Chinese Journal of Animal Nutrition >

2024 , Vol. 36 >Issue 1: 74 - 85

DOI: https://doi.org/10.12418/CJAN2024.008

REVIEW

Effects of Magnolol on Animal Intestinal Mucosal Barrier Function and Its Regulatory Mechanisms

  • YANG Kang ,
  • MEI Huadi ,
  • MA Xianyong ,
  • YU Miao , *
Expand
  • Guangdong Engineering and Technology Research Center for Quality and Safety Control and Evaluation of Livestock and Poultry Meat, Guangdong Key Laboratory of Livestock and Poultry Breeding and Nutrition, State Key Laboratory of Swine and Poultry Breeding Industry, South China Key Laboratory of Animal Nutrition and Feed, Ministry of Agriculture, Institute of Animal Science, Guangdong Academy of Agricultural Sciences, Guangzhou 510640, China
* associate professor, E-mail:

Received date: 2023-07-18

  Online published: 2024-01-12

Fold

Abstract

The intestinal mucosa barrier is an important site for interactions between the internal body environment and external environment, which can prevent the invasion of pathogenic microorganisms, toxic and harmful substances, and its integrity is critical for animal health. Magnolol is one of the active ingredients extracted from the traditional Chinese medicine Magnolia officinalis, which has the function of anti-cancer, anti-bacterial, anti-inflammatory and anti-oxidant. Recent studies have demonstrated that magnolol can maintain the integrity of intestinal barrier function via regulating the gut microbiota composition, improving the production of short-chain fatty acids and intestinal alkaline phosphatase, inhibiting the apoptosis of intestinal cells, up-regulating tight junction proteins expression in intestinal epithelial cells, modulating cytokine secretion and enhancing the activity of antioxidant enzymes. This article mainly reviewed the effects and regulatory mechanism of magnolol on the intestinal mucosal barrier function, to provide a reference for its rational application in livestock and poultry production.

Key words： magnolol; absorption and metabolism; intestinal mucosal barrier; regulatory mechanism

Cite this article

YANG Kang , MEI Huadi , MA Xianyong , YU Miao . Effects of Magnolol on Animal Intestinal Mucosal Barrier Function and Its Regulatory Mechanisms[J]. Chinese Journal of Animal Nutrition, 2024 , 36(1) : 74 -85 . DOI: 10.12418/CJAN2024.008

肠道是动物机体最重要的消化吸收场所,亦是机体最大的免疫器官。肠道黏膜屏障主要由正常微生物及其代谢物、肠上皮细胞和免疫细胞组成,通常可根据功能分为微生物屏障、化学屏障、机械屏障和免疫屏障[1]。肠道黏膜屏障的损伤不仅会影响动物机体对营养物质的吸收,而且极易导致多种肠道疾病的发生,影响动物的生长潜力[2]。因此,寻求可有效维护肠道黏膜屏障功能的策略对动物肠道健康及其生长发育至关重要。
厚朴酚是从中草药厚朴中提取出的活性物质,也是厚朴发挥药效的主要成分之一,具有抗炎[3]、抗氧化[4]、抗癌[5]和抗菌[6]等多种生理功能,被视为是天然、无公害、无毒副作用的抗生素替代品,在动物生产中具有较好的应用前景。近年来研究发现,厚朴酚可通过维护肠道形态、提高肠道免疫力、维系肠道微生态稳定和降低肠道内pH等途径,增强肠道黏膜屏障功能的完整性。本文主要就厚朴酚对动物肠道黏膜屏障功能的影响及其调控机制进行综述,以期为厚朴酚在畜禽生产中的应用提供参考。

1 厚朴酚的来源、提取工艺及吸收与代谢

1.1 厚朴酚的来源及提取工艺

厚朴酚,又名5'-二烯丙基-2,2'-二羟基联苯,是一种多酚联苯化合物,主要从中草药厚朴的茎皮中提取[7]。厚朴酚于1930年首次从中国厚朴的树皮中分离,之后研究发现,日本白玉兰、韩国白木兰等植物中也可提取出厚朴酚[8⇓⇓-11]。当前,厚朴酚的提取方法主要包括高压热水提取法、酶解法、超声波辅助提取法、超临界二氧化碳提取法、溶剂提取法等,各种提取方法的优缺点和提取率的比较见表1。高压热水法具有用时短、提取率高的特点,但随着压强增加,活性成分容易发生改变[12]。酶解法的提取率较高,谭洋等[13]采用酶解提取法提取厚朴酚,结果表明,经过酶解处理后的厚朴,水回流提取厚朴酚的转移率为88.60%,并且复合酶处理的提取率要高于单一酶处理。但由于酶的价格较高,同时对酶解时间十分苛刻,因此在生产中未得到广泛应用。超声波辅助提取法可缩短厚朴酚的提取时间,提高提取率和减少生产成本。孔玲等[14]研究发现,在超声时间为20 min、乙醇浓度为90%、温度为60 ℃、浸泡时间为50 min的条件下,厚朴中厚朴酚的提取率最高。超临界二氧化碳提取法的重复性较好、工艺稳定可行,且提取物具有良好的抗氧化活性,但其设备投入较高,操作较复杂,杂质含量较高[15]。溶剂提取法在生产中常用的溶剂为乙醇,厚朴酚提取率与乙醇浓度、乙醇用量、提取时间、回流次数等因素相关,该方法操作简单稳定,但对溶剂的浪费较大,并需要加热[16]。鉴于不同提取方法均有其优点与缺点,在实际生产中,应根据具体条件选择适宜的提取方法。
表1 厚朴酚的主要提取工艺

Table 1 Main extraction crafts of magnolol

提取方法
Extraction methods		 优缺点
Advantages and disadvantages		 提取率
Extraction yield/%		 参考文献
Reference
高压热水提取法
High pressure hot water
extraction method		 优点:能在短时间内提取到较高提取率的厚朴酚
缺点:随着压强的增加,提取成分可能发生化学变化		 22.86 [12]
酶解法
Enzymatic hydrolysis method		 优点:酶制剂反应条件温和,提取率高,安全环保
缺点:酶的价格较高,对酶解时间把控要求十分严格		 88.60 [13]
超声波辅助提取法
Ultrasonic assisted
extraction method		 优点:在溶剂提取法的基础上提高提取率,
可缩短厚朴酚的提取时间
缺点:成本高,提取物杂质含量较高		 65.21 [17]
超临界二氧化碳提取法
Supercritical carbon dioxide
extraction method		 优点:重复性较好,工艺稳定可行,且提取物
具有良好的抗氧化活性
缺点:提取率低,操作较复杂,难以工业化		 39.37 [15]
溶剂提取法
Solvent extraction method		 优点:工艺简单,提取条件易于工业化
缺点:溶剂的浪费较大,提取率受乙醇浓度、提取时间和
提取次数等因素的影响		 75.60 [16]

