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
Among 37 species of microbial strains, Cunninghamella echinulata AS 3.3400 were found to possess the ability to transform honokiol to （R）-magnolignan C （1） and （S）-magnolignan C （2） by regio-specific oxidation...Among 37 species of microbial strains, Cunninghamella echinulata AS 3.3400 were found to possess the ability to transform honokiol to （R）-magnolignan C （1） and （S）-magnolignan C （2） by regio-specific oxidation. Among them, 1 was a new compound. The structures of two compounds were determined by the analyses of CD, MS and NMR spectroscopic data.展开更多
High-performance liquid chromatography （HPLC） was used to quantify magnaldehyde B （6）, magnaldehyde E （4） and 8＇,9＇-dihydroxyhonokiol （7） simultaneously in the raw Chinese medicinal material honokiol. The se...High-performance liquid chromatography （HPLC） was used to quantify magnaldehyde B （6）, magnaldehyde E （4） and 8＇,9＇-dihydroxyhonokiol （7） simultaneously in the raw Chinese medicinal material honokiol. The separation was performed on a reversed-phase Cl8 column by using a gradient elution with mobile phases of water （A） and methanol （B）. The mobile phase gradient was run from 40% B to 56.5% B in 55 min, 55-67 rain from 56.5% to 51.5%, 67-80 min from 51.5% to 70%, 80-170 min at 70%. The elution was carried out at a flow rate of 1.0 mL/min at the column temperature of 35 ~C with the UV detection wavelength at 256 am. Magnaldehyde B, magnaldehyde E and 8＇,9＇-dihydroxyhonokiol showed good linear relationships with peak areas in the range of 0.00864 to 0.07776 mg/mL, 0.01488 to 0.13392 mg/mL and 0.01568 to 0.10976 mg/mL, respectively. Their corresponding average recoveries were 100.30%, 99.63% and 98.29%, respectively. Our results showed that the established method is simple, rapid, and accurate with good reproducibility for evaluating the quality of raw Chinese medicinal material honokiol. Moreover, another five phenolic compounds, namely erythro-7-O-methylhonoldtriol （1）, threo-7-O-methylhonokitriol （2）, 7-O-ethylhonokitriol （3）, magnaldehyde C （5）, honokiol （8）, together with compounds 4, 6 and 7, were isolated and purified from the remaining substance in the process of preparing the raw material honokiol by silica gel column and semi-preparative HPLC. Their structures were characterized by ID and 2D NMR spectroscopy. Among them, compounds 1 and 2 were reported to have common planar structures and their relative configurations were identified for the first time. Compounds 3 and 7 were not only obtained from the raw medicinal material for the first time but also novel compounds.展开更多
Honokiol （HNK） is a small organic molecule purified from magnolia species and has demonstrated anticancer activities in a variety of cancer cell lines; however, its effect on oral squamous cell carcinoma （OSCC） ce...Honokiol （HNK） is a small organic molecule purified from magnolia species and has demonstrated anticancer activities in a variety of cancer cell lines; however, its effect on oral squamous cell carcinoma （OSCC） cells is unknown. We investigated the antitumor activities of HNK on OSCC ceils in vitro for the first time. The inhibitory effects of HNK on the growth and proliferation of OSCC cells were demonstrated via in vitro 3-（4,5-dimethyl thiazol-2-yl）-2,5-diphenyltetrazolium bromide （MTT） and propidium iodide （PI） assays, and the apoptotic cells were investigated by the observation of morphological changes and detection of DNA fragmentation via PI, TdT-mediated dUTP-biotin nick end labeling （TUNEL）, and DNA ladder assays, as well as flow cytometry assay. The results showed that HNK inhibited the growth and proliferation of OSCC cells in vitro in a time and dose-dependent manner. The inhibitory effect was associated with the cell apoptosis induced by HNK, evidenced by the morphological features of apoptotic cells, TUNEL-positive cells and a degradation of chromosomal DNA into small internucleosomal fragments. The study also demonstrated here that the inhibition or apoptosis mediated by 15 μg.mL-1 or 20 μg.mL-1 of HNK were more stronger compared with those of 20 μg-mL-1 5-fluorouracil （5-Fu, the control） applied to OSCC cells, when the ratio of OSCC cell numbers were measured between the treatment of different concentrations of HNK to the 5-Fu treatment for 48 h. HNK is a promising compound that can be potentially used as a novel treatment agent for human OSCC.展开更多
BACKGROUND Cholangiocarcinoma or biliary tract cancer has a high mortality rate resulting from late presentation and ineffective treatment strategy. Since immunotherapy by dendritic cells (DC) may be beneficial for ch...BACKGROUND Cholangiocarcinoma or biliary tract cancer has a high mortality rate resulting from late presentation and ineffective treatment strategy. Since immunotherapy by dendritic cells (DC) may be beneficial for cholangiocarcinoma treatment but their efficacy against cholangiocarcinoma was low. We suggest how such antitumor activity can be increased using cell lysates derived from an honokioltreated cholangiocarcinoma cell line (KKU-213L5). AIM To increase antitumour activity of DCs pulsed with cell lysates derived from honokiol-treated cholangiocarcinoma cell line (KKU-213L5). METHODS The effect of honokiol, a phenolic compound isolated from Magnolia officinalis, on choangiocarcinoma cells was investigated in terms of the cytotoxicity and the expression of damage-associated molecular patterns (DAMPs). DCs were loaded with tumour cell lysates derived from honokiol-treated cholangiocarcinoma cells their efficacy including induction of T lymphocyte proliferation, proinflammatory cytokine production and cytotoxicity effect on target cholangiocarcinoma cells were evaluated. RESULTS Honokiol can effectively activate cholangiocarcinoma apoptosis and increase the release of damage-associated molecular patterns. DCs loaded with cell lysates derived from honokiol-treated tumour cells enhanced priming and stimulated T lymphocyte proliferation and type I cytokine production. T lymphocytes stimulated with DCs pulsed with cell lysates of honokiol-treated tumour cells significantly increased specific killing of human cholangiocarcinoma cells compared to those associated with DCs pulsed with cell lysates of untreated cholangiocarcinoma cells. CONCLUSION The present findings suggested that honokiol was able to enhance the immunogenicity of cholangiocarcinoma cells associated with increased effectiveness of DC-based vaccine formulation. Treatment of tumour cells with honokiol offers a promising approach as an ex vivo DC-based anticancer vaccine.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
