Mangiferin抑制多发性骨髓瘤恶性生物学特性与发挥抗癌效应机制的实验研究

目的:探讨纯中药提取物Mangiferin对多发性骨髓瘤(MM)细胞恶性生物学行为的影响,分析Mangiferin抗骨髓瘤效应的分子机制,为MM替代治疗提供实验依据。方法:不同浓度Mangiferin干预人MM细胞株U266、RPMI8226细胞后,CCK-8法检测细胞增殖,Annexin V/PI双染流式细胞术检测细胞凋亡,Western blot检测凋亡及相关信号通路蛋白的表达,实时荧光定量聚合酶链式反应(qRT-PCR)检测基质金属蛋白酶(MMP)、CXC趋化因子受体(CXCR)家族的表达变化。结果:Mangiferin可抑制U266、RPMI8226细胞增殖活性,并诱导其凋亡。当Mangiferin干预U266和RPMI8226细胞48 h后,U266和RPMI8226细胞中Bcl-2家族促凋亡蛋白Bax表达上调,并下调survivin、Bcl-xL蛋白的表达同时水解活化caspase-3以促进细胞凋亡,且显著下调U266细胞中Bcl-2蛋白表达以诱导细胞凋亡(P<0.05)。在Mangiferin干预MM细胞后,其不仅可增加肿瘤抑制因子p53的表达水平,同时通过抑制抗凋亡分子的表达并下调AKT、NF-κB磷酸化水平继而诱发MM细胞程序性死亡。Mangiferin干预后可明显下调U266细胞CXCR4、MMP2及MMP9的表达(P<0.05),对CXCR2、CXCR7以及MMP13的表达基本无影响(P>0.05);而干预RPMI8226细胞后可下调CXCR4、MMP9、MMP13的表达(P<0.01),对MMP2表达影响微弱,对CXCR2、CXCR7的表达基本无影响(P>0.05)。结论:Mangiferin能抑制MM细胞增殖并诱导其凋亡,其机制可能与抑制NF-κB信号通路激活并通过影响Bcl-2家族蛋白表达以及使MMP、CXCR家族核心成员表达受抑等有关。

Mangiferin联合硼替佐米对Burkitt淋巴瘤恶性生物学行为的调控机制及对CXCR表达的影响

目的:分析芒果苷(mangiferin)联合硼替佐米对人Burkitt淋巴瘤Raji细胞增殖、侵袭、凋亡和自噬的作用及对CXC趋化因子受体家族(CXCR)表达的影响,并探究其间存在的分子机制,为Burkitt淋巴瘤基础研究与临床提供科学依据。方法:采用不同浓度Mangiferin、硼替佐米单药或联合干预Raji细胞,利用CCK-8法检测细胞增殖,Transwell小室法检测细胞侵袭能力,Annexin V/PI双染流式细胞术检测细胞凋亡,Western blot检测凋亡、自噬及Akt/m TOR通路蛋白表达情况,实时荧光定量PCR检测CXCR家族的表达变化。结果:不同浓度Mangiferin干预Raji细胞不同时间后,可抑制Raji细胞活力,且呈浓度及时间依赖性(r=-0.682,r=-0.836);与单药组相比,Mangiferin联合硼替佐米干预Raji细胞时,细胞增殖与侵袭能力显著下降、凋亡水平显著升高(P<0.01)。Mangiferin联合硼替佐米干预Raji细胞后,可上调促凋亡蛋白Bax表达并显著下调抗凋亡蛋白Bcl-2的表达,同时亦使Caspase-3水解活化,继而诱导Raji细胞发生凋亡。Mangiferin联合硼替佐米干预Raji细胞后可上调LC3Ⅱ蛋白的表达,且细胞中LC3Ⅱ/LC3Ⅰ比值较单药或对照组显著上调(P<0.01)。Mangiferin联合硼替佐米可显著抑制Akt和m TOR的磷酸化水平,通过抑制Akt/m TOR通路来使Raji细胞增殖及侵袭受抑,并诱导细胞发生自噬与凋亡。Mangiferin及硼替佐米单药干预Raji细胞后,可下调CXCR4、CXCR7 m RNA的表达,当两药联合时CXCR4、CXCR7 m RNA表达下调更为显著(P<0.01)。Mangiferin单药或联合硼替佐米干预Raji细胞后CXCR5 m RNA表达无显著变化(P>0.05),但两药联合时可使CXCR3表达下调(P<0.05)。结论:Mangiferin联合硼替佐米能协同抑制Raji细胞增殖、侵袭,并诱导其发生自噬与凋亡,机制可能与抑制Akt/m TOR信号通路并通过下调抗凋亡蛋白Bcl-2和上调促凋亡蛋白Bax以及使CXCR家族表达受抑等有关。

