scholarly journals Systems Pharmacology-Dissection of the Molecular Mechanisms of Dragon’s Blood in Improving Ischemic Stroke Prognosis

2020 ◽  
Vol 2020 ◽  
pp. 1-14
Author(s):  
Meng Jiang ◽  
Xing Su ◽  
Jianling Liu ◽  
Chunli Zheng ◽  
Xiaogang Li
Keyword(s):  
Ischemic Stroke ◽  
Cell Survival ◽  
Pc12 Cells ◽  
Molecular Mechanisms ◽  
Active Compounds ◽  
Dragon’S Blood ◽  
Anti Inflammatory ◽  
Main Component ◽  
Loureirin B ◽  
Anti Inflammation

Ethnopharmacological Relevance. Dragon’s blood (DB) is a widely used traditional Chinese medicine that has many pharmacological effects, including antiplatelet aggregation, promoting epidermal growth, and anti-inflammatory and antioxidant activities. The main component of Longxuetongluo capsule and Dragon’s blood dropping pills is DB’s standard phenolic extract, which was used for ischemic stroke prognosis in China. Aim of Study. To dissect the molecular mechanisms of Dragon’s blood (DB) in improving ischemic stroke prognosis. Materials and Methods. (1) Based on system-pharmacology platform, the potential active compounds of DB are screened out according to ADME. (2) The ischemic stroke-related targets are predicted by utilizing these active compounds as probes, mapping the targets to the CTD database to establish a molecular-target-disease network. (3) To analyze the mechanism of DB treatment for the prognosis of ischemic stroke, we used the Metascape and DAVID databases to construct “ischemic stroke pathways”. (4) PC12 cells were used to explore the protective effect of loureirin B on oxygen-glucose deprivation/reperfusion (OGD/R) injury, and BV-2 cells were used to determine the anti-inflammation effect of 4′,7-dihydroxyflavone. Results. Finally, we obtained 38 active compounds and 58 stroke-related targets. Network and pathway analysis indicate that DB is effective in the treatment of ischemic stroke by enhancing cell survival and inhibiting inflammatory and antiplatelet activation. In in vitro experiments, the main component loureirin B promoted the expression of HO-1 and Bcl-2 via positive regulation of PI3K/AKT/CREB and Nrf2 signaling pathways in PC12 cells against OGD/R damage. And the anti-inflammatory activity of 4′,7-dihydroxyflavone was related to the inhibition of COX-2, TNF-α, and IL-6 in LPS-induced BV-2 cells. Conclusions. In our study, the results illustrated that DB in improving ischemic stroke prognosis may involve enhancing cell survival and antioxidant, anti-inflammation, and antiplatelet activities.

scholarly journals Xiaoxuming Decoction: A Traditional Herbal Recipe for Stroke With Emerging Therapeutic Mechanisms

2021 ◽  
Vol 12 ◽  
Author(s):  
Qian Zhang ◽  
Yue Wang ◽  
Aiwen Chen ◽  
Xinwei Huang ◽  
Qianyu Dong ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
Molecular Mechanisms ◽  
Neurovascular Unit ◽  
Alternative Therapy ◽  
Acute Stage ◽  
Therapeutic Effects ◽  
Active Compounds ◽  
Endovascular Thrombectomy ◽  
Therapeutic Mechanisms ◽  
New Perspective

Xiaoxuming decoction (XXMD) has been traditionally used to manage stroke though debates on its clinical efficacy were present in the history. Till nowadays, it is still one of the most commonly used herbal recipes for stroke. One of the reasons is that a decent proportion of ischemic stroke patients still have residue symptoms even after thrombolysis with rt-PA or endovascular thrombectomy. Numerous clinical studies have shown that XXMD is an effective alternative therapy not only at the acute stage, but also at the chronic sequelae stage of ischemic stroke. Modern techniques have isolated groups of compounds from XXMD which have shown therapeutic effects, such as dilating blood vessels, inhibiting thrombosis, suppressing oxidative stress, attenuating nitric oxide induced damage, protecting the blood brain barrier and the neurovascular unit. However, which of the active compounds is responsible for its therapeutic effects is still unknown. Emerging studies have screened and tested these active compounds aiming to find individual compounds that can be used as drugs to treat stroke. The present study summarized both clinical evidence of XXMD in managing stroke and experimental evidence on its molecular mechanisms that have been reported recently using advanced techniques. A new perspective has also been discussed with an aim to provide new targets that can be used for screening active compounds from XXMD.

scholarly journals Protective Effect ofPunica granatumL. against Serum/Glucose Deprivation-Induced PC12 Cells Injury

