Effects of Mirazid~ and myrrh volatile oil on adult Fasciola gigantica under laboratory conditions

Objective:To evaluate the effects of Mirazid and myrrh volatile oil on adult Fasciola gigantica(F.gigantica) under laboratory conditions.Methods:The effects of oleoresin extract of myrrh(Mirazid) and myrrh volatile oil on the surface morphology of adult F.gigantica following treatment in vitro had been determined by scanning electron microscopy.The results were compared with those observed in the fluke tegument following incubation in triclabendazole sulphoxide(TCBZ-SO),active form.(Fasinex,Ciba-Geigy).Results:Observations of the efficacy of Mirazid oleoresin extract and myrrh volatile oil indicated that both products showed dosedependent anthelmintic efficacy.The anterior half of the fluke was consistently more severely affected than the posterior half.The surface changes induced by Mirazid oleoresin extract were less severe than those observed after exposure to either myrrh volatile oil or TCBZ-SO.Flukes showed swelling after these treatments,but its level and blebbing were much greater with myrrh volatile oil;in which patches of tegumental sloughing were observed in the apical cone and the posterior mid-body region of flukes.This was not observed after treatment with Mirazid oleoresin extract.Conclusions:The comparatively more disruption,observed in myrrh volatile oil exposed specimens,compared to that exposed to Mirazid oleoresin extract might suggest that the anthelmintic activity of Mirazid oleo resin extract was attributed to its content of volatile oil.So,increasing the concentration of myrrh volatile oil in Mirazid might possibly help to developing its anthelmintic activity._______________________________________________

Frankincense myrrh attenuates hepatocellular carcinoma by regulating tumor blood vessel development through multiple epidermal growth factor receptor-mediated signaling pathways

BACKGROUND In traditional Chinese medicine(TCM),frankincense and myrrh are the main components of the antitumor drug Xihuang Pill.These compounds show anticancer activity in other biological systems.However,whether frankincense and/or myrrh can inhibit the occurrence of hepatocellular carcinoma(HCC)is unknown,and the potential molecular mechanism(s)has not yet been determined.AIM To predict and determine latent anti-HCC therapeutic targets and molecular mechanisms of frankincense and myrrh in vivo.METHODS In the present study,which was based on the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(http://tcmspw.com/tcmsp.php),Universal Protein database(http://www.uniprot.org),GeneCards:The Human Gene Database(http://www.genecards.org/)and Comparative Toxicogenomics Database(http://www.ctdbase.org/),the efficacy of and mechanism by which frankincense and myrrh act as anti-HCC compounds were predicted.The core prediction targets were screened by molecular docking.In vivo,SMMC-7721 human liver cancer cells were transplanted as xenografts into nude mice to establish a subcutaneous tumor model,and two doses of frankincense plus myrrh or one dose of an EGFR inhibitor was administered to these mice continuously for 14 d.The tumors were collected and evaluated:the tumor volume and growth rate were gauged to evaluate tumor growth;hematoxylineosin staining was performed to estimate histopathological changes;immunofluorescence(IF)was performed to detect the expression of CD31,α-SMA and collagen IV;transmission electron microscopy(TEM)was conducted to observe the morphological structure of vascular cells;enzyme-linked immunosorbent assay(ELISA)was performed to measure the levels of secreted HIF-1αand TNF-α;reverse transcription-polymerase chain reaction(RT-qPCR)was performed to measure the mRNA expression of HIF-1α,TNF-α,VEGF and MMP-9;and Western blot(WB)was performed to determine the levels of proteins expressed in the EGFR-mediated PI3K/Akt and MAPK signaling pathways.RESULTS The results of the network pharmacology analysis showed that there were 35 active components in the frankincense and myrrh extracts targeting 151 key targets.The molecular docking analysis showed that both boswellic acid and stigmasterol showed strong affinity for the targets,with the greatest affinity for EGFR.Frankincense and myrrh treatment may play a role in the treatment of HCC by regulating hypoxia responses and vascular system-related pathological processes,such as cytokine-receptor binding,and pathways,such as those involving serine/threonine protein kinase complexes and MAPK,HIF-1 and ErbB signaling cascades.The animal experiment results were verified.First,we found that,through frankincense and/or myrrh treatment,the volume of subcutaneously transplanted HCC tumors was significantly reduced,and the pathological morphology was attenuated.Then,IF and TEM showed that frankincense and/or myrrh treatment reduced CD31 and collagen IV expression,increased the coverage of perivascular cells,tightened the connection between cells,and improved the shape of blood vessels.In addition,ELISA,RT-qPCR and WB analyses showed that frankincense and/or myrrh treatment inhibited the levels of hypoxia-inducible factors,inflammatory factors and angiogenesis-related factors,namely,HIF-1α,TNF-α,VEGF and MMP-9.Furthermore,mechanistic experiments illustrated that the effect of frankincense plus myrrh treatment was similar to that of an EGFR inhibitor with regard to controlling EGFR activation,thereby inhibiting the phosphorylation activity of its downstream targets:the PI3K/Akt and MAPK(ERK,p38 and JNK)pathways.CONCLUSION In summary,frankincense and myrrh treatment targets tumor blood vessels to exert anti-HCC effects via EGFR-activated PI3K/Akt and MAPK signaling pathways,highlighting the potential of this dual TCM compound as an anti-HCC candidate.

