The NLRP3 inflammasome in depression: Potential mechanisms and therapies.

Increasing evidence suggests that the failure of clinical antidepressants may be related with neuroinflammation. The NOD-, LRR- and pyrin domain-containing protein 3 (NLRP3) inflammasome is an intracellular multiprotein complex, and has been considered as a key contributor to the development of neuroinflammation. Inhibition of NLRP3 inflammasome is an effective method for depression treatment. In this review, we summarized current researches highlighting the role of NLRP3 inflammasome in the pathology of depression. Firstly, we discussed NLRP3 inflammasome activation in patients with depression and animal models. Secondly, we outlined the possible mechanisms driving the activation of NLRP3 inflammasome. Thirdly, we discussed the pathogenetic role of NLRP3 inflammasome in depression. Finally, we overviewed the current and potential antidepressants targeting the NLRP3 inflammasome. Overall, the inhibition of NLRP3 inflammasome activation may be a potential therapeutic strategy for inflammation-related depression.

[Exploration of active components and mechanism of Scutellariae Radix-Phellodendri Chinensis Cortex drug pair in treatment of psoriasis based on network pharmacology and molecular docking].

This paper aims to explore active components and mechanism of Scutellariae Radix(SR)-Phellodendri Chinensis Cortex(PCC) drug pair in treatment of psoriasis by network pharmacology and molecular docking. Specifically, the chemical components of SR and PCC were retrieved from literature and TCMSP, as well as targets of these components from PharmMapper and UniProt, and the targets related to psoriasis from OMIM, TTD, PharmGkb, and DrugBank. Then the chemical component-medicinal target, protein-protein interaction(PPI), and chemical component-psoriasis target networks were constructed by Cytoscape. Gene ontology(GO) term enrichment analysis and Kyoto encyclopedia of genes and genomes(KEGG) pathway enrichment analysis were performed based on Metascape. Finally, molecular docking of the chemical components(high degree) with core therapeutic targets was carried out by AutoDock vina. The results showed 88 compounds of SR and PCC(including baicalin, wogonoside, berberine and phellodendrine) and 30 targets of the pair in the treatment of psoriasis. The 30 targets mainly involved the biological processes such as neutrophil mediated immunity(GO: 0002446) and T cell activation(GO: 0042110), and the signaling pathways such as metabolism of xenobiotics by cytochrome P450(hsa00980), apoptosis(hsa04210), and PI3 K-Akt signaling pathway(hsa04151). The results of molecular docking demonstrated that the main active components can spontaneously bind to the targets and the binding energy of 46 components with epidermal growth factor receptor(EGFR) was less than-8 kcal·mol~(-1). According to the PPI analysis, EGFR may be a key target for the treatment of psoriasis. Active components such as baicalin and berberine had high binding affinity with EGFR. This study preliminarily revealed the multi-component, multi-target and multi-pathway mechanism of SR-PCC drug pair in the treatment of psoriasis, which provided theoretical basis for the research on the mechanism of the drug pair in the treatment of psoriasis.

Identifying the mechanism underlying antidepressant-like effects of loganin by network pharmacology in combination with experimental validation.

ETHNOPHARMACOLOGICAL RELEVANCE: Loganin, an iridoid glycoside, is one of the quality control indexes of Cornus officinalis Sieb. et Zucc. Increasing evidence emphasize the important role of inflammation in the pathology of depression, which links depression with other chronic diseases. Loganin prevents inflammatory response in multiple diseases and reverses depressive-like behaviors. However, the mechanisms underlying antidepressant-like effects of loganin for the treatment of inflammation-associated depression are not utterly understood. AIM OF THE STUDY: The present study was designed to predict the potential targets of loganin against inflammation-associated depression using a network pharmacology approach. MATERIALS AND METHODS: Pharmmapper and Uniport were used to predict loganin-related targets. Targets of inflammation were identified through GeneCards databases and Online Mendelian Inheritance in Man (OMIM). Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis were used to identify the potential mechanism. Finally, qRT-PCR and ELISA were used to confirm the role of loganin on these targets. RESULTS: There were 15 nodes in the loganin-inflammation-depression intersection targets network. In the network, the degree value of CTNNB1 was above 3. Among top ten pathways identified by KEGG analysis, Th1/Th2 cell differentiation and IL-17 signaling pathways were related with both inflammation and depression. As indicated by qRT-PCR results, loganin increased CTNNB1 mRNA level. Moreover, loganin elevated M2 markers of microglia but decreased M1 markers of microglia against lipopolysaccharide (LPS), indicated by qRT-PCR results and ELISA results. CONCLUSION: CTNNB1 was the main target of loganin. Loganin alleviated LPS-induced inflammation through inhibiting M1 polarization of microglia. Our results provide a better understanding of loganin-induced antidepressant-like effects for the treatment of inflammation-associated depression.

