Mechanism of Simiao Decoction in the treatment of atherosclerosis based on network pharmacology prediction and molecular docking.

To explore the molecular mechanism of Simiao Decoction (SMD) intervening atherosclerosis (AS). The main components and potential mechanisms of SMD remain unknown. This study aims to initially clarify the potential mechanism of SMD in the treatment of AS based on network pharmacology and molecular docking techniques. The principal components and corresponding protein targets of SMD were searched on Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform and the compound-target network was constructed by Cytoscape3.9.1. AS targets were searched on DrugBank, OMIM, and TTD databases. The intersection of compound target and disease target was obtained and the coincidence target was imported into STRING database to construct a protein-protein interaction network. We further performed Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis on the targets. The molecular docking method was used to verify the interaction between core components of SMD and targets. We created the active compounds-targets network and the active compounds-AS-targets network based on the network database containing Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform, DrugBank, OMIM, and TTD. We discovered that the therapy of AS with SMD involves 3 key substances-quercetin, kaempferol, and luteolin-as well as 5 crucial targets-ALB, AKT1, TNF, IL6, and TP53. The Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analysis revealed that the shared targets involved a number of signaling pathways, including the advanced glycosylation end product-receptor of AGE signaling pathway in diabetic complications, Hepatitis B, Lipid and atherosclerosis, Chemical Carcinogenesis-Receptor Activation, and Pathways in Cancer. The molecular docking demonstrated that the binding energies of quercetin, kaempferol, and luteolin with 5 important targets were favorable. This study reveals the active ingredients and potential molecular mechanism of SMD in the treatment of AS, and provides a reference for subsequent basic research.

The pathogenesis and treatment mechanism of Parkinson's disease from the perspective of traditional Chinese medicine.

BACKGROUND: Parkinson's disease (PD) is the second most common neurodegenerative disease with no treatment currently available to modify its progression. Traditional Chinese medicine (TCM) has gained attention for its unique theoretical basis and clinical effects. Many studies have reported on the clinical effects and pharmacological mechanisms of Chinese herbs in PD. However, few studies have focused on the treatment mechanisms of anti-PD TCM drugs from the perspective of TCM itself. PURPOSE: To elaborate the treatment mechanisms of anti-PD TCM drugs in the perspective of TCM. METHODS: We performed a literature survey using traditional books of Chinese medicine and online scientific databases including PubMed, Web of Science, Google Scholar, China National Knowledge Infrastructure (CNKI), and others up to July 2021. RESULTS: TCM theory states that PD is caused by a dysfunction of the zang-fu organs (liver, spleen, kidney, and lung) and subsequent pathogenic factors (wind, fire, phlegm, and blood stasis). Based on the pathogenesis, removing pathogenic factors and restoring visceral function are two primary treatment principles for PD in TCM. The former includes dispelling wind, clearing heat, resolving phlegm, and promoting blood circulation, while the latter involves nourishing the liver and kidney and strengthening the spleen. The anti-PD mechanisms of the active ingredients of TCM compounds and herbs at different levels include anti-apoptosis, anti-inflammation, and anti-oxidative stress, as well as the restoration of mitochondrial function and the regulation of autophagy and neurotransmitters. CONCLUSION: Chinese herbs and prescriptions can be used to treat PD by targeting multiple pharmacological mechanisms.

Mechanisms of Dendrobium officinale polysaccharides in repairing gastric mucosal injuries based on mitogen-activated protein kinases (MAPK) signaling pathway.

