CN113498433A - 包含嗜柠檬酸明串珠菌wikim0104的用于预防、改善或治疗肥胖或脂肪肝疾病的组合物 - Google Patents
包含嗜柠檬酸明串珠菌wikim0104的用于预防、改善或治疗肥胖或脂肪肝疾病的组合物 Download PDFInfo
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- CN113498433A CN113498433A CN202080015888.XA CN202080015888A CN113498433A CN 113498433 A CN113498433 A CN 113498433A CN 202080015888 A CN202080015888 A CN 202080015888A CN 113498433 A CN113498433 A CN 113498433A
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Abstract
本发明涉及从泡菜中分离的新型嗜柠檬酸明串珠菌WiKim0104(Leuconostoc citreum WiKim0104)以及包含其的组合物或其用途。本发明提供通过给药从泡菜中分离的新型嗜柠檬酸明串珠菌WiKim0104或包含其的组合物来预防、改善及治疗个体的炎症、肥胖或脂肪肝疾病的方法。本发明的嗜柠檬酸明串珠菌WiKim0104通过抑制肝细胞内的脂肪积聚并减少脂肪肝相关基因的表达来表现出脂肪肝生成抑制效果,因此能够以多种方式用于预防、改善及治疗炎症、肥胖或脂肪肝疾病。
Description
技术领域
本申请要求于2019年2月28日提交且申请号为第10-2019-0024254号的韩国专利申请的优先权,其全部内容通过引用结合在本申请中。本发明涉及从泡菜中分离的新型菌株以及包含其的用于预防、改善或治疗炎症、肥胖或脂肪肝疾病的组合物。
背景技术
脂肪肝(fatty liver)为因摄入过多的脂肪和脂肪在肝内的积聚、合成的增加及代谢的减少等原因导致无法进行正常的脂肪代谢而引起的肝细胞内中性脂肪积聚的疾病,当脂肪占肝全部重量的5%以上时,归类为脂肪肝。
并且,近来,由于西式化的高脂肪、高热量的饮食生活和文明发展带来的运动不足等原因,导致脂肪肝患者激增,并且发病年龄呈从十几岁到六十多岁以上的广泛分布。持续在肝中积聚脂肪会伴随炎症从而演变为脂肪肝性肝炎,会发生因慢性炎症引起的肝组织坏死及因肝的纤维化引起的肝硬化。若症状继续恶化,则可能发展为肝癌。因此,脂肪肝是肝炎、肝硬化及肝癌最大的病因。
现在,市面上使用的药物有使用通过治疗肥胖来表现出改善脂肪肝效果的奥利司他(orlistat)作为主原料的罗氏鲜(Xenical)TM(Roche公司)、使用西布曲明(sibutramin)作为主原料的诺美婷(Reductil)TM(Abbott公司)等,但具有腹泻、腹痛、失眠症等副作用,而临床上虽把以氯贝特(clofibrate)为代表的贝特类药剂等用作脂肪肝的治疗剂,但却表现出肝功能障碍等副作用。
另一方面,虽然下述专利文献1中记载说多种乳酸菌表现出改善脂肪肝的效果,但仍切实需要开发具有根本性地预防或改善脂肪肝的效果并且不表现出上述副作用的脂肪肝治疗剂。
另一方面,专利文献1中虽然公开了双歧杆菌属、乳酸杆菌属等多种乳酸菌的脂肪肝改善效果,但至今仍未开发出具有根治脂肪肝的效果并且不具有上述副作用的治疗剂。因此,切实需要开发能够根治脂肪肝并且不具有副作用的治疗剂。
专利文献1:韩国专利申请第10-1937365号(2018年08月08日)
发明内容
技术问题
本发明提供脂肪肝疾病的预防或改善功效优良的新型嗜柠檬酸明串珠菌属乳酸菌。
技术方案
因此,本发明人致力于从传统发酵食品中寻找具有对预防或改善脂肪肝疾病的效果的乳酸菌菌株,其结果,分离、鉴别出作为新型魏斯氏菌属乳酸菌菌株的嗜柠檬酸明串珠菌WiKim0104(Leuconostoc citreum WiKim0104),从而完成本发明。
本发明的一实例提供一种用于预防或改善炎症、肥胖或脂肪肝疾病的组合物,包含嗜柠檬酸明串珠菌WiKim0104、其培养物、其破碎物或其提取物作为有效成分。
上述脂肪肝疾病可以为选自由单纯性脂肪肝、非酒精性脂肪性肝炎、肝纤维化及肝硬化组成的组中的一种以上。
上述组合物可以为食品组合物、食品发酵用乳酸菌发酵剂组合物、饲料或饲料添加剂组合物或者药学组合物。
上述食品组合物可以包括保健功能食品、饮料、棒状食品或发酵乳。
