基于不同来源的黄芩物质基础与其药效学相关性研究
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摘要
阐明中药药效物质基础一直是中医药研究者关注的热点问题。一方面,中药药效物质基础研究是推动中医药现代化的关键问题之一。另一方面,以寻找单一成份表述整体功效的指导思想和诸多研究方法又直接与传统中医药理论核心相关联。因此,如何恰当地运用现代科学理论和技术成果,采用符合中医药学自身理论特色的可行性研究思路和方法,阐明中药特定药效对应的物质基础及其作用机制是亟待解决的问题。
黄芩为唇形科植物黄芩Scutellaria baicalensis Georg的干燥根,始载于《神农本草经》,有清热燥湿,泻火解毒,止血安胎之功效。对于黄芩成份的研究,已经提取出以黄酮类化合物为主的60余种化学物质,主要包括黄芩苷、黄芩素、汉黄芩苷、汉黄芩素、黄芩新素等,更是以黄芩苷的含量较高被《药典》作为检测黄芩质量的标准。
从黄芩主要成分的药理学研究结果来看,主要化学成分的药理作用有相同的部分,但它们的作用并非完全重合,也有互补的方面。不同来源的黄芩主要成分含量也存在明显差异,作为道地药材而被广泛认可的河北承德黄芩,黄芩苷的含量与其他产地相比较少,但其在解热,抗炎等方面的药效却优于其他地区的黄芩。因此,仅以黄芩苷的含量来评价黄芩的质量可能是有局限性的,黄芩苷的含量高低有可能不能完全代表黄芩功效,黄芩中除黄芩苷外可能另有起着关键作用的有效成分,以黄芩主要活性成分的合理配比作为体现黄芩药效质量的研究,有可能揭示其药效作用的物质基础,可为其它中药材的药效学研究提供借鉴。
本课题对不同来源黄芩化学成分含量、提取、测定和活性成分的药理作用等方面予以探讨。
目的：阐明黄芩的质量特征、药效物质基础,为黄芩质量评价及临床和生产用药提供科学依据,也为优质黄芩的人工栽培及其生产质量调控奠定理论基础。
方法：本研究在中医理论指导下,以中药药理学为主要研究方法,结合中药化学与化学成分分析,针对黄芩的清热燥湿、泻火解毒两大功效,开展清热燥湿、抗炎、抗病毒、解热等药效学试验,通过中药化学分析、指纹图谱建立、数据库集成等信息处理方法进行不同来源黄芩物质基础与药效相关性研究。
结果：
1.抗炎药效学试验：不同产地黄芩提取物各组小鼠耳肿胀率与模型组比较均有显著差异(p<0.05),以河北醇组和山西醇组与模型组比较差异尤为显著(P<0.01),两组间比较无显著差异(p>0.05)；不同产地黄芩提取物各组抑制大鼠足跖肿胀的时点不同,总体疗效与模型组两两比较均有显著差异(p<0.05),河北醇提物与模型组比较差异尤为显著(P<0.01)。
黄芩成份配比组和河北醇提组小鼠耳肿胀率与模型组比较均有非常显著差异(p<0.01),配比组和河北醇组比较差异不显著(p>0.05)；黄芩成份配比组和河北醇提组大鼠足跖肿胀率与模型组总体比较均有显著差异(p<0.05),河北醇提组大鼠足跖肿胀率与模型组比较差异尤为显著(p<0.01),配比组和河北醇组比较也有显著差异(p<0.05)。
不同年限黄芩提取物各组小鼠耳肿胀率与模型组两两比较均有显著差异(p<0.05),各组大鼠足跖肿胀率与模型组总体比较均有显著差异(p<0.05),都以二年生黄芩组与模型组比较差异最为显著(P<0.01)。
不同产地同一地区栽培黄芩提取物各组小鼠耳肿胀率与模型组两两比较均有显著差异(p<0.05),以河北产二年生组差异最为显著(P<0.001)；各组提取物抑制大鼠足跖肿胀的时点不同,总体疗效与模型组两两比较差异显著(p<0.05)
2.解热药效学试验：不同年限黄芩提取物各组解热作用与模型组两两比较总体存在显著差异(p<0.05),二年生黄芩组大鼠体温总体变化与一年组、三年组比较差异显著(P<0.5),一年组、三年组大鼠体温变化比较差异不显著(P>0.05)。
不同产地同一地区栽培黄芩提取物各组解热作用与模型组两两比较总体存在显著差异(p<0.05),以河北产二年生组差异最为显著(p<0.01)。
3.抗病毒药效学试验：不同年限黄芩提取物各组死亡率与模型组比较有非常显著性差异(P<0.01),各提取物组之间两两比较无差异(P>0.05)。肺指数比较中,河北承德黄芩二年生与一年生比较无差异(P>0.05),与三年生比较有显著性差异(P<0.05),一年生与三年生比较无差异(P>0.05)。
不同产地同一地区栽培黄芩提取物各组死亡率与模型组比较,除大连三年组差异显著(P<0.05),其他各组与模型组比较有非常显著性差异(P<0.01),各提取物组间两两比较无差异(P>0.05)。肺指数比较中,河北二年组、大连三年组与模型组比较有显著性差异(P<0.05),其他提取物组与模型组比较有非常显著性差异(P<0.01),各提取物组间两两比较差异不显著(P>0.5)。
