余甘子药用价值研究进展
2024-12-26王建超张小艳谢丽雪张立杰李韬
摘要:余甘子是一种药食同源经济植物资源,药理作用显著,但其药用开发还处于初级阶段,未充分发挥其独特的药用特性和保健功效,市场开发潜力巨大。本文从余甘子的药用价值、药用成分、药用功能等方面进行综述,以期为余甘子的医药保健开发和利用提供科学依据,并指出未来研究应从余甘子的品质和药用成分鉴定评价出发,建立余甘子种质资源的整体质量控制体系,对于余甘子的产品开发、品质提升和全产业链升级具有深远意义。
关键词:余甘子;药用成分;没食子酸;抗肝损伤
中图分类号:S667.9" " " " " " " " " " " 文献标识码:A" " " " " " " " " " " "文章编号:2095-5774(2024)06-0536-11
Research Progress on Medicinal Value of Phyllanthus emblica L.
Wang Jianchao,Zhang Xiaoyan,Xie Lixue,Zhang Lijie,Li Tao*
(Fruit Research Institute,Fujian Academy of Agricultural Sciences,Fuzhou,Fujian 350013,China)
Abstract:Phyllanthus emblica(P. emblica)is a medicinal and edible economic plant resource with significant pharmacological effects. However,its medicinal development is still in its early stages,and its unique medicinal properties and health care effects have not yet been exerted,indicating substantial potential for future development. This article reviews the medicinal value,medicinal ingredients,and medicinal function of P. emblica in order to provide scientific basis for the development and utilization of P. emblica in medicine and health care. Furthermore,it also points out that future research should focus on the identification of quality and medicinal ingredients of P. emblica. By evaluating the germplasm resources of P. emblica,establishing a comprehensive quality control system will have significant implications for the product development,enhancement,and advancement of the entire industry chain.
Key words:Phyllanthus emblica;Medicinal ingredients;Gallic acid;Anti-liver injury