本发明的再一实例提供嗜柠檬酸明串珠菌WiKim0104、其培养物、其破碎物或其提取物的用途,用于预防、改善或治疗炎症、肥胖或脂肪肝疾病。
上述脂肪肝疾病可以包括选自由单纯性脂肪肝、非酒精性脂肪性肝炎、肝纤维化及肝硬化组成的组中的一种以上。
本发明可以用做食品组合物、食品发酵用乳酸菌发酵剂组合物、饲料或饲料添加剂组合物或者药学组合物。
本发明的一实例提供一种预防、改善或治疗炎症、肥胖或脂肪肝疾病的方法,包括向有需要的个体给药包含嗜柠檬酸明串珠菌WiKim0104、其培养物、其破碎物或其提取物的组合物的步骤。上述个体可以为包括人类在内的动物。
本发明提供一种预防、改善或治疗炎症、肥胖或脂肪肝疾病的方法,上述脂肪肝疾病包括选自由单纯性脂肪肝、非酒精性脂肪性肝炎、肝纤维化及肝硬化组成的组中的一种。
本发明提供一种嗜柠檬酸明串珠菌WiKim0104。
本发明的嗜柠檬酸明串珠菌WiKim0104为源自泡菜的嗜柠檬酸明串珠菌新型菌株。虽然本发明的嗜柠檬酸明串珠菌WiKim0104是从泡菜中分离、鉴定的,但其获取途径不限于此。
对通过本发明的实施例分离的乳酸菌菌株进行用于鉴定及分类微生物的16S核糖体DNA(16S rDNA)碱基序列分析的结果显示,具有SEQ ID NO:1的核酸序列。
因此,将具有SEQ ID NO:1的16S核糖体DNA碱基序列的本发明的微生物命名为嗜柠檬酸明串珠菌WiKim0104,于2018年12月14日保藏于韩国微生物保藏中心(保藏编号:KCCM12420P)。
本发明的嗜柠檬酸明串珠菌WiKim0104为革兰氏阳性菌,为在好氧条件和厌氧条件中均可生长的兼性厌氧菌(facultative anaerobe),不形成孢子,无运动性,细胞呈杆菌的形态。
在下述实施例中,确认本发明的嗜柠檬酸明串珠菌WiKim0104在肝细胞(HepG2cells)中抑制脂肪酸合成酶(FAS,fatty acid synthase)、硬脂酰辅酶A去饱和酶(SCD)(脂肪生成相关基因(lipogenic-related gene))、环氧化酶-2(COX-2,cyclooxygenase-2)、及核因子-κ(NF-κ)(炎症相关基因(inflammatory related gene))的表达。通过上述内容确认嗜柠檬酸明串珠菌WiKim0104菌株可以通过抑制约30%至35%的HepG2细胞的脂肪肝生成来预防或改善脂肪肝。因此,本发明的嗜柠檬酸明串珠菌WiKim0104能够以多种方式用于预防、治疗或改善人类或动物的脂肪肝疾病。
并且,可通过下述实施例确认,包含嗜柠檬酸明串珠菌WiKim0104作为有效成分的组合物抑制肝细胞(HepG2 cells)内脂肪的积聚及炎症,具有减少体重的功效并改善血液中的肝功能数值,减少肝组织内脂肪代谢、炎症及肝纤维化相关因子基因的表达。因此,上述组合物可以用做用于预防、治疗或改善炎症、肥胖或选自由单纯性脂肪肝、非酒精性脂肪性肝炎、肝纤维化及肝硬化组成的组中的一种以上的脂肪肝疾病的组合物的有效成分。
本发明提供一种用于预防、改善或治疗炎症、肥胖或脂肪肝疾病的组合物,包含嗜柠檬酸明串珠菌WiKim0104、其培养物、其破碎物或其提取物作为有效成分。
本发明的组合物所包含的嗜柠檬酸明串珠菌WiKim0104能够以活菌体或死菌体的形态存在,并且,还能够以干燥或冷冻干燥的形态存在。适合包含于多种组合物的乳酸菌形态及制剂化方法在本发明所属技术领域内是广为人知的。例如,嗜柠檬酸明串珠菌WiKim0104可以制剂化为在公知的液体培养基或固体培养基中培养后获得的培养物,或为将上述菌株与追加成分共同培养而获得的发酵物,或使用有机溶剂提取上述菌株的提取物,或通过溶解上述菌株的细胞膜或经破碎或均质化处理的溶解物(或破碎物)等形态,但不限定于此。
在一具体例中,上述组合物可以为包含以活菌或死菌形态存在的嗜柠檬酸明串珠菌WiKim0104菌株的组合物。
在本发明中,上述脂肪肝疾病可以包括单纯性脂肪肝、非酒精性脂肪性肝炎、肝纤维化及肝硬化。
并且,上述脂肪肝疾病可以包括所有酒精性脂肪肝和非酒精性脂肪肝,例如,可以为由高脂肪饮食诱导的非酒精性脂肪肝。上述非酒精性脂肪肝疾病(non-alcoholic fattyliver disease,NAFLD)可以包括所有原发性和继发性非酒精性脂肪肝,例如,可以为原发性高血脂症、糖尿病或因肥胖导致的非酒精性脂肪肝。
在一具体例中,上述组合物可以为包含嗜柠檬酸明串珠菌WiKim0104菌株的培养物、破碎物、发酵物或提取物的用于预防或治疗炎症、肥胖或脂肪肝疾病的药学组合物。
