Potential antioxidant and cytoprotective effects of essential oil extracted from Cymbopogon citratus on OxLDL and H_(2)O_(2) LDL induced Human Peripheral Blood Mononuclear Cells(PBMC)

Cymbopogon citratus(lemon grass)is commonly used in traditional folk medicine.The essential oil extracted from C.citratus has been reported as a potential anti-oxidant and anti-inflammatory agent.This study has been designed to explore the protective effect of C.citratus(lemon grass)against modified LDL(OxLDL and H2O2 LDL)induced cytotoxicity in Peripheral Blood Mononuclear Cells(PBMC).The essential oil extracted from C.citratus(EOC)was subjected to FT-IR spectroscopic analysis for the identification of functional groups.In vitro antioxidant assays were carried out to assess the electron donating capability of EOC as compared with a known standard L-ascorbic acid.The cytoprotective effects of EOC were determined in PBMC induced with modified LDL.Spectra obtained from FT-IR analysis showed the presence of functional groups in EOC such as H-bonded,O-H stretching,N-H stretching,aldehyde-C-H stretching,aldehyde/ketone-C=O stretching,-C=C-stretching,-CH_(3) bending,-C-H in plane bending.EOC has greater antioxidant property when compared with the standard L-ascorbic acid.EOC at all test concentrations demonstrated free radical scavenging activity and cytoprotective effect when challenged against modified LDL in PBMC.The above results show EOC as a promising antioxidant and cytoprotective agent.

Cytoprotective,antihyperglycemic and phytochemical properties of Cocos nucifera(L.) inflorescence

Objective:To analyze the eytoproteetive and antidiabetic activities as well as phytochemical composition of the immature inflorescence of Cocas nucifera belonging to the Arecaceae Family.Methods:The phytochemical screening of inflorescence was done to determine the major constituents present in Cocos nucifera inflorescence.The free radical scavenging potential of inflorescence extracts were evaluated using in vitro radical scavenging assay models.Results:The phytochemical analyses on inflorescence showed the presence of phenolic compounds,flavonoids.resins and alkaloids.The macronutrient analyses,on the other hand,showed the presence of carbohydrate,proteins and fibers.Administration of the methanol extract of coconut inflorescence to the diabetic rats showed dose dependent reduction in hyperglycemia.The cytoprotective property of coconut inflorescence was evidenced from the acute toxicological evaluation.The levels of serum aspartate aminotransferase,alanine aminotransferase,and alkaline phosphatase were significantly decreased in the diabetic rats treated with inflorescence when compared with the diabetic control rats.Conclusion:The results obtained from the present study apparently proved the non-toxic nature and the eytoproteetive and antihyperglycemic properties of coconut inflorescence.

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 H_2O_2 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 H_2O_2stimulated or induced macrophages,respectively.Conclusions:These results suggest that A.pavonina extract suppresses the intra cellular peroxide production.

HPLC Polyphenolics Profile and H2O2 Induced Cytoprotective Effect of Salacia oblonga Extracts on Human Lymphocytes

Salacia oblonga (Wall.) belonging to the family Celastraceae is an important medicinal plant available in India and Sri Lanka. It possesses an array of pharmacological and therapeutic properties. In the present study phenolic compounds of S. oblonga methanolic extracts were estimated by high performance liquid chromatography (HPLC) indicating the presence of catechin, quercetin, synapic acid and syringic acid. The study involved evaluation of S. oblonga extracts for cytotoxic and cytoprotective effects on human lymphocytes. Aerial extracts have significant protective activity against hydrogen peroxide (H2O2) induced cytotoxic activity in comparison to the root extracts. The results relate the cytoprotective effect of S. oblonga due to the presence of poly phenols and other phytochemicals, as they have significant ability to remove free radicals or reactive species and might induce the expression of antioxidant enzymes inside the cells.

