Neuro-stimulating effect of Citri Reticulata Pericarpium Viride essential oil through regulating Glu/NMDAR on olfactory bulb to improve anxiety-like behavior.

ETHNOPHARMACOLOGICAL RELEVANCE: Citri Reticulata Pericarpium Viride (also known Qing-Pi or QP) is a plant in the Rutaceae family, QP is a traditional Qi-regulating medicine in Chinese medicine that is compatible with other Chinese medicine components and has extensive clinical practice in treating anxiety and depression. Reports on the pharmacological effects of QP have demonstrated its neuroprotective effects and antioxidant capacities. Numerous pharmacological benefits of QP are attributed to its antioxidant abilities. Anxiety disorders are a broadly defined category of mental illnesses. Oxidative stress and an imbalance in the antioxidant defense system are typical pathological features of these disorders. AIM OF THE STUDY: The aim of this study was to evaluate the effects of QP essential oil on anxiety using animal models and investigate the underlying neurobiological mechanisms. MATERIALS AND METHODS: This study aimed to develop an animal model of anxiety using chronic restraint stress and investigate the effects of inhalation of Citri Reticulata Pericarpium Viride essential oil on anxiety-like behavior, olfactory function, and olfactory bulb neurogenesis in mice with anxiety. RESULTS: The results showed that long-term chronic restraint stimulation caused a decrease in olfactory function, significant anxiety-like behavior, and a notable reduction in the number of neurons in the olfactory bulb. However, inhalation of Citri Reticulata Pericarpium Viride essential oil reversed these effects, improving the olfactory function, neuro-stimulating effect, alleviating anxiety-like behavior, and regulating theta (4-12Hz) oscillation in the hippocampus DG area. These effects were associated with changes in the expression levels of glutamate receptor NMDAR and NeuN in olfactory bulb. CONCLUSIONS: The study revealed that mice with anxiety induced by chronic restraint stress exhibited significant olfactory dysfunction, providing strong evidence for the causal relationship between anxiety disorders and olfactory dysfunction. Moreover, QP essential oil has the potential to be developed as a therapeutic drug for anxiety disorders, in addition to its role as a complementary anxiolytic.

Macrophage-like rapid uptake and toxicity of tattoo ink in human monocytes.

Macrophages play a critical role for the persistence of tattoo ink in human skin. However, a comparison to other skin-resident and blood circulating immune cells and a profound analysis of REACH-compliant tattoo ink are unmet medical needs. We hence characterized the size distribution of ink particles using physicochemical methods. We studied the uptake of tattoo ink by key human skin cells and blood-derived immune cells using optical and electron microscopy as well as flow cytometry. Scanning electron microscopy of ink revealed its crystalline structure, and a tendency towards aggregations was indicated by size changes upon diluting it. Flow cytometric analyses of skin and immune cells after incubation with tattoo ink demonstrated an increase in cellular granularity upon uptake and red ink additionally evoked fluorescent signals. Human macrophages were most potent in internalizing ink in full thickness 3D skin models. Macrophage cultures demonstrated that the ink did not lead to elevated inflammatory mediators, and showed no indications for toxicity, even after nice days. Strikingly, monocytes were most efficient in ink uptake, but displayed reduced viability, whereas granulocytes and lymphocytes showed only temporary ink uptake with flow cytometric signals declining after 1 day. Mechanistic studies on ink retention by corticosteroids or dexpanthenol in macrophage cultures demonstrated that these compounds do not lead to ink excretion, but even slightly increase the ink load in macrophages. The highly motile monocytes, precursors of macrophages, may play an underrated role for tattoo ink translocation from dermal blood vessels into internal organs.

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.

By characterizing metabolic and immune microenvironment reveal potential prognostic markers in the development of colorectal cancer.

Colon adenocarcinoma (COAD) is one of the deadliest cancers in the world and survival rates vary significantly between early and advanced stage patients. Therefore, the identification of the pathogenesis in the development of COAD and prognostic markers is urgently demanded. Herein, we collected RNA-seq and somatic mutation data of COAD for statistical analysis. Clinical stage-specific differentially expressed genes (DEGs) and tumor development-dependent DEGs were identified. By characterizing the metabolic and immune features of COAD between stages, we found that the energy supply and inflammatory response of advanced tumors were suppressed. Next, the ETS1, AR, GATA1, GATA2, SREBF1, FOXP3, STAT4, and NFKB1 were identified to drive the metabolic and immune-related pathways in the development of COAD. The three potential prognostic markers (HOXC8, IRF7, and CXCL13) were identified based on Cox regression analysis. Additionally, immune infiltration analysis revealed that the resting CD4+ T cell was significantly related to the overall survival (OS) of COAD patients. Collectively, the specific metabolic and immune characteristics of advanced patients and the identified prognostic biomarkers will contribute to the development of precision medicine.

