Rehmannioside D is an indicator component of Dihuang (Rehmanniae Radix), a traditional Chinese medicine that shares the same origin in both medicine and food. Rehmannioside D, a natural iridoid glycoside, exhibits a broad spectrum of pharmacological activities, including nourishing yin and blood, cooling blood and stopping bleeding, providing analgesia, acting as an antidepressant, and preventing osteoporosis, thereby meriting intensified investigation. This paper systematically reviews the recent advances in rehmannioside D research, detailing the optimization of determination methods and the application of new technologies for rehmannioside D, as well as the content determination in different dosage forms. The principles of content variation in different producing areas, processing methods, and tissues of Rehmanniae Radix are summarized. Furthermore, it focuses on elucidating the pharmacological effects of rehmannioside D in the endocrine and cardiovascular systems, nervous system, and other aspects. In addition, this paper critically discusses the existing challenges in its research. The aim is to provide a scientific basis for the further development and clinical application of rehmannioside D, as well as the quality identification and comprehensive utilization of Rehmanniae Radix.
Key words
rehmannioside D
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method of determination
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content variation principle
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analgesic
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antidepressant
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anti-osteoporosis
ZHANG Pengyu, GAO Junge, YANG Yahe, HAO Qiuwen, HU Jingyi, WU Yanying, DING Ning.
Research progress on rehmannioside D in Rehmanniae Radix: Determination methods, content variation principles, and pharmacological actions[J].
Chinese Traditional and Herbal Drugs,
2026
, 57
(1)
: 355
-363
.
DOI: 10.7501/j.issn.0253-2670.2026.01.032
董天骄,崔元璐,田俊生,等.天然环烯醚萜类化合物研究进展[J]. 中草药, 2011, 42(1):185-194. 董娟娥,张靖.植物中环烯醚萜类化合物研究进展[J]. 西北林学院学报, 2004, 19(3):131-135. 孙宇佳,唐淑含,王姗姗,等.环烯醚萜类化合物的结构分类及生物活性[J]. 黑龙江科技信息, 2014(2):80. 余鸽,龙凤来,黄时伟.环烯醚萜药理作用研究进展[J]. 陕西林业科技, 2009, 37(2):69-73. 吴寿金.现代中草药成分化学[M]. 北京:中国医药科技出版社, 2002. 中国药典[S]. 一部. 2025:132-133. Oshio H, Inouye H. Iridoid glycosides of Rehmannia glutinosa[J]. Phytochemistry, 1982, 21(1):133-138. 李更生,王慧森,刘明,等.地黄中环烯醚萜苷类化学成分的研究[J]. 中医研究, 2008, 21(5):17-19. 杜亚朋,王美,李璐遥,等.