ReferenceID 5965
Perillyl alcohol inhibits keratinocyte proliferation and attenuates imiquimod-induced psoriasis like skin-inflammation by modulating NF-κB and STAT3 signaling pathways
Int Immunopharmacol
Psoriasis is a chronic inflammatory and proliferative skin disease characterized by pathological skin lesions which significantly impact the quality of life. Recent studies have been proven that inhibitors of farnesyltra
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- Reference Id
- 5965
- Evidence Id
- 22555
- Core Evidence Id
- 22555
- Source Reference Id
- 5191
- Herb2 Reference Id
- HBREF005988
- Subject Paper Key
- HBIN039240_34929480
- Pubmed Id
- 34929480
- Doi
- 10.1016/j.intimp.2021.108436
- Paper Title
- Perillyl alcohol inhibits keratinocyte proliferation and attenuates imiquimod-induced psoriasis like skin-inflammation by modulating NF-κB and STAT3 signaling pathways
- Paper Abstract
- Psoriasis is a chronic inflammatory and proliferative skin disease characterized by pathological skin lesions which significantly impact the quality of life. Recent studies have been proven that inhibitors of farnesyltransferase enzyme showed significant anti-psoriatic activity. Perillyl alcohol (POH) is one such natural molecule having anti proliferative, anti-inflammatory and anti-oxidant properties by inhibiting farnesyltransferase enzyme which further down regulates NF-κB and STAT3 via Ras/Raf/MAPK pathway. Hence, in the current study we aimed to find the effect of POH on human keratinocytes (HaCat) cells in in-vitro and IMQ induced psoriatic like skin inflammation model in mice. POH significantly decreased the intracellular ROS levels and inhibited the phosphorylation of NF-κB and STAT3 in in-vitro. It was found that POH (200 mg/kg, topical application) has reduced the epidermal hyperplasia, psoriasis area and severity index (PASI) scoring; splenomegaly in imiquimod (IMQ) induced psoriatic mice. Further, POH treatment has decreased the pro-inflammatory serum cytokine levels such as IL-6, IL-12/23, TNF-α and IL-1β and also reduced the expression levels of various inflammatory proteins, COX-2, iNOS, IL-17A, IL-22, NF-кB and STAT3 evidenced by Immunoblotting studies from skin samples. The levels of endogenous antioxidants like glutathione GSH, SOD, Nrf2 were restored to normal levels upon POH treatment. POH downregulated the proteins levels of TLR7, TLR8, CyclinD1 and mRNA expression of Bcl-2 in the skin samples when compared to the IMQ group. POH has ameliorated the hyper-keratosis and acanthosis which was evidenced by histopathology. Collectively, our results suggest that POH has a promising therapeutic application for ameliorating psoriasis-like skin inflammation.
- Journal
- Int Immunopharmacol
- Publish Year
- 2021
- Experiment Subject
- mouse; human; hacat) cells
- Experiment Type
- Animal & Cell Experiment
- Phenotype Related
- Psoriatic Like Skin Inflammation; Chronic Inflammatory And Proliferative Skin Disease; Epidermal Hyperplasia; Splenomegaly; Imiquimod; Skin Lesions; Psoriasis; Acanthosis; Psoriasis-like Skin Inflammation; Hyper-keratosis
- Paper Title Cn
- Paper Title En
- Perillyl alcohol inhibits keratinocyte proliferation and attenuates imiquimod-induced psoriasis like skin-inflammation by modulating NF-κB and STAT3 signaling pathways
- Bilingual Status
- semi_complete