Article(id=1308842517387375514, tenantId=1146029695717560320, journalId=1189982191388893191, issueId=1308842471539442166, articleNumber=null, orderNo=null, doi=10.16438/j.0513-4870.2025-1236, pmid=null, cstr=null, oa=null, hot=null, price=null, onlineType=0, articleFormat=0, articleType=null, articleTypeStr=null, receivedDate=1760630400000, receivedDateStr=2025-10-17, revisedDate=1766505600000, revisedDateStr=2025-12-24, acceptedDate=null, acceptedDateStr=null, onlineDate=1789981973262, onlineDateStr=2026-09-21, pubDate=1786464000000, pubDateStr=2026-08-12, doiRegisterDate=null, doiRegisterDateStr=null, onlineIssueDate=1789981973262, onlineIssueDateStr=2026-09-21, onlineJustAcceptDate=null, onlineJustAcceptDateStr=null, onlineFirstDate=null, onlineFirstDateStr=null, sourceXml=null, magXml=null, createTime=1789981973262, creator=13701087609, updateTime=1789981973262, updator=13701087609, issue=Issue{id=1308842471539442166, tenantId=1146029695717560320, journalId=1189982191388893191, year='2026', volume='61', issue='8', pageStart='2821', pageEnd='3220', issueExtLink='null', onlineDate='null', pubDate='1786464000000', pubDateStr='2026-08-12', beforeIssueId=null, nextIssueId=null, price=null, status=1, issueComplete=1, articleOrder=1, issueType=-1, specialIssue=null, createTime=1789981962332, creator='13701087609', updateTime=1789984137222, updator='13701087609', preIssue=null, nextIssue=null, articleTotal=null, ext={EN=IssueExt(id=1308851593773150481, tenantId=1146029695717560320, journalId=1189982191388893191, issueId=1308842471539442166, language=EN, specialIssueTitle=, coverIllustrator=null, specialIssueEditor=, specialIssueAbout=), CN=IssueExt(id=1308851593773150482, tenantId=1146029695717560320, journalId=1189982191388893191, issueId=1308842471539442166, language=CN, specialIssueTitle=, coverIllustrator=null, specialIssueEditor=, specialIssueAbout=)}, issueFiles=null, downloadFileDto=null}, startPage=2980, endPage=2988, ext={EN=ArticleExt(id=1308842517597090715, articleId=1308842517387375514, tenantId=1146029695717560320, journalId=1189982191388893191, language=EN, title=Research progress on delivery systems of ginsenoside Rg3, columnId=1190335348648547107, journalTitle=Acta Pharmaceutica Sinica, columnName=Reviews, runingTitle=null, highlight=null, articleAbstract=

Ginsenoside Rg3 possesses a variety of pharmacological activities. However, ginsenoside Rg3 has poor water solubility, which limits its full exertion of pharmacological effects. Existing delivery systems can not only improve the solubility of ginsenoside Rg3 but also leverage the unique advantages of each delivery system, enabling ginsenoside Rg3 to exert its pharmacological effects more effectively. This review focuses on the impact of ginsenoside Rg3 delivery systems, summarizes and compares the pharmacodynamics and pharmacokinetics of ginsenoside Rg3, and highlights the advantages of various delivery systems, provides a basis for the selection of ginsenoside Rg3 delivery systems, and serves as a cornerstone for the full development of ginsenoside Rg3.

, authors=Fang YANG, Yuan-bo JI, Juan QIU, Chen ZHANG, Yue-xian SUN, Jun LI*, authorsList=Fang YANG, Yuan-bo JI, Juan QIU, Chen ZHANG, Yue-xian SUN, Jun LI, authorCompany=null, correspAuthors=Jun LI, authorNote=null, correspAuthorsNote=null, copyrightStatement=Copyright ©2026 Acta Pharmaceutica Sinica. All rights reserved., copyrightOwner=null, extLink=null, articleAbsUrl=null, sourceXml=null, magXml=null, pdfUrl=null, pdf=null, pdfFileSize=null, pdfExtLink=null, richHtmlUrl=null, mobilePdfUrl=null, reviewReport=null, pdfFirstPage=null, abstractGraph=null, abstractGraphContent=null, abstractVideo=null, citation=null, cebUrl=null, magXmlContent=null, mapNumber=null, fund=null), CN=ArticleExt(id=1308842518725358502, articleId=1308842517387375514, tenantId=1146029695717560320, journalId=1189982191388893191, language=CN, title=人参皂苷Rg3递送系统研究进展, columnId=1190335349655180086, journalTitle=药学学报, columnName=综述, runingTitle=null, highlight=null, articleAbstract=

人参皂苷Rg3 (ginsenoside Rg3) 具有多种药理活性, 但人参皂苷Rg3水溶性差, 导致药效得不到充分发挥。现有的递送系统不仅能改善人参皂苷Rg3的溶解性, 还能发挥递送系统各自的优势, 使人参皂苷Rg3更好地发挥药效。本综述侧重于人参皂苷Rg3递送系统的影响, 对人参皂苷Rg3的药效学和药动学进行总结和对比, 突出各种递送系统的优势所在, 为人参皂苷Rg3递送系统的选择提供依据, 作为充分开发人参皂苷Rg3的基石。

, authors=杨芳, 季渊博, 邱娟, 张辰, 孙悦衔, 李俊*, authorsList=杨芳, 季渊博, 邱娟, 张辰, 孙悦衔, 李俊, authorCompany=null, correspAuthors=李俊, authorNote=

作者贡献:

