Background:Magnolol,a bioactive extract of the Chinese herb Magnolia officinalis has a protective effect against periodontitis.This study is aimed to explore the mechanisms involved in the functioning of magnolol agai...Background:Magnolol,a bioactive extract of the Chinese herb Magnolia officinalis has a protective effect against periodontitis.This study is aimed to explore the mechanisms involved in the functioning of magnolol against periodontitis and provide a basis for further research.Methods:Network pharmacology analysis was performed based on the identification of related targets from public databases.The Protein-protein interaction(PPI)network was constructed to visualize the significance between the targets of magnolol and periodontitis.Subsequently,Gene ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)analysis were performed to predict the functions and the signal regulatory pathways involved in the action of magnolol against periodontitis.The“functiontarget-pathway”networks were constructed to analyze the core targets and pathways of magnolol against periodontitis.Molecular docking was used to verify the interaction of magnolol and core targets.Results:A total of 58 active targets of magnolol and 644 periodontitis-related targets were collected from public databases.A total of 25 targets of magnolol against periodontitis were identified based on the Venn diagram.GO analysis showed that magnolol has a role in the response to oxidative stress,nicotine,and lipopolysaccharide.KEGG enrichment analysis indicated that the mechanism of magnolol against periodontitis was mainly related to the tumor necrosis factor(TNF),phosphoinositide 3-kinase(PI3K/Akt),and mitogen-activated protein kinase(MAPK)signaling pathways.Combined with PPI network and molecular docking results,the core targets of magnolol against periodontitis included AKT1,MAPK8,MAPK14,TNF,and TP53.Conclusion:To summarize,the anti-periodontitis mechanisms of magnolol are potentially through regulating the TNF,PI3K/Akt,and MAPK signaling pathways.展开更多
Liquid-phase microextraction with back extraction （LPME-BE） combined with high performance liquid chromatography （HPLC） was investigated for the extraction and determination of magnolol and honokiol in Magnolia of...Liquid-phase microextraction with back extraction （LPME-BE） combined with high performance liquid chromatography （HPLC） was investigated for the extraction and determination of magnolol and honokiol in Magnolia officinalis, a traditional Chinese medicine （TCM）, and its pharmaceutical preparations, Huo Xiang Zheng Qi peroral liquid and Xiang Sha Yang Wei pellet. Organic solvent, donor and acceptor phases, stirring rate and extraction limes were all factors which can influence the efficiency of extraction and were all optimized during the course of this work. Linear calibration curves were obtained in concentration ranges of 1,56-156 μg/mL for magnolol and 1.10-110 μg/mL for honokiol. Detection limits （S/N = 3） were 0.10 and 0.07 μg/mL, respectively. The relative recoveries were both in the range of 98.3% - 105.1% and RSD was lower than 2.5% .展开更多
AIM： To investigate the protective effects of magnolol on sepsis-induced inflammation and intestinal dysmotility. METHODS： Sepsis was induced by a single intraperitoneal injection of lipopolysaccharide （LPS）. Male...AIM： To investigate the protective effects of magnolol on sepsis-induced inflammation and intestinal dysmotility. METHODS： Sepsis was induced by a single intraperitoneal injection of lipopolysaccharide （LPS）. Male Wistar rats were randomly assigned to one of three treatment groups： magnolol prior to LPS injection （LPS/Mag group）; vehicle prior to LPS injection （LPS/Veh group）; vehicle prior to injection of saline （Control/Veh）. Intestinal transit and circular muscle mechanical activity were assessed 12 h after LPS injection. Tumor necrosis factor-α （TNF-α）, interleukin-10 （IL-10）, monocyte chemoattractant protein-1 （MCP-1） and inducible nitric oxide synthase （iNOS） mRNA in rat ileum were studied by RT-PCR 2 h after LPS injection. Nuclear factor-κB （NF-κB） activity in the intestine was also investigated at this time using electrophoretic mobility shift assay. In addition, antioxidant activity was determined by measuring malondialdehyde （MDA） concentration and superoxide dismutase （SOD） activity in the intestine 2 h after LPS iniection.RESULTS： Magnolol significantly increased intestinal transit and circular muscle mechanical activity in LPS- treated animals. TNF-α, MCP-1 and iNOS mRNA expression in the small intestine were significantly reduced after magnolol treatment in LPS-induced septic animals, compared with untreated septic animals. Additionally,magnolol significantly increased IL-10 mRNA expression in septic rat ileum. Magnolol also significantly suppressed NF-κB activity in septic rat intestine. In addition, magnolol significantly decreased MDA concentration and increased SOD activity in rat ileum. CONCLUSION： Magnolol prevents sepsis-induced suppression of intestinal motility in rats. The potential mechanism of this benefit of magnolol appears to be modulation of self-amplified inflammatory events and block of oxidative stress in the intestine.展开更多
Background:Salmonella pullorum is one of the most harmful pathogens to avian species.Magnolol and honokiol,natural compounds extracted from Magnolia officinalis,exerts anti-inflammatory,anti-oxidant and antibacterial ...Background:Salmonella pullorum is one of the most harmful pathogens to avian species.Magnolol and honokiol,natural compounds extracted from Magnolia officinalis,exerts anti-inflammatory,anti-oxidant and antibacterial activities.This study was conducted to evaluate the effects of dietary supplemental magnolol and honokiol in broilers infected with S.pullorum.A total of 360 one-day-old broilers were selected and randomly divided into four groups with six replicates:the negative control group(CTL),S.pullorum-infected group(SP),and the S.pulloruminfected group supplemented with 300 mg/kg honokiol(SPH)or magnolol(SPM).Results:The results showed that challenging with S.pullorum impaired growth performance in broilers,as indicated by the observed decreases in body weight(P<0.05)and average daily gains(P<0.05),along with increased spleen(P<0.01)and bursa of Fabricus weights(P<0.05),serum globulin contents,and the decreased intestine villus height and villus/crypt ratios(P<0.05).Notably,supplemental magnolol and honokiol attenuated these adverse changes,and the effects of magnolol were better than those of honokiol.Therefore,we performed RNA-Seq in ileum tissues and 16S rRNA gene sequencing of ileum bacteria.Our analysis revealed that magnolol increased the α-diversity(observed species,Chao1,ACE,and PD whole tree)and β-diversity of the ileum bacteria(P<0.05).In addition,magnolol supplementation increased the abundance of Lactobacillus(P<0.01)and decreased unidentified Cyanobacteria(P<0.05)both at d 14 and d 21.Further study confirmed that differentially expressed genes induced by magnolol and honokiol supplementation enriched in cytokine-cytokine receptor interactions,in the intestinal immune network for IgA production,and in the cell adhesion molecule pathways.Conclusions:Supplemental magnolol and honokiol alleviated S.pullorum-induced impairments in growth performance,and the effect of magnolol was better than that of honokiol,which could be partially due to magnolol’s ability to improve the intestinal microbial and mucosal barrier.展开更多
