Ghrelin receptor is activated by naringin and naringenin,constituents of a prokinetic agent Poncirus fructus

Ethnopharmacological relevance

Poncirus fructus (PF), also known as a dried immature fruit of Poncirus trifoliata (L.) Raf. (Rutaceae), has long been traditionally used for the various gastrointestinal disorders in Eastern Asia.

Aim of study

The aqueous extract of PF (PF-W) has the strong prokinetic effect, yet the underlying mechanism is still elusive. The present study investigated whether PF-W has any effect on motilin receptor or ghrelin receptor, since these receptors enhance intestinal motility when activated.

Materials and methods

The effect of PF-W and its components on motilin or ghrelin receptor was determined by calcium imaging and whole-cell patch clamp methods.

Results

PF-W activates the ghrelin receptor, but not the motilin receptor, resulting in a transient increase of intracellular calcium levels. Furthermore, among various constituents of PF, only naringin and naringenin evoked the intracellular calcium augmentation via the ghrelin receptor. Moreover, cortistatin-8 – a ghrelin receptor inhibitor – specifically blocked naringin- and naringenin-induced calcium increases. In addition, naringin and naringenin induced inward currents in ghrelin receptor-expressing cells under whole-cell patch clamp configuration.

Conclusion

PF-W activates the ghrelin receptor, and naringin and naringenin are key constituents responsible for the activation of ghrelin receptor. Therefore, the present study suggests that the ghrelin receptor is a molecular entity responsible for the strong prokinetic activity of PF-W.     

Anticonvulsant activity of aqueous root extract of Ficus religiosa

Ethnopharmacological relevance

Ficus religiosa Linn is frequently used for the treatment of nervous disorders among Pawara tribe of the Satpuda range, India.

Aim of the study

This study aimed to investigate the anticonvulsant activity of the aqueous aerial root extract of Ficus religiosa in chemoconvulsant-induced seizures in mice.

Materials and methods

The anticonvulsant activity of the extract (25, 50 and 100 mg/kg, p.o.) was investigated in strychnine-, pentylenetetrazole-, picrotoxin- and isoniazid-induced seizures in mice. Rat ileum and fundus strip preparations were used to study the effect of the extract on acetylcholine (Ach)- and serotonin (5-HT)-induced contractions, respectively.

Results

The extract showed no toxicity and protected the animals in the strychnine and pentylenetetrazole tests in a dose-dependent manner. Its effect in the picrotoxin and isoniazid tests, however, was less potent. The extract also exhibited dose-dependent potentiation of Ach in rat ileum but failed to potentiate the effect of 5-HT in rat fundus strip preparation.

Conclusions

The results suggest that an orally administered aqueous root extract of Ficus religiosa has dose-dependent and potent anticonvulsant activities against strychnine- and pentylenetetrazole-induced seizures. The observed activities may be ascribed to the appreciable content of zinc and magnesium in the extract.     

Long-term administration of an aqueous extract of dried,immature fruit of Poncirus trifoliata (L.) Raf. suppresses body weight gain in rats

Aim of study

The purpose of the present study was to examine the effects of daily administration of an aqueous extract of the dried, immature fruit of Poncirus trifoliata Raf. (Rutaceae) (PF-W) on body weight in rats.

Materials and methods

PF-W was used in following experiments: 10-week-long measurement of body weight and food intake, in vitro pancreatic lipase activity assay, in vivo triglyceride concentration study, and measurement of intestinal transit rate.

Results

A high dose of PF-W (200 mg/2 mL/animal/day, in aqueous solution) was administered intragastrically to rats for 10 weeks. PF-W suppressed body weight gain by 6%. However, administration of PF-W at a lower dose (20 mg/animal/day) did not reduce weight gain. Administration of low- or high-dose PF-W had no effect on food intake throughout the experimental period. Additional experiments revealed that the suppressive effect of PF-W on body weight gain was not related to pancreatic lipase activity. Moreover, co-administration of PF-W with a lipid emulsion did not reduce plasma triglyceride concentration. Of interest, the high dose of PF-W significantly increased the rate of intestinal transit, whereas oral administration of the lower dose did not. Control and PF-W-treated groups did not differ in hematological and serum biochemical parameters, or in relative organ weights after 10 weeks of high-dose PF-W administration.

