Effect of eurycomanone on cytochrome P450 isoforms CYP1A2, CYP2A6, CYP2C8, CYP2C9, CYP2C19, CYP2E1 and CYP3A4 in vitro

Eurycomanone, an active constituent isolated from Eurycoma longifolia Jack, was examined for modulatory effects on cytochrome P450 (CYP) isoforms CYP1A2, CYP2A6, CYP2C8, CYP2C9, CYP2C19, CYP2E1 and CYP3A4 using in vitro assays. The IC₅₀ value was determined to assess the potencies of modulation for each CYP isoform. Our results indicated that eurycomanone did not potently inhibit any of the CYP isoforms investigated, with IC₅₀ values greater than 250 μg/ml. Hence there appears to be little likelihood of drug–herb interaction between eurycomanone or herbal products with high content of this compound and CYP drug substrates via CYP inhibition.     

东革阿里对小鼠肾阳虚的影响

目的 采用肾虚实验模型评价东革阿里Eurycoma longifolia增强机体活力的有效性。方法 采用im氢化可的松致肾虚模型,观察东革阿里对小鼠低温游泳时间的影响;采用摘除睾丸的肾虚模型,观察东革阿里对雄性小鼠附性器官质量的影响。结果 小鼠连续ig东革阿里8 d,与模型组比较,2.4 g生药/kg明显延长肾虚小鼠低温下的存活时间;小鼠连续ig东革阿里14 d,与模型组比较,0.8、2.4 g生药/kg能明显增加精液囊和前列腺指数。结论 东革阿里可增强机体活力,具有明显的滋补作用。     

Acute oral toxicity of Polyalthia longifolia var. pendula leaf extract in Wistar albino rats

Context: Polyalthia longifolia (Sonn.) Thw. var. pendula (Annonaceae), a tall evergreen tree, is cultivated all over India. The plant is used in traditional systems of medicine for the treatment of fever, skin diseases, and hypertension.

Objective: The present study evaluated the acute oral toxicity of Polyalthia longifolia var. pendula leaf extract in Wistar albino rats.

Material and methods: The parameters evaluated daily after oral drug administration of the extract (540, 1080, 2160 and 3240 mg/kg body weight) were mortality, signs of toxicity, feed and water consumption and body weight changes up to 14 days. The effect of different doses of the extract on organ weight, biochemical and hematological parameters were evaluated on the 15th day.

Results and conclusion: Methanol extract of Polyalthia longifolia leaf up to the dose level 3240 mg/kg body weight did not produce any toxic effects or deaths; the extract was well tolerated by the rats. It did not alter body weight, feed and water consumption. The organ weight, biochemical and hematological analysis did not show any dose- dependant changes in any of the parameters examined in animals of both sexes. The acute oral administration of the methanol extract of Polyalthia longifolia leaf was not toxic and safe in a single dose.     

In vitro cultures of Bacopa monnieri and an analysis of selected groups of biologically active metabolites in their biomass

Context: Bacopa monnieri L. Pennell (Scrophulariaceae) is one of the most important plants in the system of Indian medicine (Ayurveda).

Objective: This paper studies the optimal growth of B. monnieri for effective accumulation of metabolites. Biomass growth of this plant could be accomplished in liquid cultures on Murashige & Skoog medium.

Materials and methods: Powdered shoots of in vitro cultures of B. monnieri were extracted by methanol for indole compounds, phenolic compounds and bacosides for RP-HPLC analysis. Fatty acid analysis was performed via gas chromatography. Anti-inflammatory effect of B. monnieri extracts was evaluated in the A549 cells. COX-2 and cPGES expression was analyzed using Western blots.