AIM： To study the effects of magnolol and honokiol on isolated smooth muscle of gastrointestinal tract and their relationship with Ca^2＋, and on the gastric emptying and the intestinal propulsive activity in mice.ME...AIM： To study the effects of magnolol and honokiol on isolated smooth muscle of gastrointestinal tract and their relationship with Ca^2＋, and on the gastric emptying and the intestinal propulsive activity in mice.METHODS： Routine experimental methods using isolated gastric fundus strips of rats and isolated ileum segments of guinea pigs were adopted to measure the smooth muscle tension, The effects of magnolol 10^-3, 10^-4, 10^-5 mol/L, and honokiol 10^-4, 10^-5, 10^-6 mol/L on the contractility of gastric fundus strips of rats and ileum of guinea pigs induced by acetylcholine （Ach） and 5-hydroxytryptamine （5-HT） was assessed respectively, The method using nuclein and pigment methylene blue was adopted to measure the gastric retention rate of nuclein and the intestinal propulsive ratio of a nutritional semi-solid meal for assessing the effect of magnolol and honokiol （0.5, 2, 20 mg/kg） on gastric emptying and intestinal propulsion.RESULTS： Magnolol and honokiol significantly inhibited the contractility of isolated gastric fundus strips of rats treated with Ach or 5-HT and isolated ileum guinea pigs treated with Ach or CaCl2, and both of them behaved as non-competitive muscarinic antagonists. Magnolol and honokiol inhibited the contraction induced by Ach in Ca^2＋-free medium and extracellular Ca^2＋-dependent contraction induced by Ach, Each group of magnolol and honokiol experiments significantly decreased the residual rate of nudein in the stomach and increased the intestinal propulsive ratio in mice.CONCLUSION： The inhibitory effect of magnolol and honokiol on contractility of the smooth muscles of isolated gastric fundus strips of rats and isolated ileum of guinea pigs is associated with a calcium-antagonistic effect. Magnolol and honokiol can improve the gastric emptying of a semi-solid meal and intestinal propulsive activity in mice.展开更多
BACKGROUND Sepsis is a major medical challenge.Magnolol is an active constituent of Houpu that improves tissue function and exerts strong anti-endotoxin and anti-inflammatory effects,but the mechanism by which it redu...BACKGROUND Sepsis is a major medical challenge.Magnolol is an active constituent of Houpu that improves tissue function and exerts strong anti-endotoxin and anti-inflammatory effects,but the mechanism by which it reduces intestinal inflammation in sepsis is yet unclear.AIM To assess the protective effect of magnolol on intestinal mucosal epithelial cells in sepsis and elucidate the underlying mechanisms.METHODS Enzyme-linked immunosorbent assay was used to measure tumor necrosis factor-α(TNF-α),interleukin-1β(IL-1β),IL-6,and regulated on activation,normal T-cell expressed and secreted(RANTES)levels in serum and ileal tissue in animal studies.The histopathological changes of the ileal mucosa in different groups were observed under a microscope.Cell Counting Kit-8 and cell permeability assays were used to determine the concentration of drug-containing serum that did not affect the activity of Caco2 cells but inhibited lipopolysaccharide(LPS)-induced decrease in permeability.Immunofluorescence and Western blot assays were used to detect the levels of RANTES,inhibitor of nuclear factor kappa-B kinaseβ(IKKβ),phosphorylated IKKβ(p-IKKβ),inhibitor of nuclear factor kappa-B kinaseα(IκBα),p65,and p-p65 proteins in different groups in vitro.RESULTS In rats treated with LPS by intravenous tail injection in the presence or absence of magnolol,magnolol inhibited the expression of proinflammatory cytokines,IL-1β,IL-6,and TNF-αin a dose-dependent manner.In addition,magnolol suppressed the production of RANTES in LPS-stimulated sepsis rats.Moreover,in vitro studies suggested that magnolol inhibited the increase of p65 nucleation,thereby markedly downregulating the production of the phosphorylated form of IKKβin LPS-treated Caco2 cells.Specifically,magnolol inhibited the translocation of the transcription factor nuclear factor-kappa B(NF-κB)from the cytosol into the nucleus and down-regulated the expression level of the chemokine RANTES in LPS-stimulated Caco2 cells.CONCLUSION Magnolol down-regulates RANTES levels by inhibiting the LPS/NF-κB signaling pathways,thereby suppressing IL-1β,IL-6,and TNF-αexpression to alleviate the mucosal barrier dysfunction in sepsis.展开更多
Two active principles in traditional Chinese medicine Magnolia officinalis, magnolol and honokiol, were successfully separated by means of nonaqueous capillary electrophoresis. The effect of the composition of a nonaq...Two active principles in traditional Chinese medicine Magnolia officinalis, magnolol and honokiol, were successfully separated by means of nonaqueous capillary electrophoresis. The effect of the composition of a nonaqueous buffer on column efficiency and resolution, and the effect of acid additives on peak shapes were researched. The separation was conducted with a running buffer in a mixture of methanol/aeetonitrile/formamide （ volume ratio ： 1 ： 2 ： 2 ）, in which the concentrations of Tris, acetic acid, and water were 60 retool/L, 0. 04 mmol/L and 5% （ volume fration）, respectively, and the pH^＊ （apperent pH） of the running buffer was 8.96. Magnolol and honokiol were separated on baseline within 20 min. The relative standard deviation of the analytes＇ concentrations in the sample is 1.32% for magnolol and 1.60% for honokiol, and the recoveries of the spiked sample are 98.4% for magnolol and 98. 0% for honokiol, respectively.展开更多
OBJECTIVE Right ventricular(RV)remodeling is one of the essential pathological features in pulmonary arterial hypertension(PAH).RV hypertrophy or fibrosis are the leading causes of RV remodeling.Magnolol is a compound...OBJECTIVE Right ventricular(RV)remodeling is one of the essential pathological features in pulmonary arterial hypertension(PAH).RV hypertrophy or fibrosis are the leading causes of RV remodeling.Magnolol is a compound isolated from Magnolia officinalis.It possesses multiple pharmacological activities,such as anti-oxidation and anti-inflammation.This study aims to evaluate the effects and underlying mechanisms of magnolol on RV remodeling in hypoxia-induced PAH.METHODS①Male SD rats(220 g)were randomly divided into 5 groups(n=10):the normoxia group,the hypoxia group,the hypoxia plus Magnolol(10 and 20 mg·kg^(-1)·d-1)group,and the vehicle group.Rats in the normoxia group were kept in a normoxia environment for 4 weeks,while rats in the hypoxia group were kept in a hypoxic chamber(10%O2).The rats in the hypoxia plus magnolol groups were administered with magnolol at 10 or 20 mg·kg^(-1)(ip)once a day for 4 weeks.At the end of 4 weeks,the heart function was assessed by Doppler echocardiography,and then the rats were anesthetized with sodium pentobarbital(30 mg·kg^(-1),ip).The RVSP was measured by the right heart catheterization method.The heart tissues were collected and dissected to calculate the index of RV remodeling(RV/LV+IVS,RV/tibial length,or RV/body weight).Part of the RV samples was fixed with 4%paraformaldehyde for morphological analysis,while other samples were frozen at-80℃for molecular studies(measurements of ANP,BNP,α-SMA,and collagenⅠ/ⅢmRNA expression as well as p-JAK2/JAK2 and p-STAT3/STAT3 protein levels).