CN112076236A - 盐肤木果实在制备治疗或预防非酒精性脂肪肝的药物中的应用 - Google Patents
盐肤木果实在制备治疗或预防非酒精性脂肪肝的药物中的应用 Download PDFInfo
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- CN112076236A CN112076236A CN201910519379.XA CN201910519379A CN112076236A CN 112076236 A CN112076236 A CN 112076236A CN 201910519379 A CN201910519379 A CN 201910519379A CN 112076236 A CN112076236 A CN 112076236A
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- rhus chinensis
- fatty liver
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Abstract
本发明涉及化学物质的新的医药用途领域，具体涉及一种盐肤木果实在制备治疗或预防非酒精性脂肪肝的药物中的应用，本发明经研究发现盐肤木果实不同提取物在较低剂量下均可以有效地抑制NAFLD模型大鼠肝脏中脂肪颗粒的沉积及肝细胞损伤，是非酒精性脂肪肝，尤其是单纯性脂肪肝、脂肪性肝炎、单纯性脂肪肝合并糖脂调节受损、脂肪肝炎合并糖脂调节受损、脂肪性肝炎相关性肝硬化和脂肪性肝炎相关性肝癌的候选药物，且本发明药物原料来自于天然可食用的植物原材料，安全性高。
Description
技术领域
本发明涉及化学物质的新的医药用途领域，具体涉及一种盐肤木果实在制备治疗或预防非酒精性脂肪肝的药物中的应用。
背景技术
非酒精性脂肪肝病(Non-alcoholic fatty liver disease,NAFLD)是指除酒精和其他明确的损肝因素外所致的肝细胞内脂肪过度沉积为主要特征的临床病理综合征，与胰岛素抵抗和遗传易感性密切相关的获得性代谢应激性肝损伤。包括单纯性脂肪肝(SFL)、非酒精性脂肪性肝炎(NASH)及其相关肝硬化。随着肥胖及其相关代谢综合征全球化的流行趋势，NAFLD现已成为欧美等发达国家和我国富裕地区慢性肝病的重要病因，普通成人NAFLD患病率10％～30％，其中10％～20％为NASH，后者10年内肝硬化发生率高达25％。
从发病机制看，非酒精性脂肪性肝病与酒精性脂肪性肝病(ALD)明显不同，NAFLD的发病机制主要与胰岛素抵抗、肝脏脂质代谢异常、线粒体功能障碍和氧化应激，遗传变异和代谢改变及细胞损伤的易感性等相关，NAFLD的胰岛素抵抗主要表现在肝脏、肌肉和脂肪组织的胰岛素敏感性降低，糖代谢异常，脂肪动员增加。从而使血液中游离脂肪酸含量增高，且远远超过了肝脏的转运脂质能力，便转化为脂肪沉积在肝脏。而ALD的发病机制是乙醇及其衍生物的代谢过程中直接或间接诱导的炎症反应、氧化应激和营养失衡等多种因素相互作用的结果，戒酒后显著改善。NAFLD和ALD的致病因素、自然转归及预后都不相同，治疗方法也不相同。治疗NAFLD的首要目标是改善胰岛素抵抗，纠正代谢紊乱，然后减少肝脏脂肪沉积，避免NASH和肝功能异常，主要药物有胰岛素增敏剂、抗氧化及抗炎保肝等，而严格戒酒和营养支持是ALD患者主要治疗措施。
NAFLD除可直接导致代偿性肝硬化、肝癌等疾病，还可影响其他慢性肝病的进展，并参与2型糖尿病和动脉粥样硬化的发病。代谢综合征相关恶性肿瘤、动脉硬化性心脑血管疾病以及肝硬化是影响NAFLD患者生活质量和预期寿命的重要因素。然而目前却没有专门针对NAFLD的临床治疗药物，从而使得NAFLD成为当代医学领域的巨大挑战，其对人类健康的危害仍将不断增加。
