Article(id=1236335233025495410, tenantId=1146029695717560320, journalId=1235980733773295621, issueId=1236335227262529633, articleNumber=null, orderNo=null, doi=null, pmid=null, cstr=null, oa=null, hot=null, price=null, onlineType=0, articleFormat=0, articleType=null, articleTypeStr=null, receivedDate=null, receivedDateStr=null, revisedDate=null, revisedDateStr=null, acceptedDate=1672243200000, acceptedDateStr=2022-12-29, onlineDate=1772694889551, onlineDateStr=2026-03-05, pubDate=1696003200000, pubDateStr=2023-09-30, doiRegisterDate=null, doiRegisterDateStr=null, onlineIssueDate=1772694889551, onlineIssueDateStr=2026-03-05, onlineJustAcceptDate=null, onlineJustAcceptDateStr=null, onlineFirstDate=null, onlineFirstDateStr=null, sourceXml=null, magXml=null, createTime=1772694889551, creator=13701087609, updateTime=1772694889551, updator=13701087609, issue=Issue{id=1236335227262529633, tenantId=1146029695717560320, journalId=1235980733773295621, year='2023', volume='32', issue='18', pageStart='1801', pageEnd='1904', issueExtLink='null', onlineDate='null', pubDate='null', beforeIssueId=null, nextIssueId=null, price=null, status=1, issueComplete=1, articleOrder=1, issueType=-1, specialIssue=null, createTime=1772694888176, creator=13701087609, updateTime=1772694973637, updator=13701087609, preIssue=null, nextIssue=null, ext={EN=IssueExt(id=1236335585770656362, tenantId=1146029695717560320, journalId=1235980733773295621, issueId=1236335227262529633, language=EN, specialIssueTitle=, coverIllustrator=null, specialIssueEditor=, specialIssueAbout=), CN=IssueExt(id=1236335585770656363, tenantId=1146029695717560320, journalId=1235980733773295621, issueId=1236335227262529633, language=CN, specialIssueTitle=, coverIllustrator=null, specialIssueEditor=, specialIssueAbout=)}, issueFiles=null}, startPage=1882, endPage=1892, ext={EN=ArticleExt(id=1236335233277153661, articleId=1236335233025495410, tenantId=1146029695717560320, journalId=1235980733773295621, language=EN, title=Compatibility study of the main active components of Gardenia-Panax notoginseng against Aβ_1-42-induced damage to SH-SY5Y cells based on uniform design experiments, columnId=null, journalTitle=Chinese Journal of New Drugs, columnName=null, runingTitle=null, highlight=null, articleAbstract=

Objective: To explore the effective compatibility ratio of the 5 main active ingredients in Gardenia and Panax notoginseng by uniform design test method thus to provide preliminary experimental evidence for clinical treatment of Alzheimer's disease. Methods: A model of SH-SY5Y cell injury induced by β-amyloid (Aβ_1-42) was established, and the cell survival rate was used as an indicator to study the effective concentrations of the main active ingredients against Aβ_1-42-induced SH-SY5Y neuronal injury, and according to the damage recovery rate, five ingredients with better efficacy were selected. On this basis, the five components with good efficacy were used as independent variables X₁, X₂, X₃, X₄ and X₅, respectively, the injury recovery rate (%) as the dependent variable Y, U₂₁ (21⁵) uniform design table and 2 mathematical models of linear and quadratic polynomials were selected, and the variables were screened by stepwise regression method to determine the effective compatibility ratio of the 5 active ingredients. Results: The main active components of Gardenia-Panax notoginseng, except genipin, could increase the cell survival rate of SH-SY5Y cells induced by Aβ_1-42 in a concentration-dependent manner. 5 ingredients with good efficacy were identified as notoginsenoside R1, ginsenoside Rb1, ginsenoside Rg1, geniposide, and genipin gentiobiglycoside. The results of uniform design experiments were obtained by regression analysis and Y=12.775 019 92-0.493 827 042 7X₂+0.070 634 665 58X₁X₂-0.022 126 968 533X₁X₅+0.053 000 691 95X₃X₄ (r=0.857 4, F=11.105 9, P=0.002), and the uniform design test verified that the best combination ratio was notoginsenoside R1∶ginsenoside Rb1∶ginsenoside Rg1∶geniposide∶genipin gentiobiglycoside=1∶1∶1∶1∶0. Behavioral experiments showed that compared with the model group, the number of tests and memory errors of donepezil hydrochloride group and gardenia-Panax notoginseng optimal matching were significantly reduced. The results of ROS and Western blot showed that compared with the model group, the optimal combination of donepezil hydrochloride group and gardenia-Panax notoginseng could effectively reduce the fluorescence intensity of ROS and the expression of RAGE protein. Conclusion: The optimal matching ratio obtained by uniform design screening can effectively improve Alzheimer's disease, and its mechanism of action may play an anti-Alzheimer's effect by inhibiting the activation of RAGE-ROS pathway, which provides an experimental basis for the treatment of Alzheimer's disease.

