Govaniadine Evaluation of Cytotoxicity and Permeability in Cell Culture

• Published in: Revista brasileira de farmacognosia Vol. 30; no. 3; pp. 374 - 380
• Main Authors: Marques, Lucas M. M., Behrens, Matthias, Kalinina, Svetlana, Rottkord, Ulrike, Adhikari, Achyut, (S) Shrestha, Ram L., Humpf, Hans-Ulrich, Lopes, Norberto P.
• Format: Journal Article
• Language: English
• Published: Cham Springer International Publishing 01.06.2020
• Subjects: Medicine; Original Article; Pharmacy; Passive transport; Alkaloid; Intestinal permeability
• ISSN: 1981-528X; 1981-528X
• DOI: 10.1007/s43450-020-00066-w

Govaniadine ( 1 ), a tetrahydroprotoberberine-type alkaloid, is one of the main active constituent isolated from Corydalis govaniana Wall., Papaveraceae, with several biological activities: antinociceptive, anti-urease, and leishmanicidal. Some articles reporting tetrahydroprotoberberine and structurally related alkaloids cytotoxicity prompted us to evaluate the influence of compound 1 on cellular viability in two different cell lines: human hepatoma carcinoma (HepG2) and human embryonic kidney (HEK-293T) and its permeation across the human colon carcinoma cell line (Caco-2). Cellular viability reduction of compound 1 was observed between 30 and 100 μM (HepG2) and between 70 and 100 μM (HEK-293T). However, the effects were weaker than those in the positive controls (T-2 toxin and camptothecin). Prior to proceed the transport studies, a method for compound 1 quantification in Hank’s Balanced Salt Solution medium was developed and validated by LC-MS/MS. The two calibration curves were linear over the concentration range of 6.3–200 nM and 0.2–10 μM. The apparent permeability coefficient for absorptive transport was 20.6 ± 3.9 × 10 −6  cm/s, indicating compound 1 crossed the cell monolayer by passive diffusion and it was not subjected to active efflux. Graphical abstract