Effect of methanolic extract of Dendrophthoe falcata leaves on acute hyperglycemic adult zebrafish

Background: Herbs used in medicinal practices by the indigenous healers are found to be of great importance in the management of diseases that are yet to have a cure by the available drugs. Practice of using herbs available in the vicinity by the locals as medication for ailments is a universal phenomenon. Dendropthoe falcata, an arboreal parasitic plant used in the indigenous medicine for the management of diabetes, is explored here for its acute hyperglycemic model adult zebrafishes. Aim and Objectives: The aim of the study was to determine the hypoglycemic effect of the methanolic extract of Dendrophthoe falcata leaves in alloxan-induced acute diabetic adult zebrafish. Materials and Methods: Adult zebrafishes were grouped into five groups with six fishes in each group exposing them to alloxan to induce acute hyperglycemia and then treating them with two test doses of 40 mg/dl and 60 mg/dl of the methanolic extract of the plant extract. Another group was treated with metformin with a dosage of 20 micro moles. Body mass index, blood glucose, and histopathological examination pre- and post-treatment for a period of 14 days were studied. Results: The effect of the herbal extract in both the doses was promising when compared with the standard drug metformin; however, the cytoprotective effect was very predominant with the both doses of the extract. Acute hypoglycemic was comparatively good when compared with the standard group treated with metformin. Conclusion: The antidiabetic effect of the arboreal parasitic plant has been established with a need for further exploration of this plant for a potential drug for diabetes mellitus.

In-vivo Analgesic and In-vitro Cytoprotective Potential of Various Leaf Extracts of Pongamia pinnata

Pongamia pinnata (L.) Pierre is a medium sized glabrous, perennial tree which grows in the littoral regions of South Eastern Asia and Australia. In the Indian Ayurvedic medicine, different parts of the plant have been used for pain relief in various disorders. The present study investigated the potential of different leaf extracts of Pongamia pinnata as an analgesic agent in rodents and our aim was also to study in-vitro cytoprotective effects of the various extracts from leaves of the plant. Different leaf extracts of Pongamia pinnata i.e. aqueous, alcoholic, acetone and chloroform were investigated for analgesic activity at the dose rate of 50 mg/kg and 100 mg/kg in Wistar rats. For the assessment of analgesic activity, tail flick method was used. In-vitro cytoprotective activity of various leaf extracts (at concentrations of 5% and 10%) was evaluated in ATCC acquired MDBK cell lines and for this study, cytotoxicity was induced by thiomethoxam. It was observed that almost all the extracts demonstrated the dose dependent analgesic activity with maximum response in the aqueous extract group @ 100 mg/kg when compared to control. For cytoprotective study, oxidative stress parameters- catalase, LPO, SOD and GPx were determined. Study on analgesic activity revealed the presence of dose dependent effect in all extracts with highest effect in aqueous extract of Pongamia pinnata. We believe that triterpene alkaloids and steroidal principles present in the plant products might be responsible for the analgesic effect

Effect of an extraction solvent on the antioxidant quality of Pinus densiflora needle extract / 药物分析学报

Pinus densiflora needle extract (PDNE) is widely reported to have many pharmacological activities including antioxidant potential. However, the solvent system used for extraction greatly affects its antioxidant quality. Hence, in the present study, we investigated the effect of a different ratio (vol/vol) of ethanol to water (0-100％) in the extraction of PDNE with potent antioxidant capacity. The chemical assays, 2,2-diphenyl-1 picrylhydrazyl (DPPH) and 2,2′-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) diammonium salt (ABTS), were conducted to assess the antioxidant potential of PDNE. Subsequently, the cytoprotective effect of PDNE was determined using tert-butyl hydroperoxide (TBHP)-challenged HepG2 cellular model. The needle extracts from 40％ ethanol (PDNE-40) showed greater radical scavenging activity followed by 60％, 20％, 80％, 0％ and 100％ ethanol extracts. EC50 value of the most active extract, PDNE-40, was 8.56 ± 0.51 μg/mL, relative to 1.34 ± 0.28 μg/mL of the standard trolox (for ABTS radical), and 75.96 ± 11.60 μg/mL, relative to 4.83 ± 0.26 μg/mL of the standard trolox (for DPPH radical). Either PDNE-20 or PDNE-40 pretreatment remarkably decreased the levels of reactive oxygen species (ROS), lipid peroxides and protein carbonyls in TBHP-challenged HepG2 cells. In addition, both PDNE-20 and PDNE-40 significantly reversed the decreased ratio of reduced (GSH) to oxidized (GSSG) glutathione. Moreover, these two extracts showed a significant inhibitory effect on TBHP-induced nuclear damage and loss of cell viability. In summary, the inclusion of 40％ ethanol in water for extraction of Pinus densiflora needle greatly increases the antioxidant quality of the extract.

