scholarly journals Evaluation of the anti-atherosclerosis effect of Shanhuaxiaozhi Formulation by combination of GC–MS-based metabolomics and TMT-based proteomics technology

2021 ◽  
Author(s):  
Xing Ren ◽  
Jing Yang ◽  
Baochen Zhu ◽  
Jianxun Ren ◽  
Shuai Shi ◽  
...  
Keyword(s):  
Metabolic Regulation ◽  
Molecular Mechanisms ◽  
Underlying Mechanism ◽  
Myocardial Contraction ◽  
Gas Chromatography Mass Spectrometry ◽  
Therapeutic Effects ◽  
Proteomics Data ◽  
Serum Samples ◽  
Holistic View ◽  
Proteomics Technology

Abstract Objective Shanhuaxiaozhi formulation (SHXZF) is a traditional Chinese medicine preparation composed of Saffron, Crataegi Fructus, Chrysanthemi Flos, Tangerine Peel and Fructus Lycii. It is used in clinics for treating atherosclerosis with promising evidence of efficacy. Although some of the drugs in SHXZF have been reported to have significant therapeutic effects on atherosclerosis, the metabolic regulation and underlying mechanism of SHXZF during the remission of atherosclerosis are still unclear. This study aimed to integrate proteome and metabolome data sets for a holistic view of the molecular mechanisms of SHXZF in treating atherosclerosis. Methods Serum samples and aortic arch tissue from male ApoE−/− mice and C57BL/6L mice were analyzed respectively using gas chromatography–mass spectrometry (GC–MS) based metabolomics technology and Tandem Mass Tags (TMT) based quantitative proteomics technology. Metabonomics and proteomics data were integrated to analyze the mechanism of SHXZF in the treatment of atherosclerosis. Results A total of 24 potential biomarkers and 70 differential proteins were identified. These substances were mainly involved in three biological pathways: the cAMP signaling pathway, the lipid metabolism pathway, and the myocardial contraction pathway. Conclusions The results suggested that SHXZF could effectively treat atherosclerosis, partially by regulating the above three metabolic pathways. The combination of proteomics and metabolomics provided a feasible method to uncover the underlying interventional effect and therapeutic mechanism of SHXZF on atherosclerosis.

scholarly journals Unraveling the neuroprotective effect of Tinospora cordifolia in Parkinsonian mouse model through proteomics Approach.

2021 ◽  
Author(s):  
Hareram Birla ◽  
Chetan Keswani ◽  
Saumitra Sen Singh ◽  
Walia Zahra ◽  
Hagera Dilnashin ◽  
...  
Keyword(s):  
Treatment Group ◽  
Mouse Model ◽  
Molecular Mechanisms ◽  
Neuroprotective Effect ◽  
Mitochondrial Gene ◽  
Tinospora Cordifolia ◽  
Therapeutic Effects ◽  
Proteomics Data ◽  
Proteomics Approach ◽  
Multiple Drugs

Abstract Stress-induced dopaminergic (DAergic) neuronal death in the midbrain region is the primary cause of Parkinson’s disease (PD). From the discovery of L-dopa, multiple drugs were discovered to improve lifestyle of PD patients, but they failed due to their multiple side effects. Tinospora cordifolia (Tc), a medicinal herb has been used in traditional medicines to treat neurodegenerative diseases. In our previous study, the neuroprotective role of Tc against MPTP intoxicated Parkinsonian mice was reported. Here, we further explore the neuroprotective molecular mechanisms of Tc in Rotenone (ROT) intoxicated mouse model through proteomics approach. Mice were pretreated with Tc extract by oral administration, followed by ROT-intoxication. Behavioral tests were performed to check motor functions of mice. Protein was isolated, and label free quantification (LFQ) was carried out to identify differentially expressed protein (DEPs) in control vs. PD and PD vs. treatment group. In this study, we report 800 DEPs in control vs. PD and 133 in PD vs. Treatment group. In silico tools clearly demonstrate significant enrichment of biochemical and molecular pathways with DEPs which are known to be important for PD progression including mitochondrial gene expression, PD pathways, TGF-β signaling, Alzheimer’s disease etc. This results were further validated by qRT-PCR and found that the expression of target gene were identical to the proteomics data. This study provides a novel insight for the disease progression as well new therapeutic tagets. More importantly, it demonstrates that Tc exerts the therapeutic effects through the regulation of multiple pathways to protect DAergic neurons.

scholarly journals Differences in the Hemolytic Behavior of Two Isomers in Ophiopogon japonicus In Vitro and In Vivo and Their Risk Warnings