基于化合物稳定性探讨炮制对含环烯醚萜类成分中药药性及功效影响的研究进展[J]. 中草药, 2021, 52(16):5039-5051. 朱俏峭,钟亮,戚进.地黄中环烯醚萜类化学成分的研究进展[J]. 海峡药学, 2015, 27(9):1-5. 李更生,王慧森. HPLC法测定地黄中地黄苷D含量[J]. 中草药, 2003, 34(8):752-754. 张彩,张萍,司文琪,等.怀地黄中地黄苷D的提取工艺及不同炮制品含量的比较研究[J]. 山东农业科学,2016, 48(5):127-130. 谢彩侠,李雅静,张苗,等.怀地黄中地黄苷A,地黄苷D及益母草苷含量快速分析方法的建立[J]. 中国实验方剂学杂志, 2018, 24(6):47-54. 樊克锋,汤法银,赵建平,等.红外光谱技术对生地黄整体评价[J]. 中国兽药杂志, 2017, 51(3):55-60. 黄春跃,欧阳丹薇,牛莉鑫,等.基于HPLC二维指纹图谱结合化学计量分析对生地黄质量评价研究[J]. 中国中药杂志, 2018, 43(8):1667-1674. 张留记,周志敏,屠万倩,等. HPLC同时测定地黄中5种苷类成分的含量[J]. 天然产物研究与开发, 2017,29(1):87-90. 胡轲,李珊珊,刘炜,等.双波长HPLC同时测定生地黄中6种化合物的含量[J]. 中国现代应用药学, 2020,37(12):1478-1482. 李更生,王慧森,刘明,等.高效液相色谱法测定三种中成药中地黄苷D的含量[J]. 中医研究, 2007, 20(3):26-28. 刘玉振,许伟.一测多评法测定麦芪降糖丸中的7种成分[J]. 华西药学杂志, 2021, 36(4):473-477. 汪青梅,熊永爱,魏谭军. HPLC法测定八珍液中地黄苷A、地黄苷D、去氢土莫酸和茯苓酸[J]. 现代药物与临床, 2016, 31(1):25-28. 白荣. HPLC法测定三才封髓丸中地黄苷A、地黄苷D、黄柏碱和木兰花碱[J]. 现代药物与临床, 2015, 30(11):1324-1327. 董清,支荣荣.双波长HPLC法测定藤黄健骨片中地黄苷D、水晶兰苷的含量[J]. 首都食品与医药, 2023,30(10):150-152. 徐雄飞,王海燕,何清.熟地黄配方颗粒和标准汤剂中地黄苷D的含量测定[J]. 江西中医药大学学报, 2022,34(4):86-88. 刘明,李更生,王慧森. 7种地黄丸中地黄苷D的含量测定[J]. 中国医院药学杂志, 2008, 28(13):1130-1131. 但济修,李淞明,詹常森.百合地黄汤基准样品HPLC特征图谱建立及其指标成分含量测定[J]. 中成药,2024, 46(4):1279-1283. 李玥,傅琳.高效液相色谱-电喷雾检测器法同时测定心荣颗粒的多种成分[J]. 海峡药学, 2024, 36(3):41-44. 李应才,黄合琤,马文思,等.超高效液相色谱串联质谱法同时测定养阴清肺合剂中3种成分含量[J]. 中国药业, 2023, 32(13):68-71. 李震宇,崔伊凡,秦雪梅.中药材质量评价的挑战与代谢组学应用于中药材质量评价的研究进展[J]. 中草药, 2018, 49(10):2221-2229. 李向达,曹彦刚,张宇涵,等.仲圣1号鲜地黄化学成分研究[J]. 中药材, 2024, 47(5):1158-1164. 张留记,屠万倩,杨冉,等.不同产地地黄中地黄苷D的测定[J]. 分析试验室, 2008, 27(3):56-58. 李娴,邢亚东,李姗姗,等.不同炮制方法对熟地黄中7种化学成分含量的影响[J]. 蚌埠医学院学报, 2020,45(5):634-637. 徐廉松,牛雯雯,孔雪,等.基于双波长高效液相色谱法同时测定九蒸九晒熟地黄中7种成分的含量[J]. 甘肃中医药大学学报, 2022, 39(4):1-6. 张月月,王君明,巫晓慧.基于以梓醇为主要成分的地黄环烯醚萜苷生物活性研究[J]. 中华中医药学刊,2022, 40(12):75-77. 王菲菲,张聿梅,郑笑为,等.环烯醚萜类化合物的结构和生物学活性研究进展[J]. 中国药事, 2019, 33(3):323-330. 韩笑,匡宇,赵永艳,等.九蒸九晒黄精5-HMF含量的变化[J]. 中药与临床, 2018, 9(3):4-5. 于文娜,张振凌,李柯柯,等.鲜地黄花不同部位环烯醚萜苷类成分含量测定[J]. 食品研究与开发, 2017,38(14):134-137. 史国茹.地黄叶和蝴蝶花活性物质与功能研究[D]. 北京:北京协和医学院, 2016. 赵新梅,张威,李莹莹,等.基于指纹图谱和多指标定量分析鲜地黄不同加工方式后化学成分变化[J]. 中草药, 2024, 55(12):4020-4031. 张金鼎,曹鸿云.河南四大怀药[J]. 中药材, 1987,10(3):55-56. 谢彩侠,李雅静,张苗,等.不同种质地黄块根菊花心与非菊花心部位有效成分特征分析[J]. 中国实验方剂学杂志, 2018, 24(20):75-83. 宋梦娇,董诚明,魏悦,等.怀地黄“菊花心”性状与化学成分的相关性研究[J]. 时珍国医国药, 2023, 34(5):1133-1137. 祁昱彤,张淼,刘建勋,等.中药地黄的现代研究进展及其质量标志物(Q-Marker)预测分析[J]. 中华中医药学刊, 2023, 41(12):176-184. 于震,王军,李更生,等.地黄苷D滋阴补血和降血糖作用的实验研究[J]. 辽宁中医杂志, 2001, 28(4):240-242. 曾艳,贾正平,张汝学,等.地黄寡糖在2型糖尿病大鼠模型上的降血糖作用及机制[J]. 中国药理学通报,2006, 22(4):411-415. 郭晓农.地黄寡糖改善胰岛素抵抗的作用和机理的体外研究[D]. 