Potential anticancer properties of calotropis procera: An investigation on breast and colon cancer cells.

Calotropis procera is a perennial flowering plant of the Apocynaceae family, traditionally used in medicine to treat various ailments. Recent investigations have revealed its potential therapeutic activities such as anti-inflammatory, gastroprotective, analgesic, anti-obesity, and anti-diabetic properties. RP-HPLC qualitatively and quantitatively evaluated the phenolic acids and flavonoids in the ethanolic extract at two different wavelengths, 280 and 330 nm. In addition, total phenolic and flavonoid contents were measured via spectrophotometric determination in addition to the antioxidant activity. The antiproliferative effects of C. procera were investigated on two cancer cell lines: human colon (HCT-116) and breast (MCF-7) cancer. Several methods were utilised to analyse the effectiveness of the plant extract on the cytotoxicity, apoptosis, cell cycle progression, genes involved in the cell cycle, and protein expression profiles of HCT-116 and MCF-7 cells. These included the MTT assay, Annexin V-FITC/PI, analysis of the cell cycle, and Western blot. Results indicated that ferulic and caffeic acids were the major compounds at λmax 280 nm (1.374% and 0.561%, respectively), while the major compounds at λmax 325 nm were kaempferol and luteolin (1.036% and 0.512%, respectively). The ethanolic extract had significantly higher antioxidant activity (80 ± 2.3%) compared to ascorbic acid (90 ± 3.1%). C. procera extract exhibited dose-dependent cell growth inhibition, with an estimated IC50 of 50 µg/mL for MCF-7 and 55 µg/mL for HCT-116 cells at 24 h. Annexin V-FITC/PI confirmed the induction of apoptosis. Remarkably, cell cycle arrest occurred at the sub-G1 phase in MCF-7 cells, while in HCT-116 cells, it was observed at the G2-M phase. The sub-G1 arrest was associated with dysregulation of Akt, p-AKT, mTOR, and p-mTOR proteins, as confirmed by the Western blot analysis, while downregulation of CDK1, cyclin B1, and survivin caused G2-M arrest.

Chemical composition, docking simulations and burn wound healing effect of Micromeria fruticosa extract and its isolated flavonoidal compound.

The study aimed to investigate the constituents of the ethanolic extract of Micromeria fruticosa and evaluate its antimicrobial and burn healing activities and the isolated compound, rutin. The plant was extracted with ethanol and the active constituents were isolated. The antimicrobial activities of the extract and the isolated compounds were assessed. The burn healing potentiality was evaluated in a second-degree burn model on rats. Five compounds were isolated and identified namely, oleanolic acid 3-O-ß-D-glucopyranoside, apigenin, tectochrysin, 7,4' dihydroxyflavone7-rhamnoglucoside, and rutin. Noticeable antimicrobial activities of the extract, fractions and rutin, were obtained. These effects could be attributed to the isolated flavonoids and triterpenes compounds. The topical application of the extract or rutin significantly reduced the wound size and improved the skin histology. The molecular docking simulations predicted potential inhibitory interaction between rutin and the active site of IKKß that could be responsible for blocking NF-κB activation; this could explain the possible mechanism by which rutin enhances the burn wounds healing process. Ethanolic extract, fractions and isolated compound, rutin of M. fruticosa exhibited significant antimicrobial activities. The plant extract and rutin demonstrated high potentialities to heal burns.

Upadacitinib protects against cisplatin-induced renal and hepatic dysfunction without impairing its anticancer activity.