1.2 厚朴酚的吸收与代谢

厚朴酚是一类亲脂性的多酚,有很强的脂溶性,以类脂途径在大鼠胃肠道不同部位被吸收[18]。同时,由于厚朴酚广泛的首过代谢和较差的水溶性,其口服生物利用度仅为5%[19]。采用固体分散体、固体脂质纳米颗粒、磷脂复合物、脂质体、纳米颗粒、β-环糊精包合物、乳剂、混合胶束、锆基有机金属骨架等递送系统可有效提高厚朴酚的生物学利用度[20⇓⇓⇓⇓⇓-26]。
厚朴酚经口服后,一部分通过被动扩散进入肠上皮细胞,经过代谢生成葡萄糖醛酸化和硫酸化的厚朴酚,然后厚朴酚及上述代谢物可随着血液循环系统到达肝脏、肾脏、脑、肺脏、心脏等器官或组织中;在体内未被利用的部分进入肾脏随尿液排出或经肠肝循环进入肠道再次代谢或排出;在肝脏中的厚朴酚主要以厚朴酚和葡萄糖醛酸化厚朴酚形式存在,然后以厚朴酚-2-O-葡萄糖苷酸形式分泌到胆汁中,随粪便排出;另一部分未被吸收的厚朴酚及经过肝脏代谢后的厚朴酚衍生物进入后肠,在细菌和酶的作用下生成四氢厚朴酚、异厚朴酚和其他联苯化合物等[19,27-28]。

2 厚朴酚对肠道黏膜屏障功能的影响

肠道黏膜屏障可防止肠腔内有害物质透过肠道黏膜吸收进入动物体内,当其受损时会引起肠道细菌感染、炎症和自身免疫性疾病的发生,因此维持肠道黏膜屏障结构和功能的完整性有助于保持动物机体健康[29]。厚朴酚对肠道黏膜屏障的影响机制主要是促进畜禽肠道发育,提高抵抗力和保护畜禽肠道免受外源性病原微生物的刺激等,从而发挥其对肠道黏膜屏障的保护作用。

2.1 厚朴酚对肠道微生物屏障的影响

肠道微生物屏障主要由肠道菌群在肠道黏膜上皮定植形成的菌膜屏障组成[30]。各个菌群之间相互依存、相互制约形成的肠道微生物稳态系统,为肠道提供了第1道屏障。厚朴酚可通过调节肠道菌群的组成,抑制有害菌生长,进而维持肠道微生态的稳定,保护机体免受有害菌感染。

2.1.1 优化肠道菌群

厚朴酚可作为一种肠道微生物调节剂,通过提高肠道有益菌的比例,减少致病菌的比例,从而维持肠道微生态的稳定。以小鼠为对象的研究发现,厚朴酚可通过降低致病菌变形杆菌门(Protebacteria)的相对丰度,提高有益菌拟杆菌门(Bacteroidetes)的相对丰度,进而逆转奥沙利铂引起的肠道菌群失调[31]。在断奶仔猪中的研究显示,饲粮中添加厚朴酚可通过提高粪便中有益菌瘤胃球菌属(Ruminococcus)、双歧杆菌属(Bifidobacterium)和乳杆菌属(Lactobacillus)数量,降低粪便大肠杆菌数量,继而维护肠道微生物屏障[32]。
在肉鸡饲粮中添加厚朴酚51 d后,发现盲肠中粪杆菌属(Faecalibacterium)和粪芽孢杆菌属(Coprobacillus)的相对丰度分别提高和降低[33]。Faecalibacterium的主要代谢产物是丁酸[34-35]。丁酸作为微生物代谢物,具有广泛的益生作用,如为肠上皮细胞供能和改善畜禽生长性能等[36-37]。在受鸡白痢沙门氏菌(Salmonella pullorum)感染肉鸡的研究中发现,厚朴酚可降低回肠链球菌属(Streptococcus)和蓝细菌属(Cyanobacteria)的相对丰度,提高回肠Lactobacillus的相对丰度,并增加回肠微生物α多样性和β多样性,表明厚朴酚可提高肠道微生物丰富度,维护肠道微生态平衡[38]。

2.1.2 对病原菌的抑菌活性

厚朴酚具有独特的生理活性,对不同的致病菌均表现出良好的抗菌活性。体外研究发现,厚朴酚可通过减少细菌黏附、抑制细菌自溶、减少毒力因子的产生、破坏菌体细胞壁和生物膜合成等途径抑制普通变形杆菌(Proteus vulgaris)、白色念珠菌(Candida albicans)、变形链球菌(Streptococcus mutans)、金黄色葡萄球菌(Staphylococcus aureus)、耐甲氧西林金黄色葡萄球菌(methicillin-resistant Staphylococcus aureus,MRSA)、交链孢菌(Alternaria alternata)和猪链球菌(Streptococcus suis)等潜在致病菌的增殖和感染[39⇓⇓⇓⇓⇓⇓⇓⇓-48]。一方面,厚朴酚可通过抑制生物膜形成,以发挥对Candida albicans和Staphylococcus aureus的抑制作用[39⇓⇓-42];另一方面,厚朴酚可通过抑制细菌毒力相关因子的表达,来降低Staphylococcus aureus和Streptococcus mutans的致病性,继而发挥抗菌作用[43-44]。同时,厚朴酚还可通过破坏菌体细胞壁或细胞膜的结构,从而对Proteus vulgaris、Streptococcus suis和Alternaria alternata起到抗菌功效[45⇓-47]。此外,厚朴酚还可通过抑制细胞壁质酶的活性,下调自溶素(atl)、自溶蛋白(sle1)和细胞因子诱导蛋白A(cidA)等自溶基因的表达,进而抑制Staphylococcus aureus的增殖[43];通过减少Candida albicans的黏附,以发挥其抗菌性能[42];通过抑制MRSA耐药相关基因的表达,继而起到抑制其生长的作用[48]。

2.2 厚朴酚对肠道化学屏障的影响

肠道黏膜上皮细胞分泌的抗菌肽、消化液、黏蛋白、黏液和肠腔内微生物产生的短链脂肪酸等化学物质构成了肠道的化学屏障,它们对维系肠道屏障功能具有重要作用[49⇓-51]。机体摄入厚朴酚后,可促进肠道内短链脂肪酸的合成,增强肠碱性磷酸酶(intestinal alkaline phosphatase,IAP)的活性和血清中抗炎物质的生成,对机体肠道化学屏障功能具有改善作用。