4.清热燥湿药效学试验：灌服大肠杆菌后,全部大鼠体温升高,大便次数增多,有些呈稀烂状,部分大鼠出现肛门红肿充血。全部大鼠蜷卧懒动,耸毛明显,毛色暗黄无泽,与正常组比较体重增长趋势明显减慢。各治疗组大鼠的体温下降较对照组快,大便次数减少,肛门红肿较轻。用药到第4天时,模型对照组大鼠的饮食量与正常对照组比较,有非常显著性差异(P<0.01),而各治疗组大鼠的饮食量改变没有差异(P>0.05)。SOD活性变化,不同来源黄芩提取物组间SOD活性两两比较无显著差异(p>0.05)。MDA水平变化,不同来源黄芩提取物组间MDA水平两两比较无显著差异(p>0.05)
5.抗炎活性成分组成与药效之间的谱效关系研究：河北醇提物中不同保留时间的化学物质稳定性在1.8%-2.98%之间,小于3%,重复性良好。通过灰色关联分析河北黄芩醇提物活性成份,抑制小鼠耳肿关联度大于0.74的物质顺序为保留时间为12.0min的物质>保留时间为70.1min的物质>保留时间为58.5min的物质>汉黄芩苷>汉黄芩素。对于抗大鼠足肿作用来说,关联度大于0.74的物质的顺序为保留时间为70.1min的物质>汉黄芩素>保留时间为72.9min的物质>保留时间为58.5min的物质>保留时间为43.8min的物质>黄芩苷>保留时间为8.5min的物质>保留时间为39.9min的物质>汉黄芩苷
结论：
1不同产地黄芩提取物对湿热模型大鼠均有一定的治疗作用,能改善湿热证大鼠脾胃的运化功能,降低模型大鼠体温,提高模型大鼠免疫功能,但各产地药效相当。
2不同产地黄芩提取物对二甲苯致小鼠耳肿模型、干酵母致大鼠足肿模型均有较好的抗炎作用,河北醇提物抑制急性炎症疗效最佳。
3灰色关联分析能较准确的评价指纹图谱与药效之间的关联性,为建立中药谱效关系学提供研究方法,具有一定的实用价值。
4黄芩活性成分配比物(汉黄芩苷：汉黄芩素：黄芩苷=0.68：0.47：11.9)对二甲苯致小鼠耳肿炎症有较好抑制作用,疗效与河北黄芩醇提取物相当,在某种意义能代表黄芩抗炎药效物质基础；配比物(汉黄芩素：黄芩苷：黄芩素=0.47：11.9：3.8)对干酵母致大鼠足跖肿胀也有一定的抑制作用,但检测各时点药效均低于河北黄芩醇提取物,可能除配比成分外其它活性成份仍是抑制大鼠足跖肿胀肿的重要药效物质基础。
5不同年限黄芩提取物对干酵母致大鼠发热模型表现出较好的解热作用,但各组发挥解热作用时点有差异；对二甲苯致小鼠耳肿模型、干酵母致大鼠足肿模型均有较好的抗炎作用,各实验中均为河北二年生黄芩疗效最佳；对FM1流感病毒感染小鼠均有较好的死亡保护作用,均能降低小鼠的肺指数。
6不同产地引种大连的二年、三年黄芩提取物对干酵母致大鼠发热模型在不同时点表现出一定的解热作用。对FM1流感病毒感染小鼠均有较好的死亡保护作用,均能降低小鼠的肺指数。对二甲苯致小鼠耳肿模型、干酵母致大鼠足肿模型均表现出一定的炎症抑制作用,但对于干酵母致大鼠足跖肿胀的抑制作用,各测试药物发挥抗炎药效的时点不同。
7不同年限、不同产地及异地种植黄芩横向和纵向药效学比较,河北承德二年生黄芩具有较好的解热、抗流感病毒、抗炎作用,为黄芩道地性确认及人工栽培提供一定的理论支持。
8黄芩不同药理作用对应的药效物质基础不尽相同,本课题的研究思路,在一定程度上可为后续黄芩质量标准研究提供借鉴依据和研究途径。
Clarify the material basis of Traditional Chinese Medicines Chinese medicine has always been a hot issue researchers. On the one hand, the material basis of efficacy of Chinese medicine to promote the modernization of Chinese medicine is one of key problems. On the other hand, to find a single ingredient formulation guidelines and the overall effectiveness of various research methods and direct the core of traditional Chinese medicine theory is associated. Therefore, the appropriate use of modern scientific theories and technological results, consistent with characteristics of Chinese medicine theory of the feasibility study on their own ideas and methods, to clarify specific efficacy of Chinese medicine and its corresponding material basis for the acting mechanism of urgent problems.
