Serum Metabolomics Coupled with Network Pharmacology Strategy to Explore Therapeutic Effects of Scutellaria Baicalensis Georgi on Diabetic Nephropathy

2021 ◽  
Vol 49 (1) ◽  
pp. e21001-e21013
Author(s):  
Li-Hui MEN ◽  
Zi-Feng PI ◽  
Ming-Xin HU ◽  
Shu LIU ◽  
Zhi-Qiang LIU ◽  
...  
Keyword(s):  
Diabetic Nephropathy ◽  
Scutellaria Baicalensis ◽  
Network Pharmacology ◽  
Therapeutic Effects ◽  
Scutellaria Baicalensis Georgi ◽  
Serum Metabolomics

Uncovering the Key miRNAs and Targets of the Liuwei Dihuang Pill in Diabetic Nephropathy-Related Osteoporosis based on Weighted Gene Co-Expression Network and Network Pharmacology Analysis

2021 ◽  
Vol 21 ◽  
Author(s):  
Ming Ming Liu ◽  
Nan Ning Lv ◽  
Rui Geng ◽  
Zhen Hua ◽  
Yong Ma ◽  
...  
Keyword(s):  
Diabetic Nephropathy ◽  
Network Analysis ◽  
Signaling Pathway ◽  
Diabetic Complications ◽  
Cellular Response ◽  
Mapk Signaling ◽  
Functional Enrichment ◽  
Network Pharmacology ◽  
Integrated Analysis ◽  
Therapeutic Effects

Background: Diabetic nephropathy-related osteoporosis (DNOP) is the most common comorbid bone metabolic disorder associated with diabetes mellitus (DM). The Liuwei Dihuang Pill (LWD) is a traditional Chinese herbal medicine widely used to treat diabetic complications, including diabetic nephropathy (DN). This study aimed to identify the biomarkers of the mechanisms of DNOP in LWD with systems biology approaches. Methods: Herein, we performed an integrated analysis of the GSE51674 and GSE63446 datasets from the GEO database via weighted gene co-expression network and network pharmacology (WGCNA) analysis. In addition, a network pharmacology approach, including bioactive compounds, was used with oral bioavailability (OB) and drug-likeness (DL) evaluation. Next, target prediction, functional enrichment analysis, network analysis, and virtual docking were used to investigate the mechanisms of LWD in DNOP. Results : WGCNA successfully identified 63 DNOP-related miRNAs. Among them, miR-574 was significantly upregulated in DN and OP samples. A total of 117 targets of 22 components associated with LWD in DNOP were obtained. The cellular response to nitrogen compounds, the AGE-RAGE signaling pathway in diabetic complications, and the MAPK signaling pathway were related to the main targets. Network analysis showed that kaempferol and quercetin were the most significant components. MAPK1 was identified as a potential target of miR-574 and the hub genes in the protein-protein interaction (PPI) network. The docking models demonstrated that kaempferol and quercetin had a strong binding affinity for Asp 167 of MAPK1. Conclusion: This study demonstrated that miR-574 may play important roles in DNOP, and the therapeutic effects of kaempferol and quercetin on LWD in DNOP might be mediated by miR-574 by targeting MAPK1. Our results provide new perspectives for further studies on the anti-DNOP mechanism of LWD.

scholarly journals Network Pharmacology Study Reveals the Mechanism of Astragali Radix in Treatment of Diabetic Nephropathy

2020 ◽  
Author(s):  
Chongmei Tian ◽  
Jing-bai Chen ◽  
Xiang Chen ◽  
Dao-zong Xia
Keyword(s):  
Diabetic Nephropathy ◽  
Signaling Pathway ◽  
Mapk Signaling ◽  
Mapk Signaling Pathway ◽  
Network Pharmacology ◽  
Signal Pathways ◽  
Therapeutic Effects ◽  
Disease Network ◽  
Astragali Radix ◽  
Target Disease

