ORIGINAL RESEARCH article
Front. Pharmacol.
Sec. Ethnopharmacology
Volume 16 - 2025 | doi: 10.3389/fphar.2025.1583409
This article is part of the Research TopicTreating Hepato-Intestinal Diseases with Herbal Medicines and their MetabolitesView all 4 articles
Two natural products from the seeds of Citrus reticulata Blanco (Rutaceae) inhibit estrogen biosynthesis by regulating the PI3K-aromatase pathway
Provisionally accepted
Xing Yang1
Xi Chen2
Chunqiao Shi1
Qian Zhang1Qian Liu1Yan Chuan Zhou2Wu Fa Dong3Song Jin Su1*
Deming Liu2*
Yi Zhang1*- 1School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, China
- 2Chongqing Hospital of Traditional Chinese Medicine, Chongqing, China
- 3Yunnan University of Traditional Chinese Medicine, Kunming, Yunnan Province, China
Select one of your emails
You have multiple emails registered with Frontiers:
Notify me on publication
Please enter your email address:
If you already have an account, please login
You don't have a Frontiers account ? You can register here
The seeds of Citrus reticulata Blanco (Rutaceae) (SCR), a traditional Chinese medicine derived from Citrus, is known for its diverse bioactivities, including potential anti-breast cancer effects, but the mechanism of action remains unclear. This study aims to elucidate the active ingredients of SCR and their mechanisms of action on estrogen biosynthesis. A comprehensive phytochemical analysis, employing various chromatographic techniques, led to the isolation of 26 compounds from SCR.The effects of these compounds on estrogen biosynthesis were evaluated in human ovarian granulosa-like KGN cells, which play a crucial role in the progression of hormone-dependent breast cancers. Network pharmacology analysis revealed that SCR may influence breast cancer development by modulating phosphorylation-related biological processes and the PI3K/AKT pathway. Among the isolated compounds, Callyspongidipeptide A (Calp) and Hesperetin 7-O-β-D-glucopyranoside (Hesp) exhibited significant inhibitory effects on estrogen biosynthesis. Calp and Hesp selectively regulated the expression of aromatase (Aro) PI.3 and P2 promoters via the PI3K/AKT pathway, inhibiting Aro mRNA and protein expression. These findings provide novel insights into the chemopreventive potential of SCR and support its role in the development of therapies aimed at reducing the risk of hormone-related cancers.
Keywords: The seeds of Citrus reticulata Blanco (Rutaceae), Aromatase, Callyspongidipeptide A, Hesperetin 7-O-β-D-glucopyranoside, Aromatase Inhibitors
Received: 25 Feb 2025; Accepted: 27 May 2025.
Copyright: © 2025 Yang, Chen, Shi, Zhang, Liu, Zhou, Dong, Su, Liu and Zhang. 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:
Song Jin Su, School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, China
Deming Liu, Chongqing Hospital of Traditional Chinese Medicine, Chongqing, 400021, China
Yi Zhang, School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, China
Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.