Chinese Materia Medica in Treating Depression: The Role of Intestinal Microenvironment.

Depression is a highly heterogeneous mental illness. Drug treatment is currently the main therapeutic strategy used in the clinic, but its efficacy is limited by the modulation of a single target, slow onset, and side effects. The gut-brain axis is of increasing interest because intestinal microenvironment disorders increase susceptibility to depression. In turn, depression affects intestinal microenvironment homeostasis by altering intestinal tissue structure, flora abundance and metabolism, hormone secretion, neurotransmitter transmission, and immune balance. Depression falls into the category of "stagnation syndrome" according to Traditional Chinese Medicine (TCM), which further specifies that "the heart governs the spirit and is exterior-interior with the small intestine". However, the exact mechanisms of the means by which the disordered intestinal microenvironment affects depression are still unclear. Here, we present an overview of how the Chinese materia medica (CMM) protects against depression by repairing intestinal microenvironment homeostasis. We review the past five years of research progress in classical antidepressant TCM formulae and single CMMs on regulating the intestinal microenvironment for the treatment of depression. We then analyze and clarify the multitarget functions of CMM in repairing intestinal homeostasis and aim to provide a new theoretical basis for CMM clinical application in the treatment of depression.

Untargeted Metabolomics Using UHPLC-HRMS Reveals Metabolic Changes of Fresh-Cut Potato during Browning Process.

Surface browning plays a major role in the quality loss of fresh-cut potatoes. Untargeted metabolomics were used to understand the metabolic changes of fresh-cut potato during the browning process. Their metabolites were profiled by ultra-high performance liquid chromatography coupled with high resolution mass spectrometry (UHPLC-HRMS). Data processing and metabolite annotation were completed by Compound Discoverer 3.3 software. Statistical analysis was applied to screen the key metabolites correlating with browning process. Fifteen key metabolites responsible for the browning process were putatively identified. Moreover, after analysis of the metabolic causes of glutamic acid, linolenic acid, glutathione, adenine, 12-OPDA and AMP, we found that the browning process of fresh-cut potatoes was related to the structural dissociation of the membrane, oxidation and reduction reaction and energy shortage. This work provides a reference for further investigation into the mechanism of browning in fresh-cut products.

Inhibition effect of oxyepiberberine isolated from Coptis chinensis franch. On non-small cell lung cancer based on a network pharmacology approach and experimental validation.

ETHNOPHARMACOLOGICAL RELEVANCE: As an important Chinese herb, Coptis chinensis Franch. (Huanglian, HL) has a long history of usage for clearing heat, eliminating dampness, purging fire and detoxification in Traditional Chinese Medicine (TCM). HL, also called goldthread, was frequently used for the treatment of typhoid, tuberculosis, epidemic cerebrospinal meningitis, pertussis, and other lung-related diseases. Modern research has shown that HL and its main compounds also have anti-tumor effects. However, studies have not reported whether its main compounds inhibit Non-small cell lung cancer (NSCLC) development and progression. OBJECTIVE: This study aimed to find out the potential targets and mechanisms of Oxyepiberberine (OPB) isolated from HL in the treatment of NSCLC, using network pharmacology and biological experimental. METHODS: Silica gel chromatography column was used to isolate OPB from HL, and the structure of OPB was elucidated using different spectroscopic analysis methods, including 1H-nuclear magnetic resonance (NMR), 13C-NMR and electrospray ionization mass spectrometry (ESI/MS). MTT assay was performed to determine cell proliferation of OPB on A549, H1975 and BEAS-2B cells. Then, the potential targets, pathways and hub genes of OPB for treating NSCLC were screened out through network pharmacology. Based on the results of network pharmacology, core targets of OPB for treating NSCLC were docking with OPB via molecular docking. Wound healing, plate clone, Hoechst staining, and western blot assay were used to verify the function of OPB in treatment of NSCLC. RESULTS: OPB was isolated from the HL, its molecular formula was identified as C20H17NO5. Through MTT, OPB significantly inhibited the proliferation of H1975 cells and A549 cells, and A549 was chosen as the test cancer cell. Through network pharmacology, 22 potential targets, 156 related-pathways, and 6 hub genes were screened out. The results of molecular docking showed that SRC, BRAF, and MMP9 were the core targets of OPB against NSCLC. Through biological experimental, it was found that OPB inhibited growth and migration of A549 cells. In addition, OPB induced apoptosis in A549 cells. Through western blot assay, the expressions of Src, ERK1/2 and other four proteins were down-regulated, which suggested that OPB inhibited the proliferation of lung cancer cells by down-regulating SRC-FAK-RAS-RAF-MEK-ERK pathway, so as to achieve the anti-NSCLC effect. CONCLUSION: Our study demonstrated that anti-NSCLC effect of OPB through network and experiments, which provided a theoretical basis for the clinical antitumor of OPB, and provided a foundation for further study of OPB.

Polysaccharides of Scrophularia ningpoensis Hemsl.: Extraction, Antioxidant, and Anti-Inflammatory Evaluation.