杨芳负责文献检索和文章撰写; 季渊博、邱娟、张辰、孙悦衔参与论文的修改; 李俊对论文进行整体的指导和修改。所有作者阅读并认可终稿。

, correspAuthorsNote=
李俊,Tel: 13700650862, E-mail:
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Delivery systemDoset1/2/hCmax/μg·mL-1AUC0-t /μg·mL-1·htmax/hCL/L·h-1·kg-1MRT/hRefs.
Rg3-lipo0.4913.343 050.581 98634.2660.174[14]
Rg30.542.185.0.382 31152.0810.18[14]
Rg3-lipo6.28 ± 1.758.95 ± 0.8647.93 ± 8.300.42 ± 0.140.08 ± 0.029.48 ± 1.89[15]
Rg33.28 ± 1.792.31 ± 0.3212.32 ± 1.730.25 ± 0.000.28 ± 0.067.57 ± 2.57[15]
Rg3-lipo1st12.85 ± 1.71 213.98 ± 141.0213.13 ± 0.36[16]
2nd13.80 ± 1.651 368.12 ± 120.7713.50 ± 1.08[16]
Chol-PEG-lipo1st13.62 ± 1.201 229.03 ± 110.7213.46 ± 0.57[16]
2nd8.08 ± 1.52511.39 ± 50.0010.00 ± 0.60[16]
Rg3-SMEDDS4.882 ± 0.92826.549 ± 0.526220.579 ± 2.0631.667 ± 0.2891.753 ± 0.0168.332 ± 0.424[17]
Rg32.325 ± 0.08415.926 ± 1.5195.039 ± 2.55744.204 ± 0.1117.398 ± 0.332[17]
), ArticleFig(id=1308842525360747485, tenantId=1146029695717560320, journalId=1189982191388893191, articleId=1308842517387375514, language=CN, label=Tab.1, caption=

Pharmacokinetic parameters in plasma/serum of various delivery system. PEG: Polyethylene glycol; SMEDDS: Self-microemulsifying drug delivery system. Note: The unit of AUC0-t for reference 16 in the table is %dose·h

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Delivery systemDoset1/2/hCmax/μg·mL-1AUC0-t /μg·mL-1·htmax/hCL/L·h-1·kg-1MRT/hRefs.
Rg3-lipo0.4913.343 050.581 98634.2660.174[14]
Rg30.542.185.0.382 31152.0810.18[14]
Rg3-lipo6.28 ± 1.758.95 ± 0.8647.93 ± 8.300.42 ± 0.140.08 ± 0.029.48 ± 1.89[15]
Rg33.28 ± 1.792.31 ± 0.3212.32 ± 1.730.25 ± 0.000.28 ± 0.067.57 ± 2.57[15]
Rg3-lipo1st12.85 ± 1.71 213.98 ± 141.0213.13 ± 0.36[16]
2nd13.80 ± 1.651 368.12 ± 120.7713.50 ± 1.08[16]
Chol-PEG-lipo1st13.62 ± 1.201 229.03 ± 110.7213.46 ± 0.57[16]
2nd8.08 ± 1.52511.39 ± 50.0010.00 ± 0.60[16]
Rg3-SMEDDS4.882 ± 0.92826.549 ± 0.526220.579 ± 2.0631.667 ± 0.2891.753 ± 0.0168.332 ± 0.424[17]
Rg32.325 ± 0.08415.926 ± 1.5195.039 ± 2.55744.204 ± 0.1117.398 ± 0.332[17]
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Delivery systemt1/2/hCmax/μg·mL-1AUC0-t /μg·mL-1·htmax/hCL/L·h-1·kg-1MRT/hRefs.
Rg3-lipo (brain)38.64 ± 7.628.10 ± 1.6884.06 ± 10.590.50 ± 0.000.03 ± 0.0051.71 ± 11.98[15]
Rg3 (brain)3.68 ± 1.402.74 ± 0.2510.23 ± 0.990.19 ± 0.050.34 ± 0.056.34 ± 1.75[15]
Rg3-SMEDDS (heart)14.622 ± 3.7225.319 ± 0.08335.529 ± 2.3638.486 ± 0.847.589 ± 0.346[17]
Rg3 (heart)19.549 ± 12.7384.735 ± 0.11228.362 ± 0.76839.641 ± 2.9398.124 ± 0.654[17]
Rg3-SMEDDS (liver)16.087 ± 11.78220.733 ± 2.422135.765 ± 7.3892.333 ± 0.5772.287 ± 0.5247.312 ± 0.131[17]
Rg3 (liver)9.87 ± 6.96710.132 ± 0.45380.018 ± 5.382.667 ± 0.5774.161 ± 0.9428.294 ± 0.325[17]
Rg3-SMEDDS (spleen)7.415 ± 4.29414.077 ± 0.87477.227 ± 1.74634.749 ± 0.4126.888 ± 0.095[17]
Rg3 (spleen)7.634 ± 8.0815.517 ± 0.09932.792 ± 1.835411.031 ± 1.2887.207 ± 0.459[17]
Rg3-SMEDDS (lungs)2.724 ± 0.42119.211 ± 2.194121.923 ± 7.58723.278 ± 0.1947.24 ± 0.063[17]
Rg3 (lungs)11.723 ± 11.9577.246 ± 0.58158.129 ± 5.124.667 ± 1.1555.782 ± 0.6537.308 ± 0.095[17]
Rg3-SMEDDS (kidneys)10.154 ± 5.63833.562 ± 2.858233.194 ± 4.741.409 ± 0.2418.565 ± 0.139[17]
Rg3 (kidneys)9.225 ± 5.8711.158 ± 0.77474.205 ± 1.1513.667 ± 0.5774.721 ± 0.5017.362 ± 0.275[17]
Rg3-SMEDDS (brain)4.233 ± 1.9265.756 ± 0.03639.768 ± 2.57639.735 ± 0.5376.661 ± 0.138[17]
Rg3 (brain)2.197 ± 0.5242.993 ± 0.34915.806 ± 0.558323.987 ± 1.1464.7 ± 0.06[17]
Rg3-NCs-Gel (corneal)2.37 ± 0.3538.90 ± 0.99100.79 ± 8.450.50 ± 0.003.10 ± 0.20[22]
Rg3 (corneal)6.02 ± 3.2612.84 ± 0.9162.23 ± 11.680.25 ± 0.007.54 ± 2.68[22]
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Tissue pharmacokinetic parameters of various delivery system. NCs-Gel: Nanocrystals-gel; CL: Clearance; MRT: Mean residence time. Note: The units of Cmax and AUC0-t for reference 22 in the table are μg·g-1 and μg·g-1·h, respectively

