Anti-ulcerogenic effect of methanolic extract of Elaeagnus conferta Roxb. seeds in Wistar rats.

ETHNOPHARMACOLOGICAL RELEVANCE: Elaeagnus conferta Roxb. (Elaeagnaceae) is a subtropical shrub mainly native to India, Vietnam, Malaysia and South China, whose various parts are used for treatment of diabetes, gastric ulcers, pain, oxidative stress and pulmonary disorders. Though the other parts of the plant have been reported for their ethnic use i.e. fruits as astringent locally and for cancer systemically, leaves for body pain and flowers for pain in chest and the seeds are mentioned as edible, there is no report per se on the medicinal use of seeds. Based on the fact that seeds of closely resembling species i.e. Elaeagnus rhamnoides has demonstrated significant anti-gastroulcerative property, the probability of the seeds of E. conferta possessing similar activity seemed quite significant. AIM OF THE STUDY: Phytochemical investigation and assessment of pharmacological mechanism(s) involved in anti-ulcer effect of methanolic extract of the seeds of E. conferta. MATERIALS AND METHODS: Bioactive phytoconstituents were isolated by column chromatography. These were identified by spectroscopic techniques including infrared (IR) spectroscopy, nuclear magnetic resonance (NMR) and mass spectrometry. Methanolic extract (MEC) of the seeds was prepared by cold maceration and its anti-ulcerogenic potential was evaluated using indomethacin (50 mg/kg) and water immersion stress models in male rats. The animals were pre-treated with different doses of MEC (400 and 800 mg/kg) and the therapeutic effect was compared with standard drug i.e. ranitidine (RANT; 50 mg/kg). The ameliorative effects of MEC were investigated on gastric juice pH, total acidity, free acidity and ulcer index. The assays of malionaldehyde (MDA), catalase (CAT), superoxide dismutase (SOD), glutathione (GSH) and pro-inflammatory cytokines i.e. interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-α) were carried out to find out the possible mechanism(s) of protection. Further, histopathological changes were also studied. RESULTS: Chromatography studies and further confirmation by spectroscopic techniques revealed the presence of four different compounds in MEC i.e oleic acid (1), stearic acid (2), ascorbic acid (3) and quercetin (4). MEC exhibited anti-ulcerogenic effect in dose dependent manner which may be attributed to suppression of pro-inflammatory cytokines (IL-6, TNF-α) and MDA (112.7%), and up-regulation of protective factors such as CAT (90.48%), SOD (92.77%) and GSH (90.01%). Ulcer inhibition, reduction in total and free acidity and increase in gastric juice pH were observed in MEC treated rats as compared to disease control animals. Histopathological findings confirmed decreased cell infiltration, less epithelial cell damage and regeneration of gastric mucosa in dose dependent manner. CONCLUSIONS: The anti-ulcer effect of MEC may be attributed to its ability to scavenge free radicals and anti-inflammatory property via suppression of TNF-α and IL-6, thus offers a complete and holistic approach for management of peptic ulcer.

Piper longum Linn. Extract inhibits TNF-alpha-induced expression of cell adhesion molecules by inhibiting NF-kappaB activation and microsomal lipid peroxidation.

Recruitment of specific leukocyte subpopulations at the site of inflammation requires a series of cell adhesion molecule (CAM)-mediated interactions. The major CAMs, viz., intercellular adhesion molecule-1 (ICAM-1), VCAM-1 and E-selectin are expressed on endothelium in response to various cytokines or bacterial LPS. Here, we have evaluated the effect of Piper longum chloroform extract (PlCE) on TNF-alpha-induced expression of ICAM-1 on endothelial cells and on NADPH-catalyzed rat liver microsomal lipid peroxidation with a view to identify modulators for the expression of CAMs. We demonstrate that PlCE inhibits adhesion of neutrophils to endothelial monolayer. This inhibition is due to the ability of PlCE to significantly block the TNF-alpha-induced expression of CAMs, i.e. ICAM-1, VCAM-1 at 17.5 microg/ml concentration and E-selectin at 15 microg/ml concentration on human umbilical vein endothelial cells. The inhibition of ICAM-1, VCAM-1 and E-selectin by PlCE is mediated through inhibition of NF-kappaB in endothelial cells. To demonstrate the antioxidant activity of PlCE, we showed that PlCE inhibited the NADPH-catalyzed rat liver microsomal lipid peroxidation significantly. These results suggest a possible mechanism of anti-inflammatory as well as antioxidant activity of PlCE.

Demonstration of anticonvulsant properties of an aqueous extract of Spirit Weed (Eryngium foetifdum L.)

Rats were used to investigate the anticonvulsant potential of two aqueous extracts of Spirit Weed. In this investigation, convulsions were induced by picrotoxin (4.5 mg/kg, i.p.) and these convulsions were consistently abolished by the intraperitioneal (i.p.) infections of aliquots (3ml each) of a steam distillate extract of Spirit Weed. However, those rats which served as controls as well as those which were injected with aliquots (3 ml each) of the boiled aqueous decoction of Spirit Weed, died after 2 hours of convulsions. Also, the steam distillate extract of Spirit Weed delayed (by 12 + 3 minutes) the onset of convulsions when it was given before picrotoxin (4.5 mg/kg, i.p.). Additionally, the steam distillate extract of Spirit Weed mimicked the anticonvulsant effect of phenobarbitone in the same group of rats. Moreover, the steam distillate extract of Spirit Weed did not produce generalized central nervous sustem depression in conscious rats. Therefore, it is concluded that an ingredient in the steam distillate extract of Spirit Weed has anticonvulsant properties which may be useful in the treatment of some forms of epilepsy. This requires further investigation (AU)