Effects of coenzyme Q10 supplementation on inflammation, angiogenesis, and oxidative stress in breast cancer patients: a systematic review and meta-analysis of randomized controlled- trials.

BACKGROUND/OBJECTIVE: Systemic inflammation and oxidative stress (OS) are associated with breast cancer. CoQ10 as an adjuvant treatment with conventional anti-cancer chemotherapy has been demonstrated to help in the inflammatory process and OS. This systematic review and meta-analysis of randomized clinical trials (RCTs) aimed to evaluate the efficacy of CoQ10 supplementation on levels of inflammatory markers, OS parameters, and matrix metalloproteinases/tissue inhibitor of metalloproteinases (MMPs/TIMPs) in patients with breast cancer. METHODS: A systematic literature search was carried out using electronic databases, including PubMed, Web of Science, Scopus, Google Scholar, and Embase, up to December 2020 to identify eligible RCTs evaluating the effect of CoQ10 supplementation on OS biomarkers, inflammatory cytokines, and MMPs/TIMPs. From 827 potential reports, 5 eligible studies consisting of 9 trials were finally included in the current meta-analysis. Quality assessment and heterogeneity tests of the selected trials were performed using the PRISMA checklist protocol and the I2 statistic, respectively. Fixed and random-effects models were assessed based on the heterogeneity tests, and pooled data were determined as the standardized mean difference (SMD) with a 95% confidence interval (CI). RESULTS: Our meta-analysis of the pooled findings for inflammatory biomarkers of OS and MMPs showed that CoQ10 supplementation (100 mg/day for 45-90 days) significantly decreased the levels of VEGF [SMD: - 1.88, 95% CI: (- 2. 62 to - 1.13); I2 = 93.1%, p < 0.001], IL-8 [SMD: - 2.24, 95% CI: (- 2.68 to - 1.8); I2 = 79.6%, p = 0.001], MMP-2 [SMD: - 1.49, 95% CI: (- 1.85 to - 1.14); I2 = 76.3%, p = 0.005] and MMP-9 [SMD: - 1.58, 95% CI: (- 1.97 to - 1.19); I2 = 79.6%, p = 0.002], but no significant difference was observed between CoQ10 supplementation and control group on TNF-α [SMD: - 2.30, 95% CI: (- 2.50 to - 2.11); I2 = 21.8%, p = 0.280], IL-6 [SMD: - 1.56, 95% CI: (- 1.73 to - 1.39); I2 = 0.0%, p = 0.683], IL-1ß [SMD: - 3.34, 95% CI: (- 3.58 to - 3.11); I2 = 0.0%, p = 0.561], catalase (CAT) [SMD: 1.40, 95% CI: (1.15 to 1.65); I2 = 0.0%, p = 0.598], superoxide dismutase (SOD) [SMD: 2.42, 95% CI: (2.12 to 2.71); I2 = 0.0%, p = 0.986], glutathione peroxidase (GPx) [SMD: 2.80, 95% CI: (2.49 to 3.11); I2 = 0.0%, p = 0.543]], glutathione (GSH) [SMD: 4.71, 95% CI: (4.26 to 5.16); I2 = 6.1%, p = 0.302] and thiobarbituric acid reactive substances (TBARS) [SMD: - 3.20, 95% CI: (- 3.53 to - 2.86); I2 = 29.7%, p = 0.233]. CONCLUSION: Overall, the findings showed that CoQ10 supplementation reduced some of the important markers of inflammation and MMPs in patients with breast cancer. However, further studies with controlled trials for other types of cancer are needed to better understand and confirm the effect of CoQ10 on tumor therapy.

Urtica dioica Extract Inhibits Cell Proliferation and Induces Apoptosis in HepG2 and HTC116 as Gastrointestinal Cancer Cell Lines.

BACKGROUND: Nowadays the use of plant-derived products has been extensively examined in the treatment of many types of gastrointestinal cancers such as hepatocarcinoma and colon cancer. Urtica dioica is a traditional herb that has many pharmacological effects and wildly used as a therapeutic agent in cancer. Herein, we have evaluated the effects of the different concentrations of Methanolic Extract of Urtica dioica (MEUD) on viability, death pattern, and expression of the apoptosis-related gene in normal Human Dermal Fibroblast (HDF), hepatocarcinoma cell lines (HepG2) and colon-cancer cell line (HCT116). METHODS: A high-performance liquid chromatography method was developed to simultaneously separate 3 phenolic acids in MEUD. HepG2 and HCT116 cell lines as well as HDF normal cell line were cultured in suitable media. After 24 and 48h, in the cultured cell with different concentrations of MEUD, cells viability was assessed by MTT assay, and apoptosis was also evaluated at the cellular level by Annexin V/PI flow cytometry analyzing and AO/EB staining. BCL2 and BAX gene expressions were assessed by TaqMan real-time PCR assay. RESULTS: MEUD showed antiproliferative effects on HepG2 and HTC116 cells after 48h with an IC50 value of about 410 and 420µg/ml, respectively (P < 0.001). Apoptotic cells were observed in HepG2 and HTC116 cells but not in HDF. Furthermore, the increased level of BAX/BCL-2 ratio was observed in HepG2 and HTC116 cells under the treatment of different concentrations of MEUD. CONCLUSION: The MEUD may influence hepatocarcinoma and colon-cancer cell lines at specific doses and change their proliferation rate by changing the expression of BAX and BCL2.

Effects of Aloe vera and Eucalyptus methanolic extracts on experimental toxoplasmosis in vitro and in vivo.

Toxoplasmosis is a worldwide disease caused by the protozoan parasite Toxoplasma gondii (T. gondii), which is most commonly treated by pyrimethamine and sulfadiazine. However, this treatment presents several adverse side effects; Thus, new drugs with lower toxicities are urgently needed. In this study the anti-T. gondii activity of A. vera and Eucalyptus extracts were evaluated in vitro using a MTT (3-(4, 5-dimethylthiazol-2-yl) 2, 5-diphenyltetrazolium bromide) assay and in vivo by measuring the survival rates of mice infected with 2 × 103 tachyzoites of RH strain of T. gondii and then injected intraperitoneally by different concentrations of extracts for 4 days. Biochemical parameters such as Ferric Reducing Antioxidant Potential (FRAP) and malondialdehyde (MDA) assay were also evaluated. As results, in the in vitro assay, the IC50 values were 13.2, 24.7, 2.63 µg/ml, and the selectivity indexes were 3.3, 2.4, 3.03 for the A. vera, Eucalyptus and pyrimethamine, respectively. The mice treated with Eucalyptus showed a better survival rate than others (P < 0.05). The increased weight of liver and spleen, due to infection, was reduced by treatments. In FRAP assay Eucalyptus showed a better antioxidant activity than the other extracts. MDA levels in both liver and spleen were reduced by treatment. The results show that A. Vera and Eucalyptus possess anti-T. gondii activities in vitro and in vivo, in addition, Eucalyptus shows antioxidant activity with a higher survival rate. Therefore, Eucalyptus may be a useful candidate for treating Toxoplasma infection. Moreover, further studies are required to investigate the fractionations of this plant against T. gondii.