Objective:To evaluate the effect of rosmarinic acid on tracheal smooth muscle responsiveness and lung pathological changes in ovalbumin-sensitized rats.Methods:Rats were randomly divided into six groups:the control gr...Objective:To evaluate the effect of rosmarinic acid on tracheal smooth muscle responsiveness and lung pathological changes in ovalbumin-sensitized rats.Methods:Rats were randomly divided into six groups:the control group,the asthmatic group,and the asthmatic groups treated with dexamethasone(1 mg/kg;oral gavage)or three doses of rosmarinic acid(0.5,1,and 2 mg/kg;oral gavage).For induction of asthma,rats received intraperitoneal injections and inhalation of ovalbumin.After 21 days,bronchoalveolar lavage fluid and lung samples were collected for histopathological analyses.Moreover,total and differential white blood cell counts were determined.Results:The rosmarinic acid-treated group had significantly lower tracheal smooth muscle responses to methacholine than the asthmatic group.In addition,rosmarinic acid reduced white blood cell count and the percentages of eosinophils,monocytes,and neutrophils while increasing the percentage of lymphocytes.Ovalbumin-induced lung pathological changes were significantly improved by treatment with rosmarinic acid.Conclusions:Rosmarinic acid improves tracheal smooth muscle responsiveness and lung pathological changes in ovalbumin-sensitized rats.展开更多
Objective:To investigate the antifibrotic role of rosmarinic acid(RA),a natural polyphenolic compound,on HSCs activation/proliferation and apoptosis in vitro and in vivo. Methods:The impact of RA on stellate cell line...Objective:To investigate the antifibrotic role of rosmarinic acid(RA),a natural polyphenolic compound,on HSCs activation/proliferation and apoptosis in vitro and in vivo. Methods:The impact of RA on stellate cell line(HSC-T6) proliferation,activation and apoptosis was assessed along with its safety on primary hepatocytes. In vivo,rats were divided into:(i) normal;(ii) thioacetamide(TAA)-intoxicated rats for 12 weeks;(iii) TAA+silymarin or(iv) TAA+RA. At the end of experiment,liver functions,oxidative stress,inflammatory and profibrogenic markers,tissue inhibitor metalloproteinases type-1(TIMP-1) and hydroxyproline(HP) levels were evaluated. Additionally,liver histopathology and immunohistochemical examinations of alpha-smooth muscle actin(α-SMA),caspase-3 and proliferation cellular nuclear antigen(PCNA) were determined. Results:RA exhibited anti-proliferative effects on cultured HSCs in a time and concentration dependent manner showing an IC50 of 276 μg/mL and 171 μg/mL for 24 h and 48 h,respectively,with morphological reversion of activated stellate cell morphology to quiescent form. It significantly improved ALT,AST,oxidative stress markers and reduced TIMP-1,HP levels,inflammatory markers and fibrosis score(S1 vs S4). Furthermore,reduction in α-SMA plus elevation in caspase-3 expressions of HSCs in vitro and in vivo associated with an inhibition in proliferation of damaged hepatocytes were recorded. Conclusions:RA impeded the progression of liver fibrosis through inhibition of HSCs activation/proliferation and induction of apoptosis with preservation of hepatic architecture.展开更多
The aim of this study was to characterize the polyphenolic composition by determination of chemical fingerprints of Methanolic extracts of Ocimum canum Sims, Ocimum basilicum L. and Ocimum gratissimum L. from Democrat...The aim of this study was to characterize the polyphenolic composition by determination of chemical fingerprints of Methanolic extracts of Ocimum canum Sims, Ocimum basilicum L. and Ocimum gratissimum L. from Democratic Republic of Congo and to compare their antisickling activity of that of rosmarinic acid, the major compound to those of methanolic extracts. Phytochemical analysis performed by TLC and HPLC analysis, showed that rosmarinic acid is the most abundant phenolic acid in these Ocimum species according to the following order O. basilicum L., O. gratissimum L. and O. canum Sims. Methanolic extracts of these three species and pure rosmarinic acid showed significant antisickling activities with minimal concentration of normalization values of 0.18 ± 0.03, 0.23 ± 0.04, 0.26 ± 0.04 and 0.31 ± 0.05 mg/mL for rosmarinic acid, O. basilicum L., O. gratissimum L. and O. canum Sims methanolic extracts respectively. The antisickling activity order is the same as that of the rosmarinic acid content, indicating that this polyphenolic acid would be among the main active molecules in these extracts.展开更多
<span style="font-family:Verdana;">The aim of this study was to investigate the effect of rosmarinic acid against gonadal toxicity caused by cyclophosphamide, an important anticancer drug. A total of 2...<span style="font-family:Verdana;">The aim of this study was to investigate the effect of rosmarinic acid against gonadal toxicity caused by cyclophosphamide, an important anticancer drug. A total of 28 rats were divided into 4 groups, with 7 animals in each group. The groups were created as follows;Group 1 (control) (n = 7): Subjects received only 1 ml of 0.9% saline solution per day intraperitoneally for 14 days. Group 2 (Rosmarinic Acid) (n = 7): The subjects were given 20 mg/kg Rosmarinic acid intraperitoneally for 14 days. Group 3 (Cyclophosphamide) (n = 7): Only 1 ml of 0.9% saline solution was administered intraperitoneally to the subjects for the first 7 days. Cyclophosphamide 20 mg/kg per day was administered intraperitoneally for the last 7 days (from the 8</span><sup><span style="font-family:Verdana;">th</span></sup><span style="font-family:Verdana;"> day)</span><span style="font-family:Verdana;">. Group 4 (Rosmarinic Acid</span><span style="font-family:;" "=""> </span><span style="font-family:;" "=""><span style="font-family:Verdana;">+ Cyclophosphamide) (n = 7): The subjects were given 20 mg/kg Rosmarinic acid daily intraperitoneally for 14 days. From the 8</span><sup><span style="font-family:Verdana;">th</span></sup><span style="font-family:Verdana;"> day of the experiment to the end of the experiment (last 7 days of the experiment), 20 mg/kg cyclophosphamide was given intraperitoneally daily. At the end of the experiment, body weights of all rats were measured first. Afterwards, the weights of testicular tissue samples were measured and the averages of the weights were taken. Routine tissue follows up was performed on the testicular tissues taken. Hematoxylin-eosin staining was applied to tissue sections of 5 μm thickness. As a result of the statistical analysis, it was determined that cyclophosmadine decreased body and testicular weight, but rosmarinic acid had a protective effect on the contrary. It was concluded that cyclophosmadine caused damage to the basement membrane structure, Sertoli, Leydig and germ cells, but these structures were preserved due to the protective effect of rosmarinic acid. Despite the toxic effect of CP, rosmarinic acid is thought to have a significant curative effect on the spermatogenetic process and seminiferous tubule structure in the gonads.</span></span>展开更多
