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. 2024 Dec 27;18(1):20.
doi: 10.3390/ph18010020.

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

Fengfeng Chen  1 , Jing Liu  1 , Xinwei Yu  1 , Honglei Jia  2 , Cheng Yang  1 , Bingtian Zhao  1
Affiliations

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

Fengfeng Chen et al. Pharmaceuticals (Basel). .

Abstract

Background/Objectives: Atopic dermatitis (AD) is a chronic inflammatory skin disorder that has attracted global attention, and alkaloids from Plumula Nelumbinis 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 Plumula Nelumbinis (FPN) are still unclear. Methods: 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. Results: 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 Plumula Nelumbinis was enhanced by Aspergillus oryzae 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. Conclusions: This study elucidated the potential mechanisms of alkaloids derived from fermented Plumula Nelumbinis against AD; it may also provide a scientific basis for the development of new drugs for AD.

Keywords: Plumula Nelumbinis; alkaloid; atopic dermatitis; fermentation; mechanism; network pharmacology.

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Conflict of interest statement

Author Honglei Jia was employed by the company Shanghai Fulai BioHighTech Co., Ltd. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

Figure 1
Figure 1
The Venn diagram of potential targets for FPN in the treatment of atopic dermatitis.
Figure 2
Figure 2
Compounds–target–AD network of the potential therapeutic targets and active components of FPN (C1-C6). C1~C6 represent Armepavine, N-Demethylcolletine, N-Methylcoclaurine, Neferine, Liensinine, and Isoliensinine, respectively.
Figure 3
Figure 3
PPI network of the following: (A) Common targets; (B) Core targets.
Figure 4
Figure 4
GO and KEGG enrichment analyses of potential core targets: (A) The top 20 enrichment terms for BP. (B) The top 20 enrichment terms for CC. (C) The top 20 enrichment terms for MF. (D) The top 20 KEGG pathways.
Figure 5
Figure 5
Molecular docking conformations of six compounds with the following: (A) mTOR; (B) AKT; (C) Jun.
Figure 6
Figure 6
The gene expression of the following: (A) c-Jun; (B) mTOR; (C) AKT. ## p < 0.01, ### p < 0.001 vs. control group, * p < 0.05, ** p < 0.01, *** p < 0.001 vs. model group.
Figure 7
Figure 7
Effects of FPN on protein expression: (A) Western blot bands; (B) Quantitative analysis of the relative expression of p-mTOR/mTOR; (C) p-AKT/AKT/; (D) c-Jun. # p < 0.05, ## p < 0.01, ### p < 0.001 vs. control group, * p < 0.05, ** p < 0.01 vs. model group.
Figure 8
Figure 8
Effect of FPN on neutrophil recruitment. ### p < 0.001 vs. control group, * p < 0.05, ** p < 0.01, *** p < 0.01 vs. model group.
See this image and copyright information in PMC

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