The roots of Scrophularia ningpoensis Hemsl. are a famous traditional Chinese medicinal herb and are also used as health food. However, information about polysaccharides from S. ningpoensis (SNPS) is very limited. We applied the ultrasonic-assisted extraction (UAE) process to extract SNPS. The UAE conditions were optimized using single-factor experiments and response surface analysis. Under the optimized conditions of ultrasonic power of 550 W, extraction time of 26 min, and extraction temperature at 50°C, the highest yield of 13.47% ± 1.63% was obtained, which was in accordance with the predicted value of 13.71%. In comparison with traditional hot water extraction, the optimized UAE method significantly increased the extraction yield with lower extraction temperature and shorter extraction time. Furthermore, the in vitro antioxidant evaluation showed that EC50 values of SNPS were 2.43 ± 0.21, 4.40 ± 0.35, and 0.56 ± 0.062 mg/mL for 2,2-diphenyl-1-picrylhydrazyl radical (DPPH) radical, hydroxyl free radical, and 2,2'-azinobis (3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) radical scavenging assay, respectively. The anti-inflammatory potential of SNPS was detected in lipopolysaccharide (LPS) induced ICR mice. Real-time reverse transcription-polymerase chain reaction and enzyme-linked immunosorbent assay showed that SNPS significantly improved LPS-stimulated inflammatory response by decreasing mRNA and protein expression of interleukin (IL)-6 and tumour necrosis factor (TNF)-α in a dose-dependent manner. In conclusion, the extraction process of SNPS established in this study is reliable, and SNPS possesses potential antioxidant and anti-inflammatory activities, which will provide a theoretical basis for guiding the clinical application of S. ningpoensis.

Portfolio Targeting Strategy To Realize the Assembly and Membrane Fusion-Mediated Delivery of Gold Nanoparticles to Mitochondria for Enhanced NIR Photothermal Therapies.

Targeting mitochondria has always been a challenging goal for therapeutic nanoparticle agents due to their heterotypic features and size, which usually lead to a lysosome/endosome endocytosis pathway. To overcome this limitation, in this work, a portfolio targeting strategy combining a small targeting molecule with a biomembrane was developed. Modification of small targeting molecule H2N-TPP on gold nanoparticles (GNPs) could not only facilitate the mitochondrial targeting but could also induce gold nanoparticle assembly. Therefore, the GNPs were endowed with good absorption and photothermal conversion abilities in the near-infrared (NIR) region. Meanwhile, a biomimetic strategy was adopted by wrapping the gold nanoparticle assembly (GNA) with cancer cell membranes (CCMs), which helped the GNA enter the prostatic cancer cell via a homotypic membrane-fusion process to avoid being trapped in endosomes/lysosomes. Thereafter, the GNA remaining in the cytoplasm could reach mitochondria more efficiently via guidance from H2N-TPP molecules. This "biomembrane-small molecule" combination targeting process was evidenced by fluorescence microscopy, and the highly efficient photothermal ablation of prostatic tumors in vivo was demonstrated. This portfolio targeting strategy could be extended to various nanodrugs/agents to realize an accurate subcellular targeting efficiency for cancer treatments or cell detections.

Effects of Xinjiaxiangruyin on the TLR7 pathway in influenza virus-infected lungs of mice housed in a hygrothermal environment.

BACKGROUND: To investigate the effects and immunological mechanisms of the traditional Chinese medicine Xinjiaxiangruyin on controlling influenza virus (FM1 strain) infection in mice housed in a hygrothermal environment. METHODS: Mice were housed in normal and hygrothermal environments, and intranasally infected with influenza virus (FM1). A high-performance liquid chromatography fingerprint of Xinjiaxiangruyin was used to provide an analytical method for quality control. Real-time quantitative polymerase chain reaction (RT-qPCR) was used to measure messenger RNA expression of Toll-like receptor 7 (TLR7), myeloid differentiation primary response 88 (MyD88), and nuclear factor-kappa B (NF-κB) p65 in the TLR7 signaling pathway and virus replication in the lungs. Western blotting was used to measure the expression levels of TLR7, MyD88, and NF-κB p65 proteins. Flow cytometry was used to detect the proportion of Th17/T-regulatory cells. RESULTS: Xinjiaxiangruyin effectively alleviated lung inflammation in C57BL/6 mice in hot and humid environments. Guizhimahuanggebantang significantly reduced lung inflammation in C57BL/6 mice. The expression of TLR7, MyD88, and NF-κB p65 mRNA in lung tissue of WT mice in the normal environment, GZMHGBT group was significantly lower than that in the model group (P < 0.05). In WT mice exposed to the hot and humid environment, the expression levels of TLR7, MyD88, and NF-κB p65 mRNA in the XJXRY group were significantly different from those in the virus group. The expression levels of TLR7, MyD88, and NF-κB p65 protein in lung tissue of WT mice exposed to the normal environment, GZMHGBT group was significantly lower than those in the model group. In WT mice exposed to hot and humid environments, the expression levels of TLR7, MyD88, and NF-κB p65 protein in XJXRY group were significantly different from those in the virus group. CONCLUSION: Guizhimahuanggebantang demonstrated a satisfactory therapeutic effect on mice infected with the influenza A virus (FM1 strain) in a normal environment, and Xinjiaxiangruyin demonstrated a clear therapeutic effect in damp and hot environments and may play a protective role against influenza through downregulation of the TLR7 signal pathway.

