Research on the Correlation Between Transepidermal Glycoside Penetration Enhancement Effect and Transepidermal Water Loss Values of Essential Oils from Traditional Chinese Medicine
-
摘要:
目的 研究中药挥发油透皮促渗苷类成分效果与对经皮水分散失量(Transepidermal water loss, TEWL)的相关性。 方法 采用HPLC法测定3种苷类成分(栀子苷、龙胆苦苷、芍药苷)的含量及油水分配系数，采用改良Franz扩散池法以离体SD大鼠腹部皮肤为透皮吸收屏障进行体外透皮实验，考察高良姜、干姜、薄荷、胡椒和吴茱萸5种中药挥发油对3种苷类成分的体外透皮促渗效果，采用经皮水分散失量评价5种中药挥发油对大鼠皮肤屏障功能的影响，通过相关性分析考察中药挥发油透皮促渗苷类成分效果与其对皮肤屏障功能影响之间的相关性。 结果 高良姜油、干姜油、薄荷油、胡椒油能促进3种苷类成分的透皮吸收，也能显著降低大鼠的皮肤屏障功能，相关性分析结果表明中药挥发油对苷类成分的透皮促渗效果与其对皮肤经皮水分散失量的影响显著相关。 结论 TEWL为中药挥发油透皮促渗剂的快速筛选提供了一种简便快捷的在体评价方法。 Abstract:OBJECTIVE To study the correlation between penetration enhancement effect and transepidermal water loss (TEWL) values of essential oils (EOs) from traditional Chinese medicine (TCM). METHODS The amount of 3 kinds of glycosides(geniposide, gentiopicroside, paeoniflorin)and their oil-water partition coefficient were determined by HPLC. The penetration enhancement effect of the five EOs from Gaoliangjiang (Alpiniae Officinarum Rhizoma, AOR), Ganjiang (Zingiberis Rhizoma, ZR), Bohe (Menthae Haplocalycis Herba, MHH), Hujiao (Piperis Fructus, PF) and Wuzhuyu (Euodiae Fructus, EF) on geniposide, gentiopicroside, and paeoniflorin were performed by the modified Franz diffusion cell method with the abdominal skin of rats. The TEWL values were measured to evaluate the effect of the five EOs on the skin barrier function of rats. The correlation between penetration enhancement effect of EOs and their effect on skin barrier function was investigated by correlation analysis. RESULTS AOR oil, ZR oil, MHH oil, and PF oil could improve the absorption of the three glycosides and reduce skin barrier function of rats. The results of correlation analysis showed that the penetration enhancement effect of EOs was significantly related to TEWL values following dermal administration of EOs. CONCLUSION TEWL measurement technology provides a more convenient method for the selection of penetration enhancers. -
图 1 混合对照品和接受液中苷类成分的HPLC图
注：A.对照品; B.透皮接收液; C.空白接收液; 1.栀子苷; 2.龙胆苦苷; 3.芍药苷
Figure 1. HPLC chromatograms of glycosides in mixed reference solution and receiving solution
图 2 中药挥发油对苷类成分的体外经皮渗透曲线(x±s, n=5)
Figure 2. In vitro skin permeation curves of glycoside components after treatment with the EOs (x±s, n=5)
图 3 中药挥发油经皮外用对大鼠皮肤ΔTEWL值的影响
注：与空白对照组比较，**P < 0.01, ***P < 0.001。x±s, n=6。
Figure 3. ΔTEWL values of rat skin treated with different EOs
图 4 中药挥发油经皮外用后ΔTEWL挥发油组/ΔTEWL空白对照绝对值和ER值的相关性
Figure 4. Correlation between absolute value of ΔTEWLEOs /ΔTEWLblank control and ER after dermal application of the EOs
表 1 苷类成分标准曲线
Table 1. Standard curves of glycosides
成分 标准曲线 r 线性范围/ (μg·mL-1) 栀子苷 Y=27 437X+9 476.1 0.999 9 0.60~32.00 龙胆苦苷 Y=19 806X+4 643.9 0.999 8 0.90~47.75 芍药苷 Y=19 136X-7 433.4 0.999 8 1.40~74.50 
下载: 导出CSV
表 2 苷类成分理化性质(x±s，n=3)