The present study aimed to investigate the protective effects and molecular mechanisms of Dendrobium officinale polysaccharides on gastric mucosal injuries. Following one week of continuous intragastric administration, a gastric mucosal injury model was established using intragastric administration of anhydrous ethanol. The area of gastric ulcer was measured, the contents of interleukin- 6 (IL-6), epidermal growth factor receptor (EGFR), and thyroid transcription factor 1 (TFF-1) in serum were detected by enzyme linked immunosorbent assay (ELISA), and the expressions of EGFR, TFF-1, IL-6, Raf-2, MAP kinase kinase 1 (MEK1), MEK2, and ERK1 in the gastric tissue were determined utilizing qPCR, Western blotting and immunohistochemistry. Simultaneously, Dendrobium officinale polysaccharides and anhydrous ethanol were added to the gastric mucosal cells (GES1) cultured in vitro, and the protective effects of Dendrobium officinale polysaccharides on cell viability was detected using Cell Counting Kit (CCK)-8. The addition of Dendrobium officinale polysaccharides markedly improved the gastric epithelial defect, inflammatory cell infiltration, and redness and swelling stemmed from gastric mucosal injuries and greatly reduced the area of gastric ulcer. The inhibition rates of gastric ulcer were 48.12 ± 2.98, 42.95 ± 1.52, and 27.96 ± 2.05% in the high, medium, and low concentration Dendrobium officinale polysaccharide groups, respectively. Dendrobium officinale polysaccharides could increase the expressions of EGFR and TFF-1 and decrease the expressions of IL-6, Raf-2, MEK1, MEK2, and ERK1. Dendrobium officinale polysaccharides could reduce the level of inflammatory factors and protect gastric mucosa by inhibiting the expression of MAPK pathway genes and proteins.

Inhibitory effect of Astragalus Membranaceus on osteoporosis in SAMP6 mice by regulating vitaminD/FGF23/Klotho signaling pathway.

Spontaneous senile osteoporosis severely threatens the health of the senior population which has emerged as a severe issue for society. A SAMP6 mouse model was utilized to estimate the impact of intragastrically administered Astragalus Membranaceus (AR) on spontaneous senile osteoporosis. Bone mineral density (BMD) and bone microstructure were measured using Micro-CT; contents of calcium and phosphorus were determined with the colorimetric method; and gene and protein expressions of fibroblast growth factor 23 (FGF23), Klotho, Vitamin D receptor (VDR), CYP27B1 and CYP24A1 were detected using qPCR, Western blot and ELISA assays, respectively. The findings indicated that AR could improve the femoral BMD and bone microstructure, elevate the contents of calcium and phosphorus, and increase the expression of Klotho, VDR, and CYP27B1 whereas decreasing the expression of FGF23 and CYP24A1 in SAMP6 mice in a dose independent manner. The present study has demonstrated that AR can promote osteogenesis and alleviate osteoporosis. It is also expected to provide a new insight for the treatment of spontaneous senile osteoporosis and to serve as a research basis for AR application.

Efficacy and Safety of Aidi Injection as an Adjuvant Therapy on Advanced Breast Cancer: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

BACKGROUND: Aidi injection (ADI) is being used widely for breast cancer in China. However, the efficacy and safety of it need to be summarized. We conducted a systematic review and meta-analysis to compare ADI and non-ADI treatment for advanced breast cancer. METHODS: We searched PubMed, EMBASE, CNKI, SinoMed, and CENTRAL from inception to Jan 2020 for randomized controlled trials (RCTs) with diagnosis of advanced breast cancer that compared the efficacy of ADI with non-ADI treatment. Two researchers screened the literature, extracted data, and evaluated risk of bias separately. The primary outcomes were overall response rate (ORR) and disease control rate (DCR). The secondary outcomes included the QOL, immune cells, and adverse events. Review Manager software was used for estimating risks of bias of included studies, data analysis, and plotting. The sensitivity analysis and the publication bias test were performed using the R language. I 2 and chi-square tests were used to estimate heterogeneity. If P > 0.1 or I 2 < 40%, the fixed-effect model meta-analysis was performed. A random or fixed-effect analysis was used depending on the heterogeneity testing. Weighted mean difference (WMD) or standard mean difference (SMD) was used for analysis of continuous data, and the rate ratio (RR) was calculated for the dichotomous variable, respectively. RESULTS: We included 14 studies with 1006 patients diagnosed as advanced breast cancer in total. The pooled effect showed that ADI increased ORR in advanced BC patients as an add-on therapy with little heterogeneity (RR = 1.14, 95% CI 1.03-1.27). DCR in BC patients could not be improved by ADI. ADI improved the KPS score in BC patients compared with chemotherapy alone (MD = 3.26, 95% CI 1.74-4.78). There were no improvements on immune markers except CD4/CD8 and NK%. Serum tumor markers CEA and CA153 were decreased while treated with ADI, but only one trial was involved. ADI decreased the numbers of myelosuppression in advanced BC patients, and AST, ALT, γ-GT, and CK-MB were all decreased. The sensitivity evaluation indicated that the result of the pooled effect size had good stability. CONCLUSION: This meta-analysis suggested that based on the existing evidence, treatment with ADI significantly changed the ORR of patients with advanced BC and improved their quality of life with few side effects. However, more randomized trials involving larger samples should be considered, and detailed mechanisms are needed to be uncovered.

