Preventive effect of Rumex crispus L. on surgically induced intra-abdominal adhesion model in rats.

BACKGROUND: Rumex crispus L. (Polygonaceae), known as "Labada" in Turkey, was reported to be used for the treatment of gynecological diseases such as postpartum complications and infertility in folk medicine. Earlier studies on R. crispus have shown that leaf, fruit and root extracts have anti-inflammatory and antioxidant activities and are used for the treatment of tumors in the uterus. The hypothesis of this study is that R. crispus may generate potential anti-adhesive activity against complex factors such as inflammation, oxidation and fibrosis. OBJECTIVES: We aimed to investigate the potential anti-adhesive activity of aqueous methanol extracts of leaves, fruits and roots of R. crispus. METHODS: Abdominal adhesion model was performed in 72 female Wistar Albino rats. In the first step of the experiment, the rats were divided into six groups namely, Sham, Control, Reference and Experimental Groups (consisting of three sub-groups in which R. crispus leaf, fruit and root extracts were applied at 100 mg/kg dose). The test samples were administered once to the peritoneal cavity and the rats were sacrificied at the end of the 14th day. Root extract showed prominent activity, therefore this extract was subjected to fractionation to obtain 3 fractions (30-60-100% methanol fractions) by using vacuum-liquid chromatography. In the second stage, animals were divided into 6 groups as Sham, Control, Reference and Experimental Groups (R30, R60, R100 at 100 mg/kg dose). Adhesion scoring, tissue total antioxidant and oxidant levels, histopathological and immunohistochemical (TNF-α, IL-6 and IL-8) analyzes were performed. RESULTS AND CONCLUSION: Adhesion scores, inflammatory cytokines and inflammation cells decreased by the application of R. crispus root extract. The fractions also showed similar anti-inflammatory effects, but R60 was found to be more effective in prevention of intra-abdominal adhesions and uterine fibrosis. R60 fraction, possessing potential bioactivity, was investigated in terms of phenolic composition by HPLC.

Healing effects of Cornus mas L. in experimentally induced ulcerative colitis in rats: From ethnobotany to pharmacology.

ETHNOPHARMACOLOGICAL RELEVANCE: The ethnobotanical studies conducted in Turkey and other countries have revealed that Cornus mas L., from the family Cornaceae have been used against stomachache, diarrhea and colitis. AIM OF THE STUDY: The objective the present study is to determine the possible activity of C. mas in experimentally induced ulcerative colitis in rats and to identify its phytochemical feature. MATERIALS AND METHODS: 2,4,6-Trinitrobenzene sulfonic acid-induced colitis model was induced in rats. The rats were orally treated with different doses (50, 100, 200 and 400 mg/kg) of C. mas 80% methanol extract for 14 days. Increase in body weight, consumed amount of feed, form of the stool, presence of rectal prolapse were followed every day. At the end of the experiment, colon tissues were removed and wet weights for each animal were measured and colon damages were scored. Total antioxidant and total oxidant status, cytokine (TNF-α and IL-1ß) and protein levels of colon tissues were evaluated and histopathological analyses were carried out. After the detection of the effective dose as 400 mg/kg, the aqueous methanol extract was fractionated by using liquid-liquid fractionation technique and the sub-extracts were also tested for in vivo biological activities. High Performance Liquid Chromatography analyses were conducted to determine the phytochemical profile of the active crude extract and n-butanol sub-extract. RESULTS: Amount of feed consumed per day and increase in body weight were the lowest in the control group, while those values were determined to be the highest in 80% methanol extract (at 400 mg/kg dose), n-butanol sub-extract and reference groups. Following colitis induction, it was determined that the fecal form was yellow-slippery in all groups and returned to normal after the treatment with C. mas extracts. Rectal prolapse score was less in the extract (400 mg/kg) and n-butanol sub-extract treated groups. Total antioxidant, total oxidant status, cytokine and protein levels were found to be in parallel with macroscopic findings. 80% methanol extract (400 mg/kg) and n-butanol sub-extract provided the best healing according to the wet weight measurements and colon damage scoring performed on the removed colon tissues. These findings supported the results of histopathological analysis. According to the chromatographic analysis, ellagic acid was determined in both extracts and its amount was quantified. CONCLUSIONS: The present study has verified the ethnomedical use of C. mas for the treatment of ulcerative colitis.

