Fuʼcupping Physical Permeation-Enhancing Technique Enhances the Therapeutic Efficacy of Corydalis yanhusuo Gel Plaster

Abstract

Corydalis yanhusuo, a traditional Chinese medicine, is widely used to treat various pains, and its active ingredients are alkaloids. This study aimed to develop a new type of transdermal gel plaster containing the extract of C. yanhusuo. Studies have shown that Fuʼcupping physical permeation-enhancing technique can promote the penetration of alkaloids and improve the efficacy of drugs. A transdermal gel plaster containing the extract of C. yanhusuo was prepared and optimized using an orthogonal experimental design. The skin permeation ability of the gel plaster was studied in vitro, while the anti-inflammatory and analgesic effects of the prepared patch alone or with Fuʼcupping physical permeation-enhancing technique were evaluated in a rat model. The formulation of a gel plaster containing C. yanhusuo extract was successfully prepared with an optimized composition consisting of glycerin (15 g), sodium polyacrylate (2 g), silicon dioxide (0.3 g), ethanol (2 g), aluminum oxide (0.1 g), citric acid (0.05 g), the C. yanhusuo extract (3 g), and water (15 g). The cumulative transdermal permeation of dehydrocorydaline, corypalmine, tetrahydropalmatine, and corydaline in 24 h was estimated to be 569.7 ± 63.2, 74.5 ± 13.7, 82.4 ± 17.2, and 38.9 ± 8.1 µg/cm², respectively. The in vitro diffusion of dehydrocorydaline and corydaline followed the zero-order kinetics profile, while that of corypalmine and tetrahydropalmatine followed a Higuchi equation. The prepared gel plaster significantly reduced paw swelling, downregulated inflammatory cytokines, and mitigated pain induced by mechanical or chemical stimuli. The Fuʼcupping physical permeation-enhancing technique further improved the anti-inflammatory and analgesic effects of the patch. The combined application of the Fuʼcupping physical permeation-enhancing technique and the alkaloid gel plaster may be effective against inflammation and pain.

Keywords

Corydalis yanhusuo - Papaveraceae - gel plaster - Fuʼcupping physical permeation-enhancing technique-anti-inflammation - analgesia