盐肤木(Rhus chinensis Mill.)果实又名盐肤木、叛奴盐、盐梅子等，是漆树科植物盐肤木的果实。生于海拔350-2300m的石灰山灌丛、疏林中。为我国常见的野生阳性树。分布东北及云南、四川、山西、安徽、江苏、广西等地。漆树对土壤条件要求不高，常见于未耕地，也是众所周知的五倍子的生产主体。盐肤木在中国古代各地早已用于治疗和预防疾病。例如，盐肤木叶用于治疗炎症和腹泻；根用于治疗疟疾和黄疸；果实和种子经常用于治疗痢疾。与其他部位相比，果实不仅可以作为草药使用，还可以作为鲜果、调味品和饮料使用，而且盐肤木果油在2013年已经被批准为新食品原料。此外，成熟果实在云南多个地方具有长期食用的历史。目前国内外对盐肤木果防治NAFLD的相关研究未见有专利文献报道。本发明将为开发安全有效纯天然的防治NAFLD的保健食品或药品提供一定的科学依据。
发明内容
因此，本发明人通过研究发现盐肤木果实具有改善胰岛素抵抗、纠正脂肪代谢紊乱或者调节氧化应激的作用，从而可以有效抑制脂肪颗粒的沉积及肝损伤，保护肝脏中内在的抗氧酶系，用于预防或治疗非酒精性脂肪肝。
本发明提供了一种盐肤木果实在制备治疗或预防非酒精性脂肪肝的药物或者保健食品中的应用。
本发明还提供了一种盐肤木果实在制备改善胰岛素抵抗、纠正肝脏脂质代谢紊乱和调节氧化应激的药物中的应用。
优选地，所述非酒精性脂肪肝包括单纯性脂肪肝、脂肪性肝炎、单纯性脂肪肝合并糖脂调节受损、脂肪肝炎合并糖脂调节受损、脂肪性肝炎相关性肝硬化和脂肪性肝炎相关性肝癌中的至少一种。
进一步地，所述药物进一步包括其他治疗或预防非酒精性脂肪肝的药物。
优选地，所述其他药物选自熊去氧胆酸、维生素E、水飞蓟素、牛磺酸、甜菜碱、N-乙酰半胱胺酸、二甲双胍、罗格列酮中的至少一种。
进一步地，所述药物或者保健食品还包括药学上可接受的载体。
优选地，所述药学上可接受的载体选自药学上可接受的溶剂、增溶剂、助溶剂、乳化剂、着色剂、粘合剂、崩解剂、填充剂、润滑剂、润湿剂、渗透压调节剂、稳定剂、助流剂、矫味剂、防腐剂、助悬剂、包衣材料、芳香剂、抗粘合剂、整合剂、渗透促进剂、pH值调节剂、缓冲剂、增塑剂、表面活性剂、增稠剂、包合剂、保湿剂、吸收剂、稀释剂、絮凝剂与反絮凝剂、助滤剂、释放阻滞剂、高分子骨架材料和成膜材料中的至少一种。
进一步地，所述药物或者保健食品为口服溶液、注射剂、胶囊剂、片剂、药膜剂或喷雾剂。
本发明还提供了一种用于治疗或预防非酒精性脂肪肝的药物或者保健食品，所述药物或者保健食品以盐肤木果实、盐肤木果实的水提物或醇提物，或者所述水提物或者醇提物经精制纯化后的精制物为活性成分，向盐肤木果实中加入常规辅料按照常规工艺制成临床上可接受的口服溶液、注射剂、胶囊剂、片剂、药膜剂、喷雾剂。
进一步地，所述非酒精性脂肪肝并发症包括胰岛素抵抗、肥胖和心血管疾病中的至少一种。
本发明技术方案，具有如下优点：
本发明通过实验发现盐肤木果实不同提取物在较低剂量下均可以有效地抑制NAFLD模型大鼠肝脏中脂肪颗粒的沉积及肝细胞损伤。且原料来自于天然可食用植物原材料，安全性高。
附图说明
为了更清楚地说明本发明具体实施方式或现有技术中的技术方案，下面将对具体实施方式或现有技术描述中所需要使用的附图作简单地介绍，显而易见地，下面描述中的附图是本发明的一些实施方式，对于本领域普通技术人员来讲，在不付出创造性劳动的前提下，还可以根据这些附图获得其他的附图。
图1是本发明实验例1中盐肤木果实对高脂高糖饲料所致大鼠NAFLD干预后的肝脏病理切片的HE染色图(HE×200)，其中A为对照组；B为模型组；C为醇提物低剂量组；D为醇提物高剂量组；E为水提物低剂量组；F为水提物高剂量组；
