Fuzhenghefuzhiyang Formula (FZHFZY) Improves Epidermal Differentiation via Suppression of the Akt/mTORC1/S6K1 Signalling Pathway in Psoriatic Models

Abstract

Psoriasis is a chronic proliferative skin disorder characterised by abnormal epidermal differentiation. The Fuzhenghefuzhiyang (FZHFZY) formula created by Chuanjian Lu, a master of Chinese medicine in dermatology, has been external used in the Guangdong Provincial Hospital of Chinese Medicine for the treatment of psoriasis, but its mechanisms of action against psoriasis remain poorly understood. This study involved an exploration of the effects of FZHFZY on epidermal differentiation and its underlying mechanisms in interleukin (IL)-17A/IL-22/interferon (IFN)-γ/tumour necrosis factor (TNF)-α–stimulated HaCaT cells and in a mouse model of imiquimod (IMQ)-induced psoriasis. Cell viability was assessed by MTT assay. Epidermal differentiation was detected by reverse-transcription polymerase chain reaction and western blotting. Histological evaluation of the skin tissue was performed via haematoxylin and eosin staining, and the Akt/mTORC1/S6K1 pathway was analysed by western blotting. FZHFZY inhibited proliferation and improved epidermal differentiation in IL-17A/IL-22/IFN-γ/TNF-α–induced HaCaT cells. FZHFZY ameliorated symptoms of psoriasis, regulated epidermal differentiation and inhibited phosphorylation of the Akt/mTORC1/S6K1 pathway in the skin of mice with imiquimod-induced psoriasis. Our results suggest that FZHFZY may exhibit therapeutic action against psoriasis by regulating epidermal differentiation via inhibition of the Akt/mTORC1/S6K1 pathway.

Leucosceptoside A from Devil’s Claw Modulates Psoriasis-like Inflammation via Suppression of the PI3K/AKT Signaling Pathway in Keratinocytes

“…Studies have reported hyperactivity of AKT/mTOR and its downstream molecular target ribosomal protein S6 kinase 1 (S6K1) in the skin lesions of patients with psoriasis [49,50], and the highly active PI3K/AKT/mTOR pathway can lead to the abnormal differentiation of keratinocytes, which is generally recognized as a main pathological feature of psoriasis [16,46]. Inactivation of PI3K/AKT signaling provides a novel approach in psoriasis management [61].…”

“…The chronic epidermal hyperplasia in psoriatic lesions is due to keratinocytes proliferation and main events of the immune response expressed by overactivation of PI3K/AKT/mTORC1 and STAT3 signaling cascades [46,47]. The apoptosis induction was reported as a key mechanism for regression of psoriatic hyperplasia with conventional UVA and methotrexate therapy [47,48].…”

“…The apoptosis induction was reported as a key mechanism for regression of psoriatic hyperplasia with conventional UVA and methotrexate therapy [47,48]. The PI3K/AKT/mTOR cascade plays a role on the resistance of psoriatic keratinocytes to apoptosis and dysregulation in keratinocyte differentiation [5,46,49,50].…”

Celastrol inhibits store operated calcium entry and suppresses psoriasis

“…The primer sequences used in this study are listed in Table 1 . The relative mRNA quantities were determined by the 2 −ΔΔCT method ( Lu et al, 2021 ), and further normalized to that of the GAPDH housekeeping gene.…”

The Gene Expression Analysis of Peripheral Blood Monocytes From Psoriasis Vulgaris Patients With Different Traditional Chinese Medicine Syndromes

“…Traditional Chinese Medicine (TCM) has great advantages and broad prospects in the treatment of psoriasis, and has accumulated rich treatment experience over a long time ( Yu et al, 2013 ; Zhang et al, 2014 ; Zhang et al, 2016 ; Yu et al, 2017 ). PSORI-CM02 and FZHFZY has been used for decades to treat blood stasis and blood dryness syndromes of psoriasis vulgaris at the Guangdong Provincial Hospital of Chinese Medicine ( Lu et al, 2019 ; Lu et al, 2021a ; Lu et al, 2021b ). PSORI-CM02 consists of Rhizoma Curcumae ( Curcuma longa L.), Radix Paeoniae rubra ( Paeonia lactiflora Pall.…”