Scutellaria baicalensis for the Labiatae plant dry root of Scutellaria baicalensis Georg, only contained in the "Shen Nong's Herbal Classic", a heat drying dampness, purging fire detoxification, bleeding the effect of tocolysis. The skullcap ingredients, has been extracted to flavonoid-based, more than 60 chemicals, including baicalin, baicalein, baicalin, wogonin, baicalin new factors, are also based on baicalin content higher being "Pharmacopoeia" as the detection of baicalin quality standards.
The main components from Scutellaria pharmacological research results, the pharmacological effects of the chemical composition of some of the same, but their effect is not completely overlap, there are complementary aspects. Different sources of content of main component baicalin significantly different, as the genuine medicine is widely recognized in Chengde, Hebei baicalin, baicalin content in comparison with other producing less, but their antipyretic, anti-inflammatory efficacy is so better than other parts of skullcap. Therefore, only baicalin content to evaluate the skullcap of quality might be limited, baicalin content level could not be fully representative of baicalin effect, skullcap, in addition to baicalin things might otherwise play a key role in the active ingredients, to skullcap reasonable proportion of the major active components as the embodiment of the quality of baicalin efficacy studies may reveal the role of the material basis of its efficacy, the efficacy of Chinese herbal medicines for other studies for reference
The topic of different sources of baicalin chemical composition, extraction, determination and the active ingredients of pharmacological aspects to be investigated.
Objective:To clarify the characteristics of baicalin quality, efficacy of material basis for quality assessment and clinical baicalin and production of drugs provide the scientific basis for quality and artificial cultivation of Scutellaria theoretical basis for product quality control.
Methods:In this study, under the guidance of TCM theory to Chinese pharmacology as the main research methods, combined with Chinese chemical and chemical composition analysis for the heat dampness skullcap, Xiehuo two detoxification effect, to carry out heat drying as well as anti-inflammatory, anti-virus, fever and other pharmacodynamic test, chemical analysis by traditional Chinese medicine, Fingerprint, database integration and information processing methods based on different sources of material and the efficacy of Scutellaria Correlation.
Results:
1. Antiinflammatory pharmacodynamic test:the extracts from different areas all of the mice ear swelling compared with the model group were significantly different (p <0.05), in Hebei, Shanxi alcohol alcohol group and the difference between the model group is particularly significant (P<0.01), between the two groups was no significant difference (p> 0.05); different origin groups the extracts inhibit the rat paw edema different point in time, the overall efficacy of 22 compared with the model group were significantly different (p<0.05), Hebei ethanol extract compared with the model group is particularly significant difference (P<0.01).
TDA Scutellaria Hebei ethanol group and the mice ear swelling compared with the model group were significant differences(P<0.01), ratio of group and alcohol group Hebei no significant difference (p> 0.05); TDA Group skullcap and Hebei extract group rat paw swelling compared with the model group were significantly different overall (p<0.05), Hebei alcohol extraction rate of rat paw edema model is particularly significant difference between groups (p<0.01), ratio of group and Hebei alcohol group had significant differences (p<0.05).
Different years the extracts of mice ear swelling rate and the model group,22 were significantly different (p<0.05), each rat paw edema rate and the model group, overall there was a significant difference (p<0.05) have to biennial Scutellaria group and model group difference was most significant (P<0.01).
Different areas in the same area cultivated Scutellaria all of the mice ear swelling model group 22 were significantly different (p<0.05), in Hebei Province, biennial controls were the most significant (P<0.001); the group extract inhibits rat paw edema different point in time, the overall efficacy compared with model group,22 significant differences (p<0.05).
2. Antipyretic pharmacodynamic test:the extracts of different age groups antipyretic effect compared with model group,22 were significantly different in general (p<0.05), biennial general Scutellaria rats, body temperature changes and year group, three significant difference between groups (P<0.5), year group, three rats, body temperature change was not significant difference (P> 0.05).Cultivation of different origin in the same area of each group of Scutellaria antipyretic effect compared with the model group 22 overall significant difference (p<0.05), with biennial Hebei Province, the most significant difference between groups (p<0.01).