在将本发明的组合物用作药剂学组合物的情况下,除上述嗜柠檬酸明串珠菌WiKim0104菌株以外,本发明的药剂学组合物可以使用药剂学上适合且在生理学上可接受的辅助剂来制备,上述辅助剂可以使用赋形剂、崩解剂、甜味剂、结合剂、包衣剂、膨胀剂、润滑剂、滑泽剂或香味剂等。
为了给药,除上述记载的有效成分外,上述药剂学组合物还可以包含一种以上的药剂学上可接受的载体来优选地制剂化为药剂学组合物。
例如,为了制剂化为片剂或胶囊剂的形态,有效成分可以与乙醇、甘油、水等口服、无毒且药剂学上可接受的非活性载体结合。并且,在希望或必要的情况下,可以包含适当的结合剂、润滑剂、崩解剂及发色剂或它们的混合物。适当的结合剂包括淀粉、明胶、葡萄糖或β-乳糖等的天然糖、玉米甜味剂、阿拉伯胶、黄芪胶或油酸钠等的天然或合成胶、硬脂酸钠、硬脂酸镁、苯甲酸钠、醋酸钠、氯化钠等,但不限定于此。崩解剂包括淀粉、甲基纤维素、琼脂、膨润土、黄原胶等,但不限定于此。在可制剂化为液相溶液的组合物中,药剂学上可接受的载体可以使用灭菌及适于活体的生理盐水、灭菌水、林格氏液、缓冲生理盐水、白蛋白注射溶液、葡萄糖溶液、麦芽糊精溶液、甘油、乙醇及混合上述成分中的一种以上来使用,可以根据需要添加抗氧化剂、缓冲液、抑菌剂等其他常规添加剂。并且,还可添加稀释剂、分散剂、表面活性剂、结合剂及润滑剂来制剂化为水溶液、悬浮液、乳浊液等的注射用剂型、丸药、胶囊、颗粒或片剂。
进而,可以将在Remington's Pharmaceutical Science,Mack PublishingCompany,Easton PA公开的方法用作相关领域的适当方法,根据各种疾病或根据成分来优选地进行制剂化。
在一具体例中,本发明提供一种包含嗜柠檬酸明串珠菌WiKim0104、其培养物、其破碎物、其发酵物或其提取物作为有效成分的用于预防或改善炎症、肥胖或脂肪肝疾病的食品组合物。上述食品组合物可以包括保健功能食品、饮料或棒状食物等形态。
在本发明中,包含上述菌株作为有效成分的食品组合物可以包括发酵乳等饮料。因此,本发明提供包含由嗜柠檬酸明串珠菌WiKim0104或其培养物组成的用于发酵的乳酸菌发酵剂。
本发明的食品组合物能够以与上述药剂学组合物相同的方式制剂化来用作功能性食品,或可添加于各种食品。能够添加本发明的组合物的食品有例如饮料类、维生素复合物、健康辅助食品等。
本发明的食品组合物可以包含制备食品时通常添加的成分,例如,包含蛋白质、碳水化合物、脂肪、营养素、调味剂及香味剂。上述碳水化合物的例有常规糖以及糖醇,上述常规糖为例如葡萄糖、果糖等的单糖、例如麦芽糖、蔗糖、寡糖等的二糖以及例如糊精、环糊精等的多糖,上述糖醇为木糖醇、山梨糖醇、赤藓糖醇等。香味剂可以使用天然香味剂(索马甜、甜叶菊提取物(例如莱鲍迪苷A、甘草皂苷等))及和合成香味剂(糖精、阿巴斯甜等)。例如,在将本发明的食品组合物制备为饮剂或饮料类的情况下,还可以包含柠檬酸、液相果糖、白糖、葡萄糖、草酸、苹果酸、果汁及各种植物提取液等。
上述本发明的组合物可以用作饲料添加剂或饲料。
在用作饲料添加剂的情况下,上述组合物可以制备为20%至90%的高浓缩液,或制备为粉末或颗粒形态。上述饲料添加剂还可以包含柠檬酸、富马酸、己二酸、乳酸、苹果酸等有机酸,或磷酸钠、磷酸钾、酸性焦磷酸盐、多磷酸盐(综合磷酸盐)等磷酸盐,或多酚、儿茶素、α-生育酚、迷迭香提取物、维生素C、绿茶提取物、甘草提取物、壳聚糖、鞣酸、植酸等天然抗氧化剂中的一种或一种以上。在用作饲料的情况下,上述组合物可以制剂化为常规饲料形态,可以同时包含常规饲料成分。
上述饲料添加剂及饲料还可以包含:谷物,例如粉碎或破碎的小麦、燕麦、大麦、玉米及大米;植物性蛋白质饲料,例如以油菜、大豆及向日葵为主要成分的饲料;动物性蛋白质饲料,例如血粉、肉粉、骨粉及鱼粉;糖分及乳制品,例如由各种奶粉及乳浆粉末组成的干燥成分等,此外,还可以包含营养补充剂、消化及吸收促进剂、生长促进剂等。
上述饲料添加剂可以向动物单独给药,也可以与可食用载体中的其他饲料添加剂组合来给药。并且,上述饲料添加剂可以作为追肥,或通过将它们直接与动物饲料混合,或以与饲料分开的单独的口服剂型来轻松地向动物给药。在将上述饲料添加剂与动物饲料分开给药的情况下,可以与本发明所属技术领域公知的药剂学上可接受的食用载体组合来制备为立即释放或缓释的剂型。上述可食用载体可以为固体或液体,例如玉米淀粉、乳糖、蔗糖、大豆片、花生油、橄榄油、芝麻油及丙二醇。在使用固体载体的情况下,饲料添加剂可以为片剂、胶囊剂、散剂、锭剂或含糖片剂或微分散形态的追肥。在使用液体载体的情况下,饲料添加剂可以为明胶软胶囊、糖浆剂或悬浮液、乳液或溶液剂的剂型。
