Berberine ameliorates testosterone-induced benign prostate hyperplasia in rats.

INTRODUCTION: Benign prostatic hyperplasia (BPH) is a major urologic problem that mostly develops in older males. Oxidative stress and inflammation influence the occurrence of BPH. Berberine (BBR) is a natural ingredient that has antioxidant and anti-inflammatory properties. The current research aims at examining the effects of BBR on testosterone-stimulated BPH in rats. METHODS: Animals were randomly categorized to six groups. In the control group, normal saline and olive oil were injected as the vehicle. BPH group: received testosterone (3 mg/kg, subcutaneous, 28 days), BPH + BBR groups; received BBR (25 and 50 mg/kg, p.o, 28 days), BPH + finasteride groups: received finasteride (1 mg/kg, p.o, 28 days), BBR (50 mg/kg, p.o, alone) was administered for subjects in the BBR group. On the 29th day, after anesthesia, cervical dislocation was used to kill the subjects. Serum concentration of testosterone and dihydrotestosterone was measured and prostate tissues were excised and used for biochemical, inflammation, and histological analysis. RESULTS: BBR prevented increased serum concentrations of testosterone and dihydrotestosterone. BBR considerably reduced BPH-stimulated oxidative stress and inflammation through preventing the rise in lipid peroxidation and nitrite concentration and declined the accumulations of pro-inflammatory cytokines (e.g. interleukin 1ß and tumor necrosis factor α) and declining the depletion rate of GSH and the function of catalase and superoxide dismutase. Histopathological investigations reported that administration of BBR could suppress testosterone-stimulated BPH. CONCLUSION: This study demonstrated that BBR could significantly prevent the development of BPH in rats.

Carnosol attenuates bleomycin-induced lung damage via suppressing fibrosis, oxidative stress and inflammation in rats.

AIMS: Bleomycin, an important toxic anti-cancer agent, induces pulmonary fibrosis. The significance of oxidative stress and inflammation in promoting of bleomycin-induced idiopathic pulmonary fibrosis (IPF) has been reported. Thus, we evaluated the protective effects of carnosol as a robust natural antioxidant and anti-inflammatory agent for bleomycin-related IPF in rats. MAIN METHODS: Male Wistar rats (n = 40) were randomly assigned to five groups. Group 1 was administrated with saline (intratracheally) on day 7 and oral gavage of dimethyl sulfoxide (DMSO, 0.05%) from day 1 to day 28. Group 2 received a single dose of bleomycin (intratracheally, 7.5 UI/kg) on day 7 and oral gavage of saline for 28 days. Groups 3, 4 and 5 were administrated with bleomycin (single dose) on day 7, along with oral administration of carnosol (at doses 10, 20 and 40 mg/kg, respectively) from day 1 to day 28. The lungs were isolated to measure the histopathological and biochemical and inflammatory markers. KEY FINDINGS: Carnosol treatment significantly reduced malondialdehyde, nitric oxide, protein carbonyl, tumor necrosis factor- α, interleukin-6 levels and myeloperoxidase activity in the lungs of rats exposed to bleomycin. Also, lung glutathione content, catalase, glutathione peroxidase and superoxide dismutase activities significantly increased in the carnosol/bleomycin-treated group than the bleomycin group. Lung index, hydroxyproline content, fibrosis and histopathological changes, also significantly decreased by carnosol therapy. SIGNIFICANCE: Treatment with carnosol can modulate biochemical and histological alterations caused by bleomycin. Thus, it can be regarded as an appropriate therapeutic approach for IPF.

Comparison of the effect of photodynamic therapy with curcumin and methylene Blue on streptococcus mutans bacterial colonies.