3. Antiviral-effect test:the extracts of different age groups compared with the model group mortality was significant difference (P<0.01), the extract was no significant difference between the 22 (P> 0.05). Lung index, the Hebei Chengde skullcap biennial and annual no difference (P> 0.05), and three students were significantly different (P <0.05), annual and three-year-no difference (P> 0.05).
Different areas in the same area cultivated Scutellaria the mortality compared with model group, in addition to Dalian three groups significantly different (P<0.05), the other groups compared with model group there was a significant difference (P <0.01), the extraction matter between two groups showed no differences (P> 0.05). Lung index in two groups of Hebei, Dalian three years compared with model group, there were significant differences (P<0.05), the other extracts compared with model group, there was a significant difference (P<0.01), the extract difference between groups was not significant (P> 0.5).
4. Clearing heat and dampness pharmacodynamic test:fed with E. coli, all the rats body temperature, stool frequency increased, there was pulpy form, some rats appeared swollen anal congestion. All of the rats curled lying lazy move, towering hair apparent, especially on dark coat without Ze, compared with normal weight much slower growth trend. Body temperature of rats in all treatment groups declined faster than the control group, decreased stool frequency, rectal swelling less. Medication to 4 days, the model control group eating capacity and the normal control group, there was a significant difference (P<0.01), while the treatment group differences in dietary content did not change (P> 0.05). SOD activity, the extracts from different sources SOD activity of 22 group showed no significant difference (p> 0.05). MDA levels, the extracts from different sources MDA level of 22 groups showed no significant difference (p> 0.05).
5. Anti-inflammatory efficacy of the active ingredient composition and effect relationship between the spectrum of research:Hebei ethanol extract of different retention time stability of chemicals in the 1.8%-2.98%, and less than 3%, good reproducibility. Grey relational analysis by ethanol extract of Scutellaria Hebei active ingredient, ear swelling of mice associated with the material greater than 0.74 in order to retain the material time was 12.0min> retention time 70.1min material> retention time 58.5min material>baicalin>wogonin.The role of anti-rat paw swelling, the correlation is greater than 0.74 in order of the material retention time 70.1min material> Wogonin> retention time 72.9min material> retention time 58.5min material> retention time was 43.8min material> baicalin> retention time 8.5min material> retention time 39.9min material> baicalin.
Conclusion:
1 Different origin skullcap extract on rats have a certain heat treatment can improve damp the operation of the spleen and stomach function in rats, rats reduced body temperature, improve immune function in rats, but rather the origin efficacy.
2 Different origin skullcap extract on xylene-induced mouse ear swelling model, dry yeast induced rat paw swelling models have better anti-inflammatory effect, Hebei alcohol extract the best effect of inhibition of acute inflammation.
3 Grey relational analysis can be a more accurate assessment of fingerprints and the correlation between efficacy, spectrum efficiency for the establishment of Chinese Studies, with research methods, has some practical value.
4 Ratio of the active ingredient of Scutellaria matter (baicalin:wogonin:baicalin= 0.68:0.47:11.9) on xylene-induced ear swelling and inflammation in a better inhibition effect with the alcohol extract of Scutellaria Hebei rather, in the represent a significant anti-inflammatory efficacy of Scutellaria material basis; ratio of material (wogonin: baicalin:baicalein= 0.47:11.9:3.8) on yeast-induced paw edema also has some inhibitory effects, but the detection Hebei efficacy at various time points were lower than the ethanol extract of Scutellaria, ratio of components may be outside than other active ingredient is still inhibited rat paw edema and swelling of the important material basis for efficacy.
5 Years of the extracts of different yeast-induced fever on the model showed a better antipyretic effect, antipyretic effect, but to play point in each group are different; on xylene-induced mouse ear swelling model, dry yeast-induced Foot swelling models have better anti-inflammatory effects, the experiments were the best effect of Hebei biennial skullcap; on mice infected with influenza virus FM1 has better protective effect of the death, can reduce the lung index.
6 Introduction to Dalian from different areas of two years, three years skullcap extract on the dry yeast-induced fever model at different time points show some antipyretic. On mice infected with influenza virus FM1 has better protective effect of the death, can reduce the lung index. On xylene-induced mouse ear swelling model, dry yeast induced rat paw swelling model showed a certain inhibition of inflammation, but dry yeast-induced paw edema inhibition, the efficacy of testing anti-inflammatory drugs different point in time.
7 Different years, different areas and ex situ cultivation of Scutellaria pharmacodynamic comparison of horizontal and vertical, Hebei Cheng de biennial skullcap good antipyretic, anti-virus, anti-inflammatory effects, in order to confirm the genuineness of Scutellaria and cultivated to provide a theoretical support.