Conclusion

PF-W does not suppress body weight gain by interfering with fat absorption in a pancreatic lipase-dependent manner. The suppressive effect of PF-W on weight gain is likely due to the increased rate of intestinal transit, and the consequent reduction in nutrient absorption. Moreover, it appears that PF-W is relatively safe for long-term use. Taken together, the results of the present study suggest that long-term, daily administration of PF-W successfully suppressed body weight gain—apparently due to accelerated intestinal transit and not to interference with pancreatic lipase activity. Due to its apparent long-term safety, PF-W is a potential therapeutic agent for reduction of body weight in humans.     

Intracellular replication inhibitory effects of Galla Rhois ethanol extract for Brucella abortus infection

Ethnopharmacological relevance

Galla Rhois (GR) has long been applied in traditional Korean and Oriental medicine. Although GR has an anti-bacterial effect, the anti-bacterial mechanism and therapeutic efficiency of GR for intracellular parasitic Brucella infection are still unclear.

Aim of the study

The objective of this study was to investigate the antibacterial and therapeutic effects of GR ethanol extract (GRE), which is a natural antibacterial component for the treatment of Brucella abortus infection.

Materials and methods

The antibacterial activity of GRE towards Brucella abortus was evaluated by incubating Brucella abortus with GRE. Following treatment with GRE, Brucella abortus adherence, uptake, intracellular growth, and intracellular trafficking in macrophages were monitored. Mice were infected intraperitoneally with Brucella abortus and treated orally with GRE for 14 days, and then the weight and CFUs from each spleen were monitored.

Results

The viability of Brucella abortus was markedly decreased in a dose-dependent manner. Moreover, Brucella abortus internalization and intracellular growth within macrophages were reduced in GRE-treated cells. The number of bacteria that adhered to GRE-pretreated cells was significantly lower than that of untreated cells. With regards to intracellular trafficking, treatment with GRE augmented the colocalization of Brucella abortus-containing phagosomes with LAMP-1. GRE-treated mice showed considerably decreased weight and bacterial burdens in the spleen compared to untreated mice.

Conclusion

GRE exhibits antibacterial and protective effects on Brucella abortus in vitro and in vivo. These results highlight the beneficial effects of GRE in the prevention and treatment of brucellosis.     

Influences of Fructus evodiae pretreatment on the pharmacokinetics of Rhizoma coptidis alkaloids

Ethnopharmacological relevance

Rhizoma coptidis is a traditional Chinese medicine with pharmacological properties. It is usually prescribed with Fructus evodiae as traditional Chinese medicine (TCM) formulas. Here we report the influences of Fructus evodiae on the pharmacokinetics of the Rhizoma coptidis alkaloids and propose possible mechanisms.

Materials and methods

Pharmacokinetic experiments were performed in rats. In vitro absorption experiments were performed in everted rat gut sacs, while in vitro metabolism experiments and determination of hepatic UDP-glucuronosyltransferase (UGT) 1A1 mRNA expression were performed in rat liver microsomes.

Results

Pretreatment with Fructus evodiae extract for two weeks decreased the systemic exposure of the Rhizoma coptidis alkaloids. This effect was not due to inhibition of absorption or enhanced hepatic phase I metabolism of the Rhizoma coptidis alkaloids. However, Fructus evodiae pretreatment enhanced both the activity and expression of hepatic UGT1A1.

Conclusions

The results showed that Fructus evodiae pretreatment decreased the systemic exposure of the Rhizoma coptidis alkaloids by inducing hepatic UGT1A1.     

A plasma metabonomic investigation into the intervention of volatile oil of Magnolia biondii Pamp on rat model of acute inflammation

Ethnopharmacological relevance

The dried flower buds of Magnolia biondii Pamp (Magnoliaceae) possesses significant anti-inflammatory activities.

Aim of the study

Volatile oil in Magnolia biondii Pamp (VOMbP) is considered to be important pharmacologically active individuals against acute inflammation, but its exact anti-inflammatory mechanism remains elusive. In this study, we aimed to investigate the intervention of VOMbP on rats with acute inflammation and explore the possible anti-inflammatory mechanisms of VOMbP with metabonomic strategy.

Materials and methods

Acute inflammation was induced by subcutaneously injection of carrageenan in the rats. Plasma was analyzed using gas chromatography-mass spectrometry (GC-MS), based on which the principal component analysis (PCA) and partial least squares-discriminate analysis (PLS-DA) models were established for metabonomic analysis.