Publication History

Received: 12 November 2023

Accepted after revision: 14 June 2024

Accepted Manuscript online:
14 June 2024

Article published online:
19 July 2024

• References

• 1 Chinese Pharmacopoeia Commission (CPC). Pharmacopoeia of Peopleʼs Republic of China, Vol. 1. Beijing (China): Medical Science Press; 2020
• 2 Wu L, Zhang W, Qiu X, Wang C, Liu Y, Wang Z, Yu Y, Ye RD, Zhang Y. Identification of alkaloids from Corydalis yanhusuo W. T. Wang as dopamine D receptor antagonists by using CRE-luciferase reporter gene assay. Molecules 2018; 23: 2585
• 3 Liu BB, Luo M, Meng DY, Pan H, Shen H, Shen JF, Yao M, Xu LS. Tetrahydropalmatine exerts analgesic effects by promoting apoptosis and inhibiting the activation of glial cells in rats with inflammatory pain. Mol Pain 2021; 17
• 4 Wang YF, Zhu W, Lu DD, Zhang CZ, Wang Y. Tetrahydropalmatine attenuates MSU crystal-induced gouty arthritis by inhibiting ROS-mediated NLRP3 inflammasome activation. Int Immunopharmacol 2021; 100: 108107
• 5 Cui HR, Yang XX, Wang ZD, Li GP, Li L, Huo S, Zhang BB, He R, Chen KD, Xu B, Wang PL, Lei HM. Tetrahydropalmatine triggers angiogenesis via regulation of arginine biosynthesis. Pharmacol Res 2021; 163: 105242
• 6 Kong XP, Chen ZC, Xia YJ, Liu EYL, Ren HQ, Wang C, Hu WWH, Dong TTX, Pi RB, Tsim KWK. Dehydrocorydaline accounts the majority of anti-inflammatory property of corydalis rhizoma in cultured macrophage. Evid Based Complement Alternat Med 2020; 2020: 4181696
• 7 Huo WW, Zhang Y, Liu Y, Lei YS, Sun R, Zhang W, Huang YL, Mao YT, Wang CC, Ma ZL, Gu XP. Dehydrocorydaline attenuates bone cancer pain by shifting microglial M1/M2 polarization toward the M2 phenotype. Mol Pain 2018; 14: 1744806918781733
• 8 Wen B, Dang YY, Wu SH, Huang YM, Ma KY, Xu YM, Zheng XL, Dai XY. Antiatherosclerotic effect of dehydrocorydaline on ApoE-/- mice: Inhibition of macrophage inflammation. Acta Pharmacol Sin 2022; 43: 1408-1418
• 9 Al Hanbali OA, Khan HMS, Sarfraz M, Arafat M, Ijaz S, Hameed A. Transdermal patches: Design and current approaches to painless drug delivery. Acta Pharm 2019; 69: 197-215
• 10 Hashmat D, Shoaib MH, Ali FR, Siddiqui F. Lornoxicam controlled release transdermal gel plaster: Design, characterization and optimization using co-solvents as penetration enhancers. PLoS One 2020; 15: e0228908
• 11 Ng LC, Gupta M. Transdermal drug delivery systems in diabetes management: A review. Asian J Pharm Sci 2020; 15: 13-25
• 12 Fatima GX, Suganya K, Shanmuganathan S. Development of Terminalia Chebula Loaded Ethosomal Gel for Transdermal Drug Delivery. Asian Journal of Pharmaceutical and Clinical Research 2018; 11: 380-383
• 13 Quan P, Jiao B, Shang R, Liu C, Fang L. Alternative therapy of rheumatoid arthritis with a novel transdermal patch containing Siegesbeckiae Herba extract. J Ethnopharmacol 2021; 265: 113294
• 14 Ji W, Yu X, Gao Y, Ren B, Zhang S. Q Wang, X Wang. Majie cataplasm provides a shield against asthmatic punch from the neuroimmune system. Heliyon 2020; 6: e03896
• 15 Shen S, Liu SZ, Zhang YS, Du MB, Liang AH, Song LH, Ye ZG. Compound antimalarial ethosomal cataplasm: Preparation, evaluation, and mechanism of penetration enhancement. Int J Nanomedicine 2015; 10: 4239-4253
• 16 Miao YY, Xu J, Liu Y, Yang FF, Zheng XX, Xie WJ, Zhang YP. Comparative evaluation of the transdermal permeation effectiveness of Fuʼs cupping therapy on eight different types of model drugs. Curr Drug Deliv 2021; 18: 446-459
• 17 Xie WJ, Zhang YP, Xu J, Sun XB, Yang FF. The effect and mechanism of transdermal penetration enhancement of Fuʼs cupping therapy: New physical penetration technology for transdermal administration with Traditional Chinese Medicine (TCM) characteristics. Molecules 2017; 22: 524
• 18 Zhang YP, Wang ZH, Xu J, Yang FF, Dai CY, Xie WJ, Liang Z, Su SB. Optimization of the extraction and purification of Corydalis yanhusuo W.T. Wang based on the Q-marker uniform design method. BMC Chem 2020; 14: 9