Results: l-Tryptophan and serotonin were found in biomass from in vitro cultures of B. monnieri on MS medium and in biomass from the MS mediums enriched with the different additions such as of 0.1?g/L magnesium sulphate, 0.1?g/L zinc hydroaspartate, 0.1?g/L l-tryptophan, 0.25?g/L serine, 0.5?g/L serine and 0.5?mg/L anthranilic acid. The content of l-tryptophan and serotonin compounds was significant in biomass from medium with the addition of 0.1?g/L zinc hydroaspartate (0.72?mg/g dry weight and 1.19, respectively). Phenolic compounds identified in biomass from the same variants of MS medium were chlorogenic acid (ranging from 0.20 to 0.70?mg/g dry weight), neochlorogenic acid (ranging from 0.11 to 0.40?mg/g dry weight) and caffeic acid (ranging from 0.01 to 0.04?mg/g dry weight). The main group of fatty acids in biomass was saturated fatty acids (53.4%). The predominant fatty acid was palmitic acid. A significant decrease of COX-2 and cPGES expression was observed in the A549 cells activated with LPS and treated with B. monnieri extracts.

Discussion and conclusions: As far as we know, this is the first analysis of indole compounds and phenolic acids in this plant. The multi-therapeutic effect of B. monnieri is expressed by the activity of bacosides. Information about the presence of indole and phenolic compounds, and fatty acids in this plant is limited, but the content of these compounds might participate in the physiological activity of B. monnieri.     

Antidiabetic,antioxidant, and TNF-α lowering properties of extract of the traditionally used plant Ixeris gracilis in alloxan-induced diabetic mice

Abstract

Context: Ixeris gracilis DC. Stebbins (Asteraceae) is a plant considered to be medicinal by local communities of Meghalaya, India.

Objective: To evaluate the antidiabetic potential, antioxidant activity, and effect of the 80% methanolic extract of the leaves of Ixeris gracilis on tumor necrosis factor-α (TNF-α) expression.

Materials and methods: Varying doses (250–1000?mg/kg body weight) were administered intraperitoneally to normoglycemic mice and their hypoglycemic properties noted for 24?h; the optimum dose observed was used to evaluate its antihyperglycemic activity and effect on glucose tolerance. In vitro antioxidant activity was analyzed by assessing the DPPH radicals scavenging ability of the extract and the total polyphenols, flavonoid, carbohydrate, and protein contents were determined. Diabetic mice were then subjected to daily intraperitoneal injections of the extract for 12 days after which the antioxidant enzyme activities in the tissues were assayed and serum TNF-α was evaluated by ELISA.

Results: The extract displayed varying hypoglycemic activity. The dose of 250?mg/kg body weight exhibited potent antihyperglycemic activity and improved glucose tolerance. The extract was able to scavenge free radicals (IC₅₀ 57.544?µg/ml) and contained polyphenol (76.269?±?0.204?mg GAE/g dry wt), flavonoid (70.070?±?0.626?mg rutin equivalent/g dry wt), protein (4.368?±?8.916?mg/g dry wt), and carbohydrate (558.189?±?0.002?mg/g dry wt). TNF-α level and overall activity of glutathione peroxidase and superoxide dismutase in the liver, kidney, and brain of extract-treated diabetic mice were improved.

Conclusion: The study supports the inclusion of Ixeris gracilis in the list of plants with antidiabetic potential.     

Novel trypanocide from an extract of Pleurotus sajor-caju against Trypanosoma congolense

Context: Control of African trypanosomiasis relies on chemotherapy, but the development of resistance and the problem of drug residues require research for alternatives. Triterpenes and phenolics, the major constituents of Pleurotus sajor-caju (Fr.) Singer (Pleurotaceae), are reported to be effective against trypanosomiasis.

Objective: Trypanocidal effect of whole Pleurotus sajor-caju aqueous extract was investigated in vivo against Trypanosoma congolense.

Materials and methods: Mice (25–32?g) were divided into seven groups of six animals. Mice in groups A–F received 2.5?×?10⁴ trypanosomes, while group G was uninfected. Extracts (100–250?mg/kg) were administered intraperitoneally for 5 days to groups A–D while diminazine aceturate (group E) and normal saline (group F) served as positive and negative controls, respectively. Parasitemia, survival time, body weight and haematological parameters were monitored for 60 days post-treatment.

Results: Parasitemia decreased significantly (p?50 was 221.5?mg/kg. The packed cell volume (PCV) and the weight of mice treated with 250?mg/kg extract were 46.20?±?2.6% and 32.05?±?3.63?g, respectively, which is higher than the group treated with diminazine aceturate. The mean survival time of animals in groups D and E was >60 days, while that of group F was <4 days. Differential leucocyte count on day 68 post-infection in groups C, D and E were not significantly different.

