Sex-specific effects of Semen Cuscutae aqueous extract on behavior, proteomics, and gut microbiota in rats
10.1097/st9.0000000000000086
- Author:
Zihan ZHAO
1
;
Yaling YANG
1
;
Junhui ZHOU
1
;
Jie REN
2
;
Zhiqiang LUO
1
;
Ruibin BAI
1
;
Jian YANG
1
Author Information
1. State Key Laboratory for Quality Ensurance and Sustainable Use of Dao-di Herbs, National Resource Center for Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing, China
2. Division of Chemical Biology and Medicinal Chemistry, UNC Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA
- Publication Type:Journal Article
- Keywords:
Semen Cuscutae;
Proteome;
Sex-based differences;
Gut microbiota
- From:
Science of Traditional Chinese Medicine
2026;4(1):50-61
- CountryChina
- Language:English
-
Abstract:
Background: Sex-based differences often influence the therapeutic efficacy and safety of medications. Semen Cuscutae is a traditional tonic botanical drug with sex-specific characteristics, traditionally indicated for conditions such as impotence (exclusive to males) and restless fetus (exclusive to pregnant females). However, most existing studies have focused on a single sex. Objective: To evaluate the sex-specific biological effects of Semen Cuscutae in rats and explore its molecular mechanisms, with the aim of uncovering its pharmacological characteristics through a multiomics approach. Methods: A traditional aqueous extract of Semen Cuscutae (SCA) was used as the experimental material. Forty adult Sprague-Dawley rats (equal numbers of males and females) were randomly divided into 4 groups: male control, male SCA treatment (240 mg/kg), female control, and female SCA treatment (240 mg/kg), with 10 rats in each group. The biological effects were comprehensively evaluated using a combination of open field test, biochemical analyses, proteomics, and gut microbiota profiling. Results: As a tonic botanical drug, SCA appeared to directly affect the mental and behavioral state of rats. It significantly altered the time spent by rats in the center area during the open field test, showing a sex-dependent reversal of behaviors. Proteomic analysis of brain tissue identified 624 differentially expressed proteins across the groups, with 10 key differentially expressed proteins related to sex differences, including fibroblast growth factor receptor 3, transcription elongation factor A protein-like 1, 40S ribosomal protein S25, neural cell adhesion molecule, and anion exchange protein 2 (SLC4A2). Enrichment analysis revealed that in male rats, SCA upregulated proteins involved in biological processes such as ribosome function and energy derivation, supporting protein synthesis and enhancing energy supply, showing an overall gain effect. In contrast, in female rats, SCA downregulated proteins associated with processes such as positive regulation of target of rapamycin (TOR) signaling and vesicle transport, suggesting suppression of neuronal signaling and material transport, indicative of a shift toward a more restrained physiological state. Furthermore, SCA reduced gut microbiota diversity in female rats but increased it in males, including the abundance of Akkermansia, which may serve as a crucial mediator. Conclusion: Overall, the biological effects of SCA differ significantly between male and female rats, with evidence suggesting greater health benefits in males. These findings help elucidate the scientific basis of its traditional applications and provide guidance for the precise application of SCA as a functional health food.