2.2.1 促进短链脂肪酸的合成和增强IAP的活性

短链脂肪酸可增强肠上皮细胞紧密连接(tight junctions,TJs)蛋白表达,并修复受损的肠上皮细胞TJs结构,从而维系良好的肠道屏障功能[52]。其中,乙酸可为肠上皮细胞提供能量,同时具有良好的抗炎和免疫调节作用[53]。据报道,厚朴酚可增加断奶仔猪粪便中乙酸和总短链脂肪酸的含量,表明厚朴酚有利于维护正常肠道黏膜屏障功能[32]。此外,在罗非鱼中的研究显示,厚朴酚还可提高IAP的活性[54],而IAP可通过限制肠源性脂多糖(lipopolysaccharide,LPS)由肠腔易位进入动物机体,进而降低机体发生炎症的风险[55]。

2.2.2 调节血清中化学物质和降低肠道pH

犬尿氨酸和肠道微生物群产生的吲哚衍生色氨酸代谢物作为芳香烃受体的内源配体,可通过抑制机体产生免疫应答,从而减轻肠道炎症反应[56]。Zhao等[57]在葡聚糖硫酸钠(dextran sodium sulfate,DSS)诱导的小鼠结肠炎模型中发现,厚朴酚可通过增加犬尿酸、5-羟基吲哚乙酸、吲哚乙酸、吲哚乳酸和吲哚硫酸等血清色氨酸代谢产物的含量,从而激活结肠潜在芳香烃受体,缓解DSS诱导的结肠炎症。pH是动物消化道内环境的重要指标,pH升高会抑制乳酸杆菌和双歧杆菌等有益菌定植,促进Salmonella pullorum和致病性大肠杆菌等有害菌增殖,并损害消化酶活性,导致肠道微生态环境紊乱和消化能力下降[58-59]。而在最近的研究中发现,厚朴酚可降低断奶仔猪粪便pH,表明厚朴酚对改善肠道化学屏障具有潜在的积极效果[32]。

2.3 厚朴酚对肠道机械屏障的影响

肠道黏膜机械屏障由肠道黏膜上皮细胞及细胞间的TJs组成,它不仅是阻止有害物质入侵肠道黏膜组织的结构基础,也是维持肠道内环境稳态的主要因素[60]。厚朴酚可通过调节TJs蛋白的表达、抑制肠上皮细胞凋亡和促进肠绒毛发育等途径来发挥其保护肠道黏膜机械屏障的作用。

2.3.1 抑制肠上皮细胞凋亡

肠上皮细胞由肠细胞、潘氏细胞和杯状细胞组成,这些细胞构成了一层半渗透屏障,可选择性吸收营养物质,而限制有毒大分子物质通过[61]。正常情况下,肠上皮细胞处于增殖和凋亡的动态平衡之中,而肠道上皮细胞发生大量凋亡则会导致肠道黏膜屏障受损,进而引起多种肠道疾病发生[62-63]。在大鼠中的研究发现,厚朴酚可能通过下调炎性细胞因子的分泌,以减轻产肠毒素大肠杆菌引起的肠上皮细胞凋亡[64];通过降低肠上皮细胞中p21、p27的蛋白表达量,提高E2F转录因子1(E2F1)、细胞周期蛋白依赖性激酶4(CDK4)和细胞周期蛋白D1(CCND1)的蛋白表达量并促进视网膜母细胞瘤蛋白(Rb)的磷酸化,从而抑制热应激诱导的肠上皮细胞凋亡[65],提示厚朴酚可通过减轻肠上皮细胞凋亡,从而起到维系肠道黏膜屏障功能的作用。

2.3.2 促进肠绒毛发育

肠绒毛是反映肠道黏膜屏障功能和完整性最直接的指标[66]。厚朴酚既能促进肠绒毛发育,也能逆转或减轻应激因素对肠绒毛的不利影响。在产蛋后期蛋鸡的研究中发现,随着饲粮中厚朴酚添加剂量的不断提高,其空肠和回肠绒毛高度也呈线性增加[67]。Chen等[38]对感染Salmonella pullorum诱导的肉鸡肠炎模型中发现,厚朴酚可逆转Salmonella pullorum对回肠绒毛的不利影响。此外,厚朴酚还可缓解由奥沙利铂引起的结肠绒毛损伤,其机制可能与厚朴酚抑制结肠中炎症细胞因子的产生有关[31]。以上结果表明,厚朴酚可促进肠绒毛发育,从而维护肠道黏膜屏障的完整性。

2.3.3 维护肠上皮细胞TJs结构

肠上皮细胞TJs结构主要由闭合小环蛋白-1(zonula occluden-1,ZO-1)、闭锁蛋白(Occludin)和闭合蛋白(Claudins)等TJs蛋白组成[68]。TJs蛋白磷酸化、分布和表达水平在维持肠道机械屏障功能完整性和调节细胞旁通透性方面起着重要作用[69-70]。而厚朴酚可维护肠道TJs结构,亦可修复受损的TJs结构。在肉鸡和蛋鸡中的研究发现,厚朴酚可通过增加肉仔鸡空肠中Claudin-1的mRNA表达量,增强产蛋后期鸡回肠Claudin-1和Occludin的mRNA表达水平,进而维持肠道机械屏障的完整性[67,71-72]。厚朴酚还可通过提高小鼠回肠Occludin的蛋白表达量及结肠Occludin和ZO-1的蛋白表达量,进而修复奥沙利铂、DSS诱导的小鼠肠道TJs结构损伤[31,73]。此外,厚朴酚还可降低腹泻大鼠血清中二胺氧化酶(diamine oxidase,DAO)活性和D-乳酸(D-lactic acid,DLA)含量[64],而血清中DAO活性和DLA含量是评估肠道黏膜通透性的重要生物学标志物,其活性或含量降低表明厚朴酚可降低大鼠肠道黏膜通透性,这间接反映了厚朴酚对肠道屏障的修复作用[74]。厚朴酚对细胞模型和动物模型TJs的mRNA和蛋白表达的影响见表2。
表2 厚朴酚对肠道TJs mRNA和蛋白表达量的影响

Table 2 Effects of magnolol on mRNA and protein expression level of intestinal TJs