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Delivery systemt1/2/hCmax/μg·mL-1AUC0-t /μg·mL-1·htmax/hCL/L·h-1·kg-1MRT/hRefs.
Rg3-lipo (brain)38.64 ± 7.628.10 ± 1.6884.06 ± 10.590.50 ± 0.000.03 ± 0.0051.71 ± 11.98[15]
Rg3 (brain)3.68 ± 1.402.74 ± 0.2510.23 ± 0.990.19 ± 0.050.34 ± 0.056.34 ± 1.75[15]
Rg3-SMEDDS (heart)14.622 ± 3.7225.319 ± 0.08335.529 ± 2.3638.486 ± 0.847.589 ± 0.346[17]
Rg3 (heart)19.549 ± 12.7384.735 ± 0.11228.362 ± 0.76839.641 ± 2.9398.124 ± 0.654[17]
Rg3-SMEDDS (liver)16.087 ± 11.78220.733 ± 2.422135.765 ± 7.3892.333 ± 0.5772.287 ± 0.5247.312 ± 0.131[17]
Rg3 (liver)9.87 ± 6.96710.132 ± 0.45380.018 ± 5.382.667 ± 0.5774.161 ± 0.9428.294 ± 0.325[17]
Rg3-SMEDDS (spleen)7.415 ± 4.29414.077 ± 0.87477.227 ± 1.74634.749 ± 0.4126.888 ± 0.095[17]
Rg3 (spleen)7.634 ± 8.0815.517 ± 0.09932.792 ± 1.835411.031 ± 1.2887.207 ± 0.459[17]
Rg3-SMEDDS (lungs)2.724 ± 0.42119.211 ± 2.194121.923 ± 7.58723.278 ± 0.1947.24 ± 0.063[17]
Rg3 (lungs)11.723 ± 11.9577.246 ± 0.58158.129 ± 5.124.667 ± 1.1555.782 ± 0.6537.308 ± 0.095[17]
Rg3-SMEDDS (kidneys)10.154 ± 5.63833.562 ± 2.858233.194 ± 4.741.409 ± 0.2418.565 ± 0.139[17]
Rg3 (kidneys)9.225 ± 5.8711.158 ± 0.77474.205 ± 1.1513.667 ± 0.5774.721 ± 0.5017.362 ± 0.275[17]
Rg3-SMEDDS (brain)4.233 ± 1.9265.756 ± 0.03639.768 ± 2.57639.735 ± 0.5376.661 ± 0.138[17]
Rg3 (brain)2.197 ± 0.5242.993 ± 0.34915.806 ± 0.558323.987 ± 1.1464.7 ± 0.06[17]
Rg3-NCs-Gel (corneal)2.37 ± 0.3538.90 ± 0.99100.79 ± 8.450.50 ± 0.003.10 ± 0.20[22]
Rg3 (corneal)6.02 ± 3.2612.84 ± 0.9162.23 ± 11.680.25 ± 0.007.54 ± 2.68[22]
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人参皂苷Rg3递送系统研究进展
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杨芳 , 季渊博 , 邱娟 , 张辰 , 孙悦衔 , 李俊 *
药学学报 | 综述 2026,61(8): 2980-2988
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药学学报 |综述 2026 , 61 (8) : 2980 -2988
人参皂苷Rg3递送系统研究进展
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杨芳, 季渊博, 邱娟, 张辰, 孙悦衔, 李俊*
作者信息
  • 云南中医药大学中药学院, 云南 昆明 650500
通讯作者:
李俊,Tel: 13700650862, E-mail:
作者简介:

作者贡献:

杨芳负责文献检索和文章撰写; 季渊博、邱娟、张辰、孙悦衔参与论文的修改; 李俊对论文进行整体的指导和修改。所有作者阅读并认可终稿。

Research progress on delivery systems of ginsenoside Rg3
Fang YANG, Yuan-bo JI, Juan QIU, Chen ZHANG, Yue-xian SUN, Jun LI*
Affiliations
  • School of Traditional Chinese Medicine, Yunnan University of Chinese Medicine, Kunming 650500, China
出版时间: 2026-08-12 doi: 10.16438/j.0513-4870.2025-1236
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人参皂苷Rg3 (ginsenoside Rg3) 具有多种药理活性, 但人参皂苷Rg3水溶性差, 导致药效得不到充分发挥。现有的递送系统不仅能改善人参皂苷Rg3的溶解性, 还能发挥递送系统各自的优势, 使人参皂苷Rg3更好地发挥药效。本综述侧重于人参皂苷Rg3递送系统的影响, 对人参皂苷Rg3的药效学和药动学进行总结和对比, 突出各种递送系统的优势所在, 为人参皂苷Rg3递送系统的选择提供依据, 作为充分开发人参皂苷Rg3的基石。

人参皂苷Rg3  /  递送系统  /  药理活性  /  药效学  /  药动学

Ginsenoside Rg3 possesses a variety of pharmacological activities. However, ginsenoside Rg3 has poor water solubility, which limits its full exertion of pharmacological effects. Existing delivery systems can not only improve the solubility of ginsenoside Rg3 but also leverage the unique advantages of each delivery system, enabling ginsenoside Rg3 to exert its pharmacological effects more effectively. This review focuses on the impact of ginsenoside Rg3 delivery systems, summarizes and compares the pharmacodynamics and pharmacokinetics of ginsenoside Rg3, and highlights the advantages of various delivery systems, provides a basis for the selection of ginsenoside Rg3 delivery systems, and serves as a cornerstone for the full development of ginsenoside Rg3.

