Inhalation of Curcumae Rhizoma volatile oil attenuates depression-like behaviours via activating the Nrf2 pathway to alleviate oxidative stress and improve mitochondrial dysfunction.

OBJECTIVES: Curcumae Rhizoma (CR) is a traditional Chinese medicine used frequently in clinics, which contains volatile components that exhibit various active effects. This study explores the effect of Curcumae Rhizoma volatile oil (CRVO) on depressive mice and its possible mechanism of action. METHODS: Chemical composition of CRVO was analysed by GC-MS. DPPH and ABTS free radical scavenging assays were used to evaluate the in vitro antioxidant capacity of CRVO. A chronic unpredictable mild stress (CUMS) model was used to evaluate the antidepressant effect of CRVO. The effects of CRVO on oxidative stress in vivo were investigated using Nissl staining, ELISA and transmission electron microscopy. The Nrf2/HO-1/NQO1 signalling pathway was detected by western blotting and immunofluorescence. ML385, a Nrf2 inhibitor was used to validate the effect of Nrf2 on CUMS mice with CRVO treatment. KEY FINDINGS: Phytochemical analysis showed that CRVO is rich in its characteristic components, including curzerene (31.1%), curdione (30.56%), and germacrone (12.44%). In vivo, the administration of CRVO significantly ameliorated CUMS-induced depressive-like behaviours. In addition, inhalation of CRVO significantly alleviated the oxidative stress caused by CUMS and improved neuronal damage and mitochondrial dysfunction. The results of mechanistic studies showed that the mechanism of action is related to the Nrf2/HO-1/NQO1 pathway and the antioxidant and antidepressant effects of CRVO were weakened when ML385 was used. CONCLUSIONS: In summary, by regulating the Nrf2 pathway, inhalation of CRVO can reduce oxidative stress in depressed mice, thereby reducing neuronal damage and mitochondrial dysfunction to alleviate depression-like behaviours. Our study offers a prospective research foundation to meet the diversity of clinical medication.

Yueju volatile oil plays an integral role in the antidepressant effect by up-regulating ERK/AKT-mediated GLT-1 expression to clear glutamate.

Phytochemical investigation of the volatile oil of Yueju (YJVO) and its constituent herbs induced the detection of 52 compounds in YJVO, mainly monoterpenes and sesquiterpenes as well as a small amount of aromatic and aliphatic compounds. 5 of these compounds were found only in the YJVO instead of the volatile oil of its constituent herbs. The anti-depressant effect of YJVO was proved by behavioral tests in chronic unpredictable mild stress (CUMS) mice. An acute oral toxicity evaluation determined the LD50 of YJVO was 5.780 mL/kg. Doppler ultrasound and laser speckle imaging have detected that the YJVO could improve depression-related cerebral blood flow. In addition, related neurotransmitters and proteins were analyzed through targeted metabolomics and immunofluorescence. The potential antidepressant mechanisms of YJVO related to significantly decreasing Glu in CUMS mice by up-regulating the ERK/AKT-mediated expression of GLT-1.

Pulsatilla chinensis saponins improve SCFAs regulating GPR43-NLRP3 signaling pathway in the treatment of ulcerative colitis.

ETHNOPHARMACOLOGICAL RELEVANCE: Pulsatilla decoction has been extensively used to treat ulcerative colitis (UC) in recent years. Pulsatilla chinensis saponin (PRS), the active ingredient of its monarch medicine Pulsatilla chinensis (Bunge) Regel, plays a crucial role in the treatment of UC, but its specific mechanism of action has not been fully elucidated. AIM OF THE STUDY: This study aims to investigate the protective effect and possible mechanism of PRS on DSS-induced ulcerative colitis in rats. MATERIALS AND METHODS: In this study, the DSS-induced colitis model was used to explore the metabolism and absorption of PRS under UC, detect the content of short-chain fatty acids (SCFAs) in colon tissue, the expression of receptor G Protein-Coupled Receptor 43 (GPR43) protein and inflammasome NLRP3, and observe the expression level of IL-1ß, IL-6 and TNF-α in colon tissue. The protective effect of the PRS was also observed. RESULTS: It was found that in the UC group, the absorption rate and extent of drugs increased, and the elimination was accelerated. Compared with the control group, PRS increased the content of short-chain fatty acids (SCFAs) in colon tissue, promoted the expression of SCFAs receptor GPR43 protein, inhibited the activation of the NLRP3 inflammasome, and decreased the content of IL-1ß, IL-6 and TNF-α. PRS protects the colon in DSS-induced inflammatory bowel disease by increasing the content of SCFAs, promoting the expression of GPR43 protein, inhibiting the activation of the NLRP3 inflammasome, and reversing the increase in IL-1ß, IL-6 and TNF-α levels. CONCLUSIONS: PRS can increase the content of colonic SCFAs, activate the GPR43-NLRP3 signaling pathway, and reduce the levels of pro-inflammatory cytokines, thereby improving the symptoms of DSS-induced colitis.

Gut microbiome-derived lactate promotes to anxiety-like behaviors through GPR81 receptor-mediated lipid metabolism pathway.

Accumulating evidence suggests that chronic stress could perturb the composition of the gut microbiota and induce host anxiety- and depression-like behaviors. In particular, microorganism-derived products that can directly or indirectly signal to the nervous system. This study sought to investigate whether high levels of Lactobacillus and lactate in the gut of rats under chronic unpredictable stress (CUS) were the factors leading to anxiety behavior. We collected faeces and blood samples in a sterile laboratory bench to study the microbiome and plasma metabolome from adult male rats age and environment matched healthy individuals. We sequenced the V3 and V4 regions of the 16S rRNA gene from faeces samples. UPLC-MS metabolomics were used to examine plasma samples. Search for potential biomarkers by combining the different data types. Finally, we found a regulated signaling pathway through the relative expression of protein and mRNA. Both lactate feeding and fecal microbiota transplantation caused behavioral abnormalities such as psychomotor malaise, impaired learning and memory in the recipient animals. These rats also showed inhibition of the adenylate cyclase (AC)-protein kinase A (PKA) pathway of lipolysis after activation of G protein-coupled receptor 81 (GPR81) by lactate in the liver, as well as increased tumor necrosis factor α (TNF-α), compared with healthy controls. Furthermore, we showed that sphingosine-1-phosphate receptor 2 (S1PR2) protein expression in hippocampus was reduced in chronic unpredictable stress compared to control group and its expression negatively correlates with symptom severity. Our study suggest that the gut microbiome-derived lactate promotes to anxiety-like behaviors through GPR81 receptor-mediated lipid metabolism pathway.