Abstract
Celastrol (CSL), the major constituent from traditional Chinese medicine Tripterygium wilfordii Hook, has attracted considerable interest in the medicinal society due to its multiple biological activities. However, poor solubility and obvious toxic side effect have limited its application in the pharmaceutical field. To address the problems, the inclusion complexes of mono polyamine-modified β-CD (H1) and the polyamine-brideged bis(β-CD) (H2) with CSL were prepared. The characterization of inclusion complexes was investigated by NMR, XRD FT-IR and SEM, and the binding behaviors of H1-2 with CSL were investigated by UV. The results showed that the H2 gave the binding constant (Ks) towards CSL up to 1.7 times higher than that of H1, through cooperative binding of two hydrophobic CD cavities with one guest. Remarkably, complexation with H1 and H2 improved CSL solubility in water from 0.044 mg/mL up to 2.31 and 2.68 mg/mL, respectively. The in vitro anticancer activity of H1/CSL inclusion complex was better than that of cisplatin (positive control). Meanwhile, the toxicity of CSL was slightly reduced after the formation of the inclusion complex with H1. Therefore, the complexes of CSL with H1-2 favor their use in anticancer drug formulations, broadening the field of application in clinic.
Graphic abstract
Similar content being viewed by others
References
Allen, S.D., Liu, Y.G., Kim, T., Bobbala, S., Yi, S.J., Zhang, X.H., Choi, J., Scott, E.A.: Celastrol-loaded PEG-b-PPS nanocarriers as an anti-inflammatory treatment for atherosclerosis. Biomater. Sci. 7, 657–668 (2019)
Zhang, Y., Geng, C., Liu, X., Li, M., Gao, M., Liu, X., Fang, F., Chang, Y.: Celastrol ameliorates liver metabolic damage caused by a high-fat diet through Sirt1. Mol. Metab. 6, 138–147 (2017)
Rahman, M., Beg, S., Verma, A., Al Abbasi, F.A., Anwar, F., Saini, S., Akhter, S., Kumar, V.: Phytoconstituents as pharmacotherapeutics in rheumatoid arthritis: challenges and scope of nano/submicromedicine in its effective delivery. J. Pharm. Pharmacol. 69, 1–14 (2017)
Liu, J., Lee, J., Salazar Hernandez, M.A., Mazitschek, R., Ozcan, U.: Treatment of obesity with celastrol. Cell 161, 999–1011 (2015)
Tseng, C.K., Hsu, S.P., Lin, C.K., Wu, Y.H., Lee, J.C., Young, K.C.: Celastrol inhibits hepatitis C virus replication by upregulating heme oxygenase-1 via the JNK MAPK/Nrf2 pathway in human hepatoma cells. Antivir. Res. 146, 191–200 (2017)
Bodle, C.R., Mackie, D.I., Hayes, M.P., Schamp, J.H., Miller, M.R., Henry, M.D., Doom, J.A., Houtman, J.C.D., James, M.A., Roman, D.L.: Natural products discovered in a high-throughput screen identified as inhibitors of RGS17 and as cytostatic and cytotoxic agents for lung and prostate cancer cell lines. J. Nat. Prod. 80, 1992–2000 (2017)
Ren, B., Liu, H., Gao, H., Liu, S.T., Zhang, Z.H., Fribley, A.M., Callaghan, M.U., Xu, Z.X., Zeng, Q.H., Li, Y.L.: Celastrol induces apoptosis in hepatocellular carcinoma cells via targeting ER-stress/UPR. Oncotarget 8, 93039–93050 (2017)
Diamanti, P., Cox, C.V., Moppett, J.P., Blair, A.: Dual targeting of Hsp90 in childhood acute lymphoblastic leukaemia. Brit. J. Haematol. 180, 147–149 (2018)
Jiang, Q.W., Cheng, K.J., Mei, X.L., Qiu, J.G., Zhang, W.J., Xue, Y.Q., Qin, W.M., Yang, Y., Zheng, D.W., Chen, Y., Wei, M.N., Zhang, X., Lv, M., Chen, M.W., Wei, X., Shi, Z.: Synergistic anticancer effects of triptolide and celastrol, two main compounds from thunder god vine. Oncotarget 6, 32790–32804 (2015)
Li, X.J., Wang, H.M., Ding, J., Nie, S.Z., Wang, L., Zhang, L.L., Ren, S.D.: Celastrol strongly inhibits proliferation, migration and cancer stem cell properties through suppression of Pin1 in ovarian cancer cells. Eur. J. Pharmacol. 842, 146–156 (2019)
Yang, Y.N., Cheng, S.Y., Liang, G.K., Lou, H.G., Wu, H.H.: Celastrol inhibits cancer metastasis by suppressing M2-like polarization of macrophages. Biochem. Bioph. Res. Co. 503, 414–419 (2018)
Jannuzzi, A.T., Kara, M., Alpertunga, B.: Celastrol ameliorates acetaminophen induced oxidative stress and cytotoxicity in HepG2 cells. Hum. Exp. Toxicol. 37, 742–751 (2018)
Freag, M.S., Saleh, W.M., Abdallah, O.Y.: Self-assembled phospholipid-based phytosomal nanocarriers as promising platforms for improving oral bioavailability of the anticancer celastrol. Int. J. Pharmaceut. 535, 18–26 (2018)
Fu, H.G., Chen, Y., Yu, Q.L., Liu, Y.: A Tumor-targeting Ru/polysaccharide/protein supramolecular assembly with high photodynamic therapy ability. Chem. Commun. 55, 3148–3151 (2019)
