A 5,7-dimethoxyflavone/hydroxypropyl-β-cyclodextrin Inclusion Complex with Anti-butyrylcholinesterase Activity

Overview

Journal AAPS PharmSciTech

Publisher Springer

Specialty Pharmacology

Date 2014 Jun 1

PMID 24879292

Citations 3

Authors

Supachai Songngam

Mongkol Sukwattanasinitt

Krisana Siralertmukul

Pattara Sawasdee

Affiliations

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Abstract

This study aimed to improve the water solubility of 5,7-dimethoxyflavone (5,7-DMF) isolated from Kaempferia parviflora by complexation with 2-hydroxypropyl-β-cyclodextrin (HPβ-CD). The phase solubility profile of 5,7-DMF in the presence of HPβ-CD was classified as AL-type and indicated a 1:1 mole ratio. Differential scanning colorimetry, X-ray diffraction, NMR and SEM analyses supported the formation of a 5,7-DMF/HPβ-CD inclusion complex involving the A ring of 5,7-DMF inside the HPβ-CD cavity. This is the first example of CD inclusion with the A ring of non-hydroxyl flavones. The stability and binding constants of the complexes were determined using the phase solubility and UV-vis absorption spectroscopy, respectively. The water solubility of 5,7-DMF was increased 361.8-fold by complexation with HPβ-CD and overcame the precipitation problem observed in aqueous buffers, such as during in vitro anti-butyrylcholinesterase activity assays. The 1:1 mole ratio of the 5,7-DMF/HPβ-CD complex showed a 2.7-fold higher butyrylcholinesterase inhibitory activity (in terms of the IC50 value) compared to the non-complexed compound.

Citing Articles

Combinations of Piperine with Hydroxypropyl-β-Cyclodextrin as a Multifunctional System.

Stasilowicz A, Rosiak N, Tykarska E, Kozak M, Jenczyk J, Szulc P Int J Mol Sci. 2021; 22(8).

PMID: 33919582 PMC: 8072981. DOI: 10.3390/ijms22084195.

and Its Methoxyflavones: Chemistry and Biological Activities.

Chen D, Li H, Li W, Feng S, Deng D Evid Based Complement Alternat Med. 2019; 2018:4057456.

PMID: 30643531 PMC: 6311295. DOI: 10.1155/2018/4057456.

Theoretical and Experimental Studies on Inclusion Complexes of Pinostrobin and β-Cyclodextrins.

Kicuntod J, Sangpheak K, Mueller M, Wolschann P, Viernstein H, Yanaka S Sci Pharm. 2018; 86(1).

PMID: 29385698 PMC: 5874535. DOI: 10.3390/scipharm86010005.

References

Pescitelli G, Bilia A, Bergonzi M, Vincieri F, Di Bari L . Cyclodextrins as carriers for kavalactones in aqueous media: spectroscopic characterization of (S)-7,8-dihydrokavain and beta-cyclodextrin inclusion complex. J Pharm Biomed Anal. 2010; 52(4):479-83. DOI: 10.1016/j.jpba.2010.01.037. View

Wen X, Walle U, Walle T . 5,7-Dimethoxyflavone downregulates CYP1A1 expression and benzo[a]pyrene-induced DNA binding in Hep G2 cells. Carcinogenesis. 2005; 26(4):803-9. DOI: 10.1093/carcin/bgi015. View

Cannava C, Crupi V, Ficarra P, Guardo M, Majolino D, Mazzaglia A . Physico-chemical characterization of an amphiphilic cyclodextrin/genistein complex. J Pharm Biomed Anal. 2009; 51(5):1064-8. DOI: 10.1016/j.jpba.2009.11.025. View

Loftsson T, Duchene D . Cyclodextrins and their pharmaceutical applications. Int J Pharm. 2006; 329(1-2):1-11. DOI: 10.1016/j.ijpharm.2006.10.044. View

Sermboonpaisarn T, Sawasdee P . Potent and selective butyrylcholinesterase inhibitors from Ficus foveolata. Fitoterapia. 2012; 83(4):780-4. DOI: 10.1016/j.fitote.2012.03.009. View

Temkitthawon P, Hinds T, Beavo J, Viyoch J, Suwanborirux K, Pongamornkul W . Kaempferia parviflora, a plant used in traditional medicine to enhance sexual performance contains large amounts of low affinity PDE5 inhibitors. J Ethnopharmacol. 2011; 137(3):1437-41. PMC: 4056445. DOI: 10.1016/j.jep.2011.08.025. View

