桃红四物汤治疗膝骨关节炎的疗效及机制研究

doi:10.3877/cma.j.issn.1674-134X.2026.02.009

目的

观察桃红四物汤治疗膝骨关节炎的临床疗效，并采用系统药理学探讨其作用机制。

方法

纳入2023年7月至2024年7月在佛山健翔骨伤医院就诊的膝骨关节炎患者60例，排除依从性差及合并严重心脑血管疾病、风湿疾病等患者。运用随机数字表法将患者分为治疗组、对照组各30例，治疗组给予桃红四物汤联合体外冲击波治疗，对照组给予口服塞来昔布联合体外冲击波治疗。所有患者于治疗第1、2个月后随访视觉模拟疼痛评分（VAS）、西安大略和麦克马斯特大学骨关节炎指数（WOMAC），采用t检验方法比较两组治疗效果。利用中药系统药理学数据库与分析平台（TCMSP）搜索并筛选出桃红四物汤的活性成分及其作用的靶标，利用GeneCards及人类孟德尔遗传数据库（OMIM）筛选膝骨关节炎疾病的靶标，通过R软件将获得的桃红四物汤活性成分靶标与膝骨关节炎疾病靶标取交集并绘制Venn图，使用Cytoscape软件获得中药-活性成分-疾病-靶标的可视化网络关系图，再通过线上基因/蛋白质相互作用检索工具（STRING）获得活性成分-疾病靶标蛋白相互作用的网络（PPI），最后进行基因本体（GO）功能富集分析及京都基因与基因组百科全书（KEGG）通路富集分析，再将获得的主要活性成分化合物与核心靶标蛋白进行分子对接，对接结果进一步可视化。

结果

两组的VAS疼痛评分及WOMAC评分在治疗1、2个月后均较治疗前降低，差异均具有统计学意义（t=-3.24、-1.87、-5.69、-1.56，均为P<0.05）；与对照组比较，治疗组治疗后VAS疼痛评分及WOMAC评分降低更显著，差异均具有统计学意义（t=-5.21、-6.41、-3.01、-3.69，均为P<0.01）。从桃红四物汤筛选得到40个化合物，这些化合物可作用于蛋白丝氨酸/苏氨酸蛋白激酶(AKT1)、原癌基因c-Jun(JUN)、促分裂原活化蛋白激酶1(MAPK1)等120个治疗靶点，参与调控肿瘤坏死因子、白细胞介素-17等信号通路。

结论

桃红四物汤可有效缓解膝骨关节炎的症状，其作用机制可能与桃红四物汤有效成分作用多靶点，调控多通路的特点有关。

关键词: 医学, 中国传统, 骨关节炎, 膝, 治疗结果, 网络药理学

Objective

To observe the clinical effect of Taohong Siwu decoction in the treatment of knee osteoarthritis, and explore its mechanism bysystems pharmacology.

Methods

A total of 60 patients with knee osteoarthritis admitted to Foshan Jianxiang Bone Injury Hospital from July 2023 to July 2024 were randomly enrolled, excluding those with poor compliance or comorbid severe cardiovascular and cerebrovascular diseases, rheumatic diseases, etc. They were randomly divided into treatment group and control group with 30 cases in each group. The treatment group was given Taohong Siwu decoction combined with extracorporeal shock wave therapy, while the control group was given oral celecoxib combined with extracorporeal shock wave therapy. Visual analogue scale (VAS) and Western Ontario and McMaster Universities osteoarthritis index (WOMAC) of knee joint were followed up after one and two months of treatment. T test was employed to compare the therapeutic efficacy between the two groups. Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP) was used to search and screen the active components and target of Taohong Siwu decoction. GeneCards and Online Mendelian Inheritance in Man (OMIM) Database were used to screen the targets of knee osteoarthritis disease. The intersection of the active component target of Taohong Siwu decoction and the target of knee osteoarthritis disease was selected by R software, and Venn diagram was drawn. The visualization network diagram of traditional Chinese medicine active ingredient-disease target was obtained by using the software of Cytoscape. Protein-protein interaction (PPI) of active ingredient disease target protein interaction was obtained through online string platform. Finally, gene ontology (Go) functional enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis were carried out, and then the obtained main active components were molecular docking with the core target protein, and the docking results were further visualized.

