Antibacterial and antioxidant double-layered nanofibrous mat promotes wound healing in diabetic rats.

Diabetic wounds are problematic to heal owing to microbial infections as well as decreased proliferation and high concentrations of reactive oxygen species. In this study, a double-layered nanofibrous mat containing grape seed extract (GSE) and silver sulfadiazine (SSD) was fabricated. A synthetic biodegradable polymer, e.g., polycaprolactone (PCL), and a natural material (i.e., collagen) were employed as wound dressing substances. The results showed that GSE possesses antioxidant activity which can be helpful in reducing free radicals. The platform exhibited antibacterial activity against gram-positive and -negative bacteria. The double-layered nanofibrous mat containing GSE and SSD not only was not toxic but also amplified the cell proliferation compared to a pure mat, showing the effect of plant extract. After induction of a round wound, the animals were divided into three groups, namely (1) normal group (receiving + GSE/-GSE nanofiber), (2) diabetic group (receiving + GSE/-GSE nanofiber), and (3) control group (receiving gauze). In vivo evaluation demonstrated no significant differences in the healing process of normal rats. Surprisingly, fully repaired skin was observed on day 14 in the double-layered nanofibrous mat containing GSE in the normal and diabetic groups whereas the wound of diabetic rats treated with pure mat was not completely healed. The macroscopic and microscopic results after 14 days showed the following order in wound repair: Normal/ + GES > Diabetic/ + GSE > Normal/-GES > Diabetic/-GSE > control (with gauze) (p < 0.05). Accordingly, the double-layered nanofibrous mat containing GSE and SSD used in the present study could be considered as a suitable wound dressing in order to shorten healing time and prevent infection during the wound healing process.

Metformin synergistically increases the anticancer effects of lapatinib through induction of apoptosis and modulation of Akt/AMPK pathway in SK-BR3 breast cancer cell line.

Objectives: Combination chemotherapy is a beneficial intervention for breast cancer, versus single therapy. We investigated the effect of Metformin (Met) on Lapatinib (Lap)-induced apoptosis in SK-BR3 cells. Materials and Methods: Toxic effect of Met and Lap on SK-BR3 cells was measured using MTT assay. Flow cytometry was used to measure the co-treatment effect of Met on lapatinib-induced apoptosis. The relative expression of Bax, Bcl2, and P21 was measured using a real-time PCR. The activity of caspase 3 and 9 was measured using an ELISA kit. The protein level of AMPK and Akt was determined using Western blot analysis. Results: Metformin and lapatinib alone and combined form showed significant time- and dose-dependent toxic effects on SK-BR3 cell viability. The greatest synergistic inhibitory effect on the cell viability [combination index (CI) = 0.51] was remarkable at Met 100 mM combined with Lap 100 nM. The combination has a stronger apoptotic death (46%) versus lapatinib alone. The combination considerably increased the mRNA expression of Bax and P21, and caspase 3 and 9 activity, while, decreasing the mRNA expression of Bcl2. Additionally, the combination significantly up-regulated and down-regulated the protein levels of AMPK and Akt, respectively. Conclusion: The metformin-lapatinib combination can induce more potent apoptotic death versus each compound individually. The combination may be suggested as a valuable therapeutic intervention in patients with breast cancer. However, additional in vivo studies are necessary to evaluate the clinical use of the combination for induction of apoptosis and its antitumor effects.

The Healing Effect of N-Hexan- Dichloromethane Extract Root Onosma Bulbotrichum in Second Degree Burns.

BACKGROUND: Wound healing is the process of repair following an injury to the skin and other soft tissues. In this study, the effect of n-hexane d-chloromethane extract (1: 1) of root Onosma bulbotrichum DC on the second degree burn in rabbit model was investigated. METHODS: Thirty-six adult rabbits of both sexes were randomly divided into six groups, control (without treatment), negative control (treatment with cold cream), positive control (treatment with silver sulfadiazine), and treatment groups with 5%, 1% and 2% O. bulbotrichum cream and assessed histologically. RESULTS: The best result was shown in 5% O. bulbotrichum group similar to silver sulfadiazine group. The maximum amount of collagen and the tensile strength of tissue were observed in 5% O. bulbotrichum and silver sulfadiazine groups. Histopathological examination showed that burn healing in treatment group with 5% O. bulbotrichum was faster than other groups. CONCLUSION: The 5% O. bulbotrichum cream was shown to have healing, and anti-inflammatory effects when used in treatment of second degree burns.

Enhancement of human skin fibroblasts proliferation as a result of treating with quince seed mucilage.

BACKGROUND: Quince seed mucilage (QSM) has been used in Iranian folk medicine in the treatment of wounds and burns. Experimental and clinical studies showed its wound healing activity. However, the mechanism by which this agent affects cells involved in the wound healing process is unknown. OBJECTIVES: In this study, we investigated the effects of QSM at concentrations of 50, 100, 200, and 400 µg/mL on human skin fibroblast proliferation as an aspect of promotion of wound healing. MATERIALS AND METHODS: Human skin fibroblast cell line (HNFF-P18) was used in the experiment. Cell proliferation assay was measured by a MTT assay. RESULTS: Cells treated with QSM at concentrations less than 400 µg/mL increased their proliferative activity. The concentration of 50 µg/mL was the most effective dose after 72 hours treatment. CONCLUSIONS: QSM has the ability to stimulate proliferation of human skin fibroblast. This effect suggests that this compound can act as a wound healing agent.