2013 ◽  
Vol 2013 ◽  
pp. 1-9 ◽  
Author(s):  
Fatemeh Forouzanfar ◽  
Amir Afkhami Goli ◽  
Elham Asadpour ◽  
Ahmad Ghorbani ◽  
Hamid Reza Sadeghnia
Keyword(s):  
Dna Damage ◽  
Cell Viability ◽  
Pc12 Cells ◽  
Molecular Mechanisms ◽  
Neuronal Damage ◽  
Glucose Deprivation ◽  
Serum Glucose ◽  
Pomegranate Juice ◽  
Significant Difference ◽  
Anti Inflammatory

The discovery and development of natural products with potent antioxidant, anti-inflammatory, and antiapoptotic properties have been one of the most interesting and promising approaches in the search for the treatment of many neurodegenerative diseases including ischemic stroke. Serum/glucose deprivation (SGD) has served as an excellent in vitro model for the understanding of the molecular mechanisms of neuronal damage during ischemia and for the development of neuroprotective drugs against ischemia-induced brain injury. Recent studies suggested that pomegranate (Punica granatumL.) or its active constituents exert pharmacological actions such as antioxidant, anti-inflammatory, and neuroprotective properties. Therefore, in this study we investigated the possible protective effects of different extracts of pomegranate against SGD-induced PC12 cells injury. Initially, the cells were pretreated with different concentrations of pulp hydroalcoholic extract (PHE), pulp aqueous extract (PAE) and pomegranate juice (PJ) for 2 h and then deprived of serum/glucose (SGD) for 6 and 12 h. SGD caused a significant reduction in cell viability (measured by the MTT assay) after 6 and 12 h, as compared with control cells (P<0.001). Pretreatment with PHE, PAE, and PJ significantly and concentration-dependently increased cell viability following SGD insult for 6 and 12 h. A significant increase in DNA damage (measured by the comet assay) was seen in nuclei of cells following SGD for 12 h (P<0.001). In control groups, no significant difference was seen in DNA damage between PHE, PAE, and PJ-pretreated and vehicle-pretreated PC12 cells (P>0.05). PHE, PAE, and PJ pretreatment resulted in a significant decrease in DNA damage following ischemic insult (P<0.001). This suppression of DNA damage by PHE, PAE and PJ was found to be concentration dependent. These data indicate that there is a cytoprotective property in PHE, PAE, and PJ under SGD condition in PC12 cells, suggesting that pomegranate has the potential to be used as a new therapeutic strategy for neurodegenerative disorders.

Abstract WP324: Blocking Pro-Inflammatory Platelet-Activating Factor-Receptors and Activating Cell-Survival Pathways Leads to Neuroprotection After Experimental Ischemic Stroke

Stroke ◽  
2020 ◽  
Vol 51 (Suppl_1) ◽  
Author(s):  
Madigan M Reid ◽  
Eric J Knott ◽  
Ludmila Belayev ◽  
Larissa Khoutorova ◽  
Nicolas G Bazan
Keyword(s):  
Ischemic Stroke ◽  
Cell Survival ◽  
Molecular Mechanisms ◽  
Neuroprotective Effect ◽  
Platelet Activating Factor ◽  
Thromboxane B2 ◽  
Negative Ion ◽  
Neuroprotective Activity ◽  
Inflammatory Signaling ◽  
Survival Pathways

Objective: Acute ischemic stroke triggers complex neurovascular, neuroinflammatory, and synaptic alterations. Our study tested the prediction that blocking platelet-activating factor-receptors (PAF-Rs)-induced pro-inflammatory signaling plus administering a docosahexaenoic acid (DHA) after middle cerebral artery occlusion (MCAo) would lead to sustained neurological recovery. We used two molecules: a) LAU-0901, an antagonist of the PAF-R that blocks pro-inflammatory signaling and that has shown promising efficacy in a stroke model; and b) DHA, which activates cell-survival pathways and possesses potent anti-inflammatory and neuroprotective activity in the brain. Methods: Sprague-Dawley rats received 2h MCAo. Behavior was evaluated at 3, 4 and 24h. Treatments: LAU-0901 (i.p. 30mg/kg, 2h after onset of stroke), DHA (i.v. 5mg/kg, 3h after onset of stroke), LAU-0901+DHA and vehicle. On day 1, following lipids were extracted: Prostaglandins (PGE2, PGF2-α, 6-keto-PGF1a), Hydroxyoctadecadienoic acid (HODE), 11-dehydro-thromboxane B2, Thromboxane B2 (TXB2), 12-hydroxyeicosatetraenoic acid (12-HETE). Lipidomic analysis was conducted using LC-ESI-MS/MS in negative ion mode and results were normalized to total sample protein. Results: LAU-0901 and DHA treatments alone improved behavioral scores compared to vehicle groups by 30-35%. The neuroprotective effect was enhanced using the LAU-0901+DHA, which resulted in improved behavioral scores up to 47% on day 1. Expression of 12-HETE (proinflammatory marker) was reduced by DHA, LAU, LAU+DHA (83, 67, 72%, respectively). Conclusion: It is remarkable that there is differential expression of eicosanoid pathways and of other lipid mediators, some of them are proinflammatory, and other are modulators of neuroinflammation in the ipsilateral stroke side. We are currently exploring the detailed molecular mechanisms involved in the combination treatment of the PAF-R antagonist, LAU-0901, plus DHA.

