新甲基橙皮苷二氢查耳酮及合成前体药理作用研究进展

魏静; 宋若兰; 陈翔; 王振东; 董英; 钟祥健; 吕芳; 折改梅

doi:10.13386/j.issn1002-0306.2022010176

新甲基橙皮苷二氢查耳酮及合成前体药理作用研究进展

doi: 10.13386/j.issn1002-0306.2022010176

魏静^1,,
宋若兰¹,
陈翔²,
王振东³,
董英¹,
钟祥健¹,
吕芳¹,
折改梅^1, ,

1.
北京中医药大学中药学院，北京 102488
2.
桓台史氏医院，山东淄博 256405
3.
山东奔月生物科技股份有限公司，山东东营 257000

详细信息

作者简介:
魏静（1996−），女，硕士研究生，研究方向：中（民族）药药效成分和新药创制研究，E-mail：Radiant_JJ@163.com

通讯作者:
折改梅（1976−），女，博士，研究员，研究方向：中（民族）药药效成分和新药创制研究，E-mail：shegaimei@126.com

中图分类号: R961
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- 被引次数: 0
出版历程
- 收稿日期: 2022-01-21
- 网络出版日期: 2022-10-21
- 刊出日期: 2022-11-23

Research Progress on Pharmacological Activities of Neohesperidin Dihydrochalcone and Its Synthetic Precursors

1.
School of Chinnese Materia Medica, Beijing University of Chinese Medicine, Beijing 102488, China
2.
Huantai County Shishi Hospital, Zibo 256405, China
3.
Shandong Benyue Biological Technology Co., Ltd., Dongying 257000, China

摘要

摘要: 新甲基橙皮苷二氢查耳酮（Neohesperidin dihydrochalcone，NHDC）是一种无毒、高甜度、低热量的甜味剂，具有增甜、增香、掩盖苦味、修饰风味的功能与抗氧化、抗炎、降血脂等药理活性，在食品及医药领域具有一定的开发潜力。当前NHDC的合成前体主要包括橙皮苷（Hesperidin，HSD）、新橙皮苷（Neohesperidin，NHP）和柚皮苷（Naringin，NRG），具有抗氧化、保护肝肾、抑菌和改善胃肠道等多种生物学活性。NHDC的药理研究相对具有发展进程缓慢、研究系统欠缺、机制深度缺乏等特点。本文以NHDC及其合成前体为关键词在SciFinder、Web of Science、CNKI等科学数据库中进行检索，综述了NHDC的药理作用和机制，并对其合成前体的药理研究进展进行总结，以期为NHDC的进一步综合利用和开发高附加值产品提供参考。
- 新甲基橙皮苷二氢查耳酮 /
- 橙皮苷 /
- 新橙皮苷 /
- 柚皮苷 /
- 药理作用
Abstract: Neohesperidin dihydrochalcone (NHDC) is a sweetener with non-toxic, highly sweet and low-calorie characteristics. It has abilities of adding sweetness, adding fragrance and masking the bitterness, together with modifying flavours, as well as pharmacological activities such as antioxidant, anti-inflammatory, hypolipidemic and has potential for development in the fields of food and pharmaceutical. NHDC is usually obtained by hydrogenated reduction of neohesperidin (NHP) after hydrolysis under alkaline conditions, while neohesperidin is synthesized from hesperidin (HSD) and naringenin (NRG), they are called as synthesis precursors of NHDC. The synthetic precursors of NHDC have various biological activities, including antioxidant, liver and kidney protection, antibacterial and improving gastrointestinal function, etc. The pharmacological effects of NHDC are characterized by slow development process, lack of research systems and lack of depth of mechanisms compared to other dihydrochalcone compounds. In this paper, we searches the scientific databases including SciFinder, Web of Science and CNKI with the keywords of NHDC and its synthetic precursors, and reads its relevant literature. The pharmacological activity is systematically discussed and synthetic precursors mechanism is summarized for the NHDC, which will provide reference for the further utilization and development of NHDC and produce high value-added products in future.
- neohesperidin dihydrochalcone (NHDC) /
- hesperidin (HSD) /
- neohesperidin (NHP) /
- naringin (NRG) /
- pharmacological activities

HTML全文

图 1 新甲基橙皮苷二氢查耳酮及其合成前体结构^{[1, 34-36]}

Figure 1. Chemical structures of neohesperidin dihydrochalcone and its synthetic precursors^{[1, 34-36]}

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图 2 NHDC及其合成前体抗氧化通路作用机制^{[5-7, 15-17]}

Figure 2. Action mechanism of NHDC and its synthetic precursors in the antioxidant pathway^{[5-7, 15-17]}

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图 3 NHDC及其合成前体保护肝肾作用机制^{[4, 8, 26-27]}

Figure 3. Action mechanism of hepatorenal protective effect of NHDC and its synthetic precursors^{[4, 8, 26-27]}

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图 4 NHDC及其合成前体药理作用对应疾病^{[4-8, 15, 21-27, 46-49, 54-66, 73-96]}

Figure 4. Pharmacological effects of NHDC and its synthetic precursors correspond to diseases^{[4-8, 15, 21-27, 46-49, 54-66, 73-96]}

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表 1 NHDC及其合成前体药理作用及机制

Table 1. Pharmacological effect and mechanism of NHDC and its synthetic precursors

