Chemopreventive Effects of Onosma mutabilis against Azoxymethane-Induced Colon Cancer in Rats via Amendment of Bax/Bcl-2 and NF-κB Signaling Pathways.

Onosma species (Boraginaceae) are well known as medicinal plants due to their wide range of pharmaceutical potential. The present study aims to investigate the anticancer (in vitro) and chemo-protective (in vivo) efficacies of Onosma mutabilis extract (OME) in the azoxymethane (AOM)-induced aberrant crypt foci (ACF) in rats. The in vitro antiproliferative effects of OME were determined on two human tumor cell lines (Caco-2 and HT-29) via MTT assay. The in vivo chemoprotective effects of OME were investigated by performing various biochemical analyses in serum and tissue homogenates of albino rats, along with determining oxidative stress biomarkers. Inflammatory biomarkers of colon, colonic gross morphology (by methylene blue), ACF formation, and colonic histopathology (H & E stain) were determined. The immunohistochemistry of colonic tissues was also assessed by Bax and Bcl-2 protein expression. The results showed that the antitumor activity of OME against Caco-2 and HT-29 colorectal cancer cells ranged between 22.28-36.55 µg/mL. OME supplementation caused a significant drop in the ACF values and improved the immunohistochemistry of the rats shown by up-regulation of Bax and down-regulation of Bcl-2 protein expressions. These outcomes reveal that O. mutabilis may have chemoprotective efficiency against AOM-induced colon cancer represented by the attenuation of ACF formation possibly through inhibition of free radicals, inflammation, and stimulation of the colon antioxidant armory (SOD, CAT, and GPx) and positive regulation of the Nrf2-Keap1 pathway.

Ethnobotanical, Phytochemistry, and Pharmacological Activity of Onosma (Boraginaceae): An Updated Review.

The genus Onosma belongs to the Boraginaceae family and contains over 230 species. The present review sheds light on the ethnopharmacology, phytoconstituents, bioactivity, and toxicology of the Onosma species from previous investigations. Furthermore, the paper also highlights the unresolved issues for the future investigations. The review included previous studies of the genus Onosma available from Google Scholar and Baidu Scholar, Science Direct, SciFinder, Wiley Online Library, and Web of Science. Until now, more than 200 chemical compounds have been detected from the genus Onosma, including naphthoquinone (33), flavonoids (30), hydrocarbon (23), phenolic (22), ester (17), alkaloids (20), aromatics (12), carboxylic acid (11), fatty acids (9), terpenoids (10), while the most important ones are rosmarinic, ferulic, protocatechuic, chlorogenic, caffeic, p-coumaric acids, and apigenin. The Onosma species are reported as traditional medicine for wound healing, heart disease, and kidney disorders, while the pharmacological investigations revealed that the extracts and the phytochemicals of Onosma species have different therapeutic properties including antioxidant, enzyme inhibitory, antitumor, hepatoprotective, antiviral, anti-inflammatory, and antimicrobial actions. The summarized knowledge in this review provides valuable ideas for the current and future drug discovery and a motivation for further investigation on the genus Onosma.

Onosma mutabilis: Phytochemical composition, antioxidant, cytotoxicity, and acute oral toxicity.

The traditional use of Onosma L. species as a remedy motivated scientists to discover great biological/pharmacological potentials in this plant. In the current study, in addition to the phytochemical composition of methanol (MeOH), water, and ethyl acetate extract of aerial parts of Onosma mutabilis Boiss., an endemic plant species in the flora of Kurdistan, Iraq, in vitro antioxidant, cytotoxicity, and oral toxicity activity were investigated. Results of total phenolic and total flavonoid tests show the MeOH extract superiority, and the results of Gas chromatography-mass spectrophotometer(GS/GS-MS) show 18 chemical compounds in the MeOH extract, and the majority of the detected compounds were alkaloids (78.77%) and steroids (11.48%), namely as 5,8-dihydroxy-2-(4-methylpent-3-enyl) naphthalene-1,4-dione (48.60%), 3-O-Methyl-d-glucose (27.49%), ß-Sitosterol (6.81%), Phenol, 2,4-bis (1,1-dimethyl ethyl)-, phosphite (3.46%), and 24,25-Dihydroxycholecalciferol (3.14%). Results of the antioxidant tests show the MeOH extract superiority in the phosphomolybdenum assay, radical scavenging [on 1,1-diphenyl-2-picrylhydrazyl (DPPH) and 2,2'-azino-bis (3-ethylbenzothiazoline-6-sulfonic acid) (ABTS)] assays, and reducing power [cupric reducing antioxidant capacity (CUPRAC) and ferric reducing antioxidant power (FRAP)] assays (1.45, 3.54, 2.33, 1.12, 1.62, mg/ml, respectively). The cytotoxicity results of the plant extract are presented as IC50 (inhibitory concentration at 50%) on the prostate cancer cells (DU-145), mammary cancer cells (MCF-7), and human cervix carcinoma (Hep2c), at which values ranged from 28.79 to 41.83 µg/ml. Results of the acute toxicity in the dose-dependent trail (100, 200, 300, 600 mg/kg of MeOH) show the absence of the behavior and appearance changes of female Wister rats. Overall, O. mutabilis extract exhibited significant natural potentials probably because of its polar phytochemicals, which could be an alternative source for remedial, nutrient, and cosmetic manufacture.