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ORIGINAL RESEARCH article

Front. Pharmacol.

Sec. Ethnopharmacology

Volume 16 - 2025 | doi: 10.3389/fphar.2025.1629167

This article is part of the Research TopicFungal solid-state fermentation and mycelium compositesView all articles

Optimization of response surface methodology for the extraction of isoliquiritigenin from Aspergillus niger solid-state fermentation of licorice and its antitumor effects

Provisionally accepted
Jingwei  HaoJingwei Hao1Qiuxuan  LiQiuxuan Li1Nan  DongNan Dong1Yi  ZhouYi Zhou1Yifan  SunYifan Sun1Yingying  PeiYingying Pei1Xiangkun  ZhouXiangkun Zhou1Lei  YangLei Yang2*
  • 1Mudanjiang Normal University, Mudanjiang, China
  • 2The Second Affiliated Hospital of Mudanjiang Medical University, Mudanjiang, China

The final, formatted version of the article will be published soon.

This research focused on optimizing the extraction of isoliquiritigenin (ISL) from licorice via a solid-state fermentation process involving Aspergillus niger. Isoliquiritigenin was quantified through high-performance liquid chromatography (HPLC), initially assessed with one-way analysis and optimized using the Box-Behnken response surface method. The extracted isoliquiritigenin underwent structural modification, and the modified derivatives with enhanced activity were screened for in vivo antitumor efficacy using the MTT Colorimetric (MTT) assay. Finally, the structural and compositional alterations in the intestinal flora of the mice were evaluated post-administration of the extracted isoliquiritigenin. The results indicated that the optimal extraction conditions were pH 3.7, a solid-liquid ratio of 1:2, and an Aspergillus niger inoculum concentration of 1.5 × 106, yielding 1.53 mg/g of isoliquiritigenin after fermentation for 4 days. This yield was 9 times greater than that obtained through conventional reflux extraction and 5.46 times higher than that from the ultrasonic extraction method. Nuclear Magnetic Resonance (NMR) analysis of isoliquiritigenin (ISL) and its derivatives revealed that the ISL-b high dose group exhibited the most significant tumor suppression effect, with a suppression rate of 56.3%. In the mouse model following drug intervention, histopathological examination of kidney tissue via HE staining demonstrated that the safety profile of ISL-b was superior.Studies on the intestinal flora of mice revealed that the number of species was higher in the ISL-b high-dose group.Furthermore, there were significantly more species in the community samples than in the model group, with Micrococcus wartii accounting for the largest percentage at 24.49%. In the ISL-b dosing group, there was a significant increase in the abundance of Akkermansia muciniphila and Bradyrhizobium at the species level.The discoveries offer a robust scientific groundwork for developing antitumor drugs derived from isoliquiritigenin and enhance the broader application of licorice, a traditional herbal remedy.

Keywords: licorice, Isoliquiritigenin, solid-state fermentation of Aspergillus niger, antitumor, intestinal flora

Received: 21 May 2025; Accepted: 06 Oct 2025.

Copyright: © 2025 Hao, Li, Dong, Zhou, Sun, Pei, Zhou and Yang. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: Lei Yang, 156482281@qq.com

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