Table 2. Physicochemical properties of glycosides(x±s, n=3)
活性成分 分子量 logP 熔点/℃ 栀子苷 388.37 -1.28±0.02 159 龙胆苦苷 356.33 -1.56±0.01 191 芍药苷 480.46 -0.87±0.02 196
下载: 导出CSV
表 3 中药挥发油对苷类成分的体外经皮渗透参数(x±s, n=5)
Table 3. In vitro skin permeation parameters of glycosides components after treatment with the EOs (x±s, n=5)
活性成分 促渗剂 Jss/(μg·cm-2·h-1) Tlag/h ER 栀子苷 空白对照 0.42±0.14 4.69±0.77 1.00 高良姜油 0.98±0.29** 2.95±0.49** 2.34 干姜油 0.82±0.18** 3.30±1.41 1.96 薄荷油 0.67±0.29 2.85±1.31* 1.60 胡椒油 0.61±0.16 3.51±0.51* 1.44 吴茱萸油 0.32±0.12 4.90±0.89 0.77 龙胆苦苷 空白对照 0.46±0.13 2.32±1.00 1.00 高良姜油 0.98±0.30** 0.80±0.26* 2.13 干姜油 0.86±0.15** 1.60±1.03 1.88 薄荷油 0.71±0.29 0.24±0.55** 1.54 胡椒油 0.61±0.17 -0.34±1.67* 1.33 吴茱萸油 0.43±0.07 2.21±1.39 0.93 芍药苷 空白对照 0.42±0.13 3.52±2.17 1.00 高良姜油 0.88±0.23** 1.73±0.83 2.09 干姜油 0.72±0.12** 1.33±2.98* 1.72 薄荷油 0.63±0.23 1.31±0.91 1.50 胡椒油 0.57±0.12 1.46±1.01 1.36 吴茱萸油 0.35±0.07 4.56±2.17 0.83 注：与空白对照组相比，*P < 0.05, **P < 0.01。
下载: 导出CSV
表 4 中药挥发油经皮外用对大鼠皮肤ΔTEWL值的影响(x±s, n=6)
Table 4. ΔTEWL values of rat skin after dermal application of the EOs (x±s, n=6)
PE ΔTEWL ΔTEWL挥发油组/ΔTEWL空白对照绝对值 空白对照 -0.65±1.37 1.00 高良姜油 17.58±6.12*** 27.05 干姜油 13.07±3.35*** 20.11 薄荷油 12.23±4.27*** 18.81 胡椒油 10.76±7.45** 16.55 吴茱萸油 8.24±5.55** 12.68 注：与空白对照组相比，**P < 0.01, ***P < 0.001。
下载: 导出CSV
-
[1] KOVÁČIK A, KOPEČNÁ M, VÁVROVÁ K. Permeation enhancers in transdermal drug delivery: Benefits and limitations[J]. Expert Opin Drug Deliv, 2020, 17(2): 145-155. doi: 10.1080/17425247.2020.1713087 [2] 陈军, 姚俊宏, 王裔惟, 等. 基于生物药剂学思维的外用中药药性"组分-递送-效应"三要素表征思路[J]. 南京中医药大学学报, 2021, 37(5): 654-657. doi: 10.14148/j.issn.1672-0482.2021.0654CHEN J, YAO J H, WANG Y W, et al. "Compound-Delivery-Efficacy" characterization idea of external Chinese medical properties based on biopharmaceutical thoughts[J]. J Nanjing Univ Tradit Chin Med, 2021, 37(5): 654-657. doi: 10.14148/j.issn.1672-0482.2021.0654 [3] JIANG Q D, WU Y M, ZHANG H, et al. Development of essential oils as skin permeation enhancers: Penetration enhancement effect and mechanism of action[J]. Pharm Biol, 2017, 55(1): 1592-1600. doi: 10.1080/13880209.2017.1312464 [4] 李倩, 高瑜, 邹佳, 等. 中药透皮吸收促进剂的研究进展[J]. 时珍国医国药, 2022, 33(1): 189-193. https://www.cnki.com.cn/Article/CJFDTOTAL-SZGY202201051.htmLI Q, GAO Y, ZOU J, et al. Research progress of transdermal absorption enhancers of traditional Chinese medicine[J]. Lishizhen Med Mater Med Res, 2022, 33(1): 189-193. https://www.cnki.com.cn/Article/CJFDTOTAL-SZGY202201051.htm [5] KLOTZ T, IBRAHIM A, MADDERN G, et al. Devices measuring transepidermal water loss: A systematic review of measurement properties[J]. Skin Res Technol, 2022, 28(4): 497-539. doi: 10.1111/srt.13159 [6] LIU X C, LIU M Y, LIU C, et al. An insight into the molecular mechanism of the temporary enhancement effect of isopulegol decanoate on the skin[J]. Int J Pharm, 2017, 529(1/2): 161-167. [7] 杨文国, 陈军, 刘培, 等. 