Chinese Journal of Animal Nutrition >

2024 , Vol. 36 >Issue 9: 5545 - 5556

DOI: https://doi.org/10.12418/CJAN2024.473

REVIEW

Biological Function of Fructus aurantii Extract and Its Application in Livestock and Poultry Production

  • GAN Haiqing , 1 ,
  • CHEN Fengming 2 ,
  • XIE Renjie 1 ,
  • HUANG Xingguo , 1, *
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  • 1 College of Animal Science and Technology, Hunan Agriculture University, Changsha 410128, China
  • 2 Academician Workstation, Changsha Medical University, Changsha 410219, China
* professor, E-mail:

Received date: 2024-03-15

  Online published: 2024-09-08

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Abstract

Fructus aurantii is a commonly used Chinese herbal medicine in China. The active components of its extract include flavonoids, volatile oils, alkaloids, coumarins and other compounds. It has the effects of anti-oxidation, anti-inflammation, promoting gastrointestinal motility, immune regulation and regulating lipid metabolism. This paper reviewed the biological function of Fructus aurantii extract and its application in livestock and poultry production, aiming to provide reference for the application of Fructus aurantii extract in livestock and poultry breeding.

Key words： Fructus aurantii extract; biological function; livestock and poultry production

Cite this article

GAN Haiqing , CHEN Fengming , XIE Renjie , HUANG Xingguo . Biological Function of Fructus aurantii Extract and Its Application in Livestock and Poultry Production[J]. Chinese Journal of Animal Nutrition, 2024 , 36(9) : 5545 -5556 . DOI: 10.12418/CJAN2024.473

枳壳(Fructus aurantii,FA)为我国常用的中药草,源自芸香科植物酸橙(Citrus aurantium L.)及其栽培变种(如黄皮酸橙、玳玳花、朱栾、塘橙等),主要产自我国四川、江西、湖南、浙江等地区[1]。目前,主流商品主要有“江枳壳”、“湘枳壳”、“川枳壳”、“衢枳壳”、“苏枳壳”、“温枳壳”6种[2]。2020版《中国药典》记载枳壳具有理气宽中、行滞消胀的功效[3],主要归因于枳壳所含的生物活性成分,如黄酮类、挥发油类、生物碱类等。在“饲用禁抗”大背景下,养殖业为解决禁抗后带来的养殖经济效益低下问题,寻找有效的替抗产品已成为研究热点[4]。中草药具有原料来源广、毒副作用小等优势,对动物具有预防疾病和促生长功能,是替抗的主要饲料添加剂品种[5]。枳壳提取物在畜禽养殖中具有巨大的应用潜力。因此,本文就枳壳提取物的生物学功能以及在畜禽生产中的应用进行综述,旨在为其饲用化应用提供参考。