Effectiveness and safety of light vegetarian diet and Qingjiang Tiaochang Recipe for functional constipation: An exploratory study protocol for randomized controlled trial.

INTRODUCTION: Functional constipation is a chronic disease that is common in children and adults around the world. The treatments for functional constipation include diet and lifestyle interventions, medications, and surgery. The diet pattern plays an important role in the occurrence of constipation. We found in clinical practice that simple application of drugs cannot achieve long-term relief of constipation, and a large number of patients are not satisfied with the existing treatment. We have concluded that Qingjiang Tiaochang Recipe (QJTCR) and light vegetarian diet (LVD) can effectively improve constipation. However, there is no enough evidence for the description of the effect. This protocol aims at exploratorily investigating effectiveness and safety of LVD and QJTCR following a rigorous clinical trial. METHODS AND ANALYSIS: We will recruit 90 patients to participate in this prospective, placebo-controlled, randomized trial, and exploratory study at the China-Japan Friendship Hospital, including traditional Chinese medicine group, placebo + diet group, traditional Chinese medicine + diet group. Patients in the diet intervention group must strictly abide by LVD, and the study will continue for 28 days. During the intervention period, we need to record a designed diary to assess diet quality and defecation. The primary outcomes for this clinical study were weekly complete spontaneous bowel movements. The secondary outcomes were constipation-related symptom rating scale, traditional Chinese medicine syndrome scale, and 48-hour gastrointestinal transit time, high-resolution anorectal manometry, Bristol stool score, constipation quality of life assessment scale, constipation symptoms self-assessment scale, short-chain fatty acids in feces. In addition, the study will determine the safety of the intervention.

Connexins in oligodendrocytes and astrocytes: Possible factors for demyelination in multiple sclerosis.

Increasing evidences support that glial connexins are involved in the demyelination pathology of multiple sclerosis (MS), a chronic inflammatory demyelinating disorder. Here, we review the data from patients with MS and animal models of MS that implicate connexins in demyelination. Connexins expressed in oligodendrocytes and astrocytes show diverse changes at the different phases of MS. Loss of oligodendrocyte or astrocyte connexins contributes to demyelination and exaggerates the pathology of MS. Channel-dependent and -independent connexins are involved in the pathology of demyelination, which is related with myelin integrity, metabolic homeostasis, the brain-blood barrier, the immune cell infiltration, and the inflammatory response. A comprehensive understanding of connexin function in demyelination may provide new therapeutic targets for MS.

Effectiveness and safety of light vegetarian diet on functional constipation with gastrointestinal damp-heat pattern: An exploratory study protocol for randomized controlled trial.

INTRODUCTION: Functional constipation (FC) is one of the common gastrointestinal disorders that affects people of almost every age. Persistent FC significantly affects quality of life and well-being along with economic burden on patients as well as health care system. Therapeutic efficacy of currently used treatment strategies becomes limited shortly after their discontinuation as constipation occurs again as a result of inappropriate dietary habits. Previous studies have revealed that light vegetarian diet (LVD) can significantly improve both typical and atypical subtypes of major traditional Chinese medicine (TCM) FC syndrome such as gastrointestinal damp-heat syndrome. This protocol aims at exploratorily investigating effectiveness and safety of LVD following a rigorous clinical trial. METHODS AND DESIGN: Total 92 patients in each of the 2 subtypes will be recruited in China-Japan Friendship Hospital for participating in this prospective, placebo-controlled, randomized trial and exploratory study. The patients in each subtype will be randomly divided into 4 groups according to 1:1:1:1 ratio with allocation concealment, which are drug + diet group, drug group, placebo + diet group and placebo group. Patients in the group with diet intervention will be required to strictly follow the LVD. The study will continue for a period of 28 days, including a drug or placebo supervised intervention and a 14th-day telephone follow-up. During the intervention, patients will be required to record a designed diary for controlling the diet quality (DQ) and analyzing the defecation. The study will focus investigation of complete spontaneous bowel movements (CSBM) per week as its primary outcome and constipation-related symptom rating scale (CSS), TCM syndrome scale (TCMSS), 48-hour gastrointestinal transit time (48-hour GITT), high resolution anorectal manometry (HRAM) and fecal flora detection (FFD) will be included in secondary outcomes. Furthermore, the study will also determine safety, DQ and compliance indicators. ETHICS AND DISSEMINATION: This study has been approved by China-Japan Friendship Hospital clinical research ethics committee (No. 2017-46-1). A SPIRIT checklist is available for this protocol. TRIAL REGISTRATION NUMBER: ChiCTR1800019686 in Chinese Clinical Trial Registry (WHO ICTRP member).