Conclusion: Pleurotus sajor-caju therefore could be a potential source of new trypanocidal drugs.     

Male contraceptive efficacy of poly herbal formulation,contracept-TM,composed of aqueous extracts of Terminalia chebula fruit and Musa balbisiana seed in rat

Context: Terminalia chebula Retz (Combretaceae) and Musa balbisiana Colla (Musaceae) have a traditional reputation as a male contraceptive.

Objective: To determine the hypo-testicular activity of aqueous extracts of Terminalia chebula (fruit) and Musa balbisiana (seed) separately, and in composite manner at the ratio of 1:1 named as ‘Contracept-TM’ compared to cyproterone acetate (CPA), for developing a polyherbal contraceptive.

Materials and methods: The separate extract of above said plants or ‘Contracept-TM’ at the dose of 40?mg/100?g body weight of rat/day or CPA at 2?mg/100?g body weight of rat/day was administered for 28 days. Spermiological, androgenic and oxidative stress sensors, LD₅₀ and ED₅₀/100?g body weight values were measured.

Results: Treatment of individual, ‘Contracept-TM’ or CPA resulted significant decrease in the count of spermatogonia A (36.36–49.09%), pre-leptotene spermatocyte (19.11–55.30%), mid-pachytene spermatocyte (28.65–47.28%) and step 7 spermatid (29.65–51.59%). Activities of testicular Δ⁵, 3β (21.25–48.02%),17β-hydroxysteroid dehydrogenases (29.75–55.08%), catalase (19.06–43.29%) and peroxidase (30.76–62.82%), levels of testosterone (28.15–63.44%), testicular cholesterol (19.61–49.33%), conjugated diene (29.69–84.99%) and thiobarbituric acid reactive substances (41.25–86.73%) were elevated compare to the control. The ED₅₀ and LD₅₀ values were 40?mg and 5.8?g (T. chebula), 48?mg and 6.3?g (M. bulbisiana), 40?mg and 6.0?g (‘Contracept-TM’), respectively.

Discussion and conclusion: The said spermiological and androgenic sensors’ levels were decreased significantly by ‘Contracept-TM’ than its constitutional individual plant extract and it may be comparable to standard anti-testicular drug like CPA. So, it may be concluded that above polyherbal formulation is potent for inducing hypo-testicular activity.     

Effect of Spirulina platensis ingestion on the abnormal biochemical and oxidative stress parameters in the pancreas and liver of alloxan-induced diabetic rats

Context: Previous studies have shown that Spirulina platensis Gomont (Phormidiaceae) (SP) extract has beneficial effects on many disease conditions. The putative protective effects of SP were investigated in diabetic rats.

Objective: The current study investigates the antioxidant effects of SP in diabetic Wistar rats.

Materials and methods: Alloxan monohydrate (150?mg/kg body weight) was intraperitoneally administrated to induce diabetes. An aqueous suspension of SP powder in distillate water (10% w/v) was administrated orally by gavage (1?mL/day) for 50?days. Histopathological, biochemical and antioxidant analyses were performed. Glycemia, liver function and HOMA-IR were assessed using Spinreact and ELISA kits.

Results: SP exhibited high-antioxidant activity. The IC₅₀ values of the SP aqueous extract were 70.40 and 45.69?mg/L compared to those of the standard antioxidant BHT, which were 27.97 and 19.77?mg/L, for the DPPH and ABTS tests, respectively. The diabetic animals showed a significant increase in glycaemia (from 4.05 to 4.28?g/L) and thiobarbituric acid reactive substances (50.17?mmol/g protein) levels. Treatment with SP significantly reduced glycaemia by 79% and liver function markers [glutamate pyruvate transaminase (GPT), glutamate oxaloacetate transaminase (GOT) and alkaline phosphatase (Alk-p)]) by 25, 36 and 20%, respectively, compared to that of the controls. There was a significant increase in superoxide dismutase (48%), total antioxidant status (43%), glutathione peroxidase (37%) and glutathione reductase (16%) in the diabetic rats treated with SP.

