中草药

化湿止痛凝胶的制备工艺优化及其抗痛风性关节炎作用和机制研究

PDF下载

中草药 | 海洋中药研究 2026,57(14): 5396-5415

收起

中草药 |海洋中药研究 2026 , 57 (14) : 5396 -5415

化湿止痛凝胶的制备工艺优化及其抗痛风性关节炎作用和机制研究

全屏

李泽宇^1,2,3, 庄培均^1,2, 曾雪琪^1,2, 韦成波^1,2, 曹瑞^1,2, 韦棪婷^1,2, 郝二伟^1,2, 杜正彩^1,2, 侯小涛^1,2, 邓家刚^1,2

作者信息

通讯作者:

侯小涛

作者简介:

李泽宇: 李泽宇，博士研究生，研究方向为中药复杂作用机制解析。E-mail:chestnutfish1998@126.com

Optimization of preparation of Huashi Zhitong Gel and research on its anti-gouty arthritis effect and mechanism

LI Zeyu, ZHUANG Peijun, ZENG Xueqi, WEI Chengbo, CAO Rui, WEI Yanting, HAO Erwei, DU Zhengcai, HOU Xiaotao, DENG Jiagang

Affiliations

doi: 10.7501/j.issn.0253-2670.2026.14.004

文章导航

摘要

收起

目的优化化湿止痛方的提取工艺与凝胶剂制备工艺，探究化湿止痛凝胶对痛风性关节炎的治疗效果及作用机制，为痛风性关节炎外用治疗新药研发提供候选制剂与理论依据。方法采用紫外分光光度法测定化湿止痛方的总酚酸含量，通过单因素与正交试验优化提取工艺；以外观、黏度、延展性及稳定性为指标筛选凝胶基质及辅料配比，运用Box-Behnken响应面法优化制备工艺。建立大鼠急性痛风性关节炎模型，通过检测关节肿胀、皮温、疼痛及炎症因子[白细胞介素-1β（interleukin-1β，IL-1β）、巨噬细胞炎症蛋白-1α（macrophage inflammatory protein-1α，MIP-1α）、超氧化物歧化酶（superoxide dismutase，SOD）、Toll样受体4（Toll-like receptor 4，TLR4）、基质金属蛋白酶9（matrix metalloproteinase 9，MMP9）]表达，考察化湿止痛凝胶抗痛风性关节炎的药效作用。结合GEO数据、网络药理学与分子对接构建“物质-效应组群”网络，分析化湿止痛凝胶抗痛风性关节炎的作用机制并进行实验验证。结果化湿止痛方的最佳提取工艺为60%乙醇、料液比1∶10、70 ℃提取1.5 h，提取2次；凝胶剂最佳配方为1%卡波姆940与0.2%泊洛沙姆188为基质，搭配7.5%保湿剂、1.2%促渗剂、14.7%含药量及0.07%抗氧剂。药效学实验结果显示，化湿止痛凝胶能显著减轻痛风性关节炎大鼠关节肿胀和疼痛（P＜0.01、0.001），降低血清中IL-1β、MIP-1α水平及滑膜组织TLR4、MMP9表达（P＜0.05、0.01），升高血清中SOD活性（P＜0.05、0.01）。机制研究表明，化湿止痛凝胶通过调控前列腺素内过氧化物合酶2（prostaglandin-endoperoxide synthase 2，PTGS2）、表皮生长因子受体（epidermal growth factor receptor，EGFR）、血管内皮生长因子A（vascular endothelial growth factor A，VEGFA）等靶点及环磷酸腺苷（cyclic adenosine monophosphate，cAMP）、趋化因子、钙信号等通路发挥抗痛风性关节炎的作用；免疫荧光染色和qRT-PCR实验证实化湿止痛凝胶能显著抑制痛风性关节炎大鼠滑膜组织环氧化酶-2（cyclooxygenase-2，COX-2）、VEGFA和EGFR的表达（P＜0.01）。结论成功优化化湿止痛凝胶剂的提取与制备工艺，化湿止痛凝胶具有良好的抗痛风性关节炎作用，且其作用机制与多靶点、多通路调控相关。

