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.

Alzheimer’s disease (AD) is a neurodegenerative disorder characterized by neurodegeneration, nerve loss, neurofibrillary tangles and Aβ plaques. Different process of the AD pathology present more opportunities for treatment. In addition, the holistic approaches involving network pharmacology with traditional Chinese medicine (TCM) may be viable options for AD treatment, and lead to an effective cure for AD in the future. Therefore, this study explored the therapeutic effect and mechanism of Rosmarinus officinalis L(rosemary) in the treatment of Alzheimer’s disease on basis of cell experiments, network pharmacology and molecular docking. We performed cell experiments, to investigate the therapeutic effects of Rosmarinus officinalis L on AD in vitro using CCK8 assay, flow cytometry and TMRE Kit. In addition, carnosic acid is a major antioxidant diterpenoid in Rosmarinus officinalis L. We performed cell experiments, to investigate the neuroprotective effects of carnosic acid on AD in virto using CCK8 assay and flow cytometry. Furthermore, the main antioxidant compounds of rosemary ware collected through literature reviews, PharmMapper and Swiss Target prediction ware used to identify their potential targets. Targets of AD were obtained from Genecards and OMIM. The intersection targets of the main active components of rosemary and the therapeutic targets of Alzheimer’s disease were subsequently obtained by using online Venn diagram. Protein–protein interaction, Cytoscape, Gene Ontology, and Kyoto Encyclopedia of Genes were used to analyze potential targets and key pathways of rosemary in AD. Besides, through molecular docking, the interactions of the main active components of rosemary, and the predicted candidate targets were verified. Finally, quantitative Real-Time PCR (RT-qPCR) was performed to confirm the effectiveness of the genes. It was found that rosemary could reversed Aβ25–35 induced damage to mouse hippocampal neuron HT22 cells, significantly improved the viability of damaged cells, and reduced apoptosis. The results of fluorescent staining with Hoechst 33,342 and TMRE suggested that rosemary inhibited the reduction of mitochondrial membrane potential levels induced by Aβ25–35, which had a specific protective effect on AD in vitro. Additionally, a main antioxidant compound in rosemary, carnosic acid, also has neuroprotective effects. Eight main antioxidant compounds of rosemary ware collected. Network pharmacology and molecular docking, revealed that rosemary plays a therapeutic role in the treatment of Alzheimer’s disease through the main active carnosic acid, carnosol, rosmarinol, rosmadial, genkwanin, cirsimaritin, rosmarinic acid and caffeic acid in Rosmarinus officinalis L, which affects the gene regulation of HRAS, ESR1, RHOA, IGF1, SRC, ANXA5, MMP9, MAPK14, NOS3, and PIK3R1, and participates in the PI3K-Akt, Rap1, MAPK, and estrogen signaling pathways. RT-qPCR indicated that rosemary could elevated expression of IGF1, MMP9 and decreased mRNA levels of SRC, MAPK14, compared with the control group. Rosemary is an important economic plant with multi-component, multi-target and multi-pathway synergistic effects.The findings highlight the effectiveness of rosemary in helping to increase cell viability and reduce apoptosis when treating mouse hippocampal neuron HT22 cells, thereby supporting its therapeutic potential in treating Alzheimer’s disease.

Introduction: Social rank has a profound influence on the behavior and health of humans and animals.Methods: To explore the effect of a combination of living Bifidobacterium, Lactobacillus and Streptococcus (CLB) on anxiety‐ and depression‐like behaviors and social rank, mice were subjected to a social dominance tube test (SDTT). The behaviors, rank, gut microbiota, and expression of inflammatory cytokines and brain‐derived neurotrophic factor (BDNF) in the hippocampus were measured.Results: The results indicated that CLB improved the SDTT ranking score of the losers and alleviated anxiety‐like behaviors of the winners. CLB decreased the level of Desulfovibrio and augmented the level of Mollicutes in the feces, increased BDNF content, and reduced the level of tumor necrosis factor‐α in the hippocampus.Conclusion: These findings indicated that CLB may be used for the treatment of anxiety and improvement of the rank score via regulation of gut microbiota and anti‐inflammatory effects.

The well-known toxic medicine Gelsemium elegans is widely and historically used to treat bone fracture and skin ulcers by the folk people of China. Two new monoterpenoid indole alkaloids, gelselegandines D and E, together with the known analogue gelegamine A were isolated from G. elegans. Their structures were elucidated by means of spectroscopic techniques and quantum chemical calculations. All isolated compounds were tested for the effects on RANKL-induced osteoclast formation. Interestingly, gelselegandine E and gelegamine A, respectively, showed significant promoting and inhibitory activities on osteoclastogenesis, while gelselegandine D had no activity under the same concentration. This work suggested the different configurations for the carbons near the C-19/20 oxygen rings of the isolated compounds may be the key active groups on osteoclast formation and provided the evidence for the rationality as the traditional treatment for bone-related diseases of G. elegans.