Influence of Griffonia simplicifolia on male sexual behavior in rats: Behavioral and neurochemical study

The seeds of Griffonia simplicifolia Baill. are rich in 5-HTP (5-hydroxytryptophan), a direct precursor of the neurotransmitter serotonin. In the present study we investigated the influence of the plant extract on male sexual behavior. The seed extract was orally administered to Sprague-Dawley male rats at three dose levels (25, 50 and 100 mg/kg) both acutely and subchronically (daily for 9 days). Mating test with receptive female rats was performed 60 min after the acute treatment or the last dose when repetitively administered. Mount, intromission and ejaculation latencies and post-ejaculatory interval were recorded. Food intake and body weight were measured over the 9-day period of treatment. Microdialysis technique was used to detect the extracellular levels of serotonin (5-HT) and its metabolite 5-hydroxyindoleacetic acid (5-HIAA) in rat brain following the acute administration of the extract dosed at 100 mg/kg. The acute treatment significantly increased mount latency (at any dosage), intromission and ejaculation latencies (at 100 mg/kg) and post-ejaculatory interval (at 50 and 100 mg/kg). On the contrary the subchronic treatment failed to exert a significant influence on copulatory behavior. The daily administration of the extract dosed at 50 and 100 mg/kg for 9 days significantly reduced food intake and body weight. Finally in the microdialysis experiments we found a dramatic increase in 5-HT and its metabolite 5-HIAA.     

Central nervous system activities of two diterpenes isolated from Aloysia virgata

Using the guide of a competitive assay for the benzodiazepine binding site in the γ-aminobutyric acid type A receptor (GABA_A), two active diterpenes were isolated from the aerial parts of Aloysia virgata (Ruíz & Pavón) A.L. Jussieu var. platyphylla (Briquet) Moldenke. These compounds, identified as (16R)-16,17,18-trihydroxyphyllocladan-3-one (1) and (16R)-16,17-dihydroxyphyllocladan-3-one (2) on the basis of spectral data, competitively inhibited the binding of [³H]-FNZ to the benzodiazepine binding site with K_i ± S.E.M. values of 56 ± 19 μM and 111 ± 13 μM, respectively. The behavioral actions of these diterpenes, intraperitoneally (i.p.) administered in mice, were examined in the plus-maze, holeboard, locomotor activity and light/dark tests. Compound 1 exhibited anxiolytic-like effects in mice evidenced by a significant increase of the parameters measured in the holeboard test (the number of head dips at 0.3 mg/kg and 3 mg/kg, the rears at 1 mg/kg and the time spent head-dipping at 3 mg/kg), in the plus-maze assay (the percentage of open arm entries at 1 mg/kg) and in the light/dark test (the time in light and the number of transitions at 1 mg/kg). Compound 2 augmented the number of rearings in the holeboard apparatus (at 0.3 mg/kg and 1 mg/kg) and the locomotor activity (at 1 mg/kg). These results reveal the presence of neuroactive compounds in Aloysia virgata.     

Reproductive toxicologic evaluations of Bulbine natalensis Baker stem extract in albino rats

The effects of oral administration of aqueous extract of Bulbine natalensis Baker stem at daily doses of 25, 50, and 100 mg/kg body weight on the reproductive function of Wistar rats were evaluated. The indices of mating and fertility success as well as quantal frequency increased after 7 days of treatment in all the dose groups except the 100 mg/kg body weight group. The number of litters was not statistically different (P > 0.05) from the control. Whereas the absolute weights of the epididymis, seminal vesicle, and prostate were not affected, that of the testes was significantly increased. The epididymal sperm count, motility, morphology, and viscosity were not different from the control after 7 days of treatment. The male rat serum testosterone, progesterone, luteinizing hormone, and follicle-stimulating hormone significantly increased in the 25 and 50 mg/kg body weight groups, whereas the estradiol concentration decreased significantly at all the doses. The extract dose of 100 mg/kg body weight decreased the serum testosterone and progesterone levels in male rats. The prolactin concentration was not affected by all the doses. All the indices of reproduction, maternal, embryo/fetotoxic, teratogenic, and reproductive hormones in the female rats were not statistically different from that of their control except the resorption index, which increased at the dose of 100 mg/kg body weight of the extract. Histologic examination of the cross section of rat testes that received the extract at all the doses investigated revealed well-preserved seminiferous tubules with normal amount of stroma, normal population of spermatogenic and supporting cells, as well as normal spermatocytes within the lumen. The results revealed that the aqueous extract of Bulbine natalensis stem at doses of 25 and 50 mg/kg body weight enhanced the success rate of mating and fertility due to increased libido as well as the levels of reproductive hormones in male rats. The absence of alterations in the reproductive parameters of female rats at doses of 25 and 50 mg/kg body weight of Bulbine natalensis stem extract suggest that the extract is “safe” for use at these doses by females during the organogenic period of pregnancy, whereas the extract dose of 100 mg/kg body weight portends a negative effect on some reproductive functions of male and female rats.     

