doi:10.48130/mpb-0025-0022

[1]

Han Y. 2010. Tai Ping Sheng Hui Fang yu Song Dai She Hui (《太平圣恵方》与宋代社会) [Taiping Holy Prescriptions for Universal Relief and the compilation during the early Song Dynasty]. Zhonghua yi shi za zhi [Chinese Journal of Medical History] 40:198−205

doi: 10.3760/cma.j.issn.0255-7053.2010.04.002

[2]

Liao CP, Liu XC, Dong SQ, An M, Zhao L, et al. 2021. Investigation of the metabolites of five major constituents from Berberis amurensis in normal and pseudo germ-free rats. Chinese Journal of Natural Medicines 19(10):758−71

doi: 10.1016/S1875-5364(21)60082-1

[3]

Roy NS, Park NI, Kim NS, Park Y, Kim BY, et al. 2022. Comparative transcriptomics for genes related to berberine and berbamine biosynthesis in Berberidaceae. Plants 11:2676

doi: 10.3390/plants11202676

[4]

Liu X, Jin X, Ou H, Qian C, Wu H, et al. 2022. The direct STAT3 inhibitor 6-ethoxydihydrosanguinarine exhibits anticancer activity in gastric cancer. Acta Materia Medica 1(3):365−80

doi: 10.15212/amm-2022-0027

[5]

Farrow SC, Hagel JM, Facchini PJ. 2012. Transcript and metabolite profiling in cell cultures of 18 plant species that produce benzylisoquinoline alkaloids. Phytochemistry 77:79−88

doi: 10.1016/j.phytochem.2012.02.014

[6]

Tian Y, Kong L, Li Q, Wang Y, Wang Y, et al. 2024. Structural diversity, evolutionary origin, and metabolic engineering of plant specialized benzylisoquinoline alkaloids. Natural Product Reports 41:1787−810

doi: 10.1039/D4NP00029C

[7]

An Z, Gao R, Chen S, Tian Y, Li Q, et al. 2024. Lineage-specific CYP80 expansion and benzylisoquinoline alkaloid diversity in early-diverging eudicots. Advanced Science 11:e2309990

doi: 10.1002/advs.202309990

[8]

Yusupov MM, Karimov A, Shakirov R, Gorovoi PG, Faskhutdinov MF, et al. 1993. Berberis alkaloids. XXVI. An investigation of the alkaloids of Berberis amurensis. Chemistry of Natural Compounds 29:338−40

doi: 10.1007/BF00630534

[9]

Roy NS, Choi IY, Um T, Jeon MJ, Kim BY, et al. 2021. Gene expression and isoform identification of PacBio full-length cDNA sequences for berberine biosynthesis in Berberis koreana. Plants 10:1314

doi: 10.3390/plants10071314

[10]

Fan RF, Li HT, Kuang HY, Li W. 2019. Huanglumu de Sheng Yao Xue Yan Jiu ji Yan Suan Xiao Bo Jiang de Han Liang Ce Ding (黄芦木的生药学研究及盐酸小檗碱的含量测定) [Pharmacognosical studies and content determination of berberine hydrochloride of Berberis amurensis Rupr]. Shizhen Guo Yi Guo Yao (时珍国医国药) [Lishizhen Medicine and Materia Medica Research] 30:2074−75

doi: 10.3969/j.issn.1008-0805.2019.09.008

[11]

Srivastava S, Srivastava M, Misra A, Pandey G, Rawat A. 2015. A review on biological and chemical diversity in Berberis (Berberidaceae). EXCLI Journal 14:247−67

doi: 10.17179/excli2014-399

[12]

Li T, Wang P, Guo W, Huang X, Tian X, et al. 2019. Natural berberine-based Chinese herb medicine assembled nanostructures with modified antibacterial application. ACS Nano 13:6770−81

doi: 10.1021/acsnano.9b01346

[13]

Wang K, Yin J, Chen J, Ma J, Si H, et al. 2024. Inhibition of inflammation by berberine: molecular mechanism and network pharmacology analysis. Phytomedicine 128:155258

doi: 10.1016/j.phymed.2023.155258

[14]

