The antioxidant, anti-inflammatory, and antiplatelet effects of Ribes rubrum L. fruit extract in the diabetic rats.

The prothrombotic and inflammatory state plays a significant role in the occurrence of cardiovascular complications in type 2 diabetes mellitus. In this study, the antidiabetic, anti-inflammatory, and antiplatelet potentials of the extracts obtained from Ribes rubrum were investigated. The antidiabetic, anti-inflammatory, and antioxidant activities of the ethanol and water extracts of R. rubrum were evaluated by in vitro methods. The total phenolic and flavonoid contents were also determined. The experimental diabetes model in rats was induced with streptozotocin (STZ). After hyperglycemia occurred, the ethanol extracts of R. rubrum (RRE, at 100 mg/kg and 500 mg/kg doses) were administered to the treatment groups for 14 days. Blood glucose, lipid profile, plasma, and pancreas tumor necrosis factor-α (TNF-α) levels were determined and compared at the end of the experiments. P-selectin levels and mitochondrial membrane polarization (MMP) of platelets were also measured. In vitro study, the RRE showed potent anti-inflammatory activity. Administration of RRE (at 100 mg/kg doses) to diabetic rats lowered blood glucose level insignificantly. The results showed that there was an increment in levels of TNF-α in plasma and pancreas tissue of the diabetic group compared to the control group. R. rubrum extract regulated and normalized their levels in plasma and pancreatic tissue. RRE at both doses significantly decreased platelet P-selectin levels and prevented STZ-induced loss of MMP in platelets. The results of current research indicate that RRE extract has potent anti-platelet and anti-inflammatory effects and may be beneficial in preventing diabetic complications. PRACTICAL APPLICATIONS: Hyperglycemia causes dyslipidemia, advanced oxidative stress, platelet activation, and inflammation in diabetes mellitus. Plants with various medicinal properties are of worldwide interest for the treatment of diseases due to their biological activities. In this study, the antidiabetic, anti-inflammatory, and antioxidant effects of extracts of Ribes rubrum (%100 ethanol, 50% ethanol, water) were evaluated by in vitro and in vivo methods. The diabetes model was induced with streptozotocin (STZ). The rats were divided into control, diabetic control, R. rubrum-100 mg/kg, and R. rubrum-500 mg/kg doses groups. Blood glucose levels, tumor necrosis factor-α (TNF-α), platelet P-selectin levels, mitochondrial membrane polarization of platelets were examined. The present study has shown that R. rubrum has anti-inflammatory and antiplatelet activity. R. rubrum may be beneficial in the prevention and treatment of DM complications due to its anti-inflammatory and antithrombotic effects.

Evaluation of biochemical parameters in Rubus tereticaulis treated rats and its implications in wound healing.

We evaluated the effects of Rubus tereticaulis in healing process by determining the total carbonyl content, collagen synthesis, and total protein level on rat wounded tissues. Wounds were performed in the back of 54 Wistar rats, using a biopsy punch instrument with 0.6 mm in diameter. Rats were randomly divided into three groups: (i) un-treatment wounds group served as "controls", (ii) Madecassol® used as "positive control" group, and (iii) the application of topical cream of R. tereticaulis served as "treatment" group of wound healing. The animals were killed at the end of experiment under anesthesia with ketamine, and tissue samples were collected for the evaluation at three times intervals (3rd, 7th, and 14th day). The wounded areas were analyzed for total carbonyl content, collagen, and total protein levels by HPLC, ELISA, and spectrophotometric methods, respectively. Total carbonyl content in the treatment group was significantly lower in comparison with control group on 3rd day (2.839 ± 0.438 vs. 3.216 ± 0.216 nmol carbonyl/mol protein; p < 0.5) and 14th days (4.222 ± 0.128 vs. 4.784 ± 0.077 nmol carbonyl/mol protein; p < 0.05), respectively. New collagen formation on the wound sites after the initial injury was noted in the treated and positive control groups (5.310 ± 0.331 vs. 5.164 ± 0.377 mg collagen/g wet tissue) at the 3rd day than control group (2.180 ± 0.718 mg collagen/g wet tissue, p < 0.01), and in treated and positive control groups at 7th day (9.654 ± 0.201, 9.053 ± 1.062 mg collagen/g wet tissue, p < 0.01); and in treated and positive control groups at 14th day (8.469 ± 0.236, 5.631 ± 0.531 mg collagen/g wet tissue, respectively; p < 0.05) in comparison with the control group. Total protein level of samples did not change significantly between the groups. Thus, application of R. tereticaulis ameliorated the wound healing process in rats as it facilitated collagen formation through healing of the wound. Evaluating total carbonyl content by HPLC could be useful as an advance procedure for quantification of healing.