Results

It was revealed that the pretreatment of VOMbP in acute inflammatory rats induces a substantial and characteristic change in their metabolic profiles. Some significantly changed metabolites, including hexadecanoic acid, linoleic acid, oleic acid, stearic acid, and cholesterol, were found to be reasonable in explaining the anti-inflammatory mechanism of VOMbP.

Conclusions

In all, it is likely that VOMbP intervenes the metabolic process of inflammatory rats by affecting the fatty acid and cholesterol metabolism. Our work also indicated that the metabonomics method is a promising tool for performing intervention and mechanism research of traditional Chinese medicines.     

Genotoxicity of polar and apolar extracts obtained from Qualea multiflora and Qualea grandiflora

Ethnopharmacological relevance

The species Qualea grandiflora and Qualea multiflora, which belong to the Vochysiaceae family, are common in the Brazilian savannah (Cerrado biome), and the local inhabitants use these species to treat external ulcers and gastric diseases and as an anti-inflammatory agent. Studies have demonstrated that these plants contain compounds that exhibit pharmacological activities; however, the risks associated with their consumption are not known.

Material and methods

In the present study, the mutagenicity of polar and apolar extracts from Qualea grandiflora and Qualea multiflora were assessed by employing the Ames assay with and without metabolic activation. Additionally, phytochemical analyses (HPLC-ESI-IT-MS, HPLC-UV-PDA and GC-IT-MS) were performed to identify the chemical constituents present in these species, including the evaluation of physico-chemical properties, such as polarity or apolarity of the organic compounds, which are related to each fraction obtained. These studies provide important information regarding the biochemical behaviour of these compounds.

Results

All extracts exhibited mutagenicity, inducing frameshift mutations and base substitutions in DNA. Phytochemical analysis identified terpenes, ellagic acid derivatives and phytosteroids.

Conclusions

The mutagenicity observed might be due to the presence of pentacyclic triterpenes and polyphenols, which are able to generate reactive oxygen species (ROS) and result in the potential to cause DNA damage. The genetic risk identified in this present work shows that special attention should be considered for the use of compounds obtained from these plant species in medicinal treatments. Further studies must be conducted to identify safe therapeutic doses.     

Evaluation of anticancer activity of ethanol extract of Sesbania grandiflora (Agati Sesban) against Ehrlich ascites carcinoma in Swiss albino mice

Ethno pharmacological relevance

The plant Sesbania grandiflora (Fabaceae) is commonly known as “Sesbania” and “agathi” in ayurvedic system of medicine and reputed in the indigenous medicine in India. It is also known as “Agati Sesban” or “humming bird tree” in English. All parts of this unique plant are useful and have a wide spectrum of medicinal properties. The plant has various uses in folk and traditional medicines for headache, swellings, anemia, bronchitis, pains, liver disorders and tumors.

Aim of the study

The objective of the present study was to explore the anticancer activity of the ethanol extract of Sesbania grandiflora against Ehrlich ascites carcinoma (EAC)-bearing Swiss albino mice.

Materials and methods

Anticancer activity of ethanol extract of Sesbania grandiflora (EESG) of both leaves and flowers were evaluated in Swiss albino mice against Ehrlich Ascites Carcinoma (EAC) cell line at the doses of 100 and 200 mg/kg body weight intraperitoneally. The extracts were administered for 14 consecutive days. Twenty-four hours of last dose and 18 h of fasting, the mice were sacrificed and the anticancer effect of EESG was assessed by evaluating tumor volume, viable and nonviable tumor cell count, tumor weight, hematological parameters and biochemical parameters of EAC bearing host.

Results

Sesbania grandiflora extracts showed significant decrease in (p < 0.01) tumor volume, viable cell count, tumor weight and elevated the life span of EAC bearing mice. Hematological profile such as RBC, hemoglobin and lymphocyte count reverted to normal level in EESG treated mice. The extracts significantly (p < 0.05) decreased the levels of lipid peroxidation and significantly (p < 0.05) increased the levels of GSH, SOD and CAT.

Conclusion

The results showed that the ethanol extract of Sesbania grandiflora was effective in inhibiting the tumor growth in ascitic models and that is comparable to 5-Fluorouracil.     

Anti-angiogenic activity of methanol extract of Phellinus linteus and its fractions

Aim of the study

The aim of the present study was to investigate the effects of MeOH extract of PL (PLME) and its fractions on angiogenesis.

