CN105582033A - 防治非酒精性脂肪肝病的含化合物k强化的红参浓缩物的药物组合物和保健功能食品 - Google Patents
防治非酒精性脂肪肝病的含化合物k强化的红参浓缩物的药物组合物和保健功能食品 Download PDFInfo
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Abstract
本发明涉及用于预防和治疗非酒精性脂肪肝疾病的药物组合物和保健功能食品组合物,其包含通过使用酶转化技术获得的化合物K强化的红参浓缩物作为有效成分。
Description
技术领域
本发明涉及用于预防和治疗非酒精性脂肪肝疾病的包含化合物K强化的红参浓缩物作为有效成分之药物组合物以及用于预防和改善非酒精性脂肪肝疾病的包含化合物K强化的红参浓缩物作为有效成分之保健功能食品。
背景技术
人参(PanaxginsengC.A.Mayer)是属于人参(Araliaceauginseng)属的植物,并且在中国从公元前就已用于药物,从三国时期就已用于贸易和药物,并且至今被广泛用作多个领域的药草或保健功能食品。
人参包含约3%至5%的被称为人参皂苷的次皂苷(prosaponin),人参皂苷是人参的代表性生理活性物质并且报道了约33种人参皂苷。由于人参的人参皂苷与聚合物的构成组分连接,在摄取后它不容易被吸收到体内,因此通过栖息在肠内的微生物来消化,然后被吸收到体内。也就是说,其中与人参皂苷结合的葡萄糖被消化的人参皂苷形式最终被吸收到体内,每种人参皂苷表现出各不相同的生理活性。
同时,20-O-β-D-吡喃葡萄糖基-20(S)-原人参二醇(以下称为化合物K)是一种基于原人参二醇(protopanaxadiol,PPD)的皂苷,其中葡萄糖与在糖苷配基20位上的碳结合,并且是通过肠道细菌由人参皂苷Rb1、Rc、Rb2产生的转化物(convertant)(Hasegawa,H等,PlantaMedica,62:453-457(1996))。化合物K以对癌细胞的增殖和转移具有抑制作用、抗衰老、抗过敏和免疫增强功能而著称,但本身不包含在人参或红参中,而是可作为由肠道细菌在体内的代谢产品而获得。但是,据报道,由于肠道细菌的种类和代谢能力因人而异,所以吸收和效力取决于个体而存在差别(Hasegawa,H等,PlantaMedica,63(5):436-440(1997))。
作为用于将人参皂苷转化成化合物K的方法,热处理(Kitagawa等,YakugakuZasshi.,103:612-622(1983);Kwon等,J.ChromatographyA.,921:335-339(2001);Park,FoodInd.Nutr.,9:23-27(2004)),酸处理(Han等,Plantamedica.,44:146-149(1982),Bae等,ArchPharmRes.27(1):61-67(2004)),碱处理(Chen等,Chem.Pharm.Bull.35:1653-1655(1987);Im等,KorJGinsengSci.19:291-294(1995)),有机合成(Anufriev等,CarbohydrRes.304:179-182(1997)),通过微生物的酶的转化方法等都是本领域已知的。在这些方法中,可认为通过使用酶的酶转化法是最有效的人参皂苷转化法,原因是它可通过特异性地对底物起作用而选择性地转化底物,同时几乎不形成反应副产物,它可在相对安全的条件下进行反应,它显示出高效率等。
此外,如作为本发明的前期研究的韩国专利公开No.10-2013-0085970中呈现的,已经报道了化合物K强化的人参浓缩物的最佳制备方法,其中通过使用酶转化法强化了化合物K。
肝脏负责解毒功能,也负责碳水化合物、蛋白质、脂质等(主要养分)的合成、代谢、储存和重新分布代谢过程,并且具有通过这样的过程保持身体代谢内稳态的功能。但是,肝功能可被多种原因损害,例如病毒、炎症、重度饮酒、药物、过劳等。
