence of Scutellaria baicalensis provides insights into the evolution of wogonin biosynthesis[J]. Mol Plant, 2019, 12(7): 935-950. doi: 10.1016/j.molp.2019.04.002 URL
[57]	Zhao Q, Zhang Y, Wang G, et al. A specialized flavone biosynthetic pathway has evolved in the medicinal plant, Scutellaria baicalensis[J]. Sci Adv, 2016, 2(4): e1501780.
[58]	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[J]. Mol Plant, 2018, 11(1): 135-148. doi: 10.1016/j.molp.2017.08.009 URL
[59]	Xu ZC, Gao RR, Pu XD, et al. Comparative genome analysis of Scutellaria baicalensis and Scutellaria barbata reveals the evolution of active flavonoid biosynthesis[J]. Genomics Proteomics Bioinformatics, 2020, 18(3): 230-240. doi: 10.1016/j.gpb.2020.06.002 URL
[60]	Cui MY, Lu AR, Li JX, et al. Two types of O-methyltransferase are involved in biosynthesis of anticancer methoxylated 4'-deoxyflavones in Scutellaria baicalensis Georgi[J]. Plant Biotechnol J, 2022, 20(1): 129-142. doi: 10.1111/pbi.13700 URL
[61]	MacDonald MJ, D'Cunha GB. A modern view of phenylalanine ammonia lyase[J]. Biochem Cell Biol, 2007, 85(3): 273-282. doi: 10.1139/O07-018 URL
[62]	Xu H, Park NI, Li XH, et al. Molecular cloning and characterization of phenylalanine ammonia-lyase, cinnamate 4-hydroxylase and genes involved in flavone biosynthesis in Scutellaria baicalensis[J]. Bioresour Technol, 2010, 101(24): 9715-9722. doi: 10.1016/j.biortech.2010.07.083 URL
[63]	Vogt T. Phenylpropanoid biosynthesis[J]. Mol Plant, 2010, 3(1): 2-20. doi: 10.1093/mp/ssp106 pmid: 20035037
[64]	Liu WX, Feng Y, Yu SH, et al. The flavonoid biosynthesis network in plants[J]. Int J Mol Sci, 2021, 22(23): 12824. doi: 10.3390/ijms222312824 URL
[65]	方誉民, 崔孟颖, 柳洁, 等. 黄芩属植物黄酮生物合成研究进展[J]. 中国中药杂志, 2020, 45(20): 4819-4826.
	Fang YM, Cui MY, Liu J, et al. Study advance in biosynthesis of flavone from Scutellaria[J]. China J Chin Mater Med, 2020, 45(20): 4819-4826.
[66]	Nagashima S, Hirotani M, Yoshikawa T. Purification and characterization of UDP-glucuronate: baicalein 7-O-glucuronosyltransferase from Scutellaria baicalensis Georgi. cell suspension cultures[J]. Phytochemistry, 2000, 53(5): 533-538. pmid: 10724177
[67]	陈顺钦, 黄璐琦, 袁媛, 等. 光照对黄芩悬浮细胞内源激素与有效成分相关性的影响[J]. 中国实验方剂学杂志, 2010, 16(4): 72-74.
	Chen SQ, Huang LQ, Yuan Y, et al. Effect of light on correlation between endogenous hormones and active components in Scutellaria baicalensis suspension cells[J]. Chin J Exp Tradit Med Formulae, 2010, 16(4): 72-74.
[68]	陈顺钦, 袁媛, 罗毓健, 等. 光照对黄芩黄酮类活性成分积累及其相关基因表达的影响[J]. 中国中药杂志, 2010, 35(6): 682-685.
	Chen SQ, Yuan Y, Luo YJ, et al. Effects of light on flavonoids accumulation and related gene expression in suspension cultures of Scutellaria baicalensis[J]. China J Chin Mater Med, 2010, 35(6): 682-685.
[69]	Yeo HJ, Park CH, Park SY, et al. Metabolic analysis of root, stem, and leaf of Scutellaria baicalensis plantlets treated with different LED lights[J]. Plants(Basel), 2021, 10(5): 940.
[70]	郭双双. 发根农杆菌诱导黄芩毛状根的形成与质量研究[D]. 长春: 吉林农业大学, 2016.
	Guo SS. Research of hairy roots induced and quality of Scutellaria baicalensis Georgi[D]. Changchun: Jilin Agricultural University, 2016.
[71]	王帅. 黄芩愈伤组织黄芩苷次生代谢对温度变化的响应[D]. 长春: 吉林农业大学, 2018.
	Wang S. Response of secondary metabolism of baicalin in callus of Scutellaria baicalensis Georgi to temperature change[D]. Changchun: Jilin Agricultural University, 2018.
[72]	程林. 干旱胁迫黄芩生理生态变化及其黄芩苷生物合成的分子生态机制[D]. 长春: 吉林农业大学, 2018.
