Top

BMC Complementary Medicine and Therapies

Published in:

Open Access 01-12-2023 | Alkaloids | Research

Comprehensive chemical profiling of two Dendrobium species and identification of anti-hepatoma active constituents from Dendrobium chrysotoxum by network pharmacology

Authors: Xia Jie, Yin Feng, Fang Jiahao, Lou Ganggui, Yu Jiani, Xu Zhongyu, Yuan Yuan, Zhang Tinggang, Zhang Xiaodan, Liang Zongsuo

Published in: BMC Complementary Medicine and Therapies | Issue 1/2023

Abstract

Background

Dendrobium nobile and Dendrobium chrysotoxum are important species of the genus Dendrobium and have great economic and medicinal value. However, the medicinal properties of these two plants remain poorly understood. This study aimed to investigate the medical properties of D. nobile and D. chrysotoxum by conducting a comprehensive chemical profiling of the two plants. Additionally, active compounds and predictive targets for anti-hepatoma activity in D. chrysotoxum extracts were identified using Network Pharmacology.

Results

Chemical profiling showed that altogether 65 phytochemicals were identified from D. nobile and D. chrysotoxum, with major classes as alkaloids, terpenoids, flavonoids, bibenzyls and phenanthrenes. About 18 compounds were identified as the important differential metabolites in D. nobile and D. chrysotoxum. Furtherly, CCK-8 results showed that the extracts of stems and leaves of D. nobile and D. chrysotoxum could inhibit the growth of Huh-7 cells, and the anti-hepatoma activity of extracts were dose-dependent. Among the extracts, the extract of D. chrysotoxum showed significant anti-hepatoma activity. In order to find the potential mechanism of anti-hepatoma activity of D. chrysotoxum, five key compounds and nine key targets were obtained through constructing and analyzing the compound-target-pathway network. The five key compounds were chrysotobibenzyl, chrysotoxin, moscatilin, gigantol and chrysotoxene. Nine key targets, including GAPDH, EGFR, ESR1, HRAS, SRC, CCND1, HIF1A, ERBB2 and MTOR, could be considered as the core targets of the anti-hepatoma activity of D. chrysotoxum.

Conclusions

In this study, the chemical composition difference and anti-hepatoma activity of stems and leaves of D. nobile and D. chrysotoxum were compared, and the potential anti-hepatoma mechanism of D. chrysotoxum was revealed in a multi-target and multi-pathway manner.

Available only for authorised users

Burlacu E, Tanase C. Anticancer potential of natural bark products-a review. Plants (Basel). 2021;10(9):1895. https://doi.org/10.3390/plants10091895CrossRefPubMed

Efferth T, Oesch F. Repurposing of plant alkaloids for cancer therapy: Pharmacology and toxicology. Semin Cancer Biol. 2021;68:143–63. https://doi.org/10.1016/j.semcancer.2019.12.010CrossRefPubMed

Taha KF, Khalil M, Abubakr MS, Shawky E. Identifying cancer-related molecular targets of Nandina domestica Thunb. By network pharmacology-based analysis in combination with chemical profiling and molecular docking studies. J Ethnopharmacol. 2020;249:112413. https://doi.org/10.1016/j.jep.2019.112413CrossRefPubMed

Abotaleb M, Liskova A, Kubatka P, Büsselberg D. Therapeutic potential of plant phenolic acids in the treatment of cancer. Biomolecules. 2020;10(2):221. https://doi.org/10.3390/biom10020221CrossRefPubMedPubMedCentral

Ma L, Zhang M, Zhao R, Wang D, Ma Y, Li A. Plant natural products: promising resources for cancer chemoprevention. Molecules. 2021;26(4):933. https://doi.org/10.3390/molecules26040933CrossRefPubMedPubMedCentral

Wei W, Rasul A, Sadiqa A, Sarfraz I, Hussain G, Nageen B, Liu X, Watanabe N, Selamoglu Z, Ali M, Li X, Li J. Curcumol: from plant roots to Cancer roots. Int J Biol Sci. 2019;15(8):1600–9. https://doi.org/10.7150/ijbs.34716CrossRefPubMedPubMedCentral