Cytoprotective effects of quercetin and its sugar-containing natural congeners in cultured HEK293 cells injured by anoxia/hypoglycemia and the structure-effect relationship thereto

Objective To comparatively study anti-free radical and cytoprotective effects of quercetin(Q)and its monoglucoside isoquercetin(I),diglucoside rutin(R),which differs only in glycosyl-substitution at C-3 position of the molecules,using anoxia/hypoglycemia-induced cell injury model and thereby to explore the structure-effect relationship thereto.Methods The cell injury model was established by HEK293 cells cultured in vitro with Na2S2O3 plus sugar-free Earle's fluid as incubation medium;Cell survival rate(CSR),total antioxidant capacity(TAC),SOD and LDH levels were determined;The effect intensity of the 3 flavonoids were compared by means of IC50,the concentration required to achieve 50% inhibition of the changes in the above indices in injured cells.Results Q,I and R all concentration-dependently elevated CSR,TAC and SOD,and reduced LDH level;the all of IC50s for the above indices were ranked in order of IC50,Q<IC50,I<IC50,R,namely,the effect intensity should be Q>I>R.Conclusions The 3 structurally similar flavoloids all have significant and concentration-dependent anti-free radical and cyto-protective effects with the intensity being in order of aglycone>monoglucoside>diglucoside;the substitution of-OH by sugar group at C-3 position of flavoloids and increase in the sugar-substituent number are associated with the effect intensity reduced;namely,the intensity of these effects of flavonoids is negatively related the substutution by sugar group at C-3 position.

Anti-free radical and cytoprotective effects of quercetin and its sugar-containing natural congeners in cultured HEK293 cells injured by anoxia/hypoglycemia and the structure-effect relationship thereto

Objective To comparatively study anti-free radical and cytoprotective effects of quercetin(Q)and its monoglucoside isoquercetin(I),diglucoside rutin(R),which differs only in glycosyl-substitution at C-3 position of the molecules,using anoxia/hypoglycemia-induced cell injury model and thereby to explore the structure-effect relationship thereto.Methods The cell injury model was established by HEK293 cells cultured in vitro with Na2S2O3 plus sugar-free Earle's fluid as incubation medium.Cell survival rate(CSR),total antioxidant capacity(TAC),SOD and LDH levels were determined.The effect intensity of the 3 flavonoids was compared by means of IC50,the concentration required to achieve 50% inhibition of the changes in the above indices in injured cells.Results Q,I and R all concentration-dependently elevated CSR,TAC and SOD and reduced LDH level.The all of IC50s for the above indices were ranked in order of IC50,Q<IC50,I<IC50,R,namely,the effect intensity should be Q>I >R.Conclusions The 3 structurally similar flavoloids all have significant and concentration-dependent anti-free radical and cyto-protective effects with the intensity being in order of aglycone>monoglucoside>diglucoside;the substitution of-OH by sugar group at C-3 position of flavoloids and increase in the sugar-substituent number are associated with the effect intensity reduced;namely,the intensity of these effects of flavonoids is negatively related the substutution by sugar group at C-3 position.

Cytoprotective Mechanism of the Novel Gastric Peptide BPC157 in Gastrointestinal Tract and Cultured Enteric Neurons and Glial Cells

Dear Editor,Body protection compound (BPC) 157 is a stable gastric pentadecapeptide. Predrag Sikiric’s team has carried out many investigations of its cytoprotective effects in different organs and tissues (1, 2)Their evidence indicates that BPC157 has potent cytoprotection in neural injury and gastrointestinal (GI) ulcers. Nevertheless.

αB-crystallin mini-peptides support corneal healing in vitro and in vivo in rabbit model

AIM:To evaluate if topical use of αB-crystallin minipeptides supports corneal healing following flap surgery.METHODS:Cultured corneal cells were treated with fluorescent taggedαB-crystallin mini-peptides to assess its internalization.Cultured corneal cells pre-treated with or without the mini-peptides were exposed to H_(2)O_(2) and cell viability was examined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide(MTT)assay.Elongation of neurites of cultured trigeminal neurones was examined following treatment either withαB-crystallin mini-peptides or protein.Cultured trigeminal neurones were pre-treated either with αB-crystallin mini-peptides or crystallin protein and exposed to H_(2)O_(2) and presence of beading in the dendrites and axons was assessed.Corneal flap surgery was conducted on rabbit cornea and treated topically either withαB-crystallin peptide(0.5 mg/mL thrice daily for 14d)or phosphate-buffered saline(PBS).Corneal healing was evaluated under slit-lamp biomicroscope,mRNA expression of inflammatory cytokines were assessed and the corneas were evaluated by histopathology.RESULTS:Internalization ofαB-crystallin mini-peptides was ascertained by the detection of fluorescence within the corneal cells.The MTT assay revealed that treatment withαB-crystallin mini-peptide reduced cell death induced by H_(2)O_(2) treatment.The mini-peptides did not influence the elongation of trigeminal neurites,but significantly(P<0.05)reduced beading in the neurites.In rabbit eye,the treated corneas showed reduced hyper-reflective zones(P<0.05)and suppression in the expression of inflammatory cytokines.Histopathological examination also revealed reduction of inflammatory response in treated corneas.CONCLUSION:TheαB-crystallin mini-peptides restrict the damage to corneal cells and neurons and aids in corneal healing.