ginsenoside Rg3  /  delivery system  /  pharmacological activity  /  pharmacodynamics  /  pharmacokinetics
杨芳, 季渊博, 邱娟, 张辰, 孙悦衔, 李俊. 人参皂苷Rg3递送系统研究进展. 药学学报, 2026 , 61 (8) : 2980 -2988 . DOI: 10.16438/j.0513-4870.2025-1236
Fang YANG, Yuan-bo JI, Juan QIU, Chen ZHANG, Yue-xian SUN, Jun LI. Research progress on delivery systems of ginsenoside Rg3[J]. Acta Pharmaceutica Sinica, 2026 , 61 (8) : 2980 -2988 . DOI: 10.16438/j.0513-4870.2025-1236
人参皂苷是人参的天然产物, 具有多种药理作用[1]。人参皂苷不同的化学结构和物理化学性质使其具有不同的药理作用。人参皂苷Rg3 (ginsenoside Rg3) 已被证实具有广泛的药理活性, 包括抗肿瘤、抗心血管疾病、抗炎、抗病毒、抗疲劳、抗抑郁和神经保护作用[2]。但是人参皂苷Rg3疏水性强, 水溶性差、体外溶出速度慢、口服吸收慢, 导致其生物利用度较低[3]。将人参皂苷Rg3制备成不同递送系统可以克服其缺点并改善其药效学和药动学, 本综述侧重于递送系统的影响, 对人参皂苷Rg3的药效学和药动学进行总结和对比, 为更好地开发和利用人参皂苷Rg3奠定基础。
水凝胶是一类特殊的聚合物材料, 它由凝胶单体通过化学或物理交联的方式连接, 形成具有亲水性的网状结构。这类材料有着显著的特性: 吸水性和保水性强, 质地柔软, 性质与生物体组织相似。从结构上看, 水凝胶属于三维网络状的多孔材料, 其内部的空间结构能够承载药物、细胞、细胞因子等物质[4]。
人参皂苷Rg3制备成水凝胶, 十二烷基硫酸钠(sodium dodecyl sulfate, SDS) 主要增加其在水中的溶解度, 透明质酸(hyaluronic acid, HA) 和壳聚糖(chitosan, Cs) 主要让它更容易渗透皮肤, 被皮肤更好地吸收, 而泊洛沙姆407 (poloxamer 407, P407) 主要控制凝胶的温敏化, 间接控制药物的释放。人参皂苷Rg3共聚物水凝胶中的共聚物不仅能控制Rg3的释放, 还能实现Rg3的长效缓释。因此含有人参皂苷Rg3的水凝胶材料作用于组织器官等病理位置, 不但起到仿生支架的作用, 还能够释放人参皂苷Rg3帮助组织器官恢复, 更好地发挥人参皂苷Rg3的药理活性。
人参皂苷Rg3是一种四环三萜皂苷, 根据氢在碳20上的定位, 有两个立体异构体: 20(S) 和20(R), 其结构(图1) 使其在溶剂里和生理环境中都难以溶解, 让它很难穿过皮肤的角质层, 也没法在表皮和真皮层有效留存。将人参皂苷Rg3制成水凝胶能克服以上缺点。
Wang等[5]和Peng[6]均使用SDS作为胶凝剂和助溶剂按图2开发Rg3/P407/HA/Cs水凝胶, P407、HA、Cs和SDS占比分别为18%、5%、1%和0.4%。就抗菌潜力而言, 负载Rg3的水凝胶比空白水凝胶和Rg3单体更有效。前者在每只小鼠的背部制造直径10 mm的圆形全层创面来研究其抗菌性能, 得出将人参皂苷Rg3和透明质酸水凝胶相结合, 既可以利用微环境加速伤口愈合, 又可以动态调节伤口微环境并形成适应性响应的结论。后者在抗菌性能基础上, 接着研究Rg3水凝胶对280~320 nm之间的中波紫外线(ultraviolet B, UVB) 照射的人角质形成细胞(human adult low calcium high temperature keratinocyte, HaCaT) 的抗损伤作用, 发现Rg3水凝胶对细胞凋亡的抑制作用和促炎细胞因子表达的诱导可能与活性氧(reactive oxygen species, ROS)、核因子kappa B (nuclear factor-kappa B, NF-κB) 和激活蛋白1 (activator protein 1, AP-1) 信号通路的抑制有关。最后通过清洁级雄性肿瘤研究所(Institute of Cancer Research, ICR) 小鼠研究其对皮肤伤口修复的作用及相关机制, 研究结果表明, Rg3水凝胶可显著改善伤口收缩, 促进上皮和组织再生, 增加血管生成和胶原合成, 抑制炎症, 调节NF-κB/多功能蛋白SQSTM1 (sequestosome 1, p62) 途径是Rg3水凝胶促进伤口愈合的相关机制。
Peng等[7]以P407、HA、Cs和SDS占比分别为18%、0.2%、0.5%和0.4%按照图2流程制备了一种新型含Rg3的温度敏感性注射水凝胶, 该水凝胶具有独特的多孔结构, 具有良好的生物相容性、可控制Rg3释放及具备良好的抗氧化和抗菌活性, 是理想的用于伤口愈合的材料。Jin等[8]通过开环聚合法合成共聚物聚乳酸-羟基乙酸共聚物1600-聚乙二醇1000-聚乳酸-羟基乙酸共聚物1600 [poly(lactic-co-glycolic acid)1600-poly (ethylene glycol)1000-poly(lactic-co-glycolic acid)1600, PLGA 1600-PEG 1000-PLGA 1600], 制备载Rg3水凝胶, 采用皮下注射冰醋酸建立大鼠肛周溃疡模型, 观察载Rg3水凝胶对大鼠肛周溃疡愈合15 d的治疗效果, 发现Rg3水凝胶对肛周溃疡的治疗效果最好, 有可能成为治疗肛周溃疡的候选药物。
纳米材料指的是两类物质: 一类是尺寸小于100 nm的粒子, 另一类是尺寸虽小于1 µm但能展现出纳米颗粒特有性质的材料。脂质纳米材料、聚合物纳米材料等都可以被加工成多种药物载体形式, 例如脂质体、纳米乳、固体脂质纳米粒、聚合物胶束、聚合物纳米凝胶等[9]。由纳米材料制备的药物递送系统, 具备诸多明显的优势, 比如生物相容性高、靶向效果好、毒性低, 并且还能够同时承载多种药物等。本综述主要介绍脂质体、自微乳和胶束递送系统。