Honokiol is a protective agent for cerebral ischemia injury when administered intravenously. In the present study, we aimed to investigate the oral effect of honokiol microemulsion on cerebral isehemia-reperfusion （...Honokiol is a protective agent for cerebral ischemia injury when administered intravenously. In the present study, we aimed to investigate the oral effect of honokiol microemulsion on cerebral isehemia-reperfusion （I-R） injury in rats and stroke in SHRsp. Both tMCAO and SHRsp models in rats were used to evaluate the efficacy of the microemulsion. Rat aortic segment contraction test, primary rat aortic endothelial cells and primary brain microvascular endothelial cells （BMECs） injured by OGD-R were used to explore its potential action mechanism. Oral honokiol microemulsion significantly reduced infarct volume, neurological score and brain water content in tMCAO model, and it evidently reduced neurological score and increased the survival rate of SHRsp. Moreover, honokiol significantly inhibited aortic contraction induced by KC1 and phenylephrine, and L-NAME suppressed these inhibitory effects. On the other side, honokiol increased NO and p-eNOS levels in rat endothelial cells. In addition, it also protects BMECs against OGD-R injury and increased eNOS expression in BMECs. In conclusion, oral honokiol administration has protective effects in tMCAO and in SHRsp rats, and its action mechanism is likely to be associated with its vasodilative effect produced by eNOS activation and with its protective effect on BMECs.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
Honokiol is a pleiotropic natural compound isolated from Magnolia and has multiple biological and clinically relevant effects,including anticancer and antimicrobial function.However,the antiviral activity of honokiol ...Honokiol is a pleiotropic natural compound isolated from Magnolia and has multiple biological and clinically relevant effects,including anticancer and antimicrobial function.However,the antiviral activity of honokiol has not yet been well studied.Here we showed that honokiol had no effect on herpes simplex virus-1(HSV-1)entry,but inhibited HSV-1 viral DNA replication,gene expression and the production of new progeny viruses.The combination of honokiol and clinical drug acyclovir augmented inhibition of HSV-1 infection.Our results illustrate that honokiol could be a potential new candidate for clinical consideration in the treatment of HSV-1 infection alone or combination with other therapeutics.展开更多
Honokiol is the dominant biphenolic compound isolated from the Magnolia tree,and has long been considered as the active constituent of the traditional Chinese herb,‘Houpo’,which is widely used to treat symptoms due...Honokiol is the dominant biphenolic compound isolated from the Magnolia tree,and has long been considered as the active constituent of the traditional Chinese herb,‘Houpo’,which is widely used to treat symptoms due to‘stagnation of qi’.Pharmacological studies have shown that honokiol possesses a wide range of bioactivities without obvious toxicity.Honokiol protects the liver,kidneys,nervous system,and cardiovascular system through reducing oxidative stress and relieving inflammation.Moreover,honokiol shows anti-diabetic property through enhancing insulin sensitivity,and anti-obese property through promoting browning of adipocytes.In vivo and in vitro studies indicated that honokiol functions as an anti-cancer agent through multiple mechanisms:inhibiting angiogenesis,promoting cell apoptosis,and regulating cell cycle.A variety of therapeutic effects of honokiol may be associated with its physiochemical properties,which make honokiol readily cross the blood brain barrier and the blood-cerebrospinal fluid barrier,with high bioavailability.In the future,more clinical researches on honokiol are needed to fully authenticate its therapeutic values.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:To investigate the mechanism of honokiol(HNK)on bladder cancer cells and its synergistic anticancer effect with hydroxycamptothecin(HCPT).METHODS:Control,HNK,HCPT,and HNK plus HCPT groups were established.Th...OBJECTIVE:To investigate the mechanism of honokiol(HNK)on bladder cancer cells and its synergistic anticancer effect with hydroxycamptothecin(HCPT).METHODS:Control,HNK,HCPT,and HNK plus HCPT groups were established.The morphological characteristics of T24 cells were examined microscopically.The maximal experimental concentration of HNK and HCPT were determined according to IC10 detected by MTT.T24 cell viability and the percentage of apoptotic cells were assessed on the basis of MTT and flow cytometric analysis.The expression of caspase-3,caspase-9,phosphorylated nuclear factor-kappa B(NF-κB)-p65,Akt,and extracellular signal-regulated kinase(ERK)proteins were analyzed by Western blot.RESULTS:Apoptosis in T24 cells was observed microscopically in both the HNK and HCPT groups and even more obvious in the HNK plus HCPT groups.The percentage of T24 cell viability decreased down to 19.41%,and the percentage of apoptotic cells rose to 54.08% when treated with HNK plus HCPT in an HNK dose-dependent manner.The induction of caspase-3 and caspase-9 proteins and the inhibition of phosphorylation of NF-κB-p65,Akt,and ERK proteins in T24 cells were demonstrated in the HNK groups,and more significantly in the HNK plus HCPT groups,but not in the HCPT group.CONCLUSION:The anticancer effect of HNK may be due to the activation of the caspase pathway and inhibition of phosphorylation of NF-κB,Akt,and ERK.HNK in combination with HCPT produces a synergistic cell-killing effect on bladder cancer cells.