兰州:兰州大学, 2006. Zhang Q L, Lei Y L, Deng Y, et al. Treatment progress in diminished ovarian reserve:Western and Chinese medicine[J]. Chin J Integr Med, 2023, 29(4):361-367. Buigues A, Marchante M, Herraiz S, et al. Diminished ovarian reserve chemotherapy-induced mouse model:A tool for the preclinical assessment of new therapies for ovarian damage[J]. Reprod Sci, 2020, 27(8):1609-1619. Lim S W, Jin L, Luo K, et al. Klotho enhances FoxO3-mediated manganese superoxide dismutase expression by negatively regulating PI3K/Akt pathway during tacrolimus-induced oxidative stress[J]. Cell Death Dis,2017, 8(8):e2972. Wu Z X, He Q J, Zeng B J, et al. Juvenile hormone acts through FoxO to promote Cdc2 and Orc5 transcription for polyploidy-dependent vitellogenesis[J]. Development,2020, 147(18):dev188813. Masciangelo R, Hossay C, Chiti M C, et al. Role of the PI3K and Hippo pathways in follicle activation after grafting of human ovarian tissue[J]. J Assist Reprod Genet, 2020, 37(1):101-108. Xie T T, Ye W T, Liu J, et al. The emerging key role of KLOTHO in the hypothalamus-pituitary-ovarian axis[J]. Reprod Sci, 2021, 28(2):322-331. Liang Y, Wang H M, Chen J, et al. Rehmannioside D mitigates disease progression in rats with experimentalinduced diminished ovarian reserve via forkhead box O1/KLOTHO axis[J]. Korean J Physiol Pharmacol, 2023,27(2):167-176. Zhang B X, Zhou N, Zhang Z K, et al. Study on the neuroprotective effects of eight iridoid components using cell metabolomics[J]. Molecules, 2024, 29(7):1497. Richard M J, Driban J B, McAlindon T E. Pharmaceutical treatment of osteoarthritis[J]. Osteoarthritis Cartilage,2023, 31(4):458-466. Jhun J Y, Na H S, Shin J W, et al. Notoginseng Radix and Rehmanniae Radix Preparata extract combination(YH23537)reduces pain and cartilage degeneration in rats with monosodium iodoacetate-induced osteoarthritis[J]. J Med Food, 2018, 21(8):745-754. Huang Y F, Lin Q, Tan X, et al. Rehmannia alcohol extract inhibits neuropeptide secretion and alleviates osteoarthritis pain through cartilage protection[J]. Heliyon, 2023, 9(9):e19322. Wang J M, Pei L X, Zhang Y Y, et al. Ethanol extract of Rehmannia glutinosa exerts antidepressant-like effects on a rat chronic unpredictable mild stress model by involving monoamines and BDNF[J]. Metab Brain Dis, 2018, 33(3):885-892. 赵洪庆,唐林,吴碧茹,等.百合地黄汤抑制NLRP3炎症小体激活改善焦虑性抑郁症模型大鼠海马神经元损伤[J]. 中国实验方剂学杂志, 2021, 27(20):7-14. 陈伟康,令狐婷,任燕.中药治疗抑郁症作用机制研究进展[J]. 中草药, 2025, 56(11):4090-4102. 廖韵诺,赵凯丽,郭宏伟.中药网络药理学的研究应用与挑战[J]. 中草药, 2024, 55(12):4204-4213. 涂慕鑫,孟亦浩,王庆亮,等.