Abstract Background Diabetic nephropathy (DN), a unique complication of diabetes, could contribute to an increase in mortality. In this study, we predicted and proved the molecular pharmacological mechanism concerning the protective effects of Astragali Radix on DN. Methods The same potential target genes from Astragali Radix and DN were analyzed and constructed the protein interaction network. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment-related major targets and signal pathways were performed. The drug-ingredients-target-disease network was visually built using Cytoscape 3.6.1. The beneficial pharmacological activities of quercetin from Astragali Radix were confirmed by CCK-8 assay, determination of antioxidant parameters and Western blotting analysis. Results There are 12 bioactive components from Astragali Radix and 56 same targets between Astragali Radix and DN. The GO analysis results showed that the biological processes mainly included protein homodimerization activity. KEGG analysis indicate that the screened targets were most closely linked to the mitogen-activated protein kinase (MAPK) signaling pathway. The drug-ingredients-target-disease network results revealed that the therapeutic effects of Astragali Radix mainly included oxidative stress, inflammatory reaction and apoptosis. During the verification process, quercetin from Astragali Radix could attenuate cytotoxicity, enhance catalase (CAT) and superoxide dismutase (SOD) activities and suppress MAPK signaling pathway. Conclusions In the current study, network pharmacology with experimental analysis predicted and proved the therapeutic function of Astragali Radix by improving antioxidant capacity and suppressing MAPK signaling pathway, these investigations could provide a new perspective for further exploration of Astragali Radix on DN treatment.

scholarly journals Improvement of Bronchial Immune Hypersensitivity Reaction Using Extracts from Chrysanthemum morifolium Ramatuelle and Scutellaria baicalensis Georgi

2021 ◽  
Vol 2021 ◽  
pp. 1-13
Author(s):  
Kyoungwon Cho ◽  
Sung Sun Park ◽  
Hakjoo Choi
Keyword(s):  
Inflammatory Cytokines ◽  
Immune Cell ◽  
Immunoglobulin E ◽  
Chrysanthemum Morifolium ◽  
Scutellaria Baicalensis ◽  
Control Group ◽  
Therapeutic Effects ◽  
Biochemical Tests ◽  
Scutellaria Baicalensis Georgi ◽  
Cell Counts

Chrysanthemum morifolium Ramatuelle and Scutellaria baicalensis Georgi (skullcap) have been used as safe raw materials for drinking or as traditional medicines in Korea. In this study, we investigated the potential therapeutic effects of ovalbumin-induced asthma in a mouse model. After establishing the model, mice were treated with a mixture of chrysanthemum and skullcap extracts at different mixing ratios (6 : 4, 7 : 3, and 8 : 2). Immune cell counts and the production of various inflammatory cytokines were measured using biochemical tests. Among the mixtures tested, the 7 : 3 ratio (CS73) showed the most pronounced effects. CS73 significantly reduced the levels of the inflammatory cytokines interleukin- (IL-) 1β, IL-4, IL-5, IL-6, IL-10, IL-13, IL-17A, IL-17F, and IL-17E in the serum and bronchoalveolar lavage fluid of asthmatic mice. In addition, CS73 treatment significantly increased the production of IL-2 and interferon-γ and decreased the production of immunoglobulin E, histamine, and thymic stromal lymphopoietin in asthmatic mice compared to the control group. Our results suggest that the combination of chrysanthemum and skullcap extracts, especially at a 7 : 3 ratio, can be used to improve bronchial health and contribute to improved public health.

scholarly journals Applications, phytochemistry, pharmacological effects, pharmacokinetics, toxicity of Scutellaria baicalensis Georgi. and its probably potential therapeutic effects on COVID-19: a review

2020 ◽  
Vol 15 (1) ◽  
Author(s):  
Jia-Wen Song ◽  
Jia-Ying Long ◽  
Long Xie ◽  
Lin-Lin Zhang ◽  
Qing-Xuan Xie ◽  
...  
Keyword(s):  
Animal Feed ◽  
Scutellaria Baicalensis ◽  
Research Progress ◽  
Network Pharmacology ◽  
Chemical Components ◽  
Phytochemical Analysis ◽  
Therapeutic Effects ◽  
Pharmacological Effects ◽  
Active Ingredients ◽  
Wide Range