Yang S, Zhang X, Cao Z, Zhao K, Wang S, Chen M, Hu X. Growth-promoting Sphingomonas paucimobilis ZJSH1 associated with Dendrobium officinale through phytohormone production and nitrogen fixation. Microb Biotechnol. 2014;7:611–20. https://doi.org/10.1111/1751-7915.12148CrossRefPubMedPubMedCentral

Li RQ, Li JF, Zhou ZY, Guo Y, Zhang TT, Tao FF, Hu XF, Liu WH. Antibacterial and antitumor activity of secondary metabolites of endophytic Fungi Ty5 from Dendrobium officinale. J Biobased Mater Bioenergy. 2018;12:184–93.CrossRef

Teixeira da Silva JA, Ng TB. The medicinal and pharmaceutical importance of Dendrobium species. Appl Microbiol Biotechnol. 2017;101(6):2227–39. https://doi.org/10.1007/s00253-017-8169-9CrossRefPubMed

10.

Shen YC, Korkor NL, Xiao R, Pu Q, Hu M, Zhang SS, Kong DD, Zeng GH, Hu XF. Antagonistic activity of combined bacteria strains against southern blight pathogen of Dendrobium officinale. Biol Control. 2020;151:1049–9644.CrossRef

11.

Committee NP. Pharmacopoeia of the People’s Republic of China, 2020 edn. Beijing: Chemical Industry Press.

12.

Li Q, Liu C, Huang C, Wang M, Long T, Liu J, Shi J, Shi J, Li L, He Y, Xu DL. Transcriptome and metabonomics analysis revealed the molecular mechanism of differential metabolite production of Dendrobium nobile under different epiphytic patterns. Front Plant Sci. 2022;13:868472. https://doi.org/10.3389/fpls.2022.868472CrossRefPubMedPubMedCentral

13.

Nie X, Chen Y, Li W, Lu Y. Anti-aging properties of Dendrobium nobile Lindl: from molecular mechanisms to potential treatments. J Ethnopharmacol. 2020;257:112839. https://doi.org/10.1016/j.jep.2020.112839CrossRefPubMed

14.

He L, Su Q, Bai L, Li M, Liu J, Liu X, Zhang C, Jiang Z, He J, Shi J, Huang S, Guo L. Recent research progress on natural small molecule bibenzyls and its derivatives in Dendrobium species. Eur J Med Chem. 2020;204:112530. https://doi.org/10.1016/j.ejmech.2020.112530CrossRefPubMed

15.

Ng TB, Liu J, Wong JH, Ye X, Wing Sze SC, Tong Y, Zhang KY. Review of research on Dendrobium, a prized folk medicine. Appl Microbiol Biotechnol. 2012 Mar;93(5):1795–803. https://doi.org/10.1007/s00253-011-3829-7

16.

Pei C, Mi CY, Sun LH, Liu WH, Li O, Hu XF. Diversity of endophytic bacteria of Dendrobium officinale based on culture-dependent and culture-independent methods. Biotechnol Biotechnol Equip. 2017;31:112–9.CrossRef

17.

Yang CW, Chuang TH, Wu PL, Huang WH, Lee SJ. Anti-inflammatory effects of 7-methoxycryptopleurine and structure-activity relations of phenanthroindolizidines and phenanthroquinolizidines. Biochem Biophys Res Commun. 2007;354(4):942–8. https://doi.org/10.1016/j.bbrc.2007.01.065CrossRefPubMed

18.

Wang YH. Traditional uses, chemical constituents, pharmacological activities, and toxicological effects of Dendrobium leaves: a review. J Ethnopharmacol. 2021;270:113851. https://doi.org/10.1016/j.jep.2021.113851CrossRefPubMed

19.

Cao H, Ji Y, Li S, Lu L, Tian M, Yang W, Li H. Extensive metabolic profiles of Leaves and stems from the Medicinal Plant Dendrobiumofficinale Kimura et Migo. Metabolites. 2019;9(10):215. https://doi.org/10.3390/metabo9100215CrossRefPubMedPubMedCentral

20.

Zhang Y, Chen N, Ding Z, Gu Z, Zhang L, Shi G. Characterization and bioactivity analysis of Dendrobium officinale stem and leaf polysacchride. J Food Sci Biotechnol. 2017;36:959–65.

