CN108853080A - 原花青素在制备提高肥胖男性精子质量的功能食品或药品中的应用 - Google Patents
原花青素在制备提高肥胖男性精子质量的功能食品或药品中的应用 Download PDFInfo
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Abstract
本发明公开了一种原花青素在制备提高肥胖男性精子质量的功能食品或药品中的应用,还公开了以原花青素作为活性成分与制药学上可接受附加剂的药物组合物在制备提高肥胖男性精子质量的功能食品或药品中的应用。研究证明原花青素对高脂膳食喂养大鼠体重增长率具有明显的降低作用,提高血清睾酮水平,保护睾丸结构完整性,改善肥胖所造成生精障碍,减少睾丸生精细胞的过度凋亡,提高精子数量和活力,降低精子畸形率,从而提出原花青素能提高肥胖男性精子质量,保护肥胖男性生殖功能。本发明为原花青素发掘了新的医疗用途,对于解决肥胖男性生殖障碍提供了有意义的参考。
Description
技术领域
本发明属于原花青素的医药新用途技术领域,具体涉及原花青素在制备提高肥胖男性精子质量的功能食品或药品中的应用。
背景技术
肥胖症(obesity)是指机体控制体脂、能量代谢平衡机制紊乱,导致体内脂肪堆积过多或分布异常从而导致身体质量增加,是一种多因素的慢性代谢性疾病。近年来随着生活水平的提高,包括我国在内的大多数国家存在膳食结构不合理脂肪摄入量偏高的问题,造成超重与肥胖的人数快速增加,并呈年轻化的趋势。近年来随着生活环境和饮食结构的急剧变化以及晚婚晚育比例的升高,产生了大量的生殖健康问题。近10余年来我国育龄人群的不孕不育率已由3%~5%上升至15%~20%,不孕不育严重影响家庭和谐已经成为亟待解决的重大科学问题。WHO数据也证实育龄夫妇中15%存在不孕不育现象,其中男方因素占约50%。近年大量人群流行病学研究和动物实验均发现肥胖可导致男性生殖功能下降,但其具体机制尚未完全阐明。
原花青素(Procyanidins,分子式C30H26O12)是一种有着特殊分子结构的生物类黄酮,一般为红棕色粉末,气微、味涩,溶于水和大多有机溶剂。原花青素分布广泛,存在于许多植物的皮、壳、籽、核、花、叶中,葡萄籽中原花青素含量最高,种类丰富。一般为葡萄籽提取物或法国海岸松树皮提取物。原花青素(葡萄籽提取物)是一种新型高效抗氧化剂,该类化合物具有多种生物活性,其以高效、低毒、高生物利用度和强抗氧化能力而著称,是目前国际上公认的清除人体自由基最有效的抗氧化剂。实验证明,原花青素的抗自由基氧化能力是维生素E的50倍,维生素C的20倍,并吸收迅速完全,口服20分钟即可达到最高血液浓度,代谢半衰期达7小时之久。研究表明原花青素具有改善血液循环、保护视力、消除水肿、减肥降低胆固醇、抗病毒等功效。
如公开号为CN102600127A的专利公开了原花青素或含其的植物提取物在制备预防或治疗脂质代谢紊乱性疾病的药物或保健食品中的应用。公开号为CN102940624A的专利公开了中药肉桂水提物中的原花青素在制备治疗糖尿病药物中的应用,研究发现肉桂原花青素能够以抗胰岛淀粉样多肽聚集为靶点,在制备治疗2型糖尿病药物中具有极大的应用价值。公告号为CN1745747B的专利公开了一种原花青素在制备治疗结肠炎药物的用途,尤其公开了原花青素在制备治疗溃疡性结肠炎药物的用途。公开号为CN107213147A的专利公开了原花青素在预防和治疗黄病毒感染方面的应用,尤其是其抗寨卡病毒方面的作用。
近年来,大量发现给予抗氧化剂如原花青素干预可对化学物质和药物以及肥胖所致雄性生殖功能损伤具有保护作用。研究发现原花青素对氟、镍、镉等重金属以及氨基脲、玉米赤霉烯酮、三氧化二砷、顺铂和反式脂肪酸等所致的雄性生殖功能损伤均具有一定保护作用,抗氧化作用是原花青素保护雄性生殖损伤的重要机制之一。
研究证实氧化应激以及由此诱发的睾丸生精细胞过度凋亡是肥胖致雄性生殖功能损伤的重要机制。目前,对于原花青素用途的研究开展的较为深入,但对原花青素提高肥胖男性精子质量的功效方面尚未有专利文献报道。本发明开拓了原花青素一个新的应用领域,对于解决人类生殖障碍,改善辅助生殖技术提供了有意义的参考。本发明将为开发提高肥胖男性精子质量的功能食品和药品提供一定的科学依据。
发明内容
本发明的目的是提供了原花青素的医药新用途,即原花青素在制备提高肥胖男性精子质量的功能食品或药品中的应用。