Tegumental histological effects of Mirazid~ and myrrh volatile oil on adult Fasciola gigantica

Objective:To evaluated the histological changes within the tegument of adult Fasciola gigantica(F.gigantica)that led to the gross changes that were visible externally.Methods:The effects of oleoresin extract of myrrh(Mirazid^(?)),myrrh volatile oil and triclabendazole sulphoxide(reference drug)on the tegumental structure of adult F.gigantiea following treatment in vitro had been determined by light microscopy.Results:The internal changes in the tegument observed in this study were compatible with surface changes seen in the previous scanning electron microscopy study,using the same drugs.The swelling of tegumental syncytium was a particular feature of their action,but its level was much greater with myrrh volatile oil,in which vacuolization of the tegument and loss of spines were observed.Conclusions:The present study demonstrated the fasciocidal properties of Mirazid^(?)oleoresin extract,and it might be possible to reinforce its fasciocidal activity by increasing its content of myrrh volatile oil.

Myrrh extract alleviated ROS-mediated ferroptosis through regulating TXNIP/NLRP3 axis in ischemic stroke

OBJECTIVE To investigate the neuroprotective effects and exact mechanisms of myrrh extract following cerebral ischemic stroke.METHODS Male rats were randomly divided into three groups:sham group,middle cerebral artery occlusion(MCAO)group and myrrh group.Morphological changes were assessed after 7 d of myrrh treatment.Microarray analysis with circulating mRNA was performed to identify differential gene expression profile,gene ontology and pathway enrichment analyses were carried out to predict the gene function.Gene co-expression and pathway networks were constructed to identify the potential targets.The markers of oxidative stress,inflammatory reaction and ferroptosis in the cerebral cortex were detected by ELISA assays.The identified hub pathways and genes were validated by western blotting,immunofluorescence and immunohistochemistry analyses.Neurons were exposed to transient oxygen-glucose deprivation(OGD)to model ischemia-like conditions.siRNA-TXNIP were transfected in OGD-induced neurons to explore the mechanism.RESULTS Myrrh extract significantly alleviated neurological deficits,infarct volume and histo⁃pathological damage in MCAO rats.A total of 2200 differentially expressed genes were identified among the three groups.Oxidation-reduction process,inflammatory response,ferroptosis were enriched as the significant gene ontology items.NOD-like receptor signaling were identified as the hub pathway based on the pathway relation network.TXNIP and NLRP3 were screened as the potential targets by a time sequence profile analysis.The levels of IL-1β,IL-18,TNF-α,MDA and TFR in brain tissues were increased while the CAT,SOD,GSH-px and GPX4 levels were significantly decreased in MCAO group.As expected,myrrh extract greatly reversed these changes.The similarly results were also observed in OGD treated neuron cells.The elevated expressions of TXNIP and NLRP3 induced by OGD were success⁃fully inhibited by myrrh treatment.Knockdown of TXNIP significantly alleviated OGD-induced ROS accumulation and oxidative stress,but the antioxidative effect of myrrh was impaired when TXNIP was absent in neuron cells.In addition,knockdown of TXNIP significantly decreased the expression of NLRP3 and increased the expression of GPX4 in OGDinduced neuron cells.However,myrrh treatment scarcely changed the expressions of NLRP3 and these ferroptosis markers in siRNA-TXNIP pretreated cells,compared with the siRNA-TXNIP alone treatment group.Therefore,these data demonstrated that the neuroprotective effect of myrrh extract was dependent on TXNIP-NLRP3 axis.CONCLU⁃SION Thatmyrrh extract exerts neuroprotective property through alleviated ROS-mediated ferroptosis by regulating the TXNIP/NLRP3 axis in ischemic stroke.Myrrh extract could be considered as a promising candidate for the treatment of ischemic stroke.