②To evaluate the effect of magnolol on hypoxia-induced myocardial hypertrophy and fibrosis,H9c2 or cardiac fibroblasts were divided into 7 groups:the control group,cells were cultured under normal conditions;the hypoxia group,cells were cultured under hypoxic condition(3%O2);the hypoxia plus magnolol 10 mg·kg^(-1) group,magnolol10μmol·L^(-1) was added to the culture medium before the hypoxia treatment;the hypoxia plus magnolol 30 mg·kg^(-1) group,magnolol 20μmol·L^(-1) was added to the culture medium before the hypoxia treatment;the hypoxia plus TG-101348 group,TG-101348(a specific inhibitor of JAK2)1μmol·L^(-1) was added to the culture medium before the hypoxia treatment;the hypoxia plus JSI-124 group,JSI-124(a specific inhibitor of JAK2)1μmol·L^(-1) was added to the culture medium before the hypoxia treatment;and the hypoxia plus vehicle group,an equal volume of vehicle(DMSO)was added to the culture medium before the hypoxia treatment.At the end of the experiments,the cells were collected for morphological and molecular analysis.RESULTS In vivo,male Sprang-Daley rats were exposed to 10%O2 for 4 weeks to establish an RV remodeling model,which showed hypertrophic and fibrotic features(increases of RV remodeling index,cellular size,hypertrophic and fibrotic marker expression),accompanied by an elevation in phosphorylation levels of JAK2 and STAT3;these changes were attenuated by treating rats with magnolol.In vitro,the cultured H9c2 cells or cardiac fibroblasts were exposed to 3%O2 for 48 h to induce hypertrophy or fibrosis,which showed hypertrophic(increases in cellular size as well as the expression of ANP and BNP)or fibrotic features(increases in the expression of collagenⅠ,collagenⅢandα-SMA).Administration of magnolol and TG-101348 or JSI-124 (JAK2 selective inhibitors) could prevent the process of myocardial hypertrophy and fibrosis, accompanied by the decrease in the phosphorylation level of JAK2 and STAT3. CONCLUSION Magnolol can attenuate RV hypertrophy and fibrosis in hypoxia-induced PAH rats through a mechanism involving inhibition of the JAK2/STAT3 signaling pathway.展开更多
Ionic liquids functionalized β-cyclodextrin polymer, a mono-6-deoxy-6-（1,2-dimethylimida- zolium）-β-cyclodextrin iodide polymer （ILs-β-CDCP）, was synthesized as a solid-phase adsorbent coupled with high-perform...Ionic liquids functionalized β-cyclodextrin polymer, a mono-6-deoxy-6-（1,2-dimethylimida- zolium）-β-cyclodextrin iodide polymer （ILs-β-CDCP）, was synthesized as a solid-phase adsorbent coupled with high-performance liquid chromatography for separating or analyzing magnolol in drug samples. The results showed that magnolol was adsorbed rapidly on ILs-D-CDCP and eluted with methanol. Under the optimum conditions, preconcentration factor of the proposed method was 12. The linear range, limit of detection （LOD）, correlation coefficient （R） and relative standard deviation （RSD） were found to be 0.02-8.00 μg/mL, 1.9 ng/mL, 0.9992 and 2.76% （n=3, c=2.00 pg/mL）, respectively. The interaction between 1Ls-]）-CDCP and magnolol was studied through the inclusion constant, FTIR and TGA analysis. This proposed method has been successfully applied to the determination of magnolol in real samples.展开更多
A simple sensitive and quick assay for simultaneously determining magnolol （MOL） and honokiol （HOL） has been described based on their natural fluorescence. This method is based on the fact that synchronous fluorom...A simple sensitive and quick assay for simultaneously determining magnolol （MOL） and honokiol （HOL） has been described based on their natural fluorescence. This method is based on the fact that synchronous fluorometry could resolve the overlapping of fluorescence spectra, which was aroused by their similar molecular structures. In this work, the synchronous spectrum, maintaining a constant difference of Aλ =10 nm between the emission and excitation wavelengths, has been selected for the determination of HOL and MOL. Under the optimum conditions, the fluorescence intensity is proportional to the concentration of MOL and HOL in solution over the range 0.075-0.7 μg/mL and 0.05-0.9 μg/mL with the detection limit of 0.029 μg/mL and 0.019 μg/mL, respectively. The method was applied to the simultaneous determination of MOL and HOL in pharmaceutical dosage with satisfactory results.展开更多
Objective:Investigating the anti-inflammatory effects of magnolol on lipopolysaccharide (LPS)-induced inflammation model mouse and its effect on NF-κB pathway.Methods:Mice were randomly divided into 5 group: normal c...Objective:Investigating the anti-inflammatory effects of magnolol on lipopolysaccharide (LPS)-induced inflammation model mouse and its effect on NF-κB pathway.Methods:Mice were randomly divided into 5 group: normal control group, inflammatory model group, dexamethasone positive drug group and, magnolol group. After administrating for 7 d, LPS was intraperitoneally injected to induce inflammatory on the 8th day, and blood was taken 3 h later and the thymus and spleen were weighed. The levels of serum TNF-α, IL-22 and IL-17 were detected by ELISA method. The expression levels of TNF-α, NF-κB p65 and IL-17 in thymus were detected by immunohistochemistry.Results: Magnolol could evidently reduce the levels of serum TNF-α, NF-κB p65 and IL-17 and IL-22. Immunohistochemistry result showed that magnolol could down-regulate the expression of IL-17, TNF-α and p65. Conclusion: Magnolol can prevent and treat LPS-induced inflammation. Its anti-inflammatory effect is connected with the down-regulation of TNF-α and NF-κB p65 protein levels by IL-17 inflammatory pathway. This experiment provides a theoretical basis for magnolol in anti-inflammatory.展开更多
Objective: This study is designed to investigate the mode of action of the synergistic effect of 5-fluorouracil(5-FU) and magnolol against cervical cancer.Methods: Network pharmacological approach was applied to predi...Objective: This study is designed to investigate the mode of action of the synergistic effect of 5-fluorouracil(5-FU) and magnolol against cervical cancer.Methods: Network pharmacological approach was applied to predict the molecular mechanism of 5-FU combined with magnolol against cervical cancer. CCK-8 assay, colony formation assay, immunofluorescence staining, adhesion assay, wound healing mobility assay, cell migration and invasion assay and Western blot analysis were conducted to validate the results of in silico study.Results: Phosphatidylinositol 3 kinase(PI3K)/protein kinase B(AKT)/mammalian target of rapamycin(mTOR) signaling pathway was identified as the key pathway in silico study. The experimental results showed that 5-FU combined with magnolol strongly inhibited cervical cancer cell proliferation, induced the morphological change of HeLa cells by down-regulating the expression of a-actinin, tensin-2 and vinculin. Moreover, magnolol enhanced inhibitory effect of 5-FU on the cell adhesion, migration and invasion. The phosphorylation of AKT and PI3K and the expression of mTOR were strongly inhibited by the combination of 5-FU and magnolol. Moreover, the expression of E-cadherin and β-catenin was upregulated and the expression of Snail, Slug and vimentin was down-regulated by the 5-FU together with magnolol.Conclusion: Taken together, this study suggests that 5-FU combined with magnolol exerts a synergistic anti-cervical cancer effect by regulating the PI3K/AKT/mTOR and epithelial-mesenchymal transition(EMT) signaling pathways.展开更多
