Co-decoction of Lilii bulbus and Radix Rehmannia Recens and its key bioactive ingredient verbascoside inhibit neuroinflammation and intestinal permeability associated with chronic stress-induced depression via the gut microbiota-brain axis

May 2, 2024Phytomedicine : international journal of phytotherapy and phytopharmacology

Combined Lily Bulb and Rehmannia Extract and Its Key Ingredient Verbascoside May Reduce Brain Inflammation and Gut Leakiness Linked to Stress-Related Depression Through the Gut-Brain Connection

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Abstract

LBRD and verbascoside improved depression-like behaviors and synaptic damage by reversing gut microbiota disturbances.

LBRD and verbascoside are associated with reduced inflammation and improved intestinal permeability and blood-brain barrier integrity.
Verbascoside demonstrated protective effects against nerve cell injury caused by stress-related hormones in lab tests.
Faecal microbiota transplantation indicated that verbascoside treatment reduced gut inflammation and corrected deficiencies in neurotransmitters and brain peptides.
Key gut bacteria, including Lactobacillus, Parabacteroides, Bifidobacterium, and Ruminococcus, may contribute to the antidepressant effects of LBRD through gut-brain interactions.
The findings highlight the complex interplay between gut microbiota and the antidepressant efficacy of LBRD and verbascoside.

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BACKGROUND: Gut microbiota plays a critical role in the pathogenesis of depression and are a therapeutic target via maintaining the homeostasis of the host through the gut microbiota-brain axis (GMBA). A co-decoction of Lilii bulbus and Radix Rehmannia Recens (LBRD), in which verbascoside is the key active ingredient, improves brain and gastrointestinal function in patients with depression. However, in depression treatment using verbascoside or LBRD, mechanisms underlying the bidirectional communication between the intestine and brain via the GMBA are still unclear.

PURPOSE: This study aimed to examine the role of verbascoside in alleviating depression via gut-brain bidirectional communication and to study the possible pathways involved in the GMBA.

METHODS: Key molecules and compounds involved in antidepressant action were identified using HPLC and transcriptomic analyses. The antidepressant effects of LBRD and verbascoside were observed in chronic stress induced depression model by behavioural test, neuronal morphology, and synaptic dendrite ultrastructure, and their neuroprotective function was measured in corticosterone (CORT)-stimulated nerve cell injury model. The causal link between the gut microbiota and the LBRD and verbascoside antidepressant efficacy was evaluate via gut microbiota composition analysis and faecal microbiota transplantation (FMT).

RESULTS: LBRD and Verbascoside administration ameliorated depression-like behaviours and synaptic damage by reversing gut microbiota disturbance and inhibiting inflammatory responses as the result of impaired intestinal permeability or blood-brain barrier leakiness. Furthermore, verbascoside exerted neuroprotective effects against CORT-induced cytotoxicity in an in vitro depression model. FMT therapy indicated that verbascoside treatment attenuated gut inflammation and central nervous system inflammatory responses, as well as eliminated neurotransmitter and brain-gut peptide deficiencies in the prefrontal cortex by modulating the composition of gut microbiota. Lactobacillus, Parabacteroides, Bifidobacterium, and Ruminococcus might play key roles in the antidepressant effects of LBRD via the GMBA.

CONCLUSION: The current study elucidates the multi-component, multi-target, and multi-pathway therapeutic effects of LBRD on depression by remodeling GMBA homeostasis and further verifies the causality between gut microbiota and the antidepressant effects of verbascoside and LBRD.

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Co-decoction of Lilii bulbus and Radix Rehmannia Recens and its key bioactive ingredient verbascoside inhibit neuroinflammation and intestinal permeability associated with chronic stress-induced depression via the gut microbiota-brain axis

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