Crataegus Aronia protects and reverses vascular inflammation in a high fat diet rat model by an antioxidant mechanism and modulating serum levels of oxidized low-density lipoprotein

Context: Crataegus aronia (Willd.) Bosc (Rosaceae) (syn. Azarolus L) is traditionally used to treat cardiovascular disorders.

Objectives: To investigate C. aronia protection against a high-fat diet (HFD)-induced vascular inflammation in rats.

Materials and methods: Wistar Male rats (180–220?g) were divided (n?=?10/group) as control fed a standard diet (STD), STD + C. aronia (200?mg/kg, orally), HFD, HFD + C. aronia and HFD post-treated with C. aronia. Simvastatin (20?mg/kg) was co- or post-administered as a positive control drug. HFD was given for 8?weeks, and all other treatments were administered for 4?weeks.

Results: Most significantly, co-administration of C. aronia to HFD-fed rats reduced the thickness of aorta tunica media (90?±?5 vs. 160?±?11.3?µm) and adventitia (54.3?±?3.8 vs. 93.6?±?9.4?µm). It also lowered protein levels of TNF-α (0.51?±?0.15 and 0.15?±?0.16 vs. 0.1?±?0.09%) and IL-6 (0.52?±?0.19 vs. 1.0?±?0.2%) in their aorta or serum (5.9?±?0.91 vs. 12.98?±?1.3?ng/mL and 78.1?±?6.7 vs. 439?±?78?pg/mL, respectively). It also lowered all serum lipids and increased aorta levels of GSH levels (70.4?±?4.0 vs. 40.7?µM) and activity of SOD (5.7?±?0.7 vs. 2.9?±?0.6?U/mg) and decreased serum levels of ox-LDL-c (566.7?±?46 vs. 1817?±?147?ng/mL). Such effects were more profound than all other treatments.

Conclusions: C. aronia inhibits the HFD-induced vascular inflammation and its use in clinical trials is recommended.     

Effects of the hydroalcoholic extract of Rosa damascena on learning and memory in male rats consuming a high-fat diet

Context: High-fat diet (HFD) can cause deficits in learning and memory through oxidative stress and increase Alzheimer disease risk. Rosa damascena Mill. (Rosaceae) extract possesses potent antioxidant properties.

Objective: This study investigated the effects of the hydroalcoholic extracts of petals of R. damascena on learning and memory in male rats consuming an HFD.

Materials and methods: Forty male Wistar rats (200–250?g) were randomly assigned to four groups: control, R. damascena extract, HFD and HFD?+?extract. The extract (1?g/kg bw daily) was administered by oral gavage for 1?month. Animals were allowed free access to high-fat chow for 3?months. The Morris water maze and the passive avoidance learning tests were used to assess learning and memory.

Results: In the passive avoidance learning test, the step-through latencies in the retention test (STLr) of the extract (147.4?±?23.3) and HFD (150.3?±?25.2) groups were significantly lower than those of the control group (270.4?±?10.5) (respectively, p?p?p?p?Discussion and conclusion: Our results indicate that, while HFD or R. damascena extract alone leads to memory deficits, R. damascena extract exerted a positive effect on HFD-induced memory deficits. We hypothesize that the observed effects of R. damascena extract are likely due to its strong antioxidant properties.     

Aqueous and methanol extracts of Vernonia amygdalina leaves exert their anti-obesity effects through the modulation of appetite-regulatory hormones

Context: Aqueous and methanol extracts of Vernonia amygdalina Del. (Asteraceae) (AEVA and MEVA, respectively) leaves are reported to possess anti-obesity properties, exerted through unknown mechanisms.

Objective: This study investigated the effects of AEVA and MEVA on relevant hormones and enzymes in high-fat diet (HFD)-induced obese rats.

Materials and methods: Forty-two Wistar rats were placed into seven groups. The test groups received 100?mg/kg.bw AEVA (AEVA100), 500?mg/kg.bw AEVA (AEVA500), 50?mg/kg.bw MEVA (MEVA50) and 200?mg/kg.bw MEVA (MEVA200), respectively. The positive control (PC) group received 20?mg/kg.bw Orlistat, while the negative control (NeC) and normal control (NoC) groups received distilled water. The extracts were given orally daily for 12 weeks. Thereafter, the concentrations/activities of relevant hormones/enzymes in their sera were determined.