Molecular Dynamics, Simulation of Protein-Protein Complex and their Role in Cytoprotective Process in Ethanol-induced Toxicity of HepG2 Cell Line

Aim: To examine the protein-protein interaction of Wolbachia Surface Protein (WSP of Uzifly) with six proteins involved in Ethanol-induced toxicity and the proteins involved in its cytoprotective process in HepG2 cell line (CYP2E1, Superoxide dismutase, Catalase, Death-associated protein kinase1, Alcohol dehydrogenases (Alpha/beta/gamma) and Cytochrome-C) and to study real time molecular dynamics. Methodology: Modelled structure of WSP of Uzifly was retrieved from our laboratory archive. The proteins involved in the Ethanol-induced toxicity and the proteins involved in its cytoprotective process in HepG2 cell line were chosen based on the literature study. The six proteins like CYP2E1, Superoxide dismutase, Catalase, Death-associated protein kinase1, Alcohol dehydrogenases (Alpha/beta/gamma) and Cytochrome-C which are involved in the Ethanol-induced toxicity and the proteins involved in its cytoprotective process in HepG2 cell line were retrieved from PDB database with ID: PDB (3T3Z), PDB (2C9V), PDB (1DGG), PDB (2YAK), PDB (1U3W) and PDB (3NWV) respectively. Docking study was processed using ZDOCK and the best poses of protein were sorted using rDock. Finally, the atomic level interaction was studied for the best-scored protein-protein complex. The best complex was further subjected to molecular dynamics simulation to study its stability using standard dynamics cascade tool. Results: From the results, it was observed that three proteins such as Cytochrome-C, CYP2E1 and Superoxide dismutase have more favourable shape complementarity for WSP binding to exhibit the cytoprotective process. However, the interaction analysis was done only for the top complex, Cytochrome-C-WSP. Time dependent parameter analysis of best complex Cytochrome-C-WSP showed that root-mean-square deviation (RMSD) values initially deviated but it was stabilized at the end of 1ns dynamics. The radius of gyration (Rg) during dynamics was within the limit. Conclusion: This insilico study revealed that WSP has cytoprotective potential and therapeutical application.

trans-4,4'-Dihydroxystilbene (DHS) protects PC12 cells from oxidative damage but induces reactive oxygen species-mediated apoptosis in SHSY-5Y cell line.

Polyphenols can exert both, antioxidant and pro-oxidant properties, depending on cell types as well as their concentrations. Hence, it was of interest to examine if the naturally occurring resveratrol analog, trans-4,4'-dihydroxystilbene (DHS) also exert both these activities in a biphasic or cell-specific manner. In this study, we established the cytoprotective action of DHS against hydrogen peroxide (H2O2)-induced apoptotic death of the PC12 cells. DHS reduced mitochondrial membrane permeabilization and deactivated reactive oxygen species (ROS)-mediated caspase-3 activation in the H2O2-treated PC12 cells. However, it induced apoptosis in the human neuroblastoma SHSY-5Y cell line by destabilizing mitochondrial membrane, augmenting ROS and activating caspapse-3. DHS showed better activity than resveratrol in both the chosen models.

Effect of Pithecellobium dulce (Roxb.) Benth. fruit extract on cysteamine induced duodenal ulcer in rats.

The edible fruits of Pithecellobium dulce (Roxb.) Benth. are traditionally used for various gastric complications in India. Here, we investigated the antiulcer activity of hydroalcoholic fruit extract of P. dulce (HAEPD) by applying cysteamine induced duodenal ulcer model in rats. Duodenal ulcer was induced in male albino Wistar rats by oral administration of cysteamine @ 420 mg/kg body wt. as a single dose. The rats were pre-administered orally with HAEPD @ 200 mg/kg body wt. for 30 days prior to ulcer induction. Rats pre-administered with ranitidine @ 30 mg/kg body wt. served as reference drug control. Ulcer score, thiobarbituric acid reactive substances (TBARS), glycoproteins, superoxide dismutase, catalase and glutathione peroxidase and reduced glutathione levels were measured in the duodenum. Rats pre-administered with the HAEPD showed significantly reduced ulcer score comparable to that of ranitidine pretreated rats. The co-administration of HAEPD lowered the TBARS level and also restored the levels of glycoproteins, enzymatic and non-enzymatic antioxidants. Histopathological observations confirmed the presence of inflammation, necrosis and hemorrhagic spots in the duodenum of ulcer control rats which were significantly reduced due to HAEPD treatment. No abnormal alterations were observed in normal rats treated with HAEPD at the dosage studied. The results demonstrated antioxidant and cytoprotective nature of P. dulce, and thereby its significant anti ulcer property.