Rosmarinic acid,a common ester extracted from Rosemary,Perilla frutescens,and Salvia miltiorrhiza Bunge,has been shown to have protective effects against various diseases.This is an investigation into whether rosmarin...Rosmarinic acid,a common ester extracted from Rosemary,Perilla frutescens,and Salvia miltiorrhiza Bunge,has been shown to have protective effects against various diseases.This is an investigation into whether rosmarinic acid can also affect the changes of white matter fibers and cognitive deficits caused by hypoxic injury.The right common carotid artery of 3-day-old rats was ligated for 2 hours.The rats were then prewarmed in a plastic container with holes in the lid,which was placed in 37°C water bath for 30 minutes.Afterwards,the rats were exposed to an atmosphere with 8% O2 and 92% N2 for 30 minutes to establish the perinatal hypoxia/ischemia injury models.The rat models were intraperitoneally injected with rosmarinic acid 20 mg/kg for 5 consecutive days.At 22 days after birth,rosmarinic acid was found to improve motor,anxiety,learning and spatial memory impairments induced by hypoxia/ischemia injury.Furthermore,rosmarinic acid promoted the proliferation of oligodendrocyte progenitor cells in the subventricular zone.After hypoxia/ischemia injury,rosmarinic acid reversed to some extent the downregulation of myelin basic protein and the loss of myelin sheath in the corpus callosum of white matter structure.Rosmarinic acid partially slowed down the expression of oligodendrocyte marker Olig2 and myelin basic protein and the increase of oligodendrocyte apoptosis marker inhibitors of DNA binding 2.These data indicate that rosmarinic acid ameliorated the cognitive dysfunction after perinatal hypoxia/ischemia injury by improving remyelination in corpus callosum.This study was approved by the Animal Experimental Ethics Committee of Xuzhou Medical University,China (approval No.20161636721) on September 16,2017.展开更多
AIM: To investigate the anti-fibrosis effect of rosmarinic acid(RA) in pterygium epithelial cells(PECs) to determine if RA is a potent agent for treating pterygium.METHODS: The PECs(1×10~4 cells/mL) were treated ...AIM: To investigate the anti-fibrosis effect of rosmarinic acid(RA) in pterygium epithelial cells(PECs) to determine if RA is a potent agent for treating pterygium.METHODS: The PECs(1×10~4 cells/mL) were treated with 100 μmol/L of RA for 1, 3 and 6h. After RA treatment, the cell viability was determined by staining with acridine orange/DAPI and analysis via a NucleoC ounter NC-3000. The protein expression levels of type I collagen, transforming growth factor beta-1(TGF-β1), TGF-β type Ⅱ receptor(TGF-βRⅡ), p-Smad1/5, p-Smad2, p-Smad3, and Smad4 of the cell lysates were measured by Western blot analysis.RESULTS: The cell viability of PECs was significantly decreased after RA treatment(P<0.01). As the result, RA reduced the protein expression of typeⅠcollagen and TGF-β1 of PECs. Additionally, RA also inhibited TGF-β1/Smad signaling by decreasing the protein expressions of TGF-βRII, p-Smad1/5, p-Smad2, p-Smad3, and Smad4.CONCLUSION: This study demonstrate that RA could inhibit fibrosis of PECs by down-regulating type I collagen expression and TGF-β1/Smad signaling. Therefore, RA is a potent therapeutic agent for the treatment of pterygium.展开更多
Alzheimer disease(AD) as worldwide progressive neurodegenerative disease is prevalent disease among elderly population. Due to limitation in chemical drugs along with their adverse effects of these treatments, researc...Alzheimer disease(AD) as worldwide progressive neurodegenerative disease is prevalent disease among elderly population. Due to limitation in chemical drugs along with their adverse effects of these treatments, research for finding more effective natural drugs, is one of interesting subjects among the scientists. Melissa officinalis(M. officinalis) has a long history of use in treatment of nervous system diseases. This review article evaluates the potency of M. officinalis in treatment of AD by review of experimental and clinical documents on the efficacy, safety and its mechanisms of action in management of AD. The information is extracted from electronic resources(PubMed, Wiley, Springer and Science Direct), English and Persian scientific books. In spite of different scientific and non-scientific reports on the use of M. officinalis and its main component of rosmarinic acid in neurodegenerative diseases, there is only one clinical trial on the efficacy of M. officinalis ethanol extract in management of AD. Different mechanisms of action for M. officinalis, including inhibitory effects against amyloid beta, reactive oxygen species, and acetylcholine esterase, are involved. Larger clinical trials are recommended to confirm the efficacy and safety of M. officinalis extracts in treatment of AD patients.展开更多
Rosmarinic acid(RA) can elicit a neuroprotective effect against ischemic stroke, but the precise molecular mechanism remains poorly understood. In this study, an experimental ischemic stroke model was established in C...Rosmarinic acid(RA) can elicit a neuroprotective effect against ischemic stroke, but the precise molecular mechanism remains poorly understood. In this study, an experimental ischemic stroke model was established in CD-1 mice(Beijing Vital River Laboratory Animal Technology, Beijing, China) by occluding the right middle cerebral artery for 1 hour and allowing reperfusion for 24 hours. After intraperitoneally injecting model mice with 10, 20, or 40 mg/kg RA, functional neurological deficits were evaluated using modified Longa scores. Subsequently, cerebral infarct volume was measured using TTC staining and ischemic brain tissue was examined for cell apoptosis with TUNEL staining. Superoxide dismutase activity and malondialdehyde levels were measured by spectrophometry. Expression of heme oxygenase-1(HO-1), nuclear factor erythroid 2-related factor 2(Nrf2), Bcl-2, Bax, Akt, and phospho-Ser473 Akt proteins in ischemic brain tissue was detected by western blot, while mRNA levels of Nrf2, HO-1, Bcl-2, and Bax were analyzed using real time quantitative PCR. In addition, HO-1 enzyme activity was measured spectrophotometrically. RA(20 and 40 mg/kg) greatly improved neurological function, reduced infarct volume, decreased cell apoptosis, upregulated Bcl-2 protein and mRNA expression, downregulated Bax protein and mRNA expression, increased HO-1 and Nrf2 protein and mRNA expression, increased superoxide dismutase activity, and decreased malondialdehyde levels in ischemic brain tissue of model mice. However, intraperitoneal injection of a HO-1 inhibitor(10 mg/kg zinc protoporphyrin IX) reversed the neuroprotective effects of RA on HO-1 enzyme activity and Bcl-2 and Bax protein expression. The PI3 K/Akt signaling pathway inhibitor LY294002(10 mM) inhibited Akt phosphorylation, as well as Nrf2 and HO-1 expression. Our findings suggest that RA has anti-oxidative and anti-apoptotic properties that protect against ischemic stroke by a mechanism involving upregulation of Nrf2 and HO-1 expression via the PI3 K/Akt signaling pathway.展开更多