Jain S, Tripathi S, Tripathi PK. 2023. Antioxidant and antiarthritic potential of berberine: In vitro and in vivo studies. Chinese Herbal Medicines 15:549−55

doi: 10.1016/j.chmed.2023.02.007

[15]

Zhao MM, Lu J, Li S, Wang H, Cao X, et al. 2021. Berberine is an insulin secretagogue targeting the KCNH6 potassium channel. Nature Communications 12:5616

doi: 10.1038/s41467-021-25952-2

[16]

Hu Y, Ehli EA, Kittelsrud J, Ronan PJ, Munger K, et al. 2012. Lipid-lowering effect of berberine in human subjects and rats. Phytomedicine 19:861−67

doi: 10.1016/j.phymed.2012.05.009

[17]

Wang Y, Tong Q, Ma SR, Zhao ZX, Pan LB, et al. 2021. Oral berberine improves brain dopa/dopamine levels to ameliorate Parkinson's disease by regulating gut microbiota. Signal Transduction and Targeted Therapy 6:77

doi: 10.1038/s41392-020-00456-5

[18]

Chen CY, Zhang Y. 2025. Berberine: An isoquinoline alkaloid targeting the oxidative stress and gut-brain axis in the models of depression. European Journal of Medicinal Chemistry 290:117475

doi: 10.1016/j.ejmech.2025.117475

[19]

Phogat A, Singh J, Malik V. 2024. Pharmacological effects of berberine – a Chinese medicine, against xenobiotics toxicity. Pharmacological Research - Modern Chinese Medicine 13:100507

doi: 10.1016/j.prmcm.2024.100507

[20]

Lagoa R, Silva J, Rodrigues JR, Bishayee A. 2020. Advances in phytochemical delivery systems for improved anticancer activity. Biotechnology Advances 38:107382

doi: 10.1016/j.biotechadv.2019.04.004

[21]

Yi LT, Zhu JX, Dong SQ, Chen M, Li CF. 2021. Berberine exerts antidepressant-like effects via regulating miR-34a-synaptotagmin1/Bcl-2 axis. Chinese Herbal Medicines 13:116−23

doi: 10.1016/j.chmed.2020.11.001

[22]

Bao S, Wang X, Ma Q, Wei C, Nan J, et al. 2022. Mongolian medicine in treating type 2 diabetes mellitus combined with nonalcoholic fatty liver disease via FXR/LXR-mediated P2X7R/NLRP3/NF-κB pathway activation. Chinese Herbal Medicines 14:367−75

doi: 10.1016/j.chmed.2022.06.003

[23]

Zhang C, Song Y, Sun X, Liu Q, Li Z, et al. 2023. Photoredox-catalyzed reaction as a powerful tool for rapid natural product Gem-dimethylation modification: discovery of potent anti-cancer agents with improved druggability. Acta Materia Medica 2:400−8

doi: 10.15212/amm-2023-0032

[24]

Sun C, Sha S, Shan Y, Gao X, Li L, et al. 2025. Intranasal delivery of BACE1 siRNA and berberine via engineered stem cell exosomes for the treatment of Alzheimer's disease. International Journal of Nanomedicine 20:5873−91

doi: 10.2147/IJN.S506793

[25]

Lei Y, Xie J, Xie Z, Zhao X, Huang J, et al. 2025. Comparative drug-drug interactions of berberine and astragaloside IV in normal and type 2 diabetes mellitus rats based on UPLC-QqQ-MS/MS. Acta Materia Medica 4:51−69

doi: 10.15212/amm-2024-0078

[26]

Liu Y, Wang B, Shu S, Li Z, Song C, et al. 2021. Analysis of the Coptis chinensis genome reveals the diversification of protoberberine-type alkaloids. Nature Communications 12:3276

doi: 10.1038/s41467-021-23611-0

[27]

He SM, Liang YL, Cong K, Chen G, Zhao X, et al. 2018. Identification and characterization of genes involved in benzylisoquinoline alkaloid biosynthesis in Coptis species. Frontiers in Plant Science 9:731

doi: 10.3389/fpls.2018.00731

[28]