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:To investigate the effect of honokiol on oxidative damage in HaCaT human keratinocytes.Methods:HaCaT cells were exposed to hydrogen peroxide(H_(2)O_(2)),following pretreatment with various concentrations of ...Objective:To investigate the effect of honokiol on oxidative damage in HaCaT human keratinocytes.Methods:HaCaT cells were exposed to hydrogen peroxide(H_(2)O_(2)),following pretreatment with various concentrations of honokiol.The alleviating effects of honokiol on HaCaT cell viability and cell death,reactive oxygen species(ROS)production,DNA damage,mitochondrial dynamics,and inhibition of adenosine triphoaphate production against H_(2)O_(2)were investigated.Western blotting analysis was used to analyze the expression levels of specific proteins.Results:Honokiol suppressed H_(2)O_(2)-induced cytotoxicity and DNA damage by blocking abnormal ROS accumulation.Honokiol also prevented apoptosis by inhibiting loss of mitochondrial membrane potential and release of cytochrome c from the mitochondria into the cytosol,decreasing the Bax/Bcl-2 ratio,and reducing the activity of caspase-3 in H_(2)O_(2)-stimulated HaCaT cells.In addition,honokiol attenuated H_(2)O_(2)-induced reduction of adenosine triphosphate content,and activation of AMP-activated protein kinase(AMPK)was markedly promoted by honokiol in H_(2)O_(2)-stimulated cells.Importantly,the anti-apoptosis and anti-proliferative activity of honokiol against H_(2)O_(2)was further enhanced by adding an activator of AMPK,indicating that honokiol activated AMPK in HaCaT keratinocytes to protect against oxidative damage.Conclusions:The present results indicate that honokiol may be useful as a potential therapeutic agent against various oxidative stress-related skin diseases.展开更多
Background:Glioma is a kind of tumor that easily deteriorates and originates from glial cells in nerve tissue.Honokiol is a bisphenol compound that is an essential monomeric compound extracted from the roots and bark ...Background:Glioma is a kind of tumor that easily deteriorates and originates from glial cells in nerve tissue.Honokiol is a bisphenol compound that is an essential monomeric compound extracted from the roots and bark of Magnoliaceae plants.It also has anti-infection,antitumor,and immunomodulatory effects.In this study,we found that honokiol induces cell apoptosis in the human glioma cell lines U87-MG and U251-MG.However,the mechanism through which honokiol regulates glioma cell apoptosis is still unknown.Methods:We performed RNA-seq analysis of U251-MG cells treated with honokiol and control cells.Protein-protein interaction(PPI)network analysis was performed,and the 10 top hub unigenes were examined via real-time quantitative PCR.Furthermore,MAPK signaling and ferroptosis were detected via western blotting.Results:332 differentially expressed genes(DEGs)were found,comprising 163 increased and 169 decreased genes.Analysis of the DEGs revealed that various biological processes were enriched,including‘response to hypoxia’,‘cerebellum development cellular response to hypoxia,’‘iron ion binding,’‘oxygen transporter activity,’‘oxygen binding,’‘ferric iron binding,’and‘structural constituent of cytoskeleton.’Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway analysis revealed that the DEGs were enriched in the following pathways:‘mitogen-activated protein kinases(MAPK)’,‘Hypoxia-inducible factor 1(HIF-1)’,‘ferroptosis,’‘Peroxisome proliferator-activated receptor(PPAR),’‘Phosphatidylinositol-4,5-bisphosphate 3-kinase(PI3K)-protein kinase B(Akt),’and‘phagosome.’Among these pathways,the MAPK signaling pathway and ferroptosis were verified.Conclusion:This study revealed the potential mechanism by which honokiol induces apoptosis and provided a comprehensive analysis of DEGs in honokiol-treated U251-MG cells and the associated signaling pathways.These data could lead to new ideas for future research and therapy for patients with glioma.展开更多
Honokiol(HK)usage is greatly restricted by its poor aqueous solubility and limited oral bioavailability.We synthesized and characterized a novel phosphate prodrug of honokiol(HKP)for in vitro and in vivo use.HKP great...Honokiol(HK)usage is greatly restricted by its poor aqueous solubility and limited oral bioavailability.We synthesized and characterized a novel phosphate prodrug of honokiol(HKP)for in vitro and in vivo use.HKP greatly enhanced the aqueous solubility of HK(127.54±15.53 mg/ml)and the stability in buffer solution was sufficient for intravenous administration.The enzymatic hydrolysis of HKP to HK was extremely rapid in vitro(T 1/2=8.9±2.11 s).Pharmacokinetics studies demonstrated that after intravenous administration of HKP(32 mg/kg),HKP was converted rapidly to HK with a time to reach the maximum plasma concentration of^5 min.The prodrug HKP achieved an improved T 1/2(7.97±1.30 h)and terminal volume of distribution(26.02±6.04 ml/kg)compared with direct injection of the equimolar parent drug(0.66±0.01 h)and(2.90±0.342 ml/kg),respectively.Furthermore,oral administration of HKP showed rapid and improved absorption compared with the parent drug.HKP was confirmed to maintain the bioactivity of the parent drug for ameliorating ischemia-reperfusion injury by decreasing brain infarction and improving neurologic function.Taken together,HKP is a potentially useful aqueous-soluble prodrug with improved pharmacokinetic properties which may merit further development as a potential drug candidate.展开更多
Objective:To investigate the effect of honokiol on microglia polarization and the underlying mechanism.Methods:Inflammatory factors were detected using ELISA to determine the optimal concentration of cobalt chloride t...Objective:To investigate the effect of honokiol on microglia polarization and the underlying mechanism.Methods:Inflammatory factors were detected using ELISA to determine the optimal concentration of cobalt chloride to induce,and that of honokiol to treat chronic hypoxia(48 h)in microglia cell line BV2 cells.BV2 cells were divided into four groups:control,chronic hypoxia,chronic hypoxia+honokiol,chronic hypoxia+honokiol+3-TYP(SIRT3 inhibitor).ELISA was used to measure the concentration of supernatant TNFαand IL-1βproteins,qPCR was used to detect the expression of cellular M1 and M2 polarization markers,and biochemical assays were used to detect the level of reactive oxygen species in each group.Western Blot was used to detect protein levels of SIRT3 and upstream inflammatory molecules NLRP3 and caspase1.Results:Chronic cobalt chloride stimulation of BV2 cells at an optimal concentration of 100μmol/L significantly increased the release of inflammatory fac-tors TNFαand IL-1βafter stimulation compared with the control group(P<0.05);compared with the control group,cells in the chronic hypoxia group had down-regulation of SIRT3 protein expression,whereas the ROS levels,NLRP3 and caspase1 protein levels,the M1 polarization marker CD86,iNOS mRNA levels and CD16/32 ratio were upregulated.and honokiol(10μmol/L)significantly up-regulated the SIRT3 protein and mRNA levels of M2 markers Arg-1 and CD206 in chronic hypoxic cells(P<0.05)and down-regulated levels of ROS,NLRP3/caspase1 protein,and mRNA levels of M1 markers(P<0.05),and this anti-oxidative and anti-inflammatory effect was able to be reversed by SIRT3 inhibitor.Conclusion:Honokiol inhibits chronic hypoxia-induced microglia M1 polarization and inflammatory pathway activation,and its anti-inflammatory effects are SIRT3-de-pendent.展开更多
