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Cited by 97Dermatology and Skin DiseasesMedicinal Plants and NeuroprotectionContact Dermatitis and Allergies

Anti-Inflammatory Effect of Titrated Extract of Centella asiatica in Phthalic Anhydride-Induced Allergic Dermatitis Animal Model

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Park, Ju, Choi, Ji, Son, Dong, Park, Eun, Song, Min, Hellström, Mats, Hong, Jin·2017·International Journal of Molecular Sciences
DOI 10.3390/ijms18040738PMC PMC5412323
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Abstract

has potent antioxidant and anti-inflammatory properties. However, its anti-dermatitic effect has not yet been reported. In this study, we investigated the anti-dermatitic effects of titrated extract of Centella asiatica (TECA) in a phthalic anhydride (PA)-induced atopic dermatitis (AD) animal model as well as in vitro model. An AD-like lesion was induced by the topical application of five percent PA to the dorsal skin or ear of Hos:HR-1 mouse. After AD induction, 100 μL of 0.2% and 0.4% of TECA (40 μg or 80 μg/cm²) was spread on the dorsum of the ear or back skin three times a week for four weeks. We evaluated dermatitis severity, histopathological changes and changes in protein expression by Western blotting for inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), and NF-κB activity, which were determined by electromobility shift assay (EMSA). We also measured TNF-α, IL-1β, IL-6, and IgE concentration in the blood of AD mice by enzyme-linked immunosorbent assay (ELISA). TECA treatment attenuated the development of PA-induced atopic dermatitis. Histological analysis showed that TECA inhibited hyperkeratosis, mast cells and infiltration of inflammatory cells. TECA treatment inhibited expression of iNOS and COX-2, and NF-κB activity as well as the release of TNF-α, IL-1β, IL-6, and IgE. In addition, TECA (1, 2, 5 μg/mL) potently inhibited Lipopolysaccharide (LPS) (1 μg/mL)-induced NO production, expression of iNOS and COX-2, and NF-κB DNA binding activities in RAW264.7 macrophage cells. Our data demonstrated that TECA could be a promising agent for AD by inhibition of NF-κB signaling.

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  • Phytosomal formulations of C. asiatica (0.2-0.4%) in models of atopic dermatitis have shown substantial decreases in IgE, COX-2, iNOS, TNF-α, and mast cell counts through modulation of the NF-κB signaling pathway.

    “Studies utilizing phytosomal formulations of C. asiatica (0.2–0.4%) in models of atopic dermatitis have shown substantial decreases in inflammatory markers such as immunoglobulin E (IgE), cyclooxygenase-2 (COX-2), inducible nitric oxide synthase (iNOS), tumor necrosis factor alpha (TNF-α), and mast cell counts through modulation of the NF-κB signaling pathway (Park et al. 2017).”

    From Centella asiatica (L.) Urb. in skin health and cosmeceuticals: mechanisms, clinical evidence, and advanced delivery systems (2025) · cites this paper as Park et al. 2017

    The Materials and Methods (section 4.3; page unavailable) describe topical treatment with 0.2% and 0.4% titrated extract of Centella asiatica (TECA), not a phytosomal formulation. The Discussion (section 3; page unavailable) links TECA to reduced IgE, TNF-α, iNOS and COX-2 and attenuated NF-κB activation; the paper also reports fewer mast cells. The reported effects are largely supported, but the formulation attributed to the study is not. (LLM, conf=0.90)

    Experimental — accuracy not yet measured

  • Phytosomes inhibited NF-κB, COX-2, iNOS, and IgE in dermatitis models.

    “as demonstrated by the inhibition of NF-κB, COX-2, iNOS, and IgE in dermatitis models (Park et al. 2017).”