Guo L, Winzer T, Yang X, Li Y, Ning Z, et al. 2018. The opium poppy genome and morphinan production. Science 362:343−47

doi: 10.1126/science.aat4096

[29]

Hagel JM, Beaudoin GAW, Fossati E, Ekins A, Martin VJJ, et al. 2012. Characterization of a flavoprotein oxidase from opium poppy catalyzing the final steps in sanguinarine and papaverine biosynthesis. Journal of Biological Chemistry 287:42972−83

doi: 10.1074/jbc.M112.420414

[30]

Yang H, Liu Z, Yu C, Song C, Wang C. 2023. Expression relationship between microRNA and transcription factors in Stephania japonica. Medicinal Plant Biology 2:7

doi: 10.48130/mpb-2023-0007

[31]

Liu T, Zhang W, Wang S, Tian Y, Wang Y, et al. 2024. Metabolome and transcriptome association study reveals biosynthesis of specialized benzylisoquinoline alkaloids in Phellodendron amurense. Chinese Herbal Medicines 17:178−88

doi: 10.1016/j.chmed.2024.11.003

[32]

Hagel JM, Facchini PJ. 2013. Benzylisoquinoline alkaloid metabolism: a century of discovery and a brave new world. Plant & Cell Physiology 54:647−72

doi: 10.1093/pcp/pct020

[33]

Samanani N, Facchini PJ. 2002. Purification and characterization of norcoclaurine synthase. The first committed enzyme in benzylisoquinoline alkaloid biosynthesis in plants. The Journal of Biological Chemistry 277:33878−83

doi: 10.1074/jbc.M203051200

[34]

Samanani N, Liscombe DK, Facchini PJ. 2004. Molecular cloning and characterization of norcoclaurine synthase, an enzyme catalyzing the first committed step in benzylisoquinoline alkaloid biosynthesis. The Plant Journal 40:302−13

doi: 10.1111/j.1365-313X.2004.02210.x

[35]

Lee EJ, Facchini P. 2010. Norcoclaurine synthase is a member of the pathogenesis-related 10/Bet v1 protein family. The Plant Cell 22:3489−503

doi: 10.1105/tpc.110.077958

[36]

Lee S, Park NI, Park Y, Park KC, Kim ES, et al. 2024. O- and N-Methyltransferases in benzylisoquinoline alkaloid producing plants. Genes & Genomics 46:367−78

doi: 10.1007/s13258-023-01477-4

[37]

Wu L, Zhao B, Deng Z, Wang B, Yu Y. 2024. A biosynthetic network for protoberberine production in Coptis chinensis. Horticulture Research 11:uhad259

doi: 10.1093/hr/uhad259

[38]

Sato F, Tsujita T, Katagiri Y, Yoshida S, Yamada Y. 1994. Purification and characterization of S-adenosyl-ʟ-methionine: norcoclaurine 6-O-methyltransferase from cultured Coptis japonica cells. European Journal of Biochemistry 225:125−31

doi: 10.1111/j.1432-1033.1994.00125.x

[39]

Choi KB, Morishige T, Shitan N, Yazaki K, Sato F. 2002. Molecular cloning and characterization of coclaurine N-methyltransferase from cultured cells of Coptis japonica. Journal of Biological Chemistry 277:830−35

doi: 10.1074/jbc.M106405200

[40]

Pauli HH, Kutchan TM. 1998. Molecular cloning and functional heterologous expression of two alleles encoding (S)-N-methylcoclaurine 3'-hydroxylase (CYP80B1), a new methyl jasmonate-inducible cytochrome P-450-dependent mono-oxygenase of benzylisoquinoline alkaloid biosynthesis. The Plant Journal 13:793−801

doi: 10.1046/j.1365-313X.1998.00085.x

[41]

