Keywords
Vingerbine
Caco-2
P-glycoprotein (P-gp)
Indoline alkaloids
How to Cite
Abstract
Vinca alkaloids are used extensively in the treatment of various diseases and despite their usefulness, drug resistance, attributed to a number of mechanisms associated with the multidrug-resistance phenotype including overexpression of P-glycoprotein (P-gp), remains a serious clinical problem. To identify the possible role of P-gp on the intestinal permeability of anti-arrhythmic crude alkaloids (Vingerbine) from Vinca herbaceae, Caco-2 cells were used in this study. The four Vingerbine constituent alkaloids were analyzed by high performance liquid chromatography (HPLC). Transport parameters, permeability coefficients and percent transports were calculated. Vingerbine constituent alkaloids displayed the identical tendency but with dissimilar degree of modulation in absorptive transport direction. Vincarine and Herbadine demonstrated higher-level intestinal transcellular efflux; the co-presence of verapamil, the absorptive transport of alkaloids increased, while the secretory decreased. No asymmetric permeation was observed for Herbamine and Vincamajine. The study suggests the involvement for multidrug resistance-associated proteins (MRPs) in the intestinal transcellular efflux of Vincarine and Herbadine. The further studies will be focused upon the screening appropriate nanomedicine-based strategies to combat MDR and thus improve intestinal absorption of anti-arrhythmic alkaloids.
References
Pham HNT, Vuong QV, Bowyer MC, Scarlett CJ. Phytochemicals Derived from Catharanthus roseus and Their Health Benefits. Technologies. 2020; 8(4):80.
Iqbal S, Flux C, Briggs DA, et al. Vinca alkaloid binding to P-glycoprotein occurs in a processive manner. Biochim Biophys Acta Biomembr. 2022;1864(10): Iqbal S, Flux C, Briggs DA, et al. Vinca alkaloid binding to P-glycoprotein occurs in a processive manner. Biochim Biophys Acta Biomembr. 2022;1864(10).
Mollazadeh S, Sahebkar A, Hadizadeh F, Behravan J, Arabzadeh S. Structural and functional aspects of P-glycoprotein and its inhibitors. Life Sci. 2018;214:118-123.
Mora Lagares L, Minovski N, Novič M. Multiclass Classifier for P-Glycoprotein Substrates, Inhibitors, and Non-Active Compounds. Molecules. 2019;24(10):2006.
Frezard F., Pereira-Maia E., Quidu P., Priebe W., Garnier-Suillerot A. P-Glycoprotein preferentially effluxes anthracyclines containing free basic versus charged amine. Eur. J. Biochem. 2001, 268:1561-1567
Vachnadze VYu. Vinca Alkaloids, their accumulation dynamics and formation in plants. Doctoral Dissertation. Tbilisi (Moscow), 1973: 176.
Chkhikvadze GV. Alkaloids of Vinca herbacea W. et Kit. and Vinca pubescens Urv. cultivated in Georgia. Ph.D Thesis. Tbilisi (Moscow), 1989: 120.
Dzhakeli EZ. Alkaloids from the roots of Vinca herbacea W. et Kit. growing and cultivated in Georgia. Ph.D Thesis. Tbilisi, 2004: 133.
Vachnadze VYu., Malikov VM., Mudzhiri KS and Yunusov SYu. Structure of herbadine and herbamine. Khimiya Prirodnykh Soedinenii 1972: 341.
Chkhikvadze GV, Vatchnadze VJ, Gambashidze NB, Gvishiani EF, Mudzhiri LS. Reception Method of anti-arrhythmic substance. Pat. N 834964 A61 K 35/78. 1981.
Chkhikvadze GV, Gambashidze NB, Gvishiani EF, Vatchnadze VJ, Giorgadze NI. Chemical and pharmacological investigation of Vinca herbacea W. et Kit. All-Union conference “Development, investigation and complex use of preparations applicable for cardio-vascular diseases”. Tbilisi,1982:28-29
Novicova JN, Gociredze IA, Abuladze GV. Comparative investigation of pharmacological activity of individual alkaloids and their sum isolated from Vinca herbacea W. et Kit.Pnoc. A.S. GSSR; Biol. 1984, 10 (1):54-56
Van Breemen RB, Li Y. Caco-2 cell permeability assays to measure drug absorption. Expert Opin Drug Metab Toxicol. 2005;1(2):175-185.
Artursson P, Magnusson C. Epithelial transport of drugs in cell culture. II: Effect of extracellular calcium concentration on the paracellular transport of drugs of different lipophilicities across monolayers of intestinal epithelial (Caco-2) cells. J Pharm Sci. 1990;79(7):595-600.
Tsiklauri, L. K., Hoyer, H., Chkhikvadze, G. V., Vachnadze, V. Y., Tsagareishvili, G. V., Bakuridze, A. G., & Bernkop-Schnurch, A. Role of P-glycoproteins in the transepithelial transport of indoline alkaloids isolated from Vinca herbaceae. Pharmaceutical Chemistry Journal. 2008; 42(12):693–695.
Ognyanov I, Dalev P., Dutschevska H., Mollov M. Neue Alkaloids aus Vinca herbacea W. et Kit. C.R. Acad. Bulg. Sci. 1964; 17: 153-156.
Sattler S., Schäfer U., Schneider W., Hölzl J., Lehr C. Binding uptake and transport of hypericin by Caco-2 monolayers. J. Pharm. Sci. 1997; 86(10): 1120-1126.
Zhou H., Tai Y., Sun C., Pan Y. Rapid identification of Vinca alkaloids by direct-injection electrospray ionisation tandem mass spectrometry and confirmation by high-performance liquid chromatography-mass spectrometry. Pytochem Anal. 2005;16:328-333.
Gottesman MM, Pastan I. Biochemistry of multidrug resistance mediated by the multidrug transporter. Annu Rev Biochem. 1993; 62:385-427.
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