Results: Insulin concentrations (ng/ml) in the test groups ranged from 1.08?±?0.01 (AEVA100) to 1.09?±?0.01 (AEVA500). They were all similar (p?>?.05) to the NoC and PC controls. Leptin concentrations (pg/ml) in the test rats ranged from 0.02?±?0.01 (AEVA500) to 0.03?±?0.00 (MEVA50), and were all similar to the NoC group. The ghrelin concentrations of only the AEVA500 and MEVA200 groups were similar to those of the PC group (0.10?±?0.01?pg/ml). AEVA100 and MEVA200 resulted in adiponectin concentrations (ng/ml) of the rats (0.27?±?0.04 and 0.28?±?0.04 respectively) that were similar to the PC group. The activities of lipoprotein lipase and the concentrations of intestinal amylase in the test rats were similar to values obtained for the control groups.

Conclusion: Appetite regulation may be the mechanism through which the weight-loss properties of AEVA and MEVA are expressed.     

Effects of Piper nigrum extracts: Restorative perspectives of high-fat diet-induced changes on lipid profile,body composition,and hormones in Sprague–Dawley rats

Abstract

Context: Piper nigrum Linn (Piperaceae) (PnL) is used in traditional medicine to treat gastric ailments, dyslipidemia, diabetes, and hypertension.

Objective: The present study explores the possible protective effects of P. nigrum extracts on high-fat diet-induced obesity in rats.

Materials and methods: High-fat diet-induced obese rats were treated orally with 200?mg/kg bw of different extracts (hexane, ethylacetate, ethanol, and aqueous extracts) of PnL for 42?d. The effects of PnL extracts on body composition, insulin resistance, biochemical parameters, leptin, adiponectin, lipid profile, liver marker enzymes, and antioxidants were studied.

Results and discussion: The HFD control group rats showed a substantial raise in body weight (472.8?±?9.3?g), fat% (20.8?±?0.6%), and fat-free mass (165.9?±?2.4?g) when compared with normal control rats whose body weight, fat%, and fat-free mass were 314.3?±?4.4?g, 6.4?±?1.4%, and 133.8?±?2.2?g, respectively. Oral administration of ethyl acetate or aqueous extracts of PnL markedly reduced the body weight, fat%, and fat-free mass of HFD-fed rats. In contrast to the normal control group, a profound increase in plasma glucose, insulin resistance, lipid profile, leptin, thiobarbituric acid reactive substance (TBARS), and the activities of lipase and liver marker enzymes, and a decrease in adiponectin and antioxidant enzymes were noted in HFD control rats. Administration of PnL extracts to HFD-induced obese rats significantly (p?<?0.05) restored the above profiles.

Conclusion: PnL extracts significantly reduced the body weight, fat%, and ameliorated HFD-induced hyperlipidemia and its constituents.     

1H NMR-based metabolic study reveals the improvements of bitter melon (Momordica charantia) on energy metabolism in diet-induced obese mouse

Context: Obesity can be ameliorated by some natural products such as polyphenol, flavones and saponin. As a typical medicinal plant, Momordica charantia L. (Cucurbitaceae) (bitter melon, BM) contains these natural chemicals and reduces diet-induced obesity in mice.

Objective: This study evaluates the metabolic effects of dietary BM supplement, investigates a global metabolic profile and determines associated perturbations in metabolic pathways.

Materials and methods: Male C57BL/6 mice were fed with low-fat diet (LFD), high-fat diet (HFD) and HFD supplemented with 5% BM based on 37.6?g/kg body weight in average for 12 weeks, respectively. Then energy metabolism was quantified using PhenoMaster/LabMaster. The spectroscopy of urine was acquired by nuclear magnetic resonance and latent biomarkers were identified. Pattern recognition analysis was used to discriminate associated metabolic profiles.

Results: Dietary BM supplement reduced body weight gain (?0.15-fold, p?<?0.01) and blood glucose levels (?0.19-fold, p?<?0.01) in HFD-fed mice. Meanwhile, the levels of energy metabolism were enhanced (0.08–0.11-fold, p?<?0.01). According to pattern recognition analysis, dietary BM supplement changed metabolic profiles in HFD-fed mice and the modified profiles were similar to those in LFD-fed mice. Finally, the mapping of metabolic pathways showed that dietary BM supplement primarily affected glucose metabolism-associated pathways.