OBJECTIVE To evaluate the synergistic effect of rosmarinic acid(RA)with antibiotics against Staphylococcus aureus(S.aureus)and MRSA and to identify the possible mechanism of action responsible for synergism if any.MET...OBJECTIVE To evaluate the synergistic effect of rosmarinic acid(RA)with antibiotics against Staphylococcus aureus(S.aureus)and MRSA and to identify the possible mechanism of action responsible for synergism if any.METHODS The antibacterial activity of Rosmarinic acid was studied for its zone of inhibition by agar well diffusion and MIC determination by liquid broth dilution technique against MRSA and VRSA.The synergistic effect of RA with antibiotics like amoxicillin,ofloxacin and vancomycin was evaluated by Broth checker board method and further confirmed with time kill kinetic studies.Microbial Surface Components Recognizing Adhesive Matrix Molecules(MSCRAMMs)were isolated by protein precipitation technique and its expression was studied by SDS PAGE.Further RA was evaluated for its beta lactamase inhibition property.RESULTS Rosmarinic acid exhibited antibacterial activity against S.aureus and MRSAby showing a MIC value of 0.8mg·mL-1 against S.aureus and 10mg·mL-1 against MRSA.Rosmarinic acid at 1/4X MIC value reduced the MIC of vancomycin,amoxicillin and ofloxacin by 1/4 times against S.aureus.But against MRSA,vancomycin was found to be synergistic.All the synergistic combinations have shown FIC value of 0.5.In order to measure the kinetics of the anti-bacterial activity,the bacterial growth rate with RA,antibiotics and synergistic combinations against S.aureus and MRSA was studied.It is observed that the synergistic combinations showed better time kill kinetics as compared to RA and antibiotics.Further RA could able to destruct the cell surface proteins MSCRAMMs which was studied by SDS PAGE.RA was also found to showβlactamase inhibiting property.CONCLUSION It is concluded that RA possess antibacterial activity but at a very higher concentration(in mg/mL)against S.aureus and MRSA.However it shows synergism with antibiotics and could able to reduce the MIC of antibiotics.Thus RA could be developed as an adjuvant for antibiotics against S.aureus and MRSA caused infections.Further studies are needed to identify the mechanism for its synergism with antibiotics.展开更多
[Objectives]This study aimed to investigate the inhibition effects of two chemical constituents in Salvia deserta Schang on human aldose reductase( AR). [Methods]The isolated salvianolic acid M and rosmarinic acid wer...[Objectives]This study aimed to investigate the inhibition effects of two chemical constituents in Salvia deserta Schang on human aldose reductase( AR). [Methods]The isolated salvianolic acid M and rosmarinic acid were prepared into different concentrations of solutions for in vitro enzyme kinetics experiments. [Results]Salvianolic acid M and rosmarinic acid had the strongest inhibition effects at the concentration of 1 g/L. [Conclusions]Salvianolic acid M and rosmarinic acid have inhibition effects on human aldose reductase. The IC50 of salvianolic acid M is 0. 79 μg/mL,and that of rosmarinic acid is 1. 13 μg/mL.展开更多
±)-Butyl ester of rosmarinic acid 1 was synthesized by 5-step reactions through the two key intermediates 2 and 3, the total yield was 23.9% and 25.1%, respectively.
Diabetic nephropathy(DN)is a severe complication of diabetes,characterized by changes in kidney structure and function.The natural product rosmarinic acid(RA)has demonstrated therapeutic effects,including anti-inflamm...Diabetic nephropathy(DN)is a severe complication of diabetes,characterized by changes in kidney structure and function.The natural product rosmarinic acid(RA)has demonstrated therapeutic effects,including anti-inflammation and anti-oxidative-stress,in renal damage or dysfunction.In this study,we characterized the heterogeneity of the cellular response in kidneys to DN-induced injury and RA treatment at single cell levels.Our results demonstrated that RA significantly alleviated renal tubular epithelial injury,particularly in the proximal tubular S1 segment and on glomerular epithelial cells known as podocytes,while attenuating the inflammatory response of macrophages,oxidative stress,and cytotox-icity of natural killer cells.These findings provide a comprehensive understanding of the mechanisms by which RA alleviates kidney damage,oxidative stress,and inflammation,offering valuable guidance for the clinical application of RA in the treatment of DN.展开更多
Rosmarinic acid(RA)is promising as a natural and nontoxic food additive.However,many analysis methods for RA generally depend on large instruments and single signals for quantitative detection.A new upconversion fluor...Rosmarinic acid(RA)is promising as a natural and nontoxic food additive.However,many analysis methods for RA generally depend on large instruments and single signals for quantitative detection.A new upconversion fluorescence,colorimetric and photothermal multi-modal sensing strategy is developed for the quantification of RA.β-cyclodextrin(CD)modified citric acid(Cit)wrapped NaYF_(4):Yb/Er-Cit-CD(Y:Yb/Er-Cit-CD)up-conversion nanocomposite has been synthesized,which emits green fluorescence at 550nm under 980nm near-infrared(NIR)excitation.In the presence of oxidized 3,3',5,5'-tetramethylbenzidine(oxTMB),the green fluorescence is significantly quenched attributed to the fluorescence inner filter effect(IFE)between oxTMB and Y:Yb/Er-Cit-CD.When RA is intervened,blue oxTMB is reduced to colorless 3,3',5,5'-tetramethylbenzidine(TMB)inducing the recovery of up-conversion fluorescence.At the same time,colorimetric and photothermal signals readout can be easily achieved thanks to the color indication and photothermal effect of the oxTMB.The constructed Y:Yb/Er-Cit-CD/oxTMB sensor displays high sensitivity,visibility and simplicity for RA,and the limits of detection(LOD)for fluorescence,colorimetric and photothermal were 0.004μmol/L,0.036μmol/L and 0.043μmol/L,respectively.This sensing system is successfully performed for the detection of RA in food samples.展开更多
Myocardial infarction (MI) causes irreversible damage to the heart muscle, seriously threatening the lives of patients. Injectable hydrogels have attracted extensive attention in the treatment of MI. By promoting the ...Myocardial infarction (MI) causes irreversible damage to the heart muscle, seriously threatening the lives of patients. Injectable hydrogels have attracted extensive attention in the treatment of MI. By promoting the coupling of mechanical and electrical signals between cardiomyocytes, combined with synergistic therapeutic strategies targeting the pathological processes of inflammation, proliferation, and fibrotic remodeling after MI, it is expected to improve the therapeutic effect. In this study, a pH/ROS dual-responsive injectable hydrogel was developed by modifying xanthan gum and gelatin with reversible imine bond and boronic ester bond double crosslinking. By encapsulating polydopamine-rosmarinic acid nanoparticles to achieve on-demand drug release in response to the microenvironment of MI, thereby exerting anti-inflammatory, anti-apoptotic, and anti-fibrosis effects. By adding conductive composites to improve the conductivity and mechanical strength of the hydrogel, restore electrical signal transmission in the infarct area, promote synchronous contraction of cardiomyocytes, avoid induced arrhythmias, and induce angiogenesis. Furthermore, the multifunctional hydrogel promoted the expression of cardiac-specific markers to restore cardiac function after MI. The in vivo and in vitro results demonstrate the effectiveness of this synergistic comprehensive treatment strategy in MI treatment, showing great application potential to promote the repair of infarcted hearts.展开更多
Escherichia coli O157:H7 is one of the major foodborne pathogenic bacterial that cause infectious diseases in humans.The previous found that a combination of kojic acid and tea polyphenols exhibited better activity ag...Escherichia coli O157:H7 is one of the major foodborne pathogenic bacterial that cause infectious diseases in humans.The previous found that a combination of kojic acid and tea polyphenols exhibited better activity against E.coli O157:H7 than using either alone.This study aimed to explore responses underlying the antibacterial mechanisms of kojic acid and tea polyphenols from the gene level.The functional enrichment analysis by comparing kojic acid and tea polyphenols individually or synergistically against E.coli O157:H7 found that acid resistance systems in kojic acid were activated,and the cell membrane and genomic DNA were destructed in the cells,resulting in“oxygen starvation”.The oxidative stress response triggered by tea polyphenols inhibited both sulfur uptake and the synthesis of ATP,which affected the bacteria's life metabolic process.Interestingly,we found that kojic acid combined with tea polyphenols hindered the uptake of iron that played an essential role in the synthesis of DNA,respiration,tricarboxylic acid cycle.The results suggested that the iron uptake pathways may represent a novel approach for kojic acid and tea polyphenols synergistically against E.coli O157:H7 and provided a theoretical basis for bacterial pathogen control in the food industry.展开更多