Magnolol rich in Magnolia officinalis is a bioactive polyphenolic compound. The aim of this study was to examine the effects of magnolol additive(MA) on growth performance, expression levels of antioxidantrelated gene...Magnolol rich in Magnolia officinalis is a bioactive polyphenolic compound. The aim of this study was to examine the effects of magnolol additive(MA) on growth performance, expression levels of antioxidantrelated genes, and intestinal mucosal morphology of Linwu ducks aged from 49 to 70 days, comparing with that of an antibiotic additive(colistin sulfate [CS]). A total of 275,49-day-old ducks were assigned to5 groups with 5 cages of 11 ducks each and fed diets supplemented with 0,100, 200 and 300 mg of MA/kg and 300 mg of CS/kg for 3 weeks, respectively. The results showed that the average daily body weight gain(ADG) was increased significantly in MA-fed groups(200 and 300 mg/kg), compared with the basal diet(BD) group(P < 0.05). The mRNA levels of superoxide dismutase-1(SOD1), manganese superoxide dismutase-2(MnSOD2) and catalase(CAT) were also increased significantly in MA groups(P < 0.05). In addition, hematoxylin and eosin staining revealed that Linwu ducks fed the diets with MA had more intact intestinal mucosa than those fed the BD and CS diets. In addition, ileal villus height, ileal villus height/crypt depth ratio(V/C) and duodenal V/C were also improved significantly(P < 0.05). Taken together, these data demonstrated that MA is an effective feed additive to enhance the growth performance of the Linwu ducks by improving the antioxidant and intestinal mucosal status, suggesting that MA will be a potential additive to replace antibiotic(CS).展开更多
Objective： Heat stress （HS） is an important environmental stressor that adversely influences livestock during the summer. The aim of this study was to investigate whether magnolol protects against HS-induced intest...Objective： Heat stress （HS） is an important environmental stressor that adversely influences livestock during the summer. The aim of this study was to investigate whether magnolol protects against HS-induced intestinal epithelial cell injury. Materials and methods： An intestinal epithelial cell line （IEC-6） was subjected to HS at 42℃, with and without magnolol pretreatment. Cell injury was detected by monitoring lactate dehydrogenase （LDH） release. MTS （3-（4,5-dimethyithiazol-2-yl）-5-（3-carboxymethoxyphenyl）-2-（4-sulfophenyl）-2H-tetrazolium） assay was used to as- sess cell proliferation and viability, including identifying effective concentrations of magnolol. Flow cytometry confirmed Gl-phase cell-cycle arrest and its alleviation by magnolol. Active DNA synthesis was measured by incorporation of nucleic acid 5-ethynyl-2＇-deoxyuridine （EdU）. Gl-phase cell-cycle-related gene expression was assessed by real-time reverse transcription polymerase chain reaction （RT-PCR） and levels of Gl-phase-related proteins by Western blotting Results： HS induced IEC-6 cell injury and decreased cell viability, as demonstrated by data from LDH and MTS assays respectively. Based on a number of criteria, IEC-6 cells subjected to HS were arrested in the G1 phase Of the cell cycle. Magnolol pretreatment decreased HS-induced cell injury through relief of this cell-cycle arrest. Conclusions： Magnolol pretreatment attenuates HS-induced injury in IEC-6 cells. Magnolol is potentially promising as a protective strategy for HS in livestock.展开更多
Mitochondria as a signaling platform play crucial roles in deciding cell fate.Many classic anticancer agents are known to trigger cell death through induction of mitochondrial damage.Mitophagy,one selective autophagy,...Mitochondria as a signaling platform play crucial roles in deciding cell fate.Many classic anticancer agents are known to trigger cell death through induction of mitochondrial damage.Mitophagy,one selective autophagy,is the key mitochondrial quality control that effectively removes damaged mitochondria.However,the precise roles of mitophagy in tumorigenesis and anticancer agent treatment remain largely unclear.Here,we examined the functional implication of mitophagy in the anticancer properties of magnolol,a natural product isolated from herbal Magnolia officinalis.First,we found that magnolol induces mitochondrial depolarization,causes excessive mitochondrial fragmentation,and increases mitochondrial reactive oxygen species(mtROS).Second,magnolol induces PTEN-induced putative kinase protein 1(PINK1)-Parkin-mediated mitophagy through regulating two positive feedforward amplification loops.Third,magnolol triggers cancer cell death and inhibits neuroblastoma tumor growth via the intrinsic apoptosis pathway.Moreover,magnolol prolongs the survival time of tumor-bearing mice.Finally,inhibition of mitophagy by PINK1/Parkin knockdown or using inhibitors targeting different autophagy/mitophagy stages significantly promotes magnolol-induced cell death and enhances magnolol's anticancer efficacy,both in vitro and in vivo.Altogether,our study demonstrates that magnolol can induce autophagy/mitophagy and apoptosis,whereas blockage of autophagy/mitophagy remarkably enhances the anticancer efficacy of magnolol,suggesting that targeting mitophagy may be a promising strategy to overcome chemoresistance and improve anticancer therapy.展开更多
文摘Background:Magnolol,a bioactive extract of the Chinese herb Magnolia officinalis has a protective effect against periodontitis.This study is aimed to explore the mechanisms involved in the functioning of magnolol against periodontitis and provide a basis for further research.Methods:Network pharmacology analysis was performed based on the identification of related targets from public databases.The Protein-protein interaction(PPI)network was constructed to visualize the significance between the targets of magnolol and periodontitis.Subsequently,Gene ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)analysis were performed to predict the functions and the signal regulatory pathways involved in the action of magnolol against periodontitis.The“functiontarget-pathway”networks were constructed to analyze the core targets and pathways of magnolol against periodontitis.Molecular docking was used to verify the interaction of magnolol and core targets.Results:A total of 58 active targets of magnolol and 644 periodontitis-related targets were collected from public databases.A total of 25 targets of magnolol against periodontitis were identified based on the Venn diagram.GO analysis showed that magnolol has a role in the response to oxidative stress,nicotine,and lipopolysaccharide.KEGG enrichment analysis indicated that the mechanism of magnolol against periodontitis was mainly related to the tumor necrosis factor(TNF),phosphoinositide 3-kinase(PI3K/Akt),and mitogen-activated protein kinase(MAPK)signaling pathways.Combined with PPI network and molecular docking results,the core targets of magnolol against periodontitis included AKT1,MAPK8,MAPK14,TNF,and TP53.Conclusion:To summarize,the anti-periodontitis mechanisms of magnolol are potentially through regulating the TNF,PI3K/Akt,and MAPK signaling pathways.