Discussion and conclusion: The results indicated that BM improves weight loss in diet-induced obesity and elevate energy expenditure in HFD-fed mice. The pattern recognition with metabolic study may be used as a noninvasive detection method to assess the effects of dietary BM supplement on mouse energy metabolism.     

The physicochemical properties of geraniin,a potential antihyperglycemic agent

Abstract

Context: Natural products play a vital role in the discovery of leads for novel pharmacologically active drugs. Geraniin (GE) was identified as the major compound in the rind of Nephelium lappaceum L. (Sapindaceae), while ellagic and gallic acids have been shown to be its main metabolites. GE and its metabolites possess a range of bioactive properties including being an anti-infective, anticarcinogenic, antihyperglycemic, and antihypertensive.

Objective: GE and its metabolites were investigated to establish its gastrointestinal absorption and physicochemical properties.

Materials and methods: GE was purified from N. lappaceum rind extract using reverse-phase C18 column chromatography. Lipophilicity (log P) was determined using the 1-octanol/water shake-flask method. Equilibrium solubility of GE and its metabolites (20?mg) was determined in water and four biorelevant media: simulated gastric, simulated intestinal, fasted state-simulated intestinal, and fed state-simulated intestinal after 72?h.

Results and discussion: The purification yield was 10.8%; where a 97–99% pure GE was obtained. Log P values for GE, ellagic, and gallic acids were established as ?0.73?±?0.17, 0.11?±?0.06, and 0.71?±?0.21, respectively, establishing them as polar compounds. All three compounds were found to exhibit poor solubility in gastric (0.61–8.10?mg/mL) but good solubility in intestinal fluids (3.59–14.32?mg/mL).

Conclusion: The above results indicate that the compounds have limited gastrointestinal absorption due to its polarities. To consider these compounds as oral drug candidates, formulation strategies are being developed.     

Effect of pramlintide as an adjunct to basal insulin on markers of cardiovascular risk in patients with type 2 diabetes

ABSTRACT

Objective: Intensification of insulin therapy in patients with type 2 diabetes, while improving glycemic control, often leads to an increase in body weight and other markers of cardiovascular risk. The effects of pramlintide as an adjunct to basal insulin titration (without mealtime insulin) on glycemia and cardiovascular risk markers were examined.

Research design and methods: This was a post hoc analysis of a 16-week, double-blind, placebo-controlled study in patients with type 2 diabetes (N?=?211) using insulin glargine (without mealtime insulin)?±?oral agents. Patients were randomized to treatment with placebo or pramlintide (60 or 120?µg with major meals), and insulin glargine was titrated to target a fasting plasma glucose concentration of ≥70 to <100?mg/dL.

Main outcome measures: Endpoints included the change from baseline to Week 16 in body weight, high sensitivity C-reactive protein (hsCRP), triglycerides, HDL, LDL, and blood pressure.

Results: Pramlintide-treated patients lost weight and placebo-treated patients gained weight during 16 weeks of treatment (?1.6?±?0.3?kg vs. +0.7?±?0.3?kg, p?<?0.001; mean?±?SE). hsCRP was reduced in pramlintide-treated versus placebo-treated patients (?0.8?±?0.2?mg/L vs. 0.1?±?0.2?mg/L, p?<?0.01; mean?±?SE). Patients with baseline hsCRP?>?3?mg/L (high cardiovascular risk) demonstrated greater hsCRP reductions with pramlintide versus placebo treatment at Week 16 (p?<?0.05). Patients with baseline triglycerides ≥150?mg/dL or ≥200?mg/dL (high cardiovascular risk) showed significant reductions from baseline in triglyceride concentrations with pramlintide (?43?±?14?mg/dL or ?59?±?19?mg/dL; p?<?0.05; mean?±?SE) but not with placebo (1?±?29?mg/dLor ?3?±?54?mg/dL; mean?±?SE). No significant differences between pramlintide and placebo were observed for changes in HDL, LDL, or blood pressure. Pramlintide treatment was generally well tolerated. The most frequent adverse event related to pramlintide was mild-to-moderate nausea (31% pramlintide vs. 10% placebo). Pramlintide added to basal insulin did not increase the incidence of hypoglycemia. A limitation of the study was its relatively short duration.

Conclusions: Pramlintide, as an adjunct to basal insulin, was associated with improvements in several cardiovascular risk markers, warranting long-term clinical studies to determine its potential effects on cardiovascular risk.     