基于数据挖掘方法研究挥发油透皮促渗作用与中药药性间的关联性[J]. 中国中药杂志, 2015, 40(23): 4609-4615. https://www.cnki.com.cn/Article/CJFDTOTAL-ZGZY201523014.htmYANG W G, CHEN J, LIU P, et al. Association between penetration enhancement effect of essential oils and drug properties of traditional Chinese medicine by data mining method[J]. China J Chin Mater Med, 2015, 40(23): 4609-4615. https://www.cnki.com.cn/Article/CJFDTOTAL-ZGZY201523014.htm [8] 李芸, 魏舒畅, 刘永琦, 等. 不同生物碱透皮吸收促进剂对芍药苷透皮吸收的影响[J]. 北京中医药大学学报, 2014, 37(6): 410-413. https://www.cnki.com.cn/Article/CJFDTOTAL-JZYB201406014.htmLI Y, WEI S C, LIU Y Q, et al. Influences of different alkaloid penetration enhancers on transdermal absorption of paeoniflorin[J]. J Beijing Univ Tradit Chin Med, 2014, 37(6): 410-413. https://www.cnki.com.cn/Article/CJFDTOTAL-JZYB201406014.htm [9] 蒋文文, 张媛洁, 李高攀, 等. 常绿钩吻碱平衡溶解度、油水分配系数及解离常数的测定[J]. 药学研究, 2021, 40(10): 656-659. https://www.cnki.com.cn/Article/CJFDTOTAL-SDYG202110007.htmJIANG W W, ZHANG Y J, LI G P, et al. Determination of equilibrium solubility, oil-water partition coefficient and dissociation constant of sempervirine[J]. J Pharm Res, 2021, 40(10): 656-659. https://www.cnki.com.cn/Article/CJFDTOTAL-SDYG202110007.htm [10] LIU X C, QUAN P, LI S S, et al. Time dependence of the enhancement effect of chemical enhancers: Molecular mechanisms of enhancing kinetics[J]. J Control Release, 2017, 248: 33-44. doi: 10.1016/j.jconrel.2017.01.017 [11] TANG Q H, XU F, WEI X C, et al. Investigation of β-caryophyllene as terpene penetration enhancer: Role of stratum corneum retention[J]. Eur J Pharm Sci, 2023, 183: 106401. doi: 10.1016/j.ejps.2023.106401 [12] ALEXANDER H, BROWN S, DANBY S, et al. Research techniques made simple: Transepidermal water loss measurement as a research tool[J]. J Invest Dermatol, 2018, 138(11): 2295-2300. doi: 10.1016/j.jid.2018.09.001 [13] 杨文国, 朱学敏, 吴凤烨, 等. 基于逐步判别法分析辛味中药挥发油"四气" 药性、透皮促渗能力和化学成分的关联因素[J]. 中草药, 2019, 50(17): 4219-4224. https://www.cnki.com.cn/Article/CJFDTOTAL-ZCYO201917031.htmYANG W G, ZHU X M, WU F Y, et al. Research on correlation among "four natures" drug properties, penetration enhancement abilities and chemical components of essential oils from pungent Chinese herbs based on stepwise discrimination analysis method[J]. Chin Tradit Herb Drugs, 2019, 50(17): 4219-4224. https://www.cnki.com.cn/Article/CJFDTOTAL-ZCYO201917031.htm [14] 王景雁, 兰颐, 赵馨雨, 等. 基于经皮微透析技术的薄荷挥发油促渗作用评价[J]. 中华中医药杂志, 2022, 37(1): 378-382. https://www.cnki.com.cn/Article/CJFDTOTAL-BXYY202201080.htmWANG J Y, LAN Y, ZHAO X Y, et al. Evaluation of in vivo transdermal penetration enhancing activity of essential oil from Mentha Haplocalycis Herba based on cutaneous microdialysis technique[J]. China J Tradit Chin Med Pharm, 2022, 37(1): 378-382. https://www.cnki.com.cn/Article/CJFDTOTAL-BXYY202201080.htm -
点击查看大图
计量
- 文章访问数: 67
- HTML全文浏览量: 5
- PDF下载量: 24
- 被引次数: 0