Antiviral activity of mangiferin from the rhizome of Anemarrhena asphodeloides against herpes simplex virus type 1

Objective:To evaluate the antiviral activity of pure compounds against herpes simplex virus type 1(HSV-1)from the rhizome of Anemarrhena asphodeloides.Methods:Bioassay-guided isolation was conducted to separate the active compound and its chemical structure was elucidated by spectral analysis.In vitro antiviral efficacy of active compound was detected by Cell Counting Kit-8 assay,plaque reduction assay,and fluorescence observation.RT-PCR was used to determine the viral load and the cytokine-related gene expression after HSV-1 infection.In vivo study was also conducted to further determine antiviral efficacy of an active compound against HSV-1.Results:An active compound was isolated and elucidated as mangiferin.Mangiferin significantly inhibited the replication of HSV-1 in Vero cells with a half maximal inhibitory concentration(IC_(50))of 64.0 mg/L.Time-of-addition and time-of-removal assays demonstrated that mangiferin could effectively inhibit the replication of HSV-1 in the early stage(8 h).UL12,UL42,and UL54 gene expression levels of HSV-1 in the 64 mg/L mangiferin-treated group were markedly reduced as compared with the HSV-1 group(P<0.01).Fluorescence observation showed that mangiferin attenuated the mitochondrial damage maintainingΔΨm induced by HSV-1 in Vero cells.The expression of inflammatory factors TNF-α,IL-1β,and IL-6 was remarkably increased in the virus-infected group as compared with that in the normal group(P<0.05),the levels of these inflammatory factors dropped after treatment with mangiferin.Mangiferin significantly decreased the viral load and attenuated the HSV-1-induced up-regulation of TNF-α,IL-1β,and IL-6.The relative protection rate of HSV-1-infected mice could reach up to55.5%when the concentration of mangiferin was 4 g/kg.Conclusions:Mangiferin exhibits promising antiviral activity against HSV-1 in vitro and in vivo and could be a potential antiviral agent for HSV-1.

Determination of Mangiferin and Homomangiferin in the Leaves of 93 Kinds of Mango

[Objectives]To determine the content of mangiferin and homomangiferin in mango leaves by HPLC.[Methods]The mangiferin and homomangiferin were separated and determined by Elite Hypersil C18(5μm,4.6 mm ID×250 mm)chromatographic column.Acetonitrile-0.1%(V/V)phosphoric acid solution was used as the mobile phase for gradient elution,the flow rate was 1.0 mL/min,the detection wavelength was 258 nm,the column temperature was 30℃,and the injection volume was 5μL.[Results]There was a good linear relationship between mangiferin and homomangiferin in the range of 0.0254-0.5080μg/μL(r=0.9999)and 0.000960-0.019200μg/μL(r=0.9999),respectively.The average recovery rate(n=6)of mangiferin and homomangiferin in mango leaves was 101.7%(RSD=2.0%)and 101.0%(RSD=1.7%),respectively.[Conclusions]There were great differences in the content of mangiferin and homomangiferin in the leaves of different varieties of mango.The experimental results could provide a scientific basis for further development and utilization of mango leaf resources.