图2是本发明实验例1中盐肤木果实对高脂高糖饲料所致大鼠NAFLD干预后的肝脏免疫组化FAS的染色图(FAS×400)，其中A为对照组；B为模型组；C为醇提物低剂量组；D为醇提物高剂量组；E为水提物低剂量组；F为水提物高剂量组；
图3是本发明实验例1中盐肤木果实对高脂高糖饲料所致大鼠NAFLD干预后的肝脏免疫组化p-PI3K的染色图(p-PI3K×400)，其中A为对照组；B为模型组；C为醇提物低剂量组；D为醇提物高剂量组；E为水提物低剂量组；F为水提物高剂量组。
具体实施方式
实施例1盐肤木果实的水提物
制法：取盐肤木果实按料液比为1:20加入水，煮沸1小时。煮沸以后趁热离心，转速4000r/min，上清液进行抽滤，抽滤以后的样品进行浓缩，最后冻干，得盐肤木果实的水提物。
实施例2盐肤木果实的醇提物
制法：取盐肤木果实按料液比为1:5加入80％的乙醇溶液(体积百分数)，超声提取，提取温度为25℃，提取时间为30min，滤渣复提一次，然后4000r/min离心，取上清液浓缩冻干，得盐肤木果实的醇提物。
实施例3盐肤木果实的片剂
制法：取盐肤木果实按料液比为1:5加入80％的乙醇溶液(体积百分数)，超声提取，提取温度为25℃，提取时间为30min，滤渣复提一次，然后4000r/min离心，取上清液浓缩冻干，得盐肤木果实的醇提物。取盐肤木果实的醇提物加入常规辅料按照常规工艺制成临床上可接受的片剂。
实施例4盐肤木果实的的胶囊剂
制法：取盐肤木果实按料液比为1:20加入水，煮沸1小时。煮沸以后趁热离心，转速4000r/min，上清液进行抽滤，抽滤以后的样品进行浓缩，最后冻干，得盐肤木果实的水提物。取盐肤木果实的水提物加入常规辅料按照常规工艺制成临床上可接受的胶囊剂。
其中上述实施例1-实施例4中，80％的乙醇溶液为80体积份的乙醇与20积份的水的混合溶液。
实验例1
1.实验材料
1.1实验动物
SPF级SD雄性大鼠，4-8周龄，共36只，体重在200g左右，体重偏差在5％以内，由辽宁长生生物技术股份有限公司提供，编号为SCKK(辽)2015-0002。
1.2药物与试剂
盐肤木果实的水提物(以下简称“水提物”)：按照实施例1所述的制法制备得到；
盐肤木果实的醇提物(以下简称“醇提物”)：按照实施例2所述的制法制备得到；
AST检测试剂盒、ALT检测试剂盒、TG检测试剂盒、TC检测试剂盒和CAT检测试剂盒购自南京建成生物科技有限公司；GSH检测试剂盒和SOD检测试剂盒购自上海碧云天生物技术有限公司；高脂高糖饲料由进多丰生物有限公司提供，正常饲料由昆明医科大学提供。
1.3仪器
全自动生化分析仪购自深圳雷杜生命科学股份有限公司。
2.方法与结果
2.1造模
将36只SPF级SD雄性大鼠分成6组(每笼6只)，水、醇提取物各两组。编号及对应的造模方法如下：Group K：对照组(造模期间蒸馏水灌胃，记为K)、Group M模型组(造模期间蒸馏水灌胃，记为M)、Group AL醇提物低剂量组200mg/kg(造模期间醇提物灌胃，记为AL)、Group AH醇提物高剂量组600mg/kg(造模期间醇提物灌胃，记为AH)、Group WL水提物低剂量组200mg/kg(造模期间水提物灌胃，记为WL)、Group WH水提物高剂量组600mg/kg(造模期间水提物灌胃，记为WH)。
第一次给药前所有动物禁食12h，并且在给药前记录各个老鼠的体重(禁水)。按照标准的大鼠饲养环境饲养大鼠(大鼠购买以后，在该环境下适应七天环境，参照国家标准GB/T 21757-2008)。
