Nature cures nature: Hypericum perforatum attenuates physical withdrawal signs in opium dependent rats

Context: Hypericum perforatum Linn. (Hypericaceae) (St. John’s wort) attenuates opium withdrawal signs.

Aim: To explore the therapeutic potential of Hypericum perforatum in the management of opium-induced withdrawal syndrome.

Materials and methods: The effect of the Hypericum perforatum hydro-ethanol extract was investigated for potential to reverse naloxone (0.25?mg/kg)-induced opium withdrawal physical signs. Rats received opium extract (80–650?mg/kg) twice daily for 8 days along with Hypericum perforatum (20?mg/kg, orally) twice daily in chronic treatment and the same single dose 1?h before induction of withdrawal syndrome in the acute treated group.

Results: Hypericum perforatum reduced stereotype jumps and wet dog shake number in the chronic treatment compared to the saline control group (F(2, 24)?=?3.968, p?F(2, 24)?=?3.689, p?F(2, 24)?=?4.850, p?F(2, 24)?=?4.88, p?F(2, 240?=?5.364, p?F(2, 24)?=?4.907, p?Discussion and conclusion: This study reveals that the extract of Hypericum perforatum attenuates some physical signs of opium withdrawal syndrome possibly through direct or indirect interaction with opioid receptors. Further study is needed to clarify its mechanism.     

Evaluation of the antidiarrheal and antioxidant properties of Justicia hypocrateriformis

Content: Justicia hypocrateriformis Vahl (Acanthaceae) is used as an herbal remedy for diarrhea in Cameroon folk medicine.

Objective: This study evaluates the antidiarrheal and antioxidant properties of the aqueous extract of J. hypocrateriformis (JH).

Materials and methods: Preliminary phytochemical screening and an acute toxicity testing of the extract were carried out. The antidiarrheal activity of JH extract (100, 250, and 500?mg/kg) was assessed at curative and preventive levels in castor oil-induced diarrhea in mice. The antioxidant activity was measured by ferric reducing antioxidant power (FRAP), total phenolic content, and radical scavenging activity.

Results: A high lethal dose (LD₅₀) of 14.35?g/kg obtained in acute toxicity implies the extract is not toxic. Phytochemical screening revealed the presence of phenols, tannins, flavonoids, saponins, anthraquinones, and anthocyanins. JH showed a significant protection against castor oil-induced diarrhea as evidenced by a decrease in the number of defecation and wet stool. JH (100–500?mg/kg, p.o.) produced a non-significant dose-dependent decrease in castor oil-induced intestinal transit in the preventive study. In the curative and in healthy mice study, the decrease was only significant at 500?mg/kg. JH possessed a radical scavenging activity with an IC₅₀ of 9.93?mg/ml compared to 4.90?mg/ml for catechin. JH FRAP of 2703.77?±?0?mg/g (catechin equiv) and phenolic concentration of 14?169.99?±?612.39?mg/g (catechin equiv) were also obtained.

Conclusion: Justicia hypocrateriformis extract possesses antidiarrheal activity supported by its antioxidant potential and phytochemical constituents.     

The application of 1,8-cineole,a terpenoid oxide present in medicinal plants,inhibits castor oil-induced diarrhea in rats

Abstract

Context: 1,8-Cineole, a terpene, characterized as a major constituent occurring in the essential oils of several aromatic plants. It is widely used in pharmaceutical industry, as a food additive and for culinary purposes.

Objective: This study investigates the inhibitory effect of 1,8-cineole on transit time and diarrhea in animal models.

Materials and methods: Acute toxicity and lethality of 1-8-cineole was determined by Lork’s guidelines. The antidiarrheal effect of 1,8-cineole was investigated by determining the intestinal transit and enterpooling in rats. In all experiments, different doses of 1,8-cineole (20–120?mg/kg), atropine, and loperamide were administered orally.

Results: The LD₅₀ of 1,8-cineole for oral administration was estimated to be 1280?mg/kg. 1,8-Cineole (20–120?mg/kg) did not show a significant decrease in small intestine transit (p?>?0.05); however, the highest dose displayed a significant decrease in comparison with atropine (p?<?0.05). This substance decreased the peristaltic index value to 68?±?0.36% at a dose of 120?mg/kg compared with the control group (85.22?±?4.31%) in the castor oil transit test. 1,8-Cineole significantly delayed the onset of diarrhea to ?142.33?±?6.08?min at 120?mg/kg, while the time was 103.66?±?20.73?min for the control and >240?min for the loperamide. Moreover, 1,8-cineole significantly decreased intestinal fluid accumulation (p?<?0.05).