Results

After one and two months of treatment, VAS score and WOMAC score of the two groups were lower than those before treatment, the differences were statistically significant (t=-3.24, -1.87, -5.69, -1.56, all P<0.05); compared with the control group, the VAS score and WOMAC score of the treatment group decreased more significantly after treatment, and the differences were statistically significant (t=-5.21, -6.41, -3.01, -3.69, all P<0.05). Forty compounds were screened from Taohong Siwu decoction, which could act on 120 therapeutic targets, such as serine/threonine kinase 1 (AKT1), Jun proto-oncogene (JUN), mitogen-activated protein kinase1 (MAPK1), and participate in the regulation of tumor necrosis factor, interleukin-17 and other signal pathways.

Conclusion

Taohong Siwu decoction can effectively relieve the symptoms of knee osteoarthritis, which may be related to the characteristics of multi-target and multi-channel regulation.

Key words: Medicine, Chinese traditional, Osteoarthritis, knee, Treatment outcomes, Network pharmacology

表1 随访病例一般资料对比

Table 1 Comparison of general data of follow-up cases

组别 Groups	例数 Number of cases	性别（男/女） Gender（male/female）	年龄［岁，（ $x ¯$ ±s）］ Age （year）	病程［年，（ $x ¯$ ±s）］ Course of disease（year）
治疗组 Treatment group	30	14/16	71.5±5.5	9.2±2.7
对照组 Control group	30	13/17	70.5±4.5	8.5±2.9
统计值 Statistical values		χ²= 0.07	t=0.42	t=0.90
P值		>0.05	>0.05	>0.05

表1 随访病例一般资料对比

Table 1 Comparison of general data of follow-up cases

组别 Groups	例数 Number of cases	性别（男/女） Gender（male/female）	年龄［岁，（ $x ¯$ ±s）］ Age （year）	病程［年，（ $x ¯$ ±s）］ Course of disease（year）
治疗组 Treatment group	30	14/16	71.5±5.5	9.2±2.7
对照组 Control group	30	13/17	70.5±4.5	8.5±2.9
统计值 Statistical values		χ²= 0.07	t=0.42	t=0.90
P值		>0.05	>0.05	>0.05

表2 治疗前后VAS评分（

x ¯

±s）

Table 2 VAS scores before and after treatment

组别 Groups	例数 Number of cases	治疗前 Before treatment	治疗1月后 One month after treatment	治疗2月后 Two months after treatment
治疗组 Treatment group	30	7.4±1.2	4.9±1.0^*	3.8±0.9^*
对照组 Control group	30	7.3±1.2	6.3±1.2^*	5.5±1.2^*
t值		0.45	-5.21	-6.41
P值		>0.05	<0.01	<0.01

表2 治疗前后VAS评分（

x ¯

±s）

Table 2 VAS scores before and after treatment

组别 Groups	例数 Number of cases	治疗前 Before treatment	治疗1月后 One month after treatment	治疗2月后 Two months after treatment
治疗组 Treatment group	30	7.4±1.2	4.9±1.0^*	3.8±0.9^*
对照组 Control group	30	7.3±1.2	6.3±1.2^*	5.5±1.2^*
t值		0.45	-5.21	-6.41
P值		>0.05	<0.01	<0.01

表3 治疗前后WOMAC评分（

x ¯

±s）

Table 3 WOMAC score before and after treatment

组别 Groups	例数 Number of cases	治疗前 Before treatment	治疗1月后 One month after treatment	治疗2月后 Two months after treatment
治疗组 Treatment group	30	152±22	117±18^*	98±16^*
对照组 Control group	30	145±23	130±17^*	113±15^*
t值		1.15	-3.01	-3.69
P值		>0.05	<0.01	<0.01

表3 治疗前后WOMAC评分（

x ¯

±s）

Table 3 WOMAC score before and after treatment

组别 Groups	例数 Number of cases	治疗前 Before treatment	治疗1月后 One month after treatment	治疗2月后 Two months after treatment
治疗组 Treatment group	30	152±22	117±18^*	98±16^*
对照组 Control group	30	145±23	130±17^*	113±15^*
t值		1.15	-3.01	-3.69
P值		>0.05	<0.01	<0.01

图1 桃红四物汤靶标与膝骨关节炎靶标韦恩图注：蓝色部分为疾病治疗靶点，红色为药物作用靶点

Figure 1 Venn diagram of Taohong Siwu decoction target and knee osteoarthritis target Note: The blue area represents disease treatment targets, while the red area indicates drug action targets.

