EXPERIMENTAL SUBSTANTIATION OF THE ANTI-INFLAMMATORY MECHANISM OF REFINED NAFTALAN OIL
DOI:
https://doi.org/10.11603/1811-2471.2025.v.i1.15125Keywords:
natural-origin substances, refined Naftalan oil, dermatological agents, cream, skin lesions, anti-inflammatory action, analgesic action, pharmaceutical developmentAbstract
SUMMARY. Naftalan oil is a unique natural raw material with pronounced balneological properties. However, over time it was found to contain toxic and carcinogenic substances (aromatic hydrocarbons, resins), which limited its use in modern medicine. Refined Naftalan oil (RNO) has a significantly lower content of potentially hazardous compounds while preserving the spectrum of biologically active naphthenic hydrocarbons. This opens prospects for developing new topical medicinal products based on RNO with improved pharmaceutical and pharmacological properties.
The aim – to investigate the pharmacological properties and certain aspects of the anti-inflammatory mechanism of refined Naftalan oil.
Materials and Methods. Test samples of a monocomponent cream containing 10% RNO and a combined cream containing 10 % RNO and 2 % drotaverine were studied. In vivo, pharmacological assessments of the RNO-containing creams were performed using a model of imiquimod-induced psoriasis-like skin lesions in BALB/c mice, with an additional induction of an acute inflammatory response by carrageenan injection. The in vitro anti-inflammatory activity of RNO was evaluated by measuring the production of key pro-inflammatory cytokines (IL-1β and IL-8) in a model system of psoriasis-modified human keratinocytes (HaCaT/P cell line). The efficacy of the test samples was compared to 1 % hydrocortisone cream.
Discussion. In the psoriasis-like skin lesion model enhanced by carrageenan, it was found that the monocomponent 10 % RNO cream exhibited relatively low anti-inflammatory activity (19 %). In contrast, the cream with 10 % RNO and 2 % drotaverine showed a more pronounced effect (29 %), comparable to hydrocortisone (32 %). Studies on HaCaT/P keratinocytes demonstrated that RNO markedly inhibited IL-8 synthesis – by nearly 65 % - without affecting IL-1β levels, unlike the corticosteroid hydrocortisone, which reduced both IL-8 (by 39 %) and IL-1β (by 45 %).
Conclusions. The data indicate that the monocomponent 10 % RNO cream has weak anti-inflammatory activity, whereas the combination of RNO with drotaverine demonstrates moderate efficacy. The mechanism of RNO’s anti-inflammatory action appears to involve its ability to selectively modulate the synthesis of early-phase inflammatory mediators and suppress neutrophil migration by reducing IL-8 production.
References
Alajbeg, Ivan ; Ivanković, Siniša ; Jurin, Mislav ; Alajbeg Ž., Iva ; Rošin-Grget, Kata ; Cekić-Arambašin, Ana Non-aromatic naphthalane as a potential healing medium // Periodicum biologorum. Zagreb: Hrvatsko prirodoslovno društvo, 2001. str. 89-89-x
Adigozalova V. A. Naftalan oil is a specific balneological factor of Azerbaijan / V. A. Adigozalova // Azerbaijan J. Phys. – 2023. – Vol. 38, № 1. – P. 48–56. doi: 10.59883/ajp.52. DOI: https://doi.org/10.59883/ajp.52
Krnjević-Pezić, Gordana ; Jakić-Razumović, Jasminka ; Vržogić, Pero ; Smeh-Skrbin, Ankica ; Lipozenčić, Jasna ; Pašić, Aida Effect of naphthalene therapy on proliferative activity, CD4 and CD8 cell count, apoptosis and angiogenesis in the skin of psoriasis patients // British journal of dermatology, 2005. str. 21-22
Alajbe, I., Dinter, G., Alajbeg, A., Telen, S., & Prostenik, M. (2001). Study of Croatian non-aromatic naphthalane constituents with skeletons analogous to bioactive compounds. Journal of chromatography. A, 918(1), 127–134. DOI: https://doi.org/10.1016/S0021-9673(01)00720-8