Combining drug delivery technologies with chemotherapeutic drugs is very attractive in terms of enhancing antitumor efficacy and reducing toxicity.Alginate microspheres stand out in the field of drug delivery due to t...Combining drug delivery technologies with chemotherapeutic drugs is very attractive in terms of enhancing antitumor efficacy and reducing toxicity.Alginate microspheres stand out in the field of drug delivery due to their biocompatibility and high conversion rate.However,there are certain drawbacks in their preparation technology and further research is needed on how to prepare alginate microspheres with uniform particle size using high-viscosity sodium alginate solution.Therefore,this study proposed a novel microfluidic membrane emulsification technique for the preparation of alginate microspheres from high-viscosity sodium alginate solution.A tumor microenvironment-responsive colorectal cancertargeted oral drug delivery system was constructed using a disulfide-bonded coupling of honokiol and doxorubicin as a model drug to achieve precise targeting,efficiency enhancement and toxicity reduction.The results showed that the prepared microspheres were relatively homogeneous in particle size.The in vitro model showed the high stability of the microspheres in the gastric acid environment and the colon-targeted release characteristic.And the system triggered the breakage of redox bonds and the precise release of the drug,showing good antitumor activity.This study contributes to the construction of drug delivery systems and the study of colon cancer treatment,which has a promising application.展开更多
Postoperative abdominal adhesion represents a frequent clinical challenge.Despite the numerous direct and indirect approaches developed to address this issue,standalone physical or chemical strategies exhibit inherent...Postoperative abdominal adhesion represents a frequent clinical challenge.Despite the numerous direct and indirect approaches developed to address this issue,standalone physical or chemical strategies exhibit inherent limitations and often fail to achieve optimal antiadhesion outcomes.In this study,an injectable,biodegradable hydrogel incorporating micelles formed through Schiff base cross-linking between lauric acid-modified carboxymethyl chitosan(CMCS-LA)and oxidized hyaluronic acid(OHA)is presented as an efficient physical-chemical combined antiadhesion solution.The hydrogel demonstrates rapid gelation,tunable stiffness,biodegradability,injectability,and outstanding self-healing properties.Serving as an adherent physical barrier on abdominal tissues prevents abnormal tissue attachment.The release of the hydrophobic drug honokiol,which is physically encapsulated in CMCS-LA micelles,is sustained to activate peritoneal mesothelial cells,thereby reducing postoperative adhesion formation after surgery.In a rat model of lateral wall defects and caecal abrasion,the hydrogel effectively suppressed abnormal fibrous tissue hyperplasia and inflammatory responses while preventing adhesion.This dualfunction system successfully integrates physical barrier properties with chemical activity,offering a promising approach for future antiadhesion therapies.展开更多
In cancer cells,higher reactive oxygen species(ROS)than normal cells were observed due to hypermetabolism.The redox balance in cancer cells relies on accordingly upregulated antioxidant capacity.By manipulating oxidat...In cancer cells,higher reactive oxygen species(ROS)than normal cells were observed due to hypermetabolism.The redox balance in cancer cells relies on accordingly upregulated antioxidant capacity.By manipulating oxidation and antioxidant systems,chemotherapeutic drugs can selectively kill cancer cells without hurting normal cells.As threedimensional(3D)in vitro models,such as spheroids and organoids,have become widely used in cancer research,traditional detection methods(e.g.,absorption tests or titration)are inadequate for detecting in 3D environments.Thus,it is crucial to find a new method to detect oxidative stress of 3D in vitro cancer models.Here,a nanocomposite electrochemical biosensor was exploited to evaluate oxidative stress of cancer cells cultured in the 3D environment.The oxidation-regulatory capacity of honokiol,a Magnolia genus-derived anti-cancer molecule,was evaluated.A screen-printed electrode(SPCE)was modified with reduced graphene oxide(RGO)and platinum nanoparticles(Pt NPs)to get Pt NPs/RGO/SPCE.Then the gelatin methacrylate/reduced graphene oxide(GelMA/RGO)hydrogel was applied to immobilized NCI-H1975 in a 3D bionic environment to get NCI-H1975/GelMA/RGO/Pt NPs/RGO/SPCE.After optimizing the experiment condition,the Pt NPs/RGO/SPCE showed a detection threshold of 0.65μM and a linear field from 1 to 10μM for H_(2)O_(2)detection while the NCI-H1975/GelMA/RGO/Pt NPs/RGO/SPCE sensitively responded to H_(2)O_(2)-induced oxidative stress.By utilizing the NCI-H1975/GelMA/RGO/Pt NPs/RGO/SPCE we found honokiol(a natural polyphenol constituent)inhibits NCI-H1975 by inducing oxidative stress.This simple cell-based electrochemical biosensor can in situ evaluate oxidative stress of 3D cancer models conveniently.It can also be easily extended to the study of the mechanism of action of other drugs and holds broad application prospects in the fields of new drug development and drug repurposing.展开更多
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The Fundamental Research Funds for the Central Universities(Grant No.2012GZF28)"985 Project"of Minzu University of China(Grant No.MUC985-9)
文摘Among 37 species of microbial strains, Cunninghamella echinulata AS 3.3400 were found to possess the ability to transform honokiol to （R）-magnolignan C （1） and （S）-magnolignan C （2） by regio-specific oxidation. Among them, 1 was a new compound. The structures of two compounds were determined by the analyses of CD, MS and NMR spectroscopic data.