Milk fat globule membrane(MFGM),which contains abundant glycoproteins and phospholipids,exerts beneficial effects on intestinal health and immunomodulation.The aim of this study was to evaluate the protective effects ...Milk fat globule membrane(MFGM),which contains abundant glycoproteins and phospholipids,exerts beneficial effects on intestinal health and immunomodulation.The aim of this study was to evaluate the protective effects and possible underlying mechanisms of MFGM on cow’s milk allergy(CMA)in aβ-lactoglobulin(BLG)-induced allergic mice model.MFGM was supplemented to allergic mice induced by BLG at a dose of 400 mg/kg body weight.Results demonstrated that MFGM alleviated food allergy symptoms,decreased serum levels of lipopolysaccharide,pro-inflammatory cytokines,immunoglobulin(Ig)E,Ig G1,and Th2 cytokines including interleukin(IL)-4,while increased serum levels of Th1 cytokines including interferon-γand regulatory T cells(Tregs)cytokines including IL-10 and transforming growth factor-β.MFGM modulated gut microbiota and enhanced intestinal barrier of BLG-allergic mice,as evidenced by decreased relative abundance of Desulfobacterota,Rikenellaceae,Lachnospiraceae,and Desulfovibrionaceae,while increased relative abundance of Bacteroidetes,Lactobacillaceae and Muribaculaceae,and enhanced expressions of tight junction proteins including Occludin,Claudin-1 and zonula occludens-1.Furthermore,MFGM increased fecal short-chain fatty acids(SCFAs)levels,which elevated G protein-coupled receptor(GPR)43 and GPR109A expressions.The increased expressions of GPR43 and GPR109A induced CD103+dendritic cells accumulation and promoted Tregs differentiation in mesenteric lymph node to a certain extent.In summary,MFGM alleviated CMA in a BLG-induced allergic mice model through enhancing intestinal barrier and promoting Tregs differentiation,which may be correlated with SCFAs-mediated activation of GPRs.These findings suggest that MFGM may be useful as a promising functional ingredient against CMA.展开更多
The proper recycling of spent lithium-ion batteries(LIBs)can promote the recovery and utilization of valuable resources,while also negative environmental effects resulting from the presence of toxic and hazardous subs...The proper recycling of spent lithium-ion batteries(LIBs)can promote the recovery and utilization of valuable resources,while also negative environmental effects resulting from the presence of toxic and hazardous substances.In this study,a new environmentally friendly hydro-metallurgical process was proposed for leaching lithium(Li),nickel(Ni),cobalt(Co),and manganese(Mn)from spent LIBs using sulfuric acid with citric acid as a reductant.The effects of the concentration of sulfuric acid,the leaching temperature,the leaching time,the solid-liquid ratio,and the reducing agent dosage on the leaching behavior of the above elements were investigated.Key parameters were optimized using response surface methodology(RSM)to maximize the recovery of metals from spent LIBs.The maxim-um recovery efficiencies of Li,Ni,Co,and Mn can reach 99.08%,98.76%,98.33%,and 97.63%.under the optimized conditions(the sulfuric acid concentration was 1.16 mol/L,the citric acid dosage was 15wt%,the solid-liquid ratio was 40 g/L,and the temperature was 83℃ for 120 min),respectively.It was found that in the collaborative leaching process of sulfuric acid and citric acid,the citric acid initially provided strong reducing CO_(2)^(-),and the transition metal ions in the high state underwent a reduction reaction to produce transition metal ions in the low state.Additionally,citric acid can also act as a proton donor and chelate with lower-priced transition metal ions,thus speeding up the dissolution process.展开更多
BACKGROUND Gastric cancer(GC)is associated with high mortality rates.Bile acids(BAs)reflux is a well-known risk factor for GC,but the specific mechanism remains unclear.During GC development in both humans and animals...BACKGROUND Gastric cancer(GC)is associated with high mortality rates.Bile acids(BAs)reflux is a well-known risk factor for GC,but the specific mechanism remains unclear.During GC development in both humans and animals,BAs serve as signaling molecules that induce metabolic reprogramming.This confers additional cancer phenotypes,including ferroptosis sensitivity.Ferroptosis is a novel mode of cell death characterized by lipid peroxidation that contributes universally to malignant progression.However,it is not fully defined if BAs can influence GC progression by modulating ferroptosis.AIM To reveal the mechanism of BAs regulation in ferroptosis of GC cells.METHODS In this study,we treated GC cells with various stimuli and evaluated the effect of BAs on the sensitivity to ferroptosis.We used gain and loss of function assays to examine the impacts of farnesoid X receptor(FXR)and BTB and CNC homology 1(BACH1)overexpression and knockdown to obtain further insights into the molecular mechanism involved.RESULTS Our data suggested that BAs could reverse erastin-induced ferroptosis in GC cells.This effect correlated with increased glutathione(GSH)concentrations,a reduced GSH to oxidized GSH ratio,and higher GSH peroxidase 4(GPX4)expression levels.Subsequently,we confirmed that BAs exerted these effects by activating FXR,which markedly increased the expression of GSH synthetase and GPX4.Notably,BACH1 was detected as an essential intermediate molecule in the promotion of GSH synthesis by BAs and FXR.Finally,our results suggested that FXR could significantly promote GC cell proliferation,which may be closely related to its anti-ferroptosis effect.CONCLUSION This study revealed for the first time that BAs could inhibit ferroptosis sensitivity through the FXR-BACH1-GSHGPX4 axis in GC cells.This work provided new insights into the mechanism associated with BA-mediated promotion of GC and may help identify potential therapeutic targets for GC patients with BAs reflux.展开更多
文摘Objective:To evaluate the effect of rosmarinic acid on tracheal smooth muscle responsiveness and lung pathological changes in ovalbumin-sensitized rats.Methods:Rats were randomly divided into six groups:the control group,the asthmatic group,and the asthmatic groups treated with dexamethasone(1 mg/kg;oral gavage)or three doses of rosmarinic acid(0.5,1,and 2 mg/kg;oral gavage).For induction of asthma,rats received intraperitoneal injections and inhalation of ovalbumin.After 21 days,bronchoalveolar lavage fluid and lung samples were collected for histopathological analyses.Moreover,total and differential white blood cell counts were determined.Results:The rosmarinic acid-treated group had significantly lower tracheal smooth muscle responses to methacholine than the asthmatic group.In addition,rosmarinic acid reduced white blood cell count and the percentages of eosinophils,monocytes,and neutrophils while increasing the percentage of lymphocytes.Ovalbumin-induced lung pathological changes were significantly improved by treatment with rosmarinic acid.Conclusions:Rosmarinic acid improves tracheal smooth muscle responsiveness and lung pathological changes in ovalbumin-sensitized rats.