Cytoprotective and anti-inflammatory effects of kernel extract from Adenanthera pavonina on lipopolysaccharide-stimulated rat peritoneal macrophages

OBJECTIVE@#To investigate mechanism of anti-inflammatory activity of Adenanthera pavonina (A. pavonina) extracts.@*METHODS@#Rat peritoneal macrophages were treated with different concentrations of lipopolysaccharide and H2O2 in the presence and absence of kernel extract from A. pavonina. Nitric oxide, Superoxide anion generation, cell viability and nuclear fragmentation were investigated.@*RESULTS@#The pre-treatment of kernel extract from A. pavonina suppressed nitric oxide, superoxide anion, cell death, nuclear fragmentation in lipopolysaccharide and H2O2 stimulated or induced macrophages, respectively.@*CONCLUSIONS@#These results suggest that A. pavonina extract suppresses the intra cellular peroxide production.

Cytoprotective and anti-inflammatory effects of kernel extract from adenanthera pavonina on lipopolysaccharide-stimulated rat peritoneal macrophages

Objective: To investigate mechanism of anti-inflammatory activity of Adenanthera pavonina (A. pavonina) extracts. Methods: Rat peritoneal macrophages were treated with different concentrations of lipopolysaccharide and H2O2 in the presence and absence of kernel extract from A. pavonina. Nitric oxide, Superoxide anion generation, cell viability and nuclear fragmentation were investigated. Results: The pre-treatment of kernel extract from A. pavonina suppressed nitric oxide, superoxide anion, cell death, nuclear fragmentation in lipopolysaccharide and H2O2 stimulated or induced macrophages, respectively. Conclusions: These results suggest that A. pavonina extract suppresses the intra cellular peroxide production.

Cytoprotective and anti-inflammatory effects of kernel extract from Adenanthera pavonina on lipopolysaccharide-stimulated rat peritoneal macrophages

Objective:To investigate mechanism of anti-inflammatory activity ofAdenanthera pavonina (A. pavonina) extracts.Methods:Rat peritoneal macrophages were treated with different concentrations of lipopolysaccharide andH2O2 in the presence and absence of kernel extract from A. pavonina.Nitric oxide, superoxide anion generation, cell viability and nuclear fragmentation were investigated.Results:The pre-treatment of kernel extract fromA. pavonina suppressed nitric oxide, superoxide anion, cell death, nuclear fragmentation in lipopolysaccharide andH2O2 stimulated or induced macrophages, respectively.Conclusions:These results suggest thatA. pavonina extract suppresses the intra cellular peroxide production.

Reviews of herbal and their secondary metabolites in the treatment of ulcerative colitis and peptic ulcer.

Peptic ulcer is a disease of the Gastro-intestinal tract (GIT), which includes both gastric and duodenal ulcers. The occurrence of peptic ulcer disease has been attributed to the imbalance between aggressive factors like acid, pepsin, and Helicobacter infection on one hand and the local mucosa defenses like bicarbonate and mucus secretion and prostaglandins synthesis on the other hand. The most serious complications of peptic ulcer disease include hemorrhage, perforation, penetration, and gastric outlet obstruction. Ulcerative colitis is a form of inflammatory bowel disease (IBD). It is a form of colitis, a disease of the colon that includes characteristic ulcers, or open sores. IBD is often confused with irritable bowel syndrome. Ulcerative colitis is associated with a general inflammatory process that affects many parts of the body. Sometimes these associated extra-intestinal symptoms are the initial signs of the disease, such as painful arthritic knees in a teenager and may be seen in adults also. Several classes of pharmacological agents have proved to be effective in the management of the acid peptic disorders viz., antacids, acid suppressive agents, anticholinergic, cytoprotective agents, etc. A widespread search has been launched to identify new anti-ulcer therapies from natural sources to replace currently used drugs of doubtful efficacy and safety. Herbs, medicinal plants, spices, vegetables and crude drug substances are considered to be a potential source to control various diseases including gastric ulcer and ulcerative colitis. In the scientific literature, a large number of medicinal plants and their secondary metabolites with anti-ulcer potential have been reported. As the gastro protective effect can be linked to different mechanisms, once demonstrated the activity, the extracts and more appropriately the active compounds should be assessed for action mechanisms to elucidate their mode of action. Besides, new action mechanisms may be discovered.