本发明为实现上述目的采用如下技术方案,原花青素在制备提高肥胖男性精子质量的功能食品或药品中的应用。
本发明所述的以原花青素作为活性成分与制药学上可接受附加剂的药物组合物在制备提高肥胖男性精子质量的功能食品或药品中的应用。
本发明所述的原花青素可从葡萄籽等植物果皮种子等部位分离提取得到,也可以直接通过购买获得。
本发明所述的功能食品或药品的剂型为针剂、散剂、片剂或丸剂。
本发明所述的功能食品或药品中所含原花青素的用量在有效量50~500mg/kg/天以上。
优选的,所述的功能食品或药品中所含原花青素的用量在有效量100~300mg/kg/天以上。
通过大鼠实验证明:原花青素对高脂饲料喂养大鼠体重增长率具有明显的降低作用,提高血清性激素睾酮水平,改善肥胖所造成生精障碍,保护睾丸的生精结构,减少生精细胞的过度凋亡,从而维护正常的生精过程,提高肥胖男性精子的质量。
与现有技术相比,本发明具有如下优点:
1、本发明为原花青素发掘了新的医药用途,开拓了一个新的应用领域;
2、本发明通过实验发现原花青素对治疗肥胖男性生殖功能低下所需的浓度较低,无毒副作用;
3、原花青素具有增强免疫力、保护视力、减肥等功效,不仅能提高肥胖男性精子质量,对机体健康还起到促进作用。
附图说明
图1是本发明实施例1中各试验组大鼠体重增量随时间的关系曲线;
图2是原花青素对大鼠睾丸组织形态的影响;
图3是原花青素对大鼠睾丸生精细胞凋亡率的影响(*p<0.05,**p<0.01与HFD相比);
图4是原花青素对大鼠血清睾酮水平的影响(*p<0.05,**p<0.01与HFD相比);
图5是原花青素对大鼠精子数量的影响(*p<0.05,**p<0.01与HFD相比);
图6是原花青素对大鼠精子活率的影响(*p<0.05,**p<0.01与HFD相比);
图7是原花青素对大鼠活动精子数的影响(*p<0.05,**p<0.01与HFD相比);
图8是原花青素对精子畸形率的影响(*p<0.05,**p<0.01与HFD相比)。
具体实施方式
以下通过实施例对本发明的上述内容做进一步详细说明,但不应该将此理解为本发明上述主题的范围仅限于以下的实施例,凡基于本发明上述内容实现的技术均属于本发明的范围。
实施例
原花青素改善肥胖男性精子质量
1材料与方法
1.1材料
原花青素(天津尖峰天然产物研究开发有限公司,纯度≥95%),睾酮(T)试剂盒购自北京北方生物技术研究所有限公司,饲料购自北京华阜康生物科技股份有限公司。
1.2实验动物及分组
4周龄健康雄性SD大鼠55只,体重均在90-120g购自北京维通利华实验动物技术有限公司,回后以基础饲料喂养适应一周,适应环境后随机区组分为对照组10只和模型组(高脂)45只。低脂对照组给予10%低脂饲料(LFD),其余高脂模型组均给予45%高脂饲料(HFD)。2周后,根据体重淘汰高脂模型组中对高脂模型不敏感的15只大鼠,余下的30只大鼠随机区组分为3组,每组10只。原花青素低剂量组(YL)和原花青素高剂量组(YL),分别于造模后第1天原花青素低剂量和高剂量组以灌胃方式分别和给予原花青素100mg/kg和300mg/kg,1次/d。对照组给予普通饲料,其余各组动物均给予高脂饲料,至13周后进行相关研究。
1.3血清性激素睾酮测定
动物麻醉后,腹主动脉取血,室温下放置30min后,再以3000rpm/min的离心速率离心10min分离血清,将分离的血清-20℃分装保存。性激素睾酮(T)的测定按照公司提供剂盒说明书操作。
1.4精子参数(数量、活力和形态)
取右侧附睾,放入盛有4mL 37℃预温的M199培养液中,沿附睾尾纵切4-5刀,放入37℃培养箱扩散5min,让精子从附睾尾中游出,过滤弃去杂质,获得精子悬液。取精子悬液混匀,取一滴精子悬液滴加到载玻片上,然后用22×22mm盖玻片覆盖,置于Nikon EclipseE200相差显微镜下用400倍目镜观察活动精子的比例,每只动物观察5个视野求平均值计算精子活力。取0.5mL精子悬液用9.5mL生理盐水稀释混匀,取10μL精子悬液加入血球计数板,静待5min后置于LEICA DM 1000显微镜下计数精子数量,结果以精子数/mL表示。取精子悬液一滴置于载玻片,推片晾干,甲醇固定5min,1wt%伊红染色1h,冲洗后镜下进行精子形态学观察,包括香蕉形、胖头、双头、无钩、尾折叠、双尾、无定形。每只雄鼠检查200个精子,计算精子畸形率。