药物	药理作用	作用机制及途径	参考文献
NHDC	抗氧化	通过增强SOD、GSH-Px活性，降低CAT等抑制氧化应激抑制ABTS⁺·、·O^2-、·OH、H₂O₂、HOCl等自由基	[5] [6-7]
	抗炎	抑制pq诱导的NF-κB表达和线粒体驱动的凋亡信号	[4]
	保护肝脏	抑制LPS与TLR4结合，激活Nrf2、抑制TLR4信号通路逆转Bax上调与Bcl-2下调，抑制氧化应激间接清除Nrf2/ARE信号通路激活	[8] [4] [59]
	降血脂	抑制HMG-CO还原酶和ACAT的活性，抑制脂肪肝形成	[9,65]
HSD	抗氧化	降低ROS、MDA、PCO、AOPP与caspase-3表达水平，抑制氧化应激	[15,42-51]
	抗炎	降低COX-2的过表达和炎症细胞的浸润降低IL-6、IL-8、SIRT1、PGC-1α和p-p65等表达水平	[18] [54]
	保护肝脏	上调Nrf2/HO-1/Bcl2信号通路和下调NF-κB信号通路降低ALT、ALP、GGT等水平，增强白蛋白与白蛋白/球蛋白比值	[26] [60]
	保护肾脏	提高一氧化氮的表达量，降低尿素氮和血清肌酐的表达量	[61-62]
	降血脂	提高瘦素、IL-6和TNF-α水平，改善血脂水平异常	[20]
	降血糖	影响PPAR信号通路，恢复胰岛素信号通路IRS/Akt/GLUT4蛋白表达	[66,68]
	改善肠道	增加5-HTR4和细胞内游离钙离子，增强cAMP/PKA途径和p-CREB途径相关蛋白表达，改善洛哌胺诱导的便秘大鼠结肠运动	[75]
	保护心血管系统	抑制TGF-β1和MMPs蛋白表达下调LC3II和Beclin1表达，上调p-mTOR、P-Akt和PI3K表达	[82] [83]
	神经保护	通过降低氧化应激、改善线粒体功能障碍和细胞凋亡减轻神经元损伤	[89-91]
	保护生殖系统	降低miR-181a和miR126-3p表达水平，上调SIRT1和SOD2 mRNA蛋白表达水平，提高Nrf2、HO-1蛋白表达水平	[96]
	抗癌	增强miR-132的表达，降低ZEB2的表达，促进NScLc细胞的凋亡抑制NF-κB和Akt通路，降低PD-L1表达水平，抑制乳腺癌生长	[12] [100]
NHP	抗氧化	对DPPH自由基和ABTS⁺·自由基有清除能力	[16,44]
	促炎症	与吲哚美辛联用，诱导大鼠胃细胞DNA断裂，增加了COX-2的表达	[56]
	保护肝脏	上调PParα、Acaa2、Cpt-1、Pdk4、Acox1等脂肪酸氧化基因表达下调Srebf1、Fasn、Scd1、Acc1等脂肪生成基因表达	[63]
	降血糖降血脂	抑制SCD-1和FAS的基因表达，显著上调ACOX、AMPK的表达，促进PGC-1α，增强线粒生物发生等	[21,63,69]
	神经保护	抑制神经元凋亡、抑制氧化应激、调控凋亡通路和Akt/Nrf2/HO-1通路抑制Aβ25-35诱导的内质网功能紊乱和促凋亡反应	[92] [93]
	抗癌	激活P53/Bcl-2/Bax信号通路，诱导MDA-MB-231细胞凋亡	[13]
NRG	抗氧化	抑制超氧化物自由基、黄嘌呤氧化酶、ROS和脂质过氧化等作用抑制caspase-8，caspase-3信号凋亡与Nrf2信号通路，下调相关凋亡基因	[17] [45]
	抗炎	抑制TNF-α和IL-1β产生，上调TGF-β1表达通过AMPK、p38和Nrf-2信号通路诱导巨噬细胞HO-1表达	[57] [58]
	保护肝肾	调节氧化应激、炎症、凋亡、自噬和DNA损伤增强FXR和KIM-1的mRNA表达，对抗细胞损伤	[27] [64]
	降血糖降血脂	抑制PI3K-Akt-mTOR通路介导的自噬，改善应激导致内皮功能障碍抑制HG诱导的ERK1/2和JNK MAPK信号通路，改善肾纤维化抑制LOX-1表达，下调NADPH表达，改善内皮功能障碍	[22] [70] [25]
	保护肠道	抑制TNF-α刺激下RIMVECs细胞的迁移，保护屏障完整性	[81]
	保护心肌细胞	抑制ROS激活的MAPK通路，保护H9c2细胞免受HG诱导的损伤调节ERK和IRE1α通路，减少ER应激介导的细胞凋亡	[86-87]
	神经保护	作用于PI-3K/Akt依赖的Nrf2信号通路淀粉样β代谢、Tau蛋白超磷酸化、氧化应激和细胞凋亡等	[94] [95]
	抗癌	调节miR-126/VCAM-1抑制SCLC生长，诱导细胞凋亡减少NF-κB/COX-2-caspase-1通路的激活，诱导凋亡	[14] [101]

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