作为被视为损害肝功能的主要原因和肝脏病症的症状,可以提及脂肪肝,由于近来的西方化饮食生活习惯、饮酒和压力等的影响其频率在增加。可以说,脂肪肝是由于饮酒或过度摄入脂肪以及压力等的影响中性脂肪在肝脏中过度积累(肝脏重量的5%或更多)的症状。脂肪肝可保持为不发展成任何病症并且不对健康造成很大影响的状态,但由于其可发展成诸如肝脏炎症和肝硬化等的疾病,所以它需要持续的护理和管理。
脂肪肝疾病分为由于过度摄入酒精的酒精性脂肪肝疾病和不是由于过度摄入酒精的非酒精性脂肪肝疾病(non-alchoholicfattyliverdisease,NAFLD)。
非酒精性脂肪肝疾病是一种其中中性脂肪在肝脏中积累(与饮酒无关)的病症,并且意指一系列的病症组,其包括仅仅是脂肪在肝脏过度积累的单纯脂肪变性、伴随坏死的非酒精性脂肪性肝炎(non-alcoholicsteatohepattis,NASH)、肝细胞的纤维化和炎症以及其进一步发展形式的肝硬化(livercirrhosis,LC)。
近来,不仅在很多西方国家,而且在韩国,非酒精性脂肪肝疾病的发病率正在增加,这与成人和儿童肥胖的增加有关,报道称发病率在发达国家为总人口的约20%至30%,但是在各国之间有差异。
近来,非酒精性脂肪肝疾病被认为是代谢综合征(例如肥胖、高血压、II型糖尿病、基于胰岛素抗性的脂质代谢紊乱)的一种类型。非酒精性脂肪肝疾病可以是简单的脂沉积症,但存在的问题是在患有非酒精性脂肪肝疾病的患者中约10%至20%发生非酒精性脂肪肝炎症,并且约9%至25%的患者发展成肝硬化。
通常可通过适当地摄入营养素并调节相关的代谢紊乱来治愈非酒精性脂肪肝疾病,但在忽视的情况下,预后会变差。因此,为了防止非酒精性脂肪肝疾病发展成肝硬化,应当防止脂肪在肝脏中积累,但情况是,除了降低热量摄入或增加热量消耗的方法外,没有别的方法。
发明内容
[技术问题]
在所述的情况下,作为本发明的发明人试图提供一种可预防和治疗非酒精性脂肪肝疾病的组合物的结果,制备了来自人参的化合物K强化的红参浓缩物,并且确定包含其的用于预防和治疗非酒精性脂肪肝疾病的组合物在通过动物测试中的高脂饮食引起的脂肪肝疾病中具有抑制肝脏中脂肪积累的作用,并因此完成了本发明。
本发明的另一个目的是提供一种用于预防和治疗非酒精性脂肪肝疾病的药物组合物,其包含化合物K强化的红参浓缩物作为有效成分。
本发明的另一个目的也是提供一种用于预防和治疗非酒精性脂肪肝疾病的保健功能食品,其包含化合物K强化的红参浓缩物。
[技术方案]
为了实现上述目的,本发明提供了用于预防和治疗非酒精性脂肪肝疾病的药物组合物,其包含化合物K强化的红参浓缩物作为有效成分。
本发明提供了用于预防和治疗非酒精性脂肪肝疾病的保健功能食品,其包含化合物K强化的红参浓缩物。
[有益效果]
本发明具有提供用于预防和治疗非酒精性脂肪肝疾病的药物组合物和保健功能食品的效果,其包含化合物K(其安全性通过仅用水和乙醇提取而增加)强化的红参浓缩物,并且所述组合物可提供通过降低血液和肝脏组织中中性脂质(neutrallipid,TG)的含量来抑制非酒精性脂肪肝疾病的效果。
附图说明
图1表示用于通过酶转化技术制备化合物K强化的红参浓缩物的过程。
图2a和2b表示正常饮食(NormalDiet,ND)对照、高脂饮食(High-FatDiet,HFD)对照、高脂饮食+水飞蓟素治疗组(HFD+sily)以及高脂饮食+根据本发明各种浓度的化合物K强化的人参浓缩物的治疗组(HFD+Gx100、Gx250、Gx500)之实验动物的组织病理学变化。图2a分别表示油红O(OilRedO)染色后的拍摄结果。图2b分别表示苏木精-伊红染色(hematoxylin-eosinstain)后的拍摄结果。