Effects of triptolide on pharmacokinetics of amlodipine in rats by using LC–MS/MS

Context: Triptolide and amlodipine are often simultaneously used for reducing urine protein excretion after renal transplantation in China clinics.

Objective: This study investigated the effects of triptolide on the pharmacokinetics of amlodipine in male Sprague–Dawley rats.

Materials and methods: The pharmacokinetics of amlodipine (1?mg/kg) with or without triptolide pre-treatment (2?mg/kg/day for seven?days) were investigated using a sensitive and reliable LC–MS/MS method. Additionally, the inhibitory effects of triptolide on the metabolic stability of amlodipine were investigated using rat liver microsome incubation systems.

Results: The results indicated that when the rats were pre-treated with triptolide, the C_max of amlodipine increased from 13.78?±?3.57 to 19.96?±?4.56?ng/mL (p?T_max increased from 4.04?±?1.15 to 5.89?±?1.64?h (p?AUC_0–t increased by approximately 104% (p?p?Conclusions: In conclusion, these results indicated that triptolide could affect the pharmacokinetics of amlodipine, possibly by inhibiting the metabolism of amlodipine in rat liver when they are co-administered.     

Comparative pharmacokinetics of chlorogenic acid in beagles after oral administrations of single compound,the extracts of Lonicera japanica,and the mixture of chlorogenic acid,baicalin, and Forsythia suspense

Context: Chlorogenic acid (ChA) is the major compound in Shuang-Huang-Lian (SHL), which is mainly composed of ChA, baicalin, and Forsythia suspense Thunb Vahl.

Objective: The effects of co-existing compounds in SHL and Lonicera japanica Thunb on the absorption of ChA was investigated.

Materials and methods: According to 3?×?3 Latin-square test, ChA alone, the extracts of Lonicera japanica, or the mixture of ChA, baicalin and Forsythia suspense (ChA effective doses is 60?mg/kg) was separately given to six beagles for seven days. The oral pharmacokinetic parameters of ChA in plasma, urine and faeces were quantified by HPLC/UV and analyzed.

Results: The pharmacokinetic parameters of ChA alone, the extracts of Lonicera japanica, and the mixture of ChA, baicalin, and Forsythia suspense were as followed: C_max (2.350?±?0.483, 1.655?±?0.576, 2.332?±?0.606?μg/mL), AUC_0-∞ (6.324?±?1.853, 4.216?±?1.886, 6.074?±?1.473?μg·h/mL), t_1/2 (0.911?±?0.187, 1.204?±?0.309, 1.094?±?0.193?h), and T_max (1.861?±?0.499, 1.000?±?0.459, 1.833?±?0.279?h). Accumulative fraction excretion of ChA in urine were 0.73?±?0.55, 1.25?±?1.23, 1.05?±?0.96%, while that in faeces were 0.68?±?0.94, 0.19?±?0.40, and 1.76?±?3.57%.

Discussion and conclusion: Co-existing compounds in SHL have no effect on the absorption of ChA, while the concomitant compounds in Lonicera japanica could decrease that of ChA. ChA in Beagles might have high biological transformation.     

The effects of triptolide on the pharmacokinetics of sorafenib in rats and its potential mechanism

Context: Combining sorafenib with triptolide could inhibit tumour growth with greater efficacy than single-agent treatment. However, their herb–drug interaction remains unknown.

Objective: This study investigates the herb–drug interaction between triptolide and sorafenib.

Materials and methods: The effects of triptolide (10?mg/kg) on the pharmacokinetics of different doses of sorafenib (20, 50 and 100?mg/kg) in rats, and blood samples were collected within 48?h and evaluated using LC-MS/MS. The effects of triptolide on the absorption and metabolism of sorafenib were also investigated using Caco-2 cell monolayer model and rat liver microsome incubation systems.

Results: The results showed that the C_max (low dose: 72.38?±?8.76 versus 49.15?±?5.46?ng/mL; medium dose: 178.65?±?21.05 versus 109.31?±?14.17?ng/mL; high dose: 332.81?±?29.38 versus 230.86?±?9.68?ng/mL) of sorafenib at different doses increased significantly with the pretreatment of triptolide, and while the oral clearance rate of sorafenib decreased. The t_1/2 of sorafenib increased significant (p?Discussion and conclusions: These results indicated that triptolide could change the pharmacokinetic profiles of sorafenib in rats; these effects might be exerted via decreasing the intrinsic clearance rate of sorafenib in rat liver.     