关键词

化湿止痛方 / 凝胶剂 / 痛风性关节炎 / 绿原酸 / 炎症反应 / 环氧化酶-2 / 血管内皮生长因子A / 表皮生长因子受体

Abstract

收起

Objective To optimize the extraction process of Huashi Zhitong Formula (化湿止痛方) and preparation technology of its gel formulation, elucidate the therapeutic efficacy and mechanism of Huashi Zhitong Gel against gouty arthritis, and provide a candidate formulation and theoretical basis for the development of new topical drugs for gouty arthritis. Methods The total phenolic acid content in Huashi Zhitong Formula was determined by ultraviolet spectrophotometry. The extraction process was optimized through single-factor and orthogonal tests. The gel matrix and excipient ratios were screened based on appearance, viscosity, ductility and stability, and the preparation process was further optimized using Box-Behnken response surface methodology. A rat gouty arthritis model was established, anti-gouty arthritis efficacy of Huashi Zhitong Gel was investigated by detecting joint swelling, skin temperature, pain and expressions of inflammatory factors [interleukin-1β (IL-1β), macrophage inflammatory protein-1α (MIP-1α), superoxide dismutase (SOD), Toll-like receptor 4 (TLR4), matrix metalloproteinase 9 (MMP9)]. Integrated with GEO data, network pharmacology and molecular docking, a “component-effect group” network was constructed to analyze the mechanism of Huashi Zhitong Gel against gouty arthritis, followed by experimental validation. Results The optimal extraction conditions of Huashi Zhitong Formula were determined as 60% ethanol, a solid-to-liquid ratio of 1∶10, extraction at 70 ℃ for 1.5 h (repeated twice). The optimal gel formulation consisted of 1% carbomer 940 and 0.2% poloxamer 188 as the matrix, combined with 7.5% humectant, 1.2% penetration enhancer, 14.7% drug load and 0.07% antioxidant. Pharmacodynamic experiment results demonstrated that Huashi Zhitong Gel significantly alleviated joint swelling and pain in rats with gouty arthritis (P < 0.01, 0.001), reduced the levels of IL-1β, MIP-1α in serum and expressions of TLR4, MMP9 in synovial tissue (P < 0.05, 0.01), and increased the activity of SOD in serum (P < 0.05, 0.01). The mechanism study showed that Huashi Zhitong Gel could play an anti-gouty arthritis role by regulating the targets such as prostaglandin endoperoxide synthase 2 (PTGS2), epidermal growth factor receptor (EGFR), vascular endothelial growth factor A (VEGFA), and the pathways such as cyclic adenosine monophosphate (cAMP), chemokines, and calcium signaling. Immunofluorescence staining and qRT-PCR confirmed that Huashi Zhitong Gel could significantly inhibit the expressions of cyclooxygenase-2 (COX-2), VEGFA and EGFR in synovium of rats with gouty arthritis (P < 0.01). Conclusion The extraction and preparation process of Huashi Zhitong Gel are successfully optimized. Huashi Zhitong Gel has a good anti-gouty arthritis effect, and its mechanism is related to multi target and multi pathway regulation.

Key words

Huashi Zhitong Formula / gel / gouty arthritis / chlorogenic acid / inflammatory response / cyclooxygenase-2 / vascular endothelial growth factor A / epidermal growth factor receptor

引用本文

李泽宇, 庄培均, 曾雪琪, 韦成波, 曹瑞, 韦棪婷, 郝二伟, 杜正彩, 侯小涛, 邓家刚. 化湿止痛凝胶的制备工艺优化及其抗痛风性关节炎作用和机制研究. 中草药, 2026 , 57 (14) : 5396 -5415 . DOI: 10.7501/j.issn.0253-2670.2026.14.004

LI Zeyu, ZHUANG Peijun, ZENG Xueqi, WEI Chengbo, CAO Rui, WEI Yanting, HAO Erwei, DU Zhengcai, HOU Xiaotao, DENG Jiagang. Optimization of preparation of Huashi Zhitong Gel and research on its anti-gouty arthritis effect and mechanism[J]. Chinese Traditional and Herbal Drugs, 2026 , 57 (14) : 5396 -5415 . DOI: 10.7501/j.issn.0253-2670.2026.14.004