基金Major Projects of National Science and Technology on New Drug Creation and Development(Grant No.2009ZX09102-146)
文摘High-performance liquid chromatography （HPLC） was used to quantify magnaldehyde B （6）, magnaldehyde E （4） and 8＇,9＇-dihydroxyhonokiol （7） simultaneously in the raw Chinese medicinal material honokiol. The separation was performed on a reversed-phase Cl8 column by using a gradient elution with mobile phases of water （A） and methanol （B）. The mobile phase gradient was run from 40% B to 56.5% B in 55 min, 55-67 rain from 56.5% to 51.5%, 67-80 min from 51.5% to 70%, 80-170 min at 70%. The elution was carried out at a flow rate of 1.0 mL/min at the column temperature of 35 ~C with the UV detection wavelength at 256 am. Magnaldehyde B, magnaldehyde E and 8＇,9＇-dihydroxyhonokiol showed good linear relationships with peak areas in the range of 0.00864 to 0.07776 mg/mL, 0.01488 to 0.13392 mg/mL and 0.01568 to 0.10976 mg/mL, respectively. Their corresponding average recoveries were 100.30%, 99.63% and 98.29%, respectively. Our results showed that the established method is simple, rapid, and accurate with good reproducibility for evaluating the quality of raw Chinese medicinal material honokiol. Moreover, another five phenolic compounds, namely erythro-7-O-methylhonoldtriol （1）, threo-7-O-methylhonokitriol （2）, 7-O-ethylhonokitriol （3）, magnaldehyde C （5）, honokiol （8）, together with compounds 4, 6 and 7, were isolated and purified from the remaining substance in the process of preparing the raw material honokiol by silica gel column and semi-preparative HPLC. Their structures were characterized by ID and 2D NMR spectroscopy. Among them, compounds 1 and 2 were reported to have common planar structures and their relative configurations were identified for the first time. Compounds 3 and 7 were not only obtained from the raw medicinal material for the first time but also novel compounds.
基金supported by grants from the National Science Funds for Talented Professionals of China (No. 30725041)the National Natural Science Foundation of China (No. 30930100, 30672323, 81072218)+1 种基金State Key Laboratory of Oral Diseases Open Funding (SKLODOF 2010-01) of Chinathe Changjiang Professorship Support Program of Ministry of Education, China
文摘Honokiol （HNK） is a small organic molecule purified from magnolia species and has demonstrated anticancer activities in a variety of cancer cell lines; however, its effect on oral squamous cell carcinoma （OSCC） cells is unknown. We investigated the antitumor activities of HNK on OSCC ceils in vitro for the first time. The inhibitory effects of HNK on the growth and proliferation of OSCC cells were demonstrated via in vitro 3-（4,5-dimethyl thiazol-2-yl）-2,5-diphenyltetrazolium bromide （MTT） and propidium iodide （PI） assays, and the apoptotic cells were investigated by the observation of morphological changes and detection of DNA fragmentation via PI, TdT-mediated dUTP-biotin nick end labeling （TUNEL）, and DNA ladder assays, as well as flow cytometry assay. The results showed that HNK inhibited the growth and proliferation of OSCC cells in vitro in a time and dose-dependent manner. The inhibitory effect was associated with the cell apoptosis induced by HNK, evidenced by the morphological features of apoptotic cells, TUNEL-positive cells and a degradation of chromosomal DNA into small internucleosomal fragments. The study also demonstrated here that the inhibition or apoptosis mediated by 15 μg.mL-1 or 20 μg.mL-1 of HNK were more stronger compared with those of 20 μg-mL-1 5-fluorouracil （5-Fu, the control） applied to OSCC cells, when the ratio of OSCC cell numbers were measured between the treatment of different concentrations of HNK to the 5-Fu treatment for 48 h. HNK is a promising compound that can be potentially used as a novel treatment agent for human OSCC.
基金the grant from the Thailand Research Fund,No.BRG6180010Naresuan University Research Grant,No.R2561B001
文摘BACKGROUND Cholangiocarcinoma or biliary tract cancer has a high mortality rate resulting from late presentation and ineffective treatment strategy. Since immunotherapy by dendritic cells (DC) may be beneficial for cholangiocarcinoma treatment but their efficacy against cholangiocarcinoma was low. We suggest how such antitumor activity can be increased using cell lysates derived from an honokioltreated cholangiocarcinoma cell line (KKU-213L5). AIM To increase antitumour activity of DCs pulsed with cell lysates derived from honokiol-treated cholangiocarcinoma cell line (KKU-213L5). METHODS The effect of honokiol, a phenolic compound isolated from Magnolia officinalis, on choangiocarcinoma cells was investigated in terms of the cytotoxicity and the expression of damage-associated molecular patterns (DAMPs). DCs were loaded with tumour cell lysates derived from honokiol-treated cholangiocarcinoma cells their efficacy including induction of T lymphocyte proliferation, proinflammatory cytokine production and cytotoxicity effect on target cholangiocarcinoma cells were evaluated. RESULTS Honokiol can effectively activate cholangiocarcinoma apoptosis and increase the release of damage-associated molecular patterns. DCs loaded with cell lysates derived from honokiol-treated tumour cells enhanced priming and stimulated T lymphocyte proliferation and type I cytokine production. T lymphocytes stimulated with DCs pulsed with cell lysates of honokiol-treated tumour cells significantly increased specific killing of human cholangiocarcinoma cells compared to those associated with DCs pulsed with cell lysates of untreated cholangiocarcinoma cells. CONCLUSION The present findings suggested that honokiol was able to enhance the immunogenicity of cholangiocarcinoma cells associated with increased effectiveness of DC-based vaccine formulation. Treatment of tumour cells with honokiol offers a promising approach as an ex vivo DC-based anticancer vaccine.
