ReferenceID 621

Amelioration of TPA-induced skin inflammation by the leaf extract of Vernonia amygdalina involves ERK/STAT3 (Ser727) signaling inhibition

Phytomedicine

Background: Uncontrolled inflammation causes health problems. Extracellular signal-regulated kinase (ERK) phosphorylates signal transducer and activator of transcription 3 (STAT3) at Ser727, resulting in inflammation. Th

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Reference Id
621
Evidence Id
17211
Core Evidence Id
17211
Source Reference Id
1233
Herb2 Reference Id
HBREF002030
Subject Paper Key
HERB000470_35660348
Pubmed Id
35660348
Doi
10.1016/j.phymed.2022.154194
Paper Title
Amelioration of TPA-induced skin inflammation by the leaf extract of Vernonia amygdalina involves ERK/STAT3 (Ser727) signaling inhibition
Paper Abstract
Background: Uncontrolled inflammation causes health problems. Extracellular signal-regulated kinase (ERK) phosphorylates signal transducer and activator of transcription 3 (STAT3) at Ser727, resulting in inflammation. The leaf of Vernonia amygdalina (VA) is a medicinal herb for managing inflammation-associated diseases. Oral administration or topical application of VA leaf extract exerts anti-inflammatory effects in rat models. However, the anti-inflammatory mechanisms of the herb are not fully understood. Purpose: In this study, we aimed to investigate the involvement of ERK/STAT3 (Ser727) signaling in the anti-inflammatory effects of an ethanolic extract of VA leaves. Study design and methods: Extracts of VA leaves were prepared with different concentrations of ethanol. A LPS-stimulated RAW264.7 cell model was used for in vitro assays, and a TPA (12-O-tetradecanoylphorbol-13-acetate)-induced ear edema mouse model was employed for in vivo assays. The 95% ethanol extract of VA leaves (VAE) exerted the strongest inhibitory effect on nitric oxide (NO) production in LPS-stimulated macrophages; thus it was selected for use in this study. Hematoxylin and eosin (H&E) staining was used to examine pathological conditions of mouse ear tissues. Griess reagent was employed to examine NO generation in cell cultures. Immunoblotting and ELISA were used to examine protein levels, and RT-qPCR was employed to examine mRNA levels. Results: Topical application of VAE ameliorated mouse ear edema induced by TPA. VAE suppressed the phosphorylation of ERK (Thr202/Tyr204) and STAT3 (Ser727); and decreased protein levels of inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), interleukin (IL)-6, IL-1β and tumor necrosis factor-α (TNF-α) in the mouse ear tissues and in LPS-stimulated RAW 264.7 cells. VAE also inhibited NO production, and lowered mRNA levels of IL-6, IL-1β and TNF-α in the macrophages. Conclusions: VAE ameliorates TPA-induced mouse ear edema. Suppression of ERK/STAT3 (Ser727) signaling is involved in VAE's anti-inflammatory effects. These novel data provide further pharmacological justifications for the medicinal use of VA in treating inflammation-associated diseases, and lay the groundwork for developing VAE into a new anti-inflammatory agent.
Journal
Phytomedicine
Publish Year
2022
Experiment Subject
mouse; rat; cell cultures; lps-stimulated macrophages; raw 264.7 cells; raw264.7 cell model
Experiment Type
Animal & Cell Experiment
Phenotype Related
Ear Edema; Inflammation-associated Diseases
Paper Title Cn
Paper Title En
Amelioration of TPA-induced skin inflammation by the leaf extract of Vernonia amygdalina involves ERK/STAT3 (Ser727) signaling inhibition
Bilingual Status
semi_complete