Conclusions: This study demonstrated antispasmodic and antisecretory activities of 1,8-cineole and rationalized the traditional use of the plant containing various levels of this terpene in the treatment of gastrointestinal complains such as diarrhea.     

The effect of Hypericum perforatum on isolated rat aorta

Context: Different Hypericum species such as Hypericum perforatum (HP) L. and Hypericum triquetrifolium Turra are well known and widely used traditional medicine in Turkey.

Objectives: We investigated the effect of standardized HP extract on endothelium and vascular function.

Materials and methods: After suspending the aortas with endothelium in organ baths containing Krebs solution, contractile and relaxant responses were assessed in the absence and presence of HP (0.05?mg/ml).

Results: Although there were significant reductions in the contractile responses to phenylephrine (1113.73?±?164.11; 477.40?±?39.94; p?<?0.05) and potassium chloride (745.58?±?66.73; 112.58?±?26.58; p?<?0.05), no differences in the relaxant responses to acetylcholine (94.61?±?2.65; 87.79?±?9.40) and sodium nitroprusside (108.82?±?5.06; 106.43?±?7.45) were observed.

Discussion and conclusion: These data suggest that even the high dose of HP intervention does not bring any harmful effect on endothelium and smooth muscle function; meanwhile it might be beneficial on some of diseases accompanied with increased vascular contraction.     

Evaluation of antinociceptive and antidiarrhoeal properties of Manilkara zapota leaves in Swiss albino mice

Context Manilkara zapota (L.). P. Royen. (Sapotaceae) has been used in folk medicine to treat pain, diarrhoea, inflammation, arthralgia, and other disorders.

Objective Screening of Manilkara zapota leaves ethanol extract and its different solvent soluble fractions for possible antinociceptive and antidiarrhoeal activities in Swiss albino mice.

Materials and methods The extract and various fractions (200 and 400?mg/kg body weight; p.o.) were tested for peripheral and central antinociceptive activity by acetic acid-induced writhing and radiant heat tail-flick method, respectively; castor oil-induced diarrhoeal model was used to evaluate antidiarrhoeal activity at both doses. All the samples were administered once in a day and the duration of study was approximately 5?h.

Results Ethanol extract (400?mg/kg), petroleum ether fraction (400?mg/kg), and ethyl acetate fraction (400?mg/kg) showed significant peripheral antinociceptive activity having 59.89, 58.24, and 46.7% (p?<?0.001) of writhing inhibition, respectively, which is comparable with that of standard diclofenac (59.34% inhibition). The ethanol extract (400?mg/kg) and petroleum ether fraction (400?mg/kg) also showed promising central analgesic activity having 74.15 and 82.15% (p?<?0.001) elongation of reaction time, respectively, at 90?min after administration of sample which is also similar to that obtained by morphine (85.84% elongation). In antidiarrhoeal activity screening, ethanol extract (200 and 400?mg/kg) showed significant inhibition of defecation by 53.57 and 60.71%, respectively (p?<?0.001) compared with that of loperamide (71.42%).

Discussion and conclusion The findings of the studies demonstrated antinociceptive and antidiarrhoeal activities of M. zapota leaves which could be the therapeutic option against pain and diarrhoeal disease.     

Effects of exenatide versus sitagliptin on postprandial glucose,insulin and glucagon secretion,gastric emptying,and caloric intake: a randomized,cross-over study

ABSTRACT

Background: This study evaluated the effects of exenatide, a GLP-1 receptor agonist, and sitagliptin, a DPP-4 inhibitor, on 2-h postprandial glucose (PPG), insulin and glucagon secretion, gastric emptying, and caloric intake in T2D patients.

Methods: This double-blind, randomized cross-over, multi-center study was conducted in metformin-treated T2D patients: 54% female; BMI: 33?±?5?kg/m²; HbA_1c: 8.5?±?1.2%; 2-h PPG: 245?±?65?mg/dL. Patients received exenatide (5?µg BID for 1 week, then 10?µg BID for 1 week) or sitagliptin (100?mg QAM) for 2 weeks. After 2 weeks, patients crossed-over to the alternate therapy. Postprandial glycemic measures were assessed via standard meal test; caloric intake assessed by ad libitum dinner (subset of patients). Gastric emptying was assessed by acetaminophen absorption (Clinicaltrials.gov Registry Number: NCT00477581).