A cytoprotective graphene oxide-polyelectrolytes nanoshell for single-cell encapsulation

Graphene oxide(GO)has been increasingly utilized in the fields of food,biomedicine,environment and other fields because of its benign biocompatible.We encapsulated two kinds of GO with different sizes on yeast cells with the assistance of polyelectrolytes poly(styrene sulfonic acid)sodium salt(PSS)and polyglutamic acid(PGA)(termed as Y@GO).The result does not show a significant difference between the properties of the two types of Y@GO(namely Y@GO1 and Y@GO2).The encapsulation layers are optimized as Yeast/PGA/PSS/PGA/GO/PGA/PSS based on the morphology,dispersity,colony-forming unit,and zeta potential.The encapsulation of GO increases the roughness of the yeast.It is proved that the Y@GO increases the survival time and enhance the activity of yeast cells.The GO shell improves the resistance of yeast cells against pH and salt stresses and extends the storage time of yeast cells.

Potato protease inhibitors,a functional food material with antioxidant and anticancer potential

Potato protease inhibitors(PPIs),as the main component of potato protein isolate,have good safety,nutrition and great market potential.The antioxidant and anticancer properties of PPIs were evaluated with cellbased biological assays.The results showed that when the concentration of PPIs was 5 mg/mL,the peroxyl radical scavenging value was(2119±204)mg VCE/100 g,and the cellular antioxidant activity values were(45.83±3.5)(no PBS wash)and(33.25±4.4)μmol QE/100 g(PBS wash).Cells pretreated with PPIs could significantly prevent the oxidative damage induced by H_(2)O_(2),inhibit the morphological changes of cells and maintain the integrity.Furthermore,PPIs had selective anti-proliferative effects on GIST882 cells(IC50=(10.53±3.87)mg/mL)and demonstrated potent inhibition of the growth,migration and invasion of cancer cells.These findings provide a scientific basis for PPIs as promising candidates for functional foods to aid in the prevention of oxidative damage and cancer.

Stomach perforation-induced general occlusion/occlusion-like syndrome and stable gastric pentadecapeptide BPC 157 therapy effect

BACKGROUND Using rat stomach perforation as a prototypic direct lesion applied in cytoprotection research,we focused on the first demonstration of the severe occlusion/occlusion-like syndrome induced by stomach perforation.The revealed stomachinduced occlusion/occlusion-like syndrome corresponds to the previously described occlusion/occlusion-like syndromes in rats suffering multicausal pathology and shared severe vascular and multiorgan failure.This general point was particularly reviewed.As in all the described occlusion/occlusion-like syndromes with permanent occlusion of major vessels,peripheral and central,and other similar noxious procedures that severely affect endothelium function,the stable gastric pentadecapeptide BPC 157 was resolving therapy.AIM To reveal the stomach perforation-induced general occlusion/occlusion-like syndrome and BPC 157 therapy effect.METHODS The procedure included deeply anesthetized rats,complete calvariectomy,laparotomy at 15 min thereafter,and stomach perforation to rapidly induce vascular and multiorgan failure occlusion/occlusion-like syndrome.At 5 min post-perforation time,rats received therapy[BPC 157(10μg or 10 ng/kg)or saline(5 mL/kg,1 mL/rat)(controls)]into the perforated defect in the stomach).Sacrifice was at 15 min or 60 min post-perforation time.Assessment(gross and microscopy;volume)included:Brain swelling,peripheral vessels(azygos vein,superior mesenteric vein,portal vein,inferior caval vein)and heart,other organs lesions(i.e.,stomach,defect closing or widening);superior sagittal sinus,and peripherally the portal vein,inferior caval vein,and abdominal aorta blood pressures and clots;electrocardiograms;and bleeding time from the perforation(s).RESULTS BPC 157 beneficial effects accord with those noted before in the healing of the perforated defect(raised vessel presentation;less bleeding,defect contraction)and occlusion/occlusion-like syndromes counteraction.BPC 157 therapy(into the perforated defect),induced immediate shrinking and contraction of the whole stomach(unlike considerable enlargement by saline application).Accordingly,BPC 157 therapy induced direct blood delivery via the azygos vein,and attenuated/eliminated the intracranial(superior sagittal sinus),portal and caval hypertension,and aortal hypotension.Thrombosis,peripherally(inferior caval vein,portal vein,abdominal aorta)and centrally(superior sagittal sinus)BPC 157 therapy markedly reduced/annihilated.Severe lesions in the brain(swelling,hemorrhage),heart(congestion and arrhythmias),lung(hemorrhage and congestion),and marked congestion in the liver,kidney,and gastrointestinal tract were markedly reduced.CONCLUSION We revealed stomach perforation as a severe occlusion/occlusion-like syndrome,peripherally and centrally,and rapid counteraction by BPC 157 therapy.Thereby,further BPC 157 therapy may be warranted.

