Evaluation of the protective effects of curcumin-rich turmeric (Curcuma longa) extract against isotretinoin-induced liver damage in rats.

AIM: The aim of this study was to evaluate the protective effect of curcumin-rich turmeric (CRT) extract against isotretinoin (ISO)-induced liver damage through routine biochemical parameters and oxidative stress parameters that indicate liver damage. MATERIAL AND METHOD: 42 albino Wistar rats of 200 g were randomly grouped as Group I: Healthy control, Group II: Sunflower oil, Group III: Curcumin 200 mg/kg, Group IV: ISO control groups (7.5 mg/kg), Group V: Curcumin 50 mg/kg + ISO 7.5 mg/kg, Group VI: Curcumin 100 mg/kg + ISO 7.5 mg/kg, Group VII: Curcumin 200 mg/kg + ISO 7.5 mg/kg. At the end, after the rats were killed, their blood and liver tissues were collected. ALT and AST levels in serum; superoxide dismutase activity (SOD), GSH, and MDA levels in liver tissue were determined. RESULTS: Our results showed that ALT, AST, and MDA levels increased, and SOD and GSH levels decreased in the ISO-administered group compared to the healthy control group. CRT 50, 100, and 200 mg/kg groups were compared to ISO group. A dose-dependent increase in protective effect was observed. A decrease in ALT, AST, and MDA levels, and an increase in SOD and GSH levels were determined. A protective effect was found at all doses. The best protective effect was in the CRT 200 mg/kg group. CONCLUSION: CRT extract can be considered a candidate herbal medicine for the elimination of liver damage in individuals using ISO. However, further experimental and clinical validation should be studied.

Effects of Polygonum cognatum Meissn. extract on indomethacin induced gastric damage in rats.

We investigated the anti-ulcer activity of ethanol extracts of Polygonum cognatum on indomethacin induced gastric damage in rats. We evaluated the number of ulcer areas, oxidant and antioxidant parameters as well as histopathologic features in rat stomach. We measured the total antioxidant status of P. cognatum in concentrations from 1.56-100 mg/ml. P. cognatum extract inhibited indomethacin induced ulcer formation with an effect similar to a 20 mg/kg dose of the standard anti-ulcer drug, esomeprazole. All doses of P. cognatum extract exhibited positive effects on oxidative stress markers and histopathological features in the stomach tissue of rats. We suggest that the antioxidant activity of P. cognatum extract may be responsible for its gastroprotective effect and that P. cognatum extract may be a useful gastroprotective agent.

Isolation of Major Compounds and Gastroprotective Activity of Alchemilla Caucasica on Indomethacin Induced Gastric Ulcers in Rats.

OBJECTIVE: The Alchemilla genus, which belongs to the Rosaceae family, is known as Lady's mantle and is commonly used in traditional medicine. This study was designed to investigate the major metabolites isolation and gastroprotective effects of Alchemilla caucasica. MATERIALS AND METHODS: Phytochemical studies were carried out using column chromatography on Alchemilla caucasica. The gastroprotective effect of ethanol extract of this plant was tested on indomethacin-induced gastric ulcer model in rats. In addition, superoxide dismutase (SOD), malondialdehyde (MDA), and glutathione (GSH) parameters in the stomach tissue were examined. RESULTS: Quercetin-3-O-glucuronide, apigenin, and catechin were isolated from aerial parts of Alchemilla caucasica. When macroscopic ulcer index and histopathological results were analyzed, the extract at 200 mg/kg dose was found to be most effective. All doses of extract reduced MDA level and enhanced SOD activity and GSH level. CONCLUSION: The results of this study showed that Alchemilla caucasica has significant antiulcer activity. This effect was thought to be caused by antioxidant properties of flavonoids.

Gastroprotective and antioxidant effects of Eremurus spectabilis Bieb. methanol extract and its isolated component isoorientin on indomethacin induced gastric ulcers in rats1.

PURPOSE: To investigate the gastroprotective effect of methanol extract of E. spectabilis and its major component isoorientin. METHODS: Effects of isoorientin and methanol extract of E. spectabilis were investigated in indomethacin-induced gastric damage model on rats. Famotidine was used as the standard antiulcer drug. Numerical density of ulcer areas and oxidative status were determined on stomach tissues of rats. RESULTS: All doses of isoorientin and methanol extract decreased MDA level and increased SOD activity and GSH levels in the stomach tissue of rats. When numerical density of ulcer areas were analized, the 500 mg/kg dose of methanol extract (84%) exhibited a similar effect to 20 mg/kg dose of standart drug famotidine (87%). CONCLUSIONS: The gastroprotective effects of E. spectabilis and its major constituent isoorientin in rats for the first time. Detailed analyses suggested that potential antioxidant activity of both plant extract and isoorientin mediates the gastroprotective effect.