Synthesis and evaluation of novel analogues of mangiferin as potent antipyretic

Objective:To screen different analogues of mangiferin pharmacologically for antipyretic activity. Methods:The naturally occurring xanthone glycoside mangiferin was isolated by column chromatography from the elhanolic extract of stem bark of Mangifera indica.Mangiferin was further converted to 5-(N-phenylamino methyleno) mangiferin.5-(N-p-chlorophenylamino methyleno) mangiferin,5-(N-2-methyl phenylamino methyleno) mangiferin.5-(N-p-methoxy phenylamino methyleno) mangiferin.5-(N,N-diphenylamino methyleno) mangiferin,5-(N-α-napthylamino methyleno) mangiferin and 5-(N-4-methyl phenylamino methyleno) mangiferin analogues.The synthesized compounds were further screened for antipyretic activity along with mangiferin at a dose level of 100 and 200 tng/kg.Mangiferin and its analogues were characterized by melting point and R_f value determination and through spectral technique like UV,IR,and NMR spectral analysis.Results:The antipyretic activity of mangiferin as well as all analogues was found to be more significant in at higher dose ie.200 mg/kg which was depicted thmugh a decrease in rectal temperature up to 3 h.Conclusions:The antipyretic activity of mangiferin and its analogues may be attributed to inhibition in synthesis of TNF-αand anti-oxidant activity associated with amelioration of inflammatory actions of cytokines.

Screening, Characterization and Evaluation of Mangiferin Polymorphs

Mangiferin is a compound with many pharmacological activities and exists in many natural products.Anhydrous and hydrate of mangiferin have been reported separately in two literatures,but the polymorphism of this compound has not been realized until this paper.In this study,polymorph screening of mangiferin has been carried out and five forms have been obtained including three new forms never reported.Several solid state characterization methods,such as powder X-ray diffraction,differential scanning calorimetry and thermogravimetry,are used to identify and characterize all of mangiferin forms.The comparison of the crystallographic data and hirshfeld surface analysis were first reported for mangiferin anhydrous and hydrate.Furthermore,the studies on stability,transformation and solubility have been undertaken,the results prompt that form V can be used as the dominant polymorph for the development of innovative pharmaceuticals.

Efficient Extraction and Isolation of Mangiferin from Mango Leaves by Ethyl Acetate Impurity Removal Method

[Objectives] To optimize the ethyl acetate impurity removal method for extracting and isolating mangiferin from mango leaves,and provide raw materials and technical support for development and use of mangiferin related products. [Methods]Five steps( material crushing→ ethyl acetate impurity removing → concentrated extract washing → extracting with methanol → crystallization and precipitation) were used.The single factor experiment and L9( 34) orthogonal experiment was carried out to optimize the process parameters including extraction time,ultrasonic power,extraction times,and extraction temperature.[Results] The optimum process of ethyl acetate impurity removal method for extracting and isolating mangiferin from mango leaves was as follows: the mango leaves were crushed and sieved; 3 m L/g of ethyl acetate was added,sealed and soaked for 4 h,ultrasonically shaken for 20 min( 50℃,350 W),filtered at room temperature,filtered with 100 mesh sieve,and extracted three times; added 100% methanol to the residue at 3 m L/g,extract by ultrasonic vibration for 20 min( 350 W,55℃)for four times,filtered with 100 mesh sieve when it was still hot; mixed the extract of each time,condensed by vacuum decompression to get the extract; added 100% methanol at 4 m L/g,mixed and washed for 5 min at room temperature,placed for 10 min,filtered with 100 mesh sieve,washed 3 times repeatedly,and dried the filter residue at 60℃ to obtain the crude mangiferin; added 100% methanol at 4 m L/g,mixed and washed at 50℃ for 5 min,placed at 6℃ for 8 h,dried the filter residue at 60℃,and repeatedly crystallized two times. According to the above process,crude and pure mangiferin products could be obtained,the purity of mangiferin of the crude product was higher than 64. 00%,the total recovery rate was 83. 90%,and the purity of mangiferin of the pure product was higher than 98. 00%,and the total recovery rate was about 66. 40%. [Conclusions] The optimized ethyl acetate impurity removal method is easy in operation,low in cost,and high in efficiency for extracting and isolating mangiferin,and can be applied for actual production of mangiferin.