Ning, S.X., Zhou, M.Q., Liu, C., Waterhouse, G.I.N., Dong, J., Ai, S.: Ultrasensitive electrochemical immunosensor for avian leukosis virus detection based on a b-cyclodextrin-nanogold-ferrocene host-guest label for signal amplification. Anal. Chim. Acta A (2019). https://doi.org/10.1016/j.aca.2019.02.041
Kasapoglu-Calik, M., Ozdemir, M.: Synthesis and controlled release of curcumin-beta-cyclodextrin inclusion complex from nanocomposite poly(N-isopropylacrylamide/sodium alginate) hydrogels. J. Appl. Polym. Sci. A (2019). https://doi.org/10.1002/app.47554
Zhou, W.L., Zhao, X., Chen, Y., Liu, Y.: Construction and heterogeneous photooxidization reactivity of cyclodextrin/porphyrin polyrotaxane network. Org. Chem. Front. 6, 10–14 (2019)
Mzyene, F., Moulay, S., Bal, K., Madi, F.: Biomimetic approach towards the preparation of hydroxyapatite and hydroxyapatite/chitosan/β-cyclodextrin nanoparticles: application to controlled drug release. J. Incl. Phenom. Macrocycl. Chem. 92, 381–394 (2018)
de Miranda, T.M., de Oliveira, A.R., Pereira, J.R., da Silva, J.G., Lula, I.S., Nascimento, C.S., Denadai, A.M.L.: Inclusion versus micellization in the cethylpyridine chloride/beta-cyclodextrin system: a structural and thermodynamic approach. J. Mol. Struct. A 1184, 289–297 (2019). https://doi.org/10.1016/j.molstruc.2019.02.033
Quilaqueo, M., Millao, S., Luzardo-Ocampo, I., Campos-Vega, R., Acevedok, F., Shene, C., Rubilar, M.: Inclusion of piperine in beta-cyclodextrin complexes improves their bioaccessibility and in vitro antioxidant capacity. Food Hydrocolloids 91, 143–152 (2019)
Zhou, W.L., Chen, Y., Yu, Q.L., Li, P.Y., Chen, X.M., Liu, Y.: Photo-responsive cyclodextrin/anthracene/Eu3+ supramolecular assembly for a tunable photochromic multicolor cell label and fluorescent ink. Chem. Sci. (2019). https://doi.org/10.1039/c9sc00026g
Chen, X.M., Chen, Y., Hou, X.F., Wu, X., Gu, B.H., Liu, Y.: Sulfonato-beta-cyclodextrin mediated supramolecular nanoparticle for controlled release of berberine. ACS Appl. Mater. Interfaces 10, 24987–24992 (2018)
Yang, S.L., Zhao, L.J., Chi, S.M., Du, J.J., Ruan, Q., Xiao, P.L., Zhao, Y.: Inclusion complexes of flavonoids with propylenediamine modified beta-cyclodextrin: preparation, characterization and antioxidant. J. Mol. Struct. 1183, 118–125 (2019)
Zhao, L.J., Yang, S.L., Jin, W., Yang, H.W., Li, F.Y., Chi, S.M., Zhu, H.Y., Lei, Z., Zhao, Y.: Host-guest inclusion systems of morin hydrate and quercetin with two bis(β-cyclodextrin)s: preparation, characterization and antioxidant activity. Aust. J. Chem. A (2019). https://doi.org/10.1071/CH18580
Liu, Y.Y., Fan, X.D., Zhao, Y.B.: Synthesis and characterization of a poly(N-isopropylacrylamide) with β-cyclodextrin as pendant groups. J. Polym. Sci. A 43, 3516–3524 (2005)
Liu, Y., Yang, Y.W., Yang, E.C., Guan, X.D.: Molecular recognition thermodynamics and structural elucidation of interactions between steroids and bridged bis(β-cyclodextrin)s. J. Org. Chem. 69, 6590–6602 (2004)
Du, J.J., Zhao, L.J., Yang, S.L., Huang, Y.R., Chi, S.M., Ruan, Q., Zheng, P., Hu, R., Zhao, Y.: Preparation, characterization, solubilization and antioxidant activity of polyamine modified β-cyclodextrins with baicalein inclusion complexes. J. Incl. Phenom. Macrocycl. Chem. A (2019). https://doi.org/10.1007/s10847-018-0871-4
Guo, Y.F., Li, J.L., Liu, Y.Q., Ma, Y.P., Cheng, H.L., Yang, B., Liu, D.D., Yang, R.: Inclusion complexes of anhydrolycorine with cyclodextrins: preparation, characterization, and anticancer activity. Can. J. Chem. 94, 575–582 (2016)
Wang, W.Y., Liu, K., Dong, H.W., Liu, W.H.: High-performance liquid chromatography spectrometric analysis of tripterin in rat plasma. J. Chromatogr. B 863, 163–166 (2008)
Acknowledgment
This work was supported by the National Natural Science Foundations (Nos. 21362046, 21062030) and YangFan Innovative & Entepreneurial Research Team Project (No. 201312S09), which are gratefully acknowledged.
Author information
Authors and Affiliations
Corresponding author
Additional information
Publisher's Note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Rights and permissions
About this article
Cite this article
Yang, H., Pan, Z., Jin, W. et al. Preparation, characterization and cytotoxic evaluation of inclusion complexes between celastrol with polyamine-modified β-cyclodextrins. J Incl Phenom Macrocycl Chem 95, 147–157 (2019). https://doi.org/10.1007/s10847-019-00933-7
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s10847-019-00933-7