	Cheng L. Physiological and ecological changes of Scutellaria baicalensis Georgi under drought stress and mlecular ecological mechanism of baicalin biosynthesis[D]. Changchun: Jilin Agricultural University, 2018.
[73]	齐香君, 郭乐康, 陈微娜. 诱导子对黄芩毛状根生长及黄芩苷合成的影响[J]. 中草药, 2009, 40(5): 801-803.
	Qi XJ, Guo LK, Chen WN. Influence of elicitors on growth and baicalin biosynthesis in hairy root of Scutellaria baicalensis[J]. Chin Tradit Herb Drugs, 2009, 40(5): 801-803.
[74]	张进杰, 徐茂军. NO和茉莉酸甲酯对黄芩悬浮细胞生长及黄芩苷合成的影响[J]. 植物学通报, 2006, 41(4): 374-379.
	Zhang JJ, Xu MJ. Effects of nitric oxide and methyl jasmonate on the baicalin production and cell growth in suspension cultures of Scutellaria baicalensis[J]. Chin Bull Bot, 2006, 41(4): 374-379.
[75]	孟书亦. SA和MeJA对黄芩愈伤组织黄酮类化合物含量及其合成酶的影响[D]. 长春: 吉林农业大学, 2017.
	Meng SY. Effects of SA and MeJA on callus flavonoid content and its synthetase of Scutellaria baicalensis Georgi[D]. Changchun: Jilin Agricultural University, 2017.
[76]	孟书亦, 马秀杰, 韩梅, 等. 水杨酸对黄芩愈伤组织抗氧化酶活性及黄芩苷含量的影响[J]. 分子植物育种, 2017, 15(10): 4179-4183.
	Meng SY, Ma XJ, Han M, et al. Effects of salicylic acid on antioxidant enzyme activity and content of baicalin in Scutellaria baicalensis callus[J]. Mol Plant Breed, 2017, 15(10): 4179-4183.
[77]	Zhou J, Fang L, Li X, et al. Jasmonic acid(JA)acts as a signal molecule in LaCl(3)-induced baicalin synthesis in Scutellaria baicalensis seedlings[J]. Biol Trace Elem Res, 2012, 148(3): 392-395. doi: 10.1007/s12011-012-9379-8 pmid: 22476950
[78]	Cao HB, Jiang Y, Chen JJ, et al. Arsenic accumulation in Scutellaria baicalensis Georgi and its effects on plant growth and pharmaceutical components[J]. J Hazard Mater, 2009, 171(1/2/3): 508-513. doi: 10.1016/j.jhazmat.2009.06.022 URL
[79]	Pei TL, Yan MX, Huang YB, et al. Specific flavonoids and their biosynthetic pathway in Scutellaria baicalensis[J]. Front Plant Sci, 2022, 13: 866282. doi: 10.3389/fpls.2022.866282 URL
[80]	Kawai Y, Ono E, Mizutani M. Evolution and diversity of the 2-oxoglutarate-dependent dioxygenase superfamily in plants[J]. Plant J, 2014, 78(2): 328-343. doi: 10.1111/tpj.12479 URL
[81]	Martens S, Mithöfer A. Flavones and flavone synthases[J]. Phytochemistry, 2005, 66(20): 2399-2407. doi: 10.1016/j.phytochem.2005.07.013 pmid: 16137727
[82]	Fliegmann J, Furtwängler K, Malterer G, et al. Flavone synthase II(CYP93B16)from soybean(Glycine max L.)[J]. Phytochemistry, 2010, 71(5/6): 508-514. doi: 10.1016/j.phytochem.2010.01.007 URL
[83]	李玲玲, 刘雪, 邱泽天, 等. 植物多酚的微生物合成[J]. 生物工程学报, 2021, 37(6): 2050-2076.
	Li LL, Liu X, Qiu ZT, et al. Microbial synthesis of plant polyphenols[J]. Chin J Biotechnol, 2021, 37(6): 2050-2076.
[84]	Li JH, Tian CF, Xia YH, et al. Production of plant-specific flavones baicalein and scutellarein in an engineered E. coli from available phenylalanine and tyrosine[J]. Metab Eng, 2019, 52: 124-133. doi: 10.1016/j.ymben.2018.11.008 URL
[85]	Ji DN, Li JH, Xu FL, et al. Improve the biosynthesis of baicalein and scutellarein via manufacturing self-assembly enzyme reactor in vivo[J]. ACS Synth Biol, 2021, 10(5): 1087-1094. doi: 10.1021/acssynbio.0c00606 URL
[86]	Qian ZL, Yu JH, Chen XJ, et al. De novo production of plant 4'-deoxyflavones baicalein and oroxylin A from ethanol in crabtree-negative yeast[J]. ACS Synth Biol, 2022, 11(4): 1600-1612. doi: 10.1021/acssynbio.2c00026 URL