    From Centella asiatica (L.) Urb. in skin health and cosmeceuticals: mechanisms, clinical evidence, and advanced delivery systems (2025) · cites this paper as Park et al. 2017

    The Results (§2.5–2.7) and Discussion report that titrated Centella asiatica extract (TECA) inhibited NF-κB activity, reduced COX-2 and iNOS expression, and lowered IgE in the dermatitis study. The tested treatment was TECA, not a phytosome formulation, so the citation does not support attributing those effects to phytosomes. (LLM, conf=0.89)

    Experimental — accuracy not yet measured

  • Phytosome complexes showed added anti-inflammatory effects in atopic and contact dermatitis models.

    “Phytosome complexes showed added anti-inflammatory effects in atopic and contact dermatitis models, emphasizing the importance of delivery vehicle–bioactive interactions.”

    From Centella asiatica (L.) Urb. in skin health and cosmeceuticals: mechanisms, clinical evidence, and advanced delivery systems (2025) · cites this paper as Park et al. 2017

    The Discussion (page not provided) reports that titrated Centella asiatica extract reduced inflammation in a phthalic anhydride-induced atopic dermatitis model. It does not report phytosome complexes, an added effect from a delivery vehicle, or results in a contact dermatitis model. (LLM, conf=0.84)

    Experimental — accuracy not yet measured

  • Phytosomes complexing madecassoside with phospholipids offer enhanced anti-inflammatory action and better skin permeation.

    “Phytosomes, complexing polar bioactives such as madecassoside with phospholipids, offer enhanced anti-inflammatory action and better skin permeation”

    From Centella asiatica (L.) Urb. in skin health and cosmeceuticals: mechanisms, clinical evidence, and advanced delivery systems (2025) · cites this paper as Park et al. 2017

    The Discussion reports anti-inflammatory effects of a titrated Centella asiatica extract, while the Materials and Methods describe an extract containing asiaticoside, asiatic acid, and madecassic acid—not a madecassoside phytosome. Searches for phytosomes, phospholipid complexes, and improved skin permeation found no passage addressing the claimed formulation or its comparative effects. (LLM, conf=0.76)