细胞模型
Cell models		 刺激
Stimuli		 浓度
Concentration		 表达量Expression level 参考文献
Reference
mRNA 蛋白Protein
HCT116/SW480 无 2.5、5和10 μmol/L ZO-1和Claudin增加 [75]
肉鸡空肠
Broiler jejunum		 无 100、200和
300 mg/kg		 Claudin-1增加 [71]
肉鸡回肠
Broiler ileum		 Salmonella pullorum 300 mg/kg Claudin-5增加 [38]
蛋鸡回肠
Laying chicken ileum		 无 100、200和
300 mg/kg		 Occludin增加 [67]
蛋鸡回肠
Laying chicken ileum		 无 300 mg/kg Claudin-1增加 [72]
小鼠回肠和结肠
Mouse ileum and colon		 奥沙利铂 75和
300 mg/kg		 Occludin增加 [31]
小鼠结肠
Mouse colon		 葡聚糖硫酸钠 25、50和
100 mg/kg		 Occludin和
ZO-1增加		 [73]

HCT116/SW480:人类结肠癌细胞系 human colon cancer cell line;Salmonella pullorum:鸡白痢沙门氏菌;Claudin:闭合蛋白;Occludin:闭锁蛋白;ZO-1:闭合小环蛋白-1 zonula occluden-1。

综上所述,厚朴酚通过增加TJs的mRNA和蛋白表达量,同时抑制肠上皮细胞的凋亡并促进肠道绒毛发育,从而发挥其保护肠道机械屏障的作用。

2.4 厚朴酚对肠道免疫屏障的影响

病原微生物入侵机体后,会诱导肠道免疫系统分泌白细胞介素、免疫球蛋白和干扰素等免疫因子,引发氧化应激和炎症反应的发生,导致动物肠道屏障的损伤[76-77]。厚朴酚可通过促进肠道产生和释放抗炎因子和抗氧化酶,进而增强动物肠道免疫力,改善肠道免疫屏障。

2.4.1 调节炎症反应

Toll样受体(Toll-like receptor,TLR)属于I型跨膜蛋白,是一组保守的模式识别受体,其可识别病原微生物的细胞膜成分,在调节肠道适应性和先天性免疫中发挥着重要作用[78]。多种外界刺激可激活TLR及其下游的核因子-κB(nuclear factor-κB,NF-κB)信号转导途径,促进肠道免疫细胞产生促炎因子、趋化因子,引发肠道炎症反应[79]。在小鼠中的研究发现,厚朴酚可通过抑制TLR4/NF-κB信号通路,进而抑制空肠、回肠和结肠中白细胞介素-6(interleukin-6,IL-6)、白细胞介素-17(interleukin-17,IL-17)等促炎因子的基因转录或降低其含量,从而缓解肠道的炎症反应[31,64,80-81]。此外,厚朴酚还可降低肉鸡回肠中免疫球蛋白J链(JCHAIN)、血清趋化因子配体19(CCL19)及趋化因子受体7(CCR7)等免疫相关基因的表达,这有助于减弱Salmonella pullorum诱发的肠道免疫反应[38]。

2.4.2 增强抗氧化能力

饮食与环境改变等应激因素会导致活性氧(reactive oxygen species,ROS)过度产生,引起细胞中的脂质和蛋白质过氧化,从而扰乱动物肠上皮细胞的完整性[82]。厚朴酚可增强肠道内抗氧化酶的活性,减少ROS和一氧化氮(NO)的产生,从而缓解肠道氧化应激损伤。在奥沙利铂和LPS诱导的小鼠肠道损伤模型中发现,厚朴酚可通过降低小肠中单核细胞趋化蛋白-1含量及诱导型一氧化氮合酶(inducible nitric oxide synthase,iNOS)和环氧化酶-2活性,同时增加超氧化物歧化酶(superoxide dismutase,SOD)和谷胱甘肽过氧化物酶活性及谷胱甘肽(glutathione,GSH)含量,从而减轻肠道氧化损伤[31,80];在肉鸡中的研究表明,厚朴酚通过提高肉鸡空肠总抗氧化能力、SOD活性和GSH含量,降低肉鸡或蛋鸡小肠中iNOS的mRNA表达量,进而抑制小肠中一氧化氮和丙二醛(malondialdehyde,MDA)的生成,最终维持肠道氧化还原平衡[33,67];此外,厚朴酚还可通过增加罗非鱼肠道中谷胱甘肽还原酶、SOD、过氧化氢酶和过氧化物酶活性,降低MDA和ROS含量,从而增强肠道抗氧化能力,缓解氧化应激[54]。

2.4.3 增强巨噬细胞的吞噬能力

巨噬细胞具有吞噬病原体、呈递抗原、刺激其他免疫细胞以及在炎症反应结束时清除免疫细胞等多种免疫功能,与中性粒细胞等构成机体的第2道免疫防线[83]。吞噬作用是巨噬细胞发挥免疫功能的重要手段,其可诱导细胞因子释放,促进免疫细胞对病原体的炎症反应,对宿主自身免疫和代谢性疾病的发展至关重要[84]。厚朴酚可剂量依赖性地增强U937巨噬细胞的吞噬能力,并对T细胞增殖有促进作用,提示厚朴酚可增强机体的免疫功能,进而可能增强肠道黏膜的免疫能力,但对动物肠道的具体作用机制还有待进一步研究[85]。
由此可见,厚朴酚具有良好的免疫调节和抗氧化活性,一方面通过减少炎症因子与ROS的产生和释放,另一方面通过增强巨噬细胞的吞噬、刺激T细胞的增殖等增强免疫力,最终改善肠道免疫屏障功能。

3 小结

在畜禽生产中,肠道黏膜屏障功能损伤常常伴随着多种肠道疾病的发生。在后抗生素时代,寻求一种有效维护肠道黏膜屏障功能的措施已成为畜禽养殖中关注的重点。本文综述了厚朴酚的来源、提取工艺及吸收与代谢,并重点总结了厚朴酚对肠道黏膜微生物屏障、化学屏障、机械屏障和免疫屏障的调控作用(图1)。然而,现阶段厚朴酚的研究还存在一些问题需要解决:1)厚朴酚在猪和反刍动物生产中的应用研究还相对有限;2)厚朴酚对动物肠道黏膜屏障功能的作用机理不够明确;3)厚朴酚在畜禽中的适宜添加量尚不清楚。因此,今后的研究可通过在畜禽上展开更多体内和体外试验,阐明厚朴酚调控畜禽肠道屏障功能的具体作用机制和信号通路,确定厚朴酚对不同动物的适宜添加量,研究厚朴酚与肠道微生物之间的互作关系,为厚朴酚进一步开发和利用提供科学依据。
图1 厚朴酚调节肠道黏膜屏障的途径