脂质体是一种人工构建的药物递送系统, 以天然或合成磷脂为主要原料, 磷脂分子的亲水头部朝向囊泡内外两侧的水相环境, 疏水尾部相互聚集形成闭合的双分子层膜结构, 囊泡内部可包裹水溶性物质, 双分子层膜中可嵌入脂溶性物质。这类制剂能够引导药物精准聚集在病变区域, 防止药物在体内循环时因代谢作用而失去药效。相比传统药物制剂, 脂质体制剂具有高效、低毒和靶向等特点[10]。
制备人参皂苷Rg3脂质体有多种方法, 常用的是薄膜分散法和乙醇注入法。薄膜分散法包封率一般要高于乙醇注入法, 但其存在一定的有机试剂残留风险。脂质体的成分比例(主要包括磷脂种类与比例、膜调节剂占比、药物与脂质比例)、粒径、多分散指数(polydispersity index, PDI) 和电位影响其在体内的递送、稳定性和靶向性。脂质体的成分比例直接影响其粒径、PDI和电位, 粒径进而影响脂质体的靶向性, 且处于50~200 nm粒径范围的脂质体能提高对肿瘤细胞的靶向性; PDI和zeta电位进而影响脂质体的稳定性, 四者协同优化后影响脂质体在体内的递送和脂质体的药效及药动学行为。因此将人参皂苷Rg3制成脂质体能提高靶向性, 主要充分发挥抗癌作用。由于人参皂苷和胆固醇结构相似, 又加上人参皂苷Rg3富含糖基, 目前有很多将人参皂苷Rg3代替胆固醇制备Rg3脂质体递送系统的研究, 该递送系统的糖基部分暴露在脂质体表面, 这些部分模仿人类细胞膜, 能增强载体稳定性, 且有效躲避体内吞噬系统的清除作用。
人参皂苷Rg3具有较好的抗癌活性, 能抑制多种癌细胞系的生长。但由于其靶向性的限制, 抗癌活性得不到充分发挥。将人参皂苷Rg3制备成脂质体后, 不仅能充分发挥其抗癌活性, 还能提高人参皂苷Rg3其余的药理活性。
Wen[11]采用薄膜分散法(图3) 成功制备出平均粒径为100 nm, PDI为0.16, zeta电位为-30 mV的新型靶向功能材料—叶酸-聚(2-乙基-2-噁唑啉)-胆固醇碳酸甲酯[folic acid-poly(2-ethyl-2-oxazoline)-cholesteryl methyl carbonate, FA-PEOz-CHMC, 简称FPC] 修饰的G-Rg3脂质体, 并以荷三阴性乳腺癌的BALB/c小鼠(取对数生长期4T1细胞, 皮下接种于雌性BALB/c小鼠右侧第四乳房脂肪垫处) 为动物模型, 考察其对肿瘤生长的抑制情况。发现FPC修饰的Rg3脂质体和Rg3溶液都能显著抑制小鼠肿瘤细胞的生长, 但是前者的抑制效果更明显。
Zhou[12]提出了一种Rg3治疗年龄性黄斑变性的多靶点治疗策略, 按图3流程成功构建了一种粒径为98.98 ± 4.03 nm、PDI为0.22 ± 0.005、zeta电位为-38.39 ± 0.45 mV的具有视网膜组织渗透和脉络膜新生血管靶向的脂质递药系统-视网膜靶向人参皂苷Rg3脂质体, 脂质体组成成分及比例为: 磷脂∶胆固醇= 4∶1; 药物∶脂质材料= 1∶5; 1, 2-二硬脂酰-sn-甘油-3-磷酸乙醇胺-聚乙二醇2000-精氨酸-甘氨酸-天冬氨酸[1, 2-distearoyl-sn-glycero-3-phosphoethanolamine-poly(ethylene glycol) 2000-arginine-glycine-aspartic acid, DSPE-PEG 2000-RGD]∶DSPE-PEG 2000 = 2∶1。该系统能够精准将Rg3递送到视网膜色素上皮细胞层(retinal pigment epithelial cell layer, RPE层) 和脉络膜新生血管(choroidal neovascularization, CNV) 病灶部位, 通过改善视网膜细胞的氧化损伤、抑制血管内皮生长因子(vascular endothelial growth factor, VEGF)/磷脂酰肌醇3-激酶(phosphatidylinositol 3-kinase, PI3K)/蛋白激酶B (protein kinase B, Akt) 信号通路及调控炎症因子的表达等机制协同发挥抗年龄性相关黄斑变性(age-related macular degeneration, AMD) 的作用, 从而实现了从氧化应激、血管生成和炎症反应等多个病理环节干预治疗AMD的目标。Ye等[13]采用薄膜分散法按照图3流程开展了人参皂苷Rg3脂质体的制备工作, 得到平均粒径为88.2 nm, 跨距为0.466, zeta电位为-26.75 mV的脂质体, 该脂质体磷脂与胆固醇质量比为8∶1。并重点研究其对黑色素瘤细胞生长的抑制作用。结果显示, 所制备的人参皂苷Rg3脂质体对A375黑色素瘤细胞展现出良好的生长抑制效果。
Yu等[14]采用薄膜分散法按照图3流程制备出粒径为133.9 nm, zeta电位为-23 mV的人参皂苷Rg3脂质体, 其脂药比为9.11, 蛋黄卵磷脂与胆固醇比为4.03。并对其抗肿瘤作用进行评价。通过体外细胞(人肝癌细胞HepG2、人肺癌细胞A549) 和体内动物实验(将A549细胞悬液皮下注射到小鼠右前上级肢的腋窝中建立动物模型) 得出脂质体负载人参皂苷Rg3可显著增强Rg3的细胞毒作用, 改变其体内药代动力学参数(表1[14-17]), 抑制肺癌血管生成和生长, 提高荷瘤小鼠的生存率和生活质量的结论。
Miao等[18]成功合成FPC, 并在Rg3-lipo表面修饰, 采用薄膜分散法按照流程图3得到平均粒径约为100 nm, PDI约为0.16, zeta电位约为30 mV的FPC-Rg3-lipo, 其中大豆卵磷脂∶胆固醇= 4∶1; 药脂比为3∶20; FPC∶PEOz-CHMC = 9∶1。体内抗肿瘤实验证实FPC-Rg3-lipo对三阴乳腺癌(triple-negative breast cancer, TNBC) 具有良好的拮抗作用, 改善了肿瘤纤维化程度, 并进一步降低药物的毒不良反应。