基金Natural Science Foundation of Shanxi Province(Grant No.2007011086).
文摘Liquid-phase microextraction with back extraction （LPME-BE） combined with high performance liquid chromatography （HPLC） was investigated for the extraction and determination of magnolol and honokiol in Magnolia officinalis, a traditional Chinese medicine （TCM）, and its pharmaceutical preparations, Huo Xiang Zheng Qi peroral liquid and Xiang Sha Yang Wei pellet. Organic solvent, donor and acceptor phases, stirring rate and extraction limes were all factors which can influence the efficiency of extraction and were all optimized during the course of this work. Linear calibration curves were obtained in concentration ranges of 1,56-156 μg/mL for magnolol and 1.10-110 μg/mL for honokiol. Detection limits （S/N = 3） were 0.10 and 0.07 μg/mL, respectively. The relative recoveries were both in the range of 98.3% - 105.1% and RSD was lower than 2.5% .
基金Supported by Beijing Municipal Science & Technology Commission Major Sci-tech Program, No. H020920050130
文摘AIM： To investigate the protective effects of magnolol on sepsis-induced inflammation and intestinal dysmotility. METHODS： Sepsis was induced by a single intraperitoneal injection of lipopolysaccharide （LPS）. Male Wistar rats were randomly assigned to one of three treatment groups： magnolol prior to LPS injection （LPS/Mag group）; vehicle prior to LPS injection （LPS/Veh group）; vehicle prior to injection of saline （Control/Veh）. Intestinal transit and circular muscle mechanical activity were assessed 12 h after LPS injection. Tumor necrosis factor-α （TNF-α）, interleukin-10 （IL-10）, monocyte chemoattractant protein-1 （MCP-1） and inducible nitric oxide synthase （iNOS） mRNA in rat ileum were studied by RT-PCR 2 h after LPS injection. Nuclear factor-κB （NF-κB） activity in the intestine was also investigated at this time using electrophoretic mobility shift assay. In addition, antioxidant activity was determined by measuring malondialdehyde （MDA） concentration and superoxide dismutase （SOD） activity in the intestine 2 h after LPS iniection.RESULTS： Magnolol significantly increased intestinal transit and circular muscle mechanical activity in LPS- treated animals. TNF-α, MCP-1 and iNOS mRNA expression in the small intestine were significantly reduced after magnolol treatment in LPS-induced septic animals, compared with untreated septic animals. Additionally,magnolol significantly increased IL-10 mRNA expression in septic rat ileum. Magnolol also significantly suppressed NF-κB activity in septic rat intestine. In addition, magnolol significantly decreased MDA concentration and increased SOD activity in rat ileum. CONCLUSION： Magnolol prevents sepsis-induced suppression of intestinal motility in rats. The potential mechanism of this benefit of magnolol appears to be modulation of self-amplified inflammatory events and block of oxidative stress in the intestine.
基金supported by the project of Hubei innovation center of agricultural science and technology(grant number 2016-620-000-001-028)National Natural Science Foundation of China(31702309)the Youth Fund of Hubei Academy of Agricultural Sciences(2019NKYJJ03).
文摘Background:Salmonella pullorum is one of the most harmful pathogens to avian species.Magnolol and honokiol,natural compounds extracted from Magnolia officinalis,exerts anti-inflammatory,anti-oxidant and antibacterial activities.This study was conducted to evaluate the effects of dietary supplemental magnolol and honokiol in broilers infected with S.pullorum.A total of 360 one-day-old broilers were selected and randomly divided into four groups with six replicates:the negative control group(CTL),S.pullorum-infected group(SP),and the S.pulloruminfected group supplemented with 300 mg/kg honokiol(SPH)or magnolol(SPM).Results:The results showed that challenging with S.pullorum impaired growth performance in broilers,as indicated by the observed decreases in body weight(P<0.05)and average daily gains(P<0.05),along with increased spleen(P<0.01)and bursa of Fabricus weights(P<0.05),serum globulin contents,and the decreased intestine villus height and villus/crypt ratios(P<0.05).Notably,supplemental magnolol and honokiol attenuated these adverse changes,and the effects of magnolol were better than those of honokiol.Therefore,we performed RNA-Seq in ileum tissues and 16S rRNA gene sequencing of ileum bacteria.Our analysis revealed that magnolol increased the α-diversity(observed species,Chao1,ACE,and PD whole tree)and β-diversity of the ileum bacteria(P<0.05).In addition,magnolol supplementation increased the abundance of Lactobacillus(P<0.01)and decreased unidentified Cyanobacteria(P<0.05)both at d 14 and d 21.Further study confirmed that differentially expressed genes induced by magnolol and honokiol supplementation enriched in cytokine-cytokine receptor interactions,in the intestinal immune network for IgA production,and in the cell adhesion molecule pathways.Conclusions:Supplemental magnolol and honokiol alleviated S.pullorum-induced impairments in growth performance,and the effect of magnolol was better than that of honokiol,which could be partially due to magnolol’s ability to improve the intestinal microbial and mucosal barrier.
