scholarly journals Metabolomics Study of Guizhi Fuling Capsules in Rats With Cold Coagulation Dysmenorrhea

2021 ◽  
Vol 12 ◽  
Author(s):  
Yu Zhang ◽  
Na Su ◽  
Weiyi Liu ◽  
Qingqing Wang ◽  
Jianguo Sun ◽  
...  
Keyword(s):  
Arachidonic Acid ◽  
Unsaturated Fatty Acids ◽  
Ovarian Function ◽  
Estradiol Benzoate ◽  
Control Group ◽  
Primary Dysmenorrhea ◽  
Model Group ◽  
Rat Serum ◽  
Cox 2 ◽  
Cold Coagulation

Dysmenorrhea refers to a kind of uterine cramping pain that occurs in women during the period of menstrual. Guizhi Fuling Capsules are mainly used for the treatment of various pain syndromes and especially effective in treating primary dysmenorrhea. However, the research on its modern pharmacology and mechanism of action have not been thoroughly carried out. It is not clear about the main active ingredients, potential targets and metabolic pathways involved in its efficacy. Therefore, this research project employed estradiol benzoate sensitization combined with oxytocin pain to construct the cold coagulation syndrome dysmenorrhea model, observed the anti-dysmenorrhea effect of Guizhi Fuling Capsules, and used the metabolomics to explore its mechanism. The results showed that Guizhi Fuling Capsules could considerably reduce the number of writhing times in dysmenorrhea rats, increasing the level of PGE2 and β-EP and reducing the contents of PGF2α in rat serum. Pathological sections of uterus and ovaries also showed that Guizhi Fuling Capsules could significantly relieve endometrial hyperplasia and improve ovarian function. The LC/MS-based metabolomics of rat uterine indicated that the model group has a great deviation from the control group. Compared with the model group, the Guizhi Fuling Capsules group had a tendency to shift to the control group, and the main metabolic changes was mainly concentrated on saturated and unsaturated fatty acids. Among them, arachidonic acid is in a pivotal position, and the expression of its rate-limiting enzyme (COX-2) involved in its cyclooxygenase metabolic pathway was significantly up-regulated in the model group, but significantly decreased after the intervention of Guizhi Fuling Capsules. In conclusion, Guizhi Fuling Capsules can effectively relieve primary dysmenorrhea, and this effect may be attributed to the regulation effects of Guizhi Fuling Capsules on endogenous metabolism, such as inhibiting arachidonic acid converted to prostaglandins through downregulate the expression of COX-2, which plays an anti-inflammatory effect.

scholarly journals Yan-Hou-Qing formula attenuates ammonia-induced acute pharyngitis in rats via inhibition of NF-κB and COX-2

2020 ◽  
Vol 20 (1) ◽  
Author(s):  
Min Xu ◽  
Tian-Yong Hu ◽  
Dong-Cai Li ◽  
Li Ma ◽  
Hua Zhang ◽  
...  
Keyword(s):  
Inflammatory Cells ◽  
Underlying Mechanism ◽  
Control Group ◽  
Model Group ◽  
Rat Models ◽  
Acute Pharyngitis ◽  
Histopathologic Study ◽  
Tnf Α ◽  
Protein Expressions ◽  
Cox 2

Abstract Background Yan Hou Qing (YHQ) is a Chinese medicinal formula designed to alleviate sore throat symptoms, but underlying mechanism of YHQ treatment for pharyngitis is poorly defined up to now. Methods In this study, the modulation of YHQ on pharyngitis is investigated in ammonia-induced acute pharyngitis rat models. After treatment with YHQ or dexamethasone respectively for five consecutive days, all rats were sacrificed for biomolecular and histopathologic study. Protein expressions of MAPKs, NF-κB, COX-2 and 5-LOX in pharyngitis tissue were evaluated by western blot analysis and the levels of TNF-α, IL-6, prostaglandin (PG) E2, leukotrienes (LT)-B4 and LT-D4 in pharyngeal tissue were measured via ELISA assay. Evans blue (EB) dye exudation test was performed parallelly to assess the integrity of pharyngeal tissue. Results Compared with normal control group, EB dye exudation, and inflammatory cytokines in the model group were significantly increased, and the pharynx tissue was obviously infiltrated by inflammatory cells. YHQ treatment improved the inflammatory infiltrate in pharyngeal tissue, and reduced EB dye exudation in AP rat models. The up-regulated TNF-α and IL-6 in pharyngeal tissue of AP were significantly reduced by YHQ through inhibition of phosphorylation of p38, Erk and NF-κB. YHQ treatment also reversed the increased level of PGE2 through down-regulation of COX-2. Conclusions YHQ formula attenuated the pharyngitis related symptoms via suppression of COX-2 and phosphorylation of p38, Erk and NF-κB (p65).

