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New biflavonoids isolated from Xylia kerrii leaves extract with selective cytotoxicity against MH7A human rheumatoid arthritis synovial fibroblast cells

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Abstract

Three new biflavonoids (13) and two known flavonoids (4, 5) were isolated from Xylia kerrii collected in Thailand. Compounds 15 showed selective cytotoxicity against the rheumatoid fibroblast-like synovial MH7A cell line, and these compounds showed weak cytotoxicity against the human lung synovial fibroblast WI-38 VA13 sub 2 RA cell line. Notably, compound 1 was highly selective toward MH7A cells with an IC50 value of 6.9 μM, whereas the IC50 value for WI-38 VA13 sub 2 RA cells was > 100 μM. The western blotting analysis of MH7A cells treated with compound 1 showed increased CDKN2A /p16INK4A and caspase-8 levels.

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References

  1. Bartok B, Firestein GS (2010) Fibroblast-like synoviocytes: key effector cells in rheumatoid arthritis. Immunol Rev 233:233–255. https://doi.org/10.1111/j.0105-2896.2009.00859.x

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. Bullock J, Rizvi AAS, Saleh AM, Ahmed SS, Do DP, Ansari RA, Ahmed J (2019) Rheumatoid arthritis: a brief overview of the treatment. Med Princ Pract 27:501–507. https://doi.org/10.1159/000493390

    Article  Google Scholar 

  3. Miyazawa K, Mori A, Okudaira H (1998) Establishment and characterization of a novel human rheumatoid fibroblast-like synoviocyte line, MH7A, immortalized with SV40 T antigen. J Biochem 124:1153–1162

    Article  CAS  PubMed  Google Scholar 

  4. Hashiguchi M, Suzuki K, Kaneko K, Nagaoka I (2017) Effect of aloe-emodin on the proliferation and apoptosis of human synovial MH7A cells; a comparison with methotrexate. Mol Med Rep 15:4398–4404. https://doi.org/10.3892/mmr.2017.6541

    Article  CAS  PubMed  Google Scholar 

  5. Sun HN, Luo YH, Meng LQ, Piao XJ, Wang Y, Wang JR, Wang H, Zhang Y, Li JQ, Xu WT, Liu Y, Zhang Y, Zhang T, Han YH, Jin MH, Shen GN, Zang YQ, Cao LK, Zhang DJ, Jin CH (2019) Cryptotanshinone induces reactive oxygen species-mediated apoptosis in human rheumatoid arthritis fibroblast-like synoviocytes. Int J Mol Med 43:1067–1075. https://doi.org/10.3892/ijmm.2018.4012

    Article  CAS  PubMed  Google Scholar 

  6. Fujii K, Hara Y, Arai MA, Sadhu SK, Ahmed F, Ishibashi M (2022) Natural compounds with BMI1 promoter inhibitory activity from Mammea siamensis and Andrographis paniculata. Chem Pharm Bull 70:885–891. https://doi.org/10.1248/cpb.c22-00556

    Article  CAS  Google Scholar 

  7. Hara Y, Manome T, Suehiro W, Harada S, Yamagishi Y, Takaya A, Ogra Y, Ishibashi M (2023) Isolation of two new trichorzin PA derivatives, trichorzin PA X and XI, from the terrestrial fungus Trichoderma harzianum IFM 66736. Tetrahedron Lett 121:15488. https://doi.org/10.1016/j.tetlet.2023.154488

    Article  CAS  Google Scholar 

  8. Hara Y, Totsugi Y, Ichikawa H, Harada S, Fujii K, Ahmed F, Sadhu SK, Arai MA, Ishibashi M (2021) Acacienone, a terpenoid-like natural product having an unprecedented C20 framework isolated from Acacia mangium leaves. J Nat Med 75:99–104. https://doi.org/10.1007/s11418-020-01457-y