Effects of Ginkgo leaf tablets on the pharmacokinetics of losartan and its metabolite EXP3174 in rats and its mechanism

Context: Ginkgo leaf tablets (GLTs) and losartan are often simultaneously used for the treatment of hypertension in Chinese clinics. However, the herb–drug interaction between GLT and losartan is still unknown.

Objective: This study investigates the effects of GLT on the pharmacokinetics of losartan and its metabolite EXP3174 in rats and its potential mechanism.

Materials and methods: The pharmacokinetic profiles of losartan and EXP3174 of orally administered losartan (10?mg/kg) with or without GLT pretreatment (80?mg/kg/day for 10?days) in Sprague–Dawley rats were determined. In vitro, the effects of GLT on the metabolic stability of losartan were investigated with rat liver microsomes.

Results: The C_max (1.22?±?0.25 vs 1.85?±?0.37?μg/mL) and the AUC_(0–t) (6.99?±?1.05 vs 11.94?±?1.79?mg·h/L) of losartan increased significantly (p?C_max (1.05?±?0.19 vs 0.72?±?0.12?μg/mL) of EXP3174 decreased significantly (p?t_1/2 of losartan was prolonged significantly from 3.94?±?0.62 to 4.75?±?0.52?h (p?Discussion and conclusions: The results indicate that GLT might increase the plasma concentration of losartan and decrease the concentration of EXP3174 through inhibiting the metabolism of losartan.     

Monoterpene phenolic compound thymol prevents high fat diet induced obesity in murine model

Context: Obesity has become a worldwide health problem. Most of the synthetic anti-obesity drugs have failed to manage the obesity due to either ineffectiveness or adverse effect. The research of prominent chemical constituents from herbal for the management of obesity has greatly increased.

Objective: The main objective of the present study was intended to examine the effects of thymol in high-fat diet (HFD)-induced obesity in murine model.

Methods: Male Wistar rats were fed HFD for 6 weeks to induce obesity. Thymol (14?mg/kg) administered orally twice a day to HFD-fed rats for 4 weeks. Alteration in body weight gain, visceral fat-pads weight and serum biochemical markers were assessed.

Results: At the end of study, rats fed with HFD exhibited significantly (p?p?Discussion and conclusions: Thymol prevents HFD-induced obesity in murine model through several mechanisms including attenuation of visceral fat accumulation, lipid lowering action, improvement of insulin and leptin sensitivity and enhanced antioxidant potential.     

Hesperidin,a citrus flavonoid,protects against l-methionine-induced hyperhomocysteinemia by abrogation of oxidative stress,endothelial dysfunction and neurotoxicity in Wistar rats

Context: Hesperidin (HSP), a flavanoglycone found in citrus fruits, has antioxidant, anti-inflammatory and neuroprotective properties.

Objective: This study evaluates the protective effect of HSP on l-methionine-induced hyperhomocysteinemia (HHcy) in rats.

Materials and methods: Male Wistar rats were randomly divided into seven groups as DMSO, l-methionine, HSP (25, 50 and 100?mg/kg), HSP-per se (100?mg/kg) and donepezil (0.1?mg/kg). HHcy was induced by oral administration of l-methionine (1.7?g/kg) for 32 days. From the 14^th day of study HSP (25, 50 and 100?mg/kg) and donepezil was administered orally to l-methionine-treated rats. Cognitive impairment induced by HHcy was determined using the Morris water maze (MWM) and Y-maze on video tracking system (28^th–32^nd day). Different biomarkers of HHcy in serum and brain and vascular reactivity were evaluated and histopathology (thoracic aorta and brain) was done.

Results: HSP (100?mg/kg) treatment in l-methionine-treated rats exhibited significant (p?p?l-methionine on acetylcholine-induced endothelial-dependent relaxation and increased serum nitrite and vascular nitric oxide bioavailability along with the restoration of histological aberrations.

Conclusion: HSP exerts a protective effect on HHcy by abrogating oxidative stress, ED and neurotoxicity.     