Antidepressant effect and pharmacological evaluation of standardized extract of flavonoids from Byrsonima crassifolia

Byrsonima crassifolia (Malpighiaceae) has been used in traditional medicine for the treatment of some mental-related diseases; however, its specific neuropharmacological activities remain to be defined. The present study evaluates the anxiolytic, anticonvulsant, antidepressant, sedative effects produced by the extracts of Byrsonima crassifolia, and their influence on motor activity in ICR mice. Additionally, we determine the acute toxicity profiles of the Byrsonima crassifolia extracts and the presence of neuroactive constituents. Our results show that the methanolic extract of Byrsonima crassifolia produces a significant (P < 0.05) antidepressant effect in the forced swimming test in mice at 500 mg/kg dose. However, it does not possess anxiolytic, sedative, or anticonvulsant properties, and does not cause a reduction of mice locomotion (P > 0.05). Although the main compound of the methanolic extract was identified as quercetin 3-O-xyloside (12 mg/kg), our findings suggest that flavonoids, such as rutin (4.4 mg/kg), quercetin (1.4 mg/kg) and hesperidin (0.7 mg/kg), may be involved in the antidepressant effects. To the best of our knowledge, the present study constitutes the first report on the presence of the flavonoids with neuropharmacological activity rutin and hesperidin in Byrsonima crassifolia. In conclusion, the present results showed that the methanolic extract standardized on flavonoids content of Byrsonima crassifolia possesses potential antidepressant-like effects in the FST in mice, and could be considered as relatively safe toxicologically with no deaths of mice when orally administered at 2000 mg/kg.     

Involvement of nitric oxide (NO) signalling pathway in the antidepressant activity of essential oil of Valeriana wallichii Patchouli alcohol chemotype

Valeriana wallichii DC (Valerianaceae), popularly named as Indian valerian has been shown to exist as three chemotypes. The present study evaluated the antidepressant like effect of root essential oil of Valeriana wallichii patchouli alcohol chemotype in both acute and chronic treatment study using forced swim test (FST). Mice (n = 6 per group) received 10, 20 and 40 mg/kg p.o. doses of test drug. Single administration of oil significantly inhibited the immobility period (57.6% and 46.9%) at doses 20 and 40 mg/kg respectively without changing the motor function (p < 0.05). Similarly, daily administration of essential oil (20 mg/kg) for 14 days significantly reduced the immobility period (69.9%) in FST (p < 0.05). The neurotransmitter levels in mouse brain were estimated on day 14 after the behavioral study. Significant increase in the level of norepinephrine (29%) and serotonin (19%) (p < 0.05) was found at 20 mg/kg dose, while no change was observed at 10 and 40 mg/kg doses. The antidepressant-like effect of essential oil (20 mg/kg) was prevented by pretreatment of mice with l-arginine (750 mg/kg i.p.) and sildenafil (5 mg/kg i.p). On the contrary, pretreatment of mice with l-NAME (10 mg/kg i.p.) or methylene blue (10 mg/kg i.p.) potentiated the antidepressant action of essential oil (10 mg/kg). Taken together, these findings demonstrated that nitric oxide pathway is involved in mediating antidepressant like effect of essential oil from this chemotype.     