8 Different pharmacological effects of Scutellaria corresponding material basis for efficacy of different, the subject of research ideas to a certain extent, quality standards for follow-up study of Scutellaria provides the reference and research approaches.
黄芩为唇形科植物黄芩Scutellaria baicalensis Georg的干燥根,始载于《神农本草经》,有清热燥湿,泻火解毒,止血安胎之功效。对于黄芩成份的研究,已经提取出以黄酮类化合物为主的60余种化学物质,主要包括黄芩苷、黄芩素、汉黄芩苷、汉黄芩素、黄芩新素等,更是以黄芩苷的含量较高被《药典》作为检测黄芩质量的标准。
从黄芩主要成分的药理学研究结果来看,主要化学成分的药理作用有相同的部分,但它们的作用并非完全重合,也有互补的方面。不同来源的黄芩主要成分含量也存在明显差异,作为道地药材而被广泛认可的河北承德黄芩,黄芩苷的含量与其他产地相比较少,但其在解热,抗炎等方面的药效却优于其他地区的黄芩。因此,仅以黄芩苷的含量来评价黄芩的质量可能是有局限性的,黄芩苷的含量高低有可能不能完全代表黄芩功效,黄芩中除黄芩苷外可能另有起着关键作用的有效成分,以黄芩主要活性成分的合理配比作为体现黄芩药效质量的研究,有可能揭示其药效作用的物质基础,可为其它中药材的药效学研究提供借鉴。
本课题对不同来源黄芩化学成分含量、提取、测定和活性成分的药理作用等方面予以探讨。
目的：阐明黄芩的质量特征、药效物质基础,为黄芩质量评价及临床和生产用药提供科学依据,也为优质黄芩的人工栽培及其生产质量调控奠定理论基础。
方法：本研究在中医理论指导下,以中药药理学为主要研究方法,结合中药化学与化学成分分析,针对黄芩的清热燥湿、泻火解毒两大功效,开展清热燥湿、抗炎、抗病毒、解热等药效学试验,通过中药化学分析、指纹图谱建立、数据库集成等信息处理方法进行不同来源黄芩物质基础与药效相关性研究。
结果：
1.抗炎药效学试验：不同产地黄芩提取物各组小鼠耳肿胀率与模型组比较均有显著差异(p<0.05),以河北醇组和山西醇组与模型组比较差异尤为显著(P<0.01),两组间比较无显著差异(p>0.05)；不同产地黄芩提取物各组抑制大鼠足跖肿胀的时点不同,总体疗效与模型组两两比较均有显著差异(p<0.05),河北醇提物与模型组比较差异尤为显著(P<0.01)。
黄芩成份配比组和河北醇提组小鼠耳肿胀率与模型组比较均有非常显著差异(p<0.01),配比组和河北醇组比较差异不显著(p>0.05)；黄芩成份配比组和河北醇提组大鼠足跖肿胀率与模型组总体比较均有显著差异(p<0.05),河北醇提组大鼠足跖肿胀率与模型组比较差异尤为显著(p<0.01),配比组和河北醇组比较也有显著差异(p<0.05)。
不同年限黄芩提取物各组小鼠耳肿胀率与模型组两两比较均有显著差异(p<0.05),各组大鼠足跖肿胀率与模型组总体比较均有显著差异(p<0.05),都以二年生黄芩组与模型组比较差异最为显著(P<0.01)。
不同产地同一地区栽培黄芩提取物各组小鼠耳肿胀率与模型组两两比较均有显著差异(p<0.05),以河北产二年生组差异最为显著(P<0.001)；各组提取物抑制大鼠足跖肿胀的时点不同,总体疗效与模型组两两比较差异显著(p<0.05)
2.解热药效学试验：不同年限黄芩提取物各组解热作用与模型组两两比较总体存在显著差异(p<0.05),二年生黄芩组大鼠体温总体变化与一年组、三年组比较差异显著(P<0.5),一年组、三年组大鼠体温变化比较差异不显著(P>0.05)。
不同产地同一地区栽培黄芩提取物各组解热作用与模型组两两比较总体存在显著差异(p<0.05),以河北产二年生组差异最为显著(p<0.01)。
3.抗病毒药效学试验：不同年限黄芩提取物各组死亡率与模型组比较有非常显著性差异(P<0.01),各提取物组之间两两比较无差异(P>0.05)。肺指数比较中,河北承德黄芩二年生与一年生比较无差异(P>0.05),与三年生比较有显著性差异(P<0.05),一年生与三年生比较无差异(P>0.05)。
不同产地同一地区栽培黄芩提取物各组死亡率与模型组比较,除大连三年组差异显著(P<0.05),其他各组与模型组比较有非常显著性差异(P<0.01),各提取物组间两两比较无差异(P>0.05)。肺指数比较中,河北二年组、大连三年组与模型组比较有显著性差异(P<0.05),其他提取物组与模型组比较有非常显著性差异(P<0.01),各提取物组间两两比较差异不显著(P>0.5)。