    Experimental — accuracy not yet measured

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References 48 · Cited by 97

Research works printed but not linked: 45

  1. [1]Sehra S. Krishnamurthy P. Koh B. Zhou H.M. Seymour L. Akhtar N. Travers J.B. Turner M.J. Kaplan M.H. Increased Th2 activity and diminished skin barrier function cooperate in allergic skin inflammation Eur. J. Immunol. 2016 46 2609 2613 10.1002/eji.201646421 27510401 PMC5142240 · DOI
  2. [2]Eichenfield L.F.M. Friedlander S.F.M. Simpson E.L.M.M. Irvine A.D.M. Assessing the New and Emerging Treatments for Atopic Dermatitis Semin. Cutan. Med. Surg. 2016 35 Suppl. S5 S92 S96 10.12788/j.sder.2016.043 27525671 · DOI
  3. [3]Choi J.K. Kim S.H. Inhibitory effect of galangin on atopic dermatitis-like skin lesions Food Chem. Toxicol. 2014 68 135 141 10.1016/j.fct.2014.03.021 24675422 · DOI
  4. [4]Kuramoto T. Yokoe M. Tanaka D. Yuri A. Nishitani A. Higuchi Y. Yoshimi K. Tanaka M. Kuwamura M. Hiai H. Atopic dermatitis-like skin lesions with IgE hyperproduction and pruritus in KFRS4/Kyo rats J. Dermatol. Sci. 2015 80 116 123 10.1016/j.jdermsci.2015.09.005 26454563 · DOI
  5. [5]Kwak M.H. Kim J.E. Hwang I.S. Lee Y.J. An B.S. Hong J.T. Lee S.H. Hwang D.Y. Quantitative evaluation of therapeutic effect of Liriope platyphylla on phthalic anhydride-induced atopic dermatitis in IL-4/Luc/CNS-1 Tg mice J. Ethnopharmacol. 2013 148 880 889 10.1016/j.jep.2013.05.036 23726789 · DOI
  6. [6]Sung J.E. Lee H.A. Kim J.E. Go J. Seo E.J. Yun W.B. Kim D.S. Son H.J. Lee C.Y. Lee H.S. Therapeutic effect of ethyl acetate extract from Asparagus cochinchinensis on phthalic anhydride-induced skin inflammation Lab. Anim. Res. 2016 32 34 45 10.5625/lar.2016.32.1.34 27051441 PMC4816995 · DOI
  7. [7]Park H.J. Jang Y.J. Yim J.H. Lee H.K. Pyo S. Ramalin Isolated from Ramalina Terebrata Attenuates Atopic Dermatitis-like Skin Lesions in Balb/c Mice and Cutaneous Immune Responses in Keratinocytes and Mast Cells Phytother. Res. 2016 30 1978 1987 10.1002/ptr.5703 27558640 · DOI
  8. [8]Zhang Y.Y. Wang A.X. Xu L. Shen N. Zhu J. Tu C.X. Characteristics of peripheral blood CD4+CD25+ regulatory T cells and related cytokines in severe atopic dermatitis Eur. J. Dermatol. 2016 26 240 246 27184163
  9. [9]Klewicka E. Cukrowska B. Libudzisz Z. Slizewska K. Motyl I. Changes in gut microbiota in children with atopic dermatitis administered the bacteria Lactobacillus casei DN-114001 Pol. J. Microbiol. 2011 60 329 333 22390068
  10. [10]Harada D. Takada C. Tsukumo Y. Takaba K. Manabe H. Analyses of a mouse model of the dermatitis caused by 2,4,6-trinitro-1-chlorobenzene (TNCB)-repeated application J. Dermatol. Sci. 2005 37 159 167 10.1016/j.jdermsci.2004.11.007 15734285 · DOI
  11. [11]Homey B. Steinhoff M. Ruzicka T. Leung D.Y. Cytokines and chemokines orchestrate atopic skin inflammation J. Allergy Clin. Immunol. 2006 118 178 189 10.1016/j.jaci.2006.03.047 16815153 · DOI
  12. [12]Wullaert A. Bonnet M.C. Pasparakis M. NF-kappaB in the regulation of epithelial homeostasis and inflammation Cell Res. 2011 21 146 158 10.1038/cr.2010.175 21151201 PMC3193399 · DOI
  13. [13]Barnes P.J. Karin M. Nuclear factor-κB: A pivotal transcription factor in chronic inflammatory diseases N. Engl. J. Med. 1997 336 1066 1071 10.1016/S1357-2725(96)00159-8 9091804 · DOI
  14. [14]Nakamura H. Aoki M. Tamai K. Oishi M. Ogihara T. Kaneda Y. Morishita R. Prevention and regression of atopic dermatitis by ointment containing NF-κB decoy oligodeoxynucleotides in NC/Nga atopic mouse model Gene Ther. 2002 9 1221 1229 10.1038/sj.gt.3301724 12215889 · DOI
  15. [15]Tanaka A. Konno M. Muto S. Kambe N. Morii E. Nakahata T. Itai A. Matsuda H. A novel NF-κB inhibitor, IMD-0354, suppresses neoplastic proliferation of human mast cells with constitutively activated C-kit receptors Blood 2005 105 2324 2331 10.1182/blood-2004-08-3247 15561889 · DOI