Paracetamol-induced nephrotoxicity and oxidative stress in rats: the protective role of Nigella sativa.

Context Nigella sativa L. (Ranunculaceae) (NS) is traditionally used to treat many conditions such as inflammation. Objective This study evaluates the effects of NS seeds ethanol extract in paracetamol-induced acute nephrotoxicity in rats. Materials and methods Forty-eight female Wistar Albino rats were divided into eight groups: I = sham; II = sham + 1000 mg/kg NS; III = sham + 140 mg/kg (N-acetyl cysteine) NAC; IV = 2 g/kg paracetamol; V = 2 g/kg paracetamol + 140 mg/kg NAC; VI, VII and VIII = 2 g/kg paracetamol + 250, 500 and 1000 mg/kg NS, respectively. Paracetamol administration (oral) was carried out 1 h after NS and NAC administrations (oral), and all animals were sacrificed 24 h later. Results Paracetamol administration significantly increased serum urea (88.05 U/L) and creatinine (0.80 U/L) when compared with the sham group (49.80 and 0.31 U/L, respectively). However, serum urea level was reduced to 65.60, 56.00 and 54.18 U/L, with 250, 500 and 1000 mg/kg doses of the extract, respectively. Also, serum creatinine level was reduced to 0.64, 0.57 and 0.52 U/L with 250, 500 and 1000 mg/kg doses of the extract, respectively. NS administration increased superoxide dismutase and glutathione, and decreased malondialdehyde levels in the kidneys. Kidney histopathological examinations showed that NS administration antagonized paracetamol-induced kidney pathological damage. Discussion and conclusions The results suggest NS has a significant nephroprotective activity on paracetamol-induced nephrotoxicity. It may be suggested that the antiinflammatory and antioxidant effects of NS ethanolic extract originated from different compounds of its black seeds.

Insecticidal metabolites from the rhizomes of Veratrum album against adults of Colorado potato beetle, Leptinotarsa decemlineata.

The dried rhizomes of Veratrum album were individually extracted with CHCl3 , acetone, and NH4 OH/benzene to test the toxic effects against the Colorado potato beetle, Leptinotarsa decemlineata, which is an important agricultural pest. Fifteen compounds in various amounts were isolated from the extracts using column and thin-layer chromatography. The chemical structures of 14 compounds were characterized as octacosan-1-ol (1), ß-sitosterol (2), stearic acid (3), diosgenin (4), resveratrol (5), wittifuran X (6), oxyresveratrol (7), ß-sitosterol 3-O-ß-D-glucopyranoside (8), diosgenin 3-O-α-L-rhamnopyranosyl-(1 → 2)-ß-D-glucopyronoside (9), oxyresveratrol 3-O-ß-D-glucopyranoside (10), jervine (11), pseudojervine (13), 5,6-dihydro-1-hydroxyjervine (14), and saccharose (15) using UV, IR, MS, (1) H- and (13)C-NMR, and 2D-NMR spectroscopic methods. However, the chemical structure of 12, an oligosaccharide, has not fully been elucidated. Compounds 4, 6, 9, and 10 were isolated from V. album rhizomes for the first time in the current study. The toxic effects of three extracts (acetone, CHCl3 , and NH4 OH/benzene) and six metabolites, 2, 2+4, 5, 7, 8, and 11, were evaluated against the Colorado potato beetle. The assay revealed that all three extracts, and compounds 7, 8, and 11 exhibited potent toxic effects against this pest. This is the first report on the evaluation of the toxic effects of the extracts and secondary metabolites of V. album rhizomes against L. decemlineata. Based on these results, it can be concluded that the extracts can be used as natural insecticides.

Treatment with α-lipoic acid enhances the bone healing after femoral fracture model of rats.