1 枳壳提取物的主要活性成分

枳壳提取物中含有多种天然的生物活性成分,包括黄酮类、挥发油类、生物碱类、香豆素类等化合物,此外还有柠檬苦素类、多糖类、矿物元素、有机酸、氨基酸或多肽类等成分。黄酮类化合物是枳壳的特征成分之一,具有抗氧化、抗炎、促进胃肠运动等药理作用,目前分离得到的类型主要有黄烷酮、多甲氧基黄酮(polymethoxylated flavones,PMFs)、黄酮和黄酮醇[6],如新橙皮苷、柚皮苷、圣草次苷、芸香柚皮苷、橙皮苷、川陈皮素、橘皮素等,其中柚皮苷、新橙皮苷为《中国药典》中规定作为评价枳壳药材质量的指标成分[3,7]。挥发油类成分是枳壳主要的活性成分之一,主要包括柠檬烯、芳樟醇、D-柠檬烯、γ-松油烯等化合物[8⇓⇓-11]。枳壳主要生物碱类化合物为辛弗林、水苏碱,具有降血压功效。Sun等[12]研究发现,枳壳中含有水苏碱(3.04%)、辛弗林(1.25%),水苏碱可作为辛弗林的生物活性平衡剂,具有保护心血管作用。何英杰[13]还从枳壳中分离出氨基苯甲酸、哌啶甲酸、哌啶乙酸、N-甲基酪胺、腺苷、乙酰去甲辛弗林6种生物碱类成分。此外,枳壳提取物还含有香豆素类化合物,包括水合橘皮内酯、橘皮内酯、马尔敏、葡萄内酯、异橙皮内酯、橙皮油内酯、珊瑚菜素、橙皮内酯、花椒毒酚等[14⇓-16]。枳壳中共发现108种化合物,其中黄酮类化合物25种,柠檬苦素类化合物8种,香豆素类化合物2种,挥发性化合物73种,其中含有柠檬素、黄柏酮、黄柏酮酸、米林酸、诺米林等柠檬苦素类化合物[9]。舒尊鹏[17]从枳壳中分离得到枳壳冷浸粗多糖(CALA)、枳壳热提粗多糖(CALB)和枳壳碱提粗多糖(CALC),体外试验显示,CALB抗氧化活性最强,进一步探究其成分鉴定得到CALB-1、CALB-2、CALB-3和CALB-4。另外,赵佳莹[18]用不同提取方法分离得到枳壳冷水提果胶(FWP)-60、枳壳热水提果胶(FHWP)-50、枳壳草酸铵提果胶(FAOP)、枳壳酸提果胶(FCAP)。枳壳还含有多种矿物元素,包括镁、铁、锰、铜、锌、锶、钡、钾、钙等[19-20]。曾令军等[21]研究发现,玳玳果中含有柠檬酸、L-苹果酸、酒石酸、草酸等有机酸,其中柠檬酸含量最高。枳壳提取物还含有一些畜禽必需氨基酸(如赖氨酸、色氨酸、苯丙氨酸、精氨酸、异亮氨酸、组氨酸、亮氨酸)以及非必需氨基酸(如谷氨酰胺、脯氨酸、结氨酸、络氨酸),还有多肽类柑属环肽Ⅲ(柑橘素Ⅲ)、柑属环肽Ⅰ等[16]。枳壳提取物的主要生物活性成分见表1。
表1 枳壳提取物的主要生物活性成分

Table 1 Main bioactive components of Fructus aurantii extract

类型
Types		 主要生物活性成分
Main bioactive components		 参考文献
Reference
黄酮类化合物
Flavonoids compound		 圣草次苷、芸香柚皮苷、柚皮苷、橙皮苷、
新橙皮苷、川陈皮素、橘皮素		 [7]
挥发油类化合物
Volatile oils compound		 柠檬烯、芳樟醇、α-松油醇、γ-萜品烯、
大牛儿烯D、大牛儿烯B、β-月桂烯、
α-毕澄茄醇、萜品烯、月桂烯、D-cadinene、D-柠檬烯、
γ-松油烯、(-)-α-蒎烯、(-)-水芹烯、4-蒈烯、
松油醇、百里香酚、1,6-环葵二烯、2-萘甲醇		 [8⇓⇓-11]
生物碱类化合物
Alkaloids compound		 水苏碱、辛弗林、氨基苯甲酸、哌啶甲酸、
哌啶乙酸、N-甲基酪胺、腺苷、乙酰去甲辛弗林		 [12-13]
香豆素类化合物
Coumarins compound		 水合橘皮内酯、橘皮内酯、马尔敏、葡萄内酯、异橙皮内酯、
橙皮油内酯、珊瑚菜素、橙皮内酯、花椒毒酚、氧化前胡素、
东莨菪内酯、环氧香柠檬素、异橙皮内酯、蛇床子素		 [14⇓-16]
柠檬苦素类化合物
Limonoids compound		 柠檬素、黄柏酮、黄柏酮酸、米林酸、诺米林 [9]
多糖类化合物
Polysaccharides compound		 枳壳热提粗多糖(CALB)-1、CALB-2、CALB-3、CALB-4、
枳壳冷水提果胶-60、枳壳热水提果胶-50、枳壳
草酸铵提果胶、枳壳酸提果胶		 [17-18]
矿物元素Mineral elements 镁、铁、锰、铜、锌、锶、钡、钾、钙 [19]
有机酸Organic acids 柠檬酸、L-苹果酸、酒石酸、草酸 [21]
氨基酸和多肽类化合物
Amino acids and polypeptide compound		 赖氨酸、色氨酸、苯丙氨酸、精氨酸、异亮氨酸、
组氨酸、亮氨酸、谷氨酰胺、脯氨酸、结氨酸、
络氨酸、柑属环肽Ⅲ、柑属环肽Ⅰ		 [16]