Morishige T, Tsujita T, Yamada Y, Sato F. 2000. Molecular characterization of the S-adenosyl-L-methionine: 3'-hydroxy-N-methylcoclaurine 4'-O-methyltransferase involved in isoquinoline alkaloid biosynthesis in Coptis japonica. The Journal of Biological Chemistry 275:23398−405

doi: 10.1074/jbc.M002439200

[42]

Huang P, Cheng P, Sun M, Liu X, Qing Z, et al. 2024. Systemic review of Macleaya cordata: genetics, biosynthesis of active ingredients and functions. Medicinal Plant Biology 3:e020

[43]

Xu Z, Li Z, Ren F, Gao R, Wang Z, et al. 2022. The genome of Corydalis reveals the evolution of benzylisoquinoline alkaloid biosynthesis in Ranunculales. The Plant Journal 111:217−30

doi: 10.1111/tpj.15788

[44]

Hafner J, Payne J, MohammadiPeyhani H, Hatzimanikatis V, Smolke C. 2021. A computational workflow for the expansion of heterologous biosynthetic pathways to natural product derivatives. Nature Communications 12:1760

doi: 10.1038/s41467-021-22022-5

[45]

Bu J, Zhang X, Li Q, Ma Y, Hu Z, et al. 2022. Catalytic promiscuity of O-methyltransferases from Corydalis yanhusuo leading to the structural diversity of benzylisoquinoline alkaloids. Horticulture Research 9:uhac152

doi: 10.1093/hr/uhac152

[46]

Ounaroon A, Decker G, Schmidt J, Lottspeich F, Kutchan TM. 2003. (R,S)-Reticuline 7-O-methyltransferase and (R,S)-norcoclaurine 6-O-methyltransferase of Papaver somniferum – cDNA cloning and characterization of methyl transfer enzymes of alkaloid biosynthesis in opium poppy. The Plant Journal 36:808−19

doi: 10.1046/j.1365-313X.2003.01928.x

[47]

Li H, Wei W, Xu H. 2022. Drug discovery is an eternal challenge for the biomedical sciences. Acta Materia Medica 1:1−3

doi: 10.15212/AMM-2022-1001

[48]

Li Q, Bu J, Ma Y, Yang J, Hu Z, et al. 2020. Characterization of O-methyltransferases involved in the biosynthesis of tetrandrine in Stephania tetrandra. Journal of Plant Physiolog 250:153181

doi: 10.1016/j.jplph.2020.153181

[49]

Xu Z, Tian Y, Wang J, Ma Y, Li Q, et al. 2024. Convergent evolution of berberine biosynthesis. Science Advances 10:eads3596

doi: 10.1126/sciadv.ads3596

[50]

Leng L, Xu Z, Hong B, Zhao B, Tian Y, et al. 2024. Cepharanthine analogs mining and genomes of Stephania accelerate anti-coronavirus drug discovery. Nature Communications 15:1537

doi: 10.1038/s41467-024-45690-5

[51]

Bi Z, Li H, Liang Y, Sun D, Liu S, et al. 2025. Emerging paradigms for target discovery of traditional medicines: a genome-wide pan-GPCR perspective. The Innovation 6:100774

doi: 10.1016/j.xinn.2024.100774

[52]

Raghavan V, Kraft L, Mesny F, Rigerte L. 2022. A simple guide to de novo transcriptome assembly and annotation. Briefings in Bioinformatics 23:bbab563

doi: 10.1093/bib/bbab563

[53]

Andrews S. 2010. FastQC: a quality control tool for high throughput sequence data. Bioinformatics 26(15):1968−71

[54]

Grabherr MG, Haas BJ, Yassour M, Levin JZ, Thompson DA, et al. 2011. Full-length transcriptome assembly from RNA-Seq data without a reference genome. Nature Biotechnology 29:644−52

doi: 10.1038/nbt.1883

[55]

Li W, Godzik A. 2006. Cd-hit: a fast program for clustering and comparing large sets of protein or nucleotide sequences. Bioinformatics 22:1658−59

doi: 10.1093/bioinformatics/btl158

[56]