Magnolol:厚朴酚;Microbial barrier:生物屏障;Chemical barrier:化学屏障;Physical barrier:物理屏障;Immune barrier:免疫屏障;Faecalibacterium:粪杆菌属;Protebacteria:变形杆菌门;Coprobacillus:芽孢杆菌属;Bacteroidetes:拟杆菌门;AhR:芳香烃受体 aromatic hydrocarbon receptor;SCFAs:短链脂肪酸 short chain fatty acids;IAP:肠碱性磷酸酶 intestinal alkaline phosphatase;IL-6:白细胞介素-6 interleukin-6;IL-17:白细胞介素-17 interleukin-17;NF-κB:核因子-κB nuclear factor-κB;TLR4:Toll样受体4 Toll-like receptor 4;GSH:谷胱甘肽 glutathione;NO:一氧化氮 nitric oxide;MDA:丙二醛 malondialdehyde;SOD:超氧化物歧化酶 superoxide dismutase;iNOS:诱导型一氧化氮合酶 inducible nitric oxide synthase;Oxidative stress:氧化应激;Inflammation:炎症;Permeability:渗透性;Intestinal microbiota:肠道菌群;Damage:损伤;Candida albicans:白色念珠菌;Proteus vulgaris:普通变形杆菌;Staphylococcus aureus:金黄色葡萄球菌;Streptococcus mutans:变形链球菌;B cell:B细胞;T cell:T细胞;IgA:免疫球蛋白A immunoglobulin A;IgM:免疫球蛋白M immunoglobulin M;Macrophage:巨噬细胞;TJ:紧密连接tight junction。

Fig.1 Regulatory pathway of magnolol on intestinal mucosal barrier

References

Publishing order | Descend order by publishing year | Descend order by cited within
[1]
GUSTAFSSON J K, JOHANSSON M E V. The role of goblet cells and mucus in intestinal homeostasis[J]. Nature Reviews Gastroenterology & Hepatology, 2022, 19(12):785-803.

[2]
温家姝, 胡彩虹, 崔世豪, 等. 微生态制剂对家禽肠道健康影响的研究进展[J]. 动物营养学报, 2021, 33(4):1851-1858.

DOI

WEN J S, HU C H, CUI S H, et al. Research progress on effects of microecological agents on intestinal health of poultry[J]. Chinese Journal of Animal Nutrition, 2021, 33(4):1851-1858. (in Chinese)

[3]
TIAN Y, FENG H H, HAN L, et al. Magnolol alleviates inflammatory responses and lipid accumulation by AMP-activated protein kinase-dependent peroxisome proliferator-activated receptor α activation[J]. Frontiers in Immunology, 2018, 9:147.

DOI PMID

[4]
SUBRAMANIYAN S, ALUGOJU P, SJ S, et al. Magnolol protects Saccharomyces cerevisiae antioxidant-deficient mutants from oxidative stress and extends yeast chronological life span[J]. FEMS Microbiology Letters, 2019, 366(8):fnz065.

DOI

[5]
PENG C Y, YU C C, HUANG C C, et al. Magnolol inhibits cancer stemness and IL-6/Stat3 signaling in oral carcinomas[J]. Journal of the Formosan Medical Association, 2022,121 (Pt.1):51-57.

[6]
MO F X, HU X F, DING Y, et al. Naturally produced magnolol can significantly damage the plasma membrane of Rhizoctonia solani[J]. Pesticide Biochemistry and Physiology, 2021, 178:104942.

DOI

[7]
田琦, 高凤仙, 马现永, 等. 厚朴酚的生理功能及其在家禽生产中的应用[J]. 动物营养学报, 2022, 34(4):2114-2122.

DOI

TIAN Q, GAO F X, MA X Y, et al. Biological function of magnolol and its application in poultry production[J]. Chinese Journal of Animal Nutrition, 2022, 34(4):2114-2122. (in Chinese)

[8]
CHOI N H, CHOI G J, MIN B S, et al. Effects of neolignans from the stem bark of Magnolia obovata on plant pathogenic fungi[J]. Journal of Applied Microbiology, 2009, 106(6):2057-2063.

DOI

[9]
MIN B S. Anti-complement activity of phenolic compounds from the stem bark of Magnolia obovata[J]. Natural Product Sciences, 2008, 14(3):196-201.

[10]
LEE Y K, YUK D Y, KIM T I, et al. Protective effect of the ethanol extract of Magnolia officinalis and 4-O-methylhonokiol on scopolamine-induced memory impairment and the inhibition of acetylcholinesterase activity[J]. Journal of Natural Medicines, 2009, 63(3):274-282.

DOI

[11]
YANG H G, DU G H. Magnolol and honokiol[M]//DU G H.Natural Small Molecule Drugs from Plants.Singapore:Springer, 2018:709-712.

[12]
萨如拉, 陈建兴, 春花, 等. 高压水蒸气蒸馏法提取厚朴有效精油成分[J]. 江苏农业科学, 2018, 46(4):176-179.

SA R L, CHEN J X, CHUN H, et al. Extraction of active essential oil components from Magnolia officinalis with high-pressure steam distillation[J]. Jiangsu Agricultural Sciences, 2018, 46(4):176-179. (in Chinese)

[13]
谭洋, 满兴战, 周峰, 等. 酶解法对凹叶厚朴中厚朴酚与和厚朴酚转移率的影响[J]. 广东化工, 2017, 44(24):13-14.

TAN Y, MAN X Z, ZHOU F, et al. Study on magnolol and honokio extraction rates from Magnolia officinalis Rehd.et Wils.var.biloba Rehd.et Wils. processed by enzymolysis[J]. Guangdong Chemical Industry, 2017, 44(24):13-14. (in Chinese)

[14]
孔玲, 李春霞, 付聿国, 等. 厚朴中厚朴酚与和厚朴酚的提取方法优化[J]. 陕西林业科技, 2021, 49(4):44-48.

KONG L, LI C X, FU Y G, et al. Optimized extraction of magnolol and honokiol in Magnolia officinalis[J]. Shaanxi Forest Science and Technology, 2021, 49(4):44-48. (in Chinese)

[15]
杨岩, 肖佳妹, 易子漾, 等. 厚朴超临界CO2提取工艺优化及提取物抗氧化活性研究[J]. 中草药, 2020, 51(2):381-386.

YANG Y, XIAO J M, YI Z Y, et al. Optimization of supercritical CO2 extraction process of Magnoliae officinalis cortex and anti-oxidant activities of extracts[J]. Chinese Traditional and Herbal Drugs, 2020, 51(2):381-386. (in Chinese)

[16]
覃正斌, 蔡燕, 彭强. 正交法优选厚朴提取工艺[J]. 临床医药文献杂志, 2019, 6(15):170-171.

