Role of leptin on the expression of low density lipoprotein receptor.

Background & objectives: Leptin resistance oriented hyperleptinaemia is a common problem in obese subjects in association with hypercholesterolaemia. The most common target for hypercholesterolaemia is impaired low density lipoprotein receptor (LDLR). This study was carried out to investigate whether any alteration in LDLR expression could explain the occurrence of hypercholesterolaemia in the event of hyperleptinaemia. Methods: Expression of LDLR and SREBP2 (sterol regulatory element binding protein 2) were examined in HepG2 cells by RT-PCR and Western blotting. JAK2 inhibitor II was used to verify the effect of JAK-STAT (Janus Kinase-Signal Transducer and Activator of Transcription) pathway (common mediator for cytokine signaling). Co-localization of LDLR and insulin receptor (IR) was examined by confocal microscopy. Results: Leptin was found to reduce the expression of LDLR and its transcription factor SREBP2. On the other hand, a weak signal for stimulation of LDLR by leptin was noted to be mediated by JAK2 pathway. But the joint effect of the two signaling pathways kept LDLR only in depressed mode in presence of leptin. Confocal microscopy showed that LDLR made an intensively co-localized complex with insulin receptor in presence of leptin. Interpretation & conclusions: Our results show that though leptin stimulates LDLR expression very weakly through JAK-STAT signaling pathway, it mainly imposes inhibition on LDLR expression by inhibiting transcription factor SREBP2. The inter-association between LDLR and IR may be a reason to render LDLR functionally inactive in presence of leptin.

Evaluation of the anti-ulcer activity of NR-ANX-C (a polyherbal formulation) in aspirin & pyloric ligature induced gastric ulcers in albino rats.

Background & objectives: The aetiology of gastric ulcers is not completely understood and continuous use of anti-ulcer agents leads to many side effects. In this study we evaluated the anti-ulcer efficacy of a polyherbal formulation with potent antioxidant activity in aspirin and pyloric ligature induced gastric ulcers in rats. Methods: The efficacy of the polyherbal formulation NR-ANX-C (composed of the extracts from Withania somnifera, Camellia sinensis, Ocimum sanctum, shilajith and triphala) was evaluated in terms of antioxidant potential as assessed in terms of protection from lipid peroxidation and the antiulcer activity as seen by the area of gastric lesions, gastric juice volume, gastric pH, total acidity and total adherent gastric mucus content. Results: In our study, NR-ANX-C (25 and 50 mg/kg) was more efficacious than ranitidine in reducing ulcer index in both the models. At the highest dose tested (50 mg/kg), NR-ANX-C was comparable to omeprazole in preventing ulcer formation in the pyloric ligature model. NR-ANX-C showed a dose- dependent decrease in gastric juice volume and total acidity in both the models. A dose-dependent increase in gastric pH and total adherent gastric mucus was also seen in NR-ANX-C treated groups. The extent of lipid peroxidation was also reduced in the test drug treated groups. Interpretation & conclusion: Based on our findings, we presume that the cytoprotective, anti-secretary and antioxidant properties of NR-ANX-C were responsible for its anti-ulcer activity. These findings suggest the potential for use of NR-ANX-C as an adjuvant in the treatment of gastric ulcer.

Effect of extract of Benincasa hispida on oxidative stress in rats with indomethacin induced gastric ulcers.

This study was undertaken to determine the healing of ulcers induced by indomethacin due to antioxidant role of fruit extract of Benincasa hispida (Ashgourd) on ulcers in rats. Malondialdehyde (MDA) in RBC and antral homogenate was determined to measure tissue oxidation. Superoxide dismutase (SOD) in RBC and antral homogenate, plasma and homogenate vitamin C were estimated as measures of antioxidant defense. On induction of gastric ulcer, there was significant increase in SOD in RBC and homogenate levels and vitamin C in plasma. There was an apparent decrease in ulcer index in animals treated with fruit extract. There was significant decrease in MDA with concomitant decrease in SOD and vitamin C levels in the treated rats when compared to those not treated with fruit extract. Benincasa hispida has been shown to contain certain active principles like terpenes, flavanoid C--glycosides and sterols which have antioxidant effects. These probably inhibit gastric mucosal injury by scavenging the free radicals and repress production of SOD and vitamin C in these rats.

Effect of NR-ANX-C (a polyherbal formulation) on haloperidol induced catalepsy in albino mice.

BACKGROUND & OBJECTIVE: Use of typical antipsychotics like haloperidol in treatment of schizophrenia is associated with a high incidence of extrapyramidal side effects. In rodents, administration of haloperidol leads to the development of a behavioural state called catalepsy, in which the animal is not able to correct an externally imposed posture. In the present study we evaluated the anticataleptic efficacy of NR-ANX-C, a polyherbal formulation containing bioactives of Withania somnifera, Ocimum sanctum, Camellia sinensis, triphala and shilajit in haloperidol induced catalepsy in mice. METHODS: Five groups (n = 6) of male albino mice were used in the study. Catalepsy was induced by ip administration of haloperidol (1mg/kg). The degree of catalepsy (cataleptic score) was measured as the time the animal maintained an imposed posture. We compared the anticataleptic efficacy of NR-ANX-C (10, 25 and 50 mg/kg) with scopolamine (1 mg/kg). The superoxide dismutase (SOD) level in brain tissue was also estimated to correlate the levels of oxidative stress and degree of catalepsy in the animal. RESULTS: Significant (P<0.01) reduction in the cataleptic scores was observed in all NR-ANX-C treated groups and maximum reduction was observed in the NR-ANX-C (25 mg/kg) treated group. Significant (P<0.05) reduction in SOD activity was observed in NR-ANX-C (25 and 50 mg/kg) treated groups and maximum reduction was observed in NR-ANX-C (25mg/kg) treated group. INTERPRETATION & CONCLUSION: In our study, maximum reduction in cataleptic score was observed in NR-ANX-C (25 mg/kg) treated group. The maximum reduction in SOD activity was also observed in the same group. These findings suggest a possible involvement of the antioxidant potential of NRANX- C in alleviating haloperidol induced catalepsy.