21.

Zhou GF, Pang MX, Chen SH, Lv GY, Yan MQ. [Comparison on polysaccharide content and PMP-HPLC fingerprints of polysaccharide in stems and leaves of Dendrobium officinale]. Zhongguo Zhong Yao Za Zhi. 2014;39(5):795–802. Chinese.PubMed

22.

Liu WJ, Jiang ZM, Chen Y, Xiao PT, Wang ZY, Huang TQ, Liu EH. Network pharmacology approach to elucidate possible action mechanisms of Sinomenii Caulis for treating osteoporosis. J Ethnopharmacol. 2020;15:257:112871. https://doi.org/10.1016/j.jep.2020.112871CrossRef

23.

NamNam HH, Kim JS, Lee J, Seo YH, Kim HS, Ryu SM, Choi G, Moon BC, Lee AY. Pharmacological effects of Agastache rugosa against gastritis using a network pharmacology approach. Biomolecules. 2020;10(9):1298. https://doi.org/10.3390/biom10091298CrossRef

24.

Li S, Xue X, Yang X, Zhou S, Wang S, Meng J. A network pharmacology approach used to estimate the active ingredients of Moutan cortex charcoal and the potential targets in hemorrhagic diseases. Biol Pharm Bull. 2019;42(3):432–41. https://doi.org/10.1248/bpb.b18-00756CrossRefPubMed

25.

Zhao J, Lv C, Wu Q, Zeng H, Guo X, Yang J, Tian S, Zhang W. Computational systems pharmacology reveals an antiplatelet and neuroprotective mechanism of Deng-Zhan-Xi-Xin injection in the treatment of ischemic stroke. Pharmacol Res. 2019;147:104365. https://doi.org/10.1016/j.phrs.2019.104365CrossRefPubMed

26.

Lan Q, Liu C, Wu Z, Ni C, Li J, Huang C, Wang H, Wei G. Does the metabolome of wild-like Dendrobium officinale of different origins have regional differences? Molecules. 2022;27(20):7024. https://doi.org/10.3390/molecules27207024CrossRefPubMedPubMedCentral

27.

Yu X, Wang Y, Tao S, Sun S. Geniposide plays anti-tumor effects by down-regulation of microRNA-224 in HepG2 and Huh7 cell lines. Exp Mol Pathol. 2020;112:104349. https://doi.org/10.1016/j.yexmp.2019.104349CrossRefPubMed

28.

Machon C, Catez F, Venezia ND, Vanhalle F, Guyot L, Vincent A, Garcia M, Roy B, Diaz JJ, Guitton J. Study of intracellular anabolism of 5-fluorouracil and incorporation in nucleic acids based on an LC-HRMS method. J Pharm Anal. 2021;11(1):77–87. https://doi.org/10.1016/j.jpha.2020.04.001CrossRefPubMed

29.

Xia J, Li XY, Lin M, Yu JN, Zeng ZD, Ye F, Hu GJ, Miu Q, He QL, Zhang XD, Liang ZS. Screening out biomarkers of Tetrastigma hemsleyanum for anti-cancer and anti-inflammatory based on spectrum-effect relationship coupled with UPLC-Q-TOF-MS. Molecules. 2023;28(7):3021. https://doi.org/10.3390/molecules28073021CrossRefPubMedPubMedCentral

30.

Daina A, Michielin O, Zoete V. SwissTargetPrediction: updated data and new features for efficient prediction of protein targets of small molecules. Nucleic Acids Res. 2019;47(W1):W357–64. https://doi.org/10.1093/nar/gkz382CrossRefPubMedPubMedCentral

31.

Piñero J, Queralt-Rosinach N, Bravo À, Deu-Pons J, Bauer-Mehren A, Baron M, Sanz F, Furlong LI. DisGeNET: a discovery platform for the dynamical exploration of human diseases and their genes. Database (Oxford). 2015 Apr 15;2015:bav028. https://doi.org/10.1093/database/bav028

32.