基金Supported Dy the Natural Science Foundation of Liaoning Province,No. 20032074
文摘AIM： To study the effects of magnolol and honokiol on isolated smooth muscle of gastrointestinal tract and their relationship with Ca^2＋, and on the gastric emptying and the intestinal propulsive activity in mice.METHODS： Routine experimental methods using isolated gastric fundus strips of rats and isolated ileum segments of guinea pigs were adopted to measure the smooth muscle tension, The effects of magnolol 10^-3, 10^-4, 10^-5 mol/L, and honokiol 10^-4, 10^-5, 10^-6 mol/L on the contractility of gastric fundus strips of rats and ileum of guinea pigs induced by acetylcholine （Ach） and 5-hydroxytryptamine （5-HT） was assessed respectively, The method using nuclein and pigment methylene blue was adopted to measure the gastric retention rate of nuclein and the intestinal propulsive ratio of a nutritional semi-solid meal for assessing the effect of magnolol and honokiol （0.5, 2, 20 mg/kg） on gastric emptying and intestinal propulsion.RESULTS： Magnolol and honokiol significantly inhibited the contractility of isolated gastric fundus strips of rats treated with Ach or 5-HT and isolated ileum guinea pigs treated with Ach or CaCl2, and both of them behaved as non-competitive muscarinic antagonists. Magnolol and honokiol inhibited the contraction induced by Ach in Ca^2＋-free medium and extracellular Ca^2＋-dependent contraction induced by Ach, Each group of magnolol and honokiol experiments significantly decreased the residual rate of nudein in the stomach and increased the intestinal propulsive ratio in mice.CONCLUSION： The inhibitory effect of magnolol and honokiol on contractility of the smooth muscles of isolated gastric fundus strips of rats and isolated ileum of guinea pigs is associated with a calcium-antagonistic effect. Magnolol and honokiol can improve the gastric emptying of a semi-solid meal and intestinal propulsive activity in mice.
基金Basic Public Welfare Research Foundation of Zhejiang Province,China,No.GD21H290001and Traditional Chinese Medicine Science and Technology Project Foundation of Zhejiang Province,China,No.2020ZB072.
文摘BACKGROUND Sepsis is a major medical challenge.Magnolol is an active constituent of Houpu that improves tissue function and exerts strong anti-endotoxin and anti-inflammatory effects,but the mechanism by which it reduces intestinal inflammation in sepsis is yet unclear.AIM To assess the protective effect of magnolol on intestinal mucosal epithelial cells in sepsis and elucidate the underlying mechanisms.METHODS Enzyme-linked immunosorbent assay was used to measure tumor necrosis factor-α(TNF-α),interleukin-1β(IL-1β),IL-6,and regulated on activation,normal T-cell expressed and secreted(RANTES)levels in serum and ileal tissue in animal studies.The histopathological changes of the ileal mucosa in different groups were observed under a microscope.Cell Counting Kit-8 and cell permeability assays were used to determine the concentration of drug-containing serum that did not affect the activity of Caco2 cells but inhibited lipopolysaccharide(LPS)-induced decrease in permeability.Immunofluorescence and Western blot assays were used to detect the levels of RANTES,inhibitor of nuclear factor kappa-B kinaseβ(IKKβ),phosphorylated IKKβ(p-IKKβ),inhibitor of nuclear factor kappa-B kinaseα(IκBα),p65,and p-p65 proteins in different groups in vitro.RESULTS In rats treated with LPS by intravenous tail injection in the presence or absence of magnolol,magnolol inhibited the expression of proinflammatory cytokines,IL-1β,IL-6,and TNF-αin a dose-dependent manner.In addition,magnolol suppressed the production of RANTES in LPS-stimulated sepsis rats.Moreover,in vitro studies suggested that magnolol inhibited the increase of p65 nucleation,thereby markedly downregulating the production of the phosphorylated form of IKKβin LPS-treated Caco2 cells.Specifically,magnolol inhibited the translocation of the transcription factor nuclear factor-kappa B(NF-κB)from the cytosol into the nucleus and down-regulated the expression level of the chemokine RANTES in LPS-stimulated Caco2 cells.CONCLUSION Magnolol down-regulates RANTES levels by inhibiting the LPS/NF-κB signaling pathways,thereby suppressing IL-1β,IL-6,and TNF-αexpression to alleviate the mucosal barrier dysfunction in sepsis.
文摘Two active principles in traditional Chinese medicine Magnolia officinalis, magnolol and honokiol, were successfully separated by means of nonaqueous capillary electrophoresis. The effect of the composition of a nonaqueous buffer on column efficiency and resolution, and the effect of acid additives on peak shapes were researched. The separation was conducted with a running buffer in a mixture of methanol/aeetonitrile/formamide （ volume ratio ： 1 ： 2 ： 2 ）, in which the concentrations of Tris, acetic acid, and water were 60 retool/L, 0. 04 mmol/L and 5% （ volume fration）, respectively, and the pH^＊ （apperent pH） of the running buffer was 8.96. Magnolol and honokiol were separated on baseline within 20 min. The relative standard deviation of the analytes＇ concentrations in the sample is 1.32% for magnolol and 1.60% for honokiol, and the recoveries of the spiked sample are 98.4% for magnolol and 98. 0% for honokiol, respectively.