scholarly journals Proteomics analysis of differentially-expressed proteins in uterus of primary dysmenorrhea mice following administration of nuangong zhitong

2020 ◽  
Vol 19 (2) ◽  
pp. 265-275
Author(s):  
Yazhen Xie ◽  
Jianqiang Qian ◽  
Qibin Lu
Keyword(s):  
Treatment Group ◽  
Western Blot ◽  
Differentially Expressed ◽  
Control Group ◽  
Protective Effects ◽  
Differentially Expressed Proteins ◽  
Primary Dysmenorrhea ◽  
Model Group ◽  
Mice Model ◽  
Bioinformatics Analyses

Purpose: To use label-free proteomic method to investigate the mechanism of action of nuanggong zhitong decoction (NZD) on primary dysmenorrhea (PD). Methods: A mouse model of PD was established through oxytocin administration. The mice were divided into control group (normal mice), model group (PD mice administered normal saline), and treatment group (mice given NZD). The serum levels of PGE2 and PGF2α in the mice were measured by ELISA. The differentially expressed proteins (DEPs) among the three groups were revealed by identifying the proteins that were up-regulated (or down-regulated) in model group and down-regulated (or up-regulated) in the treatment group. The DEPs in the three groups were identified using Nano- HPLC-MS/MS, and their functions were investigated using bioinformatics analyses. The accuracy of proteomics was verified with western blot analysis. Results: Thirty-eight up-regulated and 66 down-regulated DEPs were identified. Bioinformatics analysis revealed that the DEPs were related to immune response, signal conduction, protein binding, and metabolism. STRING analysis indicated a total of 53 DEPs have direct or indirect functional links. Western blot results revealed that levels of Stat1, Rock1, vinculin and vaveolin-1 were consistent with the results of proteomic analysis. Conclusion: These findings provide further insights into the mechanism underlying the protective effects of NZD. Keywords: Primary dysmenorrhea, Uterus, Nuangong zhitong decoction, Vinculin, Caveolin, Differentially expressed proteins (DEPs), Bioinformatics

scholarly journals Proteins Expression Profiling of Rat Uteruses with Primary Dysmenorrhea Syndrome

2021 ◽  
Author(s):  
Yazhen Xie ◽  
Jianqiang Qian ◽  
Mingmei Wu
Keyword(s):  
Quantitative Proteomics ◽  
Serum Levels ◽  
Estradiol Benzoate ◽  
P38 Map Kinase ◽  
Apolipoprotein A1 ◽  
Differentially Expressed ◽  
Control Group ◽  
Primary Dysmenorrhea ◽  
Label Free ◽  
Bioinformatics Analyses