Pharmacokinetic Study and Tissue Distribution of Single Mangiferin After Intravenous Administration in Rats

A simple, sensitive ane selective high performance liquid chromatographic （HPLC） method with UV detection （320 nm） was developed and validated for determination of mangiferin in rat plasma and tissues. Mangiferin and internal standard （spinosin） were separated using mobile phase of acetonitrile-water （20：80, v/v） with 1% glacial acetic acid and 1% THF on a Phenomenex gemini C18 column. The flow rate was 0.7 mL/min. The calibration curves of mangiferin in plasma and tissues were linear over the investigated ranges. The intra- and inter-run preeisions for all samples were less than 13.8 %. The time-concentration curve of mangiferin after intravenous administration to rats corresponded to two-compartment model. The main pharmacokinetic parameters T0.5α, T0.5β, CL and AUC0-T were 15.87 min, 26.15 rain, 6.1 L/（min·kg） and 3.28 mg· min/mL, respectively. The highest and lowest levels of mangiferin occurred in spleen and brain, respectively. Mangiferin was not found in liver. After intravenous administration, the drug was distributed extensively and transferred quickly in rats in vivo.

Mangiferin Promotes Bregs Level,Activates Nrf2 Antioxidant Signaling,and Inhibits Proinflammatory Cytokine Expression in Murine Splenic Mononuclear Cells In Vitro

Recent studies indicated that regulatory B cells(Bregs)and nuclear factor erythroid 2-related factor 2(Nrf2)antioxidant signaling pathway play important roles in the pathogenesis of chronic graft-versus-host disease(cGVHD).Mangiferin(MA),a polyphenol compound,has been reported to activate Nrf2/antioxidant-responsive element(ARE)signaling pathway.This study was aimed to investigate the effects of MA on Bregs and Nrf2 antioxidant signaling in murine splenic mononuclear cells(MNCs)in vitro.Our results revealed that MA could increase the Bregs level in murine splenic MNCs.Moreover,MA up-regulated the expression of Bregs-associated immunosuppressive factor interleukin-10(IL-10)by activating the Janus kinase 2(JAK2)/signal transducer and activator of transcription 3(STAT3)and extracellular signal-regulated kinase(ERK)signaling in murine splenic MNCs.Meanwhile,MA inhibited the proinflammatory cytokines IL-2 and interferon-y(INF-y)at both mRNA and protein levels.MA also enhanced the transcription and protein expression of Nrf2 and NADPH quinine oxidoreductase 1(NQOl),whereas decreased that of Kelch-like ECH-associated protein 1(Keapl)in murine splenic MNCs.Moreover,MA promoted the proliferation and inhibited the apoptosis of murine splenic MNCs.These results suggested that MA exerts immunosuppressive effects by upregulating the Bregs level,activating the Nrf2 antioxidant pathway,and inhibiting the expression of pro-immunoinflammatory factors.MA,as a natural immunomodulatory and anti-inflammatory agent,may have a potential role in the prophylaxis and treatment of cGVHD.

Effects of Mangiferin on the Expression of TNF-α,iNos,ICAM-1 and Its mRNA in the Heart,Brain and Kidneys of SHR

[Objectives] To study the effects of Mangiferin( MGF) on TNF-α,iNOS,ICAM-1 and its mRNA expression in the heart,brain and kidneys of spontaneously hypertensive rats( SHR),and reveal the mechanism of its anti-inflammatory injury in hypertension target organs.[Methods]SHRs were randomly divided into 5 groups: the model group,the high-dose,medium-dose,low-dose MGF groups and the Benazepril group,with 8 rats in each group,WKY rats were used for the normal control group. Besides,on-invasive blood pressure( BP) instruments were used to measure systolic blood pressure in the rats' tail artery,western blot was used to analyze the expression of TNF-α,iNOS,ICAM-1 and reverse transcription-polymerase chain reaction( RT-PCR) was used to analyze the expression of TNF-α,iNOS,ICAM-1 mRNA.[Results]Compared with the normal control group,the model group's BP level was significantly increased( P <0. 01)),but the MGF had no significant lowering BP effect( P > 0. 05); compared with the normal control group,the expression of TNF-α,iNOS,ICAM-1 and its' mRNA in the model group was significantly increased( P < 0. 05 or P < 0. 01),and MGF could reduce the level of expression of these inflammatory cytokines( P < 0. 05 or P < 0. 01); between the Benazepril group and high-dose,medium-dose,low-dose MGF groups,most of the indicators had no significant difference( P > 0. 05). [Conclusions]MGF had no significant lowering BP effect,SHR showed inflammatory injury in the heart,brain and kidneys,MGF showed improvement on the inflammatory injury,and the anti-inflammation mechanism may be associated with lowering TNF-α,i NOS and ICAM-1 and its mRNA expression.