  16. [16]Leung D.Y. Atopic dermatitis: New insights and opportunities for therapeutic intervention J. Allergy Clin. Immunol. 2000 105 860 876 10.1067/mai.2000.106484 10808164 · DOI
  17. [17]Simpson E.L. Atopic dermatitis: A review of topical treatment options Curr. Med. Res. Opin. 2010 26 633 640 10.1185/03007990903512156 20070141 · DOI
  18. [18]Gonzales F. Ramdane N. Delebarre-Sauvage C. Modiano P. Duhamel A. Lasek A. Monitoring of topical corticosteroid phobia in a population of parents with children with atopic dermatitis using the TOPICOP(R) scale: Prevalence, risk factors and the impact of therapeutic patient education J. Eur. Acad. Dermatol. Venereol. 2016 31 e172 e174 10.1111/jdv.13961 27608366 · DOI
  19. [19]Bylka W. Znajdek-Awizen P. Studzinska-Sroka E. Danczak-Pazdrowska A. Brzezinska M. Centella asiatica in dermatology: An overview Phytother. Res. 2014 28 1117 1124 10.1002/ptr.5110 24399761 · DOI
  20. [20]Incandela L. Cesarone M.R. DeSanctis M.T. Belcaro G. Dugall M. Acerbi G. Treatment of diabetic microangiopathy and edema with HR (Paroven, Venoruton; O-(β-hydroxyethyl)-rutosides): A prospective, placebo-controlled, randomized study J. Cardiovasc. Pharmacol. Ther. 2002 7 Suppl. S1 S11 S15 10.1177/107424840200700104 12011967 · DOI
  21. [21]Subathra M. Shila S. Devi M.A. Panneerselvam C. Emerging role of Centella asiatica in improving age-related neurological antioxidant status Exp. Gerontol. 2005 40 707 715 10.1016/j.exger.2005.06.001 16026958 · DOI
  22. [22]Chong N.J. Aziz Z. A Systematic Review of the Efficacy of Centella asiatica for Improvement of the Signs and Symptoms of Chronic Venous Insufficiency Evid. Based Complement. Altern. Med. 2013 2013 627182 10.1155/2013/627182 23533507 PMC3594936 · DOI
  23. [23]Bylka W. Znajdek-Awizen P. Studzinska-Sroka E. Brzezinska M. Centella asiatica in cosmetology Postepy Dermatol. Alergol. 2013 30 46 49 10.5114/pdia.2013.33378 24278045 PMC3834700 · DOI · Paper page
  24. [24]Suzuki H. Makino Y. Nagata M. Furuta J. Enomoto H. Hirota T. Tamari M. Noguchi E. A rare variant in CYP27A1 and its association with atopic dermatitis with high serum total IgE Allergy 2016 71 1486 1489 10.1111/all.12950 27259383 · DOI
  25. [25]Takahashi-Ando N. Jones M.A. Fujisawa S. Hama R. Patient-reported outcomes after discontinuation of long-term topical corticosteroid treatment for atopic dermatitis: A targeted cross-sectional survey Drug Healthc. Patient Saf. 2015 7 57 62 10.2147/DHPS.S78016 25897263 PMC4396455 · DOI
  26. [26]Bebawy J.F. Perioperative steroids for peritumoral intracranial edema: A review of mechanisms, efficacy, and side effects J. Neurosurg. Anesthesiol. 2012 24 173 177 10.1097/ANA.0b013e3182578bb5 22544067 · DOI
  27. [27]Park S.J. Lee Y.H. Lee K.H. Kim T.J. Effect of eriodictyol on the development of atopic dermatitis-like lesions in ICR mice Biol. Pharm. Bull. 2013 36 1375 1379 10.1248/bpb.b13-00296 23902981 · DOI
  28. [28]Hashim P. Sidek H. Helan M.H. Sabery A. Palanisamy U.D. Ilham M. Triterpene composition and bioactivities of Centella asiatica Molecules 2011 16 1310 1322 10.3390/molecules16021310 21278681 PMC6259745 · DOI · Paper page
  29. [29]Tang B. Zhu B. Liang Y. Bi L. Hu Z. Chen B. Zhang K. Zhu J. Asiaticoside suppresses collagen expression and TGF-β/Smad signaling through inducing Smad7 and inhibiting TGF-βRI and TGF-βRII in keloid fibroblasts Arch. Dermatol. Res. 2011 303 563 572 10.1007/s00403-010-1114-8 21240513 · DOI
  30. [30]Nowwarote N. Osathanon T. Jitjaturunt P. Manopattanasoontorn S. Pavasant P. Asiaticoside induces type I collagen synthesis and osteogenic differentiation in human periodontal ligament cells Phytother. Res. 2013 27 457 462 10.1002/ptr.4742 22628285 · DOI