并且,上述饲料添加剂及饲料可以包含辅助剂,例如保存剂、稳定剂、湿润剂或乳化剂、增溶剂等。上述饲料添加剂可以通过浸渍、喷雾或混合的方式添加到动物饲料中来使用。
本发明的饲料或饲料添加剂可以应用于包括哺乳动物、家禽及鱼类在内的多种动物的饮食中。
在本发明中,动物包括哺乳动物,作为哺乳动物,不仅可以用于猪、牛、羊、山羊、实验用啮齿动物,还可以用于除实验用啮齿动物之外的宠物(例如狗、猫)等,作为上述家禽,可以用于鸡、火鸡、鸭、鹅、雉鸡及鹌鹑等,作为上述鱼类,可以用于鳟鱼等,但不限于此。
基于单次剂量,本发明的组合物可以包含约106cfu/ml至1012cfu/ml的嗜柠檬酸明串珠菌WiKim0104菌株,例如,可以包含107cfu/ml至1011cfu/ml、108cfu/ml至1010cfu/ml。在给药菌株的情况下,优选地,以活菌状态给药,可以在摄取之前杀灭或以衰减(attenuation)状态给药。并且,在使用培养上清液等来制备的情况下,还可以进一步进行通过热处理过程的灭菌化过程。具备最低功效所需的菌株量及每日摄取的程度可以根据摄取者的身体或健康状态而改变,但通常可以约为106cfu/ml至1012cfu/ml,例如,可以为107cfu/ml至1011cfu/ml、108cfu/ml至1010cfu/ml。
本发明另一实例可以提供嗜柠檬酸明串珠菌WiKim0104预防、治疗或改善人类或动物的炎症、肥胖或脂肪肝疾病的用途。
本发明另一实例提供嗜柠檬酸明串珠菌WiKim0104、其培养物、其破碎物或其提取物预防、改善或治疗炎症、肥胖或脂肪肝疾病的用途。
本发明还有一实例提供用于预防、改善或治疗肥胖或脂肪肝疾病的嗜柠檬酸明串珠菌WiKim0104、其培养物、其破碎物或其提取物。
本发明的一实例提供一种预防、改善或治疗炎症、肥胖或脂肪肝疾病的方法,包括向有需要的个体给药包含嗜柠檬酸明串珠菌WiKim0104、其培养物、其破碎物或其提取物的组合物的步骤。上述个体为包括人类在内的动物,上述动物只要是摄取饲料的上述提及的动物,就都可以包括在本发明的范围内。上述脂肪肝疾病可以包括选自由单纯性脂肪肝、非酒精性脂肪性肝炎、肝纤维化及肝硬化组成的组中的一种以上。
参照详细后述的实施例,可以明确理解本发明的优点、特征以及实现这些优点及特征的方法。但是,本发明不限于以下公开的实施例,而是能够以多种不同的实施方式实现,这些实施例仅为了使本发明的公开得以完整且向本发明所属技术领域的普通技术人员充分地告知本发明的范畴而提供,本发明仅由发明要求保护范围定义。
发明的效果
本发明的嗜柠檬酸明串珠菌WiKim0104为从泡菜中分离的乳酸菌,表现出通过抑制细胞内脂肪积聚及减少脂肪肝相关基因的表达来抑制脂肪肝生成的效果,可通过多种方式用于预防、改善及治疗炎症、肥胖或脂肪肝疾病。进而,可以有效地用作用于发酵的发酵剂。
附图说明
图1为测定使用本发明的WiKim0104菌株处理的HepG2细胞相关基因的表达程度的柱状图。L-LAB1表示嗜柠檬酸明串珠菌WiKim0104(Leu.citreum WiKim0104),L-LAB2表示肠膜明串珠菌(Leu.Mesenteroides),L-LAB3及L-LAB4分别表示在实验室中分离的嗜柠檬酸明串珠菌菌株#2、#3(Leu.citreum strain#2,#3)。
图2a至图2c为示出摄取本发明的WiKim0104菌株的脂肪肝小鼠模型的体重、血液中肝功能数值(谷丙转氨酶(GPT)、谷草转氨酶(GOT))的柱状图。*P<0.05,相比于正常饮食摄取组(compare to the ND);#P<0.05,相比于高脂肪饮食摄取组(compare to theHFD),L-LAB1表示嗜柠檬酸明串珠菌WiKim0104。
图3a至图3c为测定摄取本发明的WiKim0104菌株的脂肪肝小鼠模型的肝组织相关基因表达程度的柱状图。*P<0.05,相比于正常饮食摄取组;#P<0.05,相比于高脂肪饮食摄取组,L-LAB1表示嗜柠檬酸明串珠菌WiKim0104。
图4示出本申请的SEQ ID NO:1。
具体实施方式
以下,通过实施例详细说明本发明。下述实施例仅例示本发明,本发明的范围不限于下述实施例。
实施例
实施例1:嗜柠檬酸明串珠菌WiKim0104的鉴定