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National Natural Science Foundation of China(Grant No.81503060)
文摘Honokiol is a protective agent for cerebral ischemia injury when administered intravenously. In the present study, we aimed to investigate the oral effect of honokiol microemulsion on cerebral isehemia-reperfusion （I-R） injury in rats and stroke in SHRsp. Both tMCAO and SHRsp models in rats were used to evaluate the efficacy of the microemulsion. Rat aortic segment contraction test, primary rat aortic endothelial cells and primary brain microvascular endothelial cells （BMECs） injured by OGD-R were used to explore its potential action mechanism. Oral honokiol microemulsion significantly reduced infarct volume, neurological score and brain water content in tMCAO model, and it evidently reduced neurological score and increased the survival rate of SHRsp. Moreover, honokiol significantly inhibited aortic contraction induced by KC1 and phenylephrine, and L-NAME suppressed these inhibitory effects. On the other side, honokiol increased NO and p-eNOS levels in rat endothelial cells. In addition, it also protects BMECs against OGD-R injury and increased eNOS expression in BMECs. In conclusion, oral honokiol administration has protective effects in tMCAO and in SHRsp rats, and its action mechanism is likely to be associated with its vasodilative effect produced by eNOS activation and with its protective effect on BMECs.
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supported by the grant from National Key Research and Development Program (2016YFA0502100)
文摘Honokiol is a pleiotropic natural compound isolated from Magnolia and has multiple biological and clinically relevant effects,including anticancer and antimicrobial function.However,the antiviral activity of honokiol has not yet been well studied.Here we showed that honokiol had no effect on herpes simplex virus-1(HSV-1)entry,but inhibited HSV-1 viral DNA replication,gene expression and the production of new progeny viruses.The combination of honokiol and clinical drug acyclovir augmented inhibition of HSV-1 infection.Our results illustrate that honokiol could be a potential new candidate for clinical consideration in the treatment of HSV-1 infection alone or combination with other therapeutics.
基金supported by the National Natural Science Foundation of China(No.81872754)the Science and Technology Development Fund,Macao SAR(No.FDCT 0031/2019/A1)the Research Funding of University of Macao(Nos.MYRG2017-00109-ICMS and MYRG2018-00037-ICMS).
文摘Honokiol is the dominant biphenolic compound isolated from the Magnolia tree,and has long been considered as the active constituent of the traditional Chinese herb,‘Houpo’,which is widely used to treat symptoms due to‘stagnation of qi’.Pharmacological studies have shown that honokiol possesses a wide range of bioactivities without obvious toxicity.Honokiol protects the liver,kidneys,nervous system,and cardiovascular system through reducing oxidative stress and relieving inflammation.Moreover,honokiol shows anti-diabetic property through enhancing insulin sensitivity,and anti-obese property through promoting browning of adipocytes.In vivo and in vitro studies indicated that honokiol functions as an anti-cancer agent through multiple mechanisms:inhibiting angiogenesis,promoting cell apoptosis,and regulating cell cycle.A variety of therapeutic effects of honokiol may be associated with its physiochemical properties,which make honokiol readily cross the blood brain barrier and the blood-cerebrospinal fluid barrier,with high bioavailability.In the future,more clinical researches on honokiol are needed to fully authenticate its therapeutic values.
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.
基金Supported by the Scientific Research Project of Zhejiang Provincial Health Committee:the Mechanism of Apoptotic Induction of Honokiol on T24 Bladder Cancer Cells and its Synergistic Anticancer Effect with Hydroxycamptothecin(No.2016YB089)the Project of Science and Technology of Traditional Chinese Medicine in Zhejiang Province:Study on Comprehensive Therapy for Radiocystitis by Alum Intravesical Instillation in Combination with Hyperbaric Oxygen and Rhodiola Decoction(No.2018ZA064)。
文摘OBJECTIVE:To investigate the mechanism of honokiol(HNK)on bladder cancer cells and its synergistic anticancer effect with hydroxycamptothecin(HCPT).METHODS:Control,HNK,HCPT,and HNK plus HCPT groups were established.The morphological characteristics of T24 cells were examined microscopically.The maximal experimental concentration of HNK and HCPT were determined according to IC10 detected by MTT.T24 cell viability and the percentage of apoptotic cells were assessed on the basis of MTT and flow cytometric analysis.The expression of caspase-3,caspase-9,phosphorylated nuclear factor-kappa B(NF-κB)-p65,Akt,and extracellular signal-regulated kinase(ERK)proteins were analyzed by Western blot.RESULTS:Apoptosis in T24 cells was observed microscopically in both the HNK and HCPT groups and even more obvious in the HNK plus HCPT groups.The percentage of T24 cell viability decreased down to 19.41%,and the percentage of apoptotic cells rose to 54.08% when treated with HNK plus HCPT in an HNK dose-dependent manner.The induction of caspase-3 and caspase-9 proteins and the inhibition of phosphorylation of NF-κB-p65,Akt,and ERK proteins in T24 cells were demonstrated in the HNK groups,and more significantly in the HNK plus HCPT groups,but not in the HCPT group.CONCLUSION:The anticancer effect of HNK may be due to the activation of the caspase pathway and inhibition of phosphorylation of NF-κB,Akt,and ERK.HNK in combination with HCPT produces a synergistic cell-killing effect on bladder cancer cells.