Abstract Purpose The aim of this study was to investigate differentially expressed proteins (DEPs) and their functions in the uteruses of primary dysmenorrhea (PD) rats by using label-free quantitative proteomics analysis.Methods The PD rat model was induced by injecting both estradiol benzoate and oxytocin. Twenty rats were equally divided into two groups: a control group (normal rats), a PD model group (PD rats). Writhing scores and serum levels of Prostaglandin E2 (PGE2) and Prostaglandin F2α (PGF2α) were used to evaluate the success of the rat PD model. The DEPs were identified and analyzed by label-free quantitative proteomics and bioinformatics analyses.Results A total of 276 DEPs were identified, including 119 up-regulated DEPs and 157 down-regulated DEPs. Bioinformatics revealed that the DEPs were mainly associated with ‘protein binding’, ‘metabolism’, ‘signal conduction’ and ‘focal adhesion’. The proteomic findings were verified by western blot analysis, which confirmed that myosin light chain kinase (MLCK), heat shock protein 90 AB1 (HSP90AB1), apolipoprotein A1 (Apoa1), p38 MAP kinase, c-Jun N-terminal kinase (JNK), and extracellular signal-related kinase 1/2 (ERK1/2) were significantly differentially expressed in between the control and PD samples.Conclusions These results provide a deeper understanding the molecular pathogenesis of PD. The DEPs found in the present study may provide new ideas for further study of the mechanism of PD and aid the search for biomarkers for early diagnosis and treatment.

scholarly journals Effects of Radix Scrophulariae on Hyperthyroidism Assessed by Metabonomics and Network Pharmacology

2021 ◽  
Vol 12 ◽  
Author(s):  
Ning Zhang ◽  
Fang Lu ◽  
Zihui Li ◽  
Hongwei Zhao ◽  
Mu Pang ◽  
...  
Keyword(s):  
Signaling Pathway ◽  
Unsaturated Fatty Acids ◽  
Chinese Herb ◽  
Enrichment Score ◽  
Sphingolipid Metabolism ◽  
Network Pharmacology ◽  
Control Group ◽  
Disease Genes ◽  
Model Group ◽  
System Pharmacology

Radix Scrophulariae (Chinese name: Xuanshen), a traditional Chinese herb, is used for the treatment of hyperthyroidism, and in this study, its mechanisms were evaluated by metabonomics and system pharmacology. To study the anti-hyperthyroidism effects of R. Scrophulariae, a male SD rat (180–220 g) model of hyperthyroidism induced by Euthyrox was used. Thirty rats were randomly distributed into three groups: the Model group, the R. Scrophulariae treatment group (RS group) and the healthy Control group. Using the UHPLC/Q-TOF-MS metabolomics approach, 44 metabolites were found to be profoundly altered in the model group, and the levels of these biomarkers were significantly decreased after treatment with R. Scrophulariae. Forty-four metabolites and 13 signaling pathways related to R. Scrophulariae, including the biosynthesis of unsaturated fatty acids, primary bile acid biosynthesis and sphingolipid metabolism, were explored, and linoleic acid metabolism and sphingolipid metabolism were identified as the most relevant metabolic pathways. In addition, the system pharmacology paradigm revealed that R. Scrophulariae contains 83 active ingredients and is related to 795 genes, and 804 disease genes are related to hyperthyroidism. The construction of the R. Scrophulariaceae-chemical composition-target-hyperthyroidism network identified a total of 112 intersection genes. The enriched gene targets were analyzed, and five pathways were found to be enriched. Among them pathways, the HIF signaling pathway had the highest enrichment score, which indicated that this pathway might be the main signaling pathway related to the treatment of hyperthyroidism by R. Scrophulariae.The integrated approach involving metabolomics and network pharmacology revealed that R. Scrophulariae might play a role in the treatment of hyperthyroidism by regulating the “IL6-APOA1-cholesterol” pathway and disturbing the HIF signaling pathway. The results demonstrate that the combination of metabolomics and network pharmacology could be used to reflect the effects of R. Scrophulariae on the biological network and metabolic state of hyperthyroidism and to evaluate the drug efficacy of R. Scrophulariaceae and its related mechanisms.

scholarly journals Effects of Modified Wenjing Decoction Combined with Online Publicity and Education on the Treatment of Primary Dysmenorrhea of Cold Coagulation and Blood Stasis

2022 ◽  
Vol 2022 ◽  
pp. 1-5
Author(s):  
Na Li ◽  
Jie Li ◽  
Pengpeng Gai
Keyword(s):  
Treatment Group ◽  
Clinical Symptoms ◽  
Blood Stasis ◽  
Control Group ◽  
Primary Dysmenorrhea ◽  
Menstrual Cycles ◽  
Associated Symptoms ◽  
Before And After ◽  
And Control ◽  
Cold Coagulation