Discussion and conclusion: These results showed that SP has high antioxidant activity, free radical scavenging, antihyperglycemic and hepatoprotective effects in diabetes.     

Phenolic composition,antioxidant and anti-acetylcholinesterase activities of the Tunisian Scabiosa arenaria

Abstract

Context: There is a need for the discovery of novel natural antioxidants and acetylcholinesterase inhibitors (AChEIs) that are safe and effective at a global level. This is the first study on antioxidant and anti-acethylcholinesterase activity of Scabiosa arenaria Forssk (Dipsacaceae).

Objective: The antioxidant potential and anti-acetylcholinesterase (AChE) activity of S. arenaria were investigated.

Material and methods: The crude, ethyl acetate (EtOAc), butanol (n-BuOH) and water extracts prepared from flowers, fruits and stems and leaves of S. arenaria were tested to determine their total polyphenol content (TPC), total flavonoid content (TFC), total condensed tannin content (CTC) and their antioxidant activity by using 1,1-diphenyl-2-picrylhydrazyl (DPPH), 2,2′-azinobis(3-ethylbenzothiazoline-6-sulfonic acid (ABTS), reducing power and β-carotene bleaching inhibition activity. Anti-AChE activity was also determined.

Results: EtOAc and n-BuOH fractions of fruits had both the highest (TPC) (269.09?mg gallic acid equivalents/g dry weight). The crude extract of stems and leaves had the highest TFC (10.9?mg quercetin equivalent/g dry weight). The n-BuOH fraction of stems and leaves had the highest CTC (489.75?mg catechin equivalents/g dry weight). The EtOAc fraction of flowers exhibit a higher activity in each antioxidant system with a special attention for DPPH assay (IC₅₀?=?0.017?mg/mL) and reducing power (EC₅₀?=?0.02?mg/mL). The EtOAc and n-BuOH fractions of stems and leaves showed strong inhibition of AChE (IC₅₀?=?0.016 and 0.029?mg/mL, respectively).

Discussion and conclusions: These results suggest the potential of S. arenaria as a possible source of novel compounds and as an alternative antioxidant and AChEIs.     

Appraisal of anti-arthritic and nephroprotective potential of Cuscuta reflexa

Context: Cuscuta reflexa Roxb. (Cuscutaceae) has been used traditionally for treating sore knees and kidney problems, but its efficacy has not been scientifically examined in treating arthritis and nephrotoxicity.

Objective: Present study determines antiarthritic and nephroprotective potential of the aqueous methanolic extract of Cuscuta reflexa (AMECR).

Materials and methods: Antiarthritic activity of Cuscuta reflexa in formaldehyde and turpentine oil-induced rat arthritis models was appraised at 200, 400 and 600?mg/kg doses for 10 days and 6?h period, respectively, and in vitro protein denaturation (bovine serum albumin, egg albumin) inhibition was studied at 25–800?μg/mL concentration. The nephroprotective effect involved gentamicin-induced nephrotoxicity in rats at 200, 400 and 600?mg/kg doses.

Results: Plant extract at 600?mg/kg significantly reduced paw oedema and joint swelling with maximal inhibition of 71.22% at the 6th hour for turpentine oil and 76.74% on 10th day for formaldehyde. Likewise, in vitro results corroborated significant concentration-dependent increase in percentage protection at 800?μg/mL against both bovine serum albumin (89.30%) and egg albumin (93.51%) denaturation. Similarly, 600?mg/kg dose showed maximum nephroprotection by reducing serum urea (41.400?±?0.510?mg/dL), uric acid (0.740?±?0.032?mg/dL), blood urea nitrogen (18.370?±?0.328), creatinine (3.267?±?0.076) and minimizing kidney weight gain (0.586?±?0.005) and histopathological alterations on 8th day. Furthermore, phytochemical and HPLC analysis revealed the presence of important phytoconstituents.

Discussion and conclusions: These results suggest that AMECR provides protection against arthritis and nephrotoxicity that might be due to the existence of phytoconstituents, thus supporting folkloric claim.     

Beneficial effects of tyrosol on altered glycoprotein components in streptozotocin-induced diabetic rats

Context: Olive oil is the major source of tyrosol which is a natural phenolic antioxidant. Olive oil constitutes a major component of the Mediterranean diet that is linked to a reduced incidence of chronic diseases.