Protective effects of prostaglandin E1 on hepatocytes

INTRODUCTION E Numerous studies have demonstrated the protective action of prostaglandin E1(PGE1) on experimental animal models of liver injury and on patients with

Effect of an extraction solvent on the antioxidant quality of Pinus densiflora needle extract

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.

Is autophagy induction by PARP inhibitors a target for therapeutic benefit?

PARP inhibitors have proven to be effective in conjunction with conventional therapeutics in the treatment of various solid as well as hematologic malignancies,particularly when the tumors are deficient in DNA repair pathways.However,as the case with other chemotherapeutic agents,their effectiveness is often compromised by the development of resistance.PARP inhibitors have consistently been reported to promote autophagy,a process that maintains cellular homeostasis and acts as an energy source by the degradation and reutilization of damaged subcellular organelles and proteins.Autophagy can exhibit different functional properties,the most prominent being cytoprotective.In addition,both cytotoxic and non-protective functions forms have also been identified.In this review,we explore the available literature regarding the different roles of autophagy in response to clinically-used PARP inhibitors,highlighting the possibility of targeting autophagy as an adjuvant therapy to potentially increase the effectiveness of PARP inhibition and to overcome the development of resistance.

Separation and Bio-activities of Spirostanol Saponin from Tribulus terrestris

Gross saponins of Tribulus terrestris（GSTT） have exact effect on cardiovascular and cerebrovascular diseases.But as a mixture,the specific efficient component of GSTT is still unknown.Nine monomers of spirostanol saponins were isolated and idendified as JA―JI（named transitorily） by means of NMR spectrometry.After bio-activity screening on them,we defined that monomers tigogenin 3-O-β-D-xylopyranosyl（1→2）-[β-D-xylopyranosyl（1→3）]-β-D-glucopyranosyl（1→4）-[α-L-rhamnopyranosyl（1→2）]-β-D-galactopyranoside（compound JB） and hecogenin3-O-β-D-glucopyranosyl（1→4）-β-D-galactopyranoside（compound JG） have cytoprotective bio-activity.Compound JB display effective dose in 10-8 and 10-9 mol/L,and JG in 10-6―10-9 mol/L.Survival rate,lactate dehydrogenase（LDH） and apoptosis also show that JB（at dose 10-8,10-9 and 10-10 mol/L） can protect myocardial injury caused by hypoxia/reoxygenation（H/R）.While morphology change also shows JG has cytoprotective bio-activity.

ACUPUNCTURE-MOXIBUSTION, HEAT SHOCK PROTEIN 70 AND CYTOPROTECTION

Pleat shock protein 70 （HSP70） is a kind of non-specific cytoprotective protein, and its generation can be induced by acupuncture and moxibustion. In the present paper, the authors review the protective actions of HSP70 on the heart, gastric mucosa, liver, brain tissues, kidney, etc., and the relationship among acupuncture/moxibustion, heat shock protein and the cytoprotective actions. It is worth studying the cytoprotective effect of acupuncture and moxibustion by way of the resultant generation of HSP70 in the organism.