4.清热燥湿药效学试验：灌服大肠杆菌后,全部大鼠体温升高,大便次数增多,有些呈稀烂状,部分大鼠出现肛门红肿充血。全部大鼠蜷卧懒动,耸毛明显,毛色暗黄无泽,与正常组比较体重增长趋势明显减慢。各治疗组大鼠的体温下降较对照组快,大便次数减少,肛门红肿较轻。用药到第4天时,模型对照组大鼠的饮食量与正常对照组比较,有非常显著性差异(P<0.01),而各治疗组大鼠的饮食量改变没有差异(P>0.05)。SOD活性变化,不同来源黄芩提取物组间SOD活性两两比较无显著差异(p>0.05)。MDA水平变化,不同来源黄芩提取物组间MDA水平两两比较无显著差异(p>0.05)
5.抗炎活性成分组成与药效之间的谱效关系研究：河北醇提物中不同保留时间的化学物质稳定性在1.8%-2.98%之间,小于3%,重复性良好。通过灰色关联分析河北黄芩醇提物活性成份,抑制小鼠耳肿关联度大于0.74的物质顺序为保留时间为12.0min的物质>保留时间为70.1min的物质>保留时间为58.5min的物质>汉黄芩苷>汉黄芩素。对于抗大鼠足肿作用来说,关联度大于0.74的物质的顺序为保留时间为70.1min的物质>汉黄芩素>保留时间为72.9min的物质>保留时间为58.5min的物质>保留时间为43.8min的物质>黄芩苷>保留时间为8.5min的物质>保留时间为39.9min的物质>汉黄芩苷
结论：
1不同产地黄芩提取物对湿热模型大鼠均有一定的治疗作用,能改善湿热证大鼠脾胃的运化功能,降低模型大鼠体温,提高模型大鼠免疫功能,但各产地药效相当。
2不同产地黄芩提取物对二甲苯致小鼠耳肿模型、干酵母致大鼠足肿模型均有较好的抗炎作用,河北醇提物抑制急性炎症疗效最佳。
3灰色关联分析能较准确的评价指纹图谱与药效之间的关联性,为建立中药谱效关系学提供研究方法,具有一定的实用价值。
4黄芩活性成分配比物(汉黄芩苷：汉黄芩素：黄芩苷=0.68：0.47：11.9)对二甲苯致小鼠耳肿炎症有较好抑制作用,疗效与河北黄芩醇提取物相当,在某种意义能代表黄芩抗炎药效物质基础；配比物(汉黄芩素：黄芩苷：黄芩素=0.47：11.9：3.8)对干酵母致大鼠足跖肿胀也有一定的抑制作用,但检测各时点药效均低于河北黄芩醇提取物,可能除配比成分外其它活性成份仍是抑制大鼠足跖肿胀肿的重要药效物质基础。
5不同年限黄芩提取物对干酵母致大鼠发热模型表现出较好的解热作用,但各组发挥解热作用时点有差异；对二甲苯致小鼠耳肿模型、干酵母致大鼠足肿模型均有较好的抗炎作用,各实验中均为河北二年生黄芩疗效最佳；对FM1流感病毒感染小鼠均有较好的死亡保护作用,均能降低小鼠的肺指数。
6不同产地引种大连的二年、三年黄芩提取物对干酵母致大鼠发热模型在不同时点表现出一定的解热作用。对FM1流感病毒感染小鼠均有较好的死亡保护作用,均能降低小鼠的肺指数。对二甲苯致小鼠耳肿模型、干酵母致大鼠足肿模型均表现出一定的炎症抑制作用,但对于干酵母致大鼠足跖肿胀的抑制作用,各测试药物发挥抗炎药效的时点不同。
7不同年限、不同产地及异地种植黄芩横向和纵向药效学比较,河北承德二年生黄芩具有较好的解热、抗流感病毒、抗炎作用,为黄芩道地性确认及人工栽培提供一定的理论支持。
8黄芩不同药理作用对应的药效物质基础不尽相同,本课题的研究思路,在一定程度上可为后续黄芩质量标准研究提供借鉴依据和研究途径。
Clarify the material basis of Traditional Chinese Medicines Chinese medicine has always been a hot issue researchers. On the one hand, the material basis of efficacy of Chinese medicine to promote the modernization of Chinese medicine is one of key problems. On the other hand, to find a single ingredient formulation guidelines and the overall effectiveness of various research methods and direct the core of traditional Chinese medicine theory is associated. Therefore, the appropriate use of modern scientific theories and technological results, consistent with characteristics of Chinese medicine theory of the feasibility study on their own ideas and methods, to clarify specific efficacy of Chinese medicine and its corresponding material basis for the acting mechanism of urgent problems.