图3表示根据施用正常饮食(ND)对照、高脂饮食(HFD)对照、高脂饮食(HFD)+水飞蓟素,以及施用高脂饮食(HFD)+根据本发明各种浓度的化合物K强化的人参浓缩物,在体内脂肪肝动物模型中,实验动物的生化指标中中性脂质的变化。
正常饮食(ND)相对于高脂饮食(HFD):*p<0.05,**p<0.01/高脂饮食(HFD)相对于高脂饮食+样品(HFD+样品):#p<0.05,##p<0.01。
图4表示根据施用正常饮食(ND)对照、高脂饮食(HFD)对照、高脂饮食(HFD)+水飞蓟素,以及施用高脂饮食(HFD)+根据本发明各种浓度的化合物K强化的人参浓缩物,在体内脂肪肝动物模型中,实验动物的肝脏组织中中性脂质的含量变化。
ND相对于HFD:*p<0.05,**p<0.01/HFD相对于HFD+样品:#p<0.05,##p<0.01。
图5表示与肝脏组织中脂质代谢相关的蛋白(SREBP-1c、LXR、FAS和ACC)的基因表达分析的结果。
ND相对于HFD:*p<0.05,**p<0.01/HFD相对于HFD+样品:#p<0.05,##p<0.01。
具体实施方式
以下,将对本发明进行详细地说明。
作为本发明的第一个实施方案,本发明提供了用于预防和治疗非酒精性脂肪酸肝病的药物组合物,其包含化合物K组分强化的红参浓缩物作为有效成分。
可根据包括以下步骤的方法来制备本发明中使用的化合物K组分强化的红参浓缩物:通过使用水或乙醇作为提取溶剂来获得红参浓缩物的步骤;以及通过使用酶转化技术来获得化合物K组分强化的红参浓缩物的步骤。例如,可根据韩国专利公开No.10-2013-0085970中描述的方法来制备。
本发明使用水或乙醇(根据国家食品卫生法(NationalFoodSanitationLaw)所允许的溶剂)作为提取溶剂。因此,不同于使用有机溶剂作为提取溶剂的现有技术的常规方法,根据本发明的化合物K强化的红参浓缩物可安全地用于制成食品或药品。
上述醇优选70%至90%的乙醇,更优选使用80%的乙醇。
在本发明中,为了将红参提取物转化成化合物K,所提取的红参提取物中的人参皂苷与多糖或乙醇分解酶反应。上述多糖分解酶或乙醇分解酶可以是纤维素酶、果胶酶或具有β-葡糖苷酶效价的多糖分解酶或醇分解酶,并且优选具有较高的人参皂苷化合物K转化率的cytolasePCL5并且cytolasePCL5衍生自黑曲霉(Aspergillusniger)。
优选的是上述分解酶以酶分解底物的量之2%的量使用。
在本发明中,优选的是化合物K的含量被强化至0.5mg/g至1.5mg/g的水平。
可以以药物组合物总重量的按重量计0.1%至99%包含上述化合物K强化的红参浓缩物。
可将本发明的上述药物组合物配制成包括可药用载体在内的多种形式,例如,用于口服的制剂(例如散剂、颗粒剂、片剂、胶囊剂、混悬剂、乳剂、糖浆剂、气雾剂等)、多种形式的外用制剂、栓剂和无菌注射液。特别地,它可优选制备成用于口服的制剂。
上述可药用载体包括乳糖、右旋糖、蔗糖、山梨醇、甘露醇、木糖醇、赤藓糖醇、麦芽糖醇、淀粉、阿拉伯树胶、藻酸盐、明胶、磷酸钙、硅酸钙、纤维素、甲基纤维素、微晶纤维素、聚乙烯吡咯烷酮、水、羟基苯甲酸甲酯、羟基苯甲酸丙酯、滑石、硬脂酸镁和矿物油等。
此外、根据本发明的上述药物组合物包含稀释剂或赋形剂,例如填充剂、增量剂、粘合剂、润湿剂、崩解剂、表面活性剂等。
用于口服的固体制剂包括片剂、丸剂、散剂、颗粒剂、胶囊剂等,并且这类固体制剂可包含至少一种或更多种赋形剂,例如,淀粉、碳酸钙、蔗糖或乳糖、明胶等,而且可包含润滑剂(例如硬脂酸镁、滑石)等。
用于口服的液体制剂包括混悬剂、溶液、乳剂、糖浆剂等,并且可包含稀释剂(例如水、液体石蜡等)、润湿剂、甜味剂、调味剂、防腐剂等。
肠胃外制剂包括无菌水溶液、非水溶液、混悬剂、乳剂、冻干制剂和栓剂,并且包含非水溶液、丙二醇、聚乙二醇、植物油(例如橄榄油)以及可注射酯(例如油酸乙酯)作为助悬剂。