基金supported by Theodore Bilharz Research Institute(grant number:ID-MS-99/A,2012,PI:Naglaa El-Lakkany)
文摘Objective:To investigate the antifibrotic role of rosmarinic acid(RA),a natural polyphenolic compound,on HSCs activation/proliferation and apoptosis in vitro and in vivo. Methods:The impact of RA on stellate cell line(HSC-T6) proliferation,activation and apoptosis was assessed along with its safety on primary hepatocytes. In vivo,rats were divided into:(i) normal;(ii) thioacetamide(TAA)-intoxicated rats for 12 weeks;(iii) TAA+silymarin or(iv) TAA+RA. At the end of experiment,liver functions,oxidative stress,inflammatory and profibrogenic markers,tissue inhibitor metalloproteinases type-1(TIMP-1) and hydroxyproline(HP) levels were evaluated. Additionally,liver histopathology and immunohistochemical examinations of alpha-smooth muscle actin(α-SMA),caspase-3 and proliferation cellular nuclear antigen(PCNA) were determined. Results:RA exhibited anti-proliferative effects on cultured HSCs in a time and concentration dependent manner showing an IC50 of 276 μg/mL and 171 μg/mL for 24 h and 48 h,respectively,with morphological reversion of activated stellate cell morphology to quiescent form. It significantly improved ALT,AST,oxidative stress markers and reduced TIMP-1,HP levels,inflammatory markers and fibrosis score(S1 vs S4). Furthermore,reduction in α-SMA plus elevation in caspase-3 expressions of HSCs in vitro and in vivo associated with an inhibition in proliferation of damaged hepatocytes were recorded. Conclusions:RA impeded the progression of liver fibrosis through inhibition of HSCs activation/proliferation and induction of apoptosis with preservation of hepatic architecture.
文摘The aim of this study was to characterize the polyphenolic composition by determination of chemical fingerprints of Methanolic extracts of Ocimum canum Sims, Ocimum basilicum L. and Ocimum gratissimum L. from Democratic Republic of Congo and to compare their antisickling activity of that of rosmarinic acid, the major compound to those of methanolic extracts. Phytochemical analysis performed by TLC and HPLC analysis, showed that rosmarinic acid is the most abundant phenolic acid in these Ocimum species according to the following order O. basilicum L., O. gratissimum L. and O. canum Sims. Methanolic extracts of these three species and pure rosmarinic acid showed significant antisickling activities with minimal concentration of normalization values of 0.18 ± 0.03, 0.23 ± 0.04, 0.26 ± 0.04 and 0.31 ± 0.05 mg/mL for rosmarinic acid, O. basilicum L., O. gratissimum L. and O. canum Sims methanolic extracts respectively. The antisickling activity order is the same as that of the rosmarinic acid content, indicating that this polyphenolic acid would be among the main active molecules in these extracts.
文摘<span style="font-family:Verdana;">The aim of this study was to investigate the effect of rosmarinic acid against gonadal toxicity caused by cyclophosphamide, an important anticancer drug. A total of 28 rats were divided into 4 groups, with 7 animals in each group. The groups were created as follows;Group 1 (control) (n = 7): Subjects received only 1 ml of 0.9% saline solution per day intraperitoneally for 14 days. Group 2 (Rosmarinic Acid) (n = 7): The subjects were given 20 mg/kg Rosmarinic acid intraperitoneally for 14 days. Group 3 (Cyclophosphamide) (n = 7): Only 1 ml of 0.9% saline solution was administered intraperitoneally to the subjects for the first 7 days. Cyclophosphamide 20 mg/kg per day was administered intraperitoneally for the last 7 days (from the 8</span><sup><span style="font-family:Verdana;">th</span></sup><span style="font-family:Verdana;"> day)</span><span style="font-family:Verdana;">. Group 4 (Rosmarinic Acid</span><span style="font-family:;" "=""> </span><span style="font-family:;" "=""><span style="font-family:Verdana;">+ Cyclophosphamide) (n = 7): The subjects were given 20 mg/kg Rosmarinic acid daily intraperitoneally for 14 days. From the 8</span><sup><span style="font-family:Verdana;">th</span></sup><span style="font-family:Verdana;"> day of the experiment to the end of the experiment (last 7 days of the experiment), 20 mg/kg cyclophosphamide was given intraperitoneally daily. At the end of the experiment, body weights of all rats were measured first. Afterwards, the weights of testicular tissue samples were measured and the averages of the weights were taken. Routine tissue follows up was performed on the testicular tissues taken. Hematoxylin-eosin staining was applied to tissue sections of 5 μm thickness. As a result of the statistical analysis, it was determined that cyclophosmadine decreased body and testicular weight, but rosmarinic acid had a protective effect on the contrary. It was concluded that cyclophosmadine caused damage to the basement membrane structure, Sertoli, Leydig and germ cells, but these structures were preserved due to the protective effect of rosmarinic acid. Despite the toxic effect of CP, rosmarinic acid is thought to have a significant curative effect on the spermatogenetic process and seminiferous tubule structure in the gonads.</span></span>
基金supported by the Natural Science Foundation of Jiangsu Province of China,No.BK20171180(to XRW)
文摘Rosmarinic acid,a common ester extracted from Rosemary,Perilla frutescens,and Salvia miltiorrhiza Bunge,has been shown to have protective effects against various diseases.This is an investigation into whether rosmarinic acid can also affect the changes of white matter fibers and cognitive deficits caused by hypoxic injury.The right common carotid artery of 3-day-old rats was ligated for 2 hours.The rats were then prewarmed in a plastic container with holes in the lid,which was placed in 37°C water bath for 30 minutes.Afterwards,the rats were exposed to an atmosphere with 8% O2 and 92% N2 for 30 minutes to establish the perinatal hypoxia/ischemia injury models.The rat models were intraperitoneally injected with rosmarinic acid 20 mg/kg for 5 consecutive days.At 22 days after birth,rosmarinic acid was found to improve motor,anxiety,learning and spatial memory impairments induced by hypoxia/ischemia injury.Furthermore,rosmarinic acid promoted the proliferation of oligodendrocyte progenitor cells in the subventricular zone.After hypoxia/ischemia injury,rosmarinic acid reversed to some extent the downregulation of myelin basic protein and the loss of myelin sheath in the corpus callosum of white matter structure.Rosmarinic acid partially slowed down the expression of oligodendrocyte marker Olig2 and myelin basic protein and the increase of oligodendrocyte apoptosis marker inhibitors of DNA binding 2.These data indicate that rosmarinic acid ameliorated the cognitive dysfunction after perinatal hypoxia/ischemia injury by improving remyelination in corpus callosum.This study was approved by the Animal Experimental Ethics Committee of Xuzhou Medical University,China (approval No.20161636721) on September 16,2017.