2020 ◽  
Vol 2020 ◽  
pp. 1-16
Author(s):  
Huan-Hua Xu ◽  
Zhen-Hong Jiang ◽  
Yu-Ting Sun ◽  
Li-Zhen Qiu ◽  
Long-Long Xu ◽  
...  
Keyword(s):  
Side Effect ◽  
Redox Balance ◽  
Underlying Mechanism ◽  
Therapeutic Effects ◽  
Proteomics Data ◽  
Mitochondrial Energy Metabolism ◽  
Ophiopogon Japonicus ◽  
Bioactive Ingredients

Ophiopogonin D (OPD) and Ophiopogonin D ′ (OPD ′ ) are two bioactive ingredients in Ophiopogon japonicus. Previously published studies have often focused on the therapeutic effects related to OPD’s antioxidant capacity but underestimated the cytotoxicity-related side effects of OPD ′ , which may result in unpredictable risks. In this study, we reported another side effect of OPD ′ , hemolysis, and what was unexpected was that this side effect also appeared with OPD. Although hemolysis effects for saponins are familiar to researchers, the hemolytic behavior of OPD or OPD ′ and the interactions between these two isomers are unique. Therefore, we investigated the effects of OPD and OPD ′ alone or in combination on the hemolytic behavior in vitro and in vivo and adopted chemical compatibility and proteomics methods to explain the potential mechanism. Meanwhile, to explain the drug-drug interactions (DDIs), molecular modeling was applied to explore the possible common targets. In this study, we reported that OPD ′ caused hemolysis both in vitro and in vivo, while OPD only caused hemolysis in vivo. We clarified the differences and DDIs in the hemolytic behavior of the two isomers. An analysis of the underlying mechanism governing this phenomenon showed that hemolysis caused by OPD or OPD ′ was related to the destruction of the redox balance of erythrocytes. In vivo, in addition to the redox imbalance, the proteomics data demonstrated that lipid metabolic disorders and mitochondrial energy metabolism are extensively involved by hemolysis. We provided a comprehensive description of the hemolysis of two isomers in Ophiopogon japonicus, and risk warnings related to hemolysis were presented. Our research also provided a positive reference for the development and further research of such bioactive components.

scholarly journals GC-MS-based Metabolomic Profiling of Thymoquinone in Streptozotocin-induced Diabetic Nephropathy in Rats

2017 ◽  
Vol 12 (4) ◽  
pp. 1934578X1701200 ◽  
Author(s):  
Mohammad Raish ◽  
Ajaz Ahmad ◽  
Basit L. Jan ◽  
Khalid M. Alkharfy ◽  
Kazi Mohsin ◽  
...  
Keyword(s):  
Amino Acids ◽  
Fatty Acids ◽  
Diabetic Nephropathy ◽  
Therapeutic Interventions ◽  
Gas Chromatography Mass Spectrometry ◽  
Therapeutic Effects ◽  
Serum Samples ◽  
Metabolomic Profiling ◽  
Stage Renal Disease ◽  
End Stage

Diabetic nephropathy is a common complication of diabetes mellitus and one of the major etiologies of end-stage renal disease. Specific therapeutic interventions are necessary to treat such complications. The present study was designed to investigate the metabolomic changes induced by thymoquinone for the treatment of diabetic nephropathy, using a rodent model. Rats were divided into three different groups (n = 6 each): control, diabetic, and thymoquinone-treated diabetic groups. Metabolites in serum samples were analyzed via gas chromatography-mass spectrometry. Multiple changes were observed, including those related to the metabolism of amino acids and fatty acids. The correlation analysis suggested that treatment with thymoquinone led to the reversal of diabetic nephropathy that was associated with modulations in the metabolism and proteolysis of amino acids, fatty acids, glycerol phospholipids, and organic acids. In addition, we explored the mechanisms linking the metabolic profiling of diabetic nephropathy, with a particular emphasis on the potential roles of increased reactive oxygen species production and mitochondrial dysfunctions. Our findings demonstrated that metabolomic profiling provided significant insights into the basic mechanisms of diabetic nephropathy and the therapeutic effects of thymoquinone.

scholarly journals Metabolomics and Transcriptomics Integration of Early Response of Populus tomentosa to Reduced Nitrogen Availability

