Exploring the Potential of Rosemary Derived Compounds (Rosmarinic and Carnosic Acids) as Cancer Therapeutics: Current Knowledge and Future Perspectives.

Cancer is a global health challenge with high morbidity and mortality rates. However, conventional cancer treatment methods often have severe side effects and limited success rates. In the last decade, extensive research has been conducted to develop safe, and efficient alternative treatments that do not have the limitations of existing anticancer medicines. Plant-derived compounds have shown promise in cancer treatment for their anti-carcinogenic and anti-proliferative properties. Rosmarinic acid (RA) and carnosic acid (CA) are potent polyphenolic compounds found in rosemary (Rosmarinus officinalis) extract. They have been extensively studied for their biological properties, which include anti-diabetic, anti-inflammatory, antioxidant, and anticancer activities. In addition, RA and CA have demonstrated effective anti-proliferative properties against various cancers, making them promising targets for extensive research to develop candidate or leading compounds for cancer treatment. This review discusses and summarizes the anti-tumor effect of RA and CA against various cancers and highlights the involved biochemical and mechanistic pathways.

The Effects of Medications and the Roles of Pharmacists on the Recovery of Patients with COVID-19 Infection: An Epidemiological Study from the United Arab Emirates.

Patients infected with coronavirus have new experiences and hence new needs from the healthcare sector. Acknowledging patients' experiences can exhibit promising outcomes in coronavirus management. Pharmacists are considered a vital pillar in managing patients' experiences during their infection. A cross-sectional study was conducted to assess the experiences of COVID-19-infected individuals and the roles of pharmacists in the United Arab Emirates. The survey was face- and content-validated after being developed. Three sections were included in the survey (demographics, experiences of infected individuals, and the roles of pharmacists). Data were analyzed using the Statistical Package for the Social Sciences. The study participants (n = 509) had a mean age of 34.50 (SD = 11.93). The most reported symptoms among participants were fatigue (81.5%), fever (76.8%), headache (76.6%), dry cough (74.1%), muscle or joint pain (70.7%), and sore throat (68.6%). Vitamin C was the most used supplement (88.6%), followed by pain relievers (78.2%). Female gender was the only factor associated with symptom severity. About 79.0% agreed that the pharmacist played an important and effective role during their infection. The most reported symptom was fatigue, with females reporting more severe symptoms. The role of the pharmacist proved to be vital during this pandemic.

Recent Updates on the Functional Impact of Kahweol and Cafestol on Cancer.

Kahweol and cafestol are two diterpenes extracted from Coffea arabica beans that have distinct biological activities. Recent research describes their potential activities, which include anti-inflammatory, anti-diabetic, and anti-cancer properties, among others. The two diterpenes have been shown to have anticancer effects in various in vitro and in vivo cancer models. This review aims to shed light on the recent developments regarding the potential effects of kahweol and cafestol on various cancers. A systematic literature search through Google Scholar and PubMed was performed between February and May 2022 to collect updates about the potential effects of cafestol and kahweol on different cancers in in vitro and in vivo models. The search terms "Kahweol and Cancer" and "Cafestol and Cancer" were used in this literature review as keywords; the findings demonstrated that kahweol and cafestol exhibit diverse effects on different cancers in in vitro and in vivo models, showing pro-apoptotic, cytotoxic, anti-proliferative, and anti-migratory properties. In conclusion, the diterpenes kahweol and cafestol display significant anticancer effects, while remarkably unaffecting normal cells. Our results show that both kahweol and cafestol exert their actions on various cancers via inducing apoptosis and inhibiting cell growth. Additionally, kahweol acts by inhibiting cell migration.

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.

The Coffee Diterpene, Kahweol, Ameliorates Pancreatic ß-Cell Function in Streptozotocin (STZ)-Treated Rat INS-1 Cells through NF-kB and p-AKT/Bcl-2 Pathways.