图2 药物-有效活性成分-靶标网络图注：蓝色椭圆代表白芍，黄色椭圆代表川芎，红色椭圆代表红花，粉红色椭圆代表桃仁，橙色椭圆代表共有活性成分，绿色长方形代表交集基因，灰色连线代表二者的联系；连线越多，代表联系越紧密

Figure 2 Drug-active component-target network Note: the blue ellipse represents white peony root, the yellow ellipse represents Chuanxiong, the red ellipse represents safflower, the pink ellipse represents peach kernel, the orange ellipse represents shared active ingredients, the green rectangle represents intersecting genes, and the gray line represents their connection; the more lines, the tighter the connection

图3 药物-疾病靶标蛋白相互作用网络（PPI）

Figure 3 Drug-disease target PPI (protein-protein interaction) network

图4 GO（基因本体论）功能富集分析图

Figure 4 Analysis chart of GO (gene ontology) functional enrichment

图5 KEGG（京都基因与基因组百科全书）富集信号通路柱状图

Figure 5 KEGG (Kyoto Encyclopedia of Genes and Genomes) enrichment signaling pathways barplot

图6 部分桃红四物汤有效化合物与核心受体对接情况。图A为木犀草素与AKT1（蛋白丝氨酸/苏氨酸蛋白激酶）对接；图B为槲皮素与AKT1对接；图C为木犀草素与JUN对接；图D为槲皮素与JUN（Jun原癌基因）对接

Figure 6 Docking of some effective compounds of TaohongSiwu Decoction with core receptor. A shows the binding of luteolin to AKT1 (RAC-alpha serine/threonine-protein kinase); B shows the binding of quercetin to AKT1; C shows the binding of luteolin to JUN (Jun proto oncogene); D shows the binding of quercetin to JUN