余甘子(Phyllanthus emblica L.)属大戟科(Euphorbiaceae)叶下珠属(Phyllanthus)多年生灌木或乔木[1]。又名庵摩勒(古代名,药用名)、油柑(福建、台湾)、滇橄榄(云南)、“Amla” 和“Indian gooseberry”等[2-4]。余甘子是一种药食同源经济植物资源,是世界卫生组织在全世界推广种植的三种保健植物之一[5],食品专家将余甘子、山楂和猕猴桃列为我国高营养的三大果品[6]。我国余甘子栽培历史悠久,最早的文字记载于东汉时期杨孚所著的《异物志》,距今已近2 000年的历史。《异物志》是我国第一部地区性的物产专著,记载余甘子“盐蒸尤美,可多食”是我国余甘子应用的最早记载。目前,余甘子的相关应用研究主要集中在药理学方面,本文就余甘子的药用价值、主要药用成分和药用功能进行综述,为提升余甘子的医药保健开发和创新利用提供科学依据。
1 余甘子的药用价值
据统计,世界上约有17个国家的传统药物中应用余甘子,在我国民族民间药[7](藏族、彝族、傣族、苗族、白族、纳西族、拉祜族、普米族、佤族、阿昌族、基诺族、布依族、瑶族、壮族,以及蒙古族、维吾尔族等约16个)中多用于治疗感冒、咳嗽、喉痛、腹泻、消化不良、解热消炎、生津润肺、皮肤湿疹、水火烫伤等证。自1977年以来余甘子被载入各版的《中华人民共和国药典》[8]载有:清热凉血,消食健胃,生津止咳,可用于血热血瘀,消化不良,腹胀,咳嗽,喉痛,口干等病症[9],并规定药材标准品为没食子酸,干燥品的没食子酸含量不得低于1.2%。中医学认为,余甘子苦,酸,甘,涩,微寒,归胃和肺经;公元659年唐代苏敬《新修本草》(《唐本草》),是中国第一部由政府颁布的药典,也是世界上最早的药典记载:“庵摩勒,味苦、甘,寒,无毒。主风虚热气”,书中认为印度传入的庵摩勒与我国余甘子为同一物种,表明我国和印度均为余甘子原产国,通过北方丝绸之路和南方海上贸易相互传播。李时珍的《本草纲目》(1518-1593年)在历数古代本草中对庵摩勒的记载及应用后总结:“庵摩勒……主丹石伤肺,上气咳嗽。久服,轻身延年长生”[10]。
现代医学证明余甘子的根、茎、叶、果实和种子均富含多种生物活性物质,包括有机酸、萜类、类黄酮、多糖、鞣质、生物碱、植物甾醇、氨基酸和维生素等[11];具有抗氧化[12-13]、抗癌[14-18]、抗衰老[19-20]、降胆固醇、抗糖尿病、免疫调节[21]、抗病毒[22-23]、抗血脂异常[24]、抗细胞凋亡[25]、解热、镇痛、抗炎[26]、肝保护[27-28]、心脏保护、抗诱变、抗菌特性[29]和抗腹泻[30-31]等。余甘子果实富含高稳定性的维生素C[32]、对N-亚硝基化合物的高度阻断性的抗癌效能、超氧化物歧化酶类似物的耐贮藏、耐热和小分子透皮性所带来的抗氧化、抗衰老特性在果蔬中实属罕见[33];此外,余甘子因其植株根系发达,萌发力强,耐贫瘠,耐盐碱,耐干旱,适应能力强,是荒山绿化,水土保持的先锋树种[34-35]。这些独特性质为它在医药、食品、保健品、化妆品和环境保护等领域的应用展示了广阔产业前景。
2余甘子的药用成分
余甘子植株的多个器官均可入药,富含多种药用成分:余甘子种子中含有大量的亚油酸、亚麻酸、硬脂酸、棕榈酸、肉豆蔻酸、维生素E[36]、油酸、d-肌醇、d-果糖和d-葡萄糖等物质[37];果实、叶片和树皮均含有丰富的单宁;根中含有丰富的鞣酸和羽扇豆醇[38-39];果实维生素C含量超过柠檬、柑橘等水果,与毛花猕猴桃的含量相当,还含有多种维生素,包括烟酸、胡萝卜素、核黄素和硫胺素等[40];叶中含有鞣花酸、没食子酸、芦丁、山奈酚、山奈酚-3-O-葡萄糖苷、黄腐酸、大蒜单宁、磷酸、精油、油酸、硬脂酸、棕榈酸、维生素E[41]、维生素A和棕榈酸酯等;余甘子的树皮中含有原花青素、单宁酸和白扁桃叶霉素;根部含有鞣花酸、豆酚、余甘酸和余甘酮A等[42-43]。余甘子植株不同部位的主要药用成分不同,当前文献主要关于其果实的活性成分研究。