作为栓剂的基质,可使用半合成脂肪酸酯(witepsol)、聚乙二醇(macrogol)、吐温61、可可脂、月桂酸甘油酯油(laurinoil)、甘油明胶等。
当本发明中实验动物仅用高脂饮食饲养11周时,在所述动物的肝细胞中脂肪的积累大幅增加。但是,当在仅用高脂饮食饲养实验动物的过程中向实验动物施用包含根据本发明的化合物K强化的红参浓缩物作为有效组分之药物组合物时,此类动物的肝细胞中脂肪的积累比那些仅用高脂饮食饲养的动物大幅减小。因此,可以确定,包含根据本发明的化合物K强化的红参浓缩物之药物组合物抑制实验动物中由高脂饮食引起的非酒精性脂肪肝疾病的发生。
作为本发明的第二个实施方案,本发明提供了用于预防和改善非酒精性脂肪肝疾病的保健功能食品,其包含化合物K强化的红参浓缩物作为有效成分。
可优选以保健功能食品组合物总重量的按重量计0.1%到99%包含化合物K强化的红参浓缩物。
本发明的保健功能食品组合物可用作保健功能食品。术语“保健功能食品”意指根据关于保健功能食品的法No.6727采用具有对人体有用的功能性的原料或组分制备和加工的食品,术语“功能性”意指摄入的目的在于用于获得对调节人体的结构和功能的营养物有用的效果或用于获得对保健用途(例如生理功能等)有用的效果。
本发明的保健功能食品组合物可包含常规的食品添加剂,并通过根据经韩国食品药品管理局(KoreanFood&DrugAdministration)批准的韩国食品添加剂法典和通用测试方法的一般规定的相关条款有关的标准或准则来确定。
可提及在“韩国食品添加剂法典”上所列出的项目,例如化学复合物(例如酮、甘氨酸、柠檬酸钾、烟酸、肉桂酸等)、天然添加剂(例如柿子色素(persimmonColor)、甘草提取物、结晶纤维素、高梁色素(Kaoliangcolor)、瓜尔豆胶等)以及混合制剂(例如L-谷氨酸钠剂、用于面条的碱剂、防腐剂制剂、焦油色制剂(tarcolorformulation)等)。
可以以选自饮料、胶囊剂、丸剂和颗粒剂的任何形式来制备本发明的保健功能食品组合物。
在饮料形式的保健功能食品的情况下,如果需要的话,它可包含防腐剂、稳定剂、乳剂、分散剂、调味剂、着色剂等。
在胶囊形式的保健功能食品的情况下,可通过将添加剂的混合物(例如草药提取物和赋形剂等),或其颗粒或包衣颗粒填入常规硬胶囊中来制备硬胶囊,可通过将添加剂的混合物(例如草药提取物和赋形剂等)填入胶囊基质(例如明胶等)中来制备软胶囊。如果需要的话,上述软胶囊可包含增塑剂(例如甘油或山梨糖醇等)、着色剂、防腐剂等。
可通过用适当的方法将赋形剂、粘合剂、整合剂(integratingagent)等并入草药提取物中的混合物成形来制备大丸剂形式的保健功能食品,并可通过用白糖或其他适当的包衣剂或用扑粉(dustingpowder)(例如淀粉、滑石或适当的材料)包被而覆盖。
可通过用适当的方法将赋形剂、粘合剂、整合剂等并入草药提取物中的混合物以粒状形式制备颗粒形式的保健功能食品,并且如果需要的话,可包含调味剂、矫味剂等。以上术语赋形剂、粘合剂、崩解剂、助流剂、矫味剂、调味剂等的定义记载于相关领域的已知文献中,并且包括具有相同或相似功能等的那些(ExplanationoftheKoreanPharmacopoeia,MunsungCompany,KoreanCollegeofPharmacyConference,修订版第5卷,第33-48页,1989)。
以下,将通过如下的工作实施例和实验实施例更详细地说明本发明。但是,这些工作实施例和实验实施例旨在帮助理解本发明,并且并不以任何意义将本发明的范围限制于此。
实施例
实施例1:化合物K强化的红参浓缩物的制备
在本研究中使用的人参是干燥的红参(4年根),通过添加为原料10倍(w/v)的水或乙醇并在70℃至80℃、200rpm下进行三次15小时回流提取制备了红参提取物,然后通过在室温或低温下的水浴中两次冷却红参提取物、过滤并在减压下浓缩制备了具有70白利糖度(brixs)或更高白利糖度的浓缩物。