2 枳壳提取物的生物学功能

2.1 抗氧化

动物机体易遭受外界不良因素的影响,破坏体内自由基水平恒态,产生大量的活性氧(ROS)和活性氮(RNS),导致氧化应激发生,影响动物机体健康和生长[22]。柚皮苷、新橙皮苷、芸香柚皮苷、橙皮苷、圣草次苷、枸橘苷等为枳壳主要发挥抗氧化活性的有效成分,具有较强的清除自由基能力,还可与多种活性成分协同发挥抗氧化作用[23⇓-25]。方健等[26]研究发现,常山胡柚皮对1,1-二苯基-2-三硝基苯肼(DPPH)自由基、超氧阴离子自由基(O2-·)具有较强的清除能力,柚皮苷和新橙皮苷可能是其发挥抗氧化作用的主要物质基础。研究报道,衢枳壳总黄酮具有强抗氧化性,对2,2'-联氮-双-3-乙基苯并噻唑啉-6-磺酸(ABTS)自由基的清除能力与维生素C相当,同时还具有较强的DPPH自由基清除能力,呈依赖量效关系[27]。动物机体内过量的ROS与细胞成分如不饱和脂肪酸、DNA、蛋白质等相互作用,引发脂质过氧化链式反应,导致细胞损伤[28-29]。枳壳提取物可通过抑制脂质过氧化,增强抗氧化酶活性,缓解氧化应激。体外试验发现,枳壳提取物显著抑制过氧化氢(H2O2)/亚铁离子(Fe2+)诱导的小鼠肝脏脂质过氧化[30]、抑制H2O2诱导的大鼠胰岛β细胞瘤细胞(RIN-m5F)的ROS强度[31]、降低H2O2和脂多糖(LPS)诱导的HaCaT细胞的ROS水平[32],缓解氧化应激损伤。此外,从衢枳壳和胡柚皮分离出来的黄酮类化合物可增强抗氧化酶[超氧化物歧化酶(SOD)、过氧化氢酶(CAT)、谷胱甘肽过氧化物酶(GSH-Px)]活性,降低丙二醛(MDA)含量,间接增强对ROS的清除作用,抑制脂质过氧化,抵抗氧化损伤[33⇓⇓⇓⇓⇓-39]。沉默信息调节因子1(SIRT1)是去乙酰化酶,可通过调控受体γ辅助激活因子-1α(PGC-1α)发挥抗氧化作用缓解应激损伤[40]。陈芝芸等[38]研究发现,富含柚皮苷、新橙皮苷、柚皮芸香苷的胡柚皮黄酮可通过SIRT1去乙酰化PGC-1α改善线粒体功能异常,显著抑制自由基的产生和减少脂肪酸代谢过程中ROS的产生,显著提高肝脏锰超氧化物歧化酶(MnSOD)的表达,缓解氧化应激。核因子E2相关因子2(Nrf2)-胞质阻抑蛋白Kelch样环氧氯丙烷关联蛋白1(Keapl)信号通路调控是参与动物氧化还原体系的重要枢纽,调控相关抗氧化基因和Ⅱ相解毒酶基因表达,参与动物氧化应激反应[41-42]。研究表明,富含黄酮的衢枳壳提取物具有改善2型糖尿病db/db模型小鼠肾脏氧化损伤的作用,机制可能是其可促进小鼠肾脏组织抗氧化基因谷氨酸-半胱氨酸连接酶修饰亚基(GCLM)、谷氨酸-半胱氨酸连接酶催化亚基(GCLC)以及Ⅱ相解毒酶基因依赖还原型辅酶Ⅰ(Ⅱ)醌氧化还原酶1(NQO1) mRNA表达来缓解肾脏氧化损伤[34]。Shi等[39]研究发现,衢枳壳黄酮可诱导Nrf2蛋白表达,并上调抗氧化基因血红素加氧酶-1(HO-1)和Ⅱ相解毒酶基因NQO1、谷胱甘肽S-转移酶(GST)表达,通过介导Nrf2信号通路调控来保护非酒精性脂肪性肝炎小鼠免受氧化应激,缓解肝细胞损伤。综上所述,动物机体在面对氧化应激时,枳壳富含黄酮类化合物且发挥较强的抗氧化作用,其抗氧化途径主要包括:1)直接清除自由基;2)抑制脂质过氧化反应;3)调节抗氧化酶系统;4)参与氧化还原体系。