Co-administration of walnut (Juglans regia) prevents systemic hypertension induced by long-term use of dexamethasone: a promising strategy for steroid consumers

Context: The long-term consumption of glucocorticoids (GCs) may induce serious adverse effects such as hypertension. There is sufficient evidence related to the benefit of walnuts on the cardiovascular system.

Objective: This study assesses the effect of methanol extract of walnut [Juglans regia L. (Juglandaceae)] on dexamethasone-induced hypertension and the possible mechanisms in Wistar rats.

Material and methods: Animals were randomized into control, kernel extract (100 and 200?mg/kg/d, orally), dexamethasone (0.03?mg/kg/d, subcutaneously), dexamethasone?+?kernel (100 and 200?mg/kg/d, separately), and dexamethasone?+?captopril (25?mg/kg/d, orally) groups. Animals were treated with water, kernel extract or captopril by gavage 4 d before and during 11 d of saline or dexamethasone treatment. On the 16th day, blood pressure (BP) was recorded and blood samples were collected to measure nitric oxide (NO). Animal hearts were frozen for measurement of malondialdehyde (MDA) and glutathione peroxidase (GPX).

Results: Dexamethasone increased the diastolic BP and MDA/GPX ratio in comparison with control group (128?±?7 vs. 105?±?3?mmHg, p?p?p?p?Conclusion: Similar to captopril, walnut extract normalized dexamethasone-induced hypertension. A part of this beneficial effect apparently involves maintaining balance of the redox system and NO production.     

Antidiabetic,antilipidemic, and antioxidant activities of Gouania longipetala methanol leaf extract in alloxan-induced diabetic rats

Abstract

Context: Gouania longipetala Hemsl. (Rhamnaceae) is used in folkloric medicine for treating diabetes mellitus and its associated symptoms.

Objective: This study evaluated the antidiabetic antilipidemic and antioxidant activities of the plant methanol leaf extract.

Materials and methods: Diabetes was induced in rats by intraperitoneal injection of alloxan monohydrate (160?mg/kg). Three test doses (50, 100, and 150?mg/kg) of G. longipetala extract (GLE) were administered orally and the effects were compared with glibenclamide (2?mg/kg). The effect of GLE on hyperglycemia and sub-acute study for 21?d were carried out using its effect on fasting blood sugar (FBS) level. Serum biochemistry and antioxidant activity were evaluated. Histopathological evaluation of the pancreas was also done.

Results: The LD₅₀ of G. longipetala was found to be >4000?mg/kg. The extract significantly (p?<?0.0001) decreased the FBS levels of treated rats from 16.2?±?2.03 to 6.5?±?1.52?mM/L at 150?mg/kg within 24?h. The extract decreased FBS levels of rats by 62.0, 74.8, and 75.0% on day 21 at 50, 100, and 150?mg/kg, respectively. GLE reduced the level of malondiadehyde from 23.0?±?1.34?to 10.3?±?0.43?mg/dL, increased superoxide dismutase activities from 2.97?±?0.34 to 5.80?±?0.53?IU/L at 150?mg/kg, and improved the serum lipid profile of treated rats. GLE also caused restoration of the altered histopathological changes of the pancreas.

Discussion and conclusion: Gouania longipetala demonstrated significant antidiabetic, antilipidemic, and antioxidant activities that may be due to its multiple effects involving both pancreatic and extra-pancreatic mechanisms.     

Antidepressant and anxiolytic activity of Lavandula officinalis aerial parts hydroalcoholic extract in scopolamine-treated rats

Context: Anxiety and depression are common in Alzheimer’s disease (AD). Despite some evidence, it is difficult to confirm Lavandula officinalis Chaix ex Vill (Lamiaceae) as an anxiolytic and antidepressant drug.

Objective: The effects of L. officinalis extract were studied in scopolamine-induced memory impairment, anxiety and depression-like behaviour.

Materials and methods: Male NMRI rats were divided into control, scopolamine alone-treated group received scopolamine (0.1?mg/kg) intraperitoneally (i.p.), daily and 30?min prior to performing behavioural testing on test day, for 12 continuous days and extract pretreated groups received aerial parts hydro alcoholic extract (i.p.) (100, 200 and 400?mg/kg), 30?min before each scopolamine injection. Memory impairment was assessed by Y-maze task, while, elevated plus maze and forced swimming test were used to measure anxiolytic and antidepressive-like activity.