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目的：采用均匀设计实验方法，探索栀子和三七中5个主要有效成分的有效配伍比例，为临床治疗阿尔茨海默病提供初步实验依据。方法：建立β-淀粉样蛋白（Aβ_1-42）诱导SH-SY5Y细胞损伤模型，以细胞存活率为指标，研究主要有效成分抗Aβ_1-42诱导SH-SY5Y神经细胞损伤的有效浓度，以损伤恢复率为指标选出5种药效较好的成分。在此基础上筛选出的5种药效良好的成分分别为自变量X₁，X₂，X₃，X₄，X₅，损伤恢复率（%）为因变量Y，选用U₂₁（21⁵）均匀设计表和线性、二次多项式2种数学模型，以逐步回归方法筛选变量，确定5种有效成分的有效配伍比例。结果：栀子-三七主要有效成分除京尼平外均能提高Aβ_1-42诱导SH-SY5Y细胞损伤的细胞存活率，并呈浓度依赖性。筛选得到5种药效良好的成分为三七皂苷R1、人参皂苷Rb1、人参皂苷Rg1、栀子苷、京尼平龙胆双糖苷。均匀设计实验结果经回归分析得到Y=12.775 019 92-0.493 827 042 7X₂+0.070 634 665 58X₁X₂-0.022 126 968 533X₁X₅+0.0530 006 919 5X₃X₄（r=0.857 4，F=11.105 9，P=0.002），均匀设计实验验证得到最佳配伍比例为三七皂苷R1∶人参皂苷Rb1∶人参皂苷Rg1∶栀子苷∶京尼平龙胆双糖苷=1∶1∶1∶1∶0。行为学试验显示与模型组小鼠比较，盐酸多奈哌齐组、栀子-三七最优配伍的测试次数和记忆错误次数均显著降低。ROS和Western blot结果显示与模型组比较，盐酸多奈哌齐组、栀子-三七最优配伍可以有效降低ROS的荧光强度和RAGE蛋白的表达。结论：运用均匀设计筛选获得的最优配伍比例可有效改善阿尔茨海默病，其作用机制可能为抑制RAGE-ROS通路的激活发挥抗阿尔茨海默病的作用，为治疗阿尔茨海默病提供了实验依据。

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岳钰茗，男，硕士研究生，研究方向：中药新药研发。E-mail: yueyuming123@163.com。

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岳钰茗，男，硕士研究生，研究方向：中药新药研发。E-mail: yueyuming123@163.com。

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³Tianjin Key Laboratory of Quality Marker of Traditional Medicine, Tianjin 300301, China
⁴Tianjin Institute of Pharmaceutical Research, Tianjin 300301, China, bio=null, bioImg=null, bioContent=null, aboutCorrespAuthor=null), CN=AuthorExt(id=1236341500913700884, tenantId=1146029695717560320, journalId=1235980733773295621, articleId=1236335233025495410, authorId=1236341500708179976, language=CN, stringName=杨冰, firstName=null, middleName=null, lastName=null, prefix=null, suffix=null, authorComment=null, nameInitials=null, affiliation=null, department=null, xref=^{2, 3, 4}, address=²药物成药性评价与系统转化全国重点实验室（原释药技术与药动学国家重点实验室），天津 300301
³天津市中药质量标志物重点实验室，天津 300301
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³Tianjin Key Laboratory of Quality Marker of Traditional Medicine, Tianjin 300301, China
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³天津市中药质量标志物重点实验室，天津 300301
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³Tianjin Key Laboratory of Quality Marker of Traditional Medicine, Tianjin 300301, China
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³天津市中药质量标志物重点实验室，天津 300301
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