2.2 抗炎

核转录因子-κB(NF-κB)信号通路的激活会引起多种促炎因子的转录和表达,引发炎症反应[43]。研究表明,枳壳提取物可通过抑制NF-κB的核转录,下调相关促炎因子的表达来发挥抗炎作用[44]。徐霄等[45]在LPS诱导RAW264.7细胞炎症模型中发现,衢枳壳黄酮抑制NF-κB亚基 p65(p65)蛋白表达与入核,抑制NF-κB信号通路,降低肿瘤坏死因子-α(TNF-α)、白细胞介素(IL)-6和IL-1β表达。研究报道,p38丝裂原活化蛋白激酶(p38MAPK)被激活后,可通过调控丝裂原活化蛋白激酶(MAPK)和c-Jun氨基末端激酶(JNK)磷酸化p65来调节NF-κB的转录活性[46]。Toll样受体4(TLR4)与髓样分化因子88(MyD88)相互作用以刺激转化生长因子激酶1(TAK1),从而启动NF-κB和MAPK信号级联[47]。Lan等[48]报道,枳壳黄酮可通过抑制MAPK/NF-κB信号通路改善LPS和D-半乳糖胺诱导小鼠急性肝衰竭肝脏炎症,通过抑制MyD88与TLR4的结合,显著抑制小鼠肝脏中TANK结合激酶1(TBK1)、TAK1和干扰素调节因子3(IRF3)的磷酸化,下调核转录因子-κB抑制物激酶(IKK)、核转录因子抑制蛋白(IκBα)、p65、p38MAPK、JNK和细胞外调节蛋白激酶(ERK)的表达,降低血清IL-6、TNF-α和单核细胞趋化蛋白-1(MCP-1)含量,发挥抗炎活性。类似地,Jiang等[49]在非酒精性脂肪肝大鼠模型中发现,富含芸香柚皮苷、柚皮苷、新橙皮苷等黄酮的胡柚皮可抑制NF-κB和MAPK信号通路降低炎症因子的表达,减轻大鼠肝脏损伤。腺苷酸活化蛋白激酶(AMPK)作为能量代谢调节的关键转录因子,可间接或直接调节NF-κB活性,介导炎症反应[50]。衢枳壳黄酮还可抑制MAPK和NF-κB信号通路以及激活AMPK信号通路发挥抗炎作用,主要表现在显著降低ERK、JNK、p38MAPK、p65和IκBα的磷酸化以及刺激乙酰辅酶A羟化酶(ACC)和腺苷单磷酸活化蛋白激酶α(AMPKα)的相对磷酸化,降低TNF-α、IL-6和IL-1β含量,提高IL-10含量,减轻小鼠急性肺损伤[51]。
枳壳提取物的抗炎机制可能还与抑制神经源性基因同源蛋白(Notch)/NF-κB/IL-1途径有关。研究报道,枳壳类黄酮通过调控Notch/NF-κB/IL-1信号通路的基因表达来抑制结肠炎相关癌症[52]。枳壳挥发油对氧化偶氮甲烷(AOM)联合葡聚糖硫酸钠(DSS)诱导的结肠炎相关癌症小鼠具有显著的治疗效果,显著降低了Notch信号通路介导的相关基因[锯齿状1蛋白(Jagged-1)、Notch-1、Hes-1]、核转录因子-κB1(NF-κB1)、IL-1α、细胞程序性死亡配体1(PD-L1)和细胞程序性死亡受体-1(PD-1)的表达水平,从而起到抗炎作用[53]。
干扰素基因刺激因子(STING)信号通路的激活会促使TBK1和IKK自磷酸化,进而激活IRF3和NF-κB,诱导促炎因子的释放[54]。Wei等[55]研究结果显示,衢枳壳黄酮抑制STING的活化和下游途径TBK1-IRF3和TBK1-NF-κB的信号传导,同时下调平滑肌肌动蛋白(SMA)-α的表达,抑制磷酸化IRF3(p-IRF3)和磷酸化NF-κB(p-NF-κB)入核,显著下调炎性因子和趋化因子的表达,从而缓解博莱霉素诱导的小鼠肺纤维化。
NOD样受体热蛋白结构域相关蛋白3(NLRP3)炎性小体可作为NF-κB下游靶点,活化后的NF-κB也会激活NLRP3炎症小体,增强NLRP3基因的转录活性,从而促进炎症因子的表达[56]。胡柚皮黄酮可抑制NLRP3信号通路,减少肝内炎性细胞的激活和浸润,抑制炎症反应[57]。王思为等[58]报道,枳壳黄酮通过显著抑制核转录因子-κB抑制因子激酶α/β(IKKα/β)和p65蛋白磷酸化以及IκBα蛋白降解,同时显著抑制NLRP3蛋白表达以及半胱氨酸天冬氨酸酶-1(caspase-1)蛋白剪切,减少促炎因子表达,缓解四氯化碳(CCl4)诱导的肝纤维化小鼠肝脏损伤程度,其机制与抑制NF-κB/NLRP3炎性小体介导的炎症信号通路有关。
另外,枳壳黄酮还可调节辅助性T细胞17(Th17)/调节性T细胞(Treg)的平衡,通过促进肝脏组织叉头状转录因子3(FoxP3)mRNA的表达而一定程度抑制Th17特异性的转录调控因子维生素A相关性孤儿受体(ROR)γt mRNA表达,抑制Th17的异常分化,并促进Treg细胞的分化,进而调控相关炎症因子表达[59]。
综上所述,枳壳提取物可通过多种活性成分、多靶点、多途径来发挥抗炎作用,其抗炎作用机制复杂,可调控的信号通路主要涉及到NF-κB、MAPK、AMPK、NLTRP3炎症小体、Notch等信号通路以及调节Th17/Treg的平衡等多种途径和方式影响相关炎症因子表达,减轻机体炎症反应。这也提示枳壳提取物可应用于畜禽生产中,通过多种复杂机制网络缓解动物机体炎症,改善机体健康。