This study investigated the fracture-healing effects of α-lipoic acid (α-LA), which was applied orally once daily in preventive treatment mode during 1 month after fracture induction. Rats were randomly divided into sham-operated group (group 1), femoral fracture control (group 2), femoral fracture + 25 mg/kg α-LA (group 3), and femoral fracture + 50 mg/kg α-LA (group 4). Rats in the experimental groups were orally administered 25 or 50 mg/kg α-LA once daily for 30 days starting from postoperative day 1. Thirty days postoperatively, the rats underwent X-ray imaging and were then euthanized for blood and tissue collection. Histopathological, biochemical, molecular, computed tomography (CT), and mechanical strength tests were performed on samples. The serum levels of osteocalcin (OC), osteopontin (OP), tumor necrosis factor alpha (TNF-α), and interleukin-6 (IL-6) did not differ significantly between groups 2 and 3. Serum OC, OP, TNF-α, and IL-6 levels in group 4 were significantly lower than those in group 3. From X-ray images, staging for fracture healing was scored as <2 in group 2, >2 in group 3, and >3 in group 4. In group 2, the average score of less than 2 suggests insufficient fracture healing; those of both the α-LA groups were >2, indicating progression of healing. Transforming growth factor beta (TGF-ß) messenger RNA (mRNA) levels were significantly higher in the sham group than in the femoral fracture control. Both doses of α-LA increased TGF-ß mRNA expression compared to the fracture group. CT results and biomechanical testing at 4 week after fracture demonstrated that α-LA has fastened bone healing, which was confirmed by stereological analyses in which 50 mg/kg α-LA increased the number of osteoclasts. Our findings indicate that α-LA supplementation promotes healing of femoral fractures in rats.

Nigella sativa reduces tissue damage in rat ovaries subjected to torsion and detorsion: oxidative stress, proinflammatory response and histopathological evaluation.

BACKGROUND: To evaluate biochemically and histopathologically the effects of Nigella sativa (NS) in experimental ischemia and ischemia/reperfusion (I/R) injury in rat ovaries. METHODS: Thirty-six female rats were divided into 6 groups: group I = sham operation; group II = 500 mg/kg NS + sham operation; group III = bilateral ovarian ischemia; group IV = 500 mg/kg NS + ischemia; group V = 3-hour period of ischemia + 3-hour reperfusion, and group VI: 3-hour period of ischemia + 500 mg/kg NS 2.5 h after the induction of ischemia + 3-hour reperfusion. At the end of ischemia, the bilateral vascular clips were removed, and 3-hour reperfusion was continued. IL-1ß, IL-6, and TNF-α cytokine levels in serum, and superoxide dismutase (SOD), myeloperoxidase (MPO), glutathione (GSH), and malondialdehyde (MDA) levels were determined. RESULTS: I/R increased the MDA level and MPO activity while significantly decreasing the SOD activity and GSH level when compared to the sham. The 500-mg/kg dose of NS before I/R reversed the trend in MDA levels, MPO activity, SOD activity, and GSH levels. Ischemia and I/R increased the serum levels of IL-1ß, IL-6, and TNF-α, while the administration of NS decreased the serum levels of these cytokines. CONCLUSIONS: The administration of NS is effective in reversing tissue damage induced by ischemia and/or I/R in ovaries.

Diffractaic acid, a novel proapoptotic agent, induces with olive oil both apoptosis and antioxidative systems in Ti-implanted rabbits.

Usnea longissima Ach., a lichen species, is a traditional herbal medicine with anti-detrimental effects. We evaluated the in vivo effects of a major constituent of U. longissima, diffractaic acid, and the main fatty component of the Mediterranean diet, olive oil, against apoptosis, including various caspase activations and oxidative injury in surrounding tissues after titanium implantation in rabbit femurs. Furthermore, we evaluated the underlying molecular mechanisms. In this study, this lichen metabolite and olive oil activated caspase-dependent cell death with apoptotic morphology, which is distinctly different from necrosis. Both orally and locally administered olive oil and diffractaic acid exerted pro-apoptotic induction in tissues surrounding the implants in titanium-implanted rabbits through the activation of initiator caspases (Cas-2, -8 and -9) and executioner caspase (Cas-3). In addition, they displayed strong myeloperoxidase and inducible nitric oxide synthase activities, providing an alleviating effect. Furthermore, administrations of diffractaic acid and olive oil attenuated the Ti-alloy implantation, and decreased superoxide dismutase activity and total glutathione level in peri-implant tissues. These results demonstrate that diffractaic acid and olive oil are involved in the induction of apoptotic cell death both through caspase-dependent cell death and as an antioxidant. Thus, the data suggest that both diffractaic acid and olive oil could be developed as effective proapoptotic agents in various disorders treatments.

Helichrysum plicatum DC. subsp. plicatum extract as a preventive agent in experimentally induced urolithiasis model.