2021 ◽  
Vol 12 ◽  
Author(s):  
Min Chen ◽  
Yiyi Yin ◽  
Lichun Zhang ◽  
Xiaoqian Yang ◽  
Tiantian Fu ◽  
...  
Keyword(s):  
Mass Spectrometry ◽  
High Performance ◽  
Metabolic Regulation ◽  
Molecular Mechanisms ◽  
Nitrogen Availability ◽  
Populus Tomentosa ◽  
Gas Chromatography Mass Spectrometry ◽  
Global Changes ◽  
Regulatory Pathways ◽  
N Deficiency

Nitrogen (N) is one of the most crucial elements for plant growth and development. However, little is known about the metabolic regulation of trees under conditions of N deficiency. In this investigation, gas chromatography-mass spectrometry (GC-MS) was used to determine global changes in metabolites and regulatory pathways in Populus tomentosa. Thirty metabolites were found to be changed significantly under conditions of low-N stress. N deficiency resulted in increased levels of carbohydrates and decreases in amino acids and some alcohols, as well as some secondary metabolites. Furthermore, an RNA-sequencing (RNA-Seq) analysis was performed to characterize the transcriptomic profiles, and 1,662 differentially expressed genes were identified in P. tomentosa. Intriguingly, four pathways related to carbohydrate metabolism were enriched. Genes involved in the gibberellic acid and indole-3-acetic acid pathways were found to be responsive to low-N stress, and the contents of hormones were then validated by high-performance liquid chromatography/electrospray ionization tandem mass spectrometry (HPLC-ESI-MS/MS). Coordinated metabolomics and transcriptomics analysis revealed a pattern of co-expression of five pairs of metabolites and unigenes. Overall, our investigation showed that metabolism directly related to N deficiency was depressed, while some components of energy metabolism were increased. These observations provided insights into the metabolic and molecular mechanisms underlying the interactions of N and carbon in poplar.

scholarly journals Molecular and Cellular Mechanisms of Melatonin in Osteosarcoma

Cells ◽  
2019 ◽  
Vol 8 (12) ◽  
pp. 1618 ◽  
Author(s):  
Ko-Hsiu Lu ◽  
Renn-Chia Lin ◽  
Jia-Sin Yang ◽  
Wei-En Yang ◽  
Russel J. Reiter ◽  
...  
Keyword(s):  
Molecular Mechanisms ◽  
Bone Growth ◽  
Age Distribution ◽  
Underlying Mechanism ◽  
Therapeutic Effects ◽  
Anticancer Activities ◽  
Cellular Mechanisms ◽  
Wide Range ◽  
Review Reports

Osteosarcoma, the most common primary bone malignancy, occurs most frequently in adolescents with a peak of incidence at 11–15 years. Melatonin, an indole amine hormone, shows a wide range of anticancer activities. The decrease in melatonin levels simultaneously concurs with the increase in bone growth and the peak age distribution of osteosarcoma during puberty, so melatonin has been utilized as an adjunct to chemotherapy to improve the quality of life and clinical outcomes. While a large amount of research has been conducted to understand the complex pleiotropic functions and the molecular and cellular actions elicited by melatonin in various types of cancers, a few review reports have focused on osteosarcoma. Herein, we summarized the anti-osteosarcoma effects of melatonin and its underlying molecular mechanisms to illustrate the known significance of melatonin in osteosarcoma and to address cellular signaling pathways of melatonin in vitro and in animal models. Even in the same kind of osteosarcoma, melatonin has been sparingly investigated to counteract tumor growth, apoptosis, and metastasis through different mechanisms, depending on different cell lines. We highlighted the underlying mechanism of anti-osteosarcoma properties evoked by melatonin, including antioxidant activity, anti-proliferation, induction of apoptosis, and the inhibition of invasion and metastasis. Moreover, we discussed the drug synergy effects of the role of melatonin involved and the method to fortify the anti-cancer effects on osteosarcoma. As a potential therapeutic agent, melatonin is safe for children and adolescents and is a promising candidate for an adjuvant by reinforcing the therapeutic effects and abolishing the unwanted consequences of chemotherapies.

scholarly journals Clinical Value and Underlying Mechanisms of Upregulated LINC00485 in Hepatocellular Carcinoma

2021 ◽  
Vol 11 ◽  
Author(s):  
Xinyu Zhu ◽  
Yanlin Feng ◽  
Dingdong He ◽  
Zi Wang ◽  
Fangfang Huang ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Molecular Mechanisms ◽  
Operating Characteristic ◽  
Characteristic Curve ◽  
Underlying Mechanism ◽  
Clinical Value ◽  
Serum Samples ◽  
Underlying Mechanisms ◽  
Insight Into