［1］	Wong PK, Kokabi N, Guo Y, et al. Safety and efficacy comparison of three-vs four-needle technique in the management of moderate to severe osteoarthritis of the knee using cooled radiofrequency ablation［J］. Skeletal Radiol, 2021, 50（4）: 739-750.
［2］	杨金红, 邢更彦. 体外冲击波治疗骨关节炎研究进展［J/OL］. 中国医学前沿杂志（电子版）, 2014, 6（6）: 12-14.
［3］	梅轶芳. 中国骨关节炎流行病学研究现状及规范［J］. 中国实用内科杂志, 2019, 39（8）: 663-665.
［4］	Ranawat A, Guo K, Phillips M, et al. Health economic assessments of hyaluronic acid treatments for knee osteoarthritis: asystematic review［J］. Adv Ther, 2024, 41（1）: 65-81.
［5］	丁琼浩, 敖亮, 潘正刚, 等. 膝骨性关节炎的病因病机及用药分析［J］. 中医临床研究, 2014, 6（7）: 14-17.
［6］	王曙辉, 许明珠, 崔韶阳, 等. 针刺结合刺络放血疗法治疗膝关节骨性关节炎的临床随机对照研究［J］. 针刺研究, 2010, 35（2）: 129-133.
［7］	涂荣丹, 何婷, 冷文飞. 中医药治疗骨关节炎研究进展［J］. 河南中医, 2023, 43（8）: 1280-1286.
［8］	王永刚, 王蛟龙. 桃红四物汤临床研究进展［J］. 基层中医药, 2023, 2（11）: 99-105.
［9］	Liu ZH, Sun XB. Network pharmacology: new opportunity for the modernization of traditional Chinese medicine［J］. Acta Pharm Sin, 2012, 47（6）: 696-703.
［10］	王弘德, 李升, 陈伟, 等. 《骨关节炎诊疗指南（2018年版）》膝关节骨关节炎部分的更新与解读［J］. 河北医科大学学报, 2019, 40（9）: 993-995, 1000.
［11］	国家中医药管理局. 中医病证诊断疗效标准［S］. 南京: 南京大学出版社, 1994: 245.
［12］	Wu Y, Liu X, Li G. Integrated bioinformatics and network pharmacology to identify the therapeutic target and molecular mechanisms of Huangqin decoction on ulcerative Colitis［J/OL］. Sci Rep, 2022, 12（1）: 159.
［13］	陶嘉磊, 汪受传, 陈彦臻, 等. 中药复方网络药理学研究述评［J］. 中华中医药杂志, 2019, 34（9）: 3903-3907.
［14］	Hamosh A, Amberger JS, Bocchini C, et al. Online Mendelian inheritance in man（OMIM®）: victor McKusick’s magnum opus［J］. Am J Med Genet A, 2021, 185（11）: 3259-3265.
［15］	Fishilevich S, Zimmerman S, Kohn A, et al. Genic insights from integrated human proteomics in GeneCards［J/OL］. Database, 2016, 2016: baw030.
［16］	Szklarczyk D, Gable AL, Lyon D, et al. STRING v11: protein-protein association networks with increased coverage, supporting functional discovery in genome-wide experimental datasets［J］. Nucleic Acids Res, 2019, 47（D1）: D607-D613.
［17］	钟远鸣, 何炳坤, 吴卓檀, 等. 芍药甘草汤治疗腰椎间盘突出症早期疼痛作用机制的网络药理学分析［J］. 中国组织工程研究, 2021, 25（20）: 3194-3201.
［18］	李洪刚. 中药复方治疗多种证型膝骨关节炎临床应用研究进展［J］. 辽宁中医药大学学报, 2020, 22（9）: 217-220.
［19］	陈李专, 陈斌, 林安阳, 等. 膝骨关节炎中西医疗法的临床研究进展［J］. 辽宁中医杂志, 2020, 47（2）: 203-206.
［20］	许骏, 徐浩, 梁倩倩, 等. 近5年针刺治疗膝骨关节炎的研究进展［J］. 中华中医药杂志, 2020, 35（7）: 3557-3559.
［21］	赵晓. 基于“气伤痛、形伤肿”理念探讨桃红四物汤治疗膝关节置换术后肿痛的临床疗效观察［D］. 成都: 成都中医药大学, 2019.
［22］	Wei B, Zhang Y, Tang L, et al. Protective effects of quercetin against inflammation and oxidative stress in a rabbit model of knee osteoarthritis［J］. Drug Dev Res, 2019, 80（3）: 360-367.
［23］	Fei J, Liang B, Jiang C, et al. Luteolin inhibits IL-1β-induced inflammation in rat chondrocytes and attenuates osteoarthritis progression in a rat model［J］. Biomed Pharmacother, 2019, 109: 1586-1592.
［24］	Wu W, Yang B, Qiao Y, et al. Kaempferol protects mitochondria and alleviates damages against endotheliotoxicity induced by doxorubicin［J/OL］. Biomed Pharmacother, 2020, 126: 110040.
［25］	杨波, 龙慧, 王郑钢, 等. 黄芩素通过促进miR-29a-3p抑制MAP2K6改善骨性关节炎模型大鼠软骨细胞退化［J］. 中药药理与临床, 2019, 35（6）: 32-37.
［26］	唐金烁, 周忠圣, 肖建林, 等. 骨性关节炎发病机制的研究进展［J］. 中国骨伤, 2021, 34（10）: 985-990.
［27］	Zhao X, Wang T, Cai B, et al. microRNA-495 enhances chondrocyte apoptosis, senescence and promotes the progression of osteoarthritis by targeting AKT1［J］. Am J Transl Res, 2019, 11（4）: 2232-2244.
［28］	张健博, 宋建锋, 武海发. miR-378c靶向AKT1调控骨关节炎软骨细胞增殖、凋亡的机制［J］. 中国老年学杂志, 2020, 40（17）: 3748-3753.
［29］	Li Z, Wang Q, Chen G, et al. Integration of gene expression profile data to screen and verify hub genes involved in osteoarthritis［J/OL］. Bio Med Res Int, 2018, 2018: 9482726.
［30］	Rhee J, Park SH, Kim SK, et al. Inhibition of BATF/JUN transcriptional activity protects against osteoarthritic cartilage destruction［J］. Ann Rheum Dis, 2017, 76（2）: 427-434.
［31］	赵尧烨, 刘震东, 高延征. 骨性关节炎靶向基因治疗的研究进展［J］. 中国矫形外科杂志, 2024, 32（9）: 820-824.
［32］	王迷娜, 刘璐, 赵洛鹏, 等. 膝骨关节炎炎性因子及信号通路的研究进展［J］. 中国骨伤, 2020, 33（4）: 388-392.

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Study on efficacy and mechanism of Taohong Siwu decoction in treatment of knee osteoarthritis

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Study on efficacy and mechanism of Taohong Siwu decoction in treatment of knee osteoarthritis