  31. [31]Maquart F.X. Chastang F. Simeon A. Birembaut P. Gillery P. Wegrowski Y. Triterpenes from Centella asiatica stimulate extracellular matrix accumulation in rat experimental wounds Eur. J. Dermatol. 1999 9 289 296 10356407
  32. [32]Nhiem N.X. Tai B.H. Quang T.H. Kiem P.V. Minh C.V. Nam N.H. Kim J.H. Im L.R. Lee Y.M. Kim Y.H. A new ursane-type triterpenoid glycoside from Centella asiatica leaves modulates the production of nitric oxide and secretion of TNF-α in activated RAW264.7 cells Bioorg. Med. Chem. Lett. 2011 21 1777 1781 10.1016/j.bmcl.2011.01.066 21353543 · DOI
  33. [34]Hou Q. Li M. Lu Y.H. Liu D.H. Li C.C. Burn wound healing properties of asiaticoside and madecassoside Exp. Ther. Med. 2016 12 1269 1274 10.3892/etm.2016.3459 27588048 PMC4997909 · DOI
  34. [36]Won J.H. Shin J.S. Park H.J. Jung H.J. Koh D.J. Jo B.G. Lee J.Y. Yun K. Lee K.T. Anti-inflammatory effects of madecassic acid via the suppression of NF-κB pathway in LPS-induced RAW264.7 macrophage cells Planta Med. 2010 76 251 257 10.1055/s-0029-1186142 19774506 · DOI
  35. [37]Murakami Y. Shoji M. Hirata A. Tanaka S. Yokoe I. Fujisawa S. Dehydrodiisoeugenol, an isoeugenol dimer, inhibits lipopolysaccharide-stimulated nuclear factor kappa B activation and cyclooxygenase-2 expression in macrophages Arch. Biochem. Biophys. 2005 434 326 332 10.1016/j.abb.2004.11.013 15639233 · DOI
  36. [38]Liu F.T. Goodarzi H. Chen H.Y. IgE, mast cells, and eosinophils in atopic dermatitis Clin. Rev. Allergy Immunol. 2011 41 298 310 10.1007/s12016-011-8252-4 21249468 · DOI
  37. [39]Schreiber S. Kilgus O. Payer E. Kutil R. Elbe A. Mueller C. Stingl G. Cytokine pattern of Langerhans cells isolated from murine epidermal cell cultures J. Immunol. 1992 149 3524 3534 1431123
  38. [40]Friedmann P.S. Contact sensitisation and allergic contact dermatitis: Immunobiological mechanisms Toxicol. Lett. 2006 162 49 54 10.1016/j.toxlet.2005.10.008 16361071 · DOI
  39. [41]Kim G.D. Lee S.E. Park Y.S. Shin D.H. Park G.G. Park C.S. Immunosuppressive effects of fisetin against dinitrofluorobenzene-induced atopic dermatitis-like symptoms in NC/Nga mice Food Chem. Toxicol. 2014 66 341 349 10.1016/j.fct.2014.01.057 24525099 · DOI
  40. [42]Yang G. Choi C.H. Lee K. Lee M. Ham I. Choi H.Y. Effects of Catalpa ovata stem bark on atopic dermatitis-like skin lesions in NC/Nga mice J. Ethnopharmacol. 2013 145 416 423 10.1016/j.jep.2012.10.015 23195129 · DOI
  41. [43]Lee H.J. Kim M.H. Choi Y.Y. Kim E.H. Hong J. Kim K. Yang W.M. Improvement of atopic dermatitis with topical application of Spirodela polyrhiza J. Ethnopharmacol. 2016 180 12 17 10.1016/j.jep.2016.01.010 26778605 · DOI
  42. [44]Tanaka A. Muto S. Jung K. Itai A. Matsuda H. Topical application with a new NF-κB inhibitor improves atopic dermatitis in NC/NgaTnd mice J. Investig. Dermatol. 2007 127 855 863 10.1038/sj.jid.5700603 17068475 · DOI
  43. [45]Park J.H. Kim M.S. Jeong G.S. Yoon J. Xanthii fructus extract inhibits TNF-α/IFN-γ-induced Th2-chemokines production via blockade of NF-κB, STAT1 and p38-MAPK activation in human epidermal keratinocytes J. Ethnopharmacol. 2015 171 85 93 10.1016/j.jep.2015.05.039 26051830 · DOI
  44. [46]Kim H. Lee E. Lim T. Jung J. Lyu Y. Inhibitory effect of Asparagus cochinchinensis on tumor necrosis factor-α secretion from astrocytes Int. J. Immunopharmacol. 1998 20 153 162 10.1016/S0192-0561(98)00022-8 9730251 · DOI
  45. [47]Qiu J. Yu L. Zhang X. Wu Q. Wang D. Wang X. Xia C. Feng H. Asiaticoside attenuates lipopolysaccharide-induced acute lung injury via down-regulation of NF-κB signaling pathway Int. Immunopharmacol. 2015 26 181 187 10.1016/j.intimp.2015.03.022 25835778 · DOI · Paper page