使用接种环收集通过将泡菜提取物的原液涂抹在MRS培养基来获得的单菌落后在MRS肉汤(broth)中培养。DNA提取是使用QIAamp DNA Mini Kit(QIAgen公司,德国)提取的。使用1%的琼脂糖凝胶确认提取的DNA,为了扩增16S核糖体DNA基因(16S rDNA gene),以提取的基因组(genomic)DNA为模板进行聚合酶链式反应(Polymerase Chain Reaction,PCR),聚合酶链式反应的条件为:在95℃的温度下变性(denaturation)1分钟,在45℃的温度下结合(annealing)1分钟,在72℃的温度下延伸(extension)1分30秒,将上述过程循环30次。将获得的聚合酶链式反应产物委托给Macrogen公司(首尔,韩国)进行序列分析。通过使用美国国家生物技术信息中心(National Center for Biotechnology Information)(NCBI,www.ncbi.nlm.nih.gov)的基于局部比对算法的搜索工具(Basic Local AlignmentSearch Tool,BLAST)的检索引擎诱导分析16S核糖体DNA序列来进行细菌的鉴定。
对本通过发明的实施例分离的菌株进行用于鉴定微生物的16S核糖体DNA碱基序列分析的结果显示,具有SEQ ID NO:1的核酸序列。
因此,将本发明的微生物命名为嗜柠檬酸明串珠菌WiKim0104,于2018年12月14日保藏于韩国微生物保藏中心(保藏编号:KCCM12420P)。
实施例2:确认嗜柠檬酸明串珠菌WiKim0104的肝细胞(HepG2cells)内脂肪积聚及炎症抑制功效
利用侵袭小室(transwell)设计了在体外(in vitro)模拟人体肠-肝轴(gut-liver axis)的实验方法。
在30℃的温度下,在MRS培养基中培养嗜柠檬酸明串珠菌WiKim0104乳酸菌24小时。在培养结束的时间点,以6000rpm的转速离心分离5分钟来回收菌体,使用磷酸盐缓冲溶液(PBS)洗涤去除全部剩余的培养基成分来做准备。
为了培养肠细胞(ΗΤ-29cells)和肝细胞(HepG2 cells),使用添加有青霉素/链霉素(penicillin/streptomycin)、10%胎牛血清(fetal bovine serum)的RPMI-1640培养基,使用6孔(6-well)培养板侵袭小室准备进行共同培养。在共同培养之前,将肠细胞接种于侵袭小室膜(membrane),将肝细胞接种于6孔培养板,分别在37℃、5%CO2的条件下培养来做准备。
当肠细胞(HT-29cells)和肝细胞(HepG2 cells)在培养皿(dish)内长至80%左右时,将培养液更换为不含胎牛血清(FBS free)的培养基后再培养16小时。培养后,使用1×107CFU的准备好的乳酸菌处理肠细胞,组装侵袭小室进行乳酸菌、肠细胞、肝细胞的共同培养,使用0.1mM的棕榈油(palmitic acid)处理48小时来诱导肝细胞内的脂肪生成。与0.1mM的棕榈油一起培养48小时后,实施实时定量聚合酶链式反应(quantitative real timepolymerase chain reaction,qPCR)来确认使用嗜柠檬酸明串珠菌WiKim0104菌株处理的肝细胞内的脂肪代谢、炎症相关基因的表达水平。结果如图1所示,可以确认与使用0.1mM的棕榈油处理的肝细胞(对照组)相比,在将0.1mM的棕榈油与嗜柠檬酸明串珠菌WiKim0104共同培养的肝细胞中,脂肪酸合成酶、不饱和脂肪酸合成酶(硬脂酰辅酶A去饱和酶(Stearoyl-CoA desaturase,SCD))、炎症相关因子(环氧化酶-2(COX-2,cyclooxygenase-2))、核因子κB(Nuclear factor-kappaΒ)的基因表达显著减少。
实施例3:确认减少体重的功效及改善血液中的肝功能数值