Possible fasciocidal activity of methanol extract of Dregea volubilis leaves

In eastern and southern part of India Dregea volubilis (Family Asclepediaceae) is widely used as anthelmintic in traditional system of medicine. The present study was conducted to evaluate the fasciocidal activity of the methanol extract of D. volubilis leaves (MEDV) and to observe the drug’s effect on organisms through scanning electron microscopic (SEM) study. Live parasites (Trematode: Fasciola gigantica) were collected in 0.9% phosphate-buffered saline from the bile ducts of buffalo. Those were incubated in the said media at 37 ± 1 °C either as control, or with MEDV at 5, 10, 25, 50 and 100 mg/ml as test groups or with albendazole at 10 mg/ml as standard group. The efficacy of the extract was determined on the basis of paralysis (temporary loss of spontaneous movement of the organisms) and/or death of the liver flukes. Death was confirmed when the organisms lost their motility permanently and their motility could not be revived even when vigorously shaken or dipped in warm water. MEDV at all concentration effectively paralyzed first and then killed the liver flukes (p < 0.001). Maximum fasciocidal activity was found with concentration of 100 mg/ml at 38.83 ± 3.41 min. Through SEM study, severe damages were observed in both the suckers as well as on the tegumental surfaces of the treated liver flukes. The study confirmed the fasciocidal activity of the MEDV.     

Hypotensive mechanism of the extracts and artemetin isolated from Achillea millefolium L. (Asteraceae) in rats

Traditional uses of Achillea millefolium L. (Asteraceae) include the treatment of cardiovascular diseases. In the present study, we used anesthetized rats to assess the hypotensive effect of a hydroethanolic extract (HEAM), and its dichloromethane (DCM), ethyl acetate (EA), butanolic (BT), and dichloromethane-2 (DCM-2) fractions, besides the flavonoid artemetin, isolated from A. millefolium. The oral administration of HEAM (100-300 mg/kg), DCM (20 mg/kg), DCM-2 (10-30 mg/kg), but not EA (10 mg/kg) and BT (50 mg/kg) fractions significantly reduced the mean arterial pressure (MAP) of normotensive rats. The phytochemical analysis by NMR ¹H of DCM and DCM-2 fractions revealed high amounts of artemetin, that was isolated and administered by either oral (1.5 mg/kg) or intravenous (0.15-1.5 mg/kg) routes in rats. This flavonoid was able to dose-dependently reduce the MAP, up to 11.47 ± 1.5 mm Hg (1.5 mg/kg, i.v.). To investigate if artemetin-induced hypotension was related to angiotensin-converting enzyme inhibition, we evaluated the influence of this flavonoid on the vascular effects of both angiotensin I and bradykinin. Intravenous injection of artemetin (0.75 mg/kg) significantly reduced the hypertensive response to angiotensin I while increased the average length of bradykinin-induced hypotension. Artemetin (1.5 mg/kg, p.o.) was also able to reduce plasma (about 37%) and vascular (up to 63%) ACE activity in vitro, compared to control group. On the other hand, artemetin did not change angiotensin II-induced hypertension. Our study is the first showing the hypotensive effects induced by the extract and fractions obtained from A. millefollium. In addition, our results disclosed that this effect may be, at least in part, associated with high levels of artemetin and its ability to decrease angiotensin II generation in vivo, by ACE inhibition.     

Spilanthes acmella ethanolic flower extract: LC-MS alkylamide profiling and its effects on sexual behavior in male rats

According to Indian Systems of Medicine, Spilanthes acmella (L.) Murr. (Family - Asteraceae), is considered effective in the treatment of sexual deficiencies especially due to ageing. In the present study, characterization of ethanolic extracts of the Spilanthes acmella flower and its effect on general mating pattern, penile erection and serum hormone levels of normal male Wistar albino rats were investigated and compared with sildenafil citrate. In vitro nitric oxide release was also investigated in human corpus cavernosum cell line. As N-alkylamides are a promising group, their profiling was performed using a gradient reversed phase high performance liquid chromatography/electrospray ionization ion trap mass spectrometry (HPLC/ESI-MS) method on an embedded polar column. MS¹ and MS² fragmentation data were used for identification purposes. For assessment of sexual behavior, animals were divided into five groups of eight male rats. The extracts (50, 100 and 150 mg/kg body weight/day) and sildenafil citrate (5 mg/kg body weight/day) (positive control) were administered orally for 28 days. The behavioral and sexual parameters were observed at days 0, 15, 28 and after a lapse of 7 and 14 days of discontinuance of drug treatment. Five N-isobutylamides, one 2-methylbutylamide and one 2-phenylethylamide were identified. The orally administered extract had a dose dependent positive effect on mounting frequency, intromission frequency and ejaculation frequency and the most significant effects (p < 0.05) were observed at 150 mg/kg treatment, even after a lapse of 7 and 14 days of discontinuance of drug treatment. A dose dependent effect was also observed on the FSH, LH and testosterone serum levels. With 150 mg/kg of ethanolic extract the values for FSH, LH and testosterone were 3.10 ± 0.25 mlU/ml, 6.87 ± 0.18 mlU/ml and 3.72 ± 0.12 ng/ml, respectively. In vitro nitric oxide release was 21.7 ± 2.9 μM, which was significantly higher compared to the control group (p < 0.01). Sildenafil citrate exhibited also a significant effect on NO release, but no effect on hormone levels of rats was observed. The aphrodisiac potential of an ethanolic Spilanthes acmella extract was demonstrated in vitro and in vivo. N-Alkylamides might attribute to the improved sexual potential. Study lends support to the traditional utilization of S. acmella as a sexual stimulating agent.     