Effect of Horse-chestnut seed extract on matrix metalloproteinase-1 and -9 during diabetic wound healing.

The effects of aqueous-ethanol extract of Horse chestnut (HCE) on MMP-1 and MMP-9 expressions during cutaneous wound healing in diabetic rats were investigated in this study. The expressions of MMP-1 and MMP-9, wound closure, myeloperoxidase (MPO) activity, hydroxyproline, and malondialdehyde (MDA) levels in wound tissue were measured. Quercetin glucuronide in HCE was identified as main compound using a LC-MS/MS. The hydroxyproline level was significantly increased in the treated group versus control after the 3rd and 7th days (p < 0.05). The MDA level and MPO activity were significantly lower in the treatment group (p < 0.05). MMP-1 gene expression level in treated rats was increased in the 7th day while it was reduced in 14th day. MMP-9 gene expression level in treated rats was decreased in 7th, and 14th days compared to control (p < 0.05). These results show that HCE accelerated the cutaneous wound-healing process in diabetic rats via MMP-1 and MMP-9 regulation. PRACTICAL APPLICATIONS: The main function of MMPs is to degrade and deposite the various components of the extracellular matrix. Also, they participate physiological processes such as inflammation, angiogenesis, and tissue remodeling. Horse chestnut seeds (HC) are known to be rich in saponins and flavonoids. HC are used for the treatment of abdominal pain, stomach ache, cold, hemorrhoids, arterial stiffness, rheumatism, oedema, diarrhea, chronic venous insufficiency and also as an antihemorrhagic and antipyretic in traditional medicine. It has been shown that HC has anti-inflammatory, antioedema, vessel protective, and free radical scavenging properties. This study indicates that HCE could be an effective agent for wound healing in diabetic wound model via its ability to suppress the MMP-9 gene expression and regulates MMP-1 gene expression besides its antioxidative, anti-inflammatory effects.

Synthesis and characterization of celecoxib derivatives as possible anti-inflammatory, analgesic, antioxidant, anticancer and anti-HCV agents.

A series of novel N-(3-substituted aryl/alkyl-4-oxo-1,3-thiazolidin-2-ylidene)-4-[5-(4-methylphenyl)-3-(trifluoromethyl)-1H-pyrazol-1-yl]benzenesulfonamides 2a-e were synthesized by the addition of ethyl a-bromoacetate and anhydrous sodium acetate in dry ethanol to N-(substituted aryl/alkylcarbamothioyl)-4-[5-(4-methylphenyl)-3-(trifluoro-methyl)-1H-pyrazol-1-yl]benzene sulfonamides 1a-e, which were synthesized by the reaction of alkyl/aryl isothiocyanates with celecoxib. The structures of the isolated products were determined by spectral methods and their anti-inflammatory, analgesic, antioxidant, anticancer and anti-HCV NS5B RNA-dependent RNA polymerase (RdRp) activities evaluated. The compounds were also tested for gastric toxicity and selected compound 1a was screened for its anticancer activity against 60 human tumor cell lines. These investigations revealed that compound 1a exhibited anti-inflammatory and analgesic activities and further did not cause tissue damage in liver, kidney, colon and brain compared to untreated controls or celecoxib. Compounds 1c and 1d displayed modest inhibition of HCV NS5B RdRp activity. In conclusion, N-(ethylcarbamothioyl)-4-[5-(4-methylphenyl)-3-(trifluoromethyl)-1H-pyrazol-1-yl]benzenesulfonamide (1a) may have the potential to be developed into a therapeutic agent.