基金Supported by Ministry of Science and Technology,Taiwan(No.NSC 106-2314-B-212-004)
文摘AIM: To investigate the anti-fibrosis effect of rosmarinic acid(RA) in pterygium epithelial cells(PECs) to determine if RA is a potent agent for treating pterygium.METHODS: The PECs(1×10~4 cells/mL) were treated with 100 μmol/L of RA for 1, 3 and 6h. After RA treatment, the cell viability was determined by staining with acridine orange/DAPI and analysis via a NucleoC ounter NC-3000. The protein expression levels of type I collagen, transforming growth factor beta-1(TGF-β1), TGF-β type Ⅱ receptor(TGF-βRⅡ), p-Smad1/5, p-Smad2, p-Smad3, and Smad4 of the cell lysates were measured by Western blot analysis.RESULTS: The cell viability of PECs was significantly decreased after RA treatment(P<0.01). As the result, RA reduced the protein expression of typeⅠcollagen and TGF-β1 of PECs. Additionally, RA also inhibited TGF-β1/Smad signaling by decreasing the protein expressions of TGF-βRII, p-Smad1/5, p-Smad2, p-Smad3, and Smad4.CONCLUSION: This study demonstrate that RA could inhibit fibrosis of PECs by down-regulating type I collagen expression and TGF-β1/Smad signaling. Therefore, RA is a potent therapeutic agent for the treatment of pterygium.
文摘Alzheimer disease(AD) as worldwide progressive neurodegenerative disease is prevalent disease among elderly population. Due to limitation in chemical drugs along with their adverse effects of these treatments, research for finding more effective natural drugs, is one of interesting subjects among the scientists. Melissa officinalis(M. officinalis) has a long history of use in treatment of nervous system diseases. This review article evaluates the potency of M. officinalis in treatment of AD by review of experimental and clinical documents on the efficacy, safety and its mechanisms of action in management of AD. The information is extracted from electronic resources(PubMed, Wiley, Springer and Science Direct), English and Persian scientific books. In spite of different scientific and non-scientific reports on the use of M. officinalis and its main component of rosmarinic acid in neurodegenerative diseases, there is only one clinical trial on the efficacy of M. officinalis ethanol extract in management of AD. Different mechanisms of action for M. officinalis, including inhibitory effects against amyloid beta, reactive oxygen species, and acetylcholine esterase, are involved. Larger clinical trials are recommended to confirm the efficacy and safety of M. officinalis extracts in treatment of AD patients.
基金supported by the National Natural Science Foundation of China,No.81571292(to XJZ)、81601152(to YY)the Natural Science Foundation of Hebei Province of China,No.H2017206338(to RC)
文摘Rosmarinic acid(RA) can elicit a neuroprotective effect against ischemic stroke, but the precise molecular mechanism remains poorly understood. In this study, an experimental ischemic stroke model was established in CD-1 mice(Beijing Vital River Laboratory Animal Technology, Beijing, China) by occluding the right middle cerebral artery for 1 hour and allowing reperfusion for 24 hours. After intraperitoneally injecting model mice with 10, 20, or 40 mg/kg RA, functional neurological deficits were evaluated using modified Longa scores. Subsequently, cerebral infarct volume was measured using TTC staining and ischemic brain tissue was examined for cell apoptosis with TUNEL staining. Superoxide dismutase activity and malondialdehyde levels were measured by spectrophometry. Expression of heme oxygenase-1(HO-1), nuclear factor erythroid 2-related factor 2(Nrf2), Bcl-2, Bax, Akt, and phospho-Ser473 Akt proteins in ischemic brain tissue was detected by western blot, while mRNA levels of Nrf2, HO-1, Bcl-2, and Bax were analyzed using real time quantitative PCR. In addition, HO-1 enzyme activity was measured spectrophotometrically. RA(20 and 40 mg/kg) greatly improved neurological function, reduced infarct volume, decreased cell apoptosis, upregulated Bcl-2 protein and mRNA expression, downregulated Bax protein and mRNA expression, increased HO-1 and Nrf2 protein and mRNA expression, increased superoxide dismutase activity, and decreased malondialdehyde levels in ischemic brain tissue of model mice. However, intraperitoneal injection of a HO-1 inhibitor(10 mg/kg zinc protoporphyrin IX) reversed the neuroprotective effects of RA on HO-1 enzyme activity and Bcl-2 and Bax protein expression. The PI3 K/Akt signaling pathway inhibitor LY294002(10 mM) inhibited Akt phosphorylation, as well as Nrf2 and HO-1 expression. Our findings suggest that RA has anti-oxidative and anti-apoptotic properties that protect against ischemic stroke by a mechanism involving upregulation of Nrf2 and HO-1 expression via the PI3 K/Akt signaling pathway.
基金The project supported by TEQIP PhaseⅡgrant under Anna University BIT campus,Tiruchirappalli-620024,Tamilnadu,India
文摘OBJECTIVE To evaluate the synergistic effect of rosmarinic acid(RA)with antibiotics against Staphylococcus aureus(S.aureus)and MRSA and to identify the possible mechanism of action responsible for synergism if any.METHODS The antibacterial activity of Rosmarinic acid was studied for its zone of inhibition by agar well diffusion and MIC determination by liquid broth dilution technique against MRSA and VRSA.The synergistic effect of RA with antibiotics like amoxicillin,ofloxacin and vancomycin was evaluated by Broth checker board method and further confirmed with time kill kinetic studies.Microbial Surface Components Recognizing Adhesive Matrix Molecules(MSCRAMMs)were isolated by protein precipitation technique and its expression was studied by SDS PAGE.Further RA was evaluated for its beta lactamase inhibition property.RESULTS Rosmarinic acid exhibited antibacterial activity against S.aureus and MRSAby showing a MIC value of 0.8mg·mL-1 against S.aureus and 10mg·mL-1 against MRSA.Rosmarinic acid at 1/4X MIC value reduced the MIC of vancomycin,amoxicillin and ofloxacin by 1/4 times against S.aureus.But against MRSA,vancomycin was found to be synergistic.All the synergistic combinations have shown FIC value of 0.5.In order to measure the kinetics of the anti-bacterial activity,the bacterial growth rate with RA,antibiotics and synergistic combinations against S.aureus and MRSA was studied.It is observed that the synergistic combinations showed better time kill kinetics as compared to RA and antibiotics.Further RA could able to destruct the cell surface proteins MSCRAMMs which was studied by SDS PAGE.RA was also found to showβlactamase inhibiting property.CONCLUSION It is concluded that RA possess antibacterial activity but at a very higher concentration(in mg/mL)against S.aureus and MRSA.However it shows synergism with antibiotics and could able to reduce the MIC of antibiotics.Thus RA could be developed as an adjuvant for antibiotics against S.aureus and MRSA caused infections.Further studies are needed to identify the mechanism for its synergism with antibiotics.