Abstract Scutellaria baicalensis Georgi. (SB) is a common heat-clearing medicine in traditional Chinese medicine (TCM). It has been used for thousands of years in China and its neighboring countries. Clinically, it is mostly used to treat diseases such as cold and cough. SB has different harvesting periods and processed products for different clinical symptoms. Botanical researches proved that SB included in the Chinese Pharmacopoeia (1st, 2020) was consistent with the medicinal SB described in ancient books. Modern phytochemical analysis had found that SB contains hundreds of active ingredients, of which flavonoids are its major components. These chemical components are the material basis for SB to exert pharmacological effects. Pharmacological studies had shown that SB has a wide range of pharmacological activities such as antiinflammatory, antibacterial, antiviral, anticancer, liver protection, etc. The active ingredients of SB were mostly distributed in liver and kidney, and couldn't be absorbed into brain via oral absorption. SB’s toxicity was mostly manifested in liver fibrosis and allergic reactions, mainly caused by baicalin. The non-medicinal application prospects of SB were broad, such as antibacterial plastics, UV-resistant silk, animal feed, etc. In response to the Coronavirus Disease In 2019 (COVID-19), based on the network pharmacology research, SB’s active ingredients may have potential therapeutic effects, such as baicalin and baicalein. Therefore, the exact therapeutic effects are still need to be determined in clinical trials. SB has been reviewed in the past 2 years, but the content of these articles were not comprehensive and accurate. In view of the above, we made a comprehensive overview of the research progress of SB, and expect to provide ideas for the follow-up study of SB.

scholarly journals Network pharmacology analysis of ZiShenWan for diabetic nephropathy and experimental verification of its anti-inflammatory mechanism

2020 ◽  
Author(s):  
Xiaoyuan Guo ◽  
You Wu ◽  
Chengfei Zhang ◽  
Lili Wu ◽  
Lingling Qin ◽  
...  
Keyword(s):  
Diabetic Nephropathy ◽  
Protein Kinase ◽  
Inflammatory Response ◽  
Signaling Pathways ◽  
Transforming Growth Factor ◽  
Critical Role ◽  
Mitogen Activated Protein Kinase ◽  
Network Pharmacology ◽  
Therapeutic Effects ◽  
Anti Inflammatory

Abstract Background: Diabetic nephropathy (DN) is the leading cause of end-stage renal disease (ESRD). The inflammatory response plays a critical role in the process of DN. ZiShenWan (ZSW) is a classical Chinese medicinal formula with remarkable clinical therapeutic effects on DN, but its pharmacological action mechanisms remain unclear. Methods: In this study, a network pharmacology approach was applied to investigate the pharmacological mechanism of ZSW in DN therapy. The “drug-ingredient-target” network for ZSW in DN treatment was established with Cytoscape software based on candidate active components of ZSW and targets in DN treatment obtained from databases. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were performed with the key targets. Because inflammation is important in DN, the key targets and signaling pathways associated with the anti-inflammatory, renoprotective mechanism of ZSW were partially validated in db/db mice. Results: A total of 56 active ingredients in ZSW and 166 DN-related targets were selected from databases. Various related genes and pathways participate in the inflammatory response. ZSW markedly alleviated renal injury in db/db mice by inhibiting the exaggerated release of proinflammatory cytokines such as interleukin (IL)-1β, IL-6, tumor necrosis factor -ɑ (TNF-ɑ), monocyte chemotactic protein-1 (MCP-1) and transforming growth factor-β1 (TGF-β1) and regulating the p38 mitogen-activated protein kinase (MAPK) and phosphoinositide 3-kinase-protein kinase B (PI3K-Akt) signaling pathways. Conclusions: Network pharmacology analysis demonstrated that ZSW achieved therapeutic renoprotective effects in DN by alleviating the inflammatory response via regulation of multiple targets and signaling pathways.

Systematic Investigation of Quercetin for Treating Cardiovascular Disease Based on Network Pharmacology

2019 ◽  
Vol 22 (6) ◽  
pp. 411-420 ◽  
Author(s):  
Xian-Jun Wu ◽  
Xin-Bin Zhou ◽  
Chen Chen ◽  
Wei Mao
Keyword(s):  
Cardiovascular Disease ◽  
Cardiovascular Diseases ◽  
Signaling Pathway ◽  
Kegg Pathway ◽  
Enrichment Analysis ◽  
Network Pharmacology ◽  
Pathway Enrichment Analysis ◽  
Therapeutic Effects ◽  
Pathway Enrichment ◽  
Compound Target