Jung等[19]通过薄膜分散法按照图3流程制备出粒径为136.4 ± 16.9 nm, 表面电荷为-4.8 ± 2.3 mV的Rg3脂质体, 其中卵磷脂和Rg3的比例为10∶1, 该脂质体显著降低了细胞和线粒体活性氧水平的升高, 因此, 可作为皮肤细胞健康老化的红外保护剂。Huang等[20]采用薄膜分散法通过图3开发了HA修饰的粒径为152 nm, zeta电位为-25 mV的Rg3脂质体, 其脂药比为9∶1, 该脂质体不仅显著抑制视网膜缺血再灌注(retinal ischemia-reperfusion, RIR) 损伤引起的氧化应激。还促进M1型巨噬细胞向M2型的转变, 最终逆转促炎微环境。作者还进一步发现它们可以抑制沉寂信息调节因子(silent information regulator, SIRT1)/转录因子叉头盒蛋白O3 (transcription factor forkhead box protein O3, FOXO3a) 和NF-κB/信号转导与转录激活因子3 (signal transducer and activator of transcription 3, STAT3) 信号通路。Zhou等[21]采用薄膜分散法按照图3流程研制出粒径为98.98 ± 4.03 nm, PDI为0.22 ± 0.005, zeta电位为-38.39 ± 0.45 mV的RGD-Rg3脂质体, 该脂质体的成分及比例为: 大豆卵磷脂∶胆固醇∶DSPE-PEG 2000∶DSPE-PEG 2000-RGD∶Rg3 = 6∶24∶1∶2∶6。与游离Rg3相比, Rg3脂质体显著降低了氧化应激和炎症。在体内, RGD-Rg3脂质体显著降低了AMD小鼠模型中CNV的形成和血管渗漏。从机制上讲, RGD-Rg3脂质体减弱了氧化应激, 抑制了缺氧诱导因子1亚基α (hypoxia-inducible factor 1 subunit alpha, HIF-1α)/VEGF通路, 与未修饰的脂质体和游离Rg3相比, RGD修饰显著提高了对CNV损伤的靶向性, 通过与血管表面整合素受体的特异性结合而增强了治疗效果。
Li[15]按图4高压匀质法研发出一种粒径为169.90 ± 6.07 nm, PDI为0.21 ± 0.01, zeta电位为5.68 ± 0.33 mV的经乳铁蛋白修饰的人参皂苷Rg3纳米脂质载体, 并针对该载体开展经鼻给药后的药动学研究(表1、2[15-22])。发现无论是否经过乳铁蛋白修饰, 人参皂苷Rg3纳米脂质载体经鼻给药后, 均能增强药物对脑部的靶向性; 其中, 经乳铁蛋白修饰的纳米脂质载体, 在提升脑靶向效果方面表现更为突出。
另有研究中, Zheng[23]采用乙醇注入法制备了粒径为93.95 nm, PDI为0.138, zeta电位为-2.42 mV的人参皂苷Rg3脂质体, 该脂质体的脂药比为15∶1, 膜材比为4∶1, 水相PBS的pH = 6.8。随后结合网络药理学分析与体外实验, 对该脂质体的抗肝癌活性进行评估, 并深入探究其作用机制。实验发现, 人参皂苷Rg3对肝癌细胞增殖的抑制作用呈现剂量依赖性, 具体可通过诱导肝癌细胞发生G1期周期阻滞实现; 同时, 它还能降低细胞周期蛋白D1及细胞周期蛋白依赖性激酶2/4的表达水平。此外, 人参皂苷Rg3可下调SIRT2蛋白的表达, 进而提高全细胞中H3K18ac (抗乙酰基-组蛋白H3赖氨酸18抗体) 与H4K16ac (组蛋白H4第16位赖氨酸残基的乙酰化修饰产物) 的修饰水平。该研究进一步明确, 人参皂苷Rg3脂质体的抗肝癌活性较游离药物显著提升, 且证实了该脂质体能够辅助人参皂苷Rg3实现跨膜转运, 为药物发挥作用创造条件。Han等[24]为改善2型糖尿病小鼠的症状通过乙醇注入法设计和开发粒径约为140.5 ± 1.4 nm, PDI为0.11 ± 0.08, zeta电位为-0.10 ± 0.05 mV的PEG-lipo-Rg3, 其药脂比(w/w) = 1∶5, 胆固醇/磷脂(w/w) = 5∶1, DSPE-PEG 2000添加量为7%。体内实验结果表明, PEG-lipo-Rg3具有明显的改善2型糖尿病小鼠体重和摄食量的作用, 经PEG-lipo-Rg3治疗后, 小鼠的糖耐量显著提高, 表明PEG-lipo-Rg3可能是一种潜在的治疗2型糖尿病的药物, 为人参皂苷治疗2型糖尿病提供了一条新的途径。
Shen等[25]创新性地用富含糖基的人参皂苷代替脂质体中的胆固醇作为脂质体的膜材料, 基于人参皂苷和胆固醇之间的结构相似性, 创建了一种名为Rg3-lipo的药物递送系统, 并用此系统装载紫杉醇和递送紫杉醇。发现此系统不仅能增强紫杉醇-Rg3-lipo的抗肿瘤效果, 而且在包括非人灵长类动物在内的多种动物模型中具有良好的生物利用度和安全性, 以及它对癌细胞和髓系来源的抑制性细胞(myeloid-derived suppressor cells, MDSCs) 有双重靶向作用。Zhu等[26, 27]用人参皂苷Rg3代替胆固醇, 通过薄膜分散法(图3) 分别制备出粒径为88.7 ± 0.99 nm, PDI为0.075 ± 0.011, 蛋黄卵磷脂∶Rg3∶紫杉醇(paclitaxel, PTX) 为20∶6∶3的紫杉醇Rg3脂质体和粒径为66.12 ± 0.393 nm, Rg3与蛋黄卵磷脂比例为3∶10的紫杉醇Rg3脂质体, 与传统的胆固醇脂质体相比, Rg3-PTX-lipo的耐药性逆转能力和体内抗肿瘤作用明显增强。且Rg3-PTX-lipo在体内对C6胶质瘤细胞表现出更强的抗增殖作用。Xia等[16, 28]选用Rg3代替胆固醇和PEG通过图3流程分别制备出粒径为99.74 ± 7.50 nm, PDI为0.10 ± 0.03, zeta电位为-29.9 ± 0.62 mV的Rg3脂质体和一种多功能的粒径为96.9 ± 4.5 nm, PDI为0.15 ± 0.02, zeta电位为-27.8 ± 3.0 mV的Rg3脂质体载DTX (多西他赛), 发现前者具有良好的隐形性, 利用Rg3代替PEG和胆固醇制备脂质体, 可以延长脂质体的血液循环时间, 且有降低血液清除的作用(表1); 后者可以通过Rg3实现肿瘤细胞靶向和冷热肿瘤转化, 从而提高负载DTX的治疗效果。Zhang等[29]也采用薄膜分散法(图3) 制备Rg3与大豆卵磷脂的比例为1∶7, 粒径为116.50 ± 0.72 nm, PDI为0.12 ± 0.01, zeta电位为‒26.6 ± 0.6 mV的雷公藤红素Rg3脂质体, 该脂质体中的人参皂苷Rg3被检测到散布在磷脂双分子层中, 并且其糖基暴露在脂质体的表面。通过Rg3和肥胖肿瘤细胞中过表达的葡萄糖转运蛋白1之间的相互作用促进有利的肿瘤组织积聚。