Effect of <i>Commiphora molmol</i>(Myrrh) Extract on Mice Infected by <i>Giardia lamblia</i>

Objective: To investigate the efficacy of (Commiphora molmol(Myrrh)) extract as alternative treatment in hamsters against giardiasis. This study was conducted to evaluate the effect of the new compound (Commiphora molmol(Myrrh)), as agent a natural product extracted from the roots of Zingiber officinal, on Giardia lamblia infection as anti-protozoal and to study the parasitological and Histopathological impact of this treatment on the duodenal mucosa of infected hamsters. Fifty hamsters were divided into five groups: Group (A): normal control. Group (B): Giardia lamblia infected and untreated hamsters served as control. Group (C): infected with Giardia lamblia and treated with metronidazole in dose (120 μg/kg body weight twice daily for 7 successive days). Group (D) Giardia lamblia infected and orally treated with Myrrh (500 mg/Kg for 1 week). Group (E): Giardia lamblia infected and orally treated with combination 1/3 dose of (120 μg/kg body weight) metronidazole and Myrrh (250 mg/Kg) for 1 week). After 2 weeks of the treatment, hamsters were sacrificed. The highest percentages of reduction in the number of Giardia lamblia cysts and trophozoites were in the group receiving combined metronidazole and myrrh. Histopathological examination revealed complete healing of intestinal mucosa after the combined treatment, while partial healing of the lining epithelium of the intestine was noticed after metronidazole and either myrrh plant treatment.

Effect of Antimicrobial Myrrh on the Color and Viscosity of Plain Yogurt over Its Shelf Life

Myrrh, commercially available as a brown powder, is a natural flavoring substance approved for food use by US Food and Drug Administration and has antibacterial and antifungal activity against pathogens. Myrrh is commercially available as a brown powder. The objective was to determine the effect of myrrh on the color (L*, a*, b*, C*, h*) and viscosity of yogurt over refrigerated storage. Myrrh dispersion was prepared and incorporated at a 1% v/v level into yogurt. A control with no myrrh was also prepared. Three replications were conducted. At a small usage level of 1% v/v, myrrh influenced the color attributes L*, a* and h* but did not influence the viscosity of the plain yogurts.

Antiulcer Activities of Commiphora molmol (Myrrh) Extract in Male Rats

Medicinal plants used in folk medicine contain a wide range of substances that can prevent and treat many diseases. The Antiulcer Activities effects of myrrh or Commiphora molmol extract (CME) were assessed in rats. In this experiment, thirty rats were divided into 6 groups as follows: G1) normal control (vehicle);G2) received aspirin without any treatment;G3) pretreated with Omeprazole (antiulcer drug) and groups (4), (5) and (6) were pretreated with CME at 125, 250 and 500 mg/kg b.wt, respective-ly for 2 weeks. At the end of experiment the volume, pH and total acidity of gastric juices;mucus content and ulcer lengths were measured and protection percentages were calculated. Gross and histopathological examinations of stomachs were also performed. CME induced an antiulcer effect manifested by decreased volume and total acidity of gastric juice and increased mucus content and percentages of protec-tion from ulcer as well as partial amelioration of gross and histopathological lesions seen in stomach of ulcerated rats. In conclusion, the results denote that Commiphora molmol extract possess antiulcer effects in rats. These results affirm the traditional use of Myrrh extract for the treatment of gastric ulcer.

紫苏-乳香-没药挥发油对小鼠创口愈合的促进作用

目的探讨紫苏挥发油与乳香-没药挥发油配伍对小鼠创口愈合的促进作用。方法将ICR小鼠随机分为空白组(CON)、模型组(MOD)、表皮生长因子凝胶组(GEL)、乳香-没药挥发油组(OM,50μL/mL)、紫苏-乳香-没药挥发油组(POM,70μL/mL,V(紫苏挥发油)V(乳香-没药挥发油)=25),除CON组外,其他各组在小鼠背部造一个直径0.8 cm的开放圆形创口。除MOD组外,每只小鼠涂药1次/d,连续14 d,观察小鼠创口愈合情况、病理组织形态,比较3、7、14 d小鼠血清中TNF-α、IL-1β和IL-6的表达情况。结果POM组小鼠创口愈合率大于OM组,且显著高于MOD组(P<0.05);组织病理学检查显示,POM组创口恢复情况优于MOD组;创后3 d,POM组小鼠血清中TNF-α和IL-6水平显著低于MOD组(P<0.05)。结论紫苏-乳香-没药挥发油能减少创口前期炎症反应,促进小鼠创口愈合。

