Antidepressant Effects of Rosemary Extracts Associate With Anti-inflammatory Effect and Rebalance of Gut Microbiota

Abstract

It is currently believed that inflammation acts as a central part in the pathophysiology of depression. Rosemary extracts (RE), the crucial active constituents extracted from Rosmarinus officinalis Linn, have drawn wide concerns because of their potential for anti-inflammatory effects. However, no study has highlighted the antidepressant effects of RE on chronic restraint stress (CRS) mice, and the inflammatory mechanisms related to gut microbiome have not yet been elucidated. This study showed that depressive-like behaviors, gut microbiota dysbiosis, and activation of inflammatory reactions in the hippocampus and serum of CRS mice, as well as activation of inflammatory reactions in BV-2 microglia cells induced by lipopolysaccharide (LPS), could be attenuated by RE. We found that the pretreatment with RE increased the time in the center of open field test (OFT), and decreased immobility duration in tail suspension test (TST) as well as forced swimming test (FST). Furthermore, RE enhanced the sequences proportion of Lactobacillus and Firmicutes, and reduced the sequences proportion of Bacteroidetes and Proteobacteria in feces. Moreover, RE obviously suppressed protein expression of IL-1β, TNF-α, p-NF-κ B p65 and Iba1 in hippocampus, and elevated BDNF as well as p-AKT/AKT expression. Importantly, pre-incubation with RE protected microglia by alleviating protein expression of IL-1β, TNF-α and p-NF-κ B p65 induced by LPS. Additionally, RE downregulated the level of IL-1β and TNF-α in serum. In conclusion, this study showed the antidepressant effects of RE are mediated by anti-inflammatory effects in hippocampus, serum and BV-2 microglia as well as rebalancing gut microbiota.

Carnosic acid ameliorates depressive‐like symptoms along with the modulation of FGF9 in the hippocampus of middle carotid artery occlusion‐induced Sprague Dawley rats

“…However, none of these studies demonstrated association of carnosic acid with the anti‐depressant‐like action. Although, in chronic restraint stress model of mice, it was observed that the extract was composed of ~60% of carnosic acid (Guo et al, 2018).…”

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“…The rosemary extracts were found to decrease the proportion of both Bacteroidetes and Proteobacteria while promoting an abundance of Lactobacillus and Firmicutes. With respect to the pro-inflammatory mediators, the extract reduced IL-1β, TNF-α, and p-NF-κB, indicating a protective effect for rosemary extract in mice and its implication in the antidepressant-like properties of the plant [313]. A lipid extract (D-004) of Roystonea regia increased mouse immobility in both the FST and TST but showed no effects in other behavioral tests [314].…”

“…3S, Supplementary Information), which produce biphasic modulation of GABA A receptors [312], have also been proposed as active constituents. In one interesting study, Guo et al [313] investigated the antidepressant effects of rosemary extracts on chronic restraint stress mice along with the inflammatory mechanisms related to the gut microbiome. The results showed that the extract significantly ameliorates depressive-like behaviors in chronic restraint stress mice.…”

Iron Transport Tocopheryl Polyethylene Glycol Succinate in Animal Health and Diseases

“…Currently, a large number of in vivo studies suggest that nutraceuticals (including prebiotics, probiotics, and synbiotics) are used to maintain the normal gut biota and to prevent or treat GIT-related diseases [117,118,130,131,132,133,134,135,136,137,138]. The GIT contains a complex polymicrobial community that consists of bacteria, viruses, archaea, fungi, and parasites [99,139,140,141].…”