Inflammopharmacology

In vitro biological potential of the essential oil of some aromatic species used in Iranian traditional medicine

The goal of this study is to evaluate the chemical compounds, the anti-bacterial/fungal activity, and the cytotoxicity of the essential oil of three species of lamiaceae in Iran. After the extraction of the essential oil implementing the hydrodistillation method, the analysis and identification of the compounds were carried out with a chromatograph coupled with a mass spectrometer. For the evaluation of the anti-bacterial/fungal activity of the essential oils, the measurement of the diameter of inhibition halo, the minimum inhibitory concentration (MIC), bactericidal and fungicidal concentrations (MBC/MFC) were utilized; and for the evaluation of the cytotoxic activity of the essential oils, the 3-(4,5-dimethylthiazolyl)-2,5-diphenyltetrazolium bromide (MTT) method was used. The results show that the dominant compounds in the Perovskia abrotanoides Kar essential oil were camphor (21.68%), 1,8-cineole (14.26%), and α-pinene (7.23%); moreover, the dominant compounds in the Salvia reuteriana Boiss. Essential oil were benzyl benzoate (27.10%), linalool (13.27%), and sclareol (7.75%); in addition, the dominant compounds in the Ziziphora clinopodioides subsp. rigida (Boiss.) Rech.f. were cyclofenchene (25.29%), pulegone (14.14%), and menthol (7.70%). The largest halo diameter of inhibition halo (~ 22 mm) was against Streptococcus pyogenes and the strongest inhibiting and killing activity was against Candida albicans (MIC and MFC = 125 μg/mL) shown by the S. reuteriana essential oil which, respectively, matched the control antibiotics rifampin and nystatin. The analysis of the MTT test results showed that the Z. clinopodioides subsp. rigida essential oil (with IC50 value of ~ 144.2500) had the strongest cytotoxic activity against human ovarian cancer cells (OVCAR-3). On the whole, the results show that the essential oil of the Lamiaceae family plants is a source for various compounds with potential biological activities which can serve as a possible alternative to produce herbal medicine which are effective on some microorganisms and cancer cell lines.

Melatonin induces apoptosis and cell cycle arrest in cervical cancer cells via inhibition of NF-κB pathway

Cervical cancer is the most prevalent cancer in females. Melatonin, a neurohormone has been documented as a promising therapeutic molecule for cervical cancer. However, the underlying molecular mechanism is not known. We explored the dose-dependent anti-tumor response of melatonin against cervical cancer cell lines, HeLa (HPV-18 positive) and SiHa (HPV-16 positive). The anti-cancer effect of melatonin was evaluated by MTT assay, cell imaging, colony formation, DAPI, AO/PI, LDH, Flow cytometry, scratch assay, western blot analysis and real-time PCR. Results of DAPI, AO/PI, LDH, and Annexin/PI staining revealed that melatonin induces apoptosis. The results of cell cycle analysis revealed that melatonin arrests the HeLa and SiHa cells in sub-G1 and G1 phases, respectively. Western blot analysis revealed that melatonin downregulated the expression of pro-inflammatory transcription factor, NF-κB and the expression of COX-2 protein, a key mediator in cell proliferation. In addition, melatonin downregulated the expression of an invasive marker, MMP-9, an antiapoptotic protein, Bcl-2, and upregulated the expression of pro-apoptotic protein, Bax at both transcriptional and translational levels. Overall, the results suggest that melatonin exhibited strong anti-cancer therapeutic potential against human cervical cancer cell line progression possibly through inhibition of NF-κB signalling pathway.

Curcumin potentiates the anti-inflammatory effects of Tehranolide by modulating the STAT3/NF-κB signaling pathway in breast and ovarian cancer cell lines

Studies have demonstrated that natural products, such as curcumin and artemisinin, possess anti-inflammatory effects, which can be beneficial for cancer treatment. Tehranolide, as a novel natural product, has a wide range of biological activities, including anti-cancer effects. However, many properties of Tehranolide, like its anti-inflammatory activity and its combination with curcumin, have not been investigated yet. This investigation examined the anti-inflammatory activity of Tehranolide, either alone or in combination with curcumin, via modulating the NF-κB (nuclear factor kappa-light-chain-enhancer of activated B cells) and STAT3 (signal transducer and activator of transcription 3) signaling pathways in MDA-MB-231 and SKOV3, breast and ovarian cancer cell lines. ELISA-based methods were employed to measure the pro-inflammatory cytokine levels and the NF-κB activity in lipopolysaccharide (LPS)-induced cells. The real-time PCR experiment and Griess test were performed to evaluate inducible nitric oxide synthase (iNOS) gene expression and nitrite levels, respectively. The STAT3 and NF-κB signaling pathways were investigated by Western blotting analysis. Tehranolide's anti-cancer activity was also assessed in a mouse model of breast cancer using the TUNEL (terminal deoxynucleotidyl transferase nick-end labeling) assay. Tehranolide diminished levels of pro-inflammatory cytokines in cancer cells. Additionally, it suppressed NF-κB DNA binding and STAT3 phosphorylation, reducing iNOS gene expression and nitrite production. Moreover, Western blotting showed that Tehranolide enhanced the inhibitory κB (IκBα) and Bcl-2 (B-cell lymphoma 2)-associated X (BAX) expression, and downregulated the expression of Bcl-2 proteins. Furthermore, the TUNEL assay demonstrated that Tehranolide induced apoptosis in a breast cancer mouse model. Curcumin potentiated all the anti-inflammatory effects of Tehranolide. This investigation indicated for the first time that Tehranolide, either alone or in combination with curcumin, exerted its anti-inflammatory effects by suppressing NF-κB and STAT3 signaling pathways in SKOV3 and MDA-MB-231 cells.