基金Supported by Scientific Research Plan for Colleges and Universities in Xinjiang Uygur Autonomous Region(XJEDU2018Y025)
文摘[Objectives]This study aimed to investigate the inhibition effects of two chemical constituents in Salvia deserta Schang on human aldose reductase( AR). [Methods]The isolated salvianolic acid M and rosmarinic acid were prepared into different concentrations of solutions for in vitro enzyme kinetics experiments. [Results]Salvianolic acid M and rosmarinic acid had the strongest inhibition effects at the concentration of 1 g/L. [Conclusions]Salvianolic acid M and rosmarinic acid have inhibition effects on human aldose reductase. The IC50 of salvianolic acid M is 0. 79 μg/mL,and that of rosmarinic acid is 1. 13 μg/mL.
文摘±)-Butyl ester of rosmarinic acid 1 was synthesized by 5-step reactions through the two key intermediates 2 and 3, the total yield was 23.9% and 25.1%, respectively.
基金This work was supported by the Establishment of Sino-Austria“Belt and Road”Joint Laboratory on Traditional Chinese Medicine for Severe Infectious Diseases and Joint Research(2020YFE0205100,China)National Key Research and Development Program of China(grant number 2020YFA0908000,2022YFC2303600)+6 种基金the Innovation Team and Talents Cultivation Program of the National Administration of Traditional Chinese Medicine(grant number ZYYCXTD-C-202002,China)the National Natural Science Foundation of China(grant number 82074098,81841001),the Fundamental Research Funds for the Central Public Welfare Research Institutes(grant number ZZ16-ND-10-23,ZZ15-ND-10,ZZ14-ND-010,ZZ14-FL-002,ZZ14-YQ-050,ZZ14-YQ-051,China)Shenzhen Science and Technology Innovation Commission(grant number JCYJ20210324115800001 and JCYJ20210324114014039,China)the Shenzhen Medical Research Fund(B2302051,China)the Distinguished Expert Project of Sichuan Province Tianfu Scholar(CW202002,China)CACMS Innovation Fund(CI2023E002,CI2021A05101 and CI2021A05104,China)support from State Key Laboratory for Quality Ensurance and Sustainable Use of Dao-di Herbs,Scientific and technological innovation project of China Academy of Chinese Medical Sciences(CI2023D003,CI2021B014,China).
文摘Diabetic nephropathy(DN)is a severe complication of diabetes,characterized by changes in kidney structure and function.The natural product rosmarinic acid(RA)has demonstrated therapeutic effects,including anti-inflammation and anti-oxidative-stress,in renal damage or dysfunction.In this study,we characterized the heterogeneity of the cellular response in kidneys to DN-induced injury and RA treatment at single cell levels.Our results demonstrated that RA significantly alleviated renal tubular epithelial injury,particularly in the proximal tubular S1 segment and on glomerular epithelial cells known as podocytes,while attenuating the inflammatory response of macrophages,oxidative stress,and cytotox-icity of natural killer cells.These findings provide a comprehensive understanding of the mechanisms by which RA alleviates kidney damage,oxidative stress,and inflammation,offering valuable guidance for the clinical application of RA in the treatment of DN.
基金supported by the National Natural Science Foundation of China(No.21305097)General Project of Education Department in Sichuan(No.035Z2270)+1 种基金Sichuan Key Discipline Construction Project of Traditional Chinese Medicine(No.2021-16-4)Double-Support Plan of Disciplinary Construction in Sichuan Agricultural University-Innovation Team Projects(No.P202108).
文摘Rosmarinic acid(RA)is promising as a natural and nontoxic food additive.However,many analysis methods for RA generally depend on large instruments and single signals for quantitative detection.A new upconversion fluorescence,colorimetric and photothermal multi-modal sensing strategy is developed for the quantification of RA.β-cyclodextrin(CD)modified citric acid(Cit)wrapped NaYF_(4):Yb/Er-Cit-CD(Y:Yb/Er-Cit-CD)up-conversion nanocomposite has been synthesized,which emits green fluorescence at 550nm under 980nm near-infrared(NIR)excitation.In the presence of oxidized 3,3',5,5'-tetramethylbenzidine(oxTMB),the green fluorescence is significantly quenched attributed to the fluorescence inner filter effect(IFE)between oxTMB and Y:Yb/Er-Cit-CD.When RA is intervened,blue oxTMB is reduced to colorless 3,3',5,5'-tetramethylbenzidine(TMB)inducing the recovery of up-conversion fluorescence.At the same time,colorimetric and photothermal signals readout can be easily achieved thanks to the color indication and photothermal effect of the oxTMB.The constructed Y:Yb/Er-Cit-CD/oxTMB sensor displays high sensitivity,visibility and simplicity for RA,and the limits of detection(LOD)for fluorescence,colorimetric and photothermal were 0.004μmol/L,0.036μmol/L and 0.043μmol/L,respectively.This sensing system is successfully performed for the detection of RA in food samples.
基金the National Natural Science Foundation of China(U21A20417)the Sichuan Science and Technology Program(2022YFS0333)+1 种基金the Fundamental Research Funds for the Central Universities(20826041F4138)1⋅3⋅5 project for disciplines of excellence,West China Hospital,Sichuan University(ZYGD18002).
文摘Myocardial infarction (MI) causes irreversible damage to the heart muscle, seriously threatening the lives of patients. Injectable hydrogels have attracted extensive attention in the treatment of MI. By promoting the coupling of mechanical and electrical signals between cardiomyocytes, combined with synergistic therapeutic strategies targeting the pathological processes of inflammation, proliferation, and fibrotic remodeling after MI, it is expected to improve the therapeutic effect. In this study, a pH/ROS dual-responsive injectable hydrogel was developed by modifying xanthan gum and gelatin with reversible imine bond and boronic ester bond double crosslinking. By encapsulating polydopamine-rosmarinic acid nanoparticles to achieve on-demand drug release in response to the microenvironment of MI, thereby exerting anti-inflammatory, anti-apoptotic, and anti-fibrosis effects. By adding conductive composites to improve the conductivity and mechanical strength of the hydrogel, restore electrical signal transmission in the infarct area, promote synchronous contraction of cardiomyocytes, avoid induced arrhythmias, and induce angiogenesis. Furthermore, the multifunctional hydrogel promoted the expression of cardiac-specific markers to restore cardiac function after MI. The in vivo and in vitro results demonstrate the effectiveness of this synergistic comprehensive treatment strategy in MI treatment, showing great application potential to promote the repair of infarcted hearts.