    Article  CAS  PubMed  Google Scholar 

  9. Kadota S, Takamori Y, Kim N, Kikuchi T (1990) Constituents of the leaves of Woodfordia fruticosa KURZ. I: isolation, structure, and proton and Carbon-13 nuclear magnetic resonance signal assignments of woodfruticosin (woodfordin C), an inhibitor of deoxyribonucleic acid topoisomerase II. Chem Pharm Bull 38:2687–2697. https://doi.org/10.1248/cpb.38.2687

    Article  CAS  Google Scholar 

  10. Chung SK, Kim YC, Takaya Y, Terashima K, Niwa M (2004) Novel flavonol glycoside, 7-O-methyl mearnsitrin, from Sageretia theezans. J Agric Food Chem 52:4664–4668. https://doi.org/10.1021/jf049526j

    Article  CAS  PubMed  Google Scholar 

  11. de Mello JP, Petereit FP, Nahrstedt A (1996) Prorobinetinidins from Stryphnodendron adstringens. Phytochemistry 42:857–862. https://doi.org/10.1016/0031-9422(95)00953-1

    Article  Google Scholar 

  12. Coetzee J, Mciteka L, Malan E, Ferreira D (2000) Structure and synthesis of the first procassinidin dimers based on epicatechin, and gallo- and epigallo-catechin. Phytochemistry 53:795–804. https://doi.org/10.1016/s0031-9422(00)00017-0

    Article  CAS  PubMed  Google Scholar 

  13. Lou H, Yamazaki Y, Sasaki T, Uchida M, Tanaka H, Oka S (1999) A-type proanthocyanidins from peanut skins. Phytochemistry 51:297–308. https://doi.org/10.1016/S0031-9422(98)00736-5

    Article  CAS  Google Scholar 

  14. Phansalkar RS, Nam JW, Leme-Kraus AA, Gan LS, Zhou B, McAlpine JB, Chen SN, Bedran-Russo AK, Pauli AK (2019) Proanthocyanidin dimers and trimers from Vitis vinifera provide diverse structural motifs for the evaluation of dentin biomodification. J Nat Prod 82:2387–2399. https://doi.org/10.1021/acs.jnatprod.8b00953

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Hatano T, Yamashita A, Hashimoto T, Ito H, Kubo N, Yoshiyama M, Shimura S, Itoh Y, Okuda T, Yoshida T (1997) Flavan dimers with lipase inhibitory activity from Cassia nomame. Phytochemistry 46:893–900. https://doi.org/10.1016/S0031-9422(97)00367-1

    Article  CAS  Google Scholar 

  16. Lindhagen E, Nygren P, Larsson R (2008) The fluorometric microculture cytotoxicity assay. Nat Protoc 3:1364–1369. https://doi.org/10.1038/nprot.2008.114

    Article  CAS  PubMed  Google Scholar 

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Acknowledgements

We thank the late Takashi Koyano (Temko Corporation) and late Thaworn Kowithayakorn (Khon Kaen University) for their collaboration in the collection and identification of plant materials.

Funding

This work was supported by KAKENHI (Grant nos. 20H03394, 20K16024, and 23K14369) from the Japan Society for the Promotion of Science, JST SPRING (Grant number JPMJSP2109), the Uehara Memorial Foundation, the Shorai Foundation for Science and Technology, and Kagawa University Research Promotion Program (Grant number 23K0F014).

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Conceptualization, Y.H. and M.I.; isolation of compounds and biological experiment, K.F. and I.I.; data analysis, K.F., I.I., Y.H., A.T., and M.I.; writing—original draft preparation, K.F.; writing—review and editing, Y.H., A.T., and M.I. All authors have read and agreed to the published version of the manuscript.

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Correspondence to Yasumasa Hara.

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The authors declare no conflicts of interest.

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Fujii, K., Iwata, I., Takaya, A. et al. New biflavonoids isolated from Xylia kerrii leaves extract with selective cytotoxicity against MH7A human rheumatoid arthritis synovial fibroblast cells. J Nat Med (2024). https://doi.org/10.1007/s11418-024-01801-6

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