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Isoginkgetin: Advances on Resources, Bioactivity, and Pharmacology

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Handbook of Dietary Flavonoids

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Abstract

Isoginkgetin (4′,4″-dimethylamentoflavone) is a dimeric flavonoid, isomer of the biflavonoid ginkgetin, after which it was named. It was first isolated from the leaves of ginkgo (Ginkgo biloba L.) and later from other plant sources, but its role in plants is still unknown. It is mainly known as a general pre-mRNA splicing inhibitor, and as such, it has been implicated in research as a new avenue for the development of new anticancer drugs. In addition to its potential role in cancer prevention, there is also information on its beneficial role in the treatment of neurodegenerative and cardiovascular diseases, as well as possible anti-inflammatory, antioxidant, and antimicrobial, especially antiviral, activity. Most of the current data are based on in silico or in vitro research. This chapter summarizes the information on the occurrence of isoginkgetin in different plant species and the current data on its possible pharmacological use and mechanism of action. We also provide further perspectives on isoginkgetin research.

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References

  • Balga VP, McGaw LJ, Elgorashi EE, Eloff JN (2014) Antimicrobial activity, toxicity and selectivity index of two biflavonoids and a flavone isolated from Podocarpus henkelii (Podocarpaceae) leaves. BMC Complement Altern Med 14(1):383

    Article  Google Scholar 

  • Barbalho SM, Direito R, Laurindo LF, Marton LT, Guiguer EL, Goulart RdA, Tofano RJ, Carvalho ACA, Flato UAP, Capelluppi Tofano VA, Penteado Detregiachi CR, Santos Bueno PC, Girio RSJ, Araújo AC (2022) Ginkgo biloba in the aging process: a narrative review. Antioxidants 11(3):525

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Cao Y, Tan NH, Chen JJ, Zeng GZ, Ma YB, Wu YP, Yan H, Yang J, Lu LF, Wang Q (2010) Bioactive flavones and biflavones from Selaginella moellendorffii Hieron. Fitoterapia 81(4):253–258

    Article  CAS  PubMed  Google Scholar 

  • Chen TR, Wei LH, Guan XQ, Huang C, Liu ZY, Wang FJ, Hou J, Jin Q, Liu YF, Wen PH, Zhang SJ, Ge GB, Guo WZ (2019) Biflavones from Ginkgo biloba as inhibitors of human thrombin. Bioorg Chem 92:103199

    Article  CAS  PubMed  Google Scholar 

  • Chen X, Zhong W, Shu C, Yang H, Li E (2021) Comparative analysis of chemical constituents and bioactivities of the extracts from leaves, seed coats and embryoids of Ginkgo biloba L. Nat Prod Res 35(23):5498–5501

    Article  CAS  PubMed  Google Scholar 

  • Cheng KT, Hsu FL, Chen SH, Hsieh PK, Huang HS, Lee CK, Lee MH (2007) New constituent from Podocarpus macrophyllus var. macrophyllus shows anti-tyrosinase effect and regulates tyrosinase-related proteins and mRNA in human epidermal melanocytes. Chem Pharm Bull 55(5):757–761

    Article  CAS  Google Scholar 

  • Eymin B (2021) Targeting the spliceosome machinery: a new therapeutic axis in cancer? Biochem Pharmacol 189:114039

    Article  CAS  PubMed  Google Scholar 

  • Gai QY, Jiao J, Wang X, Liu J, Fu YJ, Lu Y, Wang ZY, Xu XJ (2020) Simultaneous determination of taxoids and flavonoids in twigs and leaves of three Taxus species by UHPLC-MS/MS. J Pharm Biomed Anal 189:113456

    Article  CAS  PubMed  Google Scholar 

  • He K, Timmermann BN, Aladesanmi AJ, Zeng L (1996) A biflavonoid from Dysoxylum lenticellare gillespie. Phytochemistry 42(4):1199–1201

    Article  CAS  Google Scholar 

  • He X, Yang F, Huang X (2021) Proceedings of chemistry, pharmacology, pharmacokinetics and synthesis of biflavonoids. Molecules 26(19):6088

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Hwang YL, Lee MH, Oh HI, Kim HJ, Lim CA, Lee JH, Kim CD (2018) Isoginkgetin inhibits insulin-like growth factor-1-induced sebum production in cultured human sebocytes. Ann Dermatol 30(3):394–396

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Ismail A, Hassan HM, Moawad AS, Fattah SMA, Sherif NH, Abdelmohsen UR, Radwan MM, Rateb ME, Hetta MH (2020) Chemical composition and therapeutic potential of three Cycas species in brain damage and pancreatitis provoked by γ-radiation exposure in rats. J Radiat Res Appl Sci 13(1):200–214