Protective effect of Operculina turpethum against 7,12-dimethyl benz(a)anthracene induced oxidative stress with reference to breast cancer in experimental rats

Reactive oxygen species (ROS) directly or indirectly involves in multistage process of carcinogenesis. Antioxidant activity of methanolic extract of Operculina turpethum stems (MEOT) on 7,12 dimethylbenz(a)anthracene (DMBA) induced breast cancer was investigated in female Sprague-Dawley rats. Changes in the levels of lipid peroxidation and antioxidants system was evaluated in addition to tumour development. Twenty four female rats were divided into four groups: control, DMBA, DMBA + MEOT and MEOT. In the DMBA group, rats were intragastrically administered with 20 mg of DMBA using corn oil as vehicle. Animals of DMBA + MEOT group received a single dose of 20 mg of DMBA dissolved in corn oil intragastrically followed by O. turpethum extract (100 mg/kg body weight), while MEOT group received O. turpethum extract (100 mg/kg body weight) intragastrically daily for a period of 45 days. After the experimental period of 45 days, oxidative stress parameters were assessed in serum, liver and breast of both control and experimental groups. In addition to this, tumour weight of breast was also assessed. A significant increase in lipid peroxidation levels were observed in the tested samples of cancer induced rats while the activities of enzymic antioxidants such as superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx) and non-enzymic antioxidants like glutathione (GSH), ascorbic acid (Vitamin C) and α-tocopherol (Vitamin E) were decreased in cancer-bearing animals when compared to control animals. A significant (P < 0.05) increase in the tumour weight was observed in the breast of DMBA group and the breast tumour weight decreased significantly (P < 0.05) in the DMBA + MEOT groups. Oral administration of MEOT remarkably reduced the lipid peroxidation activity and increased the antioxidants level in drug treated animals and decreased the tumour weight significantly (P < 0.05). This result suggests that MEOT shows antioxidant activity and play a protective role against DMBA induced breast cancer.     

Protective effects of alkaloid extract from Leonurus heterophyllus on cerebral ischemia reperfusion injury by middle cerebral ischemic injury (MCAO) in rats

The neuronal damage following cerebral ischemia is a serious risk to stroke patients. The aim of this study was to investigate the neuroprotective effects of alkaloid extract from Leonurus heterophyllus (LHAE) on cerebral ischemic injury. After 24 h of reperfusion following ischemia for 2 h induced by middle cerebral artery occlusion (MCAO), some rats were intraperitoneally administered different doses of LHAE (3.6, 7.2, 14.4 mg/kg, respectively). Neurological examination was measured in all animals. Infarct volume, myeloperoxidase (MPO) activity, levels of nitrate/nitrite metabolite (NO) and apoptosis ratio of nerve fiber in brain were determined. The results showed that LHAE at 7.2 mg/kg or 14.4 mg/kg exerted significantly decreasing neurological deficit scores and reducing the infarct volume on rats with focal cerebral ischemic injury (p < 0.05). At those dose, the MPO content were significantly decreased in ischemic brain as compared with model group (p < 0.05). LHAE at 14.4 mg/kg significantly decreased the NO level compared with the model group (p < 0.05). In addition, LHAE significantly decreased the apoptosis ratio of nerve fiber compared with the model group (p < 0.05). This study suggests that LHAE may be used for treatment of ischemic stroke as a neuroprotective agent. Further studies are warranted to assess the efficacy and safety of LHAE in patients.     