BACKGROUND AND AIM: Streptococcus mutans (S. mutans) is a bacterium that colonizes in the mouth and is a common cause of dental caries and periodontal diseases. This bacterium comprises 70% of the bacteria in the dental plaque. Although tooth decay is a multifactorial complication, S. mutans biofilms are the main cause of cavitated carious lesions. Considering the importance of this microorganism, we aimed at investigating the effect of photodynamic therapy (PDT) using curcumin (CUR) and methylene blue (MB) photosensitizers on S. mutans. MATERIALS AND METHODS: In this in-vitro experimental study, first, samples of S. mutans were prepared in 110 test tubes and were randomly assigned to 11 groups after colony counting: 1) Positive control group, 2) Negative control group, 3) CUR extract group, 4) 460-nm laser group, 5) 460-nm continuous laser + CUR group, 6) 460-nm discontinues 50% duty cycle (DC) laser + CUR group, 7) 660-nm laser group, 8) 660-nm laser + MB group, 9) MB group, 10) dental light-curing group, and 11) chlorhexidine (CHX) group. After the intervention, cultivation was performed again in blood agar medium, and the bacterial colony-forming units per milliliter (CFU/ml) were counted again. Data were analyzed using analysis of variance (ANOVA) and Tukey's test. RESULTS: CHX and 460-nm low-level continuous laser + CUR had the highest and most significant effect on inhibiting the growth of S. mutans bacterial colonies and showed significant differences with other groups (P < 0.001). CONCLUSION: According to the results, MB- and CUR-mediated PDT can significantly eradicate S. mutans colonies.

In vitro comparison of the effect of photodynamic therapy with curcumin and methylene blue on Candida albicans colonies.

BACKGROUND AND AIM: Candida albicans (C. albicans) causes oral fungal infections. Considering the high prevalence of candidiasis, the toxicity of antifungal drugs, and the fungistatic property which develops drug-resistant species, the present study aimed to assess the effect of photodynamic therapy (PDT) with curcumin (CUR) and methylene blue (MB) photosensitizers and lasers with different exposure parameters on C. albicans colonies. MATERIALS AND METHODS: In this in-vitro experimental study, 150 samples of C. albicans standard strain (ATCC 10231) were examined using different combinations of CUR and MB photosensitizers with and without 460-nm and 660-nm laser irradiation with different exposure parameters in 15 groups of 10 samples each. The samples were cultured in microplates containing Sabouraud Dextrose Agar (SDA) medium, and the colony-forming units (CFU) were counted after 24 h of incubation at 37 °C. Data were analyzed using one-way analysis of variance (ANOVA) and Tukey's test. RESULTS: The maximum number of colonies was noted in the positive control group (CFU = 201,500 ± 42,093), while the minimum number was detected in the 460-nm laser+10.2% CUR group (CFU = 10,100 ± 2558), followed by the nystatin group (CFU = 22,300 ± 5578). There was a significant statistical difference between the 460-nm laser + CUR group and other studied groups (P < 0.0001). CONCLUSION: The 460-nm laser in combination with CUR has the maximum antifungal efficiency against C. albicans.

Isolation, functional characterization, and biological properties of MCh-AMP1, a novel antifungal peptide from Matricaria chamomilla L.

The antimicrobial activities of natural products have attracted much attention due to the increasing incidence of pathogens that have become resistant to drugs. Thus, it has been attempted to promisingly manage infectious diseases via a new group of therapeutic agents called antimicrobial peptides. In this study, a novel antifungal peptide, MCh-AMP1, was purified by reverse phase HPLC and sequenced by de novo sequencing and Edman degradation. The antifungal activity, safety, thermal, and pH stability of MCh-AMP1 were determined. This peptide demonstrated an antifungal activity against the tested Candida and Aspergillus species with MIC values in the range of 3.33-6.66 µM and 6.66-13.32 µM, respectively. Further, physicochemical properties and molecular modeling of MCh-AMP1 were evaluated. MCh-AMP1 demonstrated 3.65% hemolytic activity at the concentration of 13.32 µM on human red blood cells and 10% toxicity after 48 hr at the same concentration on HEK293 cell lines. The antifungal activity of MCh-AMP1 against Candida albicans was stable at a temperature range of 30-50°C and at the pH level of 7-11. The present study indicates that MCh-AMP1 may be considered as a new antifungal agent with therapeutic potential against major human pathogenic fungi.

Daptomycin.