QIN Z B, CAI Y, PENG Q. Optimized extraction of Magnoliae officinalis by orthogonal design[J]. Journal of Clinical Medical, 2019, 6(15):170-171. (in Chinese)

[17]
李卫民, 牛志强, 王治平, 等. 超声强化超临界提取厚朴酚与和厚朴酚的工艺研究[J]. 中草药, 2011, 42(4):680-683.

LI W M, NIU Z Q, WANG Z P, et al. Technology of ultrasound-enhanced supercritical extraction for magnolol and honokiol[J]. Chinese Traditional and Herbal Drugs, 2011, 42(4):680-683. (in Chinese)

[18]
牛晓晨, 程林忠, 李青. 厚朴酚与和厚朴酚在大鼠不同肠道中的吸收情况及与药物浓度关系[J]. 中药材, 2015, 38(4):817-820.

NIU X C, CHENG L Z, LI Q. Absorption of magnolol and honokiol in different intestinal tracts of rats and relation to drug concentration[J]. Journal of Chinese Medicinal Materials, 2015, 38(4):817-820. (in Chinese)

[19]
LIN S P, TSAI S Y, LEE CHAO P D, et al. Pharmacokinetics,bioavailability,and tissue distribution of magnolol following single and repeated dosing of magnolol to rats[J]. Planta Medica, 2011, 77(16):1800-1805.

DOI

[20]
刘会珍, 董丹丹, 范明松. 不同厚朴酚制剂的制备、表征及其在SD大鼠体内药动学行为比较[J]. 中草药, 2020, 51(17):4442-4448.

LIU H Z, DONG D D, FAN M S. Different preparations of magnolol:preparation,characterization and pharmacokinetics comparative study in SD rats[J]. Chinese Traditional and Herbal Drugs, 2020, 51(17):4442-4448. (in Chinese)

[21]
CHEN C Y C, WU C H. Magnolol encapsulated by liposome in inhibiting smooth muscle cell proliferation[J]. Journal of the Chinese Chemical Society, 2008, 55(3):517-521.

DOI

[22]
WANG X, GU H, ZHANG H, et al. Oral core-shell nanoparticles embedded in hydrogel microspheres for the efficient site-specific delivery of magnolol and enhanced antiulcerative colitis therapy[J]. ACS Applied Materials & Interfaces, 2021, 13(29):33948-33961.

[23]
TANG L, ZHU Z F, XIE M, et al. Effects of β-cyclodextrin and hydroxypropyl-β-cyclodextrin inclusions on the degradation of magnolol by intestinal bacteria[J]. AAPS PharmSciTech, 2019, 20(6):244.

DOI PMID

[24]
SHENG Y L, XU J H, SHI C H, et al. UPLC-MS/MS-ESI assay for simultaneous determination of magnolol and honokiol in rat plasma:application to pharmacokinetic study after administration emulsion of the isomer[J]. Journal of Ethnopharmacology, 2014, 155(3):1568-1574.

DOI

[25]
LIN H L, CHENG W T, CHEN L C, et al. Honokiol/magnolol-loaded self-assembling lecithin-based mixed polymeric micelles (lb MPMs) for improving solubility to enhance oral bioavailability[J]. International Journal of Nanomedicine, 2021, 16:651-665.

DOI

[26]
SANTOS J H, QUIMQUE M T J, MACABEO A P G, et al. Enhanced oral bioavailability of the pharmacologically active lignin magnolol via Zr-based metal organic framework impregnation[J]. Pharmaceutics, 2020, 12(5):437.

DOI

[27]
HATTORI M, ENDO Y, TAKEBE S, et al. Metabolism of magnolol from magnoliae cortex.Ⅱ.Absorption,metabolism and excretion of [ring-14C] magnolol in rats[J]. Chemical and Pharmaceutical Bulletin, 1986, 34(1):158-167.

DOI

[28]
NAKAZAWA T, YASUDA T, OHSAWA K. Metabolites of orally administered Magnolia officinalis extract in rats and man and its antidepressant-like effects in mice[J]. Journal of Pharmacy and Pharmacology, 2003, 55(11):1583-1591.

DOI

[29]
MARTENS E C, NEUMANN M, DESAI M S. Interactions of commensal and pathogenic microorganisms with the intestinal mucosal barrier[J]. Nature Reviews Microbiology, 2018, 16(8):457-470.

DOI PMID

[30]
SINGH R P, SHADAN A, MA Y. Biotechnological applications of probiotics:a multifarious weapon to disease and metabolic abnormality[J]. Probiotics and Antimicrobial Proteins, 2022, 14(6):1184-1210.

DOI

[31]
XIA T, ZHANG J Z, HAN L Y, et al. Protective effect of magnolol on oxaliplatin-induced intestinal injury in mice[J]. Phytotherapy Research, 2019, 33(4):1161-1172.

DOI PMID

[32]
梅华迪, 李袁飞, 田琦, 等. 厚朴酚对断奶仔猪营养物质表观消化率、血清生化指标、粪便主要微生物数量及其代谢产物含量的影响[J]. 动物营养学报, 2022, 34(8):4919-4931.

DOI

MEI H D, LI Y F, TIAN Q, et al. Effects of magnolol on nutrient apparent digestibility,serum biochemical indices,main fecal microorganism numbers and their metabolite contents of weaned piglets[J]. Chinese Journal of Animal Nutrition, 2022, 34(8):4919-4931. (in Chinese)

[33]
XIE Q, XIE K H, YI J H, et al. The effects of magnolol supplementation on growth performance,meat quality,oxidative capacity,and intestinal microbiota in broilers[J]. Poultry Science, 2022, 101(4):101722.

DOI

[34]
ŚLIŻEWSKA K, MARKOWIAK-KOPĆE P, ŻBIKOWSKI A, et al. The effect of synbiotic preparations on the intestinal microbiota and her metabolism in broiler chickens[J]. Scientific Reports, 2020, 10(1):4281.

DOI PMID

[35]
CHANG J, WANG T, WANG P, et al. Compound probiotics alleviating aflatoxin B1 and zearalenone toxic effects on broiler production performance and gut microbiota[J]. Ecotoxicology and Environmental Safety, 2020, 194:110420.

DOI

[36]
QAISRANI S N, VAN KRIMPEN M M, KWAKKEL R P, et al. Diet structure,butyric acid,and fermentable carbohydrates influence growth performance,gut morphology,and cecal fermentation characteristics in broilers[J]. Poultry Science, 2015, 94(9):2152-2164.