Preparative separation of isoquinoline alkaloids from Stephania yunnanensis by pH-zone-refining counter-current chromatography

In this paper, five isoquinoline alkaloids were successfully separated from a crude extract of Stephania yunnanensis using pH-zone-refining counter-current chromatography in single-step. With a two-phase solvent system composed of methyl-tert-butyl ether (MtBE)–acetonitrile–water (2:2:3, v/v) where triethylamine (10 mM) was added to the upper organic phase as a retainer and hydrochloric acid (5 mM) to the aqueous mobile phase as an eluter. From 1.4 g crude extract, 68.7 mg isocorydine, 78.2 mg corydine, 583.4 mg tetrahydropalmatine, 36.3 mg N-methylasimilobine, and 47.3 mg anonaine were separated with purities over 90%. Their structures were identified by ¹H NMR, ¹³C NMR, ESI-MS data.     

Preparative separation of alkaloids from Nelumbo nucifera leaves by conventional and pH-zone-refining counter-current chromatography

Two modes of high-speed counter-current chromatography (HSCCC) were successfully applied to the separation of alkaloids from crude extract of Nelumbo nucifera leaves. The conventional HSCCC separations were performed with a two-phase solvent system composed of tetrachloromethane–CHCl₃–methanol–0.1 M HCl at a volume ratio of 1:3:3:2 (v/v/v/v), and 120 mg crude extract could be successfully separated. pH-Zone-refining CCC was performed with a two-phase solvent system composed of petroleum ether (60–90 °C)–ethyl acetate–methanol–water (5:5:2:8, v/v/v/v) where triethylamine (10 mM) was added to the upper organic stationary phase as a retainer and hydrochloric acid (5 mM) to the aqueous mobile phase as an eluent. From 4.0 g of the crude extract, 120 mg N-nornuciferine, 1020 mg nuciferine and 96 mg roemerine were obtained in a single run each with a purity of over 98% as determined by HPLC. The structures of the isolated compounds were identified by ESI-MS, ¹H NMR and ¹³C NMR.     

Grape Seed Extract Dose-Responsively Decreases Disease Severity in a Rat Model of Mucositis; Concomitantly Enhancing Chemotherapeutic Effectiveness in Colon Cancer Cells

Objective

Mucositis is a serious disorder of the gastrointestinal tract that results from cancer chemotherapy. We investigated the effects of increasing grape seed extract doses on the severity of chemotherapy in a rat model and its coincident impact on chemotherapeutic effectiveness in colon cancer cells.

Design

Female Dark Agouti rats were gavaged with grape seed extract (400–1000 mg/kg) or water (day 3–11) and were injected intraperitoneally with 5-Fluorouracil (150 mg/kg) or saline (control) on day 9 to induce mucositis. Daily metabolic data were collected and rats were sacrificed on day 12. Intestinal tissues were collected for histological and myeloperoxidase analyses. Caco-2 cell viability was examined in response to grape seed extract in combination with 5-Fluorouracil by 3-(4,5-Dimethylthiazol-2yl)-2,5-diphenyl-tetrazolium bromide) assay.

Results

Compared with 5-Fluorouracil controls, grape seed extract (400–1000 mg/kg) significantly decreased the histological damage score (P<0.05) in the jejunum. Grape seed extract (1000 mg/kg) increased jejunal crypt depth by 25% (P<0.05) in 5-Fluorouracil treated rats compared to 5-Fluorouracil controls, and attenuated the 5-Fluorouracil -induced reduction of mucosal thickness (25%, P<0.05). Grape seed extract (600 mg/kg) decreased myeloperoxidase activity by 55% (P<0.01) compared to 5-Fluorouracil controls. Grape seed extract was more effective at ameliorating 5-Fluorouracil induced intestinal injury, with effects most pronounced in the proximal jejunum. Grape seed extract (10–25 ug/mL) significantly enhanced the growth-inhibitory effects of 5-Fluorouracil by 26% (P<0.05) in Caco-2 cells and was more potent than 5-Fluorouracil at 50–100 µg/mL.

Conclusion

Grape seed extract may represent a new therapeutic option to decrease the symptoms of intestinal mucositis while concurrently impacting on the viability of colon cancer cells.     

