Matrine alleviates depressive-like behaviors via modulating microbiota–gut–brain axis in CUMS-induced mice

Abstract

Background The realization of the “microbiota–gut–brain” axis plays a critical role in neuropsychiatric disorders, particularly depression, is advancing rapidly. Matrine is a natural bioactive compound, which has been found to possess potential antidepressant effect. However, the underlying mechanisms of regulation of the “microbiota–gut–brain” axis in the treatment of depression by oral matrine remain elusive. Methods Its antidepressant effects were initially evaluated by behavioral tests and relative levels of monoamine neurotransmitters, and matrine has been observed to attenuate the depression-like behavior and increase neurotransmitter content in CUMS-induced mice. Subsequently, studies from the “gut” to “brain” were conducted, including detection of the composition of gut microbiota by 16S rRNA sequencing; the metabolomics detection of gut metabolites and the analysis of differential metabolic pathways; the assessment of relative levels of diamine oxidase, lipopolysaccharide, pro-inflammatory cytokines, and brain-derived neurotrophic factor (BDNF) by ELISA kits or immunofluorescence. Results Matrine could regulate the disturbance of gut microbiota and metabolites, restore intestinal permeability, and reduce intestinal inflammation, thereby reducing the levels of pro-inflammatory cytokines in peripheral blood circulation and brain regions, and ultimately increase the levels of BDNF in brain. Conclusion Matrine may ameliorate CUMS-induced depression in mice by modulating the “microbiota–gut–brain” axis.

Improvement of the Thermal Stability and Aqueous Solubility of Three Matrine Salts Assembled by the Similar Structure Salt Formers

“…It has a variety of pharmacological effects, such as antiinflammation effects, oxidative stress reduction, autophagy and apoptosis regulation, and cancer cell metastasis inhibition [2][3][4][5]. Numerous studies have shown that MAT has therapeutic effects on multiple sclerosis, Alzheimer's syndrome, and other neurological disorders [6][7][8]. MAT is a member of the class I of the biopharmaceutics classification system and has the advantages of extensive sources, high safety, low price, and convenient administration [9][10][11].…”

Stress and the gut-brain axis: an inflammatory perspective

“…Importantly, experimental alteration of gut microbiota influences stress responsiveness, anxiety- and depressive-like behavior, and activates the hypothalamic-pituitary-adrenal (HPA) axis (De Palma et al, 2014 ; Golubeva et al, 2015 ; Ergang et al, 2021 ). Significant shifts in gut microbiota composition reported in animal models of CNS diseases related to early life stress, such as maternal separation (De Palma et al, 2015 ), chronic restraint stress (CRS) (Gubert et al, 2020 ) or chronic unpredictable mild stress (CUMS) (Zhang et al, 2023 ) were linked with alterations in microbiota-related metabolites and immune signaling pathways suggesting that these systems may be important in stress-related conditions including depression.…”