DOI

[37]
SPINA L, CAVALLARO F, FARDOWZA N I, et al. Butyric acid:pharmacological aspects and routes of administration[J]. Digestive and Liver Disease Supplements, 2007, 1(1):7-11.

DOI

[38]
CHEN F, ZHANG H, DU E C, et al. Supplemental magnolol or honokiol attenuates adverse effects in broilers infected with Salmonella pullorum by modulating mucosal gene expression and the gut microbiota[J]. Journal of Animal Science and Biotechnology, 2021, 12(1):87.

DOI

[39]
SUN L M, LIAO K, WANG D Y. Effects of magnolol and honokiol on adhesion,yeast-hyphal transition,and formation of biofilm by Candida albicans[J]. PLoS One, 2015, 10(2):e0117695.

DOI

[40]
WANG D C, JIN Q, XIANG H, et al. Transcriptional and functional analysis of the effects of magnolol:inhibition of autolysis and biofilms in Staphylococcus aureus[J]. PLoS One, 2011, 6(10):e26833.

DOI

[41]
ZHOU P R, FU J Y, HUA H, et al. In vitro inhibitory activities of magnolol against Candida spp[J]. Drug Design,Development and Therapy, 2017, 11:2653-2661.

DOI

[42]
向晓波, 周艳萌, 冯琳颖, 等. 基于厚朴酚对白色念珠菌黏附性及其生物膜形成的影响探讨其抗龋作用[J]. 首都医科大学学报, 2015, 36(6):942-945.

DOI

XIANG X B, ZHOU Y M, FENG L Y, et al. Based on the impact of magnolol on Candida albicans adhesion and biofilm formation for exploring its anti-caries effect[J]. Journal of Capital Medical University, 2015, 36(6):942-945. (in Chinese)

[43]
向华. 厚朴酚抗金黄色葡萄球菌作用机制的研究[D]. 博士学位论文. 长春: 吉林大学, 2010.

XIANG H. Mechanism of action of magnolol against Staphylococcus aureus[D]. Ph.D.Thesis. Changchun: Jilin University, 2010. (in Chinese)

[44]
HUANG B B, FAN M W, WANG S L, et al. The inhibitory effect of magnolol from Magnolia officinalis on glucosyltransferase[J]. Archives of Oral Biology, 2006, 51(10):899-905.

DOI

[45]
梁振生. 厚朴酚对呼吸道致病菌的体外抑菌作用研究[J]. 抗感染药学, 2022, 19(9):1256-1258.

DOI

LIANG Z S. Antibacterial effect of magnolol on respiratory pathogenic bacteria in vitro[J]. Anti-Infection Pharmacy, 2022, 19(9):1256-1258. (in Chinese)

[46]
魏婧瑶, 尤佳, 卢会奇, 等. 厚朴酚对猪链球菌的抑制作用及对其感染巨噬细胞的影响[J]. 中国饲料, 2018(9):29-32.

WEI J Y, YOU J, LU H Q, et al. Effects of magnolol on inhibiting Streptococcus suis and influences on macrophages infected[J]. China Feed, 2018(9):29-32. (in Chinese)

[47]
CHEN Y H, LU M H, GUO D S, et al. Antifungal effect of magnolol and honokiol from Magnolia officinalis on Alternaria alternata causing tobacco brown spot[J]. Molecules, 2019, 24(11):2140.

DOI

[48]
CHIU K C, SHIH Y H, WANG T H, et al. In vitro antimicrobial and antipro-inflammation potential of honokiol and magnolol against oral pathogens and macrophages[J]. Journal of the Formosan Medical Association, 2021, 120(2):827-837.

DOI

[49]
ALI Q, MA S, LA S K, et al. Microbial short-chain fatty acids:a bridge between dietary fibers and poultry gut health-a review[J]. Animal Bioscience, 2022, 35(10):1461-1478.

DOI

[50]
GARIMANO N, SCALISE M L, GÓMEZ F, et al. Intestinal mucus-derived metabolites modulate virulence of a clade 8 enterohemorrhagic Escherichia coli O157∶H7[J]. Frontiers in Cellular and Infection Microbiology, 2022, 12:975173.

DOI

[51]
MA J Y, PIAO X S, MAHFUZ S, et al. The interaction among gut microbes,the intestinal barrier and short chain fatty acids[J]. Animal Nutrition, 2022, 9:159-174.

DOI

[52]
JING Y, LIU X L, WANG J Y, et al. Production of corn protein hydrolysate with glutamine-rich peptides and its antagonistic function in ulcerative colitis in vivo[J]. Foods, 2022, 11(21):3359.

DOI

[53]
TREMAROLI V, BÄCKHED F. Functional interactions between the gut microbiota and host metabolism[J]. Nature, 2012, 489(7415):242-249.

DOI

[54]
HUANG H, SU L H, SUN Y, et al. Dietary magnolol inclusion improves the antioxidant and immune responses,and resistance to Aeromonas hydrophila in genetically improved farmed tilapia (Oreochromis niloticus)[J]. Aquaculture Reports, 2022, 23:101017.

DOI

[55]
GHOSH S S, WANG J, YANNIE P J, et al. Over-expression of intestinal alkaline phosphatase attenuates atherosclerosis[J]. Circulation Research, 2021, 128(11):1646-1659.

DOI PMID

[56]
HUBBARD T D, MURRAY I A, PERDEW G H. Indole and tryptophan metabolism:endogenous and dietary routes to Ah receptor activation[J]. Drug Metabolism and Disposition, 2015, 43(10):1522-1535.

DOI

[57]
ZHAO L, XIAO H T, MU H X, et al. Magnolol,a natural polyphenol,attenuates dextran sulfate sodium-induced colitis in mice[J]. Molecules, 2017, 22(7):1218.

DOI

[58]
SHI Z F, WANG T W, KANG J J, et al. Effects of weaning modes on the intestinal pH,activity of digestive enzymes,and intestinal morphology of piglets[J]. Animals, 2022, 12(17):2200.

DOI

[59]
SHIMIZU K, SEIKI I, GOTO Y, et al. Measurement of the intestinal pH in mice under various conditions reveals alkalization induced by antibiotics[J]. Antibiotics, 2021, 10(2):180.

DOI

[60]
BUCKLEY A, TURNER J R. Cell biology of tight junction barrier regulation and mucosal disease[J]. Cold Spring Harbor Perspectives in Biology, 2018, 10(1):a029314.