造模的方式如下：每天早上9点以5ml/kg的灌胃体积(每kg动物体重灌胃体积为5mL)，灌入上述对应剂量的两类提取物或是蒸馏水，具体为K和M以蒸馏水灌胃，AL以200mg/kg剂量的醇提物灌胃(每kg动物体重灌胃醇提物质量为200mg)，AH以600mg/kg剂量的醇提物灌胃(每kg动物体重灌胃醇提物质量为600mg)，WL以200mg/kg剂量的水提物灌胃(每kg动物体重灌胃水提物质量为200mg)，WH以600mg/kg剂量的水提物灌胃(每kg动物体重灌胃水提物质量为600mg)。在灌胃以后，除对照组外，各个组给予高脂高糖饲料的喂养，对照组给予正常饲料喂养。在饲养90天以后，对所有的大鼠禁食12h，使用10％的水合氯醛麻醉大鼠，称重，取血液制成血浆待测，随后进行血浆生化分析；取肝脏称重，随后取肝大叶和小叶，浸没在10％的福尔马林溶液中，待后续进行HE染色(小叶)和免疫组化(大叶)。
2.2实验方法与结果
2.2.1盐肤木果实提取物对非酒精性脂肪肝大鼠肝指数的影响。
先称量大鼠禁食12小时后的体重，随后解剖大鼠取出大鼠肝脏并称重。肝脏系数等于肝脏重量除以对应大鼠体重。
表1.盐肤木果实提取物对非酒精性脂肪肝大鼠肝指数的影响
| 组别 | 肝指数(g/kg) |
| K | 26.25±1.61 |
| M | 35.09±2.11<sup>*</sup> |
| AL | 30.32±4.66 |
| AH | 28.57±2.74<sup>#</sup> |
| WL | 31.13±3.82 |
| WH | 30.49±5.97 |
注：与对照组相比有显著性差异的上标*(p<0.05)；与模型组相比有显著性差异的上标是#(p<0.05)
从表1可知，模型组与对照组相比，高脂高糖模型组的肝指数显著增加；而给药组与高脂高糖模型组相比，盐肤木果实的水提取物和醇提取物均可以降低肝指数，其中AH组的效果最好。因此推测盐肤木果实可以通过抑制肝脏脂肪的积累从而有效地抑制肝指数的增加。
2.2.2盐肤木果实提取物对非酒精性脂肪肝大鼠肝功能酶的影响
大鼠中AST和ALT的测量分别使用南京建成AST检测试剂盒和ALT检测试剂盒进行有效的测量，具体步骤可以参照南京建成AST检测试剂盒和ALT检测试剂盒的说明书。
表2.盐肤木果实提取物对非酒精性脂肪肝大鼠肝功能酶的影响
注：与对照组相比有显著性差异的上标*(p<0.05)；与模型组相比有显著性差异的上标是#(p<0.05)
从表2中可以看出，与对照组相比，模型组血清中ALT和AST含量显著升高，说明高脂高糖饮食下，脂质的代谢已经超过了肝的承受量，从而造成了肝的损伤，引发非酒精性脂肪肝炎；但是给药组与模型组相比，各给药组的大鼠血清中ALT和AST含量均显著下降，说明盐肤木果实可以有效防治高脂高糖造成的脂肪肝炎，尤其是高剂量的醇提物效果最好。
2.2.3盐肤木果实提取物对非酒精性脂肪肝大鼠肝脂的影响
大鼠中TG和TC的测量分别使用南京建成TG检测试剂盒和TC检测试剂盒进行有效的测量，具体步骤可以参照南京建成TG检测试剂盒和TC检测试剂盒的说明书。
表3.盐肤木果实提取物对非酒精性脂肪肝大鼠肝脂的影响
| 组别 | 动物只数 | 肝脏TG(mmol/g prot) | 肝脏TC(mmol/g prot) |
| K | 6 | 8.16±2.96 | 3.49±0.33 |
| M | 6 | 19.42±3.10* | 5.73±0.55* |
| AL | 6 | 13.24±1.98# | 4.27±0.73# |
| AH | 6 | 11.66±2.50# | 3.94±0.42# |
| WL | 6 | 16.16±2.44*# | 4.56±0.36*# |
| WH | 6 | 14.1±1.02*# | 4.26±0.40# |
注：与对照组相比有显著性差异的上标*(p<0.05)；与模型组相比有显著性差异的上标是#(p<0.05)
