Anti-inflammatory effects of Mentha pulegium L. extract on human peripheral blood mononuclear cells are mediated by TLR-4 and NF-κB suppression.

There is great interest in evaluating the anti-inflammatory properties of new herbal products. Thus, the effects of Mentha pulegium L. extract on gene and protein expressions of pro-inflammatory mediators and transcription factors were determined. The hydro-ethanolic extract of Mentha pulegium L. was obtained and optimal non-cytotoxic concentrations of the extract were determined by MTT assay. Then, three different concentrations of Mentha pulegium L. (10, 30, and 90 µg/mL) were used to pre-treat the lipopolysaccharide (LPS)-stimulated and non-stimulated peripheral blood mononuclear cells (PBMCs) of 10 healthy individuals. Finally, the tumor necrosis factor-α (TNF-α), interleukin-1ß (IL-1ß), IL-6, Toll-like receptor-4 (TLR-4), nuclear factor-kappa B (NF-κB) p65, activator protein-1 (AP-1), inducible nitric oxide synthase (iNOS), and cyclooxygenase-2 (COX-2) gene expressions and TNF-α, IL-1ß, IL-6, TLR-4, prostaglandin E2 (PGE2), and COX-2 protein levels were measured. MTT results showed that there is no significant difference in cell viability among 10, 20, 40, and 80 µg/mL concentrations of Mentha pulegium L. extract at 24, 48, and 72 h (P > 0.05). The IC50 values were 236.1, 147.0, and 118.0 µg/mL after 24, 48, and 72 h respectively. TNF-α, IL-1ß, IL-6, TLR-4, iNOS, and NF-κB p65 mRNA levels in the pre-treated LPS-stimulated PBMCs were concentration-dependently reduced (P < 0.01 for TNF-α, TLR-4, and NF-κB p65; P < 0.05 for IL-1ß, IL-6, and iNOS). Also, the protein levels of pro-inflammatory mediators decreased and these differences were significant for TNF-α, IL-1ß, and TLR-4 (P < 0.001, P < 0.01, and P < 0.001, respectively). Mentha pulegium L. extract decreased the expression and biosynthesis of pro-inflammatory mediators. These effects are mainly mediated by TLR-4 and NF-κB suppression. Thus, Mentha pulegium L. could be useful in treating or ameliorating chronic inflammatory diseases.

Curcumin: A therapeutic strategy for targeting the Helicobacter pylori-related diseases.

Helicobacter pylori is a significant human pathogen of the stomach's epithelial lining. This type of carcinogen is associated with gastric cancer, indigestion, peptic ulcers, and upper digestive diseases. Therefore, successful treatment and eradication of this bacterium are required to reduce the prevalence of these diseases, especially in high-risk individuals. Moreover, some concerns exist regarding the extensive use of elimination therapy, such as anti-microbial resistance and rising H. pylori-associated diseases. Since there is still no effective vaccine, finding alternative therapies would appear to be a worthwhile pursuit. In this regard, curcumin exhibits anti-inflammatory, anti-carcinogenic, anti-oxidant properties and is widely used as a natural product-derived medicine or nutraceutical. Furthermore, curcumin has been reported to have anti-bacterial activity. Therefore, curcumin might be an effective herbal-based medicine for preventing, managing, or treating H. pylori infection. This review discusses the anti-inflammatory, anti-cancer, and anti-bacterial properties of curcumin as it pertains to gastric cancer and H. pylori-associated diseases.

Gastrointestinal Bleeding in Congenital Bleeding Disorders.

Gastrointestinal bleeding (GIB) is serious, intractable, and potentially life-threatening condition. There is considerable heterogeneity in GIB phenotypes among congenital bleeding disorders (CBDs), making GIB difficult to manage. Although GIB is rarely encountered in CBDs, its severity in some patients makes the need for a comprehensive and precise assessment of underlying factors and management approaches imperative. Initial evaluation of GIB begins with assessment of hematological status; GIB should be ruled out in patients with chronic anemia, and in presentations that include hematemesis, hematochezia, or melena. High-risk patients with recurrent GIB require urgent interventions such as replacement therapy for treatment of coagulation factor deficiency (CFD). However, the best management strategy for CFD-related bleeding remains controversial. While several investigations have identified CBDs as potential risk factors for GIB, research has focused on assessing the risks for individual factor deficiencies and other CBDs. This review highlights recent findings on the prevalence, management strategies, and alternative therapies of GIB related to CFDs, and platelet disorders.

