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\begin{document}

\title{Flavonoid combination therapy regulating immune system's homeostasis via
activation the FOXO3 signaling pathway for the cure of Propionibacterium
acnes infection}



\author[1]{Juan Wu}%
\author[1]{Biao LE}%
\author[1]{Xiaocong Fu}%
\author[2]{Hui Li}%
\author[3]{Jinlu Zuo}%
\author[4]{Huang Jin}%
\affil[1]{Shanghai Skin Diseases Hospital}%
\affil[2]{Shanghai East Hospital}%
\affil[3]{Guangzhou Vocational School of Finance and Business}%
\affil[4]{Shanghai University of Traditional Chinese Medicine Yueyang Hospital of Integrated Traditional Chinese and Western Medicine}%


\vspace{-1em}



  
  \date{May 18, 2024}


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\begin{abstract}
Abstract In the present study, the in vitro and in vivo anti-acne
activation by flavonoid combination therapy were investigated, and the
role and relationship between flavonoid and FOXO3 signaling pathway were
discussed. Three natural flavonoid such as quercetin, kaempferol,
luteolin had certain anti-inflammation activity. Meanwhile, the
combination therapy significantly outperforming using these flavonoids
alone, which might be attributed to the synergistic bactericidal effect
on the cells. Besides, it was also found that the FOXO3 pathway play an
important role in P acnes induced skin inflammation. It's promoted the
decreasing of FOXO3 signaling pathway activation and induced an
increasing in sebum secretion. During the acne inflammatory response,
the expression of pro-inflammatory cytokine was increased significantly.
After flavonoid combination therapy, the pro-inflammatory cytokines
expression levels such as TNF-\selectlanguage{greek}α \selectlanguage{english}(19.36 \selectlanguage{ngerman}± 2.44 pg/ml), IL-8 (1392.52 ±
131.75 pg/ml), IL-1\selectlanguage{greek}β \selectlanguage{english}(13.42 \selectlanguage{ngerman}± 4.54 pg/ml) and IL-6 (109.64±13.34 pg/ml)
were significantly reduced. Flavonoid combination therapy effectively
decreased the expression of pro-inflammatory cytokines and increased the
secretion of the anti-inflammatory cytokines. In addition, the
activation of the FOXO3 pathway was found to be inversely proportional
to the expression of pro-inflammatory cytokines. In this study, the
flavonoid combination therapy demonstrated a ``synergistic effect''
inhibiting the inflammatory process via the activation of the FOXO3
pathway. The enhanced synergy observed surpassed their individual
effects when used in combination. Consequently, the ``synergistic
effect'' of three flavonoid ingredients suggested a new approach for the
development of anti-acne reagents as FOXO3 enhancers.%
\end{abstract}\selectlanguage{ngerman}%



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