从表3可知，在动物的肝脏中，可以明显的观察到高脂高糖模型的肝中甘油三酯和总胆固醇的含量显著的提高，从数据中可以看出给药组显著地降低了TG和TC的含量，其中高剂量的醇提物对TG、TC的抑制效果最佳，且和对应的肝脏切片相互印证，从而进一步证实盐肤木果实的水和醇提物可以有效的防治NAFLD。
2.2.4盐肤木果实对NAFLD大鼠肝组织病理情况影响的结果。
HE染色用于观察组织形态是否发生病变，染色步骤如下：分别取对照组、模型组、醇提物低剂量组、醇提物高剂量组、水提物低剂量组和水提物高剂量组的造模后的小鼠肝脏组织浸泡在组织固定液中，用低浓度到高浓度酒精作脱水剂，逐渐脱去组织块中的水份。将脱水的组织进行石蜡包埋、切片。染色前，二甲苯脱去切片中的石蜡，再用苏木精(Hematoxylin，H)和伊红(Eosin，E)染色2-5min，用无水乙醇分色与脱水，二甲苯透明，风干后中性树胶封片，最后用倒置显微镜观察。结果如图1所示，在显微镜下观察非酒精性脂肪肝切片，对照组的大鼠切片中肝细胞的形状正常，细胞核状态正常，且肝细胞中没有脂肪粒的形成(图1-A)。模型组中，可以明显的观察到细胞核的聚集和肝细胞的损伤，不仅如此，在肝细胞中也有明显的脂肪滴的形成(见图1-B)。醇提物的切片中脂质过氧化对肝造成的损伤大大的减少，且脂肪滴形成的较少，尤其是高剂量组(见图1-C和1-D)。水提物组抑制脂质过氧化对肝细胞的损伤能力稍稍弱于醇提物，但是仍比模型组好，在切片中也观察不到明显的脂肪粒形成(见图1-E和1-F)，说明盐肤木果实提取物可以有效地抑制NAFLD模型大鼠肝脏中脂肪颗粒的沉积，纠正肝脏脂质代谢紊乱，可作为治疗NAFLD的候选药物。
免疫组化染色的具体步骤如下：分别取对照组、模型组、醇提物低剂量组、醇提物高剂量组、水提物低剂量组和水提物高剂量组的造模后的小鼠肝脏组织浸泡在组织固定液中，用低浓度到高浓度酒精作脱水剂，逐渐脱去组织块中的水份，将脱水的组织进行石蜡包埋、切片的蜡块，使用二甲苯进行脱蜡处理，随后使用5％牛血清白蛋白封闭10-30分钟。使用对应一抗抗体进行孵育。用PBS清洗后进行二抗的孵育(二抗是HRP偶联的IgG聚合物多克隆抗体)然后用水冲洗，在显微镜下观察。
如图2所示的免疫组化的FAS的切片图，在模型组中(见图2-B中)，脂肪酸合成酶的表达量非常的高(呈现出黄色的部分)，促进了肝细胞内脂肪酸的从头合成，加速了肝细胞内脂肪滴的形成，但是给药组中(见图2-C和图2-D中)脂肪酸合成酶的表达显著地下降，减少了肝脏中脂肪酸的合成，从而有效地抑制NAFLD的形成，说明盐肤木果实提取物可作为治疗NAFLD的候选药物。
如图3所示免疫组化的p-PI3K的切片图。肝脏是胰岛素的重要靶器官。葡萄糖代谢受PI3K蛋白质调节。胰岛素激活肝脏中PI3K(p-PI3K)蛋白,然后增加GSH3β去磷酸化的效率，从而使得GSH3β的下游蛋白质糖原合成激酶活性增强，进而合成大量的肝糖原，降低机体分泌大量的胰岛素进而很好的控制肝脏合成脂肪的速率，从而控制脂肪在肝脏中的积累，改善非酒精性脂肪肝。图中显示p-PI3K在空白组中的表达含量显著的高于模型组的含量(黄色物质即为p-PI3K蛋白，颜色越深，表达量越多)。因此表明我们模型的建立非常的成功。给药组中显示，所有给药组均得到很好的改善，其中醇提物高浓度组p-PI3K的表达量最多，因此推测盐肤木果实可以很好的激活p-PI3K蛋白来提高胰岛素的敏感性，最终改善非酒精性脂肪肝，说明盐肤木果实提取物可改善胰岛素抵抗，作为治疗NAFLD的候选药物。
综上所述，上述实验证实盐肤木果实可以有效地抑制长期高脂高糖饮食所造成的脂肪在肝细胞中的积累，从而确定盐肤木果实可以有效地防治NAFLD。
2.2.5盐肤木果实提取物对非酒精性脂肪肝大鼠肝脏氧化酶系的影响