Ulcer protective potential of standardized hesperidin, a citrus flavonoid isolated from Citrus sinensis

Free radicals play an important role in stomach ulcer formation. The present investigation validates the anti ulcer activity of hesperidin, isolated from Citrus sinensis (L.) Osbeck, Rutaceae, through the assessment of its antioxidant potential over stomach mucosal tissue by histological examination. Hesperidin was isolated from the dried peel of C. sinensis, and authenticated by TLC, IR and HPLC. The anti-ulcerogenic potential of this fruit was assessed using indomethacin and hypothermic restrain stress-induced ulceration models on rats at 150, 300 and 450 mg/kg dose orally. The parameters measured were gastric pH, volume, free and total acidity, ulcer index, and mucin, glutathione, super oxide dismutase, catalase and protein content. Hesperidin at 300 and 450 mg/kg dose showed significant (p < 0.01-0.001) increase in pH, decrease in acidity and ulcer index against indomethacin and hypothermic restrain stress, along with histological evidence of cytoprotection. Glutathione, super oxide dismutase, catalase and mucin levels increased significantly at 450 mg/kg (p < 0.05-0.001) after indomethacin ulceration, whereas hypothermic restrain stress only increased glutathione and mucin levels. Hesperidin prevents oxidative cell injury by significant rise of super oxide dismutase, glutathione and catalase levels in gastric mucosa. Hesperidin allowed the regeneration of ulcerated tissue, and prevented hemorrhagic injury of gastric mucosa. The potential anti-ulcer effect of hesperidin may be due to antioxidant, mucoprotective and cytoprotective activities.

An Open-Label, Multicenter Post Marketing Study to Assess the Symptomatic Efficacy and Safety of Troxipide [TroxipTM] in the Management of Acid Peptic Disorders in Indian Patients.

Aims: A post marketing study to assess the symptomatic efficacy and safety of Troxipide (TROXIPTM) 100mg in the management of acid peptic disorders (APDs) in Indian population. Study Design: An observational, prospective, uncontrolled, open-label, multicenter post marketing study. Place and Duration of Study: Patients were enrolled from 62 centers across 11 states of India, between October 2010 and March 2012. Methodology: Out of 1500 APD patients, 1486 (850 men, 636 women; age range 16-85 years) were prescribed Troxipide 100mg tablet orally thrice daily. The efficacy and safety assessments were performed on day 14 and day 28 after beginning the treatment and recorded in the case report forms. The efficacy of Troxipide was estimated based on the changes from the baseline in the symptom score on a 100 point visual analogue scale (VAS) for individual symptoms. Safety was assessed by adverse events reported with usage of Troxipide on day 14 and day 28 after start of the treatment. Results: Troxipide monotherapy (n=1427) significantly reduced the mean VAS score from baseline for all major symptoms, viz. nausea, vomiting, belching, heart burn, epigastric pain, acid regurgitation, abdominal bloating & loss of appetite at the end of the study. The global mean VAS score (a sum of individual symptom VAS score) of these patients decreased from 134.26 ± 75.31 to 21.88 ± 39.52 at the end of the study (P < .001). All the patients who were previously treated but uncontrolled, with acid inhibitors like proton pump inhibitors (PPIs), histamine 2 receptor antagonists (H2RAs) etc. had a significant reduction in the VAS score from 164.38 ± 64.54 to 35.56 ± 54.24 on day 28 (P<.001). Troxipide was well tolerated with overall incidence of adverse events being 1.05% (n=15) and all the events were resolved without any sequel. Conclusion: The present study demonstrates that Troxipide symptomatically controls APDs like gastritis, dyspepsia, gastro-esophageal reflux disease (GERD) and ulcers with good tolerability.

Hepatic Ischemic Preconditioning Provides Protection Against Distant Renal Ischemia and Reperfusion Injury in Mice

We previously demonstrated that there are acute and delayed phases of renal protection against renal ischemia and reperfusion (IR) injury with renal ischemic preconditioning (IPC). This study assessed whether hepatic IPC could also reduce distant renal IR injury through the blood stream-mediated supply of reactive oxygen species (ROS). Male C57BL/6 mice were randomly divided into four groups: group I, sham operated including right nephrectomy; group II (IR), left renal ischemia for 30 min and reperfusion injury; group III (IPC-IR), hepatic ischemia for 10 min followed by 10 min of reperfusion before left renal IR injury; group IV (MPG - IPC + IR), pretreated with 100 mg/kg N-(2-mercaptopropionyl)-glycine (MPG) 15 min before hepatic IPC and left renal IR injury. Renal function, histopathologic findings, proinflammatory cytokines, and cytoprotective proteins were evaluated 15 min or 24 hr after reperfusion. Hepatic IPC attenuated the expression of proinflammatory cytokines, tumor necrosis factor alpha, intercellular adhesion molecule 1, and induced inducible nitric-oxide synthase, and the phosphorylation of Akt in the murine kidney. Renal function was better preserved in mice with hepatic IPC (group III) than groups II or IV. Hepatic IPC protects against distant renal IR injury through the blood stream-delivery of hepatic IPC-induced ROS, by inducing cytoprotective proteins, and by inhibiting inflammatory reactions.