Wound healing properties of quince seed mucilage: in vivo evaluation in rabbit full-thickness wound model.

OBJECTIVE: Quince seed mucilage (QSM) has been used in Iranian traditional medicine for the treatment of skin wounds and burns. Recent studies indicated that QSM accelerated wound healing. The present study was undertaken to investigate the healing efficiency of QSM formulated as 5%, 10%, and 20% creams in eucerin base with especial attention on growth factors involving in wound healing. METHODS: Full thickness wounds were created in Iranian male rabbits divided into five experimental groups (n = 6), as negative control, eucerin and treatments. Negative control group did not receive any treatment. Eucerin group received topical eucerin, twice a day. Treatment groups were treated topically by creams of QSM 5%, 10% and 20% (w/w) in eucerin base, twice daily. The efficacy of treatment was evaluated based on wound contraction, haydroxyproline content, tensile strength of wound tissue. The levels of epidermal growth factor (EGF), transforming growth factor-ß1 (TGF-ß1), vascular endothelial growth factor (VEGF) and platelet derived growth factor (PDGF) were also determined in serum and wound fluid of tested animals. RESULTS: Results showed that there were statistically significant differences in wound contraction between QSM 10 and 20% creams treatments groups and control groups (P < 0.05) in most of the days. Rabbits treated with QSM 20% cream had the best results (completed healing in 13 days, higher hydroxyproline content, higher tissue resistance and higher wound fluid levels of evaluated growth factors). CONCLUSION: We concluded tha QSM in 10-20% concentrations have a good potential for promote wound healing thus supports its traditional use.

Protective Effect of Caffeic Acid Phenethyl Ester (CAPE) on Amiodarone-Induced Pulmonary Fibrosisin Rat.

Treatment with amiodarone, a commonly prescribed antidysrhythmic agent, is associated with pulmonary fibrosis (PF) which is a commonly progressive and untreatable disease. Caffeic acid phenethyl ester (CAPE) is a phenolic antioxidant and an active anti-inflammatory , anticancer, antimicrobial and antioxidant component of propolis (bee glue; a resinous hive product collected by honey bees). In the current study, the effects of CAPE on amiodarone-induced pulmonary fibrosis in rat were investigated. Male rats were divided in to 4 groups. The first group only received amiodarone (6.25 mg/Kg) on first and third day. The second group received only vehicle (distilled water) with the same volume and in the same time as the first group. The third and fourth groups received amiodarone and were treated with CAPE , 5 and 10 µmol /day respectively, from 2 days before the first dose of amiodarone and until 21 days after the second dose of amiodarone. At the end of treatment course, lung tissue was removed for histopathology and biochemical evaluations. Malondialdehyde (MDA) concentration, myeloperoxidase MPO) and super oxide dismutase (SOD) activities were determined in lung tissue. Histopathological evaluation was performed using light microscopy. MDA level and the activity of myeloperoxidase and superoxide dismutase enzymes significantly decreased in the group which was treated with CAPE (5 µmol/Kg). However, 10 µmol/Kg CAPE had not such an effect. Both doses of CAPE could histopathologically reduce the fibrogenic effects of amiodarone . CAPE was shown to be effective in reducing amiodarone-induced pulmonary fibrosis with the dose of 5 µmol/Kg.

Effects of aspirin and celecoxib on rigidity in a rat model of Parkinson's disease.

Parkinson's disease (PD) is a degenerative neurodopaminergic disease in nigrostriatum pathway of human and is responsible for most of the movement disorders. Increasing evidence suggests that an inflammatory reaction accompanies the pathological processes caused by Cyclooxygenase (COX) seen in many neurodegenerative disorders, including PD and according to the recent researches chronic use of Non-Steroidal Anti-Inflammatory Drugs (NSAIDs) decreases the risk of PD in human. In the study the rat left Substantia Nigra Pars Compacta (SNc) have been destroyed using electrical lesion (1 mA; DC; 8 Sec) to induce PD model. Then aspirin (30, 60 mg kg(-1)) and celecoxib (4, 8 mg kg(-1)) have been administrated orally to parkinsonian rats. When the animals were suffered to PD Murprogo's Method evaluated the rigidity ofparkinsonian rats. Both selective COX-2 inhibitor (celecoxib) and non-selective COX-2 inhibitor (aspirin) decreased the rigidity of parkinsonian rats p<0.05 but rigidity recovery after administration the selective COX-2 inhibitor was more than non-selective COX-2 inhibitor. These findings are additional pharmacological information which has suggested the use of NSAIDs as alternative way to treat the rigidity of PD.