    CAS  Google Scholar 

  • Iwashina T, Tobe H, Nakane T, Mizuno T, Jaffrè T (2022) Flavonoids and phenolic compounds from the parasitic gymnosperm Parasitaxus usta endemic to New Caledonia. Nat Prod Commun 17(1):1–6

    Google Scholar 

  • Kang SS, Lee JY, Choi YK, Song SS, Kim JS, Jeon SJ, Han YN, Son KH, Han BH (2005) Neuroprotective effects of naturally occurring biflavonoids. Bioorg Med Chem Lett 15:3588–3591

    Article  CAS  PubMed  Google Scholar 

  • Krauze-Baranowska M, Pobłocka L, El Hela AA (2005) Biflavones from Chamaecyparis obtusa. Z Naturforsch C 60(9–10):679–685

    Article  CAS  PubMed  Google Scholar 

  • Lee SJ, Choi JH, Son KH, Chang HW, Kang SS, Kim HP (1995) Suppression of mouse lymphocyte proliferation in vitro by naturally-occurring biflavonoids. Life Sci 57(6):551–558

    Article  CAS  PubMed  Google Scholar 

  • Lee MK, Lim SW, Yang H, Sung SH, Lee HS, Park MJ, Kim YC (2006) Osteoblast differentiation stimulating activity of biflavonoids from Cephalotaxus koreana. Bioorg Med Chem Lett 16(11):2850–2854

    Article  CAS  PubMed  Google Scholar 

  • Li M, Li B, Hou Y, Tian Y, Chen L, Liu S, Zhang N, Dong J (2019a) Anti-inflammatory effects of chemical components from Ginkgo biloba L. male flowers on lipopolysaccharide-stimulated RAW264.7 macrophages. Phytother Res 33(4):989–997

    Article  CAS  PubMed  Google Scholar 

  • Li M, Li B, Xia ZM, Tian Y, Zhang D, Rui WJ, Dong JX, Xiao FJ (2019b) Anticancer effects of five biflavonoids from Ginkgo biloba L. male flowers in vitro. Molecules 24(8):1496

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Li X, Ouyang X, Cai R, Chen D (2019c) 3′,8″-dimerization enhances the antioxidant capacity of flavonoids: evidence from acacetin and isoginkgetin. Molecules 24(11):2039

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Li P, Zhang F, Li Y, Zhang C, Yang Z, Zhang Y, Song C (2021a) Isoginkgetin treatment attenuated lipopolysaccharide-induced monoamine neurotransmitter deficiency and depression-like behaviors through downregulating p38/NF-κB signaling pathway and suppressing microglia-induced apoptosis. J Psychopharmacol 35(10):1285–1299

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Li Y, Meng L, Li B, Huang D, Huang X, Lin C, Li D, Qiu S, Wu Y, Wei Z, Li X (2021b) Isoginkgetin attenuates endoplasmic reticulum stress-induced autophagy of brain after ischemic reperfusion injury. Bioengineered. https://doi.org/10.1080/21655979.2021.1997564. (in press)

  • Liu PK, Weng ZM, Ge GB, Li HL, Ding LL, Dai ZR, Hou XD, Leng YH, Yu Y, Hou J (2018) Biflavones from Ginkgo biloba as novel pancreatic lipase inhibitors: inhibition potentials and mechanism. Int J Biol Macromol 118(B):2216–2223

    Article  CAS  PubMed  Google Scholar 

  • Martínez-Montiel N, Rosas-Murrieta NH, Martínez-Montiel M, Gaspariano-Cholula MP, Martínez-Contreras RD (2016) Microbial and natural metabolites that inhibit splicing: a powerful alternative for cancer treatment. Biomed Res Int 2016:3681094

    Article  PubMed  PubMed Central  Google Scholar 

  • Moawad A, El Amir D (2016) Ginkgetin or isoginkgetin: the dimethylamentoflavone of Dioon edule Lindl. leaves. Eur J Med Plants 16(3):1–7

    Article  Google Scholar 

  • Moawad A, Hetta M, Zjawiony JK, Jacob MR, Hifnawy M, Marais JPJ, Ferreira D (2010) Phytochemical investigation of Cycas circinalis and Cycas revoluta leaflets: moderately active antibacterial biflavonoids. Planta Med 76(08):796–802

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Nakano D, Ishitsuka K, Ishihara M, Tsuchihashi R, Okawa M, Tamura K, Kinjo J (2021) Screening of promising chemotherapeutic candidates from plants against human adult T-cell leukemia/lymphoma (VII): active principles from Thuja occidentalis L. Molecules 26(24):7619

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Negm WA, El-Seoud KAA, Kabbash A, Kassab AA, El-Aasr M (2020) Hepatoprotective, cytotoxic, antimicrobial and antioxidant activities of Dioon spinulosum leaves Dyer Ex Eichler and its isolated secondary metabolites. Nat Prod Res 35(23):5166–5176