基金

收起

广西中药药效研究重点实验室项目 (桂科计字[2005]6号); 中药资源循环利用广西高校工程研究中心 (桂教科研[2024]10号); 广西“带土移植”人才引育计划项目 (桂科AA23026008)

参考文献

收起

文献

收起

参考文献引证文献

排序方式：

Martins D, Tonon C R, Pacca R L, et al. Gout storm [J]. Am J Case Rep, 2021, 22: e932683.
中华医学会内分泌学分会. 中国高尿酸血症与痛风诊疗指南(2019) [J]. 中华内分泌代谢杂志, 2020, 36(1): 1-13.
Dehlin M, Jacobsson L, Roddy E. Global epidemiology of gout: Prevalence, incidence, treatment patterns and risk factors [J]. Nat Rev Rheumatol, 2020, 16(7): 380-390.
Elfishawi M M, Zleik N, Kvrgic Z, et al. The rising incidence of gout and the increasing burden of comorbidities: A population-based study over 20 years [J]. J Rheumatol, 2018, 45(4): 574-579.
王旭, 罗冬平, 茹彦海, 等. 从慢性肾脏病角度看高尿酸血症与痛风的指南更新要点[J]. 中国全科医学, 2021, 24(33): 4191-4195.
中国药典[S]. 四部. 2025: 53.
卢慧, 赵冠婕, 程梅, 等. 中药凝胶剂的研究进展[J]. 人人健康, 2019(23): 406.
李君霞, 王茂杰, 黄闰月, 等. 痛风中医证型的研究进展[J]. 中华中医药学刊, 2018, 36(12): 2956-2958.
宋倩, 刘健, 忻凌, 等. 基于关联规则挖掘健脾类中药对痛风性关节炎患者免疫、炎症指标的影响[J]. 辽宁中医杂志, 2017, 44(11): 2248-2252.
杨媛媛, 姜旭, 王宇卿. 正交试验优化复方粉背雷公藤凝胶剂处方[J]. 中国药房, 2017, 28(7): 961-963.
马鑫斌, 王利胜, 巴文强. 雷公藤凝胶剂的制备工艺研究[J]. 中国药物经济学, 2016, 11(11): 26-30.
陈积, 赵小倩, 马彦巧, 等. 复方莪术油脂质体凝胶的制备及体外透皮作用[J]. 中国新药杂志, 2018, 27(7): 830-838.
杨萌. 黄龙汤的凝胶剂制备工艺及质量标准研究[D]. 长春: 吉林农业大学, 2021.
曹日曲. 基于数据挖掘的中医药外治黄褐斑的网络药理学研究[D]. 北京: 北京中医药大学, 2021.
Miao Y R, Zhang Q, Lei Q, et al. ImmuCellAI: A unique method for comprehensive T-cell subsets abundance prediction and its application in cancer immunotherapy [J]. Adv Sci, 2020, 7(7): 1902880.
Zhao X W, Zhang L L, Wang J, et al. Identification of key biomarkers and immune infiltration in systemic lupus erythematosus by integrated bioinformatics analysis [J]. J Transl Med, 2021, 19(1): 35.
Gong Q Y, Chen Y. Correlation between P2X7 receptor gene polymorphisms and gout [J]. Rheumatol Int, 2015, 35(8): 1307-1310.
牛燕运, 郑娜, 胡翠平, 等. 祛湿清热法治疗痛风性关节炎的临床研究[J]. 中国中医急症, 2020, 29(1): 76-78.
Li J, Zhang H B, Huang W L, et al. TNF-α inhibitors with anti-oxidative stress activity from natural products [J]. Curr Top Med Chem, 2012, 12(13): 1408-1421.
Perkins N D. Emerging from NF-κB’s shadow, SUMOylated IκBα represses transcription [J]. Cancer Cell, 2013, 24(2): 139-140.
Perkins N D. The diverse and complex roles of NF-κB subunits in cancer [J]. Nat Rev Cancer, 2012, 12(2): 121-132.
Xiang X, You X M, Li L Q. Expression of HSP90AA1/ HSPA8 in hepatocellular carcinoma patients with depression [J]. OncoTargets Ther, 2018, 11: 3013-3023.
Punyte V, Vilkeviciute A, Gedvilaite G, et al. Association of VEGFA, TIMP-3, and IL-6 gene polymorphisms with predisposition to optic neuritis and optic neuritis with multiple sclerosis [J]. Ophthalmic Genet, 2021, 42(1): 35-44.
姜德友, 刘爽, 韩洁茹, 等. 补肾利湿法对急性痛风性关节炎大鼠VEGF表达水平的影响[J]. 中国实验方剂学杂志, 2013, 19(24): 236-239.