Stelzer G, Rosen N, Plaschkes I, Zimmerman S, Twik M, Fishilevich S, Stein TI, Nudel R, Lieder I, Mazor Y, Kaplan S, Dahary D, Warshawsky D, Guan-Golan Y, Kohn A, Rappaport N, Safran M, Lancet D. The GeneCards suite: from gene data mining to disease genome sequence analyses. Curr Protoc Bioinformatics. 2016;54:1. https://doi.org/10.1002/cpbi.5CrossRef

33.

Amberger JS, Bocchini CA, Scott AF, Hamosh A. OMIM.org: leveraging knowledge across phenotype-gene relationships. Nucleic Acids Res. 2019;47(D1):D1038–43. https://doi.org/10.1093/nar/gky1151CrossRefPubMed

34.

UniProt Consortium. UniProt: the universal protein knowledgebase in 2021. Nucleic Acids Res. 2021;49(D1):D480–9. https://doi.org/10.1093/nar/gkaa1100CrossRef

35.

Szklarczyk D, Morris JH, Cook H. The STRING database in 2017: quality-controlled protein-protein association networks, made broadly accessible. Nucleic Acids Res. 2017;45(D1):D362–8. https://doi.org/10.1093/nar/gkw937CrossRefPubMed

36.

Huang DW, Sherman BT, Lempicki RA. Systematic and integrative analysis of large gene lists using DAVID bioinformatics resources. Nat Protoc. 2009;4(1):44–57. https://doi.org/10.1038/nprot.2008.211CrossRefPubMed

37.

Kanehisa M, Goto S. KEGG: kyoto encyclopedia of genes and genomes. Nucleic Acids Res. 2000 Jan 1;28(1):27–30. https://doi.org/10.1093/nar/28.1.27

38.

Kanehisa M. Toward understanding the origin and evolution of cellular organisms. Protein Sci. 2019 Nov;28(11):1947–51. https://doi.org/10.1002/pro.3715

39.

Kanehisa M, Furumichi M, Sato Y, Ishiguro-Watanabe M, Tanabe M. KEGG: integrating viruses and cellular organisms. Nucleic Acids Res. 2021;49(D1):D545–51. https://doi.org/10.1093/nar/gkaa970CrossRefPubMed

40.

Prasad R, Rana NK, Koch B. Dendrobium chrysanthum ethanolic extract induces apoptosis via p53 up-regulation in HeLa cells and inhibits tumor progression in mice. J Complement Integr Med. 2017;14(2). https://doi.org/10.1515/jcim-2016-0070

41.

Wu Y, Jing R, Jiang L, Jiang Y, Kuang Q, Ye L, Yang L, Li Y, Li M. Combination use of protein-protein interaction network topological features improves the predictive scores of deleterious non-synonymous single-nucleotide polymorphisms. Amino Acids. 2014;46(8):2025–35. https://doi.org/10.1007/s00726-014-1760-9CrossRefPubMed

42.

Dennis G Jr, Sherman BT, Hosack DA, Yang J, Gao W, Lane HC, Lempicki R. A. DAVID: database for annotation, visualization, and Integrated Discovery. Genome biology;2003, 4(5), P3.

43.

Dixon RA, Strack D. Phytochemistry meets genome analysis, and beyond. Phytochemistry. 2003;62(6):815–6. https://doi.org/10.1016/s0031-9422(02)00712-4CrossRefPubMed

44.

Hu W, Zheng Y, Xia P, Liang Z. The research progresses and future prospects of Tetrastigma hemsleyanum Diels et gilg: a valuable chinese herbal medicine. J Ethnopharmacol. 2021;271:113836. https://doi.org/10.1016/j.jep.2021.113836CrossRefPubMed

45.

Hu W, Xia P, Liang Z. Molecular cloning and structural analysis of key enzymes in Tetrastigma hemsleyanum for resveratrol biosynthesis. Int J Biol Macromol. 2021;190:19–32. https://doi.org/10.1016/j.ijbiomac.2021.08.178CrossRefPubMed

46.

Xu L, Cao M, Wang Q, Xu J, Liu C, Ullah N, Li J, Hou Z, Liang Z, Zhou W, Liu A. Insights into the plateau adaptation of Salvia castanea by comparative genomic and WGCNA analyses. J Adv Res. 2022;42:221–35. https://doi.org/10.1016/j.jare.2022.02.004CrossRefPubMedPubMedCentral

47.