基于变异系数法-层次分析法综合加权结合响应面法优选樟帮炒没药炮制工艺

目的优选樟帮炒没药的最佳炮制工艺。方法采用层次分析法(AHP)结合变异系数法综合加权的复合评分法,以9-甲氧基没药酮、MCS134、没药酮、FSA的UPLC-Q-TOF-MS响应值,产出率和出粉率的综合加权评分为评价指标,以炒制温度、炒制时间、米醋用量为考察因素,运用响应面法设计优选出樟帮炒没药的最佳炮制工艺。结果樟帮炒没药的炮制最佳工艺为每50 g没药以185℃炒制12 min,期间均匀喷洒7.5 g米醋,取出,晾凉。结论该炮制工艺稳定、可行,可为樟帮炒没药的开发推广和规范化生产提供科学依据。

没药挥发性化学成分的研究

用水蒸气蒸馏法提取没药挥发性化学成分.用毛细管气相色谱-质谱联用技术进行结构鉴定.从中鉴定出45个化合物,其主要成分为:4,5,6,6A-四氢-2(1H)-并环戊烯酮、1,5,9-三甲基-1,5,9-环十二碳三烯、4-乙烯基-4-甲基-3-异丙烯基-1-异丙基-环己烯、α-毕橙茄油烯、十氢-3A-甲基-6-亚甲基-1-异丙基-环丁[1,2:3,4]二环戊烯、脱氢香橙烯、1R,3Z,9S-4,11,11-三甲基-8-亚甲基双环[7.2.0]十一碳-3-烯、柏木烯、1-乙基-1-甲基-2,4-二异丙烯基-环己烯、7-亚甲基-2,4,4-三甲基-2-乙烯基-双环[4.3.0]壬烷、1,2,3,4,4A,5,6,8A-八氢-7-甲基-4-亚甲基-1-异丙基萘.

没药倍半萜成分的分离鉴定及抗肿瘤活性

目的从没药提取物中分离纯化倍半萜单体成分,并探讨其抑制肿瘤细胞增殖的生物活性。方法没药石油醚提取部分经硅胶柱层析分离得到二十多个倍半萜类化合物。其中化合物1和2的结晶分别经熔点测定、薄层层析1、H-NMR和13C-NMR数据分析以及与已知化合物比较,确定其化学结构。利用MTT法检测化合物1和2对大肠癌细胞HT-29和激素非依赖型前列腺癌细胞PC-3、PC-3M、DU-145及正常肝的永生化细胞LO2细胞增殖的影响。结果经理化性质鉴定、波谱分析,确定化合物1的结构为[1(10)E,2R,4R]-2-甲氧基-8,12-环氧吉玛-1(10),7,11-三烯-6-酮;化合物2的结构为2-甲氧基-5-乙酰基-4-呋喃吉玛-1(10)-烯-6-酮,二者同属没药吉玛烷型倍半萜类化合物。MTT结果表明,化合物1和2对大肠癌细胞增殖的抑制作用较弱。而对三种激素非依赖型前列腺癌细胞的增殖有非常显著的抑制作用(P<0.01),且呈剂量依赖性。另外,化合物对正常肝永生化细胞的增殖无明显影响。结论经分离纯化、理化性质鉴定和波谱分析,确定了没药吉玛型倍半萜化合物1和2的结构,该化合物对前列腺癌细胞的增殖有明显的抑制作用。

没药炮制后对动物止痛及血小板粘附性的影响

目的：研究没药炮制后的药理作用的变化。方法：用热板法和扭体法进行止痛实验；用体外血小板粘附率测定法测定血小板粘附性，探讨没药炮制后是否有增强止痛和降低血小板粘附性的作用。结果：生没药和制没药都具有止痛作用，醋制后其作用更强，但生没药不能降低血小板粘附性，醋制后才具有降低血小板粘附性的作用。