余甘子果实的有机提取液可得到没食子酸、槲皮素、油柑酸A、油柑酸B[44]、无色飞燕草素、诃子勒酸[45]、老鹳草素[46]、山奈酚-3-O-葡萄糖甙、鞣云实精、3-乙基-没食子酸、3,6-二-O-没食子酰基-β-D-葡萄糖、原诃子酸、余甘子酸、余甘子酚、1-O-没食子酰基-β-D-葡萄糖、诃子酸、诃黎酸、1,6-二-O-没食子酰基-β-D-葡萄糖[47]、槲皮素-3-O-葡萄糖甙、isostrictiniin、谷甾醇[48]、月桂酸、珠子草素、没食子酸甲酯[49]和叶下珠素[50]等。Habib-Ur-Rehman等[51]从余甘子果实中分离出 2 种新型黄酮单体,为山奈酚-3-O-α-L-(6''-甲基)-鼠李糖和山奈酚-3-O-α-L-(6''-乙基)-鼠李糖。
3 余甘子的药用功能
3.1抗氧化功能
余甘子果实中含有丰富的自由基清除剂,如白藜芦醇、没食子酸、鞣酸[52]、木酚素、槲皮素、染料木素、花青素、橙皮素、山奈酚、超氧化物歧化酶、维生素C、多糖[53-54]、单宁和有机酸等植物化学成分,具有较强抗氧化能力[55]。余甘子提取液显著提升中老年红细胞的超氧化物歧化酶活性,降低过氧化脂质含量[56],可清除新陈代谢产生的羟和超氧自由基含量[57],此外,余甘子多糖也具有清除超氧自由基的作用。余甘子中的多酚类物质、单宁和有机酸可以显著降低小鼠血液中丙二醛水平。余甘子干果的甲醇提取物所含鞣云实素和老鹳草素等活性成分可有效清除NO ·自由基[49]。余甘子中富含黄酮类物质,该类物质可增强小鼠血液中内源性抗氧化剂过氧化氢酶、超氧化物歧化酶、谷胱甘肽过氧化物酶和谷胱甘肽还原酶等的活力,同时降低过氧化脂质水平[58],保护细胞抵御氧化应激反应[59]。余甘子可以通过提高血清中诱导性T细胞、抑制性T细胞、免疫球蛋白M、免疫球蛋白G等的水平以及血清中白蛋白和球蛋白水平,提高免疫调节系统的有效性[60]。此外,余甘子的叶、根和树皮均被证明有较强的抗氧化能力[61]。余甘子果实维生素C具有高度稳定性[32],超氧化物歧化酶类似物具有耐贮藏、耐热和小分子透皮性[33],且富含多种自由基清除剂和内源性抗氧化剂,可有效增强机体的抗氧化功能、抑制自由基的产生及清除过量的自由基,可在药品、食品和化妆品开发等领域发挥巨大作用。
3.2抗糖尿病功能
世界卫生组织预测,到2025年糖尿病患者有可能达到3亿或更多,开发一种效果显著且无毒副作用[62]的抗糖尿病药物尤为重要[63],余甘子具有很强的开发潜力[64-65]。研究表明,余甘子是一种有效降低血糖的药物[66],余甘子含有大量的单宁类物质,该类物质通过增加对外周组织的胰岛素敏感性来防止脂肪形成和增加葡萄糖摄取有效物质,从而降低血糖[67]。此外,余甘子的降血糖机制还有抑制消化酶的产生,刺激糖原储存,激活胰岛素信号通路,抑制糖基化终产物[68]等。余甘子提取液可抑制大鼠血液α-糖苷酶活性,效果优于降糖药物阿卡波糖[69]。
3.3 降血脂及抗动脉粥样硬化作用
高脂血症和氧化应激是动脉粥样硬化和心脑血管疾病发展的主要危险因素[70]。在多个国家的药物体系中,余甘子是有效防止动脉粥样硬化和降血脂的天然药物,且无毒副作用[71]。余甘子果实中的黄酮组分可抑制肝脏β-羟-β-甲基戊二酸单酰辅酶A还原酶的活性,有效降低血脂水平[72]。余甘子粉末提取物中的黄酮类化合物通过抑制3-羟基-3-甲基戊二酸单酰辅酶A还原酶活性,同时提高血浆卵磷脂胆固醇酰基转移酶(LCAT)活性,发挥降血脂作用[73]。
3.4 抗肝损伤作用