Walle T, Ta N, Kawamori T, Wen X, Tsuji P, Walle U . Cancer chemopreventive properties of orally bioavailable flavonoids--methylated versus unmethylated flavones. Biochem Pharmacol. 2007; 73(9):1288-96. PMC: 1868573. DOI: 10.1016/j.bcp.2006.12.028. View

Ma S, Chen W, Yang X, Zhang N, Wang S, Liu L . Alpinetin/hydroxypropyl-β-cyclodextrin host-guest system: preparation, characterization, inclusion mode, solubilization and stability. J Pharm Biomed Anal. 2012; 67-68:193-200. DOI: 10.1016/j.jpba.2012.04.038. View

Sawasdee P, Sabphon C, Sitthiwongwanit D, Kokpol U . Anticholinesterase activity of 7-methoxyflavones isolated from Kaempferia parviflora. Phytother Res. 2009; 23(12):1792-4. DOI: 10.1002/ptr.2858. View

10.

Tep-areenan P, Sawasdee P, Randall M . Possible mechanisms of vasorelaxation for 5,7-dimethoxyflavone from Kaempferia parviflora in the rat aorta. Phytother Res. 2010; 24(10):1520-5. DOI: 10.1002/ptr.3164. View

11.

Negi J, Singh S . Spectroscopic investigation on the inclusion complex formation between amisulpride and γ-cyclodextrin. Carbohydr Polym. 2013; 92(2):1835-43. DOI: 10.1016/j.carbpol.2012.11.082. View

12.

Greig N, Lahiri D, Sambamurti K . Butyrylcholinesterase: an important new target in Alzheimer's disease therapy. Int Psychogeriatr. 2003; 14 Suppl 1:77-91. DOI: 10.1017/s1041610203008676. View

13.

Sae-Wong C, Matsuda H, Tewtrakul S, Tansakul P, Nakamura S, Nomura Y . Suppressive effects of methoxyflavonoids isolated from Kaempferia parviflora on inducible nitric oxide synthase (iNOS) expression in RAW 264.7 cells. J Ethnopharmacol. 2011; 136(3):488-95. DOI: 10.1016/j.jep.2011.01.013. View

14.

Veiga F, Fernandes C, Carvalho R, Geraldes C . Molecular modelling and 1H-NMR: ultimate tools for the investigation of tolbutamide: beta-cyclodextrin and tolbutamide: hydroxypropyl-beta-cyclodextrin complexes. Chem Pharm Bull (Tokyo). 2001; 49(10):1251-6. DOI: 10.1248/cpb.49.1251. View

15.

Dreassi E, Zizzari A, Mori M, Filippi I, Belfiore A, Naldini A . 2-Hydroxypropyl-β-cyclodextrin strongly improves water solubility and anti-proliferative activity of pyrazolo[3,4-d]pyrimidines Src-Abl dual inhibitors. Eur J Med Chem. 2010; 45(12):5958-64. DOI: 10.1016/j.ejmech.2010.09.062. View

16.

Mekjaruskul C, Yang Y, Leed M, Sadgrove M, Jay M, Sripanidkulchai B . Novel formulation strategies for enhancing oral delivery of methoxyflavones in Kaempferia parviflora by SMEDDS or complexation with 2-hydroxypropyl-β-cyclodextrin. Int J Pharm. 2013; 445(1-2):1-11. DOI: 10.1016/j.ijpharm.2013.01.052. View

17.

de Araujo M, Vieira E, Silva Lazaro G, de Souza Conegero L, Ferreira O, Almeida L . Inclusion complexes of pyrimethamine in 2-hydroxypropyl-beta-cyclodextrin: characterization, phase solubility and molecular modelling. Bioorg Med Chem. 2007; 15(17):5752-9. DOI: 10.1016/j.bmc.2007.06.013. View

18.

Sae-Wong C, Tansakul P, Tewtrakul S . Anti-inflammatory mechanism of Kaempferia parviflora in murine macrophage cells (RAW 264.7) and in experimental animals. J Ethnopharmacol. 2009; 124(3):576-80. DOI: 10.1016/j.jep.2009.04.059. View

19.

Yang B, Lin J, Chen Y, Liu Y . Artemether/hydroxypropyl-beta-cyclodextrin host-guest system: characterization, phase-solubility and inclusion mode. Bioorg Med Chem. 2009; 17(17):6311-7. DOI: 10.1016/j.bmc.2009.07.060. View

20.

An G, Wu F, Morris M . 5,7-Dimethoxyflavone and multiple flavonoids in combination alter the ABCG2-mediated tissue distribution of mitoxantrone in mice. Pharm Res. 2011; 28(5):1090-9. DOI: 10.1007/s11095-011-0368-y. View