自微乳给药系统(self-microemulsifying drug delivery system, SMEDDS) 是一种由药物、油相、乳化剂和助乳化剂混合而成的均匀澄清液体。这种系统在室温下遇到水时, 会自动乳化形成水包油型(O/W) 的微乳状液。当SMEDDS经口服进入人体后, 在胃肠道环境中会先被胃液分散稀释, 形成微乳; 随后进入小肠, 在各种消化酶和胆盐等物质的作用下进一步被消化吸收。对于那些难溶于水的药物来说, SMEDDS能通过多种机制显著提升其口服后的生物利用度, 比如提高药物在体内的溶解度、增强药物对肠道细胞的渗透性, 以及触发淋巴转运途径等[30]。
人参皂苷Rg3自微乳递送系统的成分比例及粒径、电位等影响其在体内的药动学行为, 进而影响药效发挥。将人参皂苷Rg3制成磷脂复合物自微乳后不仅能增加其渗透性, 还能提高其在肠道中的分散能力、稳定性和溶解性, 从而提高口服生物利用度, 进而使其更充分地发挥药理活性。
人参皂苷Rg3表现出较低的水溶性是受其苷元和糖链的影响, 且由于其具有大骨架的达玛烷型结构, 膜渗透性较低。因此, 人参皂苷Rg3经口服进入人体后, 肠道对它的吸收比较困难, 生物利用度也比较低。将人参皂苷Rg3制成自微乳后, 主要提高其生物利用度。
Zhang[17]使用溶剂蒸发法成功制备出粒径为(73.07 ± 0.52) nm, PDI为(0.118 ± 0.01), zeta电位为(-8.98 ± 0.202) mV的人参皂苷Rg3磷脂复合物自微乳, 该自微乳的Rg3-磷脂酰胆碱(phosphatidylcholine, PC) 含量为13.2%, 油酸乙酯含量为48.82%。并围绕该制剂开展了人结直肠腺癌细胞(human colorectal adenocarcinoma cells, Caco-2) 转运实验与大鼠体内药动学研究, 以探究其吸收特性与体内分布规律。在Caco-2细胞转运实验中, 人参皂苷Rg3磷脂复合物自微乳透过Caco-2细胞单层的转运效率, 显著高于游离态的人参皂苷Rg3。进一步机制分析发现, 游离人参皂苷Rg3的肠道转运过程会受到P-糖蛋白(P-glycoprotein, P-gp)、多药耐药相关蛋白(multidrug resistance-associated protein, MRPs) 及乳腺癌耐药蛋白(breast cancer resistance protein, BCRP) 3类转运蛋白的共同影响; 而人参皂苷Rg3磷脂复合物自微乳的肠道转运, 主要受MRPs与BCRP两类转运蛋白调控, 其受转运蛋白的限制作用相对减弱。大鼠体内药动学研究结果显示(表1), 与人参皂苷Rg3相比, 人参皂苷Rg3磷脂复合物自微乳能够有效提升药物的口服吸收效率; 同时, 该制剂还能增加人参皂苷Rg3在大鼠心脏、肝脏、脾脏、肺部、肾脏及脑组织中的药物浓度, 并改变其在这些组织中的分布比例, 为药物更好地作用于靶组织创造了条件(表2)。
胶束是由表面活性剂分子聚集形成的微小集合体, 在这个集合体内部还分散着其他物质。嵌段共聚物胶束是由具有亲水和亲油双重性质的嵌段共聚物, 在水中溶解后自动形成的一种高分子聚集结构, 其形态呈现“内核-外壳”的特征。这种胶束能发挥多重作用: 不仅可以提高药物的溶解度、调控药物的释放过程, 还能避免网状内皮系统对药物的非特异性吸收, 同时改变药物在体内的代谢过程和在组织中的分布情况。
人参皂苷Rg3胶束的粒径大小和载体材料影响其药效学行为。人参皂苷Rg3胶束具有纳米尺度优势, 可利用病变组织的“高通透性和滞留效应”, 让包裹的人参皂苷Rg3更多聚集于病灶部位, 同时减少联用药物在正常组织的游离分布。人参皂苷Rg3胶束的载体材料不仅能实现对Rg3释放的调控, 还可通过表面修饰靶向配体, 进一步提升Rg3在病灶的精准富集, 降低对心肌、肝肾等健康器官的毒性攻击, 从源头减少联合用药的毒不良反应叠加。
将人参皂苷Rg3制备成胶束后, 不仅解决Rg3水溶性差的问题, 胶束的载体材料和粒径在使其充分发挥药效的基础上还降低联合用药的毒性。
Fu[31]选用甲氧基聚乙二醇-聚乳酸(methoxy polyethylene glycol-polylactic acid, mPEG-PLLA) 共聚物作为载体材料, 通过溶剂蒸发-薄膜分散法成功制备出平均粒径为(142.1 ± 8.9) nm, zeta电位为(-8.5 ± 0.4) mV, PDI为(0.145 ± 0.017) 的负载人参皂苷Rg3的载药胶束, 该胶束的聚合物和药物用量比为9∶1。并通过实验对该胶束的肿瘤抑制效果展开评价。结果证实, 人参皂苷Rg3-mPEG-PLLA载药胶束对肿瘤细胞生长具有显著的抑制作用。在动物实验中可观察到, 与注射人参皂苷Rg3原料药的裸鼠组相比, 注射人参皂苷Rg3-mPEG-PLLA载药胶束的裸鼠, 其肿瘤体积的增长速度明显更慢。作者推测, 人参皂苷Rg3-mPEG-PLLA载药胶束的外表面修饰有PEG长链, 该结构能显著提升胶束的亲水性, 帮助胶束有效规避网状内皮系统的非特异性吞噬与清除, 从而延长药物在血液中的循环时间; 更长的血药循环时间使得更多载药胶束能够到达并聚集在肿瘤部位。当载药胶束进入肿瘤细胞后, 由于肿瘤细胞内环境呈偏酸性(pH值较低), 胶束结构会发生变化, 促使药物快速释放, 最终实现对肿瘤生长的有效抑制。Li等[32]研发的粒径为49.44 ± 0.15 nm, PDI为0.339 ± 0.001的泊洛沙姆407-Rg3胶束与多柔比星联合给药可以减轻多柔比星心脏毒性, 改善线粒体和代谢功能, 改善钙处理。