Astragalus improve aging bone marrow mesenchymal stem cells (BMSCs) vitality and osteogenesis through VD-FGF23-Klotho axis.

To clarify the regulation of astragalus on the aging BMSCs model and the effect of astragalus on Vitamin D (VD)-FGF23-Klotho axis. siRNA was used to interfere the expression of VDR gene in aging BMSCs. Serum containing astragalus in different concentrations was added to the cultured cells. The expression of osteocalcin and alkaline phosphatase were detected by alizarin red staining and ELISA. Cell vitality was detected by flow cytometry, CCK-8 test, and ß-galactosidase staining. The expression of FGF23, Klotho, CYP27B1, and CYP24A1 was detected by qRT-PCR and western blot. The results showed that after reducing VDR gene expression, the aging BMSCs model showed decreased activity and osteogenic ability, increased expression of FGF23, Klotho and CYP24A1, and decreased expression of CYP27B1. After adding serum-containing astragalus, the activity of cells and the osteogenic ability was increased; the expression levels of FGF23, Klotho and CYP24A1 were decreased, the expression levels of CYP27B1 were increased, and the trend was more obvious with the increase of astragalus concentration. This study confirmed that astragalus could inhibit the aging of BMSCs and improve the osteogenesis ability by regulating the VD-FGF23-Klotho pathway. This study provided a certain research basis for the therapeutic of traditional Chinese medicine (TCM) on primary osteoporosis.

Vitamin D supplementation during pregnancy and the risk of wheezing in offspring: a systematic review and dose-response meta-analysis.

Background: In the past few years, growing evidence supports a preventive role of vitamin D supplementation during pregnancy for wheezing or asthma in offspring. However, the optimal dose of vitamin D intake is unclear. We conducted a meta-analysis to examine the linear and nonlinear dose-response pattern of vitamin D intake during pregnancy and asthma or wheezing in offspring. Questions/purposes: The purpose of this study was to answer the following question: Which dose of vitamin D is more effective in preventing wheezing in offspring? Method: We identified relevant studies by searching PubMed, EMBASE and CENTRAL up to December 2017 and by hand-searching reference lists. Meta-analysis and subgroup analysis were performed. Fixed or random effects model linear trends analyses were conducted based on the heterogeneity test. Then, if the data did not show linear trends, we considered a nonlinear trend analysis instead. Results: A total of 6068 participants were included in the study. Our analysis showed an inverse relationship between the intake of vitamin D during pregnancy and the occurrence of wheezing in offspring (pooled OR = 0.68, 95% CI = 0.55-0.83, I2 = 24%, Z statistic = 3.64, p < 0.01). We found a nonlinear U-shaped association between vitamin D supplementation during pregnancy and asthma or wheezing in offspring, with the lowest risk at approximately 800 IU/d. Publication bias was shown in a funnel plot without Egger's test. Conclusions: Vitamin D intake during pregnancy is inversely related to wheezing or asthma in offspring. Furthermore, the trend analysis indicates that offspring may benefit from approximately 800 IU/d vitamin D intake during pregnancy.