Results: Spontaneous alternation percentage in Y maze is reduced by scopolamine (36.42?±?2.60) (p?≤?0.001), whereas lavender (200 and 400?mg/kg) enhanced it (83.12?±?5.20 and 95?±?11.08, respectively) (p?≤?0.05). Also, lavender pretreatment in 200 and 400?mg/kg enhanced time spent on the open arms (15.4?±?3.37 and 32.1?±?3.46, respectively) (p?≤?0.001). On the contrary, while immobility time was enhanced by scopolamine (296?±?4.70), 100, 200 and 400?mg/kg lavender reduced it (193.88?±?22.42, 73.3?±?8.25 and 35.2?±?4.22, respectively) in a dose-dependent manner (p?≤?0.001).

Discussion and conclusion: Lavender extracts improved scopolamine-induced memory impairment and also reduced anxiety and depression-like behaviour in a dose-dependent manner.     

Guibourtia tessmannii-induced fictive ejaculation in spinal male rat: involvement of D1, D2-like receptors

Context: Guibourtia tessmannii (Caesalpiniaceae) is a plant traditionally used as aphrodisiac. We previously reported the pro-ejaculatory effects of the aqueous and methanol extracts of G. tesmannii in spinal male rat. However, the mechanism underlying such effects has not been elucidated.

Objective: This study characterizes the dopaminergic sub-type receptors involved in G. tesmannii-induced ejaculation in male Wistar rat.

Materials and methods: Urethane-anesthetized spinal male rats were intravenously treated with saline solution (1?mL/kg, control); dopamine (0.1?μmol/kg, reference); aqueous or methanol extracts of G. tesmannii (20?mg/kg) in the absence or presence of haloperidol (0.26?μmol/kg), a nonspecific dopaminergic receptor antagonist, Sch23390 (0.26?μmol/kg), a specific D1-like receptor antagonist or, sulpiride (0.26?μmol/kg), a specific D2-like receptor antagonist. Electromyography of the bulbospongiosus muscles and intraseminal pressure were recorded after urethral, penile and drug stimulations.

Results: Urethral and penile stimulations, intravenous injection of dopamine or, aqueous and methanol extracts of G. tesmannii always triggered the expression of rhythmic contraction of the bulbospongiosus muscles with an average mean of 3.33?±?0.43; 7.83?±?0.85; 9.80?±?0.86; 0.83?±?0.54 and 2.67?±?0.95 contractions, respectively. The intraseminal pressure was more expressed after urethral and penile stimulations (15.66?±?1.58 and 13.60?±?2.40?mmHg, respectively). In rats pretreated with haloperidol, Sch23390 or sulpiride, no ejaculation was recorded after intravenous injection of G. tesmannii extracts or dopamine.

Discussion and conclusion: Guibourtia tesmannii-induced ejaculation requires the integrity of D₁ and D₂-like receptors. These findings further justify the ethno-medicinal claims of G. tesmannii as an aphrodisiac.     

Quantitative analysis of anthocyanins in Euterpe oleracea (açaí) dietary supplement raw materials and capsules by Q-TOF liquid chromatography/mass spectrometry

Context: Euterpe oleracea Mart. (Arecaceae) fruits and their dietary supplements are gaining much popularity internationally. Anthocyanins and their aglycons are responsible for the dense color of açaí fruit and are associated with a wide spectrum of health promoting effects.

Objective: Quantitative analysis of anthocyanins in açaí dietary supplement raw materials; processed açaí powder (ADSR-1), organic açaí powder (ADSR-2), and nonorganic açaí powder (ADSR-3) by quadrupole-time-of-flight liquid chromatography/mass spectrometry (Q-TOF LC/MS) have been reported in this study.

Materials and methods: The chromatographic separation for anthocyanins was achieved using a C-18 column with a gradient of 0.1% formic acid in water and 0.1% formic acid in methanol and acetonitrile (50:50, v/v). MS and MS/MS experiments were carried out on an electrospray ionization-Q-TOF LC/MS.

Results: Except for ASDR-2, all the açaí samples were found to have cyanidin 3-glucoside (1), cyanidin 3-sambubioside (2), cyanidin 3-rutinoside (3), and peonidin 3-rutinoside (4). ASDR-2 contained anthocyanins 1 and 3. Among the açaí samples quantified, ADSR-3 showed higher concentration of anthocyanins compared to other raw materials and capsules tested in this study.