Daptomycin is a cyclic lipopeptide antibiotic used for the treatment of Gram-positive infections including complicated skin and skin structure infections, right-sided infective endocarditis, bacteraemia, meningitis, sepsis and urinary tract infections. Daptomycin has distinct mechanisms of action, disrupting multiple aspects of cell membrane function and inhibiting protein, DNA and RNA synthesis. Although daptomycin resistance in Gram-positive bacteria is uncommon, there are increasing reports of daptomycin resistance in Staphylococcus aureus, Enterococcus faecium and Enterococcus faecalis. Such resistance is seen largely in the context of prolonged treatment courses and infections with high bacterial burdens, but may occur in the absence of prior daptomycin exposure. Furthermore, use of inadequate treatment regimens, irregular drug supply and poor drug quality have also been recognized as other important risk factors for emergence of daptomycin-resistant strains. Antimicrobial susceptibility testing of Gram-positive bacteria, communication between clinicians and laboratories, establishment of internet-based reporting systems, development of better and more rapid diagnostic methods and continuous monitoring of drug resistance are urgent priorities.

Hepatoprotective effect of berberine against methotrexate induced liver toxicity in rats.

Hepatotoxicity is one of the major side effects of methotrexate (MTX), which restricts the clinical use of this drug. Berberine (BBR) is a natural compound with multiple pharmacological activities such as antioxidant, antiapoptotic and anti-inflammatory effects. In this study, the effect of BBR on MTX-induced hepatotoxicity was studied. A total number of 28 male Wistar rats were randomly divided into four experimental groups. Rats were pretreated with BBR orally with dose of 100mg/kg for 10 consecutive days and MTX (20mg/kg, intraperitoneally) was administrated on the 9th day. Then on day 11, blood samples were collected to determine serum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST) and alkaline phosphatase (ALP). The extracted livers were used for histological examination, biochemical assays and real time PCR studies. Malondialdehyde (MDA), glutathione (GSH), protein carbonyl (PC), nitric oxide (NO) levels, catalase (CAT), superoxide dismutase (SOD), glutathione peroxidase (GPx) and myeloperoxidase (MPO) activities were assessed in hepatic tissue. In addition, the expression of SOD and PGx was measured using real-time PCR method in hepatic tissue. Results showed that MTX administration significantly increases AST, ALT and ALP levels (all p<0.001). It also, increases MDA, PC, NO levels and MPO activity (p<0.001, p<0.01, p<0.05 and p<0.01 respectively). Moreover, MTX decreases hepatic GSH level, SOD, GPx and CAT activities (all p<0.001). Pre-treatment with BBR for 10days prevented some of these changes. Serum levels of AST and ALT decreased (all p<0.001). Hepatic MDA level decreased (p<0.001) and GSH level as well as GPx activity increased (p<0.05 and p<0.01 respectively). Our results indicated that BBR might be useful for prevention of the hepatotoxicity induced by MTX via ameliorative effects on biochemical and oxidative stress indices.

A Review on Iron Chelators in Treatment of Iron Overload Syndromes.

Iron chelation therapy is used to reduce iron overload development due to its deposition in various organs such as liver and heart after regular transfusion. In this review, different iron chelators implicated in treatment of iron overload in various clinical conditions have been evaluated using more up-to-date studies focusing on these therapeutic agents. Deferoxamine, Deferiprone and Deferasirox are the most important specific US FDA-approved iron chelators. Each of these chelators has their own advantages and disadvantages, various target diseases, levels of deposited iron and clinical symptoms of the afflicted patients which may affect their selection as the best modality. Taken together, in many clinical disorders, choosing a standard chelator does not have an accurate index which requires further clarifications. The aim of this review is to introduce and compare the different iron chelators regarding their advantages and disadvantages, usage dose and specific applications.

Protective effect of Berberis vulgaris fruit extract against Paraquat-induced pulmonary fibrosis in rats.