2.3 调节胃肠道功能

枳壳富含黄酮类和挥发油类等化合物,为常用的理气中药,具有较强的调节胃肠道功能的作用[60]。研究发现,枳壳的产地、炮制方法、提取部位等与调节胃肠动力密切相关。衢枳壳对功能性消化不良大鼠的理气作用优于江枳壳、川枳壳与湘枳壳[61]。枳壳生品具有较强烈的燥性,久服易伤阴耗液,经炮制后的枳壳具有显著的减燥作用[62]。研究报道,蜜麸炒枳壳和麸炒枳壳均可显著提高大鼠胃肠Ⅲ型受体酪氨酸激酶(c-kit)和干细胞因子(SCF)mRNA表达,进而影响胃肠道Cajal间质细胞(ICC)的数量和功能,有效缓和枳壳生品所产生的肠道燥性效应[63]。枳壳提取物可通过影响由胃肠道黏膜上内分泌细胞分泌的胃肠道激素,改善胃肠运动障碍。研究发现,不同提取部位(油醚、氯仿、乙酸乙酯、正丁醇、水)枳壳可上调5-羟色胺(5-HT)、P物质(SP)、胃动素(MLT)、胃泌素(GAS)表达和下调血管活性肠肽(VIP)表达,不同程度地促进胃肠运动障碍大鼠胃肠运动,其中乙酸乙酯部位是枳壳的主要活性部位[64-65]。ICC是胃肠道中的起搏器细胞,在胃肠活动中起着至关重要的作用。研究发现,枳壳甲醇提取物可通过5-HT3和5-HT4受体介导的信号传导调控小肠ICC胞外的钠离子(Na+)、钙离子(Ca2+)浓度和Ca2+内流,以及调节MAPK信号通路来降低ICC中起搏器电位的振幅,促进胃肠动力[66]。除此之外,枳壳提取物可双向调节胃肠道运动,Li等[67]从生枳壳和麸炒枳壳分离的主要差异活性物质为橙皮油内酯,体内试验发现,低剂量橙皮油内酯可抑制乙酰胆碱酯酶(AchE)的活性,增加乙酰胆碱的相对含量,进而促进小肠蠕动,高剂量橙皮油内酯则抑制平滑肌收缩和痉挛。He等[68]研究报道,从枳壳乙醇提取物中分离的柚皮苷的代谢产物柚皮素为潜在的多巴胺受体D2(D2R)拮抗剂,调节胃肠道平滑肌。可见,枳壳提取物调节胃肠动力机制主要是通过调节胃肠激素、Cajal间质细胞、胃肠道平滑肌、胃肠道酶活性等方面发挥作用。