Xiang Q, Hu S, Ligaba-Osena A, Yang J, Tong F, Guo W. Seasonal Variation in Transcriptomic profiling of Tetrastigma hemsleyanum fully developed tuberous roots enriches candidate genes in essential metabolic pathways and Phytohormone Signaling. Front Plant Sci. 2021;12:659645. https://doi.org/10.3389/fpls.2021.659645CrossRefPubMedPubMedCentral

48.

Ke L, Yu D, Zheng H, Xu Y, Wu Y, Jiao J, Wang X, Mei J, Cai F, Zhao Y, Sun J, Zhang X, Sun Y. Function deficiency of GhOMT1 causes anthocyanidins over-accumulation and diversifies fibre colours in cotton (Gossypium hirsutum). Plant Biotechnol J. 2022;20(8):1546–60. https://doi.org/10.1111/pbi.13832CrossRefPubMedPubMedCentral

49.

Singh D, Chaudhuri PK. A review on phytochemical and pharmacological properties of Holy basil (Ocimum sanctum L). Ind Crops Prod. 2018;118:367–82.CrossRef

50.

Xiao J, Bai W. Bioactive phytochemicals. Crit Rev Food Sci Nutr. 2019;59(6):827–9.CrossRefPubMed

51.

Fukushima A, Takahashi M, Nagasaki H, Aono Y, Kobayashi M, Kusano M, Saito K, Kobayashi N, Arita M. Development of RIKEN plant metabolome MetaDatabase. Plant Cell Physiol. 2022;63(3):433–40. https://doi.org/10.1093/pcp/pcab173CrossRefPubMed

52.

Zhou B, Xiao JF, Tuli L, Ressom HW. LC-MS-based metabolomics. Mol Biosyst. 2012;8(2):470–81. https://doi.org/10.1039/c1mb05350gCrossRefPubMed

53.

Xia PG, Li QQ, Liang ZS, Zhang XM, Yan KJ. Spaceflight breeding could improve the volatile constituents of Andrographis paniculata. Ind Crops Prod. 2021;171:113967.CrossRef

54.

Mahrous EA, Farag MA. Two dimensional NMR spectroscopic approaches for exploring plant metabolome: a review. J Adv Res. 2015;6(1):3–15. https://doi.org/10.1016/j.jare.2014.10.003CrossRefPubMed

55.

Chen XM, Xiao SY, Guo SX. [Comparison of chemical compositions between Dendrobium candidum and Dendrobium nobile]. Zhongguo Yi Xue Ke Xue Yuan Xue Bao. 2006 Aug;28(4):524–9. Chinese.

56.

Lam Y, Ng TB, Yao RM. Evaluation of chemical constituents and important mechanism of pharmacological biology in dendrobium plants. Evid Based Complement Alternat Med. 2015;2015:841752. https://doi.org/10.1155/2015/841752CrossRefPubMedPubMedCentral

57.

Liu Y, Zhang JQ, Zhan R, Chen YG. Isopentenylated bibenzyls and phenolic compounds from Dendrobium chrysotoxum Lindl. Chem Biodivers. 2022;19(6):e202200259. https://doi.org/10.1002/cbdv.202200259CrossRefPubMed

58.

Zhang Y, Zhang GQ, Zhang D, Liu XD, Xu XY, Sun WH, Yu X, Zhu X, Wang ZW, Zhao X, Zhong WY, Chen H, Yin WL, Huang T, Niu SC, Liu ZJ. Chromosome-scale assembly of the Dendrobium chrysotoxum genome enhances the understanding of orchid evolution. Hortic Res. 2021;8(1):183. https://doi.org/10.1038/s41438-021-00621-zCrossRefPubMedPubMedCentral

59.

Takamiya T, Wongsawad P, Sathapattayanon A, Tajima N, Suzuki S, Kitamura S, Shioda N, Handa T, Kitanaka S, Iijima H, Yukawa T. Molecular phylogenetics and character evolution of morphologically diverse groups, Dendrobium section Dendrobium and allies. AoB Plants. 2014;6:plu045. https://doi.org/10.1093/aobpla/plu045CrossRefPubMedPubMedCentral

60.