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:To investigate the effect of honokiol on oxidative damage in HaCaT human keratinocytes.Methods:HaCaT cells were exposed to hydrogen peroxide(H_(2)O_(2)),following pretreatment with various concentrations of honokiol.The alleviating effects of honokiol on HaCaT cell viability and cell death,reactive oxygen species(ROS)production,DNA damage,mitochondrial dynamics,and inhibition of adenosine triphoaphate production against H_(2)O_(2)were investigated.Western blotting analysis was used to analyze the expression levels of specific proteins.Results:Honokiol suppressed H_(2)O_(2)-induced cytotoxicity and DNA damage by blocking abnormal ROS accumulation.Honokiol also prevented apoptosis by inhibiting loss of mitochondrial membrane potential and release of cytochrome c from the mitochondria into the cytosol,decreasing the Bax/Bcl-2 ratio,and reducing the activity of caspase-3 in H_(2)O_(2)-stimulated HaCaT cells.In addition,honokiol attenuated H_(2)O_(2)-induced reduction of adenosine triphosphate content,and activation of AMP-activated protein kinase(AMPK)was markedly promoted by honokiol in H_(2)O_(2)-stimulated cells.Importantly,the anti-apoptosis and anti-proliferative activity of honokiol against H_(2)O_(2)was further enhanced by adding an activator of AMPK,indicating that honokiol activated AMPK in HaCaT keratinocytes to protect against oxidative damage.Conclusions:The present results indicate that honokiol may be useful as a potential therapeutic agent against various oxidative stress-related skin diseases.
基金The study was supported by the Natural Science Foundation of Jilin Province(Grant No.20200201444JC).
文摘Background:Glioma is a kind of tumor that easily deteriorates and originates from glial cells in nerve tissue.Honokiol is a bisphenol compound that is an essential monomeric compound extracted from the roots and bark of Magnoliaceae plants.It also has anti-infection,antitumor,and immunomodulatory effects.In this study,we found that honokiol induces cell apoptosis in the human glioma cell lines U87-MG and U251-MG.However,the mechanism through which honokiol regulates glioma cell apoptosis is still unknown.Methods:We performed RNA-seq analysis of U251-MG cells treated with honokiol and control cells.Protein-protein interaction(PPI)network analysis was performed,and the 10 top hub unigenes were examined via real-time quantitative PCR.Furthermore,MAPK signaling and ferroptosis were detected via western blotting.Results:332 differentially expressed genes(DEGs)were found,comprising 163 increased and 169 decreased genes.Analysis of the DEGs revealed that various biological processes were enriched,including‘response to hypoxia’,‘cerebellum development cellular response to hypoxia,’‘iron ion binding,’‘oxygen transporter activity,’‘oxygen binding,’‘ferric iron binding,’and‘structural constituent of cytoskeleton.’Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway analysis revealed that the DEGs were enriched in the following pathways:‘mitogen-activated protein kinases(MAPK)’,‘Hypoxia-inducible factor 1(HIF-1)’,‘ferroptosis,’‘Peroxisome proliferator-activated receptor(PPAR),’‘Phosphatidylinositol-4,5-bisphosphate 3-kinase(PI3K)-protein kinase B(Akt),’and‘phagosome.’Among these pathways,the MAPK signaling pathway and ferroptosis were verified.Conclusion:This study revealed the potential mechanism by which honokiol induces apoptosis and provided a comprehensive analysis of DEGs in honokiol-treated U251-MG cells and the associated signaling pathways.These data could lead to new ideas for future research and therapy for patients with glioma.
基金supported by the Scientific Research Fund of the National Natural Science Foundation of China ( 81201668 )Chengdu Science and Technology Bureau ( 2015HM01-00506-SF , 2018-YF05-00454-SN )+1 种基金Scientific Research Fund of the Sichuan Provincial Education Department (17CZ0011, 17ZA0109)the Scientific Research Fund of Chengdu Medical College (CYCG15-01)
文摘Honokiol(HK)usage is greatly restricted by its poor aqueous solubility and limited oral bioavailability.We synthesized and characterized a novel phosphate prodrug of honokiol(HKP)for in vitro and in vivo use.HKP greatly enhanced the aqueous solubility of HK(127.54±15.53 mg/ml)and the stability in buffer solution was sufficient for intravenous administration.The enzymatic hydrolysis of HKP to HK was extremely rapid in vitro(T 1/2=8.9±2.11 s).Pharmacokinetics studies demonstrated that after intravenous administration of HKP(32 mg/kg),HKP was converted rapidly to HK with a time to reach the maximum plasma concentration of^5 min.The prodrug HKP achieved an improved T 1/2(7.97±1.30 h)and terminal volume of distribution(26.02±6.04 ml/kg)compared with direct injection of the equimolar parent drug(0.66±0.01 h)and(2.90±0.342 ml/kg),respectively.Furthermore,oral administration of HKP showed rapid and improved absorption compared with the parent drug.HKP was confirmed to maintain the bioactivity of the parent drug for ameliorating ischemia-reperfusion injury by decreasing brain infarction and improving neurologic function.Taken together,HKP is a potentially useful aqueous-soluble prodrug with improved pharmacokinetic properties which may merit further development as a potential drug candidate.
基金National Natural Science Foundation of China(No.82101280)。
文摘Objective:To investigate the effect of honokiol on microglia polarization and the underlying mechanism.Methods:Inflammatory factors were detected using ELISA to determine the optimal concentration of cobalt chloride to induce,and that of honokiol to treat chronic hypoxia(48 h)in microglia cell line BV2 cells.BV2 cells were divided into four groups:control,chronic hypoxia,chronic hypoxia+honokiol,chronic hypoxia+honokiol+3-TYP(SIRT3 inhibitor).ELISA was used to measure the concentration of supernatant TNFαand IL-1βproteins,qPCR was used to detect the expression of cellular M1 and M2 polarization markers,and biochemical assays were used to detect the level of reactive oxygen species in each group.Western Blot was used to detect protein levels of SIRT3 and upstream inflammatory molecules NLRP3 and caspase1.Results:Chronic cobalt chloride stimulation of BV2 cells at an optimal concentration of 100μmol/L significantly increased the release of inflammatory fac-tors TNFαand IL-1βafter stimulation compared with the control group(P<0.05);compared with the control group,cells in the chronic hypoxia group had down-regulation of SIRT3 protein expression,whereas the ROS levels,NLRP3 and caspase1 protein levels,the M1 polarization marker CD86,iNOS mRNA levels and CD16/32 ratio were upregulated.and honokiol(10μmol/L)significantly up-regulated the SIRT3 protein and mRNA levels of M2 markers Arg-1 and CD206 in chronic hypoxic cells(P<0.05)and down-regulated levels of ROS,NLRP3/caspase1 protein,and mRNA levels of M1 markers(P<0.05),and this anti-oxidative and anti-inflammatory effect was able to be reversed by SIRT3 inhibitor.Conclusion:Honokiol inhibits chronic hypoxia-induced microglia M1 polarization and inflammatory pathway activation,and its anti-inflammatory effects are SIRT3-de-pendent.