Kahweol is a diterpene molecule found in coffee that exhibits a wide range of biological activity, including anti-inflammatory and anticancer properties. However, the impact of kahweol on pancreatic ß-cells is not known. Herein, by using clonal rat INS-1 (832/13) cells, we performed several functional experiments including; cell viability, apoptosis analysis, insulin secretion and glucose uptake measurements, reactive oxygen species (ROS) production, as well as western blotting analysis to investigate the potential role of kahweol pre-treatment on damage induced by streptozotocin (STZ) treatment. INS-1 cells pre-incubated with different concentrations of kahweol (2.5 and 5 µM) for 24 h, then exposed to STZ (3 mmol/L) for 3 h reversed the STZ-induced effect on cell viability, apoptosis, insulin content, and secretion in addition to glucose uptake and ROS production. Furthermore, Western blot analysis showed that kahweol downregulated STZ-induced nuclear factor kappa B (NF-κB), and the antioxidant proteins, Heme Oxygenase-1 (HMOX-1), and Inhibitor of DNA binding and cell differentiation (Id) proteins (ID1, ID3) while upregulated protein expression of insulin (INS), p-AKT and B-cell lymphoma 2 (BCL-2). In conclusion, our study suggested that kahweol has anti-diabetic properties on pancreatic ß-cells by suppressing STZ induced apoptosis, increasing insulin secretion and glucose uptake. Targeting NF-κB, p-AKT, and BCL-2 in addition to antioxidant proteins ID1, ID3, and HMOX-1 are possible implicated mechanisms.

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.

Therapeutic potentials of Crataegus azarolus var. eu- azarolus Maire leaves and its isolated compounds.

BACKGROUND: Hyperglycemia is a complicated condition accompanied with high incidence of infection and dyslipidemia. This study aimed to explore the phyto-constituents of Crataegus azarolus var. eu- azarolus Maire leaves, and to evaluate the therapeutic potentials particularly antimicrobial, antihyperglycemic and antihyperlipidemic of the extract and the isolated compound (3ß-O-acetyl ursolic acid). METHODS: Total phenolics and flavonoidal contents were measured by RP-HPLC analysis. Free radicals scavenging activity of different extraction solvents was tested in-vitro on DPPH free radicals. The antimicrobial activity of the ethanolic extract and its fractions as well as the isolated compounds were evaluated in-vitro on variable microorganisms. Animal models were used to evaluate the antihyperglycemic and antihyperlipidemic activities of the ethanolic extract along with the isolated compound (3ß-O acetyl ursolic acid). RESULTS: RP- HPLC analysis of the phenolics revealed high content of rutin, salicylic and ellagic acids. Six compounds belonging to triterpenes and phenolics were isolated from chloroform and n-butanol fractions namely: ursolic acid, 3ß-O-acetyl ursolic acid, ellagic acid, quercetin 3-O-ß methyl ether, rutin and apigenin7-O-rutinoside. Ethanolic extract showed the highest DPPH radical scavenger activity compared to other solvents. Ethanolic extract, hexane fraction, ursolic acid, 3ß-O acetyl ursolic acid and quercetin 3-O-methyl ether showed variable antimicrobial activity against E. coli, P. aeruginosa, S. aureus, and C. albicans. Administration of the ethanolic extract or 3ß-O acetyl ursolic acid orally to the mice reduced blood glucose significantly in a time- and dose-dependent manner. Ethanolic extract significantly reduced LDL-C, VLDL-C, TC and TG and increased HDL-C in rats. Ethanolic extract and 3ß-O acetyl ursolic acid reduced in-vitro activity of pancreatic lipase. CONCLUSION: This study reveals that Crataegus azarolus var. eu- azarolus Maire has the efficiency to control hyperglycemia with its associated complications. This study is the first to evaluate antihyperglycemic and antihyperlipidemic potentials of 3ß-O acetyl ursolic acid.

Impact of phenolic composition on hepatoprotective and antioxidant effects of four desert medicinal plants.