Adsorptive Stripping Voltammetric Determination of Mangiferin Using an Activated Chitosan Modified Carbon Paste Electrode

A medium molecular weight powdered chitosan modified carbon paste electrode was used to investigate the electrochemical behaviour by cyclic voltammetry of the pharmacologically-active ingredient mangiferin (MG). An irreversible system was observed, with a peak at ﹢0.55 V (vs Ag/AgCl). The peak current increases about fourfold, at the modified electrode in comparison with that recorded at the chitosan free carbon paste electrode. This allowed the use of adsorptive stripping voltammetry to develop a simple and sensitive electroanalytical method for the determination of MG. The influence of key parameters was investigated, including the electrolysis potential, the preconcentration time, the pH of supporting electrolyte and MG concentration. Upon optimisation of these parameters, the electrode response was found to be directly proportional to the concentration of MG in the range from 2.06 × 10﹣6 M to 6.74 × 10﹣5 M, leading to a detection limit of 1.84 μM for 240 s preconcentration at ﹣0.1 V. A mechanism was also proposed for the electrochemical oxidation of MG.

Mango malformation: II. mangiferin changes associated with <i>fusarium</i>pathogens

Mangiferin (1,3,6,7-tetrahydroxy xanthone-C2-b-D-glucoside) promoted vegetative growth and exhibited inhibitory role on the occurrence of malformation. Mangiferin changes associated with mango malformation pathogens were followed after inoculated mango seedlings (three years) with malformation pathogens i.e. Fusa-rium subglutinans, F. sterilihyphosum, F. oxysporum and F. proliferatum. Mangiferin remained at lower level in leaves of malformed shoots as compared to healthy one. The floral malformation was observed to be associated with the reduction of mangiferin. Strong positive correlations between mangiferin activity and malformation incidence were observed. Mangiferin level at panicle initiation may give a possible estimate of malformation incidence in mango.

Regulating effects of mangiferin on oxidative stress response and mitochondrial pathway apoptosis in spinal cord injury model

Objective:To study the regulating effects of mangiferin on oxidative stress response and mitochondrial pathway apoptosis in spinal cord injury model.Methods: SD rats were selected as the experimental animals and divided into the control group that underwent sham operation, the injury group that were made into spinal cord injury models and the mangiferin group that were made into spinal cord injury models and given mangiferin intervention. 30 d after the intervention, spinal cord tissue was collected, radioimmunoprecipitation kit was used to determine the contents of oxidative stress indexes ROS, H2O2, SOD, GSH-Px and CAT, and enzyme-linked immunosorbent assay kit was used to determine the contents of apoptosis indexes SKIP, ASK1, Fas, tBid, APAF-1 and Caspase-3.Results:ROS, H2O2, SKIP, ASK1, Fas, tBid, APAF-1 and caspase-3 contents in spinal cord tissue of injury group were significantly higher than those of control group whereas SOD, GSH-Px and CAT contents were significantly lower than those of control group;ROS, H2O2, SKIP, ASK1, Fas, tBid, APAF-1 and caspase-3 contents in spinal cord tissue of mangiferin group were significantly lower than those of injury group whereas SOD, GSH-Px and CAT contents were significantly higher than those of injury group.Conclusion:Mangiferin has inhibitory effect on oxidative stress response and mitochondrial pathway apoptosis in spinal cord injury model.

Mangiferin,a natural xanthone,accelerates gastrointestinal transit in mice involving cholinergic mechanism