基于UPLC-Q-TOF-MS/MS技术和网络药理学探究竹叶青酒缓解急性肝损伤作用机理[J]. 中国酿造, 2024, 43(10):56-64. 黄祖顺,郭磊,张爱荣,等.基于网络药理学和指纹图谱的安宫牛黄丸质量标志物预测与分析[J]. 药物评价研究, 2023, 46(10):2083-2093. 韩德恩,岳中胜,李红伟,等.基于UPLC-Q-Orbitrap HRMS结合网络药理学研究地黄抗抑郁成分及其作用机制[J]. 中国中药杂志, 2022, 47(4):1051-1063. 张莉,卢仁睿,王慧慧,等.地黄苷D对皮质酮诱导的PC-12细胞损伤的保护作用及机制研究[J]. 中草药,2022, 53(11):3385-3393. 徐嘉珂,白洁. BDNF及其受体在抗抑郁症中的作用及其机制研究[J]. 生命科学, 2014, 26(4):357-361. 温韫然,佟歌,高坤,等.风药治疗抑郁症作用机制探究[J]. 中国中医基础医学杂志, 2024, 30(10):1663-1666. 王慧慧,卢仁睿,张莉,等.地黄中地黄苷D通过调控小胶质细胞M1/M2极化抑制神经炎症[J]. 中药材,2021, 44(11):2683-2687. Kiecolt-Glaser J K, Derry H M, Fagundes C P.Inflammation:Depression fans the flames and feasts on the heat[J]. Am J Psychiatry, 2015, 172(11):1075-1091. Zhang X, Wang D D, Ren X D, et al. System bioinformatic approach through molecular docking, network pharmacology and microarray data analysis to determine the molecular mechanism underlying the effects of Rehmanniae Radix Praeparata on cardiovascular diseases[J]. Curr Protein Pept Sci, 2019, 20(10):964-975. 许平翠,朱赋健,郑纯威,等.基于HPLC多波长融合指纹图谱及谱效关系的熟地黄活性成分研究[J]. 中国现代应用药学, 2022, 39(22):2901-2907. 张月月,龙冰玉,王君明,等.盐制炮制对地黄凉血止血功效的增效作用探索[J/OL]. 中华中医药学刊,(2024-12-16)[2025-08-01]. https://link.cnki.net/urlid/21.1546.R.20241213.1826.010. 刘瑞頔,张振强,张效威,等.益肾通络方及活性成分地黄苷D抑制肾小管上皮-间质转化的机制研究[J]. 中药新药与临床药理, 2025, 36(1):30-40. 李更生,刘明,王慧森.一种地黄苷D标准物质的制备方法:中国, CN201110275514.4[P]. 2012-03-21. 王慧森,刘明,李更生.一种地黄环烯醚萜苷类提取物的制备方法:中国, CN201810047545.6[P]. 2021-03-26. 岳晨,肖学凤,秦文杰.六味地黄丸治疗围绝经期综合征的临床研究进展[J]. 药物评价研究, 2022, 45(4):804-809. 赵日杂,张剑光,苏学燕,等.知柏地黄丸研究进展及质量标志物预测[J]. 中华中医药学刊, 2022, 40(11):196-204. Pan J, Lu Y T, Wang S J, et al. Synergistic neuroprotective effects of two natural medicinal plants against CORTinduced nerve cell injury by correcting neurotransmitter deficits and inflammation imbalance[J]. Phytomedicine,2023, 121:155102. 徐小博,徐萍,夏然,等.地黄中环烯醚萜苷的生物合成研究进展[J]. 生物技术, 2018, 28(5):508-512. Zhi J Y, Li Y J, Zhang Z Y, et al. Molecular regulation of catalpol and acteoside accumulation in radial striation and non-radial striation of Rehmannia glutinosa tuberous root[J]. Int J Mol Sci, 2018, 19(12):3751. Li Y J, Zhai X R, Ma L G, et al. Transcriptome analysis provides insights into catalpol biosynthesis in the medicinal plant Rehmannia glutinosa and the functional characterization of RgGES genes[J]. Genes, 2024, 15(2):155. 国家卫生健康委员会,国家市场监督管理总局.国家卫生健康委员会食品安全标准与监测评估司发布《关于地黄等4种按照传统既是食品又是中药材的物质》的公告(2024年第4号)[EB/OL]. (2024-08-12)[2025-08-13]. https://www.nhc.gov.cn/sps/c100088/202408/53150d0918ec40899b5293147ec0dd01.shtml.