Cisplatin-induced renal and hepatic dysfunctions are major drawbacks and obstacles to its clinical applications. Induction of inflammation is a part of its molecular mechanism of toxicity. The impact of upadacitinib, a selective JAK1-inhibitory anti-inflammatory agent, on cisplatin-induced adverse effects, histopathologic changes, kidney and liver functions, oxidative stress, and inflammatory biomarkers were investigated compared to silymarin and losartan in male Wistar rats. The animals were treated with upadacitinib (10 mg/kg/day) for two weeks in addition to one dose of cisplatin (10 mg/kg) on the seventh day of treatment. The liver and kidney functions as well as the oxidative biomarkers and inflammatory burst, were biochemically measured. Upadacitinib pre-treatment significantly improved liver function markers (ALT and AST) and inhibited cisplatin-induced lipid profile aberrations (total cholesterol and triglycerides). Moreover, it protected the kidney functions as indicated by blood urea nitrogen, serum creatinine, creatinine clearance, and albumin levels. Upadacitinib also attenuated cisplatin-induced hepatic and renal inflammatory events, as indicated by the reduction of MDA and TNFα levels. In addition, it improved the superoxide dismutase (SOD) activity. Upadacitinib effectively diminished histopathologic structural damage in liver and kidney tissues. Western blotting of NF-kB and p-Akt confirmed the renoprotective effect of upadacitinib. Furthermore, the cell viability assay shows that upadacitinib did not have any inhibitory activity on cisplatin anticancer potency in MCF-7 and A549 cells. Moreover, upadacitinib has improved the potency of cisplatin against lung cancer cells in a dose-dependent pattern. These results highlight upadacitinib's protective effects from cisplatin-induced toxicity without impairing its anticancer activity.

Metabolic and biotransformation effects on dietary glucosinolates, their bioavailability, catabolism and biological effects in different organisms.

Glucosinolate-producing plants have long been recognized for both their distinctive benefits to human nutrition and their resistance traits against pathogens and herbivores. Despite the accumulation of glucosinolates (GLS) in plants is associated with their resistance to various biotic and abiotic stresses, the defensive and biological activities of GLS are commonly conveyed by their metabolic products. In view of this, metabolism is considered the driving factor upon the interactions of GLS-producing plants with other organisms, also influenced by plant and plant attacking or digesting organism characteristics. Several microbial pathogens and insects have evolved the capacity to detoxify GLS-hydrolysis products or inhibit their formation via different means, highlighting the relevance of their metabolic abilities for the plants' defense system activation and target organism detoxification. Strikingly, some bacteria, fungi and insects can likewise produce their own myrosinase (MYR)-like enzymes in one of the most important adaptation strategies against the GLS-MYR plant defense system. Knowledge of GLS metabolic pathways in herbivores and pathogens can impact plant protection efforts and may be harnessed upon for genetically modified plants that are more resistant to predators. In humans, the interest in the implementation of GLS in diets for the prevention of chronic diseases has grown substantially. However, the efficiency of such approaches is dependent on GLS bioavailability and metabolism, which largely involves the human gut microbiome. Among GLS-hydrolytic products, isothiocyanates (ITC) have shown exceptional properties as chemical plant defense agents against herbivores and pathogens, along with their health-promoting benefits in humans, at least if consumed in reasonable amounts. Deciphering GLS metabolic pathways provides critical information for catalyzing all types of GLS towards the generation of ITCs as the biologically most active metabolites. This review provides an overview on contrasting metabolic pathways in plants, bacteria, fungi, insects and humans towards GLS activation or detoxification. Further, suggestions for the preparation of GLS containing plants with improved health benefits are presented.

Micromeria fruticosa Induces Cell Cycle Arrest and Apoptosis in Breast and Colorectal Cancer Cells.

