Biotechnologically Produced Lavandula angustifolia Mill. Extract Rich in Rosmarinic Acid Resolves Psoriasis-Related Inflammation Through Janus Kinase/Signal Transducer and Activator of Transcription Signaling.

Ivanka K. Koycheva,Liliya V. Vasileva,Milen I. Georgiev,Kristiana M. Amirova,Zhivka P. Balcheva-Sivenova,Andrey S. Marchev

doi:10.3389/fphar.2021.680168

Abstract

Psoriasis is a common skin pathology, characterized by dysregulation of epidermal keratinocyte function attended by persistent inflammation, suggesting that molecules with anti-inflammatory potential may be effective for its management. Rosmarinic acid (RA) is a natural bioactive molecule known to have an anti-inflammatory potential. Here we examined the effect of biotechnologically produced cell suspension extract of Lavandula angustifolia Mill (LV) high in RA content as treatment for psoriasis-associated inflammation in human keratinocytes. Regulatory genes from the nuclear factor kappa B (NF-κB) and Janus kinase/signal transducer and activator of transcription (JAK/STAT) signaling pathways were upregulated upon stimulation with a combination of interferon gamma (IFN-γ), interleukin (IL)-17A and IL-22. We also observed that both LV extract and RA could inhibit JAK2, leading to reduced STAT1 phosphorylation. Further, we demonstrated that LV extract inhibited phosphoinositide 3-kinases (PI3K) and protein kinase B (AKT), which could be implicated in reduced hyperproliferation in keratinocytes. Collectively, these findings indicate that the biotechnologically produced LV extract resolved psoriasis-like inflammation in human keratinocytes by interfering the JAK2/STAT1 signaling pathway and its effectiveness is due to its high content of RA (10%). Hence, both LV extract and pure RA possess the potential to be incorporated in formulations for topical application as therapeutic approach against psoriasis.

Highlights

Psoriasis is a recurrent, chronic skin disease with complex immune-inflammatory ethology (Nestle et al, 2009; Sakurai et al, 2019)
Rosmarinic acid (RA) treatment in stimulated keratinocytes resulted in significant downregulation of JAK2 and STAT1, which was not observed upon the Lavandula angustifolia Mill (LV) extract application. These findings indicated that LV extract affects mainly genes from the NF-κB signaling in activated keratinocytes, while RA interfere with JAK/STAT signaling as well
As STAT1 expression was activated predominantly over STAT3 by cytokine stimulation in our study, we evaluated whether RA could antagonize STAT1 activation induced by IFN-γ/IL-17A/IL-22 in keratinocytes at a protein level

Summary

Introduction

Chronic skin disease with complex immune-inflammatory ethology (Nestle et al, 2009; Sakurai et al, 2019). The pathophysiology of psoriasis is complex and to a certain degree arguable, several important pathways are defined to play role in the progression of psoriatic inflammation, namely, activated nuclear factor kappa B (NF-κB), Janus kinase/signal transducer and activator of transcription (JAK/STAT), phosphoinositide 3-kinase/protein kinase B (PI3K/AKT) and mitogen activate protein kinase (MAPK) signaling (Engelman et al, 2006; Wolf et al, 2010; Andres et al, 2013; Schwartz et al, 2017; Li et al, 2019; Liang et al, 2019; Sakurai et al, 2019)

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