在温度为20±2℃、湿度为50±5%、明暗周期5(light-dark cycle)为12小时的饲育室环境中以正常饮食法(chow diet)(CD,Purina公司,韩国)使5周龄的雄性小鼠(C57BL/6J)适应一周。使实验动物摄取正常饮食(D12450B,Research Diets公司,新宾士威克,新泽西州,美国)或总卡路里的45%为脂肪的高脂肪饮食(D12451,Research Diets公司,新宾士威克,新泽西州,美国),适应一周时间的饮食后进行实验。实验组由正常饮食摄取组(ND)、高脂肪饮食摄取组(HFD)、高脂肪饮食和每日口服给药2×109CFU/200μl浓度的嗜柠檬酸明串珠菌WiKim0104的摄取组(HFD+L-LAB1)共3个组组成,通过20周的饮食供应来诱导脂肪肝。正常饮食摄取组(ND)和高脂肪饮食摄取组(HFD)每日口服给药等量的磷酸盐缓冲溶液(phosphate buffered saline,PBS)。实验进行20周后,测定各实验组的体重。并且,为了测定实验组的血液中肝功能数值(血清谷草转氨酶(serum GOT)、血清谷丙转氨酶(serumGPT)),在实验结束前16小时开始停止进食,从腹腔大静脉内采血后,分离出血清来用于实验。血清内谷草转氨酶、谷丙转氨酶使用自动生化检测仪(FUJI DRI-CHEM 7000i型,Fujifilm公司,东京,日本)来测定,图2b、图2c示出了血清谷草转氨酶(GLUTAMATE-OXALOACETATE TRANSAMINASE,GOT)、谷丙转氨酶(GLUTAMATE-PYRUVATE TRANSAMINASE,GPT)的柱状图。
结果可确认,如图2a至图2c所示,在一同摄取高脂肪饮食和嗜柠檬酸明串珠菌WiKim0104的情况下(HFD+L-LAB1),与摄取高脂肪饮食的小鼠(HFD)相比,体重和血液中肝功能数值显著减少。
实施例4:确认肝组织内脂肪代谢、炎症及肝纤维化相关基因的表达水平
使用实验结束后摘除的肝组织实施实时定量聚合酶链式反应来确认摄取嗜柠檬酸明串珠菌WiKim0104菌株的肝组织内脂肪代谢、炎症、肝纤维化相关基因的表达水平。
结果可确认,如图3a至图3c所示,随着摄取嗜柠檬酸明串珠菌WiKim0104菌株,脂肪代谢相关因子白细胞分化抗原36(CD36,Cluster of differentiation 36)、炎症相关因子核因子κB、肝纤维化相关因子I型胶原蛋白α1(Col1α1,Collagen type I alpha 1)基因的表达减少了。
产业上的可利用性
本发明提供新型菌株。并且,本发明的菌株可以用作用于预防、改善或治疗炎症、肥胖或脂肪肝疾病的食品、饲料或饲料添加剂、药学组合物等。
保藏编号
保藏机构名称:韩国微生物保藏中心(国外)
保藏编号:KCCM12420P
保藏日期:2018年12月14日
国际承认用于专利程序的微生物保藏布达佩斯条约
国际格式
对于原保藏的保藏证书
根据细则7.1发行
保藏人:韩国食品研究院
地址:邮政编码55365,韩国全罗北道完州郡伊西面农生命路245号
序列表
<110> 韩国食品研究院(Korea Food Research Institute)
<120> 包含嗜柠檬酸明串珠菌WIKIM0104的用于预防、改善或治疗肥胖或脂肪肝疾病的组合物
<150> 10-2019-0024254
<151> 2019-02-28
<160> 1
<170> SIPOSequenceListing 1.0
<210> 1
<211> 1430
<212> DNA
<213> 嗜柠檬酸明串珠菌WIKIM0104(Leuconostoc citreum WiKim0104)
<400> 1
gatgaacgct ggcggcgtgc ctaatacatg caagtcgaac gcgcagcgag aggtgcttgc 60
acctttcaag cgagtggcga acgggtgagt aacacgtgga taacctgcct caaggctggg 120
gataacattt ggaaacagat gctaataccg aataaaactt agtatcgcat gatatcaagt 180
taaaaggcgc tacggcgtca cctagagatg gatccgcggt gcattagtta gttggtgggg 240
taaaggctta ccaagacgat gatgcatagc cgagttgaga gactgatcgg ccacattggg 300
actgagacac ggcccaaact cctacgggag gctgcagtag ggaatcttcc acaatgggcg 360
caagcctgat ggagcaacgc cgcgtgtgtg atgaaggctt tcgggtcgta aagcactgtt 420
gtatgggaag aaatgctaaa atagggaatg attttagttt gacggtacca taccagaaag 480
ggacggctaa atacgtgcca gcagccgcgg taatacgtat gtcccgagcg ttatccggat 540