Objective: This study evaluates the effects of tyrosol on altered glycoprotein components in streptozotocin-induced diabetic rats.

Materials and methods: Diabetes mellitus was induced in male Wistar rats by streptozotocin (40?mg/kg body weight). These rats were administered tyrosol (20?mg/kg body weight) and glibenclamide (600?μg/kg body weight) orally daily for 45?days. Plasma glucose, plasma insulin, glycoprotein components such as hexose, hexosamine, sialic acid and fucose in the plasma, liver and kidney, and histopathogy of tissues were analyzed.

Results: Diabetic rats revealed significant (p?p?p?in vitro study revealed the antioxidant effect of tyrosol.

Discussion and conclusions: Thus, tyrosol protects streptozotocin-induced diabetic rats from the altered glycoprotein components. Further, this study can be extrapolated to humans.     

Protective mechanism of turmeric (Curcuma longa) on carbofuran-induced hematological and hepatic toxicities in a rat model

Context: Turmeric (Curcuma longa L. [Zingiberaceae]) is used in the treatment of a variety of conditions including pesticide-induced toxicity.

Objective: The study reports the antioxidant properties and the protective effects of turmeric against carbofuran (CF)-induced toxicity in rats.

Materials and methods: The antioxidant potential was determined by using free radicals scavenging activity and ferric reducing antioxidant power values. Male Wistar rats were randomly divided into four groups, designated as control, turmeric (100?mg/kg/day), CF (1?mg/kg/day) and turmeric (100?mg/kg/day)?+?CF (1?mg/kg/day) treatments. All of the doses were administered orally for 28 consecutive days. The biological activity of the turmeric and CF was determined by using several standard biochemical methods.

Results: Turmeric contains high concentrations of polyphenols (8.97?±?0.15?g GAEs), flavonoids (5.46?±?0.29?g CEs), ascorbic acid (0.06?±?0.00?mg AEs) and FRAP value (1972.66?±?104.78?μM Fe²⁺) per 100?g of sample. Oral administration of CF caused significant changes in some of the blood indices, such as, mean corpuscular volume, corpuscular hemoglobin, white blood cell, platelet distribution width and induced severe hepatic injuries associated with oxidative stress, as observed by the significantly higher lipid peroxidation (LPO) levels when compared to control, while the activities of cellular antioxidant enzymes (including superoxide dismutase and glutathione peroxidase) were significantly suppressed in the liver tissue.

Discussion and conclusion: Turmeric supplementation could protect against CF-induced hematological perturbations and hepatic injuries in rats, plausibly by the up-regulation of antioxidant enzymes and inhibition of LPO to confer the protective effect.     

Inter-species comparative antioxidant assay and HPTLC analysis of sakuranetin in the chloroform and ethanol extracts of aerial parts of Rhus retinorrhoea and Rhus tripartita

Context: Extensive research on Rhus (Anacardiaceae) shows their antioxidant potential, which warrants further evaluation of its other species.

Objective: To perform a comparative antioxidant assay on extracts of R. retinorrhoea and R. tripartita, including sakuranetin quantification by a validated HPTLC method.

Materials and methods: In vitro antioxidant assay was performed on chloroform and ethanol extracts of R. retinorrhoea Steud. ex Oliv. (RRCE and RREE) and R. tripartita (Ucria) Grande (RTCE and RTEE) by DPPH radical scavenging (at 31.25, 62.5, 125, 250 and 500?μg/mL concentrations) and β-carotene-linoleic acid bleaching methods at 500?μg/mL concentration. Densitometric HPTLC method was developed and validated using toluene: ethyl acetate: methanol (8:2:0.2; v/v/v) as mobile phase, executed on glass-backed silica gel F₂₅₄ plate and scanned at 292?nm.

