Isoquinoline Alkaloids from Coptis chinensis Franch: Focus on Coptisine as a Potential Therapeutic Candidate against Gastric Cancer Cells

Abstract

Gastric cancer (GC) has high incidence rates and constitutes a common cause of cancer mortality. Despite advances in treatment, GC remains a challenge in cancer therapy which is why novel treatment strategies are needed. The interest in natural compounds has increased significantly in recent years because of their numerous biological activities, including anti-cancer action. The isolation of the bioactive compounds from Coptis chinensis Franch was carried out with the Centrifugal Partition Chromatography (CPC) technique, using a biphasic solvent system composed of chloroform (CHCl3)—methanol (MeOH)—water (H2O) (4:3:3, v/v) with an addition of hydrochloric acid and trietylamine. The identity of the isolated alkaloids was confirmed using a high resolution HPLC-MS chromatograph. The phytochemical constituents of Coptis chinensis such as berberine, jatrorrhizine, palmatine and coptisine significantly inhibited the viability and growth of gastric cancer cell lines ACC-201 and NCI-N87 in a dose-dependent manner, with coptisine showing the highest efficacy as revealed using MTT and BrdU assays, respectively. Flow cytometry analysis confirmed the coptisine-induced population of gastric cancer cells in sub-G1 phase and apoptosis. The combination of coptisine with cisplatin at the fixed-ratio of 1:1 exerted synergistic and additive interactions in ACC-201 and NCI-N87, respectively, as determined by means of isobolographic analysis. In in vivo assay, coptisine was safe for developing zebrafish at the dose equivalent to the highest dose active in vitro, but higher doses (greater than 10 times) caused morphological abnormalities in larvae. Our findings provide a theoretical foundation to further studies on more detailed mechanisms of the bioactive compounds from Coptis chinensis Franch anti-cancer action that inhibit GC cell survival in in vitro settings.

Magnoflorine from Berberis vulgaris Roots—Impact on Hippocampal Neurons in Mice after Short-Term Exposure

“…Previously, the scientific literature delivered several examples of alkaloid purification. Nakonieczna et al [ 19 ] succeeded in the purification of isoquinoline alkaloids from Coptis chinensis ; benzylisoquinoline and aporphine alkaloids were recovered from Spirauna glycycarpa [ 20 ] using a polar solvent system composed of n-butanol-methanol-water (9:1:10, v / v ); O -tigloylcyclovirobuxeine-B was obtained via CPC fractionation of Buxus sempervirens extract with a hexane:EtOAc:MeOH:H2O (7:3:7:3) ( v/v/v/v ) solvent system [ 21 ], whereas aconitine was purified from Aconitum karacolicum by Tarbe et al [ 22 ]. In the case of this study, a composition of the following solvents: chloroform:methanol:water (4:3:3 v / v ), provided high purity MAG directly from the crude methanolic root extract of Berberis vulgaris .…”

Inhibition of Seizure-Like Paroxysms and Toxicity Effects of Securidaca longepedunculata Extracts and Constituents in Zebrafish Danio rerio

“…Wildtype adult zebrafish (genetic strain AB, Centre for Molecular Medicine Norway (NCMM), Oslo Science Park, Norway) were housed and maintained under controlled environmental conditions at temperatures of 28 °C under 14 h light and 10 h dark cycle (standard aquaculture conditions) as previously described. , Three times a day, adult zebrafish were fed, twice daily with commercial dry feed (Gemma Micro 300, Skretting, Norway) and once daily with live brine shrimp (Artemia). After natural spawning, zebrafish eggs were collected from static tanks and transferred to Petri dishes for further handling and development for the purpose of the experiments.…”

Developmental Exposure to Kynurenine Affects Zebrafish and Rat Behavior

“…Additionally, their response to touch was scored in order to choose the dose that had no negative impact on muscle performance or function [ 48 ]. The highest concentration of KYN (i.e., 100 μM) that did not induce any visible signs of toxicity and did not affect touch response was chosen as MTC for behavioral experiments [ 48 , 49 , 50 ].…”