文摘OBJECTIVE Right ventricular(RV)remodeling is one of the essential pathological features in pulmonary arterial hypertension(PAH).RV hypertrophy or fibrosis are the leading causes of RV remodeling.Magnolol is a compound isolated from Magnolia officinalis.It possesses multiple pharmacological activities,such as anti-oxidation and anti-inflammation.This study aims to evaluate the effects and underlying mechanisms of magnolol on RV remodeling in hypoxia-induced PAH.METHODS①Male SD rats(220 g)were randomly divided into 5 groups(n=10):the normoxia group,the hypoxia group,the hypoxia plus Magnolol(10 and 20 mg·kg^(-1)·d-1)group,and the vehicle group.Rats in the normoxia group were kept in a normoxia environment for 4 weeks,while rats in the hypoxia group were kept in a hypoxic chamber(10%O2).The rats in the hypoxia plus magnolol groups were administered with magnolol at 10 or 20 mg·kg^(-1)(ip)once a day for 4 weeks.At the end of 4 weeks,the heart function was assessed by Doppler echocardiography,and then the rats were anesthetized with sodium pentobarbital(30 mg·kg^(-1),ip).The RVSP was measured by the right heart catheterization method.The heart tissues were collected and dissected to calculate the index of RV remodeling(RV/LV+IVS,RV/tibial length,or RV/body weight).Part of the RV samples was fixed with 4%paraformaldehyde for morphological analysis,while other samples were frozen at-80℃for molecular studies(measurements of ANP,BNP,α-SMA,and collagenⅠ/ⅢmRNA expression as well as p-JAK2/JAK2 and p-STAT3/STAT3 protein levels).②To evaluate the effect of magnolol on hypoxia-induced myocardial hypertrophy and fibrosis,H9c2 or cardiac fibroblasts were divided into 7 groups:the control group,cells were cultured under normal conditions;the hypoxia group,cells were cultured under hypoxic condition(3%O2);the hypoxia plus magnolol 10 mg·kg^(-1) group,magnolol10μmol·L^(-1) was added to the culture medium before the hypoxia treatment;the hypoxia plus magnolol 30 mg·kg^(-1) group,magnolol 20μmol·L^(-1) was added to the culture medium before the hypoxia treatment;the hypoxia plus TG-101348 group,TG-101348(a specific inhibitor of JAK2)1μmol·L^(-1) was added to the culture medium before the hypoxia treatment;the hypoxia plus JSI-124 group,JSI-124(a specific inhibitor of JAK2)1μmol·L^(-1) was added to the culture medium before the hypoxia treatment;and the hypoxia plus vehicle group,an equal volume of vehicle(DMSO)was added to the culture medium before the hypoxia treatment.At the end of the experiments,the cells were collected for morphological and molecular analysis.RESULTS In vivo,male Sprang-Daley rats were exposed to 10%O2 for 4 weeks to establish an RV remodeling model,which showed hypertrophic and fibrotic features(increases of RV remodeling index,cellular size,hypertrophic and fibrotic marker expression),accompanied by an elevation in phosphorylation levels of JAK2 and STAT3;these changes were attenuated by treating rats with magnolol.In vitro,the cultured H9c2 cells or cardiac fibroblasts were exposed to 3%O2 for 48 h to induce hypertrophy or fibrosis,which showed hypertrophic(increases in cellular size as well as the expression of ANP and BNP)or fibrotic features(increases in the expression of collagenⅠ,collagenⅢandα-SMA).Administration of magnolol and TG-101348 or JSI-124 (JAK2 selective inhibitors) could prevent the process of myocardial hypertrophy and fibrosis, accompanied by the decrease in the phosphorylation level of JAK2 and STAT3. CONCLUSION Magnolol can attenuate RV hypertrophy and fibrosis in hypoxia-induced PAH rats through a mechanism involving inhibition of the JAK2/STAT3 signaling pathway.
基金the financial support from the National Natural Science Foundation of China(Nos.21155001 and 21375117)a project funded by the Priority Academic ProgramDevelopment of Jiangsu Higher Education Institutionsthe Foundation of the Excellence Science and Technology Invention Team in Yangzhou University
文摘Ionic liquids functionalized β-cyclodextrin polymer, a mono-6-deoxy-6-（1,2-dimethylimida- zolium）-β-cyclodextrin iodide polymer （ILs-β-CDCP）, was synthesized as a solid-phase adsorbent coupled with high-performance liquid chromatography for separating or analyzing magnolol in drug samples. The results showed that magnolol was adsorbed rapidly on ILs-D-CDCP and eluted with methanol. Under the optimum conditions, preconcentration factor of the proposed method was 12. The linear range, limit of detection （LOD）, correlation coefficient （R） and relative standard deviation （RSD） were found to be 0.02-8.00 μg/mL, 1.9 ng/mL, 0.9992 and 2.76% （n=3, c=2.00 pg/mL）, respectively. The interaction between 1Ls-]）-CDCP and magnolol was studied through the inclusion constant, FTIR and TGA analysis. This proposed method has been successfully applied to the determination of magnolol in real samples.
基金supported by the Natural Science Foundation of Shanxi(No.20041030).
文摘A simple sensitive and quick assay for simultaneously determining magnolol （MOL） and honokiol （HOL） has been described based on their natural fluorescence. This method is based on the fact that synchronous fluorometry could resolve the overlapping of fluorescence spectra, which was aroused by their similar molecular structures. In this work, the synchronous spectrum, maintaining a constant difference of Aλ =10 nm between the emission and excitation wavelengths, has been selected for the determination of HOL and MOL. Under the optimum conditions, the fluorescence intensity is proportional to the concentration of MOL and HOL in solution over the range 0.075-0.7 μg/mL and 0.05-0.9 μg/mL with the detection limit of 0.029 μg/mL and 0.019 μg/mL, respectively. The method was applied to the simultaneous determination of MOL and HOL in pharmaceutical dosage with satisfactory results.
文摘Objective:Investigating the anti-inflammatory effects of magnolol on lipopolysaccharide (LPS)-induced inflammation model mouse and its effect on NF-κB pathway.Methods:Mice were randomly divided into 5 group: normal control group, inflammatory model group, dexamethasone positive drug group and, magnolol group. After administrating for 7 d, LPS was intraperitoneally injected to induce inflammatory on the 8th day, and blood was taken 3 h later and the thymus and spleen were weighed. The levels of serum TNF-α, IL-22 and IL-17 were detected by ELISA method. The expression levels of TNF-α, NF-κB p65 and IL-17 in thymus were detected by immunohistochemistry.Results: Magnolol could evidently reduce the levels of serum TNF-α, NF-κB p65 and IL-17 and IL-22. Immunohistochemistry result showed that magnolol could down-regulate the expression of IL-17, TNF-α and p65. Conclusion: Magnolol can prevent and treat LPS-induced inflammation. Its anti-inflammatory effect is connected with the down-regulation of TNF-α and NF-κB p65 protein levels by IL-17 inflammatory pathway. This experiment provides a theoretical basis for magnolol in anti-inflammatory.
基金supported by the Scientific Research Foundation of Jiangsu Province,China(No.BK20211327)Jiangsu Province Traditional Chinese Medicine Science and Technology Project(No.2020ZX21)+1 种基金Jiangsu Qinglian Project(2022)Yangzhou University Top Talent Project(2020).