Two Species Origins Comparison of Herba Patriniae Based on Their Ingredients Profile by UPLC-QTOF/MS/MS and Orthogonal Partial Least Squares Discriminant Analysis.

Herba Patriniae (HP) is widely used as a medicinal and edible material in China. Besides food value, HP attracts more attention due to its medicinal potential. Patrinia villosa Juss. (PV) and Patrinia scabiosaefolia Fisch. (PS) are the two species origins of HP. These two of HP show different effects on cell proliferation, migration, angiogenesis and anti-diabetic. As we have previously reported, PV and PS show significant differences on their anti-inflammatory ability in the same experimental model. Comparing the ingredient profiles of two different sources will not only facilitate the understanding of their medicinal effects, but also help the development and research of new activities. However, still now, there is no systematic and detailed study to compare the components of PV and PS. In present study, ultra-high performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry was employed to achieve a high-throughput qualitative and thorough analysis of the chemical composition spectrum of HP. A total of 164 compounds were identified, among these compounds, 127 compounds were identified from PV, and 107 compounds were identified from PS. Most of the chemical components was discovered for the first time. Flavonoids, saponins, terpenoids and organic acids, as the main ingredients in PV and PS were 45.45 %vs 28.46 %, 12.61 % vs. 32.09 %, 14.33 % vs. 22.38 % and 14.58 % vs. 6.79 %, respectively. Flavonoids are the main components of PV, while PS is rich in saponins. PV and PS were classified into two groups by principal component analysis (PCA) and screened out the main molecular differences responsible by orthogonal partial least squares discriminant analysis (OPLS-DA). All the results will be a guide for the quality control, functional activity research, or better clinic use based on the ingredients profile between these two species. Besides, this first study on ingredients profile of two species origins will be beneficial for potential and best resources utilization of both PV and PS.

Study on the new anti-atherosclerosis activity of different Herba patriniae through down-regulating lysophosphatidylcholine of the glycerophospholipid metabolism pathway.

BACKGROUND: Atherosclerosis (AS) is a multifactor cardiovascular disease characterized by chronic inflammation. The safety of long-term medication is the focus of clinical treatment selection and application. It is urgent to develop more high-efficiency and low side effects drugs to treat AS. Therefore, the screening of anti-AS drugs with high efficiency and low toxicity from phytomedicine has attracted more and more attention. PURPOSE: The aim of this study was to explore the new pharmacological effect of Herba patriniae against AS, to find the best origin and extraction part of Herba patriniae, furthermore, to reveal its potential action mechanism. METHODS: Apolipoprotein E gene-knockout (ApoE-/-) mice were orally administered with different extracts of Patrinia villosa Juss (PVJ) and Patrinia scabiosaefolia Fisch (PSF). Their anti-AS effect was comprehensively evaluated by small animal ultrasound, HE staining, Oil-Red O staining, platelet aggregation rate and blood lipid level. Lipid metabolomics and network pharmacology were used to study the mechanism of drug action. Finally, the expression of related proteins were detected by western blots and immunofluorescence. RESULTS: PVJ EtOAc extract and PSF EtOAc extract could significantly reduce vascular plaque, liver inflammation, platelet aggregation and blood lipid levels in AS model. By comparison, the effect of PVJEE was better than that of PSFEE. Furthermore, the results of differential metabolites indicated that PVJEE may inhibit the apoptosis of vascular endothelial cells, proliferation and migration of smooth muscle cells by reversing lysophosphatidylcholine (LPC) in the glycerophospholipid metabolic pathway, so as to play an anti-AS role. This result was double verified by KEGG based metabolic pathway enrichment analysis and related protein expression study. CONCLUSION: By changing glycerophospholipid metabolism pathway, Herba patriniae can significantly regulate lipid metabolism and inflammatory level, showing the development potential of anti-AS, which provides new candidate drugs and good prospects for the safe treatment of AS. In addition, through comparison, this study also confirmed that PVJEE was the best origin and extraction part of anti-AS.