Objective. To explore the effects of modified Wenjing decoction combined with online publicity and education on the treatment of primary dysmenorrhea of cold coagulation and blood stasis. Methods. The materials of 111 patients with primary dysmenorrhea of cold coagulation and blood stasis in the outpatient department (January 2019–June 2021) were collected to conduct the retrospective study. The 111 patients were randomized into treatment group (n = 59) and control group (n = 52). The control group received online publicity and education and conventional treatment, and the treatment group received online publicity and education and modified Wenjing decoction. The patients in the two groups were continuously treated for three menstrual cycles. The treatment effects, the dosage of analgesics, the scores of associated symptoms before and after treatment, and other indexes were compared between the two groups. Results. The differences in the efficacy on abdominal pain were statistically significant between the two groups P < 0.05 . Compared with the control group, the treatment group had lower scores of associated symptoms after treatment p < 0.5 . After the treatment of three menstrual cycles, 54 patients in the treatment group stopped taking ibuprofen, and the average ibuprofen dosage of the other 5 patients was (0.24 ± 0.16)g. The 52 patients in the control group still needed to take ibuprofen, and the mean dosage was (0.51 ± 0.05)g. The differences in the ibuprofen dosage between the two groups had remarkable difference P < 0.001 . Conclusion. Modified Wenjing decoction combined with online publicity and education can obviously improve the clinical symptoms of the patients with primary dysmenorrhea of cold coagulation and blood stasis and reduce the dosage of analgesics. It is worth promoting and applying in practice.

scholarly journals The Therapeutic Effect of Ge-Gen Decoction on a Rat Model of Primary Dysmenorrhea: Label-Free Quantitative Proteomics and Bioinformatic Analyses

2020 ◽  
Vol 2020 ◽  
pp. 1-12
Author(s):  
Yazhen Xie ◽  
Jianqiang Qian ◽  
Qibin Lu
Keyword(s):  
Treatment Group ◽  
Rat Model ◽  
Quantitative Proteomics ◽  
Serum Levels ◽  
Control Group ◽  
Protective Mechanism ◽  
Primary Dysmenorrhea ◽  
Label Free ◽  
Model Group ◽  
Protective Function

Ge-Gen decoction (GGD) is widely used for the treatment of primary dysmenorrhea (PD) in China. However, the mechanisms that underlie this effect are unclear. We investigated the protective mechanism of GGD in a rat model of PD using label-free quantitative proteomics. The model was established by the administration of estradiol benzoate and oxytocin. Thirty rats were divided into three groups (ten rats/group): a control group (normal rats), a model group (PD rats), and a treatment group (PD rats treated with GGD). The serum levels of prostaglandin E2 (PGE2) and prostaglandin F2α (PGF2α) were measured by ELISA. Nanohigh-performance liquid chromatography-tandem mass spectrometry (nano-HPLC-MS/MS) was used to identify differentially expressed proteins (DEPs), and bioinformatics was used to investigate the protein function. Proteomic data were validated by western blot analysis. Oxytocin-induced writhing responses and abnormal serum levels of PGE2 and PGF2α were reversed following the administration of GGD. A total of 379 DEPs were identified; 276 were identified between the control group and the model group, 144 were identified between the model group and the treatment group, and 41 were identified as DEPs that were common to all groups. Bioinformatics revealed that the DEPs between the control group and the model group were mainly associated with cellular component biogenesis and binding processes. The DEPs between the model group and the treatment group were mainly involved in the protein binding and metabolic process. The expression levels of HSP90AB1 and the phosphorylation levels of ERK, JNK, and P-p38 in the uteri of rats in the three groups were consistent with the proteomic findings; MAP kinases (ERK, JNK, and p38) are known to be involved in the production of inflammatory cytokines and oxytocin signaling while HSP90AB1 is known to be associated with estrogen signaling. Collectively, these data indicate that GGD may exert its protective function on PD by regulating the inflammatory response and signaling pathways associated with oxytocin and estrogen.