用10倍(w/v)的水稀释浓缩物,通过添加柠檬酸调节至pH4.3,然后添加2%(v/v)的酶cytolasePCL5(DSMCompany,法国)并在56℃、200rpm下反应24小时至85小时。
然后,通过在沸腾的水浴中将浓缩物加热30分钟直到不再发生反应而使酶失活,然后通过在减压下将其浓缩制备了化合物K强化的红参浓缩物。在图1中示出了上面提到的步骤。
实验例1:通过体内脂肪肝动物模型验证疗效
为了研究化合物K强化的红参浓缩物对于改善非酒精性脂肪肝的功能,使用5周龄的C57BL/6雄性小鼠构建了高脂饮食诱导的肥胖动物模型并进行体内实验。
该模型主要用于啮齿动物,一般的情形是通过在模型中用高脂饮食诱导肥胖,然后向模型施用待测试的样品来验证效果。因此,我们试图通过动物实验检查由上述实施例1制备的化合物K强化的红参浓缩物的功效。
如下表1所示,将实验动物总共分为六(6)组,并施用确定的饮食和样品持续11周。向动物口服施用正常饮食(ND)或高脂饮食(HFD)作为对照,高脂饮食+水飞蓟素(HFD+Sily)(200mg/kg/天)作为阳性对照以及高脂饮食+化合物K强化的红参浓缩物(HFD+Gx)(具有不同的低、中和高浓度(100mg/kg/天、250mg/kg/天、500mg/kg/天))作为实验组。
其中,在治疗肝脏的所有种类的组分中,水飞蓟素具有最优异的疗效,特别地,以对脂肪肝、肝炎、肝硬化等具有疗效而著称。
表1
实验组 | 饮食+样品处理条件 |
ND | 正常饮食对照 |
HFD | 高脂饮食对照 |
HFD+Sily | 高脂饮食对照+水飞蓟素200mg/kg天 |
HFD+Gx100 | 高脂饮食+CJ红参浓缩物100mg/kg/天 |
HFD+Gx250 | 高脂饮食+CJ红参浓缩物250mg/kg/天 |
HFD+Gx500 | 高脂饮食+CJ红参浓缩物500mg/kg/天 |
1-1实验动物中身体和肝脏的重量变化
以每周1次的时间间隔持续测定动物的体重11周,并进行用于统计分析的StudentT检验。高脂饮食对照(HFD)与正常饮食对照(ND)相比较,但高脂饮食+水飞蓟素治疗组(HFD+Sily)或高脂饮食+化合物K强化的红参浓缩物与高脂饮食(HFD)对照相比较。在每个实验组中平均体重的变化趋势示于下表2中。
表2
正常饮食相对于高脂饮食:*(p<0.05),**(p<0.01)
高脂饮食相对于高脂饮食+样品:#(p<0.05),##(p<0.01)
在实验开始的时候,实验动物的平均体重没有显著差异,但在实验期间,高脂饮食(HFD)对照的体重相对于正常饮食(ND)对照表现出显著增加。这样的结果意味着在高脂饮食(HFD)对照的情况下高脂饮食的能量效率非常高,并且这意味着超重形成形成脂肪肝的可能性也很高。
如上文表2中所示,在最终的平均体重的情况下,显示高脂饮食对照(HFD)为35.3±1.9g且比正常饮食对照的24.0±1.0g高约47%。在化合物K强化的红参浓缩物实验组(HFD+Gx)的情况下,当将其与高脂饮食对照(HFD)比较时,最终平均体重没有显著差异,HFD+Gx100(32.9±2.7g)为约6.8%,HFD+Gx250(32.5±5.1g)为约7.9%,HFD+Gx500(33.3±2.7g)为约5.7%,但可识别平均体重降低的趋势。
在完成11周的实验后,处死动物并从所有的动物中取出肝脏,测定其重量并对各组的差异进行统计分析,然后进行统计分析的StudentT检验。高脂饮食对照(HFD)与正常饮食对照(ND)相比较,但高脂饮食+水飞蓟素治疗组(HFD+Sily)或高脂饮食+化合物K强化的红参浓缩物治疗组(HFD+GX)与高脂饮食对照(HFD)相比较。结果示于下表3中。