乳香、没药药对配伍挥发油成分的GC-MS分析

目的考察乳香、没药药对配伍对挥发油化学成分的影响。方法采用气-质联用系统对乳香、没药药材以及药对配伍中的挥发油进行分析,评价配伍对挥发油成分及含量的影响。结果采用GC-MS对乳香、没药药材和药对挥发油的成分进行分析比较,发现乳香挥发油中检出的trans-3,5,6,8 a-四氢-2,5,5,8 a-四甲基-yl-2H-1-苯并吡喃、荜澄茄-1(10),4-二烯等成分和没药挥发油中检出的2-(1,2-二甲基-2-环戊烯-1-yl)-乙酸苯酯、(1S-cis)-1,2,3,4-四氢-1,6-二甲基-4-(1-甲基乙基)-萘、1,4-二甲基-7-(1-甲基乙基)-Azulen-2-醇、(-)-匙叶桉油烯醇等成分在药对挥发油中未检出,而相对于单煎所得的挥发油,药对挥发油中新增成分有1-乙烯基-1-甲基-2,4-二异丙基-环己烷、1,2,3,4-四氢-1-甲基-8-异丙基萘等。结论乳香、没药药对配伍对所提挥发油的成分和含量都有较大的影响。

没药倍半萜抑制前列腺癌细胞的增殖活性初探

目的初步探讨没药两个倍半萜单体化合物抑制前列腺癌细胞增殖的作用机制。方法应用倍半萜单体化合物处理人前列腺癌细胞株LNCaP后,MTT检测化合物对细胞增殖的影响;流式细胞术进一步分析细胞周期时相的变化;反转录PCR(RT-PCR)检测细胞周期相关蛋白p21WAF/CIP1(p21)和cyclinD的表达水平。结果两个没药倍半萜单体化合物对前列腺癌细胞均有显著的抑制活性(P<0.001),使细胞停滞于G0/G1期;并且能在mRNA水平诱导p21的表达,同时降低cyclinD的表达。结论没药倍半萜化合物抑制前列腺癌细胞增殖,可能是通过上调p21的表达、下调cyclinD蛋白的表达来实现的。

没药倍半萜诱导的p21^(WAF/CIP1)蛋白参与抑制前列腺癌细胞增殖

目的探讨没药的两个倍半萜单体化合物抑制前列腺癌细胞增殖的作用机制。方法应用细胞增殖实验噻唑蓝(MTT)法检测化合物对人前列腺癌细胞株LNCaP的影响;流式细胞术进一步分析前列腺癌细胞经化合物处理后细胞周期时相的变化;Western blot检测化合物对细胞周期相关蛋白p21WAF/CIP1(p21)和cyclin D表达的影响;利用细胞转染技术检测化合物对cyclin D启动子表达活力的影响。结果两个没药倍半萜单体化合物对前列腺癌细胞均有显著的抑制活力,使细胞停滞于G0/G1期;且能在蛋白水平诱导p21WAF/CIP1的表达,同时降低cyclinD的表达。结论没药倍半萜化合物抑制前列腺癌细胞的增殖,可能是通过上调p21WAF/CIP1的表达、下调cyclinD蛋白的表达来实现的。

没药中一呋喃倍半萜的核磁共振研究

从没药氯仿提取物中分离得到一呋喃倍半萜类化合物:2-甲氧基-5-乙酰氧基呋喃吉马-1(10)E-烯-6-酮.通过1D NMR和2D NMR(1H1-H COSY,HSQC和HMBC)等技术确定了该化合物的结构,利用2D NMR技术对其核磁共振信号进行了全归属,修正了文献中的归属错误.通过NOESY实验以及偶合常数的分析,确定了其结构中1,10位双键和甲氧基、乙酰氧基、甲基等基团的相对构型.

没药的化学成分及其生物活性

没药属(Commiphora)植物分泌的胶状树脂作为没药(myrrh)为世界多个国家常用植物药,其所含成分包括萜类、甾体、黄酮、木脂素等次生代谢产物。现代药理研究表明没药提取物和所含的化学成分具有细胞毒、抗细菌、抗真菌、镇痛、抗氧化、抗炎等生物活性。本文综述了国内外没药化学成分和生物活性的研究概况。

骨伤酒中没药及红花的薄层色谱鉴别

采用薄层色谱法对骨伤酒中所含没药、红花进行了定性鉴别研究。所用方法特异性强 ,重复性好。

瞿麦、地榆、没药和紫花地丁的体外抑菌实验研究

目的:研究瞿麦、地榆等4种常见中草药水煎剂和乙醇制剂的体外抑菌性能。方法:采用药敏纸片扩散法确定各中草药对各病原菌抑菌性能及最小抑菌浓度(MIC)。结果:各中草药对不同受试菌均有一定的抑菌性能,其中,地榆对枯草杆菌、瞿麦对大肠杆菌和变形杆菌抑菌效果较强,MIC分别达到12.5%、6.25%和12.5%。结论:四种中草药的水煎剂和乙醇制剂对不同受试菌有特定的抑菌作用,瞿麦抑菌效果较好,有良好医用研究前景。