Results: After 2 weeks of therapy, 2-h PPG was lower with exenatide versus sitagliptin: 133?±?6?mg/dL versus 208?±?6?mg/dL, p?<?0.0001 (evaluable, N?=?61). Switching from exenatide to sitagliptin increased 2-h PPG by +73?±?11?mg/dL, while switching from sitagliptin to exenatide further reduced 2-h PPG by ?76?±?10?mg/dL. Postprandial glucose parameters (AUC, C_ave, C_max) were lower with exenatide than sitagliptin (p?<?0.0001). Reduction in fasting glucose was similar with exenatide and sitagliptin (?15?±?4?mg/dL vs. ?19?±?4?mg/dL, p?=?0.3234). Compared to sitagliptin, exenatide improved the insulinogenic index of insulin secretion (ratio exenatide to sitagliptin: 1.50?±?0.26, p?=?0.0239), reduced postprandial glucagon (AUC ratio exenatide to sitagliptin: 0.88?±?0.03, p?=?0.0011), reduced postprandial triglycerides (AUC ratio exenatide to sitagliptin: 0.90?±?0.04, p?=?0.0118), and slowed gastric emptying (acetaminophen AUC ratio exenatide to sitagliptin: 0.56?±?0.05, p?<?0.0001). Exenatide reduced total caloric intake compared to sitagliptin (?134?±?97?kcal vs. +130?±?97?kcal, p?=?0.0227, N?=?25). Common adverse events with both treatments were mild to moderate in intensity and gastrointestinal in nature.

Conclusions: Although this study was limited by a 2-week duration of exposure, these data demonstrate that, exenatide had: (i) a greater effect than sitagliptin to lower postprandial glucose and (ii) a more potent effect to increase insulin secretion and reduce postprandial glucagon secretion in T2D patients. In contrast to sitagliptin, exenatide slowed gastric emptying and reduced caloric intake. These key findings differentiate the therapeutic actions of the two incretin-based approaches, and may have meaningful clinical implications.     

Antidiarrheal mechanism of Carpolobia lutea leaf fractions in rats

Context: Carpolobia lutea G. Don (Polygalaceae) leaf is reputable as an antidiarrheal agent among the Efik and Ibibio tribe of Akwa Ibom State, Nigeria. The crude extract is reported to show antidiarrheal and antiulcer effects in rodents.

Objective: The isolation and characterization of drug molecules from the leaf fraction with antidiarrheal bioactivity and determination of mechanism of action are reported.

Material and methods: Gradient extraction by maceration yielding n-hexane, chloroform, ethyl acetate, and ethanol fractions (770?mg/kg) were used to establish the fractions suitable for drug discovery. The antidiarrheal effect of the leaf fractions of Carpolobia lutea was evaluated using castor oil–induced diarrhea, castor oil–induced intestinal transit, and enteropooling.

Results: Results indicate that all fractions produced a significant (p?<?0.01–0.001) decrease in castor oil–induced diarrhea in rats. This effect was not antagonized by isosorbide dinitrate (150?mg/kg, p.o), diphenoxylate (5?×?10^?3 mg/kg p.o) and yohimbine (1?mg/kg, s.c.) except for the chloroform fraction. The ethyl acetate fraction produced 100% inhibition of intestinal transit, an effect greater than pure drug. Phytochemical analysis of the ethyl acetate fraction yielded polyphenolic compounds.

Conclusion: The leaf fractions contain two types of antidiarrheal agents, one mediating its effect through α₁-presynaptic adrenoceptor while the other does not. Polyphenols isolated may in part lend credence for observed antidiarrheal activity.     

Pharmacological properties of lichen Cladonia clathrata

Cladonia clathrata Ahti & L. Xavier-Filho (Cladoniaceae) is a lichen; several Cladonia species extracts have been used for various remedies in folk medicine. In order to evaluate the actions of this lichen, studies were performed on antinociceptive, anti-inflammatory, and antioxidant activities. The hydroalcoholic extract (HE) of C. clathrata stems was used in the following experiments. Oral treatment with the HE of C. clathrata elicited inhibitory activity (p?<?0.001) on acetic acid-induced abdominal writhes at 100 (47.2%), 200 (47.2%), and 400?mg/kg (86.4%), and reduced the formalin-induced nociception on both the neurogenic (400?mg/kg, p?<?0.01) and inflammatory phases (200 and 400?mg/kg, p?<?0.01). It was not associated with non-specific effects, such as muscle relaxation or sedation. The HE reduced the carrageenan-induced edema formation at 100, 200, and 400?mg/kg (p?<?0.05) and inhibited neutrophil migration into the peritoneal cavity at 400?mg/kg (p?<?0.001). The HE of C. clathrata reacted with the DPPH radical and reduced the same by 50.19%, and exhibited an IC₅₀ value of 69.25?±?0.65 μg/mL. The HE of C. clathrata stems shows antinociceptive and anti-inflammatory activities, with a moderate antioxidant potential.     