Thaci D, Schindewolf M, Smeh-Skrbin A, Krnjevic-Pezic G, Vrzogic P, Dobric I, Kaufmann R, Boehncke WH. Heavy naphthen oil exhibits antipsoriatic efficacy in vivo and antiproliferative as well as differentiation-inducing effects on keratinocytes in vitro. Arch Dermatol. 2000 May;136(5):678-9. doi: 10.1001/archderm.136.5.678. PMID: 10815873. DOI: https://doi.org/10.1001/archderm.136.5.678
Teoretychne i eksperymentalne obgruntuvannia rozroblennia dermatolohichnykh likarskikh zasobiv na osnovi pryrodnykh spoluk naftalanskoii nafty / G. V. Zaychenko, N. O. Gorchakova, A. O. Gorbach [et al.] // Phytotherapy. J. – 2024. – № 3. – P. 52–61. doi: 10.32782/2522-9680-2024-3-52. DOI: https://doi.org/10.32782/2522-9680-2024-3-52
McCarson K. E. Models of inflammation: Carrageenan- or Complete Freund’s Adjuvant (CFA)-induced edema and hypersensitivity in the rat / K. E. McCarson, J. C. Fehrenbacher // Curr. Protoc. – 2021. – Vol. 1, № 7. – P. e202. doi: 10.1002/cpz1.202. DOI: https://doi.org/10.1002/cpz1.202
Hawkes J. E. The snowballing literature on imiquimod-induced skin inflammation in mice: A critical appraisal / J. E. Hawkes, J. E. Gudjonsson, N. L. Ward // J. Invest. Dermatol. – 2017. – Vol. 137, № 3. – P. 546–549. doi: 10.1016/j.jid.2016.10.024. DOI: https://doi.org/10.1016/j.jid.2016.10.024
Wu H, Ou J, Li K, Wang T, Nandakumar KS. Comparative studies on mannan and imiquimod induced experimental plaque psoriasis inflammation in inbred mice. Clin Exp Immunol. 2023 Mar 24;211(3):288-300. doi: 10.1093/cei/uxad004. PMID: 36645209; PMCID: PMC10038325. DOI: https://doi.org/10.1093/cei/uxad004
Doklinichni doslidzhennia likarskikh zasobiv : metodychni rekomendatsii: pid red. O. V. Stefanova. – К. : Avitsena, 2001. – 528 p.
Bannon A. W. Models of nociception: Hot-plate, tail-flick, and formalin tests in rodents / A. W. Bannon, A. B. Malmberg // Curr. Protoc. Neurosci. – 2007. – Chapter 8, Unit 8.9. doi: 10.1002/0471142301.ns0809s41. DOI: https://doi.org/10.1002/0471142301.ns0809s41
Alajbeg, Ivan ; Ivanković, Siniša ; Jurin, Mislav ; Alajbeg Ž., Iva ; Rošin-Grget, Kata ; Cekić-Arambašin, Ana Non-aromatic naphthalane as a potential healing medium // Periodicum biologorum. Zagreb: Hrvatsko prirodoslovno društvo, 2001. str. 89-89-x
Varma SR, Sivaprakasam TO, Mishra A, Prabhu S, M R, P R. Imiquimod-induced psoriasis-like inflammation in differentiated Human keratinocytes: Its evaluation using curcumin. Eur J Pharmacol. 2017 Oct 15;813:33-41. doi: 10.1016/j.ejphar.2017.07.040. Epub 2017 Jul 21. PMID: 28736282. DOI: https://doi.org/10.1016/j.ejphar.2017.07.040
Zhou X, Chen Y, Cui L, Shi Y, Guo C. Advances in the pathogenesis of psoriasis: from keratinocyte perspective. Cell Death Dis. 2022 Jan 24;13(1):81. doi: 10.1038/s41419-022-04523-3. PMID: 35075118; PMCID: PMC8786887. DOI: https://doi.org/10.1038/s41419-022-04523-3
Cai Y, Xue F, Quan C, Qu M, Liu N, Zhang Y, Fleming C, Hu X, Zhang HG, Weichselbaum R, Fu YX, Tieri D, Rouchka EC, Zheng J, Yan J. A Critical Role of the IL-1β-IL-1R Signaling Pathway in Skin Inflammation and Psoriasis Pathogenesis. J Invest Dermatol. 2019 Jan;139(1):146-156. doi: 10.1016/j.jid.2018.07.025. Epub 2018 Aug 16. PMID: 30120937; PMCID: PMC6392027. DOI: https://doi.org/10.1016/j.jid.2018.07.025
Flutter B, Nestle FO. TLRs to cytokines: mechanistic insights from the imiquimod mouse model of psoriasis. Eur J Immunol. 2013 Dec;43(12):3138-46. doi: 10.1002/eji.201343801. Epub 2013 Nov 20. PMID: 24254490. DOI: https://doi.org/10.1002/eji.201343801