2.4 调节免疫

枳壳提取物对免疫细胞的调节是其发挥免疫活性的关键靶点。宋洁等[69]研究发现,以高剂量(1.6 g/kg)的常山胡柚为原料制成的胡柚宝片剂可显著增强自然杀伤(NK)细胞活性。研究报道,枳壳多糖表现出较强的免疫调节活性,可调节MAPK、NF-κB信号通路,调控机体免疫功能。研究表明,代代花粗多糖(CAVAPs)[70]、代代花多糖(CAVAP)-Ⅱ[71]具有较强的免疫增强活性,可调控MAPK和NF-κB信号通路激活巨噬细胞RAW264.7,显著刺激TNF-α和IL-6、诱导型一氧化氮合酶(iNOS)、IL-1β的mRNA表达。此外,Shu等[72]通过人外周血单个核细胞(PBMCs)研究发现,枳壳果胶多糖CALB-4(0、40、80 μg/mL)促进PBMCs增殖且具有显著的剂量依赖性,并通过增加iNOS的表达显著增加一氧化氮(NO)的产生,还通过调节MAPK和p65的核易位来增加pro-IL-1的细胞质浓度。高、中剂量枳壳多糖CALB-1可提高由环磷酰胺诱导的免疫低下模型小鼠的廓清指数(K)和吞噬指数(α)及增强小鼠脾细胞增殖活性,具有体内、外免疫增强作用[73]。赵雪梅等[74]研究发现,从常山胡柚皮分离出的柚皮素、柚皮甙、柠檬苦素这3种活性成分对T、B淋巴细胞的增殖反应有较好的抑制作用,其免疫生物活性部位为氯仿部位。
综上所述,枳壳提取物对于免疫调节的研究主要集中于枳壳多糖,主要通过调节免疫细胞活性来发挥免疫调节功能,其具体作用机制需进一步探究。

2.5 调节脂质代谢

AMPK被认为是调节脂质代谢的关键酶蛋白,通过调控组织中相关基因转录活性来调节脂质代谢[75]。柚皮苷和新橙皮苷是玳玳果黄酮提取物发挥降脂活性的物质基础[76]。研究表明,玳玳果黄酮可激活AMPK信号通路促其磷酸化,抑制下游甾醇调节元件结合蛋白-1c(SREBP-1c)基因表达,进而下调靶基因ACC、脂肪酸合成酶(FAS)表达,抑制脂质从头合成;同时还上调PPARα、肉毒碱棕榈酰基转移酶1(CPT1) mRNA及蛋白表达,促进脂肪酸氧化分解,减少脂质沉积,改善脂质代谢紊乱[77-78]。汪雯等[35]也有类似的报道,结果显示,衢枳壳乙醇提取物激活AMPK信号通路,抑制SREBP-1的转录活性,下调脂质合成基因表达,减少肝脏脂质积累,缓解2型糖尿病小鼠胰岛素抵抗。胡柚皮黄酮干预高脂血症大鼠后可减轻肝脂肪变性,通过积极调控与脂肪分解代谢相关的基因表达,降低甘油三酯含量,通过上调PPARα的表达和促进PPARα、脂蛋白脂肪酶(LpL)、肝脂酶(Lipc)的蛋白表达,促进脂肪酸的氧化分解,调节脂质代谢紊乱的作用[36-37]。
枳壳黄酮还可通过优化肠道菌群组成和结构,减少脂肪组织脂质沉积,有效改善肥胖小鼠脂质代谢紊乱。研究表明,胡柚皮黄酮可提高由高脂饮食诱导的肥胖小鼠肠道菌群丰度和多样性,并增强双歧杆菌属(Bifidobacterium)、艾克曼菌属(Akkermansia)及产短链脂肪酸布劳特氏菌属(Blautia)等有益菌相对丰度,改善肠道菌群,促进细菌生成短链脂肪酸,调节肠道屏障,有效改善肥胖引起的代谢紊乱[79]。
最近一项研究报道,枳壳川陈皮素、咖啡因、柚皮苷可通过不同的方式减少巨噬细胞脂质蓄积,抑制泡沫细胞形成,改善脂质代谢紊乱。Hao等[80]研究发现,川陈皮素减少胆固醇摄取,增强胆固醇外排,主要调节三磷酸腺苷结合盒转运蛋白A1(ABCA1)、三磷酸腺苷结合盒转运蛋白G1(ABCG1)和A1类清道夫受体(SRA1)的表达;咖啡因主要通过上调ABCA1和ABCG1的表达来促进胆固醇外流;柚皮苷有效地降低人类白细胞分化抗原36(CD36)和SRA1的表达,阻断胆固醇摄取。
综上所述,枳壳提取物可以改善动物机体脂质代谢,其机制可能是通过调控脂质氧化分解相关酶活性和脂质合成相关基因及信号通路调控脂质沉积,或通过调节肠道菌群组成和结构调控脂质代谢。目前,国内外关于枳壳提取物调节脂质代谢的研究主要集中于黄酮类化合物,而关于其他活性成分调控脂质代谢及作用机制研究相对有限,还需进一步研究。

