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.
Subject(s)
Alkaloids , Berberine Alkaloids , Berberine , Coptis , Drugs, Chinese Herbal , Stomach Neoplasms , Alkaloids/analysis , Alkaloids/pharmacology , Animals , Berberine/analogs & derivatives , Berberine/pharmacology , Berberine Alkaloids/pharmacology , Bromodeoxyuridine , Chloroform , Cisplatin , Coptis/chemistry , Coptis chinensis , Drugs, Chinese Herbal/chemistry , Hydrochloric Acid , Isoquinolines , Methanol , Solvents , Stomach Neoplasms/drug therapy , Water , ZebrafishABSTRACT
Gastric cancer belongs to the heterogeneous malignancies and, according to the World Health Organization, it is the fifth most commonly diagnosed cancer in men. The aim of this review is to provide an overview on the role of natural products of plant origin in the therapy of gastric cancer and to present the potentially active metabolites which can be used in the natural therapeutical strategies as the support to the conventional treatment. Many of the naturally spread secondary metabolites have been proved to exhibit chemopreventive properties when tested on the cell lines or in vivo. This manuscript aims to discuss the pharmacological significance of both the total extracts and the single isolated metabolites in the stomach cancer prevention and to focus on their mechanisms of action. A wide variety of plant-derived anticancer metabolites from different groups presented in the manuscript that include polyphenols, terpenes, alkaloids, or sulphur-containing compounds, underlines the multidirectional nature of natural products.
Subject(s)
Phytotherapy/methods , Plant Extracts/pharmacology , Stomach Neoplasms/drug therapy , Alkaloids/pharmacology , Animals , Biological Products/pharmacology , Humans , Phytotherapy/trends , Plant Extracts/metabolism , Polyphenols/pharmacology , Stomach Neoplasms/therapy , Terpenes/pharmacologyABSTRACT
The aim of the present study was to determine the composition, antiradical and antimicrobial activity of fruits, leaves and roots of an underestimated species of barberry-Berberis iliensis-growing in Kazakhstan. Particular attention was paid to the determination of the composition of its extracts by high-performance liquid chromatography coupled with mass spectrometry (HPLC-ESI-Q-TOF-MS) analysis. As a result of the chromatographic and spectrometric study 33 secondary metabolites from the groups of phenolic acids and their esters, flavonoids, alkaloids and organic acids were identified and 15 of them-quantified. The isomers of caffeoyl-glucaric acid, caffeic acid derivatives, isoquercetin, berberine and jatrorrhizine were the most abundant components of the tested extracts. The antiradical activity tests were performed by 2,2-diphenyl-1-picrylhydrazyl (DPPH) and Folin-Ciocalteu assays on four types of extracts (water, ethanol, ethanol-water 7:3 v/v, ethanol-water 1:1 v/v) from the three organs of the plant. The highest antiradical potential (IC50 = 80 ± 6.36 µg/mL) and phenolic content (440 ± 17.1 mg gallic acid equivalents/L) was calculated for ethanol- water (1:1 v/v) extracts from the leaves and could be influenced by the abundant presence of simple phenolic acids, flavonoids and glucaric acid esters. Among reference microorganisms, M. luteus, S. epidermidis, some S. aureus and B. cereus belonging to Gram-positive bacteria and yeasts from Candida species were the most sensitive to roots extract that was found the most active among the studied samples. The results of the study classify Berberis iliensis as a strong antioxidant agent and as a plant with an antimicrobial potential.