Micromeria fruticosa (L.) Druce subsp. Serpyllifolia (Lamiaceae) has been used widely in folk medicine to alleviate various ailments such as abdominal pains, diarrhea, colds, eye infections, heart disorders and wounds. A few reports have confirmed different therapeutic potentialities of its extracts, including the anti-inflammatory, gastroprotective, analgesic, antiobesity and antidiabetic activities. This study aimed to investigate the mechanistic pathway of the antiproliferative activity of the ethanolic extract of M. fruticose on two different cancer cell lines, namely human breast (mammary carcinoma F7 (MCF-7)) and human colorectal (human colon tumor cells (HCT-116)) cell lines. The 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide tetrazolium (MTT) assay, Annexin V-FITC/PI, caspases 8/9 and cell cycle analyses, qRT-PCR and Western blot were used to assess the effect of M. fruticosa on cytotoxicity, apoptosis, cell cycle, cell cycle-related genes and protein expression profiles in MCF-7 and HCT-116. The extract inhibits cell proliferation in a time- and dose-dependent manner. The half-maximal inhibitory concentration (IC50) for both cell lines was found to be 100 µg/mL. Apoptosis induction was confirmed by Annexin V-FITC/PI, that was related to caspases 8 and 9 activities induction. Furthermore, the cell cycle analysis revealed arrest at G2/M phase. The underlying mechanism involved in the G2/M arrest was found to be associated with the downregulation of CDK1, cyclin B1 and survivin that was confirmed by qRT-PCR and Western blotting.

Antihyperuricemic and xanthine oxidase inhibitory activities of Tribulus arabicus and its isolated compound, ursolic acid: In vitro and in vivo investigation and docking simulations.

BACKGROUND: Hyperurecemia is usually associated with gout and various metabolic arthritis disorders. Limited medications are available to manage such conditions. This study aimed to isolate the triterpenes constituent of the plant and to assess xanthine oxidase (XO) inhibitory and antihyperuricemic activities of Tribulus arabicus ethanolic extract, its fractions and the isolated compound using in vitro and in vivo approaches. METHODS: The ethanolic extract, fractions; n-hexane, chloroform and n-butanol and the isolated compound (ursolic acid) were evaluated in vitro for their XO inhibitory activity. Those that demonstrated significant activity were further evaluated for their antihyperuricemic activity on potassium oxonate-induced hyperuricemia in mice. RESULTS: The ethanolic extract was found to be safe up to 5000 mg/kg. The extract and its n-hexane fraction exhibited significant inhibitory activity on XO, whilst only a modest reduction in the enzymatic activity was noticed with n-butanol and chloroform fractions. Furthermore, administration of the ethanolic extract at low and high doses significantly reduced serum urate levels in mice by 31.1 and 64.6% respectively. The isolated active constituent, ursolic acid, showed potent XO inhibition activity (Half maximal inhibitory concentration, IC50 = 10.3 µg/mL), and significantly reduced uric acid level in vivo by 79.9%. Virtually, the binding mode of ursolic acid with XO was determined using molecular docking simulations. CONCLUSIONS: The activity of the ethanolic extract of T. arabicus and its n-hexane fraction can be attributed to the isolated compound, ursolic acid. Ursolic acid has good hypouricemic activity and therefore has high potential to be used for the treatment of gout and hyperuricemia-related diseases.

Botanical study of Meryta denhamii Seem. and its antihelminthic activity against Fasciola gigantica.

The anthelmintic activity of the ethanolic extracts of stems and leaves of Meryta denhamii Seem. against adult liver flukes "Fasciola gigantica" was studied in vitro. Although leaves extract was inactive, stems extract exhibited anthelmintic activity and recorded LC50 and LC90 values, 16 and 26 gm/l respectively. The mode of action of the ethanolic extract of the stems on the adult flukes was evaluated by scanning electron microscopy (SEM). Tegumental sloughing, loss of spines and deformity of suckers were observed. These damages are responsible for the vermicidal effect of the ethanolic extract of the stems. The saponin contents of the stems (4.25%) and leaves (2.45%) were determined using haemolytic index. The plant was identified based on the macro and micromorphological features of the stem and leaf.

Antitrypanosomal activity of some pregnane glycosides isolated from Caralluma species.

Pregnane glycosides previously isolated from genus Caralluma (C. Penicillata, C. tuberculata and C. russelliana) were tested for their antitrypanosomal activity. Penicilloside E showed the highest antitrypanosomal activity (IC(50) 1.01 microg/ml) followed by caratuberside C (IC(50) 1.85 microg/ml), which exhibited the highest selectivity index (SI 12.04). It was noticed that acylation is required for the antitrypanosomal activity while glycosylation at C-20 has no significant effect on the activity.