Pharmacodynamic interaction of Momordica charantia with rosiglitazone in rats

The present study was undertaken to determine the interaction of rosiglitazone, a PPAR-γ agonist with methanolic extract of Momordica charantia L (MC), an herbal drug used widely as an antidiabetic agent. The pharmacodynamic interaction was evaluated in oral glucose tolerance test, streptozotocin (STZ) induced diabetes in adult rats and STZ induced diabetes in neonatal rats. Rosiglitazone was given orally at two different doses of 2 mg/kg and 5 mg/kg and MC was administered at a dose of 500 mg/kg, p.o. The serum glucose level estimation and histopathological studies of pancreas, liver and kidney were carried out. Both rosiglitazone and MC showed hypoglycaemic effect in oral glucose tolerance test. The hypoglycaemic effect observed with combination of rosiglitazone and MC was significantly more compared to either of the drugs given alone. MC also augmented the hypoglycaemic effect of rosiglitazone in both STZ induced diabetes in adult animals and STZ induced diabetes in neonatal rats. Histopathological studies revealed that administration of rosiglitazone with MC increased the volume of islet cell in pancreas and prevented the hepatic damage when compared to control. It was concluded that MC augments hypoglycaemic effect of rosiglitazone. This could be important in reducing the dose of rosiglitazone to achieve enhanced therapeutic effect with minimal adverse effects.     

Antiproliferative and newly attributed apoptotic activities from an invasive marine alga: Caulerpa racemosa var. cylindracea

Caulerpa racemosa (Forsskål) is a green marine alga which spreads from tropical to warm-water regions. Due to having invasive capacity C. racemosa var. cylindracea is a well-known biological pollution in Mediterranean Sea. One of the most important secondary metabolites of C. racemosa is Caulerpenyne (CPN). In the present study, antiproliferative and apoptotic effects of C. racemosa var. cylindracea extract and purified CPN on two well-known neuroblastoma cell lines, SHSY5Y and Kelly, are investigated. The antiproliferative and, additionally, newly attributed apoptotic effects of both C. racemosa var. cylindracea extract and purified CPN on SHSY5Y and Kelly cell lines have been shown in the present study. IC₅₀ values are 0.59 ± 0.06; 1.06 ± 0.23 g wet alga/methanol and 5.64 ± 0.09; 6.02 ± 0.09 μM CPN for C. racemosa var. cylindracea extract and purified CPN on SHSY5Y and Kelly cell lines, respectively. Percentages of apoptotic cells of SHSY5Y and Kelly in 0, 0.1 and 1 μM CPN conditions were 1.00 ± 0.71, 3.00 ± 0.71 and 49.40 ± 3.78, 39.60 ± 6.19 and 78.00 ± 2.74, 69.40 ± 3.78, respectively. In conclusion, the present study shows the antiproliferative effect of C. racemosa var. cylindracea extract and newly attributed apoptotic effects of C. racemosa var. cylindracea this extract. Compared to other alkylating anticancer drugs, CPN and also C. racemosa var. cylindracea extract might be considered as an alternative native source of antitumor drugs. Inasmuch as both C. racemosa extract and CPN have shown both antiproliferative and apoptotic effects on SHSY5Y and Kelly cell lines, the CPN and CPN derivatives might be considered as multifunctional agents in cell metabolism.     

Elimination of Taenia solium transmission to pigs in a field trial of the TSOL18 vaccine in Cameroon

A pilot field trial of the TSOL18 vaccine was undertaken in Cameroon. Two hundred and forty, 2-3 month-old piglets were distributed to 114 individual households in pairs. Vaccinated animals received three immunisations with 200 μg TSOL18 plus 5 mg Quil A and 30 mg/kg oxfendazole at the time of the second immunisation. Necropsies were undertaken when the pigs were approximately 12 months of age. Viable Taenia solium cysticerci were identified in 20 control pigs (prevalence 19.6%); no cysticerci were found in any of the vaccinated animals (P < 0.0001). Combined application of TSOL18 vaccination and a single oxfendazole treatment in pigs may be a relatively simple and sustainable procedure that has the potential to control T. solium transmission in endemic areas and, indirectly, reduce the number of new cases of neurocysticercosis in humans.     