二十世纪八十年代,Antarkar等[74]已报道余甘子可用于多种保肝药物。Ghosal等[75]认为余甘子保肝作用是单宁水解物油柑酸A和油柑酸B抗氧化作用的结果。余甘子的乙醇提取液能降低甲状腺大鼠肝脏过氧化脂质水平,提高超氧化物歧化酶和过氧化氢酶活力,防止肝脂肪过氧化[76]。余甘子果实的水提取液可有效降低小鼠肝细胞过氧化脂质含量,缓解急性和慢性肝中毒症状,降低肝细胞的过氧化脂质、谷丙转氨酶和碱性磷酸脂酶[77]的水平,防止肝脂肪变性和肝纤维化[78]。
3.5 抑制病原微生物及抗炎作用
余甘子水提液具有抑制沙门氏菌的作用[79],可治疗肠道疾病,对引起皮炎的真菌也有较强的抑制作用。余甘子可以促进支气管髓鞘的黏液分泌,起到镇咳效果[80]。侯海燕[81]从余甘子干燥果实的乙醇提取物中,分离鉴定到多种抗乙肝病毒(HBV)化合物,鉴定为鞣花酸、β-香树脂酮、β-胡萝卜苷、没食子酸、β-谷甾醇、杜英素、双没食子酸、粘酸-1-甲酯-6-乙酸、粘酸二甲酯-2-O-没食子酸等。el-Mekkawy等[82]从余甘子果实甲醇提取物中分离到抑制滋病毒(HIV-I-RT)的6种化合物(核实木素A、1,6-二-O-没食子酰基-β-D-葡萄糖、双没食子酸、山奈酚-3-O-糖甙、槲皮素-3-O-糖甙和1-O-没食子酰基-β-D-葡萄糖)。余甘子果实中活性成分异柯里拉京不仅抑制病毒DNA的复制,还可灭活病毒[83],多糖成分可抑菌[84]。余甘子含有丰富的总黄酮类化合物,表现出显著抗甲型流感病毒感染效果[85]。余甘子提取液能抑制引起炎症的病原微生物的DNA和转录因子(NF-k B/DNA)交互作用,从而抑制病原微生物基因的转录[86]。氮氧化物(NO)过量生产可导致病理紊乱或异常,如炎症、心血管损伤等,余甘子提取物可抑制NO的产生,避免巨噬细胞和环氧酶(COX-2)过量产生,表现出较强的抗炎活性[87]。
3.6抗诱变、致畸和抗肿瘤作用
余甘子可“解金石毒[10]”,其提取物对铝、铅、砷、镍引起的细胞中毒和染色体畸形有显著抑制效果[88-90];余甘子丙酮提取物对诱变剂的致突性有显著的抑制作用[91]。Sairam等[92]研究表明余甘子果实的单宁水解物可有效抗诱变和抗肿瘤;余甘子富含的倍半萜内酯类化合物和多酚类化合物有效抑制人宫颈癌细胞、胃癌细胞、黑色素瘤细胞(B16-F10)的增殖[93]。余甘子抑制活性蛋白(AP-1)和宫颈癌致癌基因的转录,表明其在人类乳头瘤病毒诱导的宫颈癌细胞治疗中具有潜在的应用价值[94-95]。余甘子果汁可明显的抑制S-180腹水肿瘤[96]。余甘子提取物对强致癌物质N-亚硝基化合物的合成阻断率高达93%[97],余甘子多糖对肝癌细胞(HepG-2)增殖具有抑制作用[98]。余甘子的树皮具有较强抗细胞增殖作用,与其含有较高的酚酸和类黄酮含量有关[99]。
综上所述,余甘子含有丰富的功能性代谢产物,包括黄酮类、单宁酸、多酚类、抗坏血酸、生物碱、植物甾醇、萜类、有机酸、氨基酸和维生素等,表现出显著的抗氧化、抗炎、抗菌活性、抗糖尿病、抗癌和心脏保护等药理作用,这些独特的性质为余甘子在食品和医药领域的开发提供广阔的应用前景,余甘子深度开发为天然药物、候选药物、保健食品和化妆品的相关研究需更全方位且深入开展,展现其更多的应用价值,为余甘子的高效利用提供保障,从而推动余甘子产业快速且多样化发展。
4 余甘子的其他应用