ttattgggcg taaagcgagc gcagacggtt gattaagtct gatgtgaaag cccggagctc 600
aactccggaa tggcattgga aactggttaa cttgagtgtt gtagaggtaa gtggaactcc 660
atgtgtagcg gtggaatgcg tagatatatg gaagaacacc agtggcgaag gcggcttact 720
ggacaacaac tgacgttgag gctcgaaagt gtgggtagca aacaggatta gataccctgg 780
tagtccacac cgtaaacgat gaatactagg tgttaggagg tttccgcctc ttagtgccga 840
agctaacgca ttaagtattc cgcctgggga gtacgaccgc aaggttgaaa ctcaaaggaa 900
ttgacgggga cccgcacaag cggtggagca tgtggtttaa ttcgaagcaa cgcgaagaac 960
cttaccaggt cttgacatcc tttgaagctt ttagagatag aagtgttctc ttcggagaca 1020
aagtgacagg tggtgcatgg tcgtcgtcag ctcgtgtcgt gagatgttgg gttaagtccc 1080
gcaacgagcg caacccttat tgttagttgc cagcattcag ttgggcactc tagcgagact 1140
gccggtgaca aaccggagga aggcggggac gacgtcagat catcatgccc cttatgacct 1200
gggctacaca cgtgctacaa tggcgtatac aacgagttgc caacctgcga aggtgagcta 1260
atctcttaaa gtacgtctca gttcggactg cagtctgcaa ctcgactgca cgaagtcgga 1320
atcgctagta atcgcggatc agcacgccgc ggtgaatacg ttcccgggtc ttgtacacac 1380
cgcccgtcac accatgggag tttgtaatgc ccaaagccgg tggcctaacc 1430
Claims (12)
1.一种嗜柠檬酸明串珠菌WiKim0104,其特征在于,保藏编号为KCCM12420P。
2.一种用于预防或改善炎症、肥胖或脂肪肝疾病的组合物,其特征在于,包含保藏编号为KCCM12420P的嗜柠檬酸明串珠菌WiKim0104、其培养物、其破碎物或其提取物作为有效成分。
3.根据权利要求2所述的用于预防或改善炎症、肥胖或脂肪肝疾病的组合物,其特征在于,上述脂肪肝疾病包括单纯性脂肪肝、非酒精性脂肪性肝炎、肝纤维化及肝硬化。
4.根据权利要求2所述的用于预防或改善炎症、肥胖或脂肪肝疾病的组合物,其特征在于,上述组合物为食品组合物、食品发酵用乳酸菌发酵剂组合物、饲料或饲料添加剂组合物或者药学组合物。
5.根据权利要求4所述的用于预防或改善炎症、肥胖或脂肪肝疾病的组合物,其特征在于,上述食品为保健功能食品、饮料、棒状食品或发酵乳。
6.一种保藏编号为KCCM12420P的嗜柠檬酸明串珠菌WiKim0104、其培养物、其破碎物或其提取物在预防、改善或治疗炎症、肥胖或脂肪肝疾病中的用途。
7.根据权利要求6所述的用途,其特征在于,上述脂肪肝疾病包括选自由单纯性脂肪肝、非酒精性脂肪性肝炎、肝纤维化及肝硬化组成的组中的一种以上。
8.根据权利要求6所述的用途,其特征在于,用作食品组合物、食品发酵用乳酸菌发酵剂组合物、饲料或饲料添加剂组合物或者药学组合物。
9.根据权利要求8所述的用途,其特征在于,上述食品组合物为保健功能食品、饮料、棒状食品或发酵乳。
10.一种预防、改善或治疗炎症、肥胖或脂肪肝疾病的方法,其特征在于,包括向有需要的个体给药包含保藏编号为KCCM12420P的嗜柠檬酸明串珠菌WiKim0104、其培养物、其破碎物或其提取物的组合物的步骤。
11.根据权利要求10所述的预防、改善或治疗炎症、肥胖或脂肪肝疾病的方法,其特征在于,上述个体为包括人类在内的动物。