DOI

[61]
OHLAND C L, MACNAUGHTON W K. Probiotic bacteria and intestinal epithelial barrier function[J]. American Journal of Physiology:Gastrointestinal and Liver Physiology, 2010, 298(6):G807-G819.

DOI

[62]
YU J, YIN P, YIN J D, et al. Involvement of ERK1/2 signalling and growth-related molecules expression in response to heat stress-induced damage in rat jejunum and IEC-6 cells[J]. International Journal of Hyperthermia, 2010, 26(6):538-555.

DOI

[63]
李华善. 干扰素-γ调控肠上皮细胞坏死和增殖分化的机制研究[D]. 博士学位论文. 苏州: 苏州大学, 2020.

LI H S. The regulation of interferon-γ on intestinal epithelial cell necroptosis,proliferation,and differentiation[D]. Ph.D.Thesis. Suzhou: Soochow University, 2020. (in Chinese)

[64]
DENG Y L, HAN X F, TANG S X, et al. Magnolol and honokiol attenuate apoptosis of enterotoxigenic Escherichia coli-induced intestinal epithelium by maintaining secretion and absorption homeostasis and protecting mucosal integrity[J]. Medical Science Monitor, 2018, 24:3348-3356.

DOI

[65]
MEI C, HE S S, YIN P, et al. Magnolol pretreatment attenuates heat stress-induced IEC-6 cell injury[J]. Journal of Zhejiang University Science B, 2016, 17(6):413-424.

DOI PMID

[66]
GAO Y, HAN F, HUANG X, et al. Changes in gut microbial populations,intestinal morphology,expression of tight junction proteins,and cytokine production between two pig breeds after challenge with Escherichia coli K88:a comparative study[J]. Journal of Animal Science, 2013, 91(12):5614-5625.

DOI

[67]
CHEN F, ZHANG H, DU E C, et al. Effects of magnolol on egg production,egg quality,antioxidant capacity,and intestinal health of laying hens in the late phase of the laying cycle[J]. Poultry Science, 2021, 100(2):835-843.

DOI

[68]
TURNER J R. Intestinal mucosal barrier function in health and disease[J]. Nature Reviews Immunology, 2009, 9(11):799-809.

DOI PMID

[69]
CHELAKKOT C, GHIM J, RYU S H. Mechanisms regulating intestinal barrier integrity and its pathological implications[J]. Experimental & Molecular Medicine, 2018, 50(8):1-9.

[70]
WANG Y X, HONG C M, WU Z B, et al. Resveratrol in intestinal health and disease:focusing on intestinal barrier[J]. Frontiers in Nutrition, 2022, 9:848400.

DOI

[71]
DU E C, FAN Q W, ZHAO N, et al. Supplemental magnolol improves the antioxidant capacity and intestinal health of broiler chickens[J]. Animal Science Journal, 2021, 92(1):e13665.

DOI

[72]
CHEN F, ZHANG H, ZHAO N, et al. Effects of magnolol and honokiol blend on performance,egg quality,hepatic lipid metabolism,and intestinal morphology of hens at late laying cycle[J]. Animal, 2022, 16(6):100532.

DOI

[73]
SHEN P, ZHANG Z C, HE Y, et al. Magnolol treatment attenuates dextran sulphate sodium-induced murine experimental colitis by regulating inflammation and mucosal damage[J]. Life Sciences, 2018, 196:69-76.

DOI PMID

[74]
EVENNETT N J, PETROV M S, MITTAL A, et al. Systematic review and pooled estimates for the diagnostic accuracy of serological markers for intestinal ischemia[J]. World Journal of Surgery, 2009, 33(7):1374-1383.

DOI PMID

[75]
CHEI S, OH H J, SONG J H, et al. Magnolol suppresses TGF-β-induced epithelial-to-mesenchymal transition in human colorectal cancer cells[J]. Frontiers in Oncology, 2019, 9:752.

DOI PMID

[76]
NIKOLAKIS D, DE VOOGD F A E, PRUIJT M J, et al. The role of the lymphatic system in the pathogenesis and treatment of inflammatory bowel disease[J]. International Journal of Molecular Sciences, 2022, 23(3):1854.

DOI

[77]
SODERHOLM A T, PEDICORD V A. Intestinal epithelial cells:at the interface of the microbiota and mucosal immunity[J]. Immunology, 2019, 158(4):267-280.

DOI

[78]
ROCHA D M, CALDAS A P, OLIVEIRA L L, et al. Saturated fatty acids trigger TLR4-mediated inflammatory response[J]. Atherosclerosis, 2016, 244:211-215.

DOI PMID

[79]
NGO D H, TRAN Q T, KIM Y S, et al. GABA-enriched rice bran inhibits inflammation in LPS-stimulated macrophages via suppression of TLR4-MAPK/NF-κB signaling cascades[J]. Journal of Food Biochemistry, 2022, 46(12):e14421.

[80]
YANG T C, ZHANG S W, SUN L N, et al. Magnolol attenuates sepsis-induced gastrointestinal dysmotility in rats by modulating inflammatory mediators[J]. World Journal of Gastroenterology, 2008, 14(48):7353-7360.

DOI

[81]
ZHANG Y, FU L T, TANG F. The protective effects of magnolol on acute trinitrobenzene sulfonic acid?induced colitis in rats[J]. Molecular Medicine Reports, 2018, 17(3):3455-3464.

[82]
DENG Y P, JIANG W D, LIU Y, et al. Differential growth performance,intestinal antioxidant status and relative expression of Nrf2 and its target genes in young grass carp (Ctenopharyngodon idella) fed with graded levels of leucine[J]. Aquaculture, 2014, 434:66-73.

DOI

[83]
KARAVITIS J, KOVACS E J. Macrophage phagocytosis:effects of environmental pollutants,alcohol,cigarette smoke,and other external factors[J]. Journal of Leukocyte Biology, 2011, 90(6):1065-1078.

DOI

[84]
GORDON S. Phagocytosis:an immunobiologic process[J]. Immunity, 2016, 44(3):463-475.

DOI

[85]
符吴萸. 厚朴酚的免疫抗炎作用及其对相关信号转导通路的调控[D]. 硕士学位论文. 广州: 广东药科大学, 2016.

FU W Y. Immune and anti-inflammatory effects of magnolol and its mechanisms[D]. Master’s Thesis. Guangzhou: Guangdong Pharmaceutical University, 2016. (in Chinese)

Options
Outlines

/

〈 〉

京ICP备17050989号-2
Copyright © Chinese Journal of Animal Nutrition, All Rights Reserved.
Tel: 010－62817823　E-mail: cjan@vip.163.com
Powered by Beijing Magtech Co., Ltd.