基金supported by National Natural Science Foundation of China(31972021)R&D Projects in Key Areas of Guangdong Province(2019B020212003)+4 种基金the Science and Technology Program of Guangzhou,China(202206010177)Guangdong key research and development program(2021B0202060001)Foshan and agricultural academy cooperation projectGuangdong Modern Agriculture project(2022KJ117)Aquatic Products Center Project of GAAS。
文摘Escherichia coli O157:H7 is one of the major foodborne pathogenic bacterial that cause infectious diseases in humans.The previous found that a combination of kojic acid and tea polyphenols exhibited better activity against E.coli O157:H7 than using either alone.This study aimed to explore responses underlying the antibacterial mechanisms of kojic acid and tea polyphenols from the gene level.The functional enrichment analysis by comparing kojic acid and tea polyphenols individually or synergistically against E.coli O157:H7 found that acid resistance systems in kojic acid were activated,and the cell membrane and genomic DNA were destructed in the cells,resulting in“oxygen starvation”.The oxidative stress response triggered by tea polyphenols inhibited both sulfur uptake and the synthesis of ATP,which affected the bacteria's life metabolic process.Interestingly,we found that kojic acid combined with tea polyphenols hindered the uptake of iron that played an essential role in the synthesis of DNA,respiration,tricarboxylic acid cycle.The results suggested that the iron uptake pathways may represent a novel approach for kojic acid and tea polyphenols synergistically against E.coli O157:H7 and provided a theoretical basis for bacterial pathogen control in the food industry.
基金supported by the National Key Research and Development Program of China(Grant No.2019YFC1605000)National Natural Science Foundation of China(Grant No.31871806)the Beijing Livestock Industry Innovation Team(BAIC05-2023)。
文摘Milk fat globule membrane(MFGM),which contains abundant glycoproteins and phospholipids,exerts beneficial effects on intestinal health and immunomodulation.The aim of this study was to evaluate the protective effects and possible underlying mechanisms of MFGM on cow’s milk allergy(CMA)in aβ-lactoglobulin(BLG)-induced allergic mice model.MFGM was supplemented to allergic mice induced by BLG at a dose of 400 mg/kg body weight.Results demonstrated that MFGM alleviated food allergy symptoms,decreased serum levels of lipopolysaccharide,pro-inflammatory cytokines,immunoglobulin(Ig)E,Ig G1,and Th2 cytokines including interleukin(IL)-4,while increased serum levels of Th1 cytokines including interferon-γand regulatory T cells(Tregs)cytokines including IL-10 and transforming growth factor-β.MFGM modulated gut microbiota and enhanced intestinal barrier of BLG-allergic mice,as evidenced by decreased relative abundance of Desulfobacterota,Rikenellaceae,Lachnospiraceae,and Desulfovibrionaceae,while increased relative abundance of Bacteroidetes,Lactobacillaceae and Muribaculaceae,and enhanced expressions of tight junction proteins including Occludin,Claudin-1 and zonula occludens-1.Furthermore,MFGM increased fecal short-chain fatty acids(SCFAs)levels,which elevated G protein-coupled receptor(GPR)43 and GPR109A expressions.The increased expressions of GPR43 and GPR109A induced CD103+dendritic cells accumulation and promoted Tregs differentiation in mesenteric lymph node to a certain extent.In summary,MFGM alleviated CMA in a BLG-induced allergic mice model through enhancing intestinal barrier and promoting Tregs differentiation,which may be correlated with SCFAs-mediated activation of GPRs.These findings suggest that MFGM may be useful as a promising functional ingredient against CMA.
基金supported by Key R&D Program of Zhejiang Province,China (No.2022C03061)the National Natural Science Foundation of China (No.52074204)the Fundamental Research Funds for the Central Universities (No.2023-vb-032).
文摘The proper recycling of spent lithium-ion batteries(LIBs)can promote the recovery and utilization of valuable resources,while also negative environmental effects resulting from the presence of toxic and hazardous substances.In this study,a new environmentally friendly hydro-metallurgical process was proposed for leaching lithium(Li),nickel(Ni),cobalt(Co),and manganese(Mn)from spent LIBs using sulfuric acid with citric acid as a reductant.The effects of the concentration of sulfuric acid,the leaching temperature,the leaching time,the solid-liquid ratio,and the reducing agent dosage on the leaching behavior of the above elements were investigated.Key parameters were optimized using response surface methodology(RSM)to maximize the recovery of metals from spent LIBs.The maxim-um recovery efficiencies of Li,Ni,Co,and Mn can reach 99.08%,98.76%,98.33%,and 97.63%.under the optimized conditions(the sulfuric acid concentration was 1.16 mol/L,the citric acid dosage was 15wt%,the solid-liquid ratio was 40 g/L,and the temperature was 83℃ for 120 min),respectively.It was found that in the collaborative leaching process of sulfuric acid and citric acid,the citric acid initially provided strong reducing CO_(2)^(-),and the transition metal ions in the high state underwent a reduction reaction to produce transition metal ions in the low state.Additionally,citric acid can also act as a proton donor and chelate with lower-priced transition metal ions,thus speeding up the dissolution process.
基金Supported by the Major Basic Research Project of Natural Science Foundation of Shandong Province,No.ZR2020ZD15.
文摘BACKGROUND Gastric cancer(GC)is associated with high mortality rates.Bile acids(BAs)reflux is a well-known risk factor for GC,but the specific mechanism remains unclear.During GC development in both humans and animals,BAs serve as signaling molecules that induce metabolic reprogramming.This confers additional cancer phenotypes,including ferroptosis sensitivity.Ferroptosis is a novel mode of cell death characterized by lipid peroxidation that contributes universally to malignant progression.However,it is not fully defined if BAs can influence GC progression by modulating ferroptosis.AIM To reveal the mechanism of BAs regulation in ferroptosis of GC cells.METHODS In this study,we treated GC cells with various stimuli and evaluated the effect of BAs on the sensitivity to ferroptosis.We used gain and loss of function assays to examine the impacts of farnesoid X receptor(FXR)and BTB and CNC homology 1(BACH1)overexpression and knockdown to obtain further insights into the molecular mechanism involved.RESULTS Our data suggested that BAs could reverse erastin-induced ferroptosis in GC cells.This effect correlated with increased glutathione(GSH)concentrations,a reduced GSH to oxidized GSH ratio,and higher GSH peroxidase 4(GPX4)expression levels.Subsequently,we confirmed that BAs exerted these effects by activating FXR,which markedly increased the expression of GSH synthetase and GPX4.Notably,BACH1 was detected as an essential intermediate molecule in the promotion of GSH synthesis by BAs and FXR.Finally,our results suggested that FXR could significantly promote GC cell proliferation,which may be closely related to its anti-ferroptosis effect.CONCLUSION This study revealed for the first time that BAs could inhibit ferroptosis sensitivity through the FXR-BACH1-GSHGPX4 axis in GC cells.This work provided new insights into the mechanism associated with BA-mediated promotion of GC and may help identify potential therapeutic targets for GC patients with BAs reflux.