Aim and Objective: Cardiovascular disease is a serious threat to human health because of its high mortality and morbidity rates. At present, there is no effective treatment. In Southeast Asia, traditional Chinese medicine is widely used in the treatment of cardiovascular diseases. Quercetin is a flavonoid extract of Ginkgo biloba leaves. Basic experiments and clinical studies have shown that quercetin has a significant effect on the treatment of cardiovascular diseases. However, its precise mechanism is still unclear. Therefore, it is necessary to exploit the network pharmacological potential effects of quercetin on cardiovascular disease. Materials and Methods: In the present study, a novel network pharmacology strategy based on pharmacokinetic filtering, target fishing, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis, compound-target-pathway network structured was performed to explore the anti- cardiovascular disease mechanism of quercetin. Results:: The outcomes showed that quercetin possesses favorable pharmacokinetic profiles, which have interactions with 47 cardiovascular disease-related targets and 12 KEGG signaling pathways to provide potential synergistic therapeutic effects. Following the construction of Compound-Target-Pathway (C-T-P) network, and the network topological feature calculation, we obtained top 10 core genes in this network which were AKT1, IL1B, TNF, IL6, JUN, CCL2, FOS, VEGFA, CXCL8, and ICAM1. KEGG pathway enrichment analysis. These indicated that quercetin produced the therapeutic effects against cardiovascular disease by systemically and holistically regulating many signaling pathways, including Fluid shear stress and atherosclerosis, AGE-RAGE signaling pathway in diabetic complications, TNF signaling pathway, MAPK signaling pathway, IL-17 signaling pathway and PI3K-Akt signaling pathway.

Network pharmacology combined with metabolomics to study the mechanism of Shenyan Kangfu Tablets in the treatment of diabetic nephropathy

2021 ◽  
Vol 270 ◽  
pp. 113817
Author(s):  
Xiaoli Wang ◽  
Qiaoyu He ◽  
Qian Chen ◽  
Beibei Xue ◽  
Jia Wang ◽  
...  
Keyword(s):  
Diabetic Nephropathy ◽  
Network Pharmacology

scholarly journals Processed Scutellaria baicalensis Georgi Extract Alleviates LPS-Induced Inflammatory and Oxidative Stress through a Crosstalk between NF-κB and KEAP1/NRF2 Signaling in Macrophage Cells

2021 ◽  
Vol 11 (13) ◽  
pp. 6055
Author(s):  
Akhtar Ali ◽  
En-Hyung Kim ◽  
Jong-Hyun Lee ◽  
Kang-Hyun Leem ◽  
Shin Seong ◽  
...  
Keyword(s):  
Scutellaria Baicalensis ◽  
Raw 264.7 Cells ◽  
Prostaglandin E ◽  
Scutellaria Baicalensis Georgi ◽  
Anticancer Effects ◽  
Tnf Α ◽  
Clinical Benefits ◽  
Anti Oxidant ◽  
Cox 2 ◽  
Anti Inflammatory

Prolonged inflammation results in chronic diseases that can be associated with a range of factors. Medicinal plants and herbs provide synergistic benefits based on the interaction of multiple phytochemicals. The dried root of Scutellaria baicalensis Georgi and its compounds possess anti-inflammatory, anti-oxidative, and anticancer effects. Processing is a traditional method to achieve clinical benefits by improving therapeutic efficacy and lowering toxicity. In this study, we investigated the anti-inflammatory and anti-oxidant effect of processed Scutellaria baicalensis Georgi extract (PSGE) against lipopolysaccharide (LPS) stimulated RAW 264.7 cells. Data using Griess assay and ELISA showed that PSGE decreased nitric oxide and prostaglandin E2 (PGE2) levels against LPS. PSGE treatment up-regulated 15-hydroxyprostaglandin dehydrogenase (PGDH), while cyclooxygenase (COX)-2 and microsomal prostaglandin E synthase (mPGES)-1 expression did not change. Interestingly, PGE2 inhibition was regulated by prostaglandin catabolic enzyme 15-PGDH rather than COX-2/mPGES-1, enzymes essential for PGE2 synthesis. Additionally, PSGE-suppressed LPS-induced IL-6 and TNF-α production through NF-κB signaling. NF-κB release from an inactive complex was inhibited by HO-1 which blocked IκBα phosphorylation. The ROS levels lowered by PSGE were measured with the H2DCFDA probe. PSGE activated NRF2 signaling and increased antioxidant Hmox1, Nqo1, and Txn1 gene expression, while reducing KEAP1 expression. In addition, pharmacological inhibition of HO-1 confirmed that the antioxidant enzyme induction by PSGE was responsible for ROS reduction. In conclusion, PSGE demonstrated anti-inflammatory and anti-oxidant effects due to NRF2/HO-1-mediated NF-κB and ROS inhibition.

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