Effect of Bacopasides on acquisition and expression of morphine tolerance

Opioids are extensively used for the management of both chronic malignant and non malignant pains. One major serious limitation associated with chronic use of opioids is the development of tolerance to its analgesic effect. The effect of Bacopa monnieri, a renowned ayurvedic medicine for acquisition and expression of morphine tolerance in mice, was investigated. Bacopa monnieri, n-Butanol fraction was analyzed on High performance liquid chromatography (HPLC), for Bacopaside A major components i.e. Bacoside A₃, Bacopaside ll and Bacosaponin C. Antinociceptive effect of n-Butanol extract of Bacopa monnieri (n Bt-ext BM) (5, 10 and 15 mg/kg) was assessed on hot plate. Effect of different doses of n Bt-ext BM on morphine antinociception was also assessed. n Bt-ext BM was also screened for development of tolerance to antinociceptive effect of Bacopa monnieri by administering 15 mg/kg n Bt-ext BM for seven days. Tolerance to morphine analgesia was induced in mice by administering intraperitoneally (I.P.) 20 mg/kg morphine twice daily for five days. Acute and Chronic administration of 5, 10 and 15 mg/kg n Bt-ext BM significantly reduced both expression and development of tolerance to morphine analgesia in mice. Additionally, Bacopa monnieri was found to enhance antinociceptive effect of morphine in intolerant animals. However, no tolerance to Bacopa monnieri antinociceptive effect was observed in seven days treatment schedule. These findings indicate effectiveness of Bacopa monnieri for management of morphine tolerance.     

The effect of dietary nickel on the immune responses of Spodoptera litura Fabricius larvae

By exposing Spodoptera litura Fabricius larvae to nickel (Ni) in artificial diets for successive three generations, we investigated the impacts of the dietary Ni on growth and immune response of the fifth and sixth instar larvae at 24 h intervals. The time of newly moulted fifth instar larvae was labelled as 0 h. After exposure to 5 mg/kg Ni for two generations, Ni exposure significantly improved larval phenoloxidase activity and encapsulation grade in fifth instar larvae when compared to controls, except for encapsulation grade at 72-120 h in the second generation. However, higher concentrations of Ni (≥10 mg/kg) only significantly reduced encapsulation grade at 72-120 h. In the third generation, insects given higher dietary levels of Ni (≥10 mg/kg) showed lower immune responses and retarded relative growth rate (RGR) compared to controls, but those exposed to lower Ni levels (≤5 mg/kg) had a significantly improved encapsulation grade at 24-72 h. Larvae at lower Ni level (≤5 mg/kg) treatments had significantly higher RGR in comparison with that in controls. There was no significant difference in food relative consumption rate (RCR) and RGR among any treatment of the fifth instar larvae in three successive generations. These results indicated that the type and extent of effects on growth and immune responses of S. litura varied with the Ni concentrations and exposure periods.     

The effects of the Brazilian antDinoponera quadriceps venom on chemically induced seizure models

Arthropod venoms are potential sources of neuroactive substances, providing new tools for the design of drugs. The aim of this study was to evaluate the effects of Dinoponera quadriceps venom (DqV) on seizure models in mice induced by pentylenetetrazole (PTZ), pilocarpine, and strychnine. In the PTZ model, intraperitoneal treatment with DqV (0.5 mg/kg) increased the time until the first seizure and the percentage of survival (155.4 ± 27.7 s/12.5%, p < 0.05) compared to the control group (79.75 ± 3.97 s/0%), whereas endovenous treatment (0.1 and 0.5 mg/kg) decreased the time until the first seizure (0.1 mg/kg: 77.83 ± 5.3 s versus 101.0 ± 3.3 s in the control group; 0.5 mg/kg: 74.43 ± 3.9 s versus 101.0 ± 3.3 s for the control group, p < 0.05). We did not observe significant changes in the pilocarpine- and strychnine-induced seizure models. In assays that measured oxidative parameters in the PTZ model, intraperitoneal treatment with DqV (0.5 and 2.0 mg/kg) only decreased the levels of MDA and nitrite in the cortex. However, endovenous treatment with DqV (0.1 and 0.5 mg/kg) increased the levels of MDA in the cortex and hippocampus and at a dose of 0.5 mg/kg in the striatum. Moreover, increased in nitrite content was observed in all three of the brain regions analyzed. Taken together, the D. quadriceps venom caused both neuroprotective and neurotoxic effects in a PTZ-induced seizure model, and this effect was dependent on the route of administration used.