scholarly journals A Study of the Protective Effect of Bushen Huoxue Prescription on Cerebral Microvascular Endothelia Based on Proteomics and Bioinformatics

2022 ◽  
Vol 2022 ◽  
pp. 1-13
Author(s):  
Shao-Yang Zhao ◽  
Huan-Huan Zhao ◽  
Yi-Ming Li ◽  
Bao-Hua Wang ◽  
Sai-Mei Li

Diabetic cognitive dysfunction is a serious complication of type 2 diabetes mellitus (T2DM), which can cause neurological and microvascular damage in the brain. At present, there is no effective treatment for this complication. Bushen Huoxue prescription (BSHX) is a newly formulated compound Chinese medicine containing 7 components. Previous research indicated that BSHX was neuroprotective against advanced glycosylation end product (AGE)-induced PC12 cell insult; however, the effect of BSHX on AGE-induced cerebral microvascular endothelia injury has not been studied. In the current research, we investigated the protective effects of BSHX on AGE-induced injury in bEnd.3 cells. Our findings revealed that BSHX could effectively protect bEnd.3 cells from apoptosis. Moreover, we analyzed the network regulation effect of BSHX on AGE-induced bEnd.3 cells injury at the proteomic level. The LC-MS/MS-based shotgun proteomics analysis showed BSHX negatively regulated multiple AGE-elicited proteins. Bioinformatics analysis revealed these differential proteins were involved in multiple processes, such as Foxo signaling pathway. Further molecular biology analysis confirmed that BSHX could downregulate the expression of FoxO1/3 protein and inhibit its nuclear transfer and inhibit the expression of downstream apoptotic protein Bim and the activation of caspase, so as to play a protective role in AGE-induced bEnd.3 injury. Taken together, these findings demonstrated the role of BSHX in the management of diabetic cerebral microangiopathy and provide some insights into the proteomics-guided pharmacological mechanism study of traditional Chinese Medicine.

2017 ◽  
Vol 42 (11) ◽  
pp. 1172-1178 ◽  
Author(s):  
Ana C. Colpo ◽  
Maria Eduarda de Lima ◽  
Marisol Maya-López ◽  
Hemerson Rosa ◽  
Cristina Márquez-Curiel ◽  
...  

Immobilization induces oxidative damage to the brain. Ilex paraguariensis extracts (Mate) and their major natural compound, chlorogenic acid (CGA), exert protective effects against reactive oxygen species formation. Here, the effects of Mate and CGA on oxidative damage induced by chronic immobilization stress (CIS) in the cortex, hippocampus, and striatum were investigated. For CIS, animals were immobilized for 6 h every day for 21 consecutive days. Rats received Mate or CGA by intragastric gavage 30 min before every restraint session. Endpoints of oxidative stress (levels of lipid peroxidation, protein carbonylation, and reduced (GSH) and oxidized (GSSG) forms of glutathione) were evaluated following CIS. While CIS increased oxidized lipid and carbonyl levels in all brain regions, CGA (and Mate to a lesser extent) attenuated lipid and protein oxidation as compared with control groups. GSH/GSSG balance showed a tendency to increase in all regions in response to stress and antioxidants. Taken together, our results support a protective role of dietary antioxidants against the neuronal consequences of stress.


Antioxidants ◽  
2021 ◽  
Vol 10 (3) ◽  
pp. 341 ◽  
Author(s):  
Hyun-Su Lee ◽  
Gil-Saeng Jeong

Since hypoxia-induced neurotoxicity is one of the major causes of neurodegenerative disorders, including the Alzheimer’s disease, continuous efforts to find a novel antioxidant from natural products are required for public health. 6,7,4′-trihydroxyflavanone (THF), isolated from Dalbergia odorifera, has been shown to inhibit osteoclast formation and have an antibacterial activity. However, no evidence has reported whether THF has a protective role against hypoxia-induced neurotoxicity. In this study, we found that THF is not cytotoxic, but pre-treatment with THF has a cytoprotective effect on CoCl2-induced hypoxia by restoring the expression of anti-apoptotic proteins in SH-SY5y cells. In addition, pre-treatment with THF suppressed CoCl2-induced hypoxia-related genes including HIF1α, p53, VEGF, and GLUT1 at the mRNA and protein levels. Pre-treatment with THF also attenuated the oxidative stress occurred by CoCl2-induced hypoxia by preserving antioxidant proteins, including SOD and CAT. We revealed that treatment with THF promotes HO-1 expression through Nrf2 nuclear translocation. An inhibitor assay using tin protoporphyrin IX (SnPP) confirmed that the enhancement of HO-1 by pre-treatment with THF protects SH-SY5y cells from CoCl2-induced neurotoxicity under hypoxic conditions. Our results demonstrate the advantageous effects of THF against hypoxia-induced neurotoxicity through the HO-1/Nrf2 signaling pathway and provide a therapeutic insight for neurodegenerative disorders.


Author(s):  
Mairi Pucci ◽  
Diletta Onorato ◽  
Giovanni Carpene ◽  
Brandon Michael Henry ◽  
Fabian Sanchis-Gomar ◽  
...  

