Aspergillus oryzae Fermented Plumula Nelumbinis Against Atopic Dermatitis Through AKT/mTOR and Jun Pathways

<b>Background/Objectives:</b> Atopic dermatitis (AD) is a chronic inflammatory skin disorder that has attracted global attention, and alkaloids from <i>Plumula Nelumbinis</i> have been shown to have anti-inflammatory activity. Fermentation has been used for the structural modification of natural compounds to improve bioavailability and activity, but the AD therapeutic efficacy and mechanism of the fermented <i>Plumula Nelumbinis</i> (FPN) are still unclear. <b>Methods:</b> The potential targets of FPN for AD were preliminarily screened using network pharmacology, and then PCR and WB were used to prove the therapeutic effect of FPN in AD. <b>Results:</b> Network pharmacology indicated that mTOR and Jun were key targets for AD. The experiments in vitro showed that FPN could effectively block AKT/mTOR and AKT/Jun-mediated inflammatory signaling pathways. Moreover, FPN can also alleviate SDS-induced inflammation in zebrafish. It is also found that the anti-inflammatory activity of <i>Plumula Nelumbinis</i> was enhanced by <i>Aspergillus oryzae</i> fermentation, and the oil phase of the fermentation product showed better activity, which may be due to microbial fermentation changing the structure of the original alkaloids. <b>Conclusions:</b> This study elucidated the potential mechanisms of alkaloids derived from fermented <i>Plumula Nelumbinis</i> against AD; it may also provide a scientific basis for the development of new drugs for AD.