AIM:To investigate the effects of mangiferin on gastrointestinal transit(GIT) in normal and constipated mice,together with the possible mechanism.METHODS:Intragastrically-administered charcoal mealwas used to measure GIT in overnight starved Swiss mice.In the first experiments,mangiferin(3 mg/kg,10 mg/kg,30 mg/kg,and 100 mg/kg,po) or tegaserod(1 mg/kg,ip) were administered 30 min before the charcoal meal to study their effects on normal transit.In the second series,mangiferin(30 mg/kg) was tested on delayed GIT induced by several different pharmacological agonists(morphine,clonidine,capsaicin) or antagonists(ondansetron,verapamil,and atropine) whereas in the third series,mangiferin(30 mg/kg,100 mg/kg and 300 mg/kg) or tegaserod(1 mg/kg) were tested on 6 h fecal pellets outputted by freely fed mice.The ratio of wet to dry weight was calculated and used as a marker of fecal water content.RESULTS:Mangiferin administered orally significantly(P < 0.05) accelerated GIT at 30 mg/kg and 100 mg/kg(89% and 93%,respectively),similarly to 5-hydroxytryptamine4(5-HT4) agonist tegaserod(81%) when compared to vehicle-treated control(63%).Co-administered mangiferin(30 mg/kg) totally reversed the inhibitory effect of opioid agonist morphine,5-HT3-receptor antagonist ondansetron and transient receptor potential vanilloid-1 receptor agonist capsaicin on GIT,but only to a partial extent with the GIT-delay induced by 2-adrenoceptor agonist clonidine,and calcium antagonist verapamil.However,co-administered atropine completely blocked the stimulant effect of mangiferin on GIT,suggesting the involvement of muscarinic acetylcholine receptor activation.Although mangiferin significantly enhanced the 6 h fecal output at higher doses(245.5 ± 10.43 mg vs 161.9 ± 10.82 mg and 227.1 ± 20.11 mg vs 161.9 ± 10.82 mg of vehicle-treated control,at 30 and 100 mg/kg,P < 0.05,respectively),the effect of tegaserod was more potent(297.4 ± 7.42 mg vs 161.9 ± 10.82 mg of vehicle-treated control,P < 0.05).Unlike tegaserod,which showed an enhanced water content in fecal pellets(59.20% ± 1.09% vs 51.44% ± 1.19% of control,P < 0.05),mangiferin evidenced no such effect,indi-cating that it has only a motor and not a secretomotor effect.CONCLUSION:Our data indicate the prokinetic action of mangiferin.It can stimulate the normal GIT and also overcome the drug-induced transit delay,via a cholinergic physiological mechanism.

Synthesis of mangiferin derivates and study their potent PTP1B inhibitory activity

蛋白质酷氨酸磷酸酶 1B (PTP1B ) 为糖尿病 mellitus 作为一个潜在的处理从药工业收到了可观的注意。Mangiferin 被报导了拥有重要的反糖尿病患者活动。基于以前的学习，八新 mangiferin derivates 为他们的 PTP1B 禁止的活动被综合并且评估。他们中的一些在 PTP1B 上显示了好禁止的活动。

Mangiferin ameliorates hyperglycemia by inhibiting oxidation and α-glucosidase activity

目的：芒果苷（MF）是从知母根提取出来的-种多元酚.本研究旨在探讨芒果苷对胰岛素抵抗和链脲霉素（STZ）引起的糖尿病动物模型的高血糖的影响.方法：通过多次皮下注射氢化可的松琥珀酸钠（HCSS）（70mg/kg）或单次静脉内注射STZ（130mg/kg）建立糖尿病模型.同时连续口服10天不同剂量（50,100和200mg/kg）的MF.腹腔注射胰岛素（0.5U/kg）后,收集不同时间的血糖数值来检测胰岛素抵抗.同时测定肾脏氧自由基吸收能力（ORAC）和超氧化物歧化酶（SOD）活性.建立体外实验,研究MF对α-葡萄糖苷酶的抑制能力.结果：口服芒果苷能够显著抑制由注射HCSS引起的胰岛素抵抗.STZ诱导的糖尿病症状也有所改善,包括空腹血糖,糖化血红蛋白,血浆甘油三酯,肝糖原,肾脏SOD和ORAC水平.体外实验证明芒果苷具有较强的α-葡萄糖苷酶抑制活性.结论：结果表明芒果苷能改善胰岛素抵抗和STZ诱导的糖代谢紊乱.芒果苷通过提高抗氧化能力,促进肝糖原合成,抑制α-葡萄糖苷酶活性发挥保护作用.