Ameliorative effect of Allium sativum extract on busulfan-induced oxidative stress in mice sperm.

Busulfan is known to cause several adverse effects including reproductive toxicity in humans. Garlic (Allium sativum), a widely distributed medicinal plant, is highly regarded for its medicinal activities including antioxidant property. This study was conducted to assess whether garlic extract could serve as protective agents against testicular toxicity during busulfan treatment in a mice model. Seventy-two adult male mice were randomly divided into nine groups. In groups 1,2 and 3, distilled water, busulfan, and dimethyl sulfoxide and in the treatment groups hydro-alcoholic extract of garlic was administered orally at different doses per day (groups 4, 5 and 6; 200, 400, 800 mg kg-1 respectively). Groups 7, 8 and 9 were treated with the extract (200, 400 and 800 mg kg-1, respectively) plus busulfan. Following euthanasia, blood samples and epididymal sperm were collected. The busulfan-treated group showed significant decreases in sperm quality parameters, and serum levels of testosterone, LH and FSH was observed in the busulfan-treated mice. In addition, the TAC levels and antioxidant enzymes activities were reduced and malondialdehyde (MDA) levels were increased in the busulfan-treated mice. Notably, garlic extract co-administration caused a considerable recovery in sperm quality parameters, TAC levels, antioxidant enzymes activities, hormonal changes and MDA level. Based on our results, garlic has antioxidant effects against busulfan-induced testicular damages in mice.

Protection of cisplatin-induced spermatotoxicity, DNA damage and chromatin abnormality by selenium nano-particles.

Cisplatin (CIS), an anticancer alkylating agent, induces DNA adducts and effectively cross links the DNA strands and so affects spermatozoa as a male reproductive toxicant. The present study investigated the cellular/biochemical mechanisms underlying possible protective effect of selenium nano-particles (Nano-Se) as an established strong antioxidant with more bioavailability and less toxicity, on reproductive toxicity of CIS by assessment of sperm characteristics, sperm DNA integrity, chromatin quality and spermatogenic disorders. To determine the role of oxidative stress (OS) in the pathogenesis of CIS gonadotoxicity, the level of lipid peroxidation (LPO), antioxidant enzymes including superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GSH-Px) and peroxynitrite (ONOO) as a marker of nitrosative stress (NS) and testosterone (T) concentration as a biomarker of testicular function were measured in the blood and testes. Thirty-two male Wistar rats were equally divided into four groups. A single IP dose of CIS (7 mg/kg) and protective dose of Nano-Se (2 mg/kg/day) were administered alone or in combination. The CIS-exposed rats showed a significant increase in testicular and serum LPO and ONOO level, along with a significant decrease in enzymatic antioxidants levels, diminished serum T concentration and abnormal histologic findings with impaired sperm quality associated with increased DNA damage and decreased chromatin quality. Coadministration of Nano-Se significantly improved the serum T, sperm quality, and spermatogenesis and reduced CIS-induced free radical toxic stress and spermatic DNA damage. In conclusion, the current study demonstrated that Nano-Se may be useful to prevent CIS-induced gonadotoxicity through its antioxidant potential.

Investigation of optimal extraction, antioxidant, and antimicrobial activities of Achillea biebersteinii and A. wilhelmsii.