scholarly journals CURCUMIN FOR ALZHEIMER’S DISEASE (AD) POTENTIAL TREATMENT

Jurnal BIOMA ◽  
2017 ◽  
Vol 13 (2) ◽  
pp. 17-21
Author(s):  
Dias Rima Sutiono ◽  
Steven Iasmartua
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Neurodegenerative Disease ◽  
Cholesterol Level ◽  
Molecular Mechanisms ◽  
Metal Chelation ◽  
Potential Treatment ◽  
Anti Oxidant ◽  
Anti Inflammatory ◽  
Anti Inflammation

Various studies had been conducted regarding the effect of curcumin on AD patients, thus, many of the studies had suggested that curcumin had the potential to prevent and treat AD through several molecular mechanisms including act as anti-inflammatory, anti-oxidant, binding the Aβ plaques, metal chelation, and lowering cholesterol level. One of the prominent characteristics of this neurodegenerative disease is shown by the presence of beta amyloids plaques (Aβ) and inflammation inside the patient’s brains; and as mention above curcumin had shown its capabilities in inhibiting the Aβ plaques and act as an anti-inflammation agent.

scholarly journals Experimental evidence and network pharmacology-based analysis reveal the molecular mechanism of Tongxinluo capsule administered in coronary heart diseases

2020 ◽  
Vol 40 (10) ◽  
Author(s):  
Guode Li ◽  
Qingbo Xu ◽  
Kedong Han ◽  
Wenhe Yan ◽  
Chaopei Huang
Keyword(s):  
Fluid Shear Stress ◽  
Heart Diseases ◽  
Underlying Mechanism ◽  
Mendelian Inheritance ◽  
Network Pharmacology ◽  
Molecular Evidence ◽  
Active Compounds ◽  
Coronary Heart Diseases ◽  
Anti Inflammatory ◽  
Main Component

Abstract Background: Tongxinluo (TXL) capsule, a polypharmacy derived from traditional Chinese medicine (TCM), has been widely used in coronary heart disease (CHD), while the underlying mechanism of TXL capsule is still unclear. The present study aimed at investigating the underlying mechanism of TXL acting on CHD patients and providing substantial evidence in molecular evidence by means of a network pharmacological analysis. Method: Active compounds and targeted genes of TXL were retrieved from TCM systems pharmacology (TCMSP) and TCM integrative database (TCMID). CHD and coronary artery disease were treated as search queries in GeneCards and Online Mendelian Inheritance in Man (OMIM) databases to obtain disease-related genes. Visualization of disease–targets network was performed under administration of Cytoscape software. Besides, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were administered. H9c2 cells were used to validate the predicted results in cardiomyocytes/reoxygenation model, and anti-inflammatory ability was examined. Results: A network of a total of 212 nodes and 1016 edges was obtained. Peptide and ubiquitin-like protein ligase binding occupied a leading position of GO enrichment. For KEGG analysis, fluid shear stress and atherosclerosis, as well as inflammation-related pathways were enriched. Cellular validation revealed the anti-inflammatory effect of β-sitosterol, eriodictyol, odoricarpin, and tirucallol as active compounds of TXL. Conclusion: Our study provided substantial molecular evidence that TXL capsule possessed the characteristics of multitargets with safe profile, and the main component is capable of regulating cytokine level in CHD patients.

scholarly journals CURRENT DEVELOPMENTS ON ANTI-INFLAMMATORY NATURAL MEDICINES

2018 ◽  
Vol 11 (8) ◽  
pp. 61 ◽  
Author(s):  
Sayanna Das ◽  
Sudip Kumar Mandal
Keyword(s):  
Natural Products ◽  
Molecular Mechanisms ◽  
Biological Activities ◽  
Marine Sponges ◽  
The Novel ◽  
Plant Products ◽  
Inflammatory Drugs ◽  
Anti Inflammatory ◽  
Natural Medicines ◽  
Anti Inflammation