AbstractSevere acute respiratory syndrome coronavirus 2 has spread rapidly throughout the world, becoming an overwhelming global health emergency. The array of injuries caused by this virus is broad and not limited to the respiratory system, but encompassing also extensive endothelial and systemic tissue damage. Since statins effectively improve endothelial function, these drugs may have beneficial effects in patients with coronavirus disease 2019 (COVID-19). Therefore, this investigation aimed to provide an updated overview on the interplay between statins and COVID-19, with particular focus on their potentially protective role against progression toward severe or critical illness and death. A systematic electronic search was performed in Scopus and PubMed up to present time. Data on statins use and COVID-19 outcomes especially in studies performed in Europe and North America were extracted and pooled. A total of seven studies met our inclusion criteria, totaling 2,398 patients (1,075 taking statins, i.e., 44.8%). Overall, statin usage in Western patients hospitalized with COVID-19 was associated with nearly 40% lower odds of progressing toward severe illness or death (odds ratio: 0.59; 95% confidence interval: 0.35–0.99). After excluding studies in which statin therapy was started during hospital admission, the beneficial effect of these drugs was magnified (odds ratio: 0.51; 95% confidence interval: 0.41–0.64). In conclusion, although randomized trials would be necessary to confirm these preliminary findings, current evidence would support a favorable effect of statins as adjuvant therapy in patients with COVID-19. Irrespective of these considerations, suspension of statin therapy seems highly unadvisable in COVID-19 patients.


2009 ◽  
Vol 25 (3) ◽  
pp. 183-188 ◽  
Author(s):  
L Alpsoy ◽  
G Agar ◽  
M Ikbal

In this study, we aimed to evaluate the effect of vitamins A, C, and E against aflatoxin B1 (AFB1) on blood cultures in relation to induction of sister chromatid exchange (SCE). The results indicated genotoxic and mutagenic damage in cultured human lymphocytes exposed to AFB1. The results showed that 5 μM concentration of AFB1 increased SCE. When vitamins A, C, and E were added to AFB1, the frequency of SCE decreased. These results suggest that vitamins A, C, and E could effectively inhibit AFB1-induced SCE, which may partially responsible for its mutagenic effect of AFB1. Besides, the protective effect of vitamins A, C, and E against AFB1 was increased in a dose-dependent manner (i.e., as the doses increased, their protective effects also increased). There was a significant decrease in the SCE frequency in AFB1-treated group compared with the groups receiving AFB1 and also vitamins A, C, and E. The most effective concentration was 100 microM vitamin C, and the lowest effective concentration was 0.5 microM vitamin A. Vitamin C has the most effective concentration of 100 μM, and vitamin A has the lowest effective concentration of 0.5 μM. The order of the decreasing effect of the SCE frequency of vitamins was as follows: vitamin C > vitamin E > vitamin A.


2021 ◽  
Vol 11 ◽  
Author(s):  
Yu-qiang Pei ◽  
Yong-qiu Zheng ◽  
Yao-dong Ding ◽  
Qi-xiang Xu ◽  
Di Cao ◽  
...  

Background: Triptolide (TP), a naturally derived compound from Tripterygium wilfordii, has been proven effective in protecting against cardiovascular system, but the molecular mechanisms underlying its protective effects are poorly understood. In the current study, we sought to test the potential protective role of TP in the regulation of vascular calcification in a rat model and explore whether TP attenuates medial vascular calcification by upregulating miRNA-204.Methods: Vitamin D3 plus nicotine (VDN) was used to induce a vascular calcification (VC) model of rat aorta. Von Kossa and Hematoxylin-Eosin staining were applied to assess the degree of calcification of rat aortas. Calcium content and alkaline phosphatase activity were measured. Quantitative reverse-transcription polymerase chain reaction (qRT-PCR) was applied to quantify miRNA-204 expression. The localization of runt-related transcription factor-2 (RUNX2) and bone morphogenetic protein-2 (BMP2) expressions were detected by immunohistochemistry and western blotting.Results: Administration of TP greatly reduced vascular calcification in a dose-dependent manner compared with VC controls. The increase in ALP activity and calcium content was ameliorated by TP. Moreover, protein expression levels of BMP2 and RUNX2 were significantly reduced in calcified aortas. MiRNA-204 expression was increased in the TP-treated groups compared with VC controls and the effects of TP were reversed by the intravenous injection of miRNA-204-interfering lentivirus. However, the miRNA-204-overexpressing lentivirus had no additional effects on ALP activity, calcium content, BMP2 and RUNX2 expressions compared with those from TP group.Conclusion: TP inhibited BMP2 and RUNX2 expression and attenuated vascular calcification via upregulating the level of miRNA-204. TP appears to be a potential new therapeutic option for treating vascular calcification.


2020 ◽  
Vol 14 (1) ◽  
pp. 25-32
Author(s):  
Adewuyi Hassan Abdulsalam ◽  
◽  
Muhammad L. Hadiza ◽  
Onukogu Stella Chiamaka ◽  
Ibrahim Jonathan ◽  
...  

Background: Leptadenia hastata (L. Hastata) is a plant used for various diseases in Nigeria. This study evaluated the protective effects of L. hastate on the haematological and biochemical alterations in adrenaline-induced hypertensive rats. Methods: Twenty-five rats were divided equally into five groups (A-E). Groups A-D were given 0.5 mg/kg adrenaline, groups A and B were treated with 100 and 200 mg/kg the extract of L. Hastata, respectively, while groups C and D were treated with 5 mg/kg amlodipine (standard