基金supported by the Fundamental Research Funds for the Central Universities(grant No.PTYX202449).
文摘Combining drug delivery technologies with chemotherapeutic drugs is very attractive in terms of enhancing antitumor efficacy and reducing toxicity.Alginate microspheres stand out in the field of drug delivery due to their biocompatibility and high conversion rate.However,there are certain drawbacks in their preparation technology and further research is needed on how to prepare alginate microspheres with uniform particle size using high-viscosity sodium alginate solution.Therefore,this study proposed a novel microfluidic membrane emulsification technique for the preparation of alginate microspheres from high-viscosity sodium alginate solution.A tumor microenvironment-responsive colorectal cancertargeted oral drug delivery system was constructed using a disulfide-bonded coupling of honokiol and doxorubicin as a model drug to achieve precise targeting,efficiency enhancement and toxicity reduction.The results showed that the prepared microspheres were relatively homogeneous in particle size.The in vitro model showed the high stability of the microspheres in the gastric acid environment and the colon-targeted release characteristic.And the system triggered the breakage of redox bonds and the precise release of the drug,showing good antitumor activity.This study contributes to the construction of drug delivery systems and the study of colon cancer treatment,which has a promising application.
基金supported by the National Natural Science Foundation of China(Grant Nos.82200563,52273149,82272155)the Shaanxi Provincial Natural Science Foundation(Grant Nos.2022JQ-763,2023-YBSF-420,2024SF-YBXM-205)+2 种基金the Key Science and Technology Innovation Team of Shaanxi Province(Grant No.2024RSCXTD66)the World-Class Universities(Disciplines)and Characteristic Development Guidance Funds for the Central UniversitiesFundamental Research Funds for the Central Universities。
文摘Postoperative abdominal adhesion represents a frequent clinical challenge.Despite the numerous direct and indirect approaches developed to address this issue,standalone physical or chemical strategies exhibit inherent limitations and often fail to achieve optimal antiadhesion outcomes.In this study,an injectable,biodegradable hydrogel incorporating micelles formed through Schiff base cross-linking between lauric acid-modified carboxymethyl chitosan(CMCS-LA)and oxidized hyaluronic acid(OHA)is presented as an efficient physical-chemical combined antiadhesion solution.The hydrogel demonstrates rapid gelation,tunable stiffness,biodegradability,injectability,and outstanding self-healing properties.Serving as an adherent physical barrier on abdominal tissues prevents abnormal tissue attachment.The release of the hydrophobic drug honokiol,which is physically encapsulated in CMCS-LA micelles,is sustained to activate peritoneal mesothelial cells,thereby reducing postoperative adhesion formation after surgery.In a rat model of lateral wall defects and caecal abrasion,the hydrogel effectively suppressed abnormal fibrous tissue hyperplasia and inflammatory responses while preventing adhesion.This dualfunction system successfully integrates physical barrier properties with chemical activity,offering a promising approach for future antiadhesion therapies.
基金supported by National Natural Science Foundation of China(62120106004)Key Project of Zhejiang Province(2023C03104,2024C03146)the Fundamental Research Funds for the Central Universities(226-2024-00059).
文摘In cancer cells,higher reactive oxygen species(ROS)than normal cells were observed due to hypermetabolism.The redox balance in cancer cells relies on accordingly upregulated antioxidant capacity.By manipulating oxidation and antioxidant systems,chemotherapeutic drugs can selectively kill cancer cells without hurting normal cells.As threedimensional(3D)in vitro models,such as spheroids and organoids,have become widely used in cancer research,traditional detection methods(e.g.,absorption tests or titration)are inadequate for detecting in 3D environments.Thus,it is crucial to find a new method to detect oxidative stress of 3D in vitro cancer models.Here,a nanocomposite electrochemical biosensor was exploited to evaluate oxidative stress of cancer cells cultured in the 3D environment.The oxidation-regulatory capacity of honokiol,a Magnolia genus-derived anti-cancer molecule,was evaluated.A screen-printed electrode(SPCE)was modified with reduced graphene oxide(RGO)and platinum nanoparticles(Pt NPs)to get Pt NPs/RGO/SPCE.Then the gelatin methacrylate/reduced graphene oxide(GelMA/RGO)hydrogel was applied to immobilized NCI-H1975 in a 3D bionic environment to get NCI-H1975/GelMA/RGO/Pt NPs/RGO/SPCE.After optimizing the experiment condition,the Pt NPs/RGO/SPCE showed a detection threshold of 0.65μM and a linear field from 1 to 10μM for H_(2)O_(2)detection while the NCI-H1975/GelMA/RGO/Pt NPs/RGO/SPCE sensitively responded to H_(2)O_(2)-induced oxidative stress.By utilizing the NCI-H1975/GelMA/RGO/Pt NPs/RGO/SPCE we found honokiol(a natural polyphenol constituent)inhibits NCI-H1975 by inducing oxidative stress.This simple cell-based electrochemical biosensor can in situ evaluate oxidative stress of 3D cancer models conveniently.It can also be easily extended to the study of the mechanism of action of other drugs and holds broad application prospects in the fields of new drug development and drug repurposing.