Mangiferin alleviates renal infammatory injury in spontaneously hypertensive rats by inhibiting MCP-1/CCR2 signaling pathway

Objective: Hypertension is a low-grade infammation state of the disease and was easily complicated by kidneys’ infammatory response. Mangiferin(MGF), a pharmacologically active compound in various plants including Mangifera indica, has a strong anti-infammatory activity. However, the effects of MGF on renal infammatory injury in spontaneously hypertensive rats(SHRs) remain unclear. The purpose of this study was to investigate the protective effects and mechanisms of MGF on renal infammatory injury in SHRs.Methods: MGF was used in SHRs at the doses of 10, 20, 40 mg/kg/d for 8 weeks consecutively. The blood and urine were collected for assessment of renal function. Renal tissues were collected for histological,immunohistochemistry, ELISA, Western blot and real time reverse transcription PCR(RT-PCR) analysis.Results: The results showed that the levels of interleukin 6(IL-6), tumor necrosis factor-a(TNF-a), monocyte chemoattractant protein-1(MCP-1) and recombinant chemokine C-C-Motif receptor 2(CCR2) were increased in SHRs, meanwhile, the level of IL-10 was decreased in SHR. Treatment of MGF inhibited the expression of IL-6, TNF-a, MCP-1 and CCR2, and promoted the expression of IL-10. Furthermore, the content of blood urea nitrogen(BUN) and serum uric acid(SUA) was significantly increased in the model group, and treatment of MGF had no obvious effects on these parameters at all dose levels.Conclusion: Our study proved that the kidneys of SHRs had significant infammatory injury, and MGF had the protective effects on renal infammatory injury in SHRs;The protective mechanism may be mediated partly by the MCP-1/CCR2 signaling pathway. Thus, it is a potential new drug for the treatment of hypertension.

正交设计优选枣仁安神酒的回流提取工艺

目的筛选回流法制备枣仁安神酒的最佳提取工艺。方法以芒果苷、阿魏酸、甘草苷、斯皮诺素、甘草酸铵5种指标性成分的含量和总固体含量为指标,通过单因素及正交实验考察酒的度数、加酒量及回流时间对提取工艺的影响,从而优选出制备枣仁安神酒的最佳提取工艺。结果确定枣仁安神酒的最佳回流提取工艺为加10倍量的60度白酒,回流提取70 min。3批验证实验结果表明该工艺条件稳定、合理、可靠。结论经筛选出的最佳工艺制备的枣仁安神酒有效成分提取率高、稳定性好,为该制剂的深入开发提供了实验基础。

广西百色芒果叶提取物稳定性的研究

采用HPLC法和紫外分光光度法,对芒果苷的吸光度和浓度进行测定,系统研究了其对光、热、酸碱的耐受情况。结果发现芒果苷在有光无光、高温变化下的吸光值波动起伏不大,在酸性和强碱性条件下芒果苷含量显著降低,说明芒果苷能耐受光照、高温,但强酸强碱能迅速破坏芒果苷的稳定性。

Effects of ethanol extract of Bombax ceiba leaves and its main constituent mangiferin on diabetic nephropathy in mice

The present study was designed to explore the mechanism by which ethanol extract of Bombax ceiba leaves(BCE) and its main constituent mangiferin(MGF) affect diabetic nephropathy by combating oxidative stress. Oral administration of BCE and MGF to normal and streptozotocin(STZ)-induced diabetic mice were carried out. Fasting blood glucose, 24-h urinary albumin, serum creatinine, and blood urea nitrogen were tested, histopathology, and immunohistochemical analysis of kidney tissues were performed. Moreover, mesangial cells were treated with BCE and MGF for 48 h with or without 25 mmol·L^(-1) of glucose. Immunofluorescence, Western blot and apoptosis analyses were used to investigate their regulation of oxidative stress and mitochondrial function. BCE and MGF ameliorated biochemical parameters and restored STZ-induced renal injury in the model mice. In vitro study showed that high glucose stimulation increased oxidative stress and cell apoptosis in mesangial cells. BCE and MGF limited mitochondrial membrane potential(Δψm) collapse by inhibiting Nox4, mitochondrially bound hexokinase II dissociation, and subsequent ROS production, which effectively reduced oxidative stress, cleaved caspase-3 expression and cell apoptosis. Our work indicated that BCE and MGF had protective effects on diabetic caused kidney injury and prevented oxidative stress in mesangial cells by regulation of hexokinase II binding and Nox4 oxidase signaling.