OBJECTIVE: Achillea species are endowed with multiple biological activities including antioxidant properties. However, no study has yet investigated the impact of extraction method and pH on the biological activities of these plants. The present study aimed to investigate the antioxidant and antimicrobial effects of methanol extracts from the aerial parts of the species Achillea biebersteinii Afan and Achillea wilhelmsii C. Koch (Asteraceae). In addition, the impact of extraction method and pH on these biological activities was evaluated. MATERIALS AND METHODS: Methanol extracts of A. biebersteinii and A. wilhelmsii were prepared using classical maceration and high-intensity ultrasound methods. Ultrasound-assisted extraction was performed at three different pH values: 5.7, 6.3 and 6.9. RESULTS: Total phenolic compounds (range: 20.16-108.54 vs. 17.18-59.61 mg gallic acid equivalent/g sample in A. biebersteinii and A. wilhelmsii, respectively), total flavonoids (range: 8.33-12.97 vs. 7.79-9.41 mg catechin equivalent/g sample), 2,2-diphenyl-1-picrylhydrazyl radical scavenging activity (IC50: 40.63-346.34 vs. 84.02-462.41) and reducing power (IC50: 504.44-4406.67 vs. 1710.00-5501.67) were significantly higher in A. biebersteinii vs. A. wilhelmsii and ultrasound-assisted vs. classical maceration extracts of both species. The aforementioned items were higher at pH = 6.3, followed by pHs of 6.9 and 5.7, respectively. Overall, A. biebersteinii extracts were more active against all of the tested microorganisms than A. wilhelmsii. Sensitivities of Gram-positive bacteria were higher for both Achillea extracts than the Gram-negative bacteria. No observable inhibitory activity was found from different extracts against Aspergillus niger. CONCLUSION: The findings of the present study suggest that methanol extracts of A. biebersteinii and A. wilhelmsii possess antioxidant and antimicrobial activity, being higher in the former. Ultrasound-assisted extraction and pH of 6.3 have significant augmenting impact on the total phenolic and flavonoid content as well as antioxidant activities of both species.

Effects of selenium, calcium and calcium ionophore on human oocytes in vitro maturation in a chemically defined medium.

BACKGROUND: In vitro maturation (IVM) of human oocytes is an emerging procedure quickly incorporated into the world of assisted reproductive technologies. As an effective method of in vitro maturation, several studies have reported the critical role of differentions on activating the complex process involved in both gamete maturation and fertilization. OBJECTIVE: In this study, we supplemented a chemically defined medium with different combinations of selenium, calcium and calcium ionophore concentrations to obtain the best rate of human oocytes maturation, survival, and fertilization. MATERIALS AND METHODS: As an experimental study, Three combinations of [selenium (5 µg/ml), calcium (5 µg/ml) and calcium ionophore (1 µg/ml)], [selenium (10 µg/ml), calcium (7 µg/ml) and calcium ionophore (2 µg/ml)] and [selenium (15 µg/ml), calcium (10 µg/ml) and calcium ionophore (5 µg/ml)] added to the chemically defined medium and the morphology of oocytes assessed after 22-24 hours in vitro maturation of the oocytes. RESULTS: The highest percentage of MII (meiosis II) oocytes (68%), developing beyond the morula (20.1%) and the blastocyst formation (11.1%) observed in oocytes treated with 15µg/ml selenium, 10µg/ml calcium and 5µg/ml calcium ionophore. Moreover, we showed the significant rate of survival in each three combinations after 36, 72 and 96 hours. CONCLUSION: Maturation and activation of oocytes may be triggered by changes in intracellular ion concentrations as second messengers in signal transduction pathways. Here, we received the highest percentage of in vitro maturation and fertilization among three combinations of selenium, calcium and calcium ionophore treatments. Using this combination of ions beside other factors might be useful for the enrichment of the human oocytes IVM medium.

Benefit of Satureja khuzestanica in subchronically rat model of cyclophosphamide-induced hemorrhagic cystitis.

Cyclophosphamide (CP) as a widely used antineoplastic drug causes hemorrhagic cystitis (HC) mainly via induction of oxidative stress. Regarding established antioxidant potential of Satureja khuzestanica (Lamiaceae) essential oil (SKEO), we aimed to investigate its protective effects in a subchronic rat model of CP-induced HC. CP (6mg/kg/day) and SKEO (225mg/kg/day) were administered alone or in combination by gavage for 28 days. Histopathological changes were investigated by light microscopy. Plasma samples were assayed for lipid peroxidation and total antioxidant power as biomarkers of toxic stress. In the CP-treated animals, irregular mucus layer, severe hemorrhage and edema, infiltration of inflammatory cells, and accumulation of mast cells were observed. In the CP+SKEO group, a relatively normal urothelial topography with decreased number of mucosal mast cells and inflammatory cells were observed. Increased lipid peroxidation along with decreased total antioxidant capacity resulting from CP treatment was significantly recovered by SKEO co-treatment. It is concluded that SKEO protects rats from CP-induced HC by reduction of free radical-induced toxic stress. It is strongly recommended to examine SKEO in the clinic to approve its benefit in patients undertaking CP.