Zheng S, Hu Y, Zhao R, Zhao T, Li H, Rao D, Chun Z. Quantitative assessment of secondary metabolites and cancer cell inhibiting activity by high performance liquid chromatography fingerprinting in Dendrobium nobile. J Chromatogr B Analyt Technol Biomed Life Sci. 2020;1140:122017. https://doi.org/10.1016/j.jchromb.2020.122017CrossRefPubMed

61.

Gong YQ, Fan Y, Wu DZ, Yang H, Hu ZB, Wang ZT. In vivo and in vitro evaluation of erianin, a novel anti-angiogenic agent. Eur J Cancer. 2004;40(10):1554–65. https://doi.org/10.1016/j.ejca.2004.01.041CrossRefPubMed

62.

Yang LC, Deng H, Yi Y, Zhang XM, Wang YZ, Lin JQ. [Identification of medical Dendrobium herbs by ISSR marker]. Zhong Yao Cai. 2010;33(12):1841–4. Chinese.PubMed

63.

Hindson J. Lenvatinib plus EGFR inhibition for liver cancer. Nat Reviews Gastroenterology&Hepatology. 2021;18:675. https://doi.org/10.1038/s41575-021-00513-6CrossRef

64.

Yamada K, Kizawa R, Yoshida A, Koizumi R, Motohashi S, Shimoyama Y, Hannya Y, Yoshida S, Oikawa T, Shimoda M, Yoshida K. Extracellular PKCδ signals to epidermal growth factor receptor for tumor proliferation in liver cancer cells. Cancer Sci. 2022;113(7):2378–85. https://doi.org/10.1111/cas.15386CrossRefPubMedPubMedCentral

65.

Yang L, Peng F, Qin J, Zhou H, Wang B. Downregulation of microRNA-196a inhibits human liver cancer cell proliferation and invasion by targeting FOXO1. Oncol Rep. 2017;38:2148–54. https://doi.org/10.3892/or.2017.5873CrossRefPubMedPubMedCentral

66.

Wang Q, Yang X, Zhou X, Wu B, Zhu D, Jia W, Chu J, Wang J, Wu J, Kong L. MiR-3174 promotes proliferation and inhibits apoptosis by targeting FOXO1 in hepatocellular carcinoma. Biochem Biophys Res Commun. 2020;526:889–97. https://doi.org/10.1016/j.bbrc.2020.03.152CrossRefPubMed

Title: Comprehensive chemical profiling of two Dendrobium species and identification of anti-hepatoma active constituents from Dendrobium chrysotoxum by network pharmacology
Authors: Xia Jie
Yin Feng
Fang Jiahao
Lou Ganggui
Yu Jiani
Xu Zhongyu
Yuan Yuan
Zhang Tinggang
Zhang Xiaodan
Liang Zongsuo
Publication date: 01-12-2023
Publisher: BioMed Central
Keywords: Alkaloids
Alkaloids
Published in: BMC Complementary Medicine and Therapies / Issue 1/2023
Electronic ISSN: 2662-7671
DOI: https://doi.org/10.1186/s12906-023-04048-y

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Comprehensive chemical profiling of two Dendrobium species and identification of anti-hepatoma active constituents from Dendrobium chrysotoxum by network pharmacology

Abstract

Background

Results

Conclusions

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Background

Results

Conclusions

Please log in to get access to this content

Other articles of this Issue 1/2023

Integrated traditional herbal medicine in the treatment of gastrointestinal disorder: the pattern of use and the knowledge of safety among the Eastern Region Saudi population

Comparative anticancer effects of Annona muricata Linn (Annonaceae) leaves and fruits on DMBA-induced breast cancer in female rats

A comparative analysis of complementary therapies use among patients attending diabetic clinics in Taiwan: 2007 vs. 2023

Correction: Anti-inflammatory effect of naringin and sericin combination on human peripheral blood mononuclear cells (hPBMCs) from patient with psoriasis

Correction : Icariin-conditioned serum engineered with hyaluronic acid promote repair of articular cartilage defects in rabbit knees

Screening of major hepatotoxic components of Tripterygium wilfordii based on hepatotoxic injury patterns