表3
正常饮食相对于高脂饮食:*(P<0.05),**(P<0.01)
高脂饮食相对于高脂饮食+样品:#(P<0.05),##(P<0.01)
为了考虑由于体重引起的肝脏重量的差异,用每个实验动物的肝脏重量除以体重并转化成肝脏/体重%(w/w%),并再次计算各组的平均值。
作为确定处死动物时取出的肝脏的重量并互相比较的结果,高脂饮食对照(HFD)的平均肝重为0.88±0.05g并且相对于正常饮食对照(ND)的平均肝重(0.78±0.07g)显示出约13%的显著增加。可以认为通过摄取高脂饮食脂肪在肝脏中积累,因此出现肝脏的肥胖现象。
1-2.组织病理学变化
通过喂食高脂饮食(HFD)11周来诱导脂肪肝。当用肉眼观察时,高脂饮食(HFD)对照的肝脏颜色相对于正常饮食(ND)对照的肝脏颜色显示出微黄颜色。可以确定脂肪在肝脏组织中的大量积累是由高脂饮食导致的。
在完成11周的实验之后,鉴定了肝脏组织的组织病理学变化。
为了鉴定肝脏组织的组织病理学变化,将处死动物时取出的肝脏样品固定在载玻片上,进行了用于鉴定细胞中脂质的油红O染色以及用于脂肪组织的组织化学分析的苏木精和伊红染色(H&E染色),然后通过显微镜鉴定它们。结果示于图2a和2b中。
从图2a中看出,在油红O染色后通过显微镜对其进行鉴定时,发现染成红色的脂滴在高脂饮食对照(HFD)的细胞中无处不在。
在图2b中,在高脂饮食对照(HFD)的肝脏中出现了大量的大圆形囊泡,意味着脂质在肝细胞中的积累,而在化合物K强化的红参浓缩物实验组(HFD+Gx)的情况下,脂滴的大小相对于高脂饮食对照(HFD)中的脂滴大小大幅减小。此外,可识别相对于高脂饮食对照(HFD),中性脂质的积累降低。
1-3.血液中生化指标的变化
当肝功能的一部分被脂肪肝损害时,相关的生化指标就出现变化。该实验中选择了可与脂肪肝的诊断关联使用的主要肝功能指标并分析了各组间的差异。
从图3中注意到,对于TG(血液中的中性脂质)含量,高脂饮食(HFD)对照相对于正常饮食(ND)对照显示出约2.1倍的显著高的值,并且在化合物K强化的红参浓缩物实验组(HFD+Gx)的情况下,不论化合物K强化的红参浓缩物的浓度高低,均显示出中性脂质的含量相对于高脂饮食(HFD)对照显著降低。
该结果可解释为化合物K强化的红参浓缩物可对血液中的脂质代谢提供直接影响。
1-4.肝脏组织中中性脂质的含量变化
分析了肝脏组织中中性脂质(甘油三酯,TG)的含量,结果示于图4中。
如在图4中,高脂饮食(HFD)对照的平均TG含量相对于正常饮食(ND)对照增加2倍或更多倍并且化合物K强化的红参浓缩物实验组(HFD+GX100、HFD+GX250、HFD+GX500)再次显示出TG含量降低的趋势。
这样的结果意味着,化合物K强化的红参浓缩物具有调节血液和肝脏组织中的中性脂质代谢的功能。
实验实施例2:与肝脏组织中脂质代谢相关的蛋白质的基因表达的分析
作为研究化合物K强化的红参浓缩物在肝脏组织中调节脂质代谢之调节机制的第一个步骤,通过实时RT-PCR法分析参与肝脏组织中脂肪生成和脂肪分解的主要蛋白质的基因表达,结果示于图5中。
分析了作为调节肝细胞从头脂肪合成蛋白质的SREBP-1c(固醇调节元件结合转录因子1(SterolRegulatoryElementBindingtranscriptionfactor))、FAS(脂肪酸合酶)、ACC(乙酰辅酶A羧化酶)、LXRα(肝X受体α)。
管家基因36B4(酸性核糖体磷蛋白质PO)的PCR用作分析基因表达的内标。
SREBP-1c是肝细胞中调节脂质生物合成基因(例如FAS、ACC等)之表达的转录因子,也是肝细胞中作为脂质传感器用于LXRα启动的主要靶基因。因此,当LXRα由任何外部信号启动时,通过促进SREBP-1c的表达来激活脂质生物合成酶基因(例如FAS、ACC等)的表达。