Fischeriana A, a meroterpenoid with an unusual 6/6/5/5/5/6/6 heptacyclic carbon skeleton from the roots of Euphorbia fischeriana.

Fischeriana A (1), a new meroterpenoid with a rare carbon skeleton, along with one of its known biosynthesis-related compounds 2,4-dihydroxy-6-methoxyacetophenone (2) and two known ent-abietane-type diterpenoids (3-4), were isolated from the roots of Euphorbia fischeriana. Their structures, including the stereochemistry, were elucidated using comprehensive spectroscopic methods, single-crystal X-ray diffraction, and electronic circular dichroism analysis. Compound 1 was found to be made up of an unusual heptacyclic ring system (6/6/5/5/5/6/6) featuring a modified ent-abietane diterpene with a phloroglucinol moiety. A possible biogenetic pathway for 1 was proposed. Compound 1 exhibited marked anti-tumor activities against the HepG2 cell line.

[A new lignan from rhizome of Stellera chamaejasme].

To investigate the chemical compounds from the rhizome of Stellera chamaejasme, nine lignans, including stellerachamin A (1), 8-hydroxypluviatolide (2), wikstromol (3), pinoresinol (4), matairesinol (5), dextrobursehernin (6), hinokinin(7), (-)-glaberide I (8) and （-） medioresinol (9) were isolated by various chromatographic methods. Their structures were extensively determined on basis of MS and NMR spectroscopic data analysis. Among them, compound 1 was a new lignan, and compounds 2 and 7 were isolated from Thymelaeaceae for the first time.

An unusual racemic C12-norabietane diterpene and a new abietane diterpene alkaloid from Salvia miltiorrhiza Bunge.

A rare C12-norabietane diterpene racemate (1) and a new abietane diterpene alkaloid (2) were isolated from the roots of Salvia miltiorrhiza Bunge. Their structures were established by comprehensive spectroscopic analyses, and 1 was successfully resolved by chiral HPLC, demonstrating that 1 is racemic. The absolute configurations of 1a [(+)-miltiorolide A], 1b [(-)-miltiorolide A], and 2 were determined using TDDFT-ECD calculations. 1a and 1b are the first examples of enantiomeric C12-norabietane diterpenes featuring an isobutylene with a tetrahydronaphthalene-butyrolactone ring system. The cytotoxic activities of the isolates (1 and 2) were evaluated against three human cancer cell lines BEL-7402, HT-29 and PANC-28. A plausible biogenetic pathway of 1 was also proposed.

Four new iridoid glucosides containing the furan ring from the fruit of Cornus officinalis.

Four new and rare iridoid glucosides, cornusfuroside A-D (1-4), containing the furan ring were identified from water extract of the fruit of Cornus officinalis. These new chemical structures were determined through extensive spectroscopic analysis, including 1D and 2D NMR, IR, HRESIMS, experimental and calculated electronic circular dichroism (ECD). Notably, this study is the first report on the isolation of four iridoid glucoside structures with acetal functions in the sugar moiety. The neuroprotective effects of these compounds were also evaluated in vitro.

Rapid detection and characterization of major phenolic compounds in Radix Actinidia chinensis Planch by ultra-performance liquid chromatography tandem mass spectrometry.

Radix Actinidia chinensis Planch is a traditional Chinese herb, and its decotion had been widely used clinically to treat several types of cancer. In our study, the phenolic compounds constituting the major water soluble components of Radix A. chinensis were profiled and characterized by ultraperformance liquid chromatography electrospray ionization tandem mass spectrometry. A total of 50 compounds were identified or tentatively characterized, including caffeic acid, p-coumaric acid, 29 catechin derivatives, 12 quinic acid derivatives and 7 coumarin derivatives. Most of the identified compounds were firstly reported from A. chinensis. Among them, scopoletin, scoplin, isofraxoside and quinic acid derivatives have not ever been reported from genus Actinidia previously. These phenolic compounds might be responsible for the antitumor activity of the water extract of radix A. chinensis, and the established analytical method could be applied to further study of quality evaluation and active components of Radix A. chinensis.

[Analysis of traditional and modern application of prepared decoction pieces of herbal medicine].

The paper described the rationality of traditional and modern application of prepared decoction pieces of herbal medicine on basis of application, statistics and comparison analysis of three forms of drugs of traditional Chinese herbal pieces prepared for decoction, prepared decoction pieces in small packing and granules; and illustrated different opinions correlative to the three forms of drugs; put forward the counter-measures and proposals for the problems facing the traditional Chinese herbal pieces for decoction; the paper stated clearly that the traditional Chinese herbal pieces for decoction should not be replaced, instead, the viewpoint and the reasons on its application must be holding on; and the trend of development and expectations of the Chinese herbal pieces for decoction were predicted as well.