BACKGROUND: Pulmonary fibrosis induced by paraquat (PQ) has caused a large number of human fatalities all over the world, especially in Asian region. The main potential mechanism of PQ toxicity has been thought to be mediated by ROS. The present study was designed to evaluate the efficacy of the Berberis vulgaris fruit extract (BVFE) against PQ-induced pulmonary fibrosis in rats. METHODS: Forty male rats were randomly divided into five experimental groups each containing eight rats. Groups 1 and 2, served as a negative and positive control and received a single dose of intratracheal instillation of saline and PQ (20mg/kg), respectively. Groups 3-5 were treated with different doses of BVFE (100, 200, 400mg/kg/day, orally) 1 week before the PQ injection and continued for 3 weeks. The rats were sacrificed 21days after PQ. Malondialdehyde (MDA), Hydroxyproline, inflammatory and fibrogenic cytokine tumor necrosis factor (TNF)-α, interleukin (IL)-6 and transforming growth factor (TGF)-ß1 in lung tissue were determined. Presence of fibrosis, inflammatory cells, connective tissue and collagen deposition in lung were evaluated microscopically by hematoxylin and eosin (H&E) staining. Dried extract was standardized by amount of berberine by HPTLC methods by silica gel plate. RESULTS: The results showed that PQ could significantly increase the lung MDA, hydroxyproline, TNF-α, IL-6 and TGF-ß1 levels. BVFE ameliorated the biochemical and histological lung alterations induced by PQ. CONCLUSIONS: The present study indicates the hydroalcolic extract of Berberis vulgaris fruit has beneficial effects in rat pulmonary fibrosis induced by PQ in a dose-dependent manner, possibly by anti-oxidant and anti- inflammatory properties, which might be due to its berberine alkaloid content.

Aloe vera Gel: Effective Therapeutic Agent against Multidrug-Resistant Pseudomonas aeruginosa Isolates Recovered from Burn Wound Infections.

Objective. Aloe vera is an herbal medicinal plant with biological activities, such as antimicrobial, anticancer, anti-inflammatory, and antidiabetic ones, and immunomodulatory properties. The purpose of this study was investigation of in vitro antimicrobial activity of A. vera gel against multidrug-resistant (MDR) Pseudomonas aeruginosa isolated from patients with burn wound infections. Methods. During a 6-month study, 140 clinical isolates of P. aeruginosa were collected from patients admitted to the burn wards of a hospital in Tehran, Iran. Antimicrobial susceptibility test was carried out against the pathogens using the A. vera gel and antibiotics (imipenem, gentamicin, and ciprofloxacin). Results. The antibiogram revealed that 47 (33.6%) of all isolates were MDR P. aeruginosa. The extract isolated from A. vera has antibacterial activity against all of isolates. Also, 42 (89.4%) isolates were inhibited by A. vera gel extract at minimum inhibitory concentration (MIC) ≤ 200 µg/mL. MIC value of A. vera gel for other isolates (10.6%) was 800 µg/mL. All of MDR P. aeruginosa strains were inhibited by A. vera at similar MIC50 and MIC90 200 µg/mL. Conclusion. Based on our results, A. vera gel at various concentrations can be used as an effective antibacterial agent in order to prevent wound infection caused by P. aeruginosa.

Determination of integron frequency by a polymerase chain reaction-restriction fragment length polymorphism method in multidrug-resistant Escherichia coli, which causes urinary tract infections.

The purpose of this study was to determine the presence of integrons in Escherichia coli, which cause urinary tract infections, and to define the association between integrons and antimicrobial susceptibility. Susceptibility of 200 isolates from urine samples of patients suffering from urinary tract infections to 13 antibiotics was determined by the Kirby-Bauer disk diffusion method. The existence of class1 and 2 integrons in resistant isolates was assessed by polymerase chain reaction-restriction fragment length polymorphism and sequencing. Antibiotic resistance patterns were observed as follows: amoxicillin 78%, tetracycline 76.1%, co-trimoxazole 67.7%, cephalotin 60%, nalidixic acid 57.4%, chloramphenicol 49%, gentamicin 46.4%, ceftazidim 38.1%, ciprofloxacin 36.2%, nitrofurantoin 33.5%, amikacin 32.1%, norfloxacin 36.1%, and imipenem 27.1%. Of 200 isolates, 155 (77.5%) were multidrug resistant (MDR). The existence of integrons was confirmed in 50.3% of isolates. Three class 1 integron types, aadA2 being the most frequently found, and four class 2 integron types are described. Significant association between resistance to gentamicin, co-trimoxazole, cephalotin, ceftazidim, imipenem, chloramphenicol, and nalidixic acid with the existence of integrons was observed. Multidrug resistance suggests that the strategy for treatment of patients with E.coli infections needs to be revised. Furthermore, it was shown that integrons may be partly responsible for multidrug resistance. Imipenem and norfloxacin were the most effective antibiotics against isolates.