A Traditional Chinese Medicine Formula Danshen Baibixiao Ameliorates Imiquimod-Induced Psoriasis-Like Inflammation in Mice

Background: Danshen Baibixiao (DB) is a traditional Chinese medicine formula, which has been used to treat psoriasis for decades. Although DB shows good efficacy in clinical practice, the pharmacological effects and underlying mechanisms of DB remain elusive. This study aimed to evaluate the anti-psoriatic effects of DB and explore its underlying mechanisms in an imiquimod (IMQ)-induced psoriasis-like mouse model.Materials and methods: DB was orally administered on IMQ-induced psoriatic mice. Psoriasis area severity index (PASI) was used to evaluate the severity of the inflammation in skin, and histological changes were evaluated by hematoxylin and eosin (H and E) staining. Levels of inflammatory cytokines, such as tumor necrosis factor α (TNF-α), interleukin (IL)-17A, IL-23, IL-6, IL-1β and IL-22 in serum were assessed by enzyme-linked immunosorbent assay (ELISA). mRNA expressions of IL-17A, IL-23, IL-6 and IL-22 were determined by real-time polymerase chain reaction (PCR). Expression levels of proteins related to NF-κB, STAT3 and MAPKs signaling pathways were measured by western blotting (WB).Results: DB significantly ameliorated the psoriatic symptoms in IMQ-induced mice. The serum levels of inflammatory cytokines (TNF-α, IL-17A, IL-23, IL-6, IL-1β and IL-22) were decreased, and mRNA expressions of IL-17A, IL-23, IL-6 and IL-22 in skin tissues were down-regulated. Moreover, WB analysis indicated that DB inhibited the activation of NF-κB, STAT3 and MAPKs signaling pathways.Conclusion: This study confirms the anti-psoriatic activity of DB in IMQ-induced psoriasis-like mice. The possible mechanism may relate to the activities of regulating the IL-23/TH-17 axis and suppressing the activation of NF-κB, STAT3 and MAPKs signaling pathways.

Effect of traditional Chinese medicine formula Guilu Xian on in vitro fertilization and embryo transfer outcome in older women with low prognosis: study protocol for a prospective, multicenter, randomized double-blind study

Introduction In recent years, the prevalence of infertility has significantly increased and has become a global reproductive health problem. The female ovarian reserves have been shown to decrease progressively with an increase in age. Besides, the rate of embryo implantation and clinical pregnancy also decreases. Traditional Chinese medicine has been widely applied in assisted reproductive technology. It is reported to have a significant influence on improving the quality of oocytes, improving endometrial receptivity, increasing clinical pregnancy rate, reducing pregnancy-related complications, etc. Therefore, this study will investigate the effect of Guilu Xian, a traditional Chinese medicine formula on IVF-ET outcome in older women with low prognosis. Methods and analysis This trial is a prospective, multicenter, randomized double-blind clinical trial. A total of 120 infertile patients with low prognosis and receiving IVF or ICSI in 3 public hospitals in China will be randomly divided into two parallel groups: Guilu Xian group (n = 60) and placebo group (n = 60). Patients in both groups will be treated with antagonist regimens to promote ovulation, and all the patients will be required to take the medication from the 2nd to 4th day of the menstrual cycle to the day of egg retrieval. A comparison of the total number of oocytes obtained, the fertilization rate, clinical pregnancy rate, embryo quality, embryo implantation rate, and early spontaneous abortion rate between the experimental group and the placebo group will be performed. Trial registration Chinese Clinical Trials Registry ChiCTR1900028255. Registered on 16 December 2019.

Effects of a traditional Chinese medicine formula containing the Coix seed and Lotus seed on the intestinal morphology and microbiota of local piglets

A traditional Chinese medicine formula based on the Coix seed and Lotus seed has been used as a general treatment of malnutrition, excessive fatigue, dysfunction of the spleen and stomach, and disorders of water transport in humans in China. However, there is limited information on its effects on the gut microbiota of piglets in vivo. In this study, the mix of Coix seed and Lotus were added the diet of forty weaned piglets (local piglets), and then evaluated it’s affected on the gut microbiota of piglets and on the relations within the gut bacterial community. The results indicated that this traditional Chinese medicine formula (LM) and the extract of the traditional Chinese medicine formula (LMT) downregulated pH of succus gastricus and raised pH of the ileum, and LMT obviously decreased the feed conversion ratio. Further study showed LMT and LM also significantly increased the thick and long of gastrointestinal villi. And then, 16S ribosomal DNA sequencing revealed that groups LMT and LM have higher relative abundance of the genus Lactobacillus in the colon, succus gastricus, and jejunum, which are beneficial bacteria sold as dietary supplements to aid digestion or to augment health. Meanwhile, the relative abundance levels of Prevotellaceae, Alloprevotella, and Prevotella in the colon and Clostridium in succus gastricus and jejunum were lower. These experiments highlight the usefulness of the traditional Chinese medicine formula based on the Coix seed and Lotus seed for decreasing pH in succus gastricus, for improving the structure of intestinal villi and gut microflora, and then for achieving improvements in pig production performance.