Results: Antioxidant activity of Rhus extracts tested by the two methods (DPPH/BCB) was found in order of RTEE?>?RREE?>?RTCE?>?RRCE with IC₅₀ 118.67/256.26, 315.75/82.35, 827.92/380.0 and 443.69/292.75, respectively. Scanning of the HPTLC plate provided an intense peak of sakuranetin at R_f =?0.59. The estimated sakuranetin content in the dry weight of the extracts was highest in RREE (27.95?μg/mg) followed by RRCE (25.22?μg/mg), RTEE (0.487?μg/mg) and RTCE (0.0?μg/mg). Presence of sakuranetin in RREE, RRCE and RTEE supported the highest antioxidant property of the two Rhus species. Nonetheless, low sakuratenin in R. tripartita indicated the presence of other bioactive constituents responsible for synergistic antioxidant activity.

Conclusion: The developed HPTLC method therefore guarantees its application in quality control of commercialized herbal drugs and formulations containing sakuranetin.     

Haematopoietic effects of Angelica sinensis root cap polysaccharides against lisinopril-induced anaemia in albino rats

Context: Angelica sinensis L. (Umbelliferae) has medicinal properties.

Objectives: The present study evaluates the haematopoietic effects of A. sinensis polysaccharides (ASP) against lisinopril-induced anaemia.

Materials and methods: Thirty healthy adult male albino rats were randomly divided into five groups (n?=?6). Group I was control group. Group II was treated with angiotensin-converting enzyme inhibitor (ACEI, 20?mg/kg/day) to induce anaemia. In group III, erythropoietin (EPO, 100?IU/kg/each) was administered in combination with ACEI. Group IV was treated with ASP (1?g/kg/day), extracted from A. sinensis root caps. In Group V, ASP (1?g/kg/day) was treated with ACEI. After 28 days, blood and tissue samples were collected for haematological and histopathological analysis, respectively.

Results: The results showed that ACEI significantly reduced the haemoglobin (Hb, 10.0?g/dL), packed cell volume (PCV, 39.5%), red blood cells (RBCs, 6.2 million/mm³), mean corpuscular volume (MCV, 53.5 fL) and mean corpuscular haemoglobin (MCH, 16.2?pg/cell) values. In the group treated with ASP, the Hb (13.7?g/dL) and RBCs (7.8 million/mm³) increased significantly (p?p?3), MCV (54.42 fL) and MCH (16.44?pg/cell) values. While histopathological examination of the liver and kidney cells showed a mild degree of toxicity in the ASP-treated group.

Conclusion: ASP has a potentiating effect on haematological parameters when given alone. However, when administered simultaneously with lisinopril, it showed an unfavourable effect with more complicated anaemia so it should not be used with ACEIs.     

Calendula officinalis ameliorates l-arginine-induced acute necrotizing pancreatitis in rats

Context: Calendula officinalis L. (Asteraceae) has been traditionally used in treating inflammation of internal organs, gastrointestinal tract ulcers and wound healing.

Objective: The present study investigates the effect of ethanol extract (95%) of Calendula officinalis flowers in l-arginine induced acute necrotizing pancreatitis in rats.

Materials and methods: Rats were divided into four groups: normal control, l-arginine control, Calendula officinalis extract (COE) treated and melatonin treated (positive control), which were further divided into subgroups (24?h, day 3 and 14) according to time points. Two injections of l-arginine 2?g/kg i.p. at 1?h intervals were administered in l-arginine control, COE and melatonin-treated groups to produce acute necrotizing pancreatitis. Biochemical parameters [serum amylase, lipase, pancreatic amylase, nucleic acid content, total proteins, transforming growth factor-β1 (TGF-β1), collagen content, lipid peroxidation, reduced glutathione and nitrite/nitrate] and histopathological studies were carried out.

Results: COE treatment (400?mg/kg p.o.) was found to be beneficial. This was evidenced by significantly lowered histopathological scores (2 at day 14). Nucleic acid content (DNA 21.1 and RNA 5.44?mg/g pancreas), total proteins (0.66?mg/mL pancreas) and pancreatic amylase (1031.3 100 SU/g pancreas) were significantly improved. Marked reduction in pancreatic oxidative and nitrosative stress; collagen (122 μmoles/100?mg pancreas) and TGF-β1 (118.56?pg/mL) levels were noted. Results obtained were comparable to those of positive control.

Discussion and conclusion: The beneficial effect of COE may be attributed to its antioxidant, antinitrosative and antifibrotic actions. Hence, the study concludes that COE promotes spontaneous repair and regeneration of the pancreas.     