Evaluation of the anti-diarrheal activity of Salvia connivens

Context: Diarrheal disease is a leading cause of mortality and morbidity and accounts for 5–8 million deaths worldwide each year. Salvia connivens Epling (Lamiaceae) is used to treat sore throat, fevers, diarrhea, malaria, and also is used as an antipyretic.

Objective: The present study evaluates the efficacy of S. connivens in the treatment of diarrhea using animal models.

Materials and methods: The anti-diarrheal effect of methanol extract of S. connivens was investigated on mice with castor oil, arachidonic acid (AA) or prostaglandin E₂ (PGE₂)-induced diarrhea. On Wistar rats, the activity was evaluated on the intestinal transit and Castor oil-induced enteropooling.

Results: The methanol extract at doses of 6.25, 12.5, 25, 50, 100, and 200?mg/kg on castor oil-induced diarrhea reduced the diarrhea by 32.3, 41.9, 67.7, 74.2, 83.3, and 100%, respectively. Additionally, this extract, at doses of 200?mg/kg, inhibited AA-induced diarrhea by 100%. The methanol extract produced no effect on PGE₂-induced diarrhea at the same doses. In Wistar rats, at dose of 200?mg/kg, the methanol extract inhibited intestinal transit and decreased the volume of intestinal secretion induced by castor oil.

Discussion: The methanol extract showed anti-diarrheal effect on the animal models used. Phytochemical screening revealed the presence of alkaloids, tannins, and saponins which may be responsible for this effect. The extract did not cause any mortality or any visible signs of toxicity or differences in food and water uptake were seen.

Conclusions: These results justify the use of S. connivens as an anti-diarrheal agent.     

Protective Effect of Aegle marmelos Fruit in Gastrointestinal Dysfunction in rats

The effect of the ethanol extract of the unriped fruits of Aegle marmelos Correa was assessed on experimentally induced diarrhoea and gastric ulceration in rats. The extract (50, 100 and 200?mg/kg, p.o.) exhibited a dose-dependent decrease in the intestinal propulsion from 61.79–39.32% which is equivalent to 38.21–60.68% intestinal propulsion inhibition (control 58.3 ± 3.4 inhibition, P < 0.5 to P < 0.001) and caused a dose-dependent decrease in the total number of faecal matter in castor oil-induced diarrhoea (control 70, reduced to 51 and 42 at 100 and 200?mg/kg extract, p.o.). Further, yohimbine, a α₂ adrenoreceptor blocker, attenuated the antidiarrhoeal effect of the extract in a dose of 200?mg/kg to 17.14%, and diphenoxylate by 74.28%. The extract also reduced the ulcer index induced by ethanol (control 18.7 ± 4.4, 34.22–72.73% protection), aspirin (control 22.6 ± 3.4, 36.73–81.42% protection) and cold restraint stress (control 23.8 ± 3.2, 56.72% and 81.51% protection). Further study on tissue lipid peroxidation was significantly increased (P < 0.001) as evidenced by accumulation of malondialdehyde in cold restraint stress ulcers. Administration of A. marmelos (100 and 200?mg/kg), cimetidine 50?mg/kg and reduced glutathione (150?mg/kg) prior to cold restraint stress causes significant decrease in ulcer index and lipid peroxidation (P < 0.01 to P < 0.001). The result showed that A. marmelos had significant antidiarrhoeal and ulcer protective activity by scavenging the reactive oxygen species on the cold restraint stress-induced gastric damage.     

Alteration of pentylenetetrazole-induced seizure threshold by chronic administration of ginger (Zingiber officinale) extract in male mice

Abstract

Context: Zingiber officinale Roscoe (Zingiberaceae), or ginger, used in traditional Chinese medicine, has antioxidant activity and neuroprotective effects. The effects of this plant on clonic seizure have not yet been studied.