Discussion and conclusion: The anthocyanins 1–4 present in ADSR-3 were 27.13?±?0.37, 1.76?±?0.04, 31.07?±?0.49, and 3.46?±?0.08?mg/100?g dry wt, respectively. The LOQ values for anthocyanins 1–4 were in the range of 2.44–9.76?ng/mL. Accuracy of the method was assessed by performing a recovery experiments. The intraday and interday variations (RSDs) were <10%. This is the first report on quantitation of anthocyanins in açaí dietary supplement raw materials and capsules.     

Mineral pitch stimulates humoral,cellular and innate immune responses in mice

Abstract

Context: Mineral pitch (MP), a traditional medicine, is proposed to boost immunity in conditions that suppress Th1 cytokines such as AIDS/HIV, tuberculosis, leishmaniasis and cancer.

Objective: This study investigates the immunoregulatory mechanisms of MP in innate, humoral and cell-mediated immunity.

Materials and methods: Mice given MP (100, 200, 300 or 400?mg/kg, orally) for 10 consecutive days were immunized intravenously with goat RBC or ovalbumin, and investigated for plaque-forming cells (PFC), hemagglutination titer, hypersensitivity response, lymphocyte proliferation and macrophage function.

Results: MP increased PFC (330.2 versus 182.2/10⁶ splenocytes) in mice immunized with goat RBC and elicited ovalbumin-specific IgG titer at 400?mg/kg. Increase in Th1 immunity was correlated with the increased level of IFN-γ (724 versus 470?pg/ml) and decreased IL-4 (96 versus 178?pg/ml). CD4⁺/CD3⁺ ratio and delayed-type hypersensitivity response also increased to, respectively, 20.62?±?0.59 (versus 16.47?±?0.72) and 1.59?±?0.12 (versus 0.87?±?0.10?mm) in MP-treated mice. MP increased lymphocyte proliferation (11.14?±?0.60 versus 5.81?±?0.40 SI) and macrophage phagocyte response (0.24?±?0.02 versus 0.15?±?0.009), expressed as absorbance at 570?nm, but decreased nitrite production (17.4?±?1.10 versus 24.3?±?1.30?µM/10⁶ cells). We also observed an increased bone marrow cellularity (24.5?±?1.10 versus 17.10?±?0.70 cells/femur) and WBC count (12?667?±?377 versus 9178?±?213 cells/mm³) following MP treatment. There was no sign of toxicity at 400?mg/kg, 1/12th of reported LD₅₀.

Conclusion: MP elicits a dose-dependent Th1 immune response.     

Effects of garlic polysaccharide on alcoholic liver fibrosis and intestinal microflora in mice

Context: Alcoholic liver fibrosis (ALF) is treatable and reversible consequence of liver disease. Intestinal microflora plays an important role in the progression of liver disease. Garlic (Allium sativum L. [Amaryllidaceae]) has been consumed as a traditional medicine to treat liver injury.

Objective: To investigate the effects of garlic polysaccharide (GP) on ALF and intestinal microflora in mice.

Materials and methods: KM mice were orally administered with alcohol (56%, 6?mL/kg) for 30?d to establish ALF model, and divided into four groups together with control group (water only). Hugan tablet (60?mg/kg) or GP (250 and 150?mg/kg) were given 5?h after each dose of alcohol. Biochemical markers in serum and liver homogenate were determined with kits. Alteration of intestinal microflora, and protein expressions of TGF-β1, TNF-α and decorin were detected.

Results: In GP-H group, ALT and AST decreased to 18.85?±?4.71?U/L and 40.84?±?7.89?U/L. MDA, TC, TG and LDL-C decreased to 2.32?±?0.86?mmol/mg, 0.21?±?0.12?mmol/L, 0.96?±?0.31?mmol/L and 0.084?±?0.027?mmol/L. SOD, GSH-Px and GSH increased to 118.32?±?16.32?U/mg, 523.72?±?64.20?U/mg and 0.56?±?0.05?mg/g. Ratios of TGF-β1 and TNF-α decreased to 0.608?±?0.170 and 1.057?±?0.058, decorin increased to 2.182?±?0.129. Lachnospiraceae and Lactobacillus increased, Facklamia and Firmicutes decreased with GP pretreatment.

Discussion and conclusions: Intestinal microflora provides novel insight into the mechanisms of GP that may be used to treat ALF and intestinal microflora dysbiosis.