Prophylactic and curative effect of rosemary leaves extract in a bleomycin model of pulmonary fibrosis

Context: Pulmonary fibrosis is a devastating disease without effective treatment. Rosemary is appreciated since ancient times for its medicinal properties, while biomolecules originated from the plant have an antioxidant and antifibrotic effect.

Objective: The effects of Rosmarinus officinalis L. (Lamiaceae) leaves extract (RO) on bleomycin-induced lung fibrosis were investigated.

Materials and methods: Male Wistar rats were given a single dose of bleomycin (BLM, 4?mg/kg, intratracheal), while RO (75?mg/kg, intraperitoneal) was administered 3 days later and continued for 4 weeks (BLM/RO1-curative group). Alternatively, RO was administered 2 weeks before BLM and continued 15 days thereafter (BLM/RO2-prophylactic group). Antioxidant activities of RO and lung tissues were studied by standard methods. Histological staining revealed lung architecture and collagen deposition. RO was characterized for its polyphenol content and by high-performance liquid chromatography.

Results: RO polyphenol content was 60.52?mg/g of dry weight, carnosic and rosmarinic acids being major components (6.886 and 2.351?mg/g). Antioxidant effect of RO (DPPH and FRAP assay) expressed as IC₅₀ values were 2.23?μg/mL and 0.074?μg/mL, respectively. In BLM/RO1 and BLM/RO2 lung architecture was less compromised compared to BLM, which was reflected in lower fibrosis score (2.33?±?0.33 and 1.8?±?0.32 vs 3.7?±?0.3). Malondialdehyde levels were attenuated (141% and 108% vs 258% of normal value). Catalase and glutathione-S-transferase activities were normalized (103% and 117% vs 59%, 85% and 69% vs 23%, respectively).

Discussion and conclusion: RO has a protective effect against BLM-induced oxidative stress and lung fibrosis due to its phenolic compounds.     

Urtica dioica attenuates ovalbumin-induced inflammation and lipid peroxidation of lung tissues in rat asthma model

Context: To find bioactive medicinal herbs exerting anti-asthmatic activity, we investigated the effect of an aqueous extract of Urtica dioica L. (Urticaceae) leaves (UD), the closest extract to the Algerian traditional use.

Objective: In this study, we investigated the in vivo anti-asthmatic and antioxidant activities of nettle extract.

Materials and methods: Adult male Wistar rats were divided into four groups: Group I: negative control; group II: Ovalbumin sensitized/challenged rats (positive control); group III: received UD extract (1.5?g/kg/day) orally along the experimental protocol; group IV: received UD extract (1.5?g/kg/day) orally along the experimental protocol and sensitized/challenged with ovalbumin. After 25?days, blood and tissue samples were collected for haematological and histopathological analysis, respectively. The oxidative stress parameters were evaluated in the lungs, liver and erythrocytes. Then, correlations between markers of airway inflammation and markers of oxidative stress were explored.

Results: UD extract significantly (p?p?50 value.

Conclusions: The results confirmed that UD administration might be responsible for the protective effects of this extract against airway inflammation.     

Oxidant effects and toxicity of Croton campestris in Drosophila melanogaster

Context: Croton campestris A.St.-Hil. (Euphorbiaceae) is a species native to Northeast Brazil used by traditional communities for the treatment of a variety of health problems. However, potential toxicological effects of this plant are unknown.

Objective: The potential toxicity of the hydroalcoholic extract of C. campestris leaves on Drosophila melanogaster insect model, additionally with phytochemical constitution and cellular mechanisms mediating the action of extract were analysed in this study.

Materials and methods: Constituents of the extract were evaluated by HPLC. In vitro antioxidant potential of extract was analysed by DPPH, ABTS and FRAP. Flies injected culture medium mixed with extract (0.1–50?mg/mL) for 72?h. After, ROS production was evaluated by DCF-DA oxidation. Phosphorylation of MAPK signalling pathway was investigated by Western blotting method. Activity of antioxidant enzymes was analysed in homogenates.