    Article  PubMed  Google Scholar 

  • O’Brien K, Matlin AJ, Lowell AM, Moore MJ (2008) The biflavonoid isoginkgetin is a general inhibitor of pre-mRNA splicing. J Biol Chem 283(48):33147–33154

    Article  PubMed  PubMed Central  Google Scholar 

  • Raj V, Lee JH, Shim JJ, Lee J (2022) Antiviral activities of 4H-chromen-4-one scaffold-containing flavonoids against SARS–CoV–2 using computational and in vitro approaches. J Mol Liq 353:118775

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Šamec D, Karalija E, Šola I, Vujčić BV, Salopek-Sondi B (2021) The role of polyphenols in abiotic stress response: the influence of molecular structure. Plan Theory 10:118

    Google Scholar 

  • Šamec D, Karalija E, Dahija S, Hassan STS (2022) Biflavonoids: important contributions to the health benefits of ginkgo (Ginkgo biloba L.). Plants 11:1381

    Article  PubMed  PubMed Central  Google Scholar 

  • Sasaki H, Kitoh Y, Tsukada M, Miki K, Koyama K, Juliawaty LD, Hakim EH, Takahashi K, Kinoshita K (2015) Inhibitory activities of biflavonoids against amyloid-β peptide 42 cytotoxicity in PC-12 cells. Bioorg Med Chem Let 25(14):2831–2833

    Article  CAS  Google Scholar 

  • Semwal RB, Semwal DK, Combrinck S, Trill J, Gibbons S, Viljoen A (2019) Acacetin – a simple flavone exhibiting diverse pharmacological activities. Phytochem Lett 32:56–65

    Article  CAS  Google Scholar 

  • Shao N, Feng Z, Li N (2022) Isoginkgetin inhibits inflammatory response in the fibroblast-like synoviocytes of rheumatoid arthritis by suppressing matrix metallopeptidase 9 expression. Chem Biol Drug Des 99(6):923–929

    Article  CAS  PubMed  Google Scholar 

  • Song YQ, He RJ, Pu D, Guan XQ, Shi JH, Li YG, Hou J, Jia SN, Qin WW, Fang SQ, Ge GB (2021) Discovery and characterization of the biflavones from Ginkgo biloba as highly specific and potent inhibitors against human carboxylesterase 2. Front Pharmacol 12:655659

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Theerawatanasirikul S, Thangthamniyom N, Kuo CJ, Semkum P, Phecharat N, Chankeeree P, Lekcharoensuk P (2021) Natural phytochemicals, luteolin and isoginkgetin, inhibit 3C protease and infection of FMDV, in silico and in vitro. Viruses 13:2118

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Tsalikis J, Abdel-Nour M, Farahvash A, Sorbara MT, Poon S, Philpott DJ, Girardin SE (2019) Isoginkgetin, a natural biflavonoid proteasome inhibitor, sensitizes cancer cells to apoptosis via disruption of lysosomal homeostasis and impaired protein clearance. Mol Cell Biol 39(10):e00489–e00418

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Uddin S, Kabir T, Tewari D, Mathew B, Aleya L (2020) Emerging signal regulating potential of small molecule biflavonoids to combat neuropathological insults of Alzheimer disease. Sci Total Environ 700:134836

    Article  CAS  PubMed  Google Scholar 

  • Vanzyl EJ, Rick KRC, Blackmore AB, MacFarlane EM, McKay BC (2018) Flow cytometric analysis identifies changes in S and M phases as novel cell cycle alterations induced by the splicing inhibitor isoginkgetin. PLoS One 13(1):e0191178

    Article  PubMed  PubMed Central  Google Scholar 

  • Vanzyl EJ, Sayed H, Blackmore AB, Rick KRC, Fernando P, McKay BC (2020) The spliceosome inhibitors isoginkgetin and pladienolide B induce ATF3-dependent cell death. PLoS One 15(12):e0224953

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Wang J, Chen X, Bai W, Wang Z, Xiao W, Zhu J (2021) Study on mechanism of Ginkgo biloba L. leaves for the treatment of neurodegenerative diseases based on network pharmacology. Neurochem Res 46:1881–1894

    Article  CAS  PubMed  Google Scholar 

  • Weniger B, Vonthron-Sénécheau C, Kaiser M, Brun R, Anton R (2006) Comparative antiplasmodial, leishmanicidal and antitrypanosomal activities of several biflavonoids. Phytomedicine 13(3):176–180