Scutellaria baicalensis for the Labiatae plant dry root of Scutellaria baicalensis Georg, only contained in the "Shen Nong's Herbal Classic", a heat drying dampness, purging fire detoxification, bleeding the effect of tocolysis. The skullcap ingredients, has been extracted to flavonoid-based, more than 60 chemicals, including baicalin, baicalein, baicalin, wogonin, baicalin new factors, are also based on baicalin content higher being "Pharmacopoeia" as the detection of baicalin quality standards.
The main components from Scutellaria pharmacological research results, the pharmacological effects of the chemical composition of some of the same, but their effect is not completely overlap, there are complementary aspects. Different sources of content of main component baicalin significantly different, as the genuine medicine is widely recognized in Chengde, Hebei baicalin, baicalin content in comparison with other producing less, but their antipyretic, anti-inflammatory efficacy is so better than other parts of skullcap. Therefore, only baicalin content to evaluate the skullcap of quality might be limited, baicalin content level could not be fully representative of baicalin effect, skullcap, in addition to baicalin things might otherwise play a key role in the active ingredients, to skullcap reasonable proportion of the major active components as the embodiment of the quality of baicalin efficacy studies may reveal the role of the material basis of its efficacy, the efficacy of Chinese herbal medicines for other studies for reference
The topic of different sources of baicalin chemical composition, extraction, determination and the active ingredients of pharmacological aspects to be investigated.
Objective:To clarify the characteristics of baicalin quality, efficacy of material basis for quality assessment and clinical baicalin and production of drugs provide the scientific basis for quality and artificial cultivation of Scutellaria theoretical basis for product quality control.
Methods:In this study, under the guidance of TCM theory to Chinese pharmacology as the main research methods, combined with Chinese chemical and chemical composition analysis for the heat dampness skullcap, Xiehuo two detoxification effect, to carry out heat drying as well as anti-inflammatory, anti-virus, fever and other pharmacodynamic test, chemical analysis by traditional Chinese medicine, Fingerprint, database integration and information processing methods based on different sources of material and the efficacy of Scutellaria Correlation.
Results:
1. Antiinflammatory pharmacodynamic test:the extracts from different areas all of the mice ear swelling compared with the model group were significantly different (p <0.05), in Hebei, Shanxi alcohol alcohol group and the difference between the model group is particularly significant (P<0.01), between the two groups was no significant difference (p> 0.05); different origin groups the extracts inhibit the rat paw edema different point in time, the overall efficacy of 22 compared with the model group were significantly different (p<0.05), Hebei ethanol extract compared with the model group is particularly significant difference (P<0.01).
TDA Scutellaria Hebei ethanol group and the mice ear swelling compared with the model group were significant differences(P<0.01), ratio of group and alcohol group Hebei no significant difference (p> 0.05); TDA Group skullcap and Hebei extract group rat paw swelling compared with the model group were significantly different overall (p<0.05), Hebei alcohol extraction rate of rat paw edema model is particularly significant difference between groups (p<0.01), ratio of group and Hebei alcohol group had significant differences (p<0.05).
Different years the extracts of mice ear swelling rate and the model group,22 were significantly different (p<0.05), each rat paw edema rate and the model group, overall there was a significant difference (p<0.05) have to biennial Scutellaria group and model group difference was most significant (P<0.01).
Different areas in the same area cultivated Scutellaria all of the mice ear swelling model group 22 were significantly different (p<0.05), in Hebei Province, biennial controls were the most significant (P<0.001); the group extract inhibits rat paw edema different point in time, the overall efficacy compared with model group,22 significant differences (p<0.05).
2. Antipyretic pharmacodynamic test:the extracts of different age groups antipyretic effect compared with model group,22 were significantly different in general (p<0.05), biennial general Scutellaria rats, body temperature changes and year group, three significant difference between groups (P<0.5), year group, three rats, body temperature change was not significant difference (P> 0.05).Cultivation of different origin in the same area of each group of Scutellaria antipyretic effect compared with the model group 22 overall significant difference (p<0.05), with biennial Hebei Province, the most significant difference between groups (p<0.01).
3. Antiviral-effect test:the extracts of different age groups compared with the model group mortality was significant difference (P<0.01), the extract was no significant difference between the 22 (P> 0.05). Lung index, the Hebei Chengde skullcap biennial and annual no difference (P> 0.05), and three students were significantly different (P <0.05), annual and three-year-no difference (P> 0.05).