2.6 其他

除以上生物学功能外,枳壳提取物还具有抗菌、抗癌等生物学功能。枳壳精油对单核细胞增生李斯特菌生长具有显著的抑制作用,其机制可能是破坏细胞壁的完整性,改变细胞膜的通透性,从而导致细胞形态发生改变,同时还可降低细菌生物量和细胞活性以抑制生物膜的形成[81]。高亮等[82]研究发现,衢枳壳黄酮能够显著抑制人肝癌细胞HepG2细胞的活力,并降低HepG2细胞的线粒体膜电位,促进细胞凋亡。

3 枳壳在畜禽生产中的应用

曲枳散是由山楂、枳壳、神曲等配伍的中草药,邹璐[83]研究发现,饲喂3%曲枳散显著提高断奶仔猪胃蛋白酶、十二指肠蔗糖酶和麦芽糖酶活性,同时提高仔猪回肠绒毛高度,提高仔猪对营养物质的吸收能力。王宏军等[84]研究表明,在猪饲粮中添加0.1%、0.3%由六神曲、枳壳、当归等配制的中草药添加剂,结果显示均显著提高荷包猪平均日增重和瘦肉率,增加肌内脂肪含量,显著降低料重比、失水率及背标厚度,改善猪肉品质。武晋孝等[85]将由含枳壳配制的中草药饲喂肉鸡,结果发现显著提高了血清和肝脏中SOD、GSH-Px活性,并降低MDA含量,提高机体抗氧化性能。徐海滨等[86]研究结果显示,饲喂益气健脾方剂(黄芪60 g/头+升麻60 g/头+白术24 g/头+枳壳60 g/头)显著提高奶牛平均日增重,同时显著提高血清IL-2含量和降低TNF-α含量。林萌萌等[87]将厚朴、枳壳、山楂等14味中草药组成方剂作为饲料添加剂饲喂肉羊,结果表明,0.8%中草药含量的饲料添加剂提高了肉羊平均采食量和平均日增重,提高生长性能。可见,枳壳与其他中草药饲料添加剂组成的复方中草药添加剂可有效改善畜禽肠道形态,增强消化酶活性,提高抗氧化能力,改善畜禽生长性能和肉品质。但目前枳壳在畜禽生产中的应用主要以复方中草药添加剂的方式饲喂,单一的枳壳或枳壳提取物在畜禽生产的应用效果研究较少。

4 小结

枳壳提取物含有多种生物活性成分,具有抗氧化、抗炎、促进胃肠动力、调节脂质代谢、增强免疫力等功效,可通过多靶点、多途径发挥其功能,还可多靶点互作来发挥作用。枳壳与其他中草药饲料添加剂组成的复方中草药添加剂可有效改善畜禽肠道形态,增强消化酶活性,提高抗氧化能力,改善畜禽生长性能和肉品质。目前,针对枳壳提取物的研究主要集中在细胞和大鼠或小鼠上,而枳壳在畜禽生产中的应用主要以复方中草药添加剂的方式饲喂,单一的枳壳或枳壳提取物在畜禽生产中的应用效果研究较少。未来应深入开发枳壳提取物作为饲料添加剂资源,明确其在畜禽不同生长阶段的最佳添加剂量和作用效果,推动绿色生态养殖发展。

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