余甘子是一个极具开发潜力的资源,近年来,除药用外,余甘子的相关产品也逐步实现多元化,如保健果酒、果茶、果冻、果脯、果酱、果汁饮料、余甘冲剂、余甘子冻干粉、速溶余甘乌龙茶、保健胶囊、功能口服液、洗发液和美容化妆品等产品[100]。此外,余甘子保健品的研发越来越多,据报道余甘子可以和一些谷物、豆类等混合为原料,加入淀粉酶生产低黏度的速溶食品作为婴儿的断奶食品[101];余甘子种子油制品,作为一种孕妇和哺乳期的多不饱和脂肪酸补充强化剂[102];余甘子提取物作为一种天然油脂抗氧化剂添加到烘焙饼干中[103];Chaudhuri[104-105]研究发现余甘子的富含低分子量的水解单宁,可提取开发为美白护肤化妆品,特别是余甘子低分子量可水解单宁对黑色素合成的抑制作用[106],且具有生物安全性,无药害反应,具有开发天然产物美白润肤市场的潜力。
5 展望
余甘子的全身都是宝,根、叶、果实、种子均可入药,具有抗氧化、抗癌、抗衰老、降低胆固醇、抗糖尿病、免疫调节、抗病毒、抗血脂异常、抗细胞凋亡、解热、镇痛、抗炎、肝保护、心脏保护、抗诱变、抗菌特性和抗腹泻等多种药理作用,且毒性小、无不良反应,有望将其多个有效部位或成分开发为医药或功能性保健食品,特别是应用余甘子的抗氧化能力、抗糖尿病能力、降血脂及抗动脉粥样硬化、抗肝损伤作用、抑制病原微生物及抗炎作用和抗诱变、抗致畸和抗肿瘤作用开发高附加值医药保健或食品,有巨大的市场发展潜力。目前余甘子相关的研究多数是在体外或动物模型中进行,需要进一步的临床试验来确定基于余甘子的干预措施对人体的有效性和安全性。余甘子相关医药、保健品和食品的开发还处于初级阶段,未发挥余甘子独特的资源特性和药用保健功效,同时表明余甘子在食品和医药保健领域拥有广阔的应用前景,开发潜力巨大,随着现代科技和新技术的不断进步,开发高品质的余甘子新产品、新技术,提高余甘子种质资源的生物利用率和产品附加值,对于天然产物资源的合理利用和地区特色经济的可持续发展有重要意义。
余甘子种质资源分布于东经70°~122°,北纬1°~29°的热带或亚热带地区,分布区域广大,种质资源丰富,表型性状复杂,不同余甘子资源化学成分差异显著。开展61份成熟期余甘子果实非靶代谢组学和主要化学品质分析结果表明,总体689个代谢物的平均变异系数达63.85%,表现丰富的遗传多样性;果实主要化学品质的平均变异系数为28.51%,遗传多样性指数D和信息指数H范围分别为0.977 8~0.983 6和3.96~4.11,多样性数值均较高,多样性丰富[107]。所以要提高余甘子的创新利用效率,需从余甘子遗传多样性评价和品质鉴评入手,明确余甘子不同种质的主要功能或药用成分差异,为余甘子的资源挖掘、质量控制和开发高附加值产品提供理论基础。近年来,国家热带植物种质资源库—余甘子种质资源分库广泛收集保存了我国大部分余甘子地方品种和国内外重要遗传材料,可为余甘子药用成分的遗传多样性研究提供丰富的研究材料。利用圃内保存资源开展药用成分鉴定评价研究,建立余甘子种质资源的整体质量控制体系,对于余甘子的质量控制、品质提升和全产业链升级具有深远意义。
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(责任编辑:许" " 玲)
DOI:10.20023/j.cnki.2095-5774.2024.06.012
收稿日期:2024-10-23
基金项目:国家热带植物种质资源库-余甘子种质资源分库(NTPGRC2024-011);福建省属公益类科研院所基本科研专项
(2022R1028-004);福建省人民政府与中国农业科学院农业高质量发展超越“5511”协同创新工程项目
(XTCXGC2021019-GSS01);福建省农业科学院科技创新平台(CXPT2023004)
作者简介:*为通讯作者,李韬(1969-),男,副研究员,主要从事果树种质资源与分子生物学研究,E-mail: leetao06@163.com。
王建超(1988-),男,助理研究员,博士,主要从事特色果树种质资源保护与生理生化研究,E-mail:447327289@qq.com