Pyrolytic oils from Amphipterygium adstringens bark inhibit IL-8 production of IL-17-stimulated HaCaT keratinocytes

Highlights

• Pyrolytic oils from Amphipterygium adstringens bark were obtained by slow pyrolysis.

• Phenols were identified to be the dominant compounds identified in pyrolytic oils.

• Pyrolytic oils inhibit the IL-8 production of IL-17-stimulated keratinocytes.

• Oil-2 showed a similar inhibitory effect on IL-8 production as dexamethasone.

• Pyrolytic oils could be explored for treating IL-17 driven dermatological diseases.

Abstract

Pyrolytic products have been historically used as a therapeutic treatment for psoriasis, a dermatological inflammatory disease. However, little is known about the mechanisms involved in their pharmacological activity. The main goals of this work were to characterize pyrolytic fractions derived from Amphipterygium adstringens bark, a plant used in Mexican traditional medicine, and to study the effects of pyrolytic oils as anti-IL-17 agents on HaCaT keratinocytes. A. adstringens biomass and pyrolytic fractions were first characterized by proximate, elemental analysis, FTIR, Py-GC–MS, GC–MS, UV-fluorescence and HPLC-DAD to determine its physicochemical composition. Toxicity of pyrolytic oils was further assessed on HaCaT keratinocytes by the MTT method and the non-cytotoxic concentrations were used to determine their effects on IL-8 production of IL-17-stimulated HaCaT keratinocytes. The result obtained show that pyrolytic oils are very rich in phenols, some of them recognized by their anti-inflammatory properties. Pyrolytic oils showed significant inhibitory effects on IL-8 production, suggesting that they could be potentially explored for treating IL-17 driven dermatological diseases such as psoriasis.

Introduction

Psoriasis is a cutaneous disorder characterized by the presence of desquamative erythematous plaques [1]. The prevalence of this disease in adults worldwide ranges from 0.51 to 11.43 % [2]. The estimated prevalence in Mexico is 2.9 %, so more than 3 million Mexicans are affected [3], 12.4–25.9 % of them having moderate to severe forms of the disease [4]. The incidence of death directly caused by this disease is low, but its physical and psychological manifestations are comparable to those observed in cancer, diabetes, and depression [5]. Although psoriasis’ pathogenesis has not been fully elucidated; it is recognized that the disturbances in keratinocytes and the hyperproliferation of these cells are distinctive features of this disorder [6]. In recent years, it has been shown that the pathogenesis of this disease involves a complex interaction between neutrophils, dendritic cells (CD), T lymphocytes (mainly Th1 and Th17) and keratinocytes [7].

The crucial role of cytokines, such as interleukin (IL)-17 in the pathophysiology of psoriasis is now widely recognized by the scientific community. Indeed, it has been postulated that psoriasis is an IL-17-driven disease [8]. In psoriasis, IL-17 is mainly produced by T cells, mast cells and neutrophils [9,10]. Once released, IL-17 cytokines bind their respective transmembrane IL-17 receptor (IL-17R) which is expressed, among others, on keratinocyte surface, making these cutaneous cells important targets for IL-17 promoting effects [11]. IL-17 induces the keratinocyte proliferation with a negative impact on their differentiation [12], contributing to the skin barrier disruption. Additionally, IL-17 cytokines amplify the psoriasis inflammatory network as they can promote the keratinocyte release of other proinflammatory chemokines such as IL-8 [11] (a potent neutrophil chemoattractant), overexpressed in psoriatic lesions [13]. In psoriasis context, keratinocytes have been suggested to be a major IL-8 source [13,14] and psoriasis improvement correlates with the diminution of this chemokine in the skin [15].

Biological agents that neutralize IL-17 (secukinumab, ixekizumab) or antagonize its receptor (brodalumab) have been demonstrated to be highly efficacious in clinical studies for psoriasis [16]. However, some adverse events have been described with these drugs such as nasopharyngitis, headache, upper respiratory tract infection, arthralgia, hypertension, back pain and cough [17,18].

Global surveys have clearly shown that some psoriasis patients are dissatisfied with biological treatments (10–25 %), mainly due to adverse events (12–28 %), lack of effectiveness and high costs [19,20]. As their quality of life is affected, those patients usually use alternative therapies [21] such as coal tar and medicinal plants to treat their disease [22]. The use of distillation and pyrolysis products from coal, such as tar and pitch, became popular after 1925 when W.H. Goeckerman established a method to use them as a therapeutic option for psoriasis treatment [23]. Nowadays, research on the use of coal tar as an antipsoriatic drug continues, due to its efficacy and safety [24,25]. Despite its wide use, little is known about its exact mechanism of action [26]. Some compounds isolated from the coal tar such as carbazole and its derivatives have shown antipsoriatic activity in human cell lines [27]. Tar from other sources such as pinewood has also been used as part of the therapy to treat this skin illness because of its antipruritic, antimicrobial and anti-inflammatory properties [28].

Amphipterygium adstringens (Schltdl.) Standl. is a species endemic to Mexico belonging to the Anacardiaceae family that inhabits the tropical deciduous forest region [29]. The bark from this tree is widely used in Mexican traditional medicine for the treatment of various diseases, including dermatological disorders [29,30]. The chemical characterization of A. adstringens bark has been performed using conventional natural extracts obtained by ebullition or maceration [[31], [32], [33]]. Some compounds have been isolated from bark extracts, such as anacardic acid, masticadienonic acid, and β-sitosterol [32], which have shown anti-inflammatory and gastroprotective properties [31,33]. During the filtration process of these conventional extracts, the recovered residual biomass has been considered waste and nothing is known about its chemical characterization and/or biological properties.

Considering that it has not been described if pyrolytic fractions of the bark from this tree have biological actions, the aims of this study were to chemically characterize the pyrolytic fractions and residual biomass from A. adstringens bark and to evaluate the capacity of pyrolytic oils to inhibit IL-8 production of IL-17-stimulated HaCaT keratinocytes in order to propose future applications of pyrolytic oils of this species for psoriasis treatment.