Testosterone Potentiation of Ionophore and ADP Induced Platelet Aggregation : Relationship to Arachidonic Acid Metabolism

1981 ◽  
Vol 46 (02) ◽  
pp. 538-542 ◽  
Author(s):  
R Pilo ◽  
D Aharony ◽  
A Raz
Keyword(s):  
Arachidonic Acid ◽  
Platelet Aggregation ◽  
Unsaturated Fatty Acids ◽  
Human Platelet ◽  
Platelet Rich Plasma ◽  
Arachidonic Acid Metabolism ◽  
Ionophore A23187 ◽  
Low Concentrations ◽  
Induced Aggregation

SummaryThe role of arachidonic acid oxygenated products in human platelet aggregation induced by the ionophore A23187 was investigated. The ionophore produced an increased release of both saturated and unsaturated fatty acids and a concomitant increased formation of TxA2 and other arachidonate products. TxA2 (and possibly other cyclo oxygenase products) appears to have a significant role in ionophore-induced aggregation only when low concentrations (<1 μM) of the ionophore are employed.Testosterone added to rat or human platelet-rich plasma (PRP) was shown previously to potentiate platelet aggregation induced by ADP, adrenaline, collagen and arachidonic acid (1, 2). We show that testosterone also potentiates ionophore induced aggregation in washed platelets and in PRP. This potentiation was dose and time dependent and resulted from increased lipolysis and concomitant generation of TxA2 and other prostaglandin products. The testosterone potentiating effect was abolished by preincubation of the platelets with indomethacin.

PGE2 release by bradykinin in human airway smooth muscle cells: involvement of cyclooxygenase-2 induction

1997 ◽  
Vol 273 (6) ◽  
pp. L1132-L1140 ◽  
Author(s):  
Linhua Pang ◽  
Alan J. Knox
Keyword(s):  
Arachidonic Acid ◽  
Smooth Muscle ◽  
Airway Smooth Muscle ◽  
Arachidonic Acid Release ◽  
Human Airway Smooth Muscle ◽  
Short Term ◽  
Human Airway ◽  
Acid Release ◽  
Cox 2

Prostanoids may be involved in bradykinin (BK)-induced bronchoconstriction in asthma. We investigated whether cyclooxygenase (COX)-2 induction was involved in prostaglandin (PG) E2 release by BK in cultured human airway smooth muscle (ASM) cells and analyzed the BK receptor subtypes responsible. BK stimulated PGE2release, COX activity, and COX-2 induction in a concentration- and time-dependent manner. It also time dependently enhanced arachidonic acid release. In short-term (15-min) experiments, BK stimulated PGE2 generation but did not increase COX activity or induce COX-2. In long-term (4-h) experiments, BK enhanced PGE2 release and COX activity and induced COX-2. The long-term responses were inhibited by the protein synthesis inhibitors cycloheximide and actinomycin D and the steroid dexamethasone. The effects of BK were mimicked by the B2-receptor agonist [Tyr(Me)8]BK, whereas the B1 agonist des-Arg9-BK was weakly effective at high concentrations. The B2antagonist HOE-140 potently inhibited all the effects, but the B1 antagonist des-Arg9,(Leu8)-BK was inactive. This study is the first to demonstrate that BK can induce COX-2. Conversion of increased arachidonic acid release to PGE2 by COX-1 is mainly involved in the short-term effect, whereas B2 receptor-related COX-2 induction is important in the long-term PGE2 release.

scholarly journals Study on the Mechanism of Shugan Xiaozhi Fang on Cells with Non-alcoholic Fatty Liver Disease

2019 ◽  
Vol 17 (1) ◽  
pp. 1328-1338
Author(s):  
Yufeng Xing ◽  
Chuantao Zhang ◽  
Fenfen Zhai ◽  
Tianran Zhou ◽  
Xiang Cui ◽  
...  
Keyword(s):  
Liver Disease ◽  
Fatty Liver Disease ◽  
Dose Group ◽  
Control Group ◽  
High Dose ◽  
Model Group ◽  
Alcoholic Fatty Liver ◽  
Oil Red O Staining ◽  
Alcoholic Fatty Liver Disease ◽  
Oil Red O