BACKGROUND: Flavonoids and other polyphenols play a protective role in liver diseases and possess a high antioxidant capacity. OBJECTIVE: To compare and evaluate the antioxidant and hepatotoprotective activities of 4 deserts plants, Fagonia indica Burm. f., Calotropis procera R.Br., Zygophylum hamiense Schweinf. and Salsola imbricata Forssk. in correlation to their composition especially their phenolic content. METHODS: The influence of extracting solvent on total phenolic and flavonoidal contents was assessed spectrophotometrically. The flavonoid and other polyphenolic components of the methanol extracts were analyzed by RP-HPLC. DPPH radical scavenging potential of the different extracts was estimated. The hepatoprotective and antioxidant activities of the extracts against CCl4-induced hepatotoxicity in mice were evaluated. RESULTS: The flavonol quercitrin and rosmarinic acid were major in the F. indica, C. procera and S. imbricata samples, while rutin prevailed in that of Z. hamiense. The ethanolic and methanolic extracts showed noticeable DPPH radical-scavenging activity as compared to ascorbic acid. Assessment of liver enzymes revealed that oral administration of the extracts did not show any evidence of hepatotoxicity. Moreover, protection against CCl4-induced liver damage was evident upon administration of three plants extracts namely, F. indica, C. procera and S. imbricata. CONCLUSION: Overall, hepatotoxicity induced by CCl4 was effectively prevented by the three plants extracts through scavenging of free radicals and by boosting the antioxidant capacity of the liver. The protective effect of the plants could be attributed to their high quercitrin and rosmarinic acid contents.

Alleviation of antioxidant defense system by ozonized olive oil in DNBS-induced colitis in rats.

The aim of the study was to evaluate the potential protective effect of ozonized olive oil (OZO) in 2,4-dinitrobenzene sulphuric acid (DNBS) induced colitis in rats and to elucidate the role of some antioxidant defense system (superoxide dismutase "SOD," glutathione peroxidase "GSH-Px," and catalase "CAT") in these effects. The physicochemical parameters including viscosity, peroxide, and acid values of olive oil and OZO were evaluated. The animals were divided into several groups and the colitis was induced in the rats by intracolonic instillation of DNBS at dose of 15 mg/rat. Olive oil (OO) at dose of 6 mg/kg and OZO at doses of 3 and 6 mg/kg was administered orally for 7 days, starting the day before induction of colitis. Our results showed that macroscopic and microscopic damage scores were significantly reduced in a dose response manner in rats pretreated with OZO only. In contrast, CAT, GSH-Px, and SOD activities were significantly increased in the distal colon of inflamed animals pretreated with OZO with respect to control group dose dependently. Results demonstrate that OZO pretreatment exerts protective effects in DNBS induced colitis in rats and provide evidence that the protective effects of OZO are mediated by stimulation of some antioxidant enzymes.

Phenolic Profiling and Evaluation of Contraceptive Effect of the Ethanolic Extract of Salsola imbricata Forssk. in Male Albino Rats.

Reported researches dealing with either composition or bioactivity of Salsola imbricata are limited. This study was conducted aiming to investigate the phenolic composition of the plant and evaluate its efficacy as male contraceptive. Polyphenols, namely, phenolic acids and flavonoids, were qualitatively and quantitatively analysed by RP-HPLC in the hydrolysed methanol extract using two different wavelengths, 280 and 330 nm. The efficiency of different solvents in extracting the plant phenolics was assessed via spectrophotometric determination of the total phenolic and flavonoid contents. Acute toxicity study was carried out on the ethanolic extract to ascertain its safety prior to biological evaluation. The contraceptive effect was assessed, in male rats, by oral administration of the extract at two doses (250 and 500 mg/kg b. wt.), over a period of 65 days. HPLC analyses allowed the identification and quantification of a total of 13 and 8 components in the hydrolysed-methanol extract; the overall phenolic composition was dominated by quercitrin (12.692%) followed by coumaric acid (4.251%). Prolonged oral administration of the ethanolic extract caused slight reduction in the testis weight only. A significant decrease in the sperm count was observed (P < 0.01) in the two treated groups while significant decrease in the epididymal sperm motility was only observed in the high dose group. Morphological abnormalities were observed in sperms of treated animals. No distinct change in serum FSH, LH, and testosterone concentration was recorded. The histopathological findings supported to a high extent these results. The male contraceptive activity of Salsola imbricata could be ascribed to its phenolic components, especially quercitrin.

Anti-inflammatory and gastroprotective activities of the aqueous extract of Micromeria fruticosa (L.) Druce ssp Serpyllifolia in mice.