• 19 Lu Y, Ma Q, Fu C, Chen C, Zhang D. Quality evaluation of Corydalis yanhusuo by High-Performance Liquid Chromatography fingerprinting coupled with multicomponent quantitative analysis. Sci Rep 2020; 10: 4996
• 20 Huang W, Pan Y, Jiang H, Chen Y, Hu L, Zhang H, Yan J. A comprehensive quality evaluation method of Corydalis yanhusuo by HPLC fingerprints, chemometrics, and correlation analysis. J Sep Sci 2021; 44: 2054-2064
• 21 Wan L, Zhao Y, Zhang Q, Gao G, Zhang S, Gao Y, Chen X, Qian X. Alkaloid extract of Corydalis yanhusuo inhibits angiogenesis via targeting vascular endothelial growth factor receptor signaling. BMC Complement Altern Med 2019; 19: 359
• 22 Zhang Y, Wang C, Wang L, Parks GS, Zhang X, Guo Z, Ke Y, Li KW, Kim MK, Vo B. A novel analgesic isolated from a traditional Chinese medicine. Curr Biol 2014; 24: 117-123
• 23 Dey P, Kundu A, Kumar A, Gupta M, Lee BM, Bhakta T, Dash S, Kim HS. Chapter 15 – Analysis of alkaloids (indole alkaloids, isoquinoline alkaloids, tropane alkaloids). In: Sanches Silva A, Nabavi SF, Saeedi M, Nabavi SM. eds. Recent Advances in Natural Products Analysis. Amsterdam: Elsevier; 2020: 505-567
• 24 Kong X, Chen Z, Xia Y, Liu EYL, Ren H, Wang C, Hu WH, Dong TX, Pi R, Tsim KWK. Dehydrocorydaline accounts the majority of anti-inflammatory property of corydalis rhizoma in cultured macrophage. Evid Based Complement Alternat Med 2020; 2020: 4181696
• 25 Yin ZY, Li L, Chu SS, Sun Q, Ma ZL, Gu XP. Antinociceptive effects of dehydrocorydaline in mouse models of inflammatory pain involve the opioid receptor and inflammatory cytokines. Sci Rep 2016; 6: 27129
• 26 Liu J, Dai R, Damiescu R, Efferth T, Lee DYW. Role of Levo-tetrahydropalmatine and its metabolites for management of chronic pain and opioid use disorders. Phytomedicine 2021; 90: 153594
• 27 Kaserer T, Steinacher T, Kainhofer R, Erli F, Sturm S, Waltenberger B, Schuster D, Spetea M. Identification and characterization of plant-derived alkaloids, corydine and corydaline, as novel mu opioid receptor agonists. Sci Rep 2020; 10: 13804
• 28 Cahlikova L, Hulova L, Hrabinova M, Chlebek J, Hostalkova A, Adamcova M, Safratova M, Jun D, Opletal L, Locarek M, Macakova K. Isoquinoline alkaloids as prolyl oligopeptidase inhibitors. Fitoterapia 2015; 103: 192-196
• 29 Shen S, Liu SZ, Zhang YS, Du MB, Liang AH, Song LH, Ye ZG. Compound antimalarial ethosomal cataplasm: Preparation, evaluation, and mechanism of penetration enhancement. Int J Nanomedicine 2015; 10: 4239-4253
• 30 Bastos CM, Rocha F, Cerqueira Â, Terroso D, Sequeira C, Tilley P. Assessment of clayey peloid formulations prior to clinical use in equine rehabilitation. Int J Environ Res Public Health 2020; 17: 3365
• 31 Ji WY, Ma JJ, Li JW, Liu XS. Research progress in TCM gel plaster. Chinese J Inf Tradit Chinese Med 2022; 29: 152-156
• 32 Zhu CY, Zhang YT, Wu T, He ZH, Guo T, Feng NP. Optimizing glycerosome formulations via an orthogonal experimental design to enhance transdermal triptolide delivery. Acta Pharm 2021; 72: 135-146
• 33 Jiang J, Quan P, Chen Y, Fang L. Mechanistic investigation and reversible effect of 2-isopropyl-5-methylcyclohexyl heptanoate on the in vitro percutaneous absorption of indomethacin. Drug Deliv 2014; 21: 26-33
• 34 Yang B, Han Y, Zhang QY, Dong H, Sun H, Wang XJ. [Study on absorbed components of Aconitum kusnezoffii under Yunnan Baiyao compatibility in effect of activating blood circulation and removing blood stasis]. Zhongguo Zhong Yao Za Zhi 2019; 44: 3349-3357
• 35 Ren XB, Zhang MZ, Chen LX, Huang WL, Luo HZ, Li L, He HB. The anti-inflammatory effects of Yunnan Baiyao are involved in regulation of the phospholipase A2/arachidonic acid metabolites pathways in acute inflammation rat model. Mol Med Rep 2017; 16: 4045-4053
• 36 Doncheva ND, Vasileva L, Saracheva K, Dimitrova D, Getova D. Study of antinociceptive effect of ketamine in acute and neuropathic pain models in rats. Adv Clin Exp Med 2019; 28: 573-579