12.根据权利要求10所述的预防、改善或治疗炎症、肥胖或脂肪肝疾病的方法,其特征在于,上述脂肪肝疾病包括选自由单纯性脂肪肝、非酒精性脂肪性肝炎、肝纤维化及肝硬化组成的组中的一种。
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KR1020190024254A KR102032982B1 (ko) | 2019-02-28 | 2019-02-28 | 류코노스톡 시트래움 WiKim0104를 포함하는 비만 또는 지방간 질환의 예방, 개선 또는 치료용 조성물 |
KR10-2019-0024254 | 2019-02-28 | ||
PCT/KR2020/002845 WO2020175940A1 (ko) | 2019-02-28 | 2020-02-27 | 류코노스톡 시트래움 wikim0104를 포함하는 비만 또는 지방간 질환의 예방, 개선 또는 치료용 조성물 |
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KR20220091428A (ko) | 2020-12-23 | 2022-06-30 | 주식회사 리스큐어바이오사이언시스 | 류코노스톡 시트리움 유래 세포밖 소포체를 유효성분으로 포함하는 지방간 개선, 예방 또는 치료용 조성물 |
WO2022139531A1 (ko) * | 2020-12-23 | 2022-06-30 | 주식회사 리스큐어바이오사이언시스 | 류코노스톡 시트리움 유래 세포밖 소포체를 유효성분으로 포함하는 지방간 개선, 예방 또는 치료용 조성물 |
EP4289441A1 (en) * | 2021-02-08 | 2023-12-13 | Liscure Biosciences Co., Ltd. | Pharmaceutical composition comprising leuconostoc citreum strain as active ingredient for preventing or treating cholestatic liver injuries |
WO2022169337A1 (ko) * | 2021-02-08 | 2022-08-11 | 주식회사 리스큐어바이오사이언시스 | 류코노스톡 시트래움 균주를 유효성분으로 포함하는 장 손상의 예방 또는 치료용 약학 조성물 |
JP2024506625A (ja) * | 2021-02-08 | 2024-02-14 | リスキュア・バイオサイエンシーズ・カンパニー・リミテッド | ロイコノストック・シトレウム菌株を有効成分として含む線維症の予防または治療用医薬組成物 |
KR102390715B1 (ko) * | 2021-07-13 | 2022-04-29 | 한국식품연구원 | 류코노스톡 시트리움 WiKim0129를 포함하는 암의 예방, 개선 또는 치료용 조성물 |
CN115380998B (zh) * | 2022-05-17 | 2023-07-07 | 西北工业大学 | 可获得改善人肝纤维化天然功能羊奶的奶山羊全混合日粮 |
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US20220047652A1 (en) | 2022-02-17 |
CN113498433B (zh) | 2024-04-05 |
AU2020228247B2 (en) | 2024-08-01 |
WO2020175940A1 (ko) | 2020-09-03 |
JP2022522300A (ja) | 2022-04-15 |
BR112021016879A2 (pt) | 2021-11-03 |
CA3131258A1 (en) | 2020-09-03 |
JP7201837B2 (ja) | 2023-01-10 |
MX2021010350A (es) | 2022-01-06 |
EP3933031A1 (en) | 2022-01-05 |
AU2020228247A1 (en) | 2021-09-30 |
EP3933031A4 (en) | 2023-02-15 |
KR102032982B1 (ko) | 2019-10-16 |
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