Micromeria fruticosa is used widely in many Mediterranean regions for various inflammatory conditions. The aim of this work was to assess the anti-inflammatory and gastroprotective activities of the aqueous extract of Micromeria fruticosa. The aqueous extract of Micromeria fruticosa was tested orally in mice at doses of 50, 100 and 200 mg/kg in carrageenan-induced paw edema, vascular permeability, myeloperoxidase activity (MPO) and indomethacin-induced gastric ulceration. In the paw edema model, the extract at dose of 200 mg/ kg, exhibited a significant anti-inflammatory effect, while the extract at 100 and 200 mg/kg reduced significantly the vascular permeability and MPO activity in a dose dependant manner. Oral pretreatment of the aqueous extract reduced significantly the development of gastric lesions induced by indomethacin at dose of 200 mg/kg only. Results suggest that the aqueous extract of Micromeria fruticosa has both anti-inflammatory as well as, gastroprotective activities. Thus it could be used as an alternative or supplementary herbal remedy for the treatment of inflammatory diseases especially when combined with strong anti-inflammatory medications that have ulcerogenic side effects such as NSAIDs.

Constituents and biological activity of the essential oil and the aqueous extract of Micromeria fruticosa (L.) Druce subsp. serpyllifolia.

Micromeria fruticosa L Druce subsp. serpyllifolia is a medicinal herb that is widely used as folk medicine in the treatment of abdominal pains, diarrhea, eye infections, heart disorders, elevated blood pressure, colds and wounds. This study aims to investigation the constituents and biological activity of the essential oil and aqueous extract of the plant that had been collected from Nablus. The oil was prepared by hydro-distillation method and analyzed by GC/MS. The oxygenated constituents were prevalent (87.4%) with the pulegone (58.5%) was the major constituents. Antitumor and analgesic activities of the isolated oil and the aqueous extract of M. fruticosa were investigated. Both the oil and the aqueous extract exhibited marked antitumor activities against Human Colon Tumor cells (HCT) and Mammary Carcinoma F7 (MCF7). The oil showed less IC(50s) against both cell lines (10, 12.7 µg/ml respectively). Also the extract significantly inhibited acetic acid-induced writhing response (p<0.05) and increased hot-plate pain threshold of mice at doses of 100 and 200 mg/kg while the oil did not show any analgesic activity on both models. Therefore, we concluded that the aqueous extract of M. fruticosa has a remarkable inhibitory activity in non-inflammatory reactions as well as inflammatory pain.

Antioxidant, antihyperuricemic and xanthine oxidase inhibitory activities of Hyoscyamus reticulatus.

CONTEXT: Xanthine oxidase (XO) is a key enzyme in the pathophysiological homeostasis of hyperuricemia. It catalyzes the oxidation of hypoxanthine to xanthine and then to uric acid, the reaction involves the formation of free radical intermediates and superoxide byproducts. OBJECTIVES: This study was undertaken to investigate the antioxidant, antihyperuricemic, and xanthine oxidase inhibitory potentials of Hyoscyamus reticulatus L. (Solanaceae) extract. MATERIALS AND METHODS: The antioxidant potency was measured using the ABTS•+ scavenging capacity system, which includes Trolox as a standard. The xanthine oxidase inhibitory activity of the extract was quantitated in vitro by measuring the decline in the catalytic rate of xanthine oxidase following incubations with the plant extracts and using xanthine as a substrate. The hypouricemic potential of the extract was evaluated using an in vivo model for hyperuricemia. We tested three different doses of the extract and allopurinol was used as standard antihyperuricemic positive control. RESULTS: H. reticulatus aqueous extract exhibited significant antioxidant scavenging properties (533.26 µmol TE/g dry extract weight) and inhibitory effect on xanthine oxidase activity (IC50 12.8 µg/mL). Furthermore, oral administration of the aqueous extract significantly reduced serum urate levels in oxonate-induced hyperuricemic mice in a dose-dependent manner. DISCUSSION AND CONCLUSION: Our results suggest that the aqueous extract of H. reticulatus aerial parts might have great potential as an antioxidant and a hypouricemic agent. Our lab is currently identifying the active compounds in the extract to which the biological activities could be attributed.