Antioxidant Activity and Protective Effects of Alcalase-Hydrolyzed Soybean Hydrolysate in Human Intestinal Epithelial Caco-2 Cells

Soybeans are known as a promising source of bioactive peptides.However,knowledge on the antioxidant behaviors of soybean protein hydrolysate(SPH)in the human intestinal epithelium is limited.In this study,SPH was prepared with Alcalase and subsequently ultrafiltered into four peptide fractions as SPH-I(<3 kDa),SPH-II(3~5 k Da),SPH-III(5~10 k Da)and SPH-IV(>10 kDa).The antioxidant properties of SPH and membrane fractions were investigated using different chemical assays and their protective effects against oxidative stress were evaluated using H2 O2-stressed human intestinal Caco-2 cells.Results showed that SPH-I exhibited the strongest 2,2-diphenyl-1-picrylhydrazyl(DPPH)radical scavenging activity(IC50=2.56 mg/m L)and reducing capacity while SPH-III had the best metal ion-chelating activity(IC50=0.29 mg/m L).Both SPH and the peptide fractions dose-dependently suppressed intracellular reactive oxygen species(ROS)accumulation induced by H2O2 in Caco-2 cells,but the strongest inhibitory effect was observed for SPH-I.Amino acid(AA)results revealed that SPH-I was rich in hydrophobic and antioxidant AAs,which could contribute to its stronger antioxidant properties.Additionally,SPH-I protected Caco-2 cells from H2O2-induced oxidative stress via inhibiting lipid peroxidation and stimulating antioxidant enzyme activities.These results suggest that SPH-I and constitutive peptides can be beneficial ingredients with antioxidant properties and protective effects against ROS-mediated intestinal injury.

Heme in intestinal epithelial cell turnover, differentiation, detoxification, inflammation, carcinogenesis, absorption and motility

The gastrointestinal tract is lined by a simple epithelium that undergoes constant renewal involving cell division, differentiation and cell death. In addition, the epithelial lining separates the hostile processes of digestion and absorption that occur in the intestinal lumen from the aseptic environment of the internal milieu by defensive mechanisms that protect the epithelium from being breached. Central to these defensive processes is the synthesis of heme and its catabolism by heme oxygenase （HO）. Dietary heme is also an important source of iron for the body which is taken up intact by the enterocyte. This review describes the recent literature on the diverse properties of heme/HO in the intestine tract. The roles of heme/HO in the regulation of the cell cycle/ apoptosis, detoxification of xenobiotics, oxidative stress, inflammation, development of colon cancer, hemeiron absorption and intestinal motility are specifically examined.

Heme oxygenase-1 and gut ischemia/reperfusion injury: A short review

Ischemia/reperfusion (I/R) injury of the gut is a significant problem in a variety of clinical settings and is associated with a high morbidity and mortality. Although the mechanisms involved in the pathogenesis of gut I/R injury have not been fully elucidated, it is generally believed that oxidative stress with subsequent inflammatory injury plays an important role. Heme oxygenase (HO) is the rate-limiting enzyme in the catabolism of heme, followed by production of CO, biliverdin, and free iron. The HO system is believed to confer cytoprotection by inhibiting inflammation, oxidation, and apoptosis, and maintaining microcirculation. HO-1, an inducible form of HO, serves a vital metabolic function as the rate-limiting step in the heme degradation pathway, and affords protection in models of intestinal I/R injury. HO-1 system is an important player in intestinal I/R injury condition, and may offer new targets for the management of this condition.

A prospective randomized trial of lafutidine vs rabeprazole on post-ESD gastric ulcers

AIM:To compare the effects of rabeprazole and lafutidine on post-endoscopic submucosal dissection(ESD) gastric ulcers.METHODS:Patients with gastric tumors indicated for ESD were prospectively studied.After ESD,all patients were treated with intravenous omeprazole for the first 3 d.Patients were then randomly assigned to oral lafutidine or rabeprazole.Ulcer size,ulcer size reduction rate,and ulcer stage were evaluated 4 wk later.Occurrence of complication was monitored throughout the 4-wk period.RESULTS:Sixty five patients were enrolled in the study,and 60 patients were subjected to the final analysis.In the lafutidine group(30 lesions in 29 patients),initial and 4-wk post-ESD ulcer sizes were 33.3 ± 9.2 and 10.5 ± 4.8 mm,respectively.In the rabeprazole group(34 lesions in 31 patients),the values were 34.7 ± 11.3 and 11.8 ± 6.7 mm,respectively.Ulcer size reduction rates in lafutidine and rabeprazole groups were 32.3% and 33.5%,respectively(P=0.974).Ulcer stage 4 wk post-ESD did not differ significantly between the two groups(P=0.868).Two cases in the rabeprazole group and no cases in the lafutidine group developed ulcer bleeding during the oral dose period,although the difference of bleeding rate between the two groups was not statistically significant(P=0.157).CONCLUSION:Lafutidine and rabeprazole have equivalent therapeutic effects on post-ESD gastric ulcers.