Manni M, Berkeley MR, Seppey M, Simão FA, Zdobnov EM. 2021. BUSCO Update: novel and streamlined workflows along with broader and deeper phylogenetic coverage for scoring of eukaryotic, prokaryotic, and viral genomes. Molecular Biology and Evolution 38:4647−54

doi: 10.1093/molbev/msab199

[57]

Cantalapiedra CP, Hernández-Plaza A, Letunic I, Bork P, Huerta-Cepas J. 2021. eggNOG-mapper v2: functional annotation, orthology assignments, and domain prediction at the metagenomic scale. Molecular Biology and Evolution 38:5825−29

doi: 10.1093/molbev/msab293

[58]

Kanehisa M. 2016. KEGG bioinformatics resource for plant genomics and metabolomics. Methods in Molecular Biology 1374:55−70

doi: 10.1007/978-1-4939-3167-5_3

[59]

Ye J, Fang L, Zheng H, Zhang Y, Chen J, et al. 2006. WEGO: a web tool for plotting GO annotations. Nucleic Acids Research 34:293−97

doi: 10.1093/nar/gkl031

[60]

Hung JH, Weng Z. 2016. Sequence alignment and homology search with BLAST and ClustalW. Cold Spring Harbor Protocols 2016:pdb.prot093088

doi: 10.1101/pdb.prot093088

[61]

Kumar S, Stecher G, Li M, Knyaz C, Tamura K. 2018. MEGA X: molecular evolutionary genetics analysis across computing platforms. Molecular Biology and Evolution 35:1547−49

doi: 10.1093/molbev/msy096

[62]

Trapnell C, Williams BA, Pertea G, Mortazavi A, Kwan G, et al. 2010. Transcript assembly and quantification by RNA-Seq reveals unannotated transcripts and isoform switching during cell differentiation. Nature Biotechnology 28:511−15

doi: 10.1038/nbt.1621

[63]

Chen C, Chen H, Zhang Y, Thomas HR, Frank MH, et al. 2020. TBtools: an integrative Toolkit developed for interactive analyses of big biological data. Molecular Plant 13:1194−202

doi: 10.1016/j.molp.2020.06.009

[64]

The Angiosperm Phylogeny Group, Chase MW, Christenhusz MJM, Fay MF, Byng JW, et al. 2016. An update of the Angiosperm Phylogeny Group classification for the orders and families of flowering plants: APG IV. Botanical Journal of the Linnean Society 181(1):1−20

doi: 10.1111/boj.12385

[65]

Zhong F, Huang L, Qi L, Ma Y, Yan Z. 2020. Full-length transcriptome analysis of Coptis deltoidea and identification of putative genes involved in benzylisoquinoline alkaloids biosynthesis based on combined sequencing platforms. Plant Molecular Biology 102:477−99

doi: 10.1007/s11103-019-00959-y

[66]

Winzer T, Gazda V, He Z, Kaminski F, Kern M, et al. 2012. A Papaver somniferum 10-gene cluster for synthesis of the anticancer alkaloid noscapine. Science 336:1704−8

doi: 10.1126/science.1220757

[67]

Menéndez-Perdomo IM, Facchini PJ. 2023. Elucidation of the (R)-enantiospecific benzylisoquinoline alkaloid biosynthetic pathways in sacred lotus (Nelumbo nucifera). Scientific Reports 13:2955

doi: 10.1038/s41598-023-29415-0

[68]

Li F, Yuan Z, Gao Y, Deng Z, Zhang Y, et al. 2025. A concise enzyme cascade enables the manufacture of natural and halogenated protoberberine alkaloids. Nature Communications 16:1904

doi: 10.1038/s41467-025-57280-0

[69]

Han J, Li S. 2023. De novo biosynthesis of berberine and halogenated benzylisoquinoline alkaloids in Saccharomyces cerevisiae. Communications Chemistry 6:27

doi: 10.1038/s42004-023-00821-9

[70]

Jiao X, Fu X, Li Q, Bu J, Liu X, et al. 2024. De novo production of protoberberine and benzophenanthridine alkaloids through metabolic engineering of yeast. Nature Communications 15:8759

doi: 10.1038/s41467-024-53045-3