复合递送系统是指将两种或多种不同递送系统的优势结合, 通过合理的处方设计与工艺优化, 形成的一种新型药物递送系统。它不是简单的剂型叠加, 而是通过协同作用弥补单一剂型的缺陷, 提升药物的稳定性、生物利用度或靶向性, 同时兼顾临床使用的便利性。
人参皂苷Rg3制成纳米晶凝胶, 纳米晶的粒径优势主要提高Rg3的吸收, 水凝胶的基质及组成主要增强皮肤黏附与缓释效果, 两者共同提升经皮吸收效率。人参皂苷Rg3制成脂质体水凝胶滴眼液, 脂质体组成成分克服了Rg3水溶性差的问题, 脂质体粒径等参数和水凝胶基质及组成改善了药物在伤口部位的吸收和滞留, 滴眼液实现了用药的便捷性, 三者协同充分发挥Rg3抗炎作用。
Zhang[22]选择介质研磨法先将Rg3制备成粒径为157.30 ± 0.46 nm, PDI为0.16 ± 0.02, 电位为-16.33 ± 0.06 mV的纳米晶, 再以泊洛沙姆407、泊洛沙姆188和卡波姆934为基质, 将纳米晶制成温敏凝胶, 制成的Rg3纳米晶凝胶粒径和电位大小与纳米晶几乎一致。并通过家兔考察Rg3纳米晶凝胶的眼部吸收药动学。Rg3纳米晶凝胶可以延长角膜滞留时间、提高角膜通透性(表2)。Tang等[33]首先通过薄膜分散法将Rg3制成粒径为90.19 ± 0.55 nm, PDI为0.140 ± 0.029的脂质体, 该脂质体的蛋黄卵磷脂、Rg3和DSPE-mPEG 2000的比例为3∶1∶0.15, 再通过巯基壳聚糖将脂质体嵌入水凝胶, 最后制成滴眼液, 并通过小鼠考察其治疗角膜碱烧伤的效果。结果表明: 此滴眼液可显著延长药物在眼表的滞留时间, 具有良好的安全性, 对角膜损伤具有良好的治疗效果。
递送系统是药物发挥药效的关键, 不同的药物有不同的物理化学性质, 选择合适的递送系统能使药物充分发挥药效, 有时甚至起到事半功倍的效果。将人参皂苷Rg3制备成不同递送系统后不仅解决水溶性差的问题, 其药效学和药动学行为也大相径庭。
综上所述, 人参皂苷Rg3凝胶递送系统主要通过组成成分及比例改变Rg3的药效学行为; 脂质体、自微乳、胶束递送系统主要凭借辅料组成及比例和粒径优势, 改变Rg3在体内的药动学行为, 进而充分发挥其药理活性; 复合递送系统则是将前两种甚至3种递送系统的优势叠加起来, 进而增强Rg3的药效。通过对不同递送系统的自身优势对比, 得出了不同递送系统的药效学和药动学差异(图5), 发现Rg3水凝胶递送系统主要是在抗菌、抗氧化、皮肤修复能力上占有优势, 这为将来Rg3治疗皮肤性疾病递送系统的选择奠定基础。Rg3脂质体和胶束递送系统都显著提高抗肿瘤作用, 而且两者加以修饰后都具有靶向性, 还能调控Rg3的释放, 这为各种癌症的治疗开辟了新道路。此外, Rg3代替胆固醇制备的脂质体, 其在体内可以逃避吞噬和清除。Rg3胶束还可以降低联合用药的毒性, 这为联合用药的疾病提供了新路径。Rg3自微乳递送系统主要是能提高跨膜效率, 改变药物组织分布, 从而提高口服生物利用度, 这为减少口服药物的首过效应提供了一种手段。Rg3复合递送系统起到双重作用, 不仅克服Rg3自身缺点, 还充分发挥其药效。人参皂苷Rg3不同递送系统药效学和药动学差异为进一步开发和利用Rg3做贡献, 在此基础上, 它也为其他疏水性药物递送系统的选择提供参考。
但各种递送系统也有各自的缺点, 脂质体递送系统、自微乳递送系统和胶束递送系统较为明显。脂质体的载药空间有限, 尤其是对小分子药物的包封率较低, 且载药量易受药物亲疏水性影响; 同时生产过程中对温度、pH等条件要求严苛, 规模化生产时易出现批次差异, 成本较高。自微乳递送系统需添加大量表面活性剂和助表面活性剂, 这些成分可能刺激胃肠道黏膜, 破坏肠道屏障, 这是将来研究人员需要关注的问题。且自微乳制剂长期放置后, 可能因油相、水相分层或表面活性剂析出, 导致制剂外观变化、药效下降, 对储存条件(如避光、低温) 要求较高。胶束疏水内核的容积固定, 载药能力有限, 后续研究人员可以往其疏水内核的容积入手来提高载药量。

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doi: 10.16438/j.0513-4870.2025-1236
  • 接收时间:2025-10-17
  • 首发时间:2026-09-21
  • 出版时间:2026-08-12
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  • 收稿日期:2025-10-17
  • 修回日期:2025-12-24
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    云南中医药大学中药学院, 云南 昆明 650500

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鹅膏菌科Amanitaceae 2 11 5.26 鹅膏菌属 Amanita 10 4.78
小菇科 Mycenaceae 2 12 5.74 丝盖伞属 Inocybe 5 2.39
多孔菌科 Polyporaceae 8 14 6.70 蜡蘑属 Laccaria 5 2.39
红菇科 Russulaceae 3 23 11.00 小皮伞属 Marasmius 6 2.87
小菇属 Mycena 11 5.26
光柄菇属 Pluteus 5 2.39
红菇属 Russula 17 8.13
栓菌属 Trametes 5 2.39
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