Anti-influenza activity of berberine improves prognosis by reducing viral replication in mice.

Berberine, a natural isoquinoline alkaloid isolated from the berberis species, has a wide array of biological properties such as anti-inflammatory, antibacterial, antifungal, and antihelminthic effects. We evaluated the antiviral effect of berberine against influenza A/FM1/1/47 (H1N1) in vivo and in vitro. The results showed that berberine strongly suppressed viral replication in A549 cells and in mouse lungs. Meanwhile, berberine relieved pulmonary inflammation and reduced necrosis, inflammatory cell infiltration, and pulmonary edema induced by viral infection in mice when compared with vehicle-treated mice. Berberine suppressed the viral infection-induced up-regulation of TLR7 signaling pathway, such as TLR7, MyD88, and NF-κB (p65), at both the mRNA and protein levels. Furthermore, berberine significantly inhibited the viral infection-induced increase in Th1/Th2 and Th17/Treg ratios as well as the production of inflammatory cytokines. Our data provide new insight into the potential of berberine as a therapeutic agent for viral infection via its antiviral activity.

Effects of different principles of Traditional Chinese Medicine treatment on TLR7/NF-κB signaling pathway in influenza virus infected mice.

BACKGROUND: Influenza virus is a single-stranded RNA virus that causes influenza in humans and animals. About 600 million people around the world suffer from influenza every year. Upon recognizing viral RNA molecules, TLR7 (Toll-like receptor) initiates corresponding immune responses. Traditional Chinese Medicines (TCMs), including Yinqiao powder, Xinjiaxiangruyin and Guizhi-and-Mahuang decoction, have been extensively applied in clinical treatment of influenza. Although the therapeutic efficacy of TCMs against influenza virus in vivo was reported previously, its underlying mechanisms are not clearly understood. This study aimed to investigate the immunological mechanisms in the treatment of influenza virus infected mice with three Chinese herbal compounds as well as the effect on TLR7/NF-κB signaling pathway during recovery. METHODS: Wild type and TLR7 KO C57BL/6 mice were infected with influenza virus FM1 and then treated with three TCMs. The physical parameters of mice (body weight and lung index) and the expression levels of components in TLR7/NF-κB signaling pathway were evaluated. RESULTS: After viral infection, Guizhi-and-Mahuang decoction and Yinqiao powder showed better anti-viral effect under normal condition. Compared to the viral control group, expression levels of TLR7, MyD88, IRAK4 and NF-κB were significantly reduced in all treatment groups. Furthermore, the three TCM treatment groups showed poor therapeutic efficacy and no difference in viral load compared to the viral control group in TLR7 KO mice. CONCLUSION: Our study indicated that Guizhi-and-Mahuang decoction and Yinqiao powder might play a crucial role of anti-influenza virus by regulating TLR7/NF-κB signal pathway.

Effects of Gui Zhi Ma Huang Ge Ban Tang on the TLR7 Pathway in Influenza Virus Infected Mouse Lungs in a Cold Environment.

OBJECTIVE: We wished to investigate the effects of the traditional Chinese medicine Gui Zhi Ma Huang Ge Ban Tang on controlling influenza A virus (IAV) infection and improving inflammation in mouse lungs. METHOD: Mice were maintained in normal and cold environments and infected with IAV by intranasal application, respectively. Real-time quantitative polymerase chain reaction was used to measure mRNA expression of TLR7, myeloid differentiation primary response 88 (MyD88), and nuclear factor-kappa B (NF-κB)p65 in the TLR7 signaling pathway and virus replication in lungs. Western blotting was used to measure expression levels of TLR7, MyD88, and NF-κB p65 proteins. Flow cytometry was used to detect the proportion of T-helper (Th)1/Th2 and Th17/T-regulatory (Treg) cells. RESULTS: Application of Gui Zhi Ma Huang Ge Ban Tang in influenza-infected mice in a cold environment showed (i) downregulation of TLR7, MyD88, and NF-κBp65; (ii) inhibition of transcriptional activities of promoters coding for TLR7, MyD88, and NF-κBp65; (iii) reduction in the proportion of Th1/Th2 and Th17/Treg cells. CONCLUSIONS: Gui Zhi Ma Huang Ge Ban Tang had a good therapeutic effect on mice infected with IAV, especially in the cold environment. It could reduce lung inflammation in mice significantly and elicit an anti-influenza effect by downregulating expression of the key factors in TLR7 signaling pathway.