New anti-inflammatory substances are still vitally necessary due to intolerable side effects of the marketed anti-inflammatory drugs; however, the search for the novel entity against inflammation is challenging because of the complexity of the inflammatory process and its role in host defense to infections. Nature is the source of remedies for the mankind. Among the different biological activities of natural products that have been published till date, anti-inflammation is one of the most reported effects. In this review, we have discussed the current (2009–2018) information of some single natural products (quercetin, parthenolide, resveratrol, curcumin, cucurbitacin, capsicin, 1,8-cineole, bromelain, boswellic acid, lyprinol, and coumarin), plant products (garlic, ginger, papaya, blueberry, aloe, broccoli, olive, and rosemary), and non-plant products (marine sponges, mushrooms, and honey) having anti-inflammatory effects. Current information is mainly based on the molecular mechanisms of the above-mentioned products.

Irisin Ameliorates Hypoxia/Reoxygenation-Induced Inflammation and Apoptosis in PC12 Cells by Inhibiting TLR4/MYD88 Signaling Pathway

2019 ◽  
Vol 17 (3) ◽  
pp. 329-336
Author(s):  
Wang Jinli ◽  
Xu Fenfen ◽  
Zheng Yuan ◽  
Cheng Xu ◽  
Zhang Piaopiao ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
Signaling Pathway ◽  
Pc12 Cells ◽  
Major Complication ◽  
Lactic Dehydrogenase ◽  
Dependent Manner ◽  
Cerebral Ischemic Stroke ◽  
Cerebral Ischemic ◽  
Myd88 Signaling ◽  
Hypoxia Reoxygenation

Cardiovascular disease including cerebral ischemic stroke is the major complication that increases the morbidity and mortality in patients with diabetes mellitus as much as four times. It has been well established that irisin, with its ability to regulate glucose and lipid homeostasis as well as anti-inflammatory and anti-apoptotic properties, has been widely examined for its therapeutic potentials in managing metabolic disorders. However, the mechanism of irisin in the regulation of cerebral ischemic stroke remains unclear. Using PC12 cells as a model, we have shown that hypoxia/reoxygenation inhibits cell viability and increases lactic dehydrogenase. Irisin, in a dose-dependent manner, reversed these changes. The increase in inflammatory mediators (IL-1β, IL-6, and TNF-α) by hypoxia/reoxygenation was reversed by irisin. Furthermore, the cell apoptosis promoted by hypoxia/reoxygenation was also inhibited by irisin. Irisin suppressed TLR4/MyD88 signaling pathway leading to amelioration of inflammation and apoptosis in PC12 cells. Thus, inhibition of TLR4/MyD88 signaling pathway via irisin could be an important mechanism in the regulation of hypoxia/reoxygenation-induced inflammation and apoptosis in PC12 cells.

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.

scholarly journals Protective Effect of Psoralea corylifolia L. Seed Extract against Palmitate-Induced Neuronal Apoptosis in PC12 Cells

2016 ◽  
Vol 2016 ◽  
pp. 1-11 ◽  
Author(s):  
Yunkyoung Lee ◽  
Hee-Sook Jun ◽  
Yoon Sin Oh
Keyword(s):  
Pc12 Cells ◽  
Molecular Mechanisms ◽  
Neuronal Cell ◽  
Marker Genes ◽  
Heme Oxygenase 1 ◽  
Mrna Levels ◽  
Protective Effects ◽  
Psoralea Corylifolia ◽  
Antioxidant Genes ◽  
Bax Protein

The extract of Psoralea corylifolia seeds (PCE) has been widely used as a herbal medicine because of its beneficial effect on human health. In this study, we investigated the protective effects and molecular mechanisms of PCE on palmitate- (PA-) induced toxicity in PC12 cells, a neuron-like cell line. PCE significantly increased cell viability in PA-treated PC12 cells and showed antiapoptotic effects, as evidenced by decreased expression of cleaved caspase-3, cleaved poly(ADP-ribose) polymerase, and bax protein as well as increased expression of bcl-2 protein. In addition, PCE treatment reduced PA-induced reactive oxygen species production and upregulated mRNA levels of antioxidant genes such as nuclear factor (erythroid-derived 2)-like 2 and heme oxygenase 1. Moreover, PCE treatment recovered the expression of autophagy marker genes such as beclin-1 and p62, which was decreased by PA treatment. Treatment with isopsoralen, one of the major components of PCE extract, also recovered the expression of autophagy marker genes and reduced PA-induced apoptosis. In conclusion, PCE exerts protective effects against lipotoxicity via its antioxidant function, and this effect is mediated by activation of autophagy. PCE might be a potential pharmacological agent to protect against neuronal cell injury caused by oxidative stress or lipotoxicity.

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