1.5睾丸病理学
各组动物经上述处理后,取睾丸等相关脏器称重;经4wt%多聚甲醛固定后,常规石蜡包埋,制作病理切片,HE染色后,于显微镜下观察睾丸等生殖相关器官的组织结构。
1.6精细胞凋亡水平
TUNEL检测细胞凋亡:按照TUNEL试剂盒说明进行操作。光学显微镜下细胞核中有棕黄色颗粒者为凋亡细胞。凋亡指数(AI)计算:每张切片选取5个高倍光镜视野(×400),计数500个细胞,AI=凋亡细胞数/500×100%。
1.7统计学方法
采用SPSS 180软件进行统计学分析。计量资料实验数据均以进行表示,多组间比较采用方差齐性检验和单因素方差分析(One Way ANOVA)进一步进行组间两两比较时,若方差齐时,采用LSD检验;若方差不齐时,采用Games-Howell检验。以P<0.05为差异有统计学意义。
2实验结果
如图1所示,各组大鼠体重增长情况显示,原花青素具有抑制高脂饲料喂养大鼠体重增长的作用。如图2所示,肥胖模型组大鼠睾丸完整结构受到破坏,各级精子细胞数量显著减少,YL和YH干预组睾丸结构较为完整。图3中TUNEL染色显肥胖模型组大鼠睾丸生精细胞凋亡较对照组显著增加,YL和YH干预能减少肥胖导致的睾丸生精细胞凋亡水平,并具有一定的剂量依赖关系,提示原花青素能抑制肥胖雄性睾丸生精细胞过度凋亡,对肥胖导致的雄性生殖功能低下具有一定的保护作用。图4-8显示原花青素能提高肥胖雄性睾酮水平,提高精子质量。以上研究结果证实,原花青素不但具有减肥功能,还能提高肥胖雄性睾酮水平减少睾丸生精细胞过度凋亡,提高精子质量,具有保护肥胖男性生殖功能的作用。
以上实施例描述了本发明的基本原理、主要特征及优点,本行业的技术人员应该了解,本发明不受上述实施例的限制,上述实施例和说明书中描述的只是说明本发明的原理,在不脱离本发明原理的范围下,本发明还会有各种变化和改进,这些变化和改进均落入本发明保护的范围内。
Claims (6)
1.原花青素在制备提高肥胖男性精子质量的功能食品或药品中的应用。
2.以原花青素作为活性成分与制药学上可接受附加剂的药物组合物在制备提高肥胖男性精子质量的功能食品或药品中的应用。
3.根据权利要求1或2所述的应用,其特征在于:所述的原花青素是由葡萄籽分离提取得到的。
4.根据权利要求1或2所述的应用,其特征在于:所述的功能食品或药品的剂型为针剂、散剂、片剂或丸剂。
5.根据权利要求1或2所述的应用,其特征在于:权利要求1或2所述的功能食品或药品中所含原花青素的用量在有效量50~500mg/kg/天以上。
6.根据权利要求1或2所述的应用,其特征在于:所述的功能食品或药品中所含原花青素的用量在有效量100~300mg/kg/天以上。
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JP2021016341A (ja) * | 2019-07-19 | 2021-02-15 | 国立大学法人 筑波大学 | コーヒーチェリー素材 |
CN113476440A (zh) * | 2021-07-06 | 2021-10-08 | 宁夏医科大学 | 芝麻素在制备治疗生精功能障碍药物中的用途 |
CN114632092A (zh) * | 2022-05-17 | 2022-06-17 | 北京第一生物化学药业有限公司 | 睾丸片在制备具有降糖活性的药物中的应用 |
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JP2021016341A (ja) * | 2019-07-19 | 2021-02-15 | 国立大学法人 筑波大学 | コーヒーチェリー素材 |
JP7376065B2 (ja) | 2019-07-19 | 2023-11-08 | 国立大学法人 筑波大学 | コーヒーチェリー素材 |
CN113476440A (zh) * | 2021-07-06 | 2021-10-08 | 宁夏医科大学 | 芝麻素在制备治疗生精功能障碍药物中的用途 |
CN114632092A (zh) * | 2022-05-17 | 2022-06-17 | 北京第一生物化学药业有限公司 | 睾丸片在制备具有降糖活性的药物中的应用 |
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