Objective: The present study evaluated the anticonvulsant effect of ginger in a model of clonic seizures induced with pentylenetetrazole (PTZ) in male mice.

Materials and methods: The anticonvulsant effect of Z. officinale was investigated using i.v. PTZ-induced seizure models in mice. Different doses of the hydroethanolic extract of Z. officinale (25, 50, and 100?mg/kg) were administered intraperitonal (i.p.), daily for 1 week before induction of PTZ. Phenobarbital sodium (30?mg/kg), a reference standard, was also tested for comparison. The effect of ginger on to the appearance of three separate seizure endpoints, e.g., myoclonic, generalized clonic, and tonic extension phase, was recorded.

Results: Hydroethanolic extract of Z. officinale significantly increased the onset time of myoclonic seizure at doses of 25–100?mg/kg (55.33?±?1.91 versus 24.47?±?1.33?mg/kg, p?<?0.001) and significantly prevented generalized clonic (74.64?±?3.52 versus 47.72?±?2.31?mg/kg, p?<?0.001) and increased the threshold for the forelimb tonic extension (102.6?±?5.39 versus 71.82?±?7.82?mg/kg, p?<?0.01) seizure induced by PTZ compared with the control group.

Discussion and conclusion: Based on the results, the hydroethanolic extract of ginger has anticonvulsant effects, possibly through an interaction with inhibitory and excitatory systems, antioxidant mechanisms, and oxidative stress inhibition.     

Dual targeting of TNF-α and free radical toxic stress as a promising strategy to manage experimental polycystic ovary

Context: It is now clear that oxidative stress (OS) and chronic low-grade inflammation are two main pathways involved in polycystic ovary syndrome (PCOS) pathogenesis. Therefore, simultaneous targeting of these pathways by means of carvedilol and Semelil (ANGIPARS?), as established medicines with dual anti-cytokine and anti-oxidant potential may be a therapeutic alternative approach to the current treatments.

Objective: The objective of this study is to study the protective effects of carvedilol and ANGIPARS? on inflammatory and oxidative response in hyperandrogenism-induced polycystic ovary (PCO).

Materials and methods: The murine model of PCO was induced by letrozole (1?mg/kg/d; orally) and effective doses of carvedilol (10?mg/kg/d; orally) and ANGIPARS? (2.1?mg/kg/d; orally) were administrated for 21?d in PCO and non-PCO healthy rats. Ovarian folliculogenesis, sex hormones concentrations, OS, inflammatory, and metabolic biomarkers were assessed in serum and ovaries.

Results: PCO rats exhibited ovarian cystogenesis which was preserved by the application of carvedilol and ANGIPARS?. In comparison with controls, decreased level of the total antioxidant power (TAP) and higher levels of reactive oxygen species (ROS) and lipid peroxidation (LPO) in serum and ovaries (2.41?±?0.67 versus 0.72?±?0.11; and 0.17?±?0.04 versus 0.05?±?0.01; 5.48?±?1.30 versus 10.56?±?0.77; and 7.06?±?1.94 versus 17.98?±?0.98; p?<?0.05, respectively) were detected in PCO rats. Moreover, the PCO rats exhibited hyperandrogenism due to a 3.7-fold increase in serum testosterone concentration (35.04?±?3.17 versus 131.09?±?13.24; p?<?0.05) along with a 2.98-fold decrease in serum progesterone (6.19?±?0.40 versus 18.50?±?1.03; p?<?0.05) and 5.2-fold decrease in serum estradiol (9.30?±?0.61 versus 48.3?±?2.10; p?<?0.05) when compared with those of the control group. However, similar to the control group, normal levels of OS markers and sex hormones were detected in ANGIPARS? and carvedilol co-treated PCO rats. Besides, when compared with controls, increased levels of TNF-α (770.75?±?42.06 versus 477.14?±?28.77; p?<?0.05) and insulin (1.27?±?0.10 versus 0.36?±?0.05; p?<?0.05) in PCO rats were significantly inhibited by carvedilol and ANGIPARS? co-treatment.

Discussion and conclusion: We evidenced the beneficial effects of carvedilol and ANGIPARS? in PCO, which underpin the new alternative approach in using these kinds of medicines in female reproductive disorders.     