如图5所示,作为实时RT-PCR实验的结果,在肝细胞中生脂基因的表达被HFD显著激活,并且可以注意到,该表达也被化合物K强化的红参浓缩物的处理所抑制。从所述结果中可推断,化合物K强化的红参浓缩物抑制LXRα介导的SREBBP-1c诱导机制,因此,具有控制由HFD激活的脂质生物合成的功能。
Claims (6)
1.一种用于治疗和预防非酒精性脂肪肝疾病的药物组合物,其包含化合物K强化的红参浓缩物。
2.根据权利要求1所述的药物组合物,其中以相对于所述药物组合物的总重量按重量计0.1%至99%的量包含所述化合物K强化的红参浓缩物。
3.根据权利要求1所述的药物组合物,其中所述化合物K的含量增加0.5mg/g至1.5mg/g。
4.一种保健功能食品,其包含化合物K强化的红参浓缩物作为有效成分。
5.根据权利要求4所述的保健功能食品,其中以相对于所述保健功能食品总重量按重量计0.1%至99%的量包含所述化合物K强化的红参浓缩物。
6.根据权利要求1所述的保健功能食品,其中所述化合物K的含量增加0.5mg/g至1.5mg/g。
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KR1020140156917A KR20160056554A (ko) | 2014-11-12 | 2014-11-12 | Compound K 성분이 강화된 홍삼농축액을 함유하는 비알코올성 지방간증의 예방 및 치료용 약제학적 조성물 및 건강기능 식품 |
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EP (1) | EP3020406A1 (zh) |
JP (1) | JP6140789B2 (zh) |
KR (1) | KR20160056554A (zh) |
CN (1) | CN105582033A (zh) |
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CN109689020A (zh) * | 2016-09-08 | 2019-04-26 | 株式会社爱茉莉太平洋 | 用于皮肤抗老化的、包含脱氢松香酸及化合物k的组合物 |
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KR101978819B1 (ko) * | 2018-11-21 | 2019-05-15 | 주식회사 엠진바이오 | 진세노사이드 화합물 k를 이용한 지방성 간질환 개선용 조성물 |
KR102494672B1 (ko) * | 2019-11-27 | 2023-02-06 | 한희주 | 홍삼, 효소 및 천연물을 이용한 컴파운드 k의 제조방법 |
KR102239804B1 (ko) * | 2020-08-03 | 2021-04-27 | 제너럴바이오(주) | 발효인삼을 함유하는 비알콜성 지방간염 예방 또는 개선용 건강기능성식품 조성물 |
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WO2016076607A2 (ko) | 2016-05-19 |
JP6140789B2 (ja) | 2017-05-31 |
US20160129061A1 (en) | 2016-05-12 |
WO2016076607A3 (ko) | 2016-07-07 |
HK1220123A1 (zh) | 2017-04-28 |
JP2016094414A (ja) | 2016-05-26 |
KR20160056554A (ko) | 2016-05-20 |
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