文摘Objective: This study is designed to investigate the mode of action of the synergistic effect of 5-fluorouracil(5-FU) and magnolol against cervical cancer.Methods: Network pharmacological approach was applied to predict the molecular mechanism of 5-FU combined with magnolol against cervical cancer. CCK-8 assay, colony formation assay, immunofluorescence staining, adhesion assay, wound healing mobility assay, cell migration and invasion assay and Western blot analysis were conducted to validate the results of in silico study.Results: Phosphatidylinositol 3 kinase(PI3K)/protein kinase B(AKT)/mammalian target of rapamycin(mTOR) signaling pathway was identified as the key pathway in silico study. The experimental results showed that 5-FU combined with magnolol strongly inhibited cervical cancer cell proliferation, induced the morphological change of HeLa cells by down-regulating the expression of a-actinin, tensin-2 and vinculin. Moreover, magnolol enhanced inhibitory effect of 5-FU on the cell adhesion, migration and invasion. The phosphorylation of AKT and PI3K and the expression of mTOR were strongly inhibited by the combination of 5-FU and magnolol. Moreover, the expression of E-cadherin and β-catenin was upregulated and the expression of Snail, Slug and vimentin was down-regulated by the 5-FU together with magnolol.Conclusion: Taken together, this study suggests that 5-FU combined with magnolol exerts a synergistic anti-cervical cancer effect by regulating the PI3K/AKT/mTOR and epithelial-mesenchymal transition(EMT) signaling pathways.
基金PhD Program supported by China Scholarship Councilsupported by the Special Fund for National Key R&D Program(Grant:2016YFD0501209)+5 种基金Agro-scientific Research in the Public Interest(Grant:201403047)National Science and Technology Basic Project(Grant:2014FY111000-3)Hunan Key Scientific and Technological Project(Grant:2016NK2124)Core Research Program 1515 of Hunan Agricultural UniversityHunan Postgraduate Scientific Research and Innovation Projects(Grant:CX2014B284)Excellent Doctoral Dissertation Cultivating Fund of Hunan Agricultural University(Grant:YB2015003)
文摘Magnolol rich in Magnolia officinalis is a bioactive polyphenolic compound. The aim of this study was to examine the effects of magnolol additive(MA) on growth performance, expression levels of antioxidantrelated genes, and intestinal mucosal morphology of Linwu ducks aged from 49 to 70 days, comparing with that of an antibiotic additive(colistin sulfate [CS]). A total of 275,49-day-old ducks were assigned to5 groups with 5 cages of 11 ducks each and fed diets supplemented with 0,100, 200 and 300 mg of MA/kg and 300 mg of CS/kg for 3 weeks, respectively. The results showed that the average daily body weight gain(ADG) was increased significantly in MA-fed groups(200 and 300 mg/kg), compared with the basal diet(BD) group(P < 0.05). The mRNA levels of superoxide dismutase-1(SOD1), manganese superoxide dismutase-2(MnSOD2) and catalase(CAT) were also increased significantly in MA groups(P < 0.05). In addition, hematoxylin and eosin staining revealed that Linwu ducks fed the diets with MA had more intact intestinal mucosa than those fed the BD and CS diets. In addition, ileal villus height, ileal villus height/crypt depth ratio(V/C) and duodenal V/C were also improved significantly(P < 0.05). Taken together, these data demonstrated that MA is an effective feed additive to enhance the growth performance of the Linwu ducks by improving the antioxidant and intestinal mucosal status, suggesting that MA will be a potential additive to replace antibiotic(CS).
基金Project supported by the National Natural Science Foundation of China(No.31272478)the National Twelve-Five Technological Supported Plan of China(No.2013BAD10B04)+1 种基金the Ministry of Agriculture,Public Service Sectors Agriculture Research Projects(No.201403051-07)the Importation and Development of High-Caliber Talents Project of Beijing Municipal Institutions(No.CIT&TCD20130324),China
文摘Objective： Heat stress （HS） is an important environmental stressor that adversely influences livestock during the summer. The aim of this study was to investigate whether magnolol protects against HS-induced intestinal epithelial cell injury. Materials and methods： An intestinal epithelial cell line （IEC-6） was subjected to HS at 42℃, with and without magnolol pretreatment. Cell injury was detected by monitoring lactate dehydrogenase （LDH） release. MTS （3-（4,5-dimethyithiazol-2-yl）-5-（3-carboxymethoxyphenyl）-2-（4-sulfophenyl）-2H-tetrazolium） assay was used to as- sess cell proliferation and viability, including identifying effective concentrations of magnolol. Flow cytometry confirmed Gl-phase cell-cycle arrest and its alleviation by magnolol. Active DNA synthesis was measured by incorporation of nucleic acid 5-ethynyl-2＇-deoxyuridine （EdU）. Gl-phase cell-cycle-related gene expression was assessed by real-time reverse transcription polymerase chain reaction （RT-PCR） and levels of Gl-phase-related proteins by Western blotting Results： HS induced IEC-6 cell injury and decreased cell viability, as demonstrated by data from LDH and MTS assays respectively. Based on a number of criteria, IEC-6 cells subjected to HS were arrested in the G1 phase Of the cell cycle. Magnolol pretreatment decreased HS-induced cell injury through relief of this cell-cycle arrest. Conclusions： Magnolol pretreatment attenuates HS-induced injury in IEC-6 cells. Magnolol is potentially promising as a protective strategy for HS in livestock.
基金supported by research grants from Innovation and Technology Fund(PRP/036/20FX,China)Health and Medical Research Fund(MHRF-16170251,China)of Hong Kong to Hu-Biao Chen+1 种基金Singapore Ministry of Education(MOE)Tier 2(MOE2018-T2-1-060,Singapore)to Han-Ming ShenNational Natural Science Foundation of China(82074123 to Hu-Biao Chen,31501116 to Yingying Lu,82071441 to Liming Wang)。
文摘Mitochondria as a signaling platform play crucial roles in deciding cell fate.Many classic anticancer agents are known to trigger cell death through induction of mitochondrial damage.Mitophagy,one selective autophagy,is the key mitochondrial quality control that effectively removes damaged mitochondria.However,the precise roles of mitophagy in tumorigenesis and anticancer agent treatment remain largely unclear.Here,we examined the functional implication of mitophagy in the anticancer properties of magnolol,a natural product isolated from herbal Magnolia officinalis.First,we found that magnolol induces mitochondrial depolarization,causes excessive mitochondrial fragmentation,and increases mitochondrial reactive oxygen species(mtROS).Second,magnolol induces PTEN-induced putative kinase protein 1(PINK1)-Parkin-mediated mitophagy through regulating two positive feedforward amplification loops.Third,magnolol triggers cancer cell death and inhibits neuroblastoma tumor growth via the intrinsic apoptosis pathway.Moreover,magnolol prolongs the survival time of tumor-bearing mice.Finally,inhibition of mitophagy by PINK1/Parkin knockdown or using inhibitors targeting different autophagy/mitophagy stages significantly promotes magnolol-induced cell death and enhances magnolol's anticancer efficacy,both in vitro and in vivo.Altogether,our study demonstrates that magnolol can induce autophagy/mitophagy and apoptosis,whereas blockage of autophagy/mitophagy remarkably enhances the anticancer efficacy of magnolol,suggesting that targeting mitophagy may be a promising strategy to overcome chemoresistance and improve anticancer therapy.