Materials and methods

PLME and its subsequent fractions (methylene chloride, ethyl acetate, n-butanol and aqueous fractions) were evaluated in vitro. Specifically, the anti-angiogenic activities of PLME and its fractions were investigated by measuring their effects on the proliferation, migration, tube formation and phosphorylation of vascular endothelial growth factor receptor (VEGFR)-2 in human umbilical vein endothelial cells (HUVECs). In addition, the in vivo Matrigel plug model was applied to evaluate new vessel formation.

Results

The results revealed that PLME and its subsequent fractions, except for the aqueous fraction, led to significant inhibition of the proliferation, migration, tube formation and VEGFR-2 phosphorylation of HUVECs as well as in vivo angiogenesis.

Conclusions

These findings indicate the potential for the use of PLME in pathological situations involving stimulated angiogenesis, such as inflammation and tumor development.     

Pharmacological actions of the South African medicinal and functional food plant Sceletium tortuosum and its principal alkaloids

Ethnopharmacological relevance

The South African plant Sceletium tortuosum has been known for centuries for a variety of traditional uses, and, more recently, as a possible source of anti-anxiety or anti-depressant effects. A standardised extract Zembrin^® was used to test for pharmacological activities that might be relevant to the ethnopharmacological uses, and three of the main alkaloids were also tested.

Materials and methods

A standardised ethanolic extract was prepared from dried plant material, along with the purified alkaloids mesembrine, mesembrenone and mesembrenol. These were tested on a panel of receptors, enzymes and other drug targets, and for cytotoxic effects on mammalian cells.

Results

The extract was a potent blocker in 5-HT transporter binding assays (IC₅₀ 4.3 μg/ml) and had powerful inhibitory effects on phosphodiesterase 4 (PDE4) (IC₅₀ 8.5 μg/ml), but not other phosphodiesterases. There were no cytotoxic effects. Mesembrine was the most active alkaloid against the 5-HT transporter (K_i 1.4 nM), while mesembrenone was active against the 5-HT transporter and PDE4 (IC₅₀'s < 1 μM).

Conclusions

The activity of the Sceletium tortuosum extract on the 5-HT transporter and PDE4 may explain the clinical effects of preparations made from this plant. The activities relate to the presence of alkaloids, particularly mesembrine and mesembrenone.     

Protective effects of methanolic extract of Hedyotis puberula (G. Don) R. Br. ex Arn. against experimentally induced gastric ulcers in rat

Aim of the study

This study was aimed to evaluate the antiulcer activity of the whole plants of Hedyotis puberula (G. Don) R. Br. ex Arn.

Materials and methods

Gastroprotective potential of the Hedyotis puberula methanol extract (200 and 400 mg/kg body weight) was studied on indomethacin (IND), ethanol and pyloric ligation (PL)-induced gastric ulcer models in rats.

Results

The treatment with Hedyotis puberula extract at 400 mg/kg p.o. protected the rats against the ulceration which was comparable to the reference drug omeprazole. Pretreatment with extract protected rats from gastric lesion development by way of increased pH and decreased volume, acidity and pepsin content of gastric secretion. Furthermore, total carbohydrate: protein ratio of the gastric juice were noticeably increased in pretreated rats.

Conclusion

Results of our study showed that Hedyotis puberula possess significant gastroprotective activity and validate the folklore claim.     

Anti-osteoporotic activity of aqueous-methanol extract of Berberis aristata in ovariectomized rats

Ethnopharmacological relevance

Traditionally Berberis aristata is employed for its supposed properties in treatment of joint pain and also used in alleviating symptoms of menopause.

Aim of the study

The aim of the present study is to evaluate the antiosteoporotic effect of Berberis aristata in ovariectomized (OVX) rats.

Materials and methods

Sprague-Dawley rats were divided into sham and OVX groups. The OVX rats were further divided into four groups, which received standard estrogen (0.0563 mg/kg) and 100, 300, and 500 mg/kg aqueous-methanol extract of Berberis aristata, daily for 42 days. The uterine weight, bone loss, ash content, biomechanical, biochemical and histopathological observation were carried out for antiosteoporotic activity.

Results

The experimental animals treated with Berberis aristata aqueous-methanol extract showed dose dependent activity. The significant increase in uterine weight, femur BMD, ash content and lumbar hardness were observed. In addition, increased levels of calcium and phosphorus in serum and significant decreased in urine were observed as compared to control OVX group. The histopathological results also confirm the protective effect of extract.