Authors
Park, J., Choi, J., Son, D., Park, E., Song, M., Hellström, M., & Hong, J.
Affiliations
  • Chungbuk National University (KR)
  • The Catholic University of Korea Daejeon St. Mary's Hospital (KR)
  • University of Gothenburg (SE)
Corresponding author
Hong, Jin
ORCID
Venue
International Journal of Molecular Sciences
Publisher
MDPI AG
Published
2017-03-30
Volume
18
Issue
4
Pages
738
ISSN
1422-0067 (ISSN-L)
DOI
10.3390/ijms18040738
PMC
PMC5412323
OpenAlex
W2600159981
Cited by
97
References
48
Citations by year
2026: 9 · 2025: 10 · 2024: 14 · 2023: 10 · 2022: 11 · 2021: 16 · 2020: 13 · 2019: 7 · 2018: 5 · 2017: 2
FWCI
8.41
Type
journal article
Language
en
Open access
Licence
Locations
  • International Journal of Molecular Sciences (publishedVersion, cc-by)
  • Europe PMC (PubMed Central) (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
Funders
  • National Research Foundation
  • Ministry of Trade, Industry and Energy (1415139249, MOTIE, 1415139249)
  • Ministry of Science, ICT and Future Planning (MRC.2008-0062275, 2008-0062275)
  • National Research Foundation of Korea (MRC 2008‐0062275, 2008‐0062275)
  • Medical Research Council (2008-0062275)
Topics
  • Health Sciences › Medicine › Dermatology › Dermatology and Skin Diseases
  • Health Sciences › Medicine › Complementary and alternative medicine › Medicinal Plants and Neuroprotection
  • Health Sciences › Medicine › Dermatology › Contact Dermatitis and Allergies
Keywords
Centella asiatica, atopic dermatitis, anti-inflammatory activity, NF-κB signaling, inducible nitric oxide synthase, cyclooxygenase-2, mast cells, hyperkeratosis, cytokines, IgE, lipopolysaccharide-induced nitric oxide, macrophages, topical herbal extract
MeSH terms
Animals, Anti-Inflammatory Agents, Cell Line, Interleukins, Macrophages, Phthalic Anhydrides, Plant Extracts, Skin, Triterpenes, Tumor Necrosis Factor-alpha, NF-kappa B, Dermatitis, Allergic Contact, Centella, Mice, Cyclooxygenase 2, Nitric Oxide Synthase Type II

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