    Article  CAS  PubMed  Google Scholar 

  • Yao X, Zhou GS, Tang YP, Qian YF, Guan HL, Pang H, Zhu S, Mo X, Su SL, Jin C, Qin Y, Qian DW, Duan JA (2013) Simultaneous quantification of flavonol glycosides, terpene lactones, biflavones, proanthocyanidins, and ginkgolic acids in Ginkgo biloba leaves from fruit cultivars by ultrahigh-performance liquid chromatography coupled with triple quadrupole mass spectrometry. Biomed Res Int 2013:582591

    Article  PubMed  Google Scholar 

  • Yoon SO, Shin S, Lee HJ, Chun HK, Chung AS (2006) Isoginkgetin inhibits tumor cell invasion by regulating phosphatidylinositol 3-kinase/Akt-dependent matrix metalloproteinase-9 expression. Mol Cancer Ther 5(11):2666–2675

    Article  CAS  PubMed  Google Scholar 

  • Yue T, Sheng Q, Luo Y, Xiao Z, Wang Y, Song W, Yan M, Niu H, Zhang T, Li N (2021) Biflavonoids and oligomeric flavonoids from food. In: Handbook of dietary phytochemicals. Springer, pp 155–203

    Chapter  Google Scholar 

  • Zhang L, Wu T, Xiao W, Wang Z, Ding G, Zhao L (2018) Enrichment and purification of total ginkgo flavonoid O-glycosides from Ginkgo biloba extract with macroporous resin and evaluation of anti-inflammation activities in vitro. Molecules 23(5):1167

    Article  PubMed  PubMed Central  Google Scholar 

  • Zhao C, Han S, Yang S, Xin W (2019) Validation and application of a novel LC/MS/MS method for the determination of isoginkgetin in rat plasma. Biomed Chromatogr 33(11):e4667

    Article  CAS  PubMed  Google Scholar 

  • Zhou Z, Fu C (2013) A new flavanone and other constituents from the rhizomes of Cyperus rotundus and their antioxidant activities. Chem Nat Compd 48(6):963–965

    Article  CAS  Google Scholar 

  • Zhou HF, Xie C, Jian R, Kang J, Li Y, Zhuang CL, Yang F, Zhang LL, Lai L, Wu T, Wu X (2011) Biflavonoids from carper (Capparis spinosa L.) fruits and their effects in inhibiting NF-kappa B activation. J Agric Food Chem 59(7):3060–3065

    Article  CAS  PubMed  Google Scholar 

  • Zhou GS, Zhang J, Huan XY, Zhuang Y, Xu SY, Liu JS, Tan YJ, Tao HJ, Chen JQ, Pu ZJ, Zhu ZH, Shi X-Q, Tang Y, Tan Y, Dua J-A (2021) Simultaneous quantification of multiple active components of the combination of ginkgo ketoester tablet and donepezil in four biological matrices from dementia mice: application to study the distribution patterns of the two drugs based on “brain-gut” axis. https://ssrn.com/abstract=3937061

  • Zyl E, Tolls V, Blackmore A, McKay BC (2021) Isoginkgetin leads to decreased protein synthesis and activates an ATF4-dependent transcriptional response. Biochim Biophys Acta (BBA) Mol Cell Res 1868(12):119123

    Article  Google Scholar 

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Acknowledgments

This work has been supported by Croatian Science Foundation project “Biflavonoids role in plants: Ginkgo biloba L. as a model system” under the project no. UIP-2019-04-1018.

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Authors and Affiliations

  1. Department of Food Technology, University Center Koprivnica, University North, Koprivnica, Croatia

    Dunja Šamec

  2. Department of Food Technology, University Center Koprivnica, Koprivnica, Croatia

    Iva Jurčević-Šangut

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  1. Dunja Šamec
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  2. Iva Jurčević-Šangut
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Correspondence to Dunja Šamec .

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Editors and Affiliations

  1. Department of Analytical Chemistry and Food Science, Universidade de Vigo, Vigo, Spain

    Jianbo Xiao

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Šamec, D., Jurčević-Šangut, I. (2024). Isoginkgetin: Advances on Resources, Bioactivity, and Pharmacology. In: Xiao, J. (eds) Handbook of Dietary Flavonoids. Springer, Cham. https://doi.org/10.1007/978-3-030-94753-8_65-2

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  • DOI: https://doi.org/10.1007/978-3-030-94753-8_65-2

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  • Publisher Name: Springer, Cham

  • Print ISBN: 978-3-030-94753-8

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  1. Latest

    Isoginkgetin: Advances on Resources, Bioactivity, and Pharmacology
    Published:
    20 November 2023

    DOI: https://doi.org/10.1007/978-3-030-94753-8_65-2

  2. Original

    Isoginkgetin: Advances on Resources, Bioactivity, and Pharmacology
    Published:
    09 September 2023

    DOI: https://doi.org/10.1007/978-3-030-94753-8_65-1

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