Berberine (BBR), a natural isoquinoline alkaloid isolated from Coptis chinensis, has been widely used in China to treat intestinal infections, especially bacterial gastroenteritis, for thousands of years. Multiple studies have also shown that BBR has a protective effect on the central nervous system, exhibiting antidepressant, anxiolytic, and anti-inflammatory effects. BBR has been reported to reduce depression-like and anxiety-like behaviors by suppressing neuroinflammation in stressed mice. In another study, it was suggested that BBR exerts antidepressant-like effects in OVX mice through the BDNF-CREB and eEF2 pathways.
The gut microbiota is considered a promising target for treating anxiety disorders. Berberine (BBR) has shown efficacy in the treatment of postmenopausal osteoporosis, obesity and type 2 diabetes by modulating the gut microbiota. However, the effect of BBR on postmenopausal anxiety remains unclear. The purpose of this study was to examine whether BBR improves anxiety by modulating the gut microbiota in conditions of estrogen deficiency. Experimental anxiety was established in specific pathogen-free (SPF) ovariectomized (OVX) rats, which were then treated with BBR for 4 weeks prior to behavioral testing. Open-field and elevated plus maze tests showed that BBR treatment significantly improved anxiety-like behaviors in OVX rats compared to their vehicle-treated counterparts. In addition, BBR-treated OVX rats harbored more beneficial gut microbes such as Bacteroides, Bifidobacterium, Lactobacillus, and Arabidopsis, as demonstrated by 16S rRNA sequencing and liquid chromatography/mass spectrometry (LC/MS) analysis Klebsiella and exhibited increased equol production. Notably, gavage of BBR did not have significant anxiolytic effects on ovariectomized germ-free (GF) rats, whereas GF rats transplanted with SPF rat fecal microbiota showed significant anxiety-like symptoms and isoflavone levels Phenotypic replication in donor rats.
This study demonstrates that the gut microbiota is critical in the management of oophorectomy-exacerbated anxiety and that BBR modulation of the gut microbiota is a promising therapeutic strategy for postmenopausal anxiety symptoms.
