Researchers in China found that the Quince (Cydonia oblonga) extract improved behavioral outcomes, reduced inflammatory markers, altered gut microbiota composition, and changed serum metabolites in mice treated with lipopolysaccharide (LPS), indicating that quince may influence the gut–brain axis.
“Our findings suggest that HECO may represent a promising natural candidate for the management of inflammation-related depression and highlight the potential value of Cydonia oblonga-derived flavonoids in preclinical mental health research,” they wrote in the journal Nutrients.
Inflammation and gut dysbiosis offer new targets for mental health
Research has shown that changes in the composition and function of the gut microbiota may influence the development and progression of depression through the gut–brain axis, and as dysbiosis is known to contribute to depression, researchers are increasingly considering it as a promising therapeutic target.
Inflammation also contributes to depression through the TLR4/MyD88/NF-κB signaling pathway, which regulates the body’s inflammatory response. When lipopolysaccharide (LPS), a bacterial toxin, binds to TLR4 receptors on immune cells in the brain, it activates this pathway and triggers the release of inflammatory molecules, including IL-6, IL-1β, TNF-α, COX-2 and iNOS.
The researchers suggest that the TLR4/MyD88/NF-κB pathway could be a promising target for developing new treatments for depression, particularly dietary flavonoids which have been suggested to reduce depressive symptoms by regulating the gut microbiota, altering microbial metabolites, and reducing inflammation. Quince in particular contains high levels of flavonoids, and previous studies have shown that quince has antioxidant and anti-inflammatory properties.
Study design: Quince extract tested against LPS-induced depression
The researchers prepared a hydroethanolic extract of quince, identifying its main flavonoids as rutin, L-epicatechin, catechin and glycitin. They randomly assigned 30 male mice to a control group, an LPS-treated group, or an LPS plus HECO group.
The HECO group received 600 mg/kg of the extract orally once daily for 21 days. From days 14 to 21, the LPS and HECO groups also received daily LPS injections to induce depression-like behaviors, while the control group received saline.
Following treatment, the researchers tested the mice for changes in behaviour using standard movement and mood-related tests. They then collected blood, brain and intestinal samples to measure inflammation, examine key proteins involved in immune signaling, assess brain tissue, analyze the gut microbiome and identify changes in blood metabolites.
Quince reduced brain inflammation in mice
Results found that HECO reduced depression-like behaviors in mice treated with LPS, as well as changing the gut microbiota, altering serum metabolites, and reducing inflammation.
The researchers identified 262 metabolites that differed between the untreated mice and those that received the HECO extract, with the top potential biomarkers predominantly categorized into lipids, flavonoid-containing phenylpropanoids, organic acids and peptides. Lipids, particularly glycerophospholipids, showed the greatest changes. These molecules play important roles in inflammation and maintaining healthy cell membranes, both of which are disrupted by LPS-induced depression-like changes.
“Collectively, these metabolomic alterations suggest that HECO may contribute to the improvement of LPS-induced depressive-like behaviors through coordinated regulation of lipid metabolism and inflammatory signaling, although causal relationships require further validation,” the researchers noted.
HECO supplementation was also found to reduce the inflammatory markers IL-6 and COX-2 in the blood, both of which have been linked to depression.
The researchers also examined the hippocampus, and HECO was found to reduce the LPS-induced increase in TLR4, MyD88, and NF-κB proteins, showing that it inhibited a major inflammatory signaling pathway. HECO also restored two proteins, occludin and ZO-1, that help maintain the integrity of the blood–brain barrier. The researchers suggest that the extract reduced inflammation in the brain and helped protect it from inflammation-related damage.
Results also showed that HECO increased levels of bacteria linked to better gut health and lower inflammation, while reducing bacteria associated with inflammation. HECO increased levels of Deferribacterota, a group linked to better gut health and lower inflammation. It also increased Parabacteroides, which has anti-inflammatory properties, while LPS increased Parasutterella, a bacterial group associated with gut inflammation.
The researchers proposed that the HECO extract reduced depression-like behaviours by acting on several biological pathways at the same time, changing the composition of the gut microbiome and blood metabolites, reducing inflammation, blocking immune signaling in the brain, and helping restore proteins that maintain the gut barrier.
“These multi-level biological changes may collectively contribute to the observed behavioral improvements,” they concluded.
They noted that larger studies are needed to confirm the findings and better understand the mechanisms of the extract.
Source: Nutrients doi: 10.3390/nu18142322; “Cydonia oblonga Mill. Fruit Extract Ameliorates Lipopolysaccharide-Induced Depression-like Behaviors in Mice by Modulating Inflammation, Metabolites and Gut Microbiota.” Authors: Maitiniyazi, G. et al.