AimsThis study aimed to reveal the functional role of LINC00485 in hepatocellular carcinoma (HCC).Materials & Methods210 serum samples from Zhongnan Hospital of Wuhan University were employed to evaluate clinical value of LINC00485. Bioinformatics analysis was adopted to explore its potential mechanisms.ResultsLINC00485 was confirmed to be upregulated in HCC tissues and serum samples. Survival analysis and receiver operating characteristic curve revealed its prognostic and diagnostic roles. The combination of serum LINC00485 with AFP can remarkably improve diagnostic ability of HCC. Exploration of the underlying mechanism demonstrated that LINC00485 might exert pro-oncogenic activity by LINC00485—three miRNAs—four mRNAs network.ConclusionsOur study unveiled that upregulated LINC00485 could act as a potential diagnostic and prognostic biomarker and provide a novel insight into the molecular mechanisms of LINC00485 in HCC pathogenesis.

Role of Resveratrol in Modulating microRNAs in Human Diseases: From Cancer to Inflammatory Disorder

2020 ◽  
Vol 28 (2) ◽  
pp. 360-376 ◽  
Author(s):  
Atefeh Amiri ◽  
Maryam Mahjoubin-Tehran ◽  
Zatollah Asemi ◽  
Alimohammad Shafiee ◽  
Sarah Hajighadimi ◽  
...  
Keyword(s):  
Molecular Mechanisms ◽  
Antioxidant Activities ◽  
Natural Compounds ◽  
Therapeutic Effects ◽  
Inflammatory Disorder ◽  
Inflammatory Disorders ◽  
Therapeutic Modalities ◽  
Anti Cancer ◽  
Current Therapies ◽  
Anti Inflammatory

: Cancer and inflammatory disorders are two important public health issues worldwide with significant socio.economic impacts. Despite several efforts, the current therapeutic platforms are associated with severe limitations. Therefore, developing new therapeutic strategies for the treatment of these diseases is a top priority. Besides current therapies, the utilization of natural compounds has emerged as a new horizon for the treatment of cancer and inflammatory disorders as well. Such natural compounds could be used either alone or in combination with the standard cancer therapeutic modalities such as chemotherapy, radiotherapy, and immunotherapy. Resveratrol is a polyphenolic compound that is found in grapes as well as other foods. It has been found that this medicinal agent displays a wide pharmacological spectrum, including anti-cancer, anti-inflammatory, anti-microbial, and antioxidant activities. Recently, clinical and pre-clinical studies have highlighted the anti-cancer and anti-inflammatory effects of resveratrol. Increasing evidence revealed that resveratrol exerts its therapeutic effects by targeting various cellular and molecular mechanisms. Among cellular and molecular targets that are modulated by resveratrol, microRNAs (miRNAs) have appeared as key targets. MiRNAs are short non-coding RNAs that act as epigenetic regulators. These molecules are involved in many processes that are involved in the initiation and progression of cancer and inflammatory disorders. Herein, we summarized various miRNAs that are directly/indirectly influenced by resveratrol in cancer and inflammatory disorders.

Pharmacology of Ivabradine and the Effect on Chronic Heart Failure

2019 ◽  
Vol 19 (21) ◽  
pp. 1878-1901 ◽  
Author(s):  
Yue Zhou ◽  
Jian Wang ◽  
Zhuo Meng ◽  
Shuang Zhou ◽  
Jiayu Peng ◽  
...  
Keyword(s):  
Heart Failure ◽  
Heart Rate ◽  
Chronic Heart Failure ◽  
Underlying Mechanism ◽  
Clinical Syndrome ◽  
Hcn Channels ◽  
Therapeutic Effects ◽  
Diastolic Depolarization ◽  
High Incidence ◽  
Spontaneous Phase

Chronic Heart Failure (CHF) is a complex clinical syndrome with a high incidence worldwide. Although various types of pharmacological and device therapies are available for CHF, the prognosis is not ideal, for which, the control of increased Heart Rate (HR) is critical. Recently, a bradycardic agent, ivabradine, is found to reduce HR by inhibiting the funny current (If). The underlying mechanism states that ivabradine can enter the Hyperpolarization-activated Cyclic Nucleotide-gated (HCN) channels and bind to the intracellular side, subsequently inhibiting the If. This phenomenon can prolong the slow spontaneous phase in the diastolic depolarization, and thus, reduce HR. The clinical trials demonstrated the significant effects of the drug on reducing HR and improving the symptoms of CHF with fewer adverse effects. This review primarily introduces the chemical features and pharmacological characteristics of ivabradine and the mechanism of treating CHF. Also, some expected therapeutic effects on different diseases were also concluded. However, ivabradine, as a typical If channel inhibitor, necessitates additional research to verify its pharmacological functions.