Results: Major components of the extract include quercetin (38.11?±?0.06?mg/g), caffeic acid (20.06?±?0.17?mg/g) and kaempferol (15.45?±?0.05?mg/g). Consumption of the extract impaired locomotor performance and induced fly death of flies (LC₅₀ of 26.51?mg/mL). Augmented ROS formation and SOD, CAT and GST activity were observed from 0.1?mg/mL. JNK and p38 kinases phosphorylation was modulated and Paraquat-induced toxicity was augmented by extract.

Discussion and conclusion: Our data show important toxicological effects of C. campestris leading to increased mortality and impaired locomotor performance accompanied by induction of cell stress markers in flies. The study draws attention to the indiscriminate use of plant extracts.     

Therapeutic role of quercetin on oxidative damage induced by acrylamide in rat brain

Context Quercetin (QE), a bioflavonoid present abundantly in fruits and vegetables, has been reported to possess antioxidant properties. Acrylamide (ACR) is formed in foods during cooking and is known to be neurotoxic.

Objective The present study was designed to evaluate the protective effect of QE against neurotoxicity induced by ACR.

Materials and methods Four groups of Wistar rats consisting of six rats each: (i) control group; (ii) acrylamide treated group (50?mg/kg body weight as single dose); (iii) quercetin group: rats were treated intraperitoneally (i.p.) with QE (10?mg/kg body weight alone every day for 5 d); (iv) quercetin?+?acrylamide group: quercetin (10?mg/kg bw) was given i.p. every day for 5 d followed by acrylamide i.p. injection (50?mg/kg bw) on fifth day (single dose). Rats were killed after 48?h.

Results Administration of ACR (50?mg/kg bw) in Wistar rats resulted in significant increase of dopamine, interferon-γ and 8-hydroxyguanosine with concomitant decrease of serotonin (p?<?0.001) in the rat brain. Treatment of rats with QE intraperitonealy (10?mg/kg body weight) before ACR assault resulted in the diminution of ACR-mediated neurotoxicity as evident from decreased levels of dopamine, interferon-γ (p?<?0.001) and 8-hydroxyguanosine with concomitant restoration of serotonin levels (p?<?0.001).

Discussion and conclusion On the basis of the above results, the present study suggests that quercetin may be a potential therapeutic agent for restoration of oxidative damage to neurons.     

Zanthoxylum alatum abrogates lipopolysaccharide-induced depression-like behaviours in mice by modulating neuroinflammation and monoamine neurotransmitters in the hippocampus

Context: Depression is an inflammatory, commonly occurring and lethal psychiatric disorder having high lifetime prevalence. Zanthoxylum alatum Roxb. (Rutaceae), commonly called Timur, has high medicinal value and is used ethnomedicinally for the treatment of various diseases.

Objective: To evaluate the effect of hexane extract of Z. alatum seeds (ZAHE) on lipopolysaccharide (LPS)-induced depression-like behaviour in Swiss albino mice.

Materials and methods: Mice were treated with ZAHE (100 and 200?mg/kg, p.o.) and imipramine (10?mg/kg injected i.p.) for 14?days. On 14th day of the treatment, depression-like behaviour was induced by LPS (0.83?mg/kg injected i.p.) and after 24?h of LPS administration, it was assessed by measuring behavioural parameters and biochemical estimations.

Results: Behavioural tests, including the open field test, forced swimming test, tail suspension test and sucrose preference test revealed that ZAHE (100 and 200?mg/kg, p.o.) and imipramine (10?mg/kg injected i.p.) alleviated the depression symptoms of LPS-induced mice. Moreover, ZAHE treatments reversed the LPS-induced alterations in the concentrations of norepinephrine and serotonin (5-HT) and inhibited the expression of brain-derived neurotrophic factor, pro-inflammatory cytokines and oxido-nitrosative stress in the mice. Acute toxicity was calculated to be LD₅₀ >?2500?mg/kg.

Discussion and conclusions: This study showed that LPS-induced depression in mice was significantly prevented by ZAHE at both the dosages. In conclusion, ZAHE exhibited an antidepressant activity by altering monoaminergic neurotransmitters in the brain combined with its anti-inflammatory potential. Thus, it could be an effective therapeutic against inflammation-induced depression and other brain disorders.