AbstractCells with non-alcoholic fatty liver disease (NAFLD) were studied to determine the mechanism of liver deficiency via the AdipoR2-PPARa pathway. NAFLD cells were randomly divided into a normal control group, blank control group, model group, low dose group, medium dose group, and high dose group. The NAFLD models were established by incubating the cells with linoleic acid (LA) and palmitic acid (PA) (2:1) for 24 h. The test groups were incubated with different doses of Shugan Xiaozhi Fang extract. The pathological changes in cells that accumulated lipids were detected by Oil Red O staining. Malondialdehyde (MDA) and triglyceride (TG) levels were measured. The apoptosis of cells was evaluated by flow cytometry. The levels of AdipoR2, PPARa, CD36, acyl-CoA mRNA, and protein were confirmed by RT- PCR and Western blot. The results of the Oil Red O staining demonstrated that the NAFLD cell model was successfully established. Compared with the model group, the levels of TG and MDA in the groups that received low, medium, and high doses of Shugan Xiaozhi were significantly lower (P<0.01), and a dose effect was evident. In addition, the expression of AdipoR2, PPARa, CD36, acyl-CoA protein, and mRNA in the Shugan Xiaozhi-treated groups was upregulated. Furthermore, the levels of AdipoR2, PPAR, CD36, acyl-CoA protein, and mRNA in all drug treatment groups that were extracted from L-O2 normal human hepatocytes were significantly upregulated (P<0.01). Moreover, the factor pattern of HepG2 human liver carcinoma cells was similar to that of L-O2. The levels of AdipoR, CD36, acyl-CoA, and AdipoR mRNA in the HepG2 low group were increased (P<0.05). AdipoR, PPAR, CD36, and acyl-CoA protein levels and AdipoR mRNA expression were significantly increased in the intermediate dose group and high dose group (P<0.01). Shugan Xiaozhi Fang attenuates hepatic lipid deposition in NAFLD induced by incubating with LA and PA for 24 h, which is associated with the activation of the AdipoR2-PPARα pathway.

scholarly journals Berberine, A Phytoalkaloid, Inhibits Inflammatory Response Induced by LPS through NF-Kappaβ Pathway: Possible Involvement of the IKKα

Molecules ◽  
2021 ◽  
Vol 26 (16) ◽  
pp. 4733
Author(s):  
Kiran Reddi ◽  
Hanxuan Li ◽  
Wei Li ◽  
Sarada Tetali
Keyword(s):  
Arachidonic Acid ◽  
Molecular Modeling ◽  
Direct Interaction ◽  
Ligand Binding Site ◽  
Quantitative Real Time Pcr ◽  
Tnf Α ◽  
Molecular Modeling Studies ◽  
Therapeutic Properties ◽  
Cox 2 ◽  
Activated Monocytes

Berberine (BBR), a plant alkaloid, is known for its therapeutic properties of anticancer, cardioprotective, antidiabetic, hypolipidemic, neuroprotective, and hepatoprotective activities. The present study was to determine the molecular mechanism of BBR’s pharmacological activity in human monocytic (THP-1) cells induced by arachidonic acid (AA) or lipopolysaccharide (LPS). The effect of BBR on AA/LPS activated proinflammatory markers including TNF-α, MCP-1, IL-8 and COX-2 was measured by ELISA or quantitative real-time PCR. Furthermore, the effect of BBR on LPS-induced NF-κB translocation was determined by immunoblotting and confocal microscopy. AA/ LPS-induced TNF-α, MCP-1, IL-6, IL-8, and COX-2 markers were markedly attenuated by BBR treatment in THP-1 cells by inhibiting NF-κB translocation into the nucleus. Molecular modeling studies suggested the direct interaction of BBR to IKKα at its ligand binding site, which led to the inhibition of the LPS-induced NF-κB translocation to the nucleus. Thus, the present study demonstrated the anti-inflammatory potential of BBR via NF-κB in activated monocytes, whose interplay is key in health and in the pathophysiology of atherosclerotic development in blood vessel walls. The present study findings suggest that BBR has the potential for treating various chronic inflammatory disorders.

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