目的 考察当归、白术、花椒、干姜、细辛、羌活、桂枝、川芎、荆芥9种中药挥发油对秦艽Gentianae Macrophyllae Radix（GMR）-独活Angelicae Pubescentis Radix（APR）药对主要成分的经皮渗透性能、体外抗炎能力及皮肤细胞毒性的影响，以筛选出兼具高效促渗与低刺激性潜力的中药挥发油促渗剂。方法 以马钱苷酸、6′-O-β-D-葡萄糖基龙胆苦苷、二氢欧山芹醇、当药苦苷、龙胆苦苷、当药苷、蛇床子素7种成分为指标，建立秦艽-独活药对提取物的多成分含量测定方法；采用水蒸气蒸馏法提取当归等9种中药挥发油，通过Franz扩散池法考察3%中药挥发油对秦艽-独活药对的7种主要成分的体外渗透效果；采用MTT法评估不同挥发油对人永生化表皮HaCaT细胞的毒性；ELISA实验检测不同挥发油作为促渗剂对肿瘤坏死因子-α（tumor necrosis factor-α，TNF-α）诱导的成纤维样滑膜细胞（MH7A）中类风湿因子（rheumatoid factor，RF）、前列腺素E2（prostaglandin E2，PGE2）、TNF-α、白细胞介素-1β（interleukin-1β，IL-1β）、白细胞介素-6（interleukin-6，IL-6）的表达水平。结果 所建立的HPLC方法专属性良好，各成分均有良好的线性关系、精密度、重复性、稳定性及加样回收率；花椒挥发油对6′-O-β-D-葡萄糖基龙胆苦苷、二氢欧山芹醇以及当药苷的促渗效果最强；中药挥发油对皮肤细胞毒性强度依次为氮酮＞当归油＞川芎油＞干姜油＞羌活油＞桂枝油＞细辛油＞荆芥油＞花椒油＞白术油；体外抗炎结果显示，与TNF-α模型组相比，花椒挥发油能降低细胞上清液中RF等炎症因子水平（P＜0.01）。结论 花椒挥发油可以提升秦艽-独活药对中6′-O-β-D-葡萄糖基龙胆苦苷等活性成分的透皮渗透效果，增强抗炎作用且皮肤细胞毒性小。为开发以中药挥发油作为透皮促渗剂的秦艽-独活药对透皮给药系统治疗类风湿性关节炎提供了实验依据。

Objective This study investigated the effects of volatile oils from nine Chinese herbal medicines, including Danggui (Angelicae Sinensis Radix, ASR), Baizhu (Atractylodis Macrocephalae Rhizoma, AMR), Huajiao (Zanthoxyli Pericarpium, ZP), Ganjiang (Zingiberis Rhizoma, ZR), Xixin (Asari Radix et Rhizoma, ARR), Qianghuo (Notopterygii Rhizoma et Radix, NRR), Guizhi (Cinnamomi Ramulus, CR), Chuanxiong (Chuanxiong Rhizoma), and Jingjie (Schizonepetae Herba, SH) on the transdermal penetration efficiency, in vitro anti-inflammatory capacity, and skin cell cytotoxicity of the main components of the Qinjiao (Gentianae Macrophyllae Radix, GMR)-Duhuo (Angelicae Pubescentis Radix, APR) drug pair. The objective was to identify Chinese herbal volatile oil permeation enhancers that offer high penetration efficiency alongside low irritation potential. Methods A multi-component content determination method for GMR-APR drug pair extracts was established using seven indicators, including loganic acid, 6'-O-β-D-glucosylgentiopicroside, columbianetin, swertiamarin, gentiopicroside,sweroside, osthol. Water vapor distillation was used to extract volatile oils from nine Chinese herbal medicines, including angelica sinensis. The Franz diffusion cell method was employed to investigate the in vitro penetration effects of 3% Chinese herbal volatile oils on the seven main components of GMR-APR drug pair. The MTT assay was utilized to evaluate the toxicity of various essential oils on human immortalized epidermal HaCaT cells, while ELISA experiments were conducted to ascertain the impact of these essential oils as permeation enhancers on the levels of rheumatoid factor (RF), prostaglandin E2 (PGE2), tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), interleukin-6 (IL-6) induced by TNF-α in fibroblast-like synoviocyte MH7A cells. Results The results showed that the established HPLC method demonstrates excellent specificity, with all components exhibiting satisfactory linear relationships, precision, repeatability, stability, and sample recovery. ZP essential oil has been demonstrated to exhibit the strongest osmotic effect on 6'-O-β-D-glucosylgentiopicroside, columbianetin, and sweroside. The toxic intensity of volatile oil of traditional Chinese medicine on skin cells was as follows: Azone > ASR essential oil > Chuanxiong Rhizoma essential oil > ZR essential oil > NRR volatile oil > CR volatile oils > ARR volatile oil > SH volatile oil > ZP essential oil > AMR volatile oil. In vitro anti-inflammatory results showed that, compared with the TNF-α model group, volatile oil from ZP significantly reduced levels of the inflammatory factors such as inflammatory factor RF in the cell supernatant, and the differences were statistically significant (P < 0.01). Conclusion This study demonstrates that ZP essential oil significantly enhances the skin permeability of active components, such as 6'-O-β-D-glucosylgentiopicroside, in GMR-APR drug combinations. This has the effect of strengthening the anti-inflammatory effects while having low cytotoxicity. The present study provides experimental evidence for the development of GMR-APR drug pair transdermal systems using traditional Chinese medicine essential oils as transdermal permeation enhancers for the treatment of rheumatoid arthritis.

R283.6

陕西省科技厅项目(2024SF-YBXM-496)