De Tursi M, Zilli M, Carella C, et al. Skin toxicity evaluation in patients treated with cetuximab for metastatic colorectal cancer: A new tool for more accurate comprehension of quality of life impacts [J]. OncoTargets Ther, 2017, 10: 3007-3015.
孙晓波. 中药复方益糖康对DN大鼠肾脏nephrin、VEGF表达的影响[D]. 沈阳: 辽宁中医药大学, 2014.
杨欣雨, 胡梦情, 罗雪, 等. 霍山石斛鲜、干品对急性胃炎模型大鼠作用的差异研究[J]. 中草药, 2025, 56(17): 6242-6251.
Wang G S, Zhou B, Wang Z Y, et al. Pharmacological mechanisms underlying the anti-asthmatic effects of modified Guomin Decoction determined by network pharmacology and molecular docking [J]. Front Mol Biosci, 2021, 8: 644561.
Zhou C, Zhou H, Zhang F R, et al. Active ingredients and potential mechanisms of the Gan Jiang-Huang Qin-Huang Lian-Ren Shen Decoction against ulcerative colitis: A network pharmacology and molecular docking-based study [J]. Evid Based Complement Altern Med, 2021, 2021: 1925718.
Shi H S, Tian S S, Tian H. Network pharmacology interpretation of Fuzheng-Jiedu Decoction against colorectal cancer [J]. Evid Based Complement Altern Med, 2021, 2021(1): 4652492.
Wang G X, Zeng L, Huang Q, et al. Exploring the molecular mechanism of Liuwei Dihuang Pills for treating diabetic nephropathy by combined network pharmacology and molecular docking [J]. Evid Based Complement Alternat Med, 2021, 2021: 7262208.
Kim Y, Oh Y, Lee H, et al. Prediction of the therapeutic mechanism responsible for the effects of Sophora japonica flower buds on contact dermatitis by network-based pharmacological analysis [J]. J Ethnopharmacol, 2021, 271: 113843.
Cao J H, Xue R, He B. Quercetin protects oral mucosal keratinocytes against lipopolysaccharide-induced inflammatory toxicity by suppressing the Akt/AMPK/ mTOR pathway [J]. Immunopharmacol Immunotoxicol, 2021, 43(5): 519-526.
Li C Y, Cheng S E, Wang S H, et al. The anti-inflammatory effects of the bioactive compounds isolated from Alpinia officinarum Hance mediated by the suppression of NF-kappaB and MAPK signaling [J]. Chin J Physiol, 2021, 64(1): 32-42.
Guo X Y, Yu X, Zheng B Q, et al. Network pharmacology-based identification of potential targets of Lonicerae Japonicae Flos acting on anti-inflammatory effects [J]. BioMed Res Int, 2021, 2021(1): 5507003.

2026年第57卷第14期

PDF下载

引用本文

BibTeX

文章信息

doi: 10.7501/j.issn.0253-2670.2026.14.004

接收时间：2026-02-02
首发时间：2026-09-10

补充材料

相关文章

文章信息

作者

出版历史

收稿日期：2026-02-02

基金

作者信息

参考文献

分享链接

https://castjournals.cast.org.cn/joweb/zcy/CN/10.7501/j.issn.0253-2670.2026.14.004

分享至

全文二维码

扫描看全文

引用本文

BibTeX

本文的引用情况

2种不同金属材料的力学参数

科 Family	属数 Number of genus	种数 Number of species	占总种数比例 Percentage of total species (%)	属 Genus	种数 Number of species	占总种数比例 Percentage of total species (%)
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

关闭全屏

BibTeX
EndNote
RefWorks
TxT