Evaluation of ameliorating effect of lycopene against testicular toxicity due to diethylnitrosamine using biochemical, spermatological and histopathological data.

The aim of this study was to evaluate the possible therapeutic or protective effects of lycopene on diethylnitrosamine (DEN)-induced testicular lipid peroxidation and on the associated changes in spermatological parameters and histopathological architecture of rat testis. DEN is a carcinogenic substance that can be derived from chemicals used in agriculture, such as insecticides and nitrate. The rats were assigned to control, lycopene, DEN(1), DEN(2), lycopene + DEN(1), lycopene + DEN(2), DEN(1) + lycopene and DEN(2) + lycopene groups. During the study, lycopene was administered by oral gavage at a dose of 10 mg kg-1  bw-1 every other day for 10 days and DEN was administered at a dose of 200 mg  kg-1  bw-1 as a single dose intraperitoneally. DEN was applied for 30 days in group DEN(1) and for 90 days in group DEN(2). Malondialdehyde (MDA) and reduced glutathione (GSH) levels, antioxidant enzymes activities, spermatological parameters, the weight of the reproductive organs (v. seminalis, prostate, testis and epididymis) and the histopathological structure were determined. MDA levels significantly increased, while GSH and antioxidant enzymes' activities decreased in DEN groups (p < 0.001). There was an increase in the rate of abnormal spermatozoa and a decrease in sperm density and motility, and reproductive organ weight (the weight of the right and left testis) in both DEN groups. Lycopene has normalised biochemical and spermatological parameters and reproductive organ weight. The histopathological examination of testicular tissue showed that the most significant histopathological change in DEN groups was the seminiferous tubule dilatation. These results suggest that besides the protective effects, the therapeutic effect of lycopene is possibly due to its antioxidant effects on DEN-induced testicular toxicity.

Activity evaluation on Ribes species, traditionally used to speed up healing of wounds: With special focus on Ribes nigrum.

ETHNOPHARMACOLOGICAL RELEVANCE: Ribes species are usually evergreen shrubs, represented by eight species in Turkey. Although they are known for their fruits with commercial importance, their leaves have been used as folk remedy in various areas in Turkey by rural population owing to their wound healing potential. AIM OF THE STUDY: In the present study we aimed to assess the wound healing activity of the leaves of Ribes species growing in Turkey, namely, Ribes alpinum L., R. anatolica Behçet, R. petraeum Wulfen, R. multiflorum Kit. ex Romer & Schultes, R. nigrum L., R. orientale Desf., R. rubrum L., R. uva-crispa L. MATERIALS AND METHODS: Wounds were surgically induced on the dorsal parts of the rats and mice. Prepared herbal ointments were topically applied onto the wounds once daily. The effects of the extracts were evaluated by measuring the breaking strength and percentage of reduction in wounded area by comparing the results with the registered reference ointment, FITO Krem®. Histopathological and antioxidant assays were also conducted. Since, R. nigrum was determined to be the most active species, we further investigated the wound healing potential of the subextracts of the methanol extract of R. nigrum leaves. RESULTS: R. nigrum and R. multiflorum extracts significantly increased wound breaking strength. Significant reduction in the areas was determined for the wounded tissues treated with the ointments of R. nigrum and R. multiflorum extracts. Oxidative Stress Index was found to be lowest for R. orientale, R. nigrum and R. multiflorum. Among the subextracts of R. nigrum, ethyl acetate subextract was found to have promising effect. CONCLUSIONS: Methanol extracts of leaves of R. nigrum and R. multiflorum demonstrated significant wound healing effect. We can suggest that ethyl acetate subextract of R. nigrum may be a potential candidate to be used for the development of a wound healing agent.

Lycopene and ellagic acid prevent testicular apoptosis induced by cisplatin.