天然抗氧化防御系统，如超氧化物歧化酶(SOD)、谷胱甘肽(GSH)和过氧化氢酶(CAT)，可以消除活性氧，维持氧化还原平衡，保护细胞。过量的脂质积累在肝脏中会诱发脂质在线粒体中大量的氧化，从而产生大量的脂质过氧化物，进而氧化细胞，缩短细胞寿命，消耗GSH最终导致受损的肝细胞难以修复加重脂肪肝。分别取对照组、模型组、醇提物低剂量组、醇提物高剂量组、水提物低剂量组和水提物高剂量组的造模后的小鼠肝脏组织分别测量CAT、SOD和GSH的的含量，其中大鼠中CAT的测量使用南京建成的CAT检测试剂盒进行有效的测量具，SOD和GSH检测分别使用碧云天SOD检测试剂盒和GSH检测试剂盒进行测量。具体步骤可以参照南京建成和碧云天对应试剂盒的说明书。
表4盐肤木果实提取物对非酒精性脂肪肝大鼠肝脂的影响
CAT:过氧化氢酶；SOD：超氧化物歧化酶；GSH:谷胱甘肽
从表4中可以看出，天然抗氧化酶系在经过盐肤木果实提取物治疗以后，得到了显著的改善。表明盐肤木果实提取物可能通过修复天然抗氧化防御系统，降低ROS的生成和脂质过氧化，从而减少非酒精性脂肪肝中氧化应激和脂质过氧化对其的促进作用，说明盐肤木果实提取物可以调节氧化应激，在非酒精性脂肪肝的初期起到预防和治疗效果。
显然，上述实施例仅仅是为清楚地说明所作的举例，而并非对实施方式的限定。对于所属领域的普通技术人员来说，在上述说明的基础上还可以做出其它不同形式的变化或变动。这里无需也无法对所有的实施方式予以穷举。而由此所引伸出的显而易见的变化或变动仍处于本发明创造的保护范围之中。
Claims (10)
1.盐肤木果实在制备治疗或预防非酒精性脂肪肝的药物或者保健食品中的应用。
2.盐肤木果实在制备改善胰岛素抵抗、纠正肝脏脂质代谢紊乱和调节氧化应激的药物中的应用。
3.根据权利要求1所述的应用，其特征在于，所述非酒精性脂肪肝包括单纯性脂肪肝、脂肪性肝炎、单纯性脂肪肝合并糖脂调节受损、脂肪肝炎合并糖脂调节受损、脂肪性肝炎相关性肝硬化和脂肪性肝炎相关性肝癌中的至少一种。
4.根据权利要求1-3中任一所述的应用，其特征在于，所述药物还包括其他治疗或预防非酒精性脂肪肝的药物。
5.根据权利要求4所述的应用，其特征在于，所述其他药物选自熊去氧胆酸、维生素E、水飞蓟素、牛磺酸、甜菜碱、N-乙酰半胱胺酸、二甲双胍、罗格列酮中的至少一种。
6.根据权利要求1-5中任一所述的应用，所述药物或者保健食品还包括药学上可接受的载体。
7.根据权利要求6所述的应用，其特征在于，所述药学上可接受的载体选自药学上可接受的溶剂、增溶剂、助溶剂、乳化剂、着色剂、粘合剂、崩解剂、填充剂、润滑剂、润湿剂、渗透压调节剂、稳定剂、助流剂、矫味剂、防腐剂、助悬剂、包衣材料、芳香剂、抗粘合剂、整合剂、渗透促进剂、pH值调节剂、缓冲剂、增塑剂、表面活性剂、增稠剂、包合剂、保湿剂、吸收剂、稀释剂、絮凝剂与反絮凝剂、助滤剂、释放阻滞剂、高分子骨架材料和成膜材料中的至少一种。
8.根据权利要求1-7中任一所述的应用，其特征在于，所述药物或者保健食品为口服溶液、注射剂、胶囊剂、片剂、药膜剂或喷雾剂。
9.一种用于治疗或预防非酒精性脂肪肝的药物或者保健食品，其特征在于，所述药物或者保健食品以盐肤木果实、盐肤木果实的水提物或醇提物，或者所述水提物或者醇提物经精制纯化后的精制物为活性成分，向盐肤木果实中加入常规辅料按照常规工艺制成临床上可接受的口服溶液、注射剂、胶囊剂、片剂、药膜剂、喷雾剂。
10.盐肤木果实在制备治疗或预防非酒精性脂肪肝并发症的药物或者保健食品中的应用，其特征在于，所述非酒精性脂肪肝并发症包括胰岛素抵抗、肥胖和心血管疾病中的至少一种。
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