Combination therapy of Chinese herbal medicine Fructus Ligustri Lucidi with high calcium diet on calcium imbalance induced by ovariectomy in mice

Abstract

Context: Our previous biological study demonstrated that Fructus Ligustri Lucidi (FLL), the fruit of Ligustrum lucidum Ait. (Oleaceae), could be used to maintain calcium balance and prevent age-related osteoporosis since it effectively decreased calcium loss and increased calcium retention in rats.

Objective: This study investigates the combination effect of the Chinese herbal medicine FLL and a high calcium diet on calcium imbalance induced by ovariectomy in mice.

Materials and methods: The ovariectomized (OVX) mice were orally treated with vehicle, FLL extract (700?mg/kg), milk powder (5?g/mice) fortified with calcium (1.0% Ca) and the combination of FLL with milk powder. After 6 weeks of treatment, urine, serum, and tibia were preserved for biochemical analysis and kidneys were taken for gene expression analysis.

Results: The combination treatment of FLL and a high calcium diet significantly increased bone calcium content (6.80?±?0.34?mg) by 22% (p?<?0.05) and decreased urine calcium excretion (0.099?±?0.009?mg/mg) by 62% (p?<?0.01) as compared with those of the OVX group (bone Ca, 5.57?±?0.31?mg; urine Ca/Cr, 0.261?±?0.017?mg/mg). The mRNA expression of renal calcium-binding protein-9k (CaBP-9k) and calcium-sensing receptor (CaSR) in combination treatment group was significantly up-regulated and down-regulated, respectively, as compared with those of the OVX group.

Conclusion: The beneficial effects of this combination therapy on calcium balance of OVX mice were, at least partially, attributed to its regulation on mRNA expression of CaBP-9k and CaSR in kidney.     

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.     

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.     

St. John's wort may relieve negative effects of stress on spatial working memory by changing synaptic plasticity

Beneficial effects of St. John's wort (Hypericum perforatum) in the treatment of stress-evoked memory impairment were recently described. In this study, we tested a hypothesis that St. John's wort alleviates stress- and corticosterone-related memory impairments by restoring levels of synaptic plasticity proteins: neuromoduline (GAP-43) and synaptophysin (SYP) in hippocampus and prefrontal cortex. Stressed and corticosterone-treated rats displayed a decline in the acquisition of spatial working memory (p?<?0.001) in the Barnes maze (BM). Chronic administration of H. perforatum (350?mg?kg^?1 for 21?days), potently and significantly improved processing of spatial information in the stressed and corticosterone-injected rats (p?<?0.001). Also, St Johns' wort statistically significantly (p?<?0.05) increased levels of GAP-43 and SYP, respectively in the hippocampi and prefrontal cortex as measured by western immunoblotting. We found that H. perforatum prevented the deleterious effects of both chronic restraint stress and prolonged corticosterone administration on working memory measured in the BM test. The herb significantly (p?<?0.01) improved hippocampus-dependent spatial working memory in comparison with control and alleviated some other negative effects of stress on cognitive functions. These findings increase our understanding of the reaction of the hippocampus and prefrontal cortex to stressful assaults and provide new insight into the possible actions of H. perforatum in the treatment of patients with impaired adaptation to environmental stressors and simultaneously suffering from cognitive impairment.     

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.     

Naringenin ameliorates streptozotocin-induced diabetic rat renal impairment by downregulation of TGF-β1 and IL-1 via modulation of oxidative stress correlates with decreased apoptotic events

Context: Naringenin, a flavonone and a nutritive antioxidant which is mostly obtained from grapefruit, orange or tomato skin, has been extensively studied due to its radical scavenging activity.

Objective: The present study investigates the protective effect of naringenin on rat kidney after streptozotocin-induced diabetes.

Materials and methods: Sixty male Wistar rats were divided into six groups. Diabetes was induced by a single intraperitoneal injection of streptozotocin (50?mg/kg) in groups II, III and IV. Naringenin 5?mg/kg body weight was given to groups III and V, but 10?mg/kg was given to groups IV and VI, orally once a day for 10 weeks. After which all animals were sacrificed, and the biochemical, histopathological, immunohistochemical and apoptotic assays were conducted.