ETHNOPHARMACOLOGICAL RELEVANCE: Since ancient times, various herbal preparations have been used in treatment of urolithiasis, which is basically formation of calcium oxalate stones in kidney. The aim of our study is to assess the effects of Helichrysum plicatum DC. subsp. plicatum (HP) as a preventive agent in experimentally induced urolithiasis model in rats. MATERIALS AND METHODS: The efficacy of 125, 250, and 500 mg/kg HP extract was studied in 1% ethylene glycol and 1% ammonium chloride-induced urolithiasis for 21 days in rats. The weight difference and the levels of calcium, magnesium, phosphorus, urea nitrogen, creatinine and uric acid in both serum and 24h-urine were measured. The calcium oxalate (CaOx) and pH were defined in urine. Histo-pathological analyses in kidneys were also performed. RESULTS: The rats' weights were higher in HP groups than urolithiasis group. Urolithiasis caused a significant increase in both serum and urine biochemical parameters compared to healthy rats. HP extract decreased levels of these parameters. Urine CaOx level was high in urolithiasis rats, whereas it was decreased by HP extract. Histopathological examinations revealed extensive intratubular crystal depositions and degenerative tubular structures in urolithiasis group, but not in HP treatment groups. CONCLUSION: More studies will be necessary to elucidate the antiurolithiatic activity of HP. Nonetheless, having a beneficial effect in preventing and eliminating CaOx deposition into kidneys, HP extract may be a potential drug for urolithiasis treatment.

The effects of methanol extract of Lobaria pulmonaria, a lichen species, on indometacin-induced gastric mucosal damage, oxidative stress and neutrophil infiltration.

Lobaria pulmonaria, a lichen species, has been used in traditional medicine for the treatment of various diseases. This study was designed to determine the gastroprotective effect of the methanol extract of L. pulmonaria in an indometacin-induced ulcer model in rats. The results showed that gastric lesions were significantly reduced in a dose-dependent manner. Furthermore, the administration of indometacin caused a significant decrease in the levels of superoxide, glutathione peroxidase and reduced glutathione and an increase in the lipid peroxidation level. Administration of the lichen extract, however, produced an increase in the levels of these enzymes and a decrease in lipid peroxidation levels, although catalase and myeloperoxidase levels were unaffected. The present results suggested that Lobaria pulmonaria has a gastroprotective effect, probably due to reducing oxidative stress and neutrophil infiltration.

Gastroprotective and antioxidant effects of usnic acid on indomethacin-induced gastric ulcer in rats.

Usnea longissima, a medicinal lichen of Anatolia (Turkey), is used in the treatment of gastric ulcer in local folk medicine. In this paper, the gastroprotective effect of usnic acid (UA) isolated from Usnea longissima was investigated in the indomethacin-induced gastric ulcers in rats at doses of 25, 50, 100 and 200 mg/kg body weight. The gastric lesions were significantly reduced by all doses of UA as compared with the indomethacin (25 mg/kg body weight) treated group. In the stomach tissues of treated animals, the in vivo antioxidant levels were evaluated. The administration of indomethacin caused a significant decrease in the levels of superoxide dismutase (SOD), glutathione peroxidase (GPx) and reduced glutathione (GSH), and an increase in the lipid peroxidation (LPO) level (p < 0.05). The administration of all doses of UA reversed the trend, inducing a significant increase of SOD, GSH and GPx levels and a reduction in LPO level in tissues. However, catalase (CAT), glutathione reductase (GR) and myeloperoxidase (MPx) activities, increased by indomethacin, were found to be lower in the UA- and ranitidine-treated groups. The gastric mucosal constitutive NO synthase (cNOS) and inducible NO synthase (iNOS) activities were also investigated in tissues of UA- (100 mg/kg), ranitidine- (50 mg/kg) and indomethacin-treated rat groups. The administration of UA and ranitidine increased the cNOS activity and lowered the iNOS activity as compared with indomethacin-treated group. These results suggest that the gastroprotective effect of UA can be attributed to its reducing effect on the oxidative damage and neutrophil infiltration in tissues.

Comparison of antioxidant activity and phenolic content of three lichen species.

The antioxidant activities (AA), reducing powers (RP) and total phenolic contents (TPC) of methanol and water extracts of three lichen species, Usnea longissima Ach., Usnea florida (L.) Weber ex Wigg. and Lobaria pulmonaria (L.) Hoffm. were determined in vitro. Of the extracts tested, the methanol extracts of Lobaria pulmonaria and Usnea longissima showed potent antioxidant activities. The methanol extract of L. pulmonaria also had the highest total phenolic contents (87.9 mg/g lyophylisate). For the methanol extract of this species, there was also a strong correlation between antioxidant activity and total phenolic contents. However, a similar correlation was not observed for U. longissima. Although the methanol extract of U. longissima had a lower phenolic content (38.6 mg/g lyophylisate), it exhibited potent antioxidant activity. On the other hand, there was a strong correlation between the reducing powers and the total phenolic contents of the extracts. The highest reducing power was determined for the methanol extract of L. pulmonaria.