The Role for GABAergic Interneurons Subtypes in the Antidepressant Efficacy of Traditional Chinese Medicine Formula Lily Bulb and Rehmannia Decoction

Background Depression is associated with reduced γ-aminobutyric acid (GABA) and alterations of GABAergic interneurons in medial prefrontal cortex (mPFC), which can be normalized by traditional Chinese medicine formula lily bulb and Rehmannia decoction (LBRD) standard decoction. However, the impact of GABAergic interneurons subtypes including parvalbumin (PV), somatostatin (SST), and vasoactive intestinal peptide (VIP), in depressive episodes as well as in the LBRD standard decoction antidepressant effects remains to be elucidated. Methods We assessed the effects of LBRD standard decoction intervention on the expression of GABA associated miRNA/mRNA and GABAergic subtype-specific markers in chronic stress induced depression by western blot and qRT-PCR. The lncRNA/miRNA/GABA regulatory axis was verified by luciferase reporter assay, RNA immunoprecipitation, RNA pull-down assay and then detect its changes in LBRD standard decoction administration with use of immunofluorescence staining and RNA-fluorescence in situ hybridization (FISH). Results In the current study, we found that LBRD standard decoction exerted antidepressant effects based on the results of behavioral tests. Meanwhile, LBRD also revised the reduced GABA levels in depression by increasing the expression of lncRNA Neat1 and Malat1, as well as decreasing miRNA-144-3p and miRNA-15b-5p. Moreover, the expression of SST mRNA and protein in the mPFC tissues from depression group, was significantly lower than those in the control cases, while LBRD standard decoction treatment revised these changes. Whereas, neither chronic stress nor treatment can obviously change the level of PV and VIP mRNA and protein expression. In the SST-positive neurons of mPFC tissues, treatment with LBRD standard decoction resulted in the elevation of Gad-67, VGAT, GAT-3 and an reduction of miRNA-144-3p expression. Conclusion Taken together, these findings suggest that SST interneurons may be served as a preferentially vulnerable GABAergic neuronal subtype in depression and LBRD standard decoction antidepressant activities potentially relate to against the SST cells deficits by regulating the miRNA-144-3p mediated GABA synthesis, release.

Antidepressant Mechanism of Traditional Chinese Medicine Formula Xiaoyaosan in CUMS-Induced Depressed Mouse Model via RIPK1-RIPK3-MLKL Mediated Necroptosis Based on Network Pharmacology Analysis

Background: Depression is a stress-related disorder that seriously threatens people’s physical and mental health. Xiaoyaosan is a classical traditional Chinese medicine formula, which has been used to treat mental depression since ancient times. More and more notice has been given to the relationship between the occurrence of necroptosis and the pathogenesis of mental disorders.Objective: The purpose of present study is to explore the potential mechanism of Xiaoyaosan for the treatment of depression using network pharmacology and experimental research, and identify the potential targets of necroptosis underlying the antidepressant mechanism of Xiaoyaosan.Methods: The mice model of depression was induced by chronic unpredictable mild stress (CUMS) for 6 weeks. Adult C57BL/6 mice were randomly divided into five groups, including control group, chronic unpredictable mild stress group, Xiaoyaosan treatment group, necrostatin-1 (Nec-1) group and solvent group. Drug intervention performed from 4th to 6th week of modeling. The mice in Xiaoyaosan treatment group received Xiaoyaosan by intragastric administration (0.254 g/kg/d), and mice in CUMS group received 0.5 ml physiological saline. Meanwhile, the mice in Nec-1 group were injected intraperitoneally (i.p.) with Nec-1 (10 mg/kg/d), and the equivalent volume of DMSO/PBS (8.3%) was injected into solvent group mice. The behavior tests such as sucrose preference test, forced swimming test and novelty-suppressed feeding test were measured to evaluate depressive-like behaviors of model mice. Then, the active ingredients in Xiaoyaosan and the related targets of depression and necroptosis were compiled through appropriate databases, while the “botanical drugs-active ingredients-target genes” network was constructed by network pharmacology analysis. The expressions of RIPK1, RIPK3, MLKL, p-MLKL were detected as critical target genes of necroptosis and the potential therapeutic target compounds of Xiaoyaosan. Furthermore, the levels of neuroinflammation and microglial activation of hippocampus were measured by detecting the expressions of IL-1β, Lipocalin-2 and IBA1, and the hematoxylin and eosin (H&E) stained was used to observe the morphology in hippocampus sections.Results: After 6-weeks of modeling, the behavioral data showed that mice in CUMS group and solvent group had obvious depressive-like behaviors, and the medication of Xiaoyaosan or Nec-1 could improve these behavioral changes. A total of 96 active ingredients in Xiaoyaosan which could regulate the 23 key target genes were selected from databases. Xiaoyaosan could alleviate the core target genes in necroptosis and improve the hippocampal function and neuroinflammation in depressed mice.Conclusion: The activation of necroptosis existed in the hippocampus of CUMS-induced mice, which was closely related to the pathogenesis of depression. The antidepressant mechanism of Xiaoyaosan included the regulation of multiple targets in necroptosis. It also suggested that necroptosis could be a new potential target for the treatment of depression.