Results: Naringenin treatment with 5 and 10?mg/kg significantly decreased (p?<?0.05) the serum biochemical parameters, elevated tissue malondialdehyde levels and increased (p?<?0.01) the reduced superoxide dismutase, catalase and reduced glutathione enzyme activities in the diabetic kidney. Diabetes-induced naringenin-treated groups showed an improved histology and revealed a significant reduction in apoptosis activity (7.2?±?0.01 and 1.8?±?0.05) and in expression of TGF-β1 (18.9?±?3.4 and 10.2?±?2.1) at a dose of 5 and 10?mg/kg, respectively. Similarly, in contrast to the diabetic group, a significant difference was observed in the IL-1 expression (15.68?±?4.3) in 5?mg/kg and (9.85?±?2.1) in 10?mg/kg naringenin-treated groups.

Conclusion: Naringenin acts as a protective agent in diabetic renal impairment by altering oxidative stress, modulation of cytokines expression and apoptotic events.     

Antidiarrhoeal activity of the standardised extract of <Emphasis Type="Italic">Cinnamomum tamala</Emphasis> in experimental rats

The present study was designed to investigate the antidiarrhoeal potential of 50% ethanolic extract of Cinnamomum tamala on experimentally induced castor oil diarrhoea, gastric emptying of phenol red meal, gastrointestinal transit of charcoal meal and in vitro mast cell degranulation activity. C. tamala extract (25, 50 and 100 mg/kg, orally) produced a dose-dependent reduction in the total amount of faecal matter in castor oil-induced diarrhoea. The mean distance travelled by charcoal meal at 50 and 100 mg/kg of extract showed a significant reduction in the secretion of gastrointestinal fluid accumulation by 32.5–65.0%. The Na⁺ and K⁺ concentrations on castor oil-induced fluid accumulation showed a greater inhibitory effect on Na⁺ levels than on K⁺ concentrations. C. tamala significantly reduced the lipid peroxidation (P < 0.001) and increased the catalase (P < 0.01) activity in comparison to the castor oil-induced groups. C. tamala leaf extract did not show any significant effect at a higher dose (15 mg/ml) on mast cell degranulation. However, the extract in the dose of 5 and 10 mg/ml conferred significant mast cell protective action (P < 0.001). The percentage of eugenol in extract is 3.8% w/w, and total tannin is 247.5 mg/g. The result indicates the Indian spice C. tamala is useful for diarrhoea.     

Prevention of arsenic-mediated reproductive toxicity in adult female rats by high protein diet

Abstract

Context: The detrimental effects of arsenic on female reproductive functions may involve overt oxidative stress. Casein and pea [Pisum sativum Linn. (Fabaceae)] proteins have antioxidant properties.

Objective: To investigate the role of casein- and pea-supplemented high-protein diet (HPD) in utero-ovarian protection from arsenic toxicity.

Materials and methods: Adult female Wistar rats were orally gavaged with vehicle (Gr-I) or arsenic at 3?ppm/rat/d (Gr-II and Gr-III) for 30 consecutive days, when they were maintained on either regular diet containing 18% protein (Gr-I and Gr-II), or HPD containing 27% protein in the form of casein (20%) and pea (7%) (Gr-III). Reproductive functions were evaluated using a battery of biochemical and histological techniques.

Results: As compared to Gr-I, the Gr-II rats suffered from loss of estrous cyclicity, reduction in weight (mg/100?g body weight) of ovary (Gr-I: 54.3?±?4.2 versus Gr-II: 35.8?±?1.6; p?<?0.001) and uterus (Gr-I: 161.7?±?24.6 versus Gr-II: 94.44?±?13.2; p?<?0.05), utero-ovarian degeneration, attenuated ovarian activities (unit/mg tissue/h) of Δ⁵, 3β-hydroxysteroid dehydrogenase (Gr-I: 3.41?±?0.12 versus Gr-II: 2.31?±?0.09; p?<?0.01) and 17β-hydroxysteroid dehydrogenase (Gr-I: 3.82?±?0.57 versus Gr-II: 1.24?±?0.19; p?<?0.001), and decreased serum estradiol level (pg/ml) (Gr-I: 61.5?±?2.06 versus 34.1?±?2.34; p?<?0.001). Ovarian DNA damage was preponderant with blatant generation of malondialdehyde (nM/mg tissue; Gr-I: 15.10?±?2.45 versus Gr-II: 29.51?±?3.44; p?<?0.01) and attenuated superoxide dismutase activity (unit/mg tissue) (Gr-I: 2.18?±?0.19 versus Gr-II: 1.33?±?0.18; p?<?0.05). The Gr-III rats were significantly protected from these ill effects of arsenic.

Discussion and conclusion: HPD, by way of antioxidant properties, may find prospective role in the protection of reproductive damage caused by arsenic.