Nano-Curcumin Regulates p53 Phosphorylation and PAI-1 Expression during Bleomycin Induced Injury in Alveolar Basal Epithelial Cells

2020 ◽  
Vol 16 (1) ◽  
pp. 85-89
Author(s):  
Mahesh M. Gouda ◽  
Ashwini Prabhu ◽  
Varsha Reddy S.V. ◽  
Rafa Jahan ◽  
Yashodhar P. Bhandary
Keyword(s):  
Epithelial Cells ◽  
Lung Injury ◽  
Molecular Mechanisms ◽  
A549 Cells ◽  
Plasminogen Activator Inhibitor ◽  
Underlying Mechanism ◽  
Protective Role ◽  
Alveolar Epithelial Cells ◽  
Cellular Damage

Background: Bleomycin (BLM) is known to cause DNA damage in the Alveolar Epithelial Cells (AECs). It is reported that BLM is involved in the up-regulation of inflammatory molecules such as neutrophils, macrophages, chemokines and cytokines. The complex underlying mechanism for inflammation mediated progression of lung injury is still unclear. This investigation was designed to understand the molecular mechanisms associated with p53 mediated modulation of Plasminogen Activator Inhibitor-I (PAI-I) expression and its regulation by nano-curcumin formulation. Methods: A549 cells were treated with BLM to cause the cellular damage in vitro and commercially available nano-curcumin formulation was used as an intervention. Cytotoxic effect of nano-curcumin was analyzed using Methyl Thiazolyl Tetrazolium (MTT) assay. Protein expressions were analyzed using western blot to evaluate the p53 mediated changes in PAI-I expression. Results: Nano-curcumin showed cytotoxicity up to 88.5 % at a concentration of 20 μg/ml after 48 h of treatment. BLM exposure to the cells activated the phosphorylation of p53, which in turn increased PAII expression. Nano-curcumin treatment showed a protective role against phosphorylation of p53 and PAI-I expression, which in turn regulated the fibro-proliferative phase of injury induced by bleomycin. Conclusion: Nano-curcumin could be used as an effective intervention to regulate the severity of lung injury, apoptosis of AECs and fibro-proliferation during pulmonary injury.

scholarly journals Polyphenols Extracted from Shanxi-Aged Vinegar Inhibit Inflammation in LPS-Induced RAW264.7 Macrophages and ICR Mice via the Suppression of MAPK/NF-κB Pathway Activation

Molecules ◽  
2021 ◽  
Vol 26 (9) ◽  
pp. 2745
Author(s):  
Peng Du ◽  
Jia Song ◽  
Huirui Qiu ◽  
Haorui Liu ◽  
Li Zhang ◽  
...  
Keyword(s):  
Comprehensive Evaluation ◽  
Fermented Food ◽  
Gas Chromatography Mass Spectrometry ◽  
Inflammatory Factors ◽  
Therapeutic Effects ◽  
Inflammatory Stress ◽  
Icr Mice ◽  
Raw264.7 Macrophages ◽  
Pathway Activation ◽  
Anti Inflammatory

Shanxi-aged vinegar, a traditional Chinese grain-fermented food that is rich in polyphenols, has been shown to have therapeutic effects on a variety of diseases. However, there has been no comprehensive evaluation of the anti-inflammatory activity of polyphenols extracted from Shanxi-aged vinegar (SAVEP) to date. The anti-inflammatory activities of SAVEP, both in RAW 264.7 macrophages and mice, were extensively investigated for the potential application of SAVEP as a novel anti-inflammatory agent. In order to confirm the notion that polyphenols could improve inflammatory symptoms, SAVEP was firstly detected by gas chromatography mass spectrometry (GC-MS). In total, 19 polyphenols were detected, including 12 phenolic acids. The study further investigated the protective effect of SAVEP on lipopolysaccharide-induced inflammation in RAW264.7 macrophages and ICR mice. The results showed that compared with those of the model group, SAVEP could remarkably recover the inflammation of macrophage RAW264.7 and ICR mice. SAVEP can normalise the expression of related proteins via the suppression of MAPK/NF-κB pathway activation, inhibiting the expression of iNOS and COX-2 proteins, and consequently the production of inflammatory factors, thus alleviating inflammatory stress. These results suggest that SAVEP may have a potential function against inflammation.

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