Different areas in the same area cultivated Scutellaria the mortality compared with model group, in addition to Dalian three groups significantly different (P<0.05), the other groups compared with model group there was a significant difference (P <0.01), the extraction matter between two groups showed no differences (P> 0.05). Lung index in two groups of Hebei, Dalian three years compared with model group, there were significant differences (P<0.05), the other extracts compared with model group, there was a significant difference (P<0.01), the extract difference between groups was not significant (P> 0.5).
4. Clearing heat and dampness pharmacodynamic test:fed with E. coli, all the rats body temperature, stool frequency increased, there was pulpy form, some rats appeared swollen anal congestion. All of the rats curled lying lazy move, towering hair apparent, especially on dark coat without Ze, compared with normal weight much slower growth trend. Body temperature of rats in all treatment groups declined faster than the control group, decreased stool frequency, rectal swelling less. Medication to 4 days, the model control group eating capacity and the normal control group, there was a significant difference (P<0.01), while the treatment group differences in dietary content did not change (P> 0.05). SOD activity, the extracts from different sources SOD activity of 22 group showed no significant difference (p> 0.05). MDA levels, the extracts from different sources MDA level of 22 groups showed no significant difference (p> 0.05).
5. Anti-inflammatory efficacy of the active ingredient composition and effect relationship between the spectrum of research:Hebei ethanol extract of different retention time stability of chemicals in the 1.8%-2.98%, and less than 3%, good reproducibility. Grey relational analysis by ethanol extract of Scutellaria Hebei active ingredient, ear swelling of mice associated with the material greater than 0.74 in order to retain the material time was 12.0min> retention time 70.1min material> retention time 58.5min material>baicalin>wogonin.The role of anti-rat paw swelling, the correlation is greater than 0.74 in order of the material retention time 70.1min material> Wogonin> retention time 72.9min material> retention time 58.5min material> retention time was 43.8min material> baicalin> retention time 8.5min material> retention time 39.9min material> baicalin.
Conclusion:
1 Different origin skullcap extract on rats have a certain heat treatment can improve damp the operation of the spleen and stomach function in rats, rats reduced body temperature, improve immune function in rats, but rather the origin efficacy.
2 Different origin skullcap extract on xylene-induced mouse ear swelling model, dry yeast induced rat paw swelling models have better anti-inflammatory effect, Hebei alcohol extract the best effect of inhibition of acute inflammation.
3 Grey relational analysis can be a more accurate assessment of fingerprints and the correlation between efficacy, spectrum efficiency for the establishment of Chinese Studies, with research methods, has some practical value.
4 Ratio of the active ingredient of Scutellaria matter (baicalin:wogonin:baicalin= 0.68:0.47:11.9) on xylene-induced ear swelling and inflammation in a better inhibition effect with the alcohol extract of Scutellaria Hebei rather, in the represent a significant anti-inflammatory efficacy of Scutellaria material basis; ratio of material (wogonin: baicalin:baicalein= 0.47:11.9:3.8) on yeast-induced paw edema also has some inhibitory effects, but the detection Hebei efficacy at various time points were lower than the ethanol extract of Scutellaria, ratio of components may be outside than other active ingredient is still inhibited rat paw edema and swelling of the important material basis for efficacy.
5 Years of the extracts of different yeast-induced fever on the model showed a better antipyretic effect, antipyretic effect, but to play point in each group are different; on xylene-induced mouse ear swelling model, dry yeast-induced Foot swelling models have better anti-inflammatory effects, the experiments were the best effect of Hebei biennial skullcap; on mice infected with influenza virus FM1 has better protective effect of the death, can reduce the lung index.
6 Introduction to Dalian from different areas of two years, three years skullcap extract on the dry yeast-induced fever model at different time points show some antipyretic. On mice infected with influenza virus FM1 has better protective effect of the death, can reduce the lung index. On xylene-induced mouse ear swelling model, dry yeast induced rat paw swelling model showed a certain inhibition of inflammation, but dry yeast-induced paw edema inhibition, the efficacy of testing anti-inflammatory drugs different point in time.
7 Different years, different areas and ex situ cultivation of Scutellaria pharmacodynamic comparison of horizontal and vertical, Hebei Cheng de biennial skullcap good antipyretic, anti-virus, anti-inflammatory effects, in order to confirm the genuineness of Scutellaria and cultivated to provide a theoretical support.
8 Different pharmacological effects of Scutellaria corresponding material basis for efficacy of different, the subject of research ideas to a certain extent, quality standards for follow-up study of Scutellaria provides the reference and research approaches.
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