The aim of this study was to investigate the possible protective effects of lycopene (LC) and ellagic acid (EA) on cisplatin (CP)-induced testicular apoptosis in male rats. The control group was treated with placebo; LC, EA and CP groups were given alone LC, EA and CP, respectively; the CP+LC group was treated with a combination of CP and LC; and the CP+EA group was treated with a combination of CP and EA. Although CP significantly increased the number of Bax-positive (apoptotic) cells it had no effect on the number of Bcl-2-positive (antiapoptotic) cells compared with the control group. Administration of CP caused significant increase in lipid peroxidation and nonsignificant decrease in superoxide dismutase (SOD) activity along with some histopathological lesions in testicular tissue. However, combined treatments of LC or EA in addition to CP tended to prevent the CP-induced testicular apoptosis, histopathological lesions and lipid peroxidation.

Improvement of cisplatin-induced injuries to sperm quality, the oxidant-antioxidant system, and the histologic structure of the rat testis by ellagic acid.

OBJECTIVE: To investigate whether ellagic acid (EA) has a possible protective effect against cisplatin (CP)-induced negative changes in epididymal sperm characteristics and the histologic structure of testis and prostate associated with oxidative stress in rats. DESIGN: Experimental study. SETTING: Firat University Medical School Experimental Research Center, Elazig, Turkey. PATIENT(S): Eight-week-old adult male Sprague Dawley rats (n = 24). INTERVENTION(S): Cisplatin was administered to rats at a single dose of 7 mg/kg IP. Ellagic acid was administered both separately and simultaneously with CP by gavage daily for 10 days at the dose of 10 mg/kg. MAIN OUTCOME MEASURE(S): Reproductive organ weights, epididymal sperm characteristics, and histopathologic structure of testes and ventral prostate were determined along with malondialdehyde (MDA) and glutathione (GSH) levels and glutathione-peroxidase (GSH-Px) and catalase (CAT) activities of plasma, sperm, and testicular tissue. RESULT(S): Ellagic acid ameliorated the CP-induced reductions in weights of testes, epididymides, seminal vesicles, and prostate along with epididymal sperm concentration and motility. Additionally, EA decreased the CP-induced increments in abnormalities of sperm. Whereas CP increased the MDA levels of plasma, sperm, and testicular tissue, it decreased the GSH-Px and CAT activities in the study samples compared with the control group. The administration of EA to CP-treated rats decreased the MDA level and increased GSH-Px and CAT activities in these samples. Cisplatin caused degeneration, necrosis, interstitial edema, and reduction in germinative cell layer thickness and rarely reduction in spermatogenic activity in some seminiferous tubules. The CP-induced changes in histopathologic findings of testis were partially reversed by treatment with EA. No significant changes were observed in the histopathologic structure of the prostate among any of groups. CONCLUSION(S): Ellagic acid has a protective effect against testicular toxicity caused by CP. This protective effect of EA seems to be closely involved with the suppressing of oxidative stress.

Ellagic acid prevents cisplatin-induced oxidative stress in liver and heart tissue of rats.

Cisplatin is one of the most active cytotoxic agents in the treatment of cancer. High doses of cisplatin have also been known to produce hepatotoxicity, and several studies suggest that supplemental antioxidants can reduce cisplatin-induced hepatotoxicity. The present study was designed to determine the effects on the liver and heart oxidant/antioxidant system and the possible protective effects of ellagic acid on liver and heart toxicity induced by cisplatin. The control group received 0.9% saline; animals in the ellagic acid group received only ellagic acid (10 mg/kg); animals in the cisplatin group received only cisplatin (7 mg/kg); animals in cisplatin + ellagic acid group received ellagic acid for 10 days after cisplatin. The rats were killed at the end of the treatment period. Malondialdehyde (MDA) and glutathione (GSH) levels, glutathione-peroxidase (GSH-Px) and catalase (CAT) activities were determined in liver and heart tissue. While administration of cisplatin increased the MDA levels in liver and heart tissues, it decreased the GSH, GSH-Px and CAT in these samples when compared to the control group. The administration of ellagic acid to cisplatin-treated rats decreased the MDA levels, and increased GSH, GSH-Px and CAT in these samples. Cisplatin caused marked damages in the histopathological status of liver and heart tissues. These damages were ameliorated by ellagic acid administration. In conclusion, ellagic acid may be used in combination with cisplatin in chemotherapy to improve cisplatin-induced oxidative stress parameters.