Conclusion

The present findings strongly suggest that Berberis aristata possess the potent antiosteoporosis activity in ovariectomized rats and substantiates the ethnic use in treatment of postmenopausal osteoporosis.     

Sedative, hypnotic and anticonvulsant activities of the ethanol fraction from Rhizoma Pinelliae Praeparatum

Ethnopharmacological relevance

Rhizoma Pinelliae Praeparatum is the product of raw Rhizoma Pinellia processed with alkaline solution and Licorice, which had been widely used for treatment of insomnia in traditional Chinese medicine. The present study aimed to investigate the sedative, hypnotic and anticonvulsant activities of ethanol fraction from Rhizoma Pinelliae Praeparatum (EFRP) and to determine whether these effects were related to GABAergic mechanism.

Materials and methods

The sedative, hypnotic and anticonvulsant activities of EFRP were investigated with locomotion activity, pentobarbital-induced sleeping and nikethamide (NKTM)-induced convulsion tests, respectively. Additionally, the effects of flumazenil (an antagonist of GABA_A receptor) and l-malic acid (blocker of synthetic enzyme for GABA) on the hypnotic activity of EFRP were evaluated.

Results

EFRP at dose of 12 g/kg significantly inhibited the locomotion activity of mice. EFRP showed synergic effect on pentobarbital-induced sleeping by increased numbers of mice falling asleep, reduced the sleep latency and prolonged the sleeping time. l-malic acid and flumazenil inhibited the augment effects of EFRP on pentobarbital-induced sleeping. EFRP promoted a significant protection to NKTM-induced convulsion, by prolonged the death latency and decreased mortality.

Conclusion

EFRP possessed sedative, hypnotic and anticonvulsant activities and these activities may be related to the GABAergic system.     

Effect of an aqueous extract of dried immature fruit of Poncirus trifoliata (L.) Raf. on intestinal transit in rodents with experimental gastrointestinal motility dysfunctions

The effect of an aqueous extract of the dried immature fruit of Poncirus trifoliata Raf. (Rutaceae) (PF-W) on gastrointestinal (GI) motor function was investigated by measuring the intestinal transit rate (ITR) of Evans blue in rats and mice with experimental GI motility dysfunctions (GMDs). GMD was induced by appropriate surgery or by the administration of acetic acid, atropine, L-DOPA, or morphine to the animals. The ITR in these GMD animals was significantly retarded compared to normal animals. The retardation, however, was significantly inhibited by the intragastric administration of PF-W (0.1-1g/kg) in a dose dependent manner for all GMD models except for L-DOPA-induced GMD. The above results suggest that PF-W has the potential for development as a prokinetic agent that may prevent or alleviate GMD in human patients.     

Prokinetic and laxative activities of Lepidium sativum seed extract with species and tissue selective gut stimulatory actions

Aim of the study

To provide ethnopharmacological basis for the medicinal use of Lepidium sativum seeds in indigestion and constipation.

Materials and methods

The in vivo studies were conducted in mice, while isolated tissues of mouse, guinea-pig and rabbit were suspended in tissue bath to measure isotonic contractions.

Results

The aqueous-methanolic extract of Lepidium sativum seeds (Ls.Cr) at 30 and 100 mg/kg showed atropine-sensitive prokinetic and laxative activities in mice, which were partially sensitive to atropine. In isolated gut preparations of mouse and guinea-pig, Ls.Cr (0.1-1 mg/mL) caused a concentration-dependent stimulatory effects both in jejunum and ileum, which was blocked in the presence of atropine. In rabbit jejunum, the stimulant effect of Ls.Cr remained unchanged in the presence of atropine, pyrilamine or SB203186, while in rabbit ileum, the stimulatory effect was partially blocked by atropine. The Ls.Cr was more efficacious in gut preparations of rabbit than in guinea-pig or mouse. The phytochemical analysis of the plant extract detected alkaloids, saponins and anthraquinones as plant constituents.

Conclusion

This study showed the prokinetic and laxative effects of Lepidium sativum in mice, which were partially mediated through a cholinergic pathway. The in vitro spasmodic effect of the plant extract mediated through a similar mechanism with species and tissue-selectivity, provides a rationale for the medicinal use of the seeds of Lepidium sativum in indigestion and constipation, and suggests studying the plant extracts on more than one species to get the wider picture.     

Euonymus alatus extract attenuates LPS-induced NF-κB activation via IKKβ inhibition in RAW 264.7 cells

Aim of the study

The present study was performed to investigate the underlying mechanisms of anti-inflammatory effects with the extract of Euonymus alatus (EEA), and specially focused on nuclear factor κB (NF-κB) signaling pathway by targeting the IκB kinase β (IKKβ).

Materials and methods

The effect of EEA for IKKβ activity was analyzed using an immobilized metal affinity for phosphochemicals (IMAP)-based time-resolved fluorescence resonance energy transfer (TR-FRET) assay. The effect of EEA on lipopolysaccharide (LPS)-induced NF-κB activation in murine macrophage RAW 264.7 cells with western blotting and immunofluorescent staining was evaluated.

Results

IKKβ studies based on IMAP-TR-FRET showed that EEA possesses a potent IKKβ inhibitory activity with IC₅₀ value of 11.83 μg/ml. EEA (10, 30 μg/ml) also attenuated the LPS-induced IκBα phosphorylation/degradation, NF-κB translocation and subsequent NO synthesis in RAW 264.7 cells.

Conclusions

These results suggest that EEA abrogates LPS-induced NF-κB signaling pathway by targeting the IKKβ in RAW 264.7 cells and these properties may provide a molecular basis for understanding the inhibitory effects of EEA on LPS-mediated inflammation.     

Bacopa monniera leaf extract up-regulates tryptophan hydroxylase (TPH2) and serotonin transporter (SERT) expression: implications in memory formation

Aim of the study

To examine the effect of Bacopa monniera leaf ethanolic extract (BMEE) on the serotonergic system of postnatal rats with reference to learning and memory.

Materials and methods

From postnatal day (PND)-15-29, rats were treated with BMEE (40 mg/kg BW + 0.5% gum acacia) by oral gavage. Behavioural tests (Y-maze, hole-board and passive avoidance) were used to evaluate their learning (PND-32-37) and retention of memory (PND-47-53). Effect of BMEE on neurotransmitter system was analyzed by ELISA and semi-quantitative polymerase chain reaction (PCR).

Results

Oral administration of BMEE improved learning and retention of memory significantly in all behavioural tasks. Following BMEE treatment, the level of serotonin (5-HT) increased while dopamine (DA) decreased significantly. We also found variation in the level of acetylcholine (ACh). However, no significant changes were observed in the level of ACh and glutamate (Glu). The level of 5-HT was significantly elevated up to PND-37 and was then restored to normal level on PND-53. Interestingly, concomitant up-regulation was recorded in the mRNA expression of serotonin synthesizing enzyme tryptophan hydroxylase-2 (TPH2) and serotonin transporter (SERT) on PND-29 and PND-37, which was restored on PND-53.

Conclusions

The results suggest that BMEE treatment significantly enhances the learning and retention of memory in postnatal rats possibly through regulating the expression of TPH2, 5-HT metabolism and transport.     

Anti-angiogenic activity of Gynura segetum leaf extracts and its fractions

Ethnopharmacological relevance

Gynura segetum is a popular medicinal plant in Indonesia and Malaysia, known to possess various medicinal properties especially for treatment of cancer, diabetes and hypertension.

Aim of the study

This study was carried out to evaluate the anti-angiogenic effect of Gynura segetum leaves extracts and its fractions. The chemical compositions of the active extracts were also determined.

Materials and methods

The anti-angiogenic activity of Gynura segetum leaves extracts and its fractions was evaluated in vivo using the chick embryo chorioallantoic membrane (CAM) assay. Gas chromatography-mass spectrometry (GC-MS) analysis was carried out to identify the chemical compositions of the active extracts.

Results

The CAM treated with Gynura segetum leaves extracts and its fractions (100 μg/disc) showed a significantly greater anti-angiogenic effect compared to the positive control suramin (50 μg/disc). Chemical analysis of the active extracts from the leaves of Gynura segetum yielded nine known compounds: undecane (1), neophytadine (2), hexadecanoic acid, methyl ester (3), 9,12-octadecadienoic acid, methyl ester (4), 9,12,15-octadecatrienoic acid, methyl ester (5), phytol (6), tetradecanal (7), octadecanoic acid, methyl ester (8) and γ-sitosterol (9).

Conclusions

These results suggested that Gynura segetum has anti-angiogenic activity. The plant may be used as a potential source for protection against cancer.     

Abrogation of nimesulide induced oxidative stress and mitochondria mediated apoptosis by Fumaria parviflora Lam. extract

Ethanopharmacological relevance

Fumaria parviflora Lam. is used for treating aches and pains, diarrhea, fever, influenza and other complications. The herb mixed with honey is taken to prevent vomiting as per Ayurvedic text.

Aim of the study

In vivo studies were conducted to explore the hepatoprotective potential of Fumaria parviflora Lam. Fp extract against nimesulide induced oxidative stress and regulation of critical events in mitochondria mediated apoptosis.

Materials and methods

Group of Wistar rats were fed with nimesulide for 5 days (80 mg/kg/day, po), another group was pre-treated with Fp extract/silymarin (200 mg/kg/day, po) for 5 days followed by nimesulide exposure. Liver serum biomarkers and histopathology were done to assess hepatotoxicity caused by nimesulide. Antioxidant enzymes (SOD, LPO, GPx, GR) were assessed using biochemical assays as well as gene expression by RT-PCR. GSH content and ROS generation was also evaluated using flow cytometry. Key apoptotic markers like phosphatidyl serine externalization, Bax, Bcl-2 translocation, mitochondrial membrane potential, cytochrome c release, caspases (9/3) activation and DNA damage were also observed in all the groups to confirm involvement of mitochondrial pathway.

Results

Pre-treatment with Fp extract for 5 days significantly reduced the impact of nimesulide induced toxicity as evident from the serum biomarkers of liver damage and histopathology. It also modulated antioxidant enzymes mRNA expression as well as activity (SOD, glutathione peroxidase, glutathione reductase) and reduced lipid peroxidation during nimesulide toxicity. Nimesulide exposure decreased GSH content (92.9%) and increased reactive oxygen species (9.29 fold) which was attenuated in Fp treated rats. Fp pre-treatment significantly altered key apoptotic events like Bcl2 and Bax translocation, inhibited mitochondrial depolarization, prevented cytochrome c release, caspase-9/caspase-3 activation and DNA damage.

Conclusion

Our in vivo findings regarding protection accorded by Fp extract against nimesulide toxicity suggest that Fp not only reduced hepatotoxicity but attenuated critical control points of apoptotic cell death.     

Anti-inflammatory activity of Trichosanthes cucumerina Linn. in rats

Aim of the study

Trichosanthes cucumerina Linn. (Family: Cucurbitaceae) is one of the medicinal plants that is often used in Sri Lankan traditional systems of medicine. One of its uses is the treatment of inflammatory conditions. However, validity of the anti-inflammatory activity has not been scientifically investigated so far. Therefore, the aim of this study was to investigate the anti-inflammatory potential of Trichosanthes cucumerina hot water extract (HWE) and its fractions.

Materials and methods

The anti-inflammatory activity of Trichosanthes cucumerina was evaluated by use of the carrageenan-induced paw oedema model in Wistar rats. In addition, the mechanism/s by which Trichosanthes cucumerina is mediated the anti-inflammatory activity was assessed by determining its effects on (a) membrane stabilizing activity and (b) nitric oxide inhibitory activity.

Results

Apart from the lowest dose of the HWE, other tested doses (500, 750, 1000 mg/kg) produced a significant (P ≤ 0.05) inhibition of the inflammation, most pronounced at 5 h after the injection of carrageenan. The anti-inflammatory effect induced by 750 mg/kg, was comparable to that of the reference drug, indomethacin at 4 and 5 h. Inhibition of nitric oxide (NO) production and membrane stabilization activities are probable mechanisms by which Trichosanthes cucumerina mediates its anti-inflammatory actions. Among the tested fractions, methanol fraction (MEF) and aqueous fraction (AQF) at a dose of 75 mg/kg exhibited marked inhibition against carrageenan-induced hind paw oedema. The anti-inflammatory effect induced by MEF, was comparable to that of the reference drug, indomethacin and as well as to the 750 mg/kg of HWE at 4 and 5 h.

Conclusions

(a) These findings rationalize the traditional usage of this plant as an anti-inflammatory agent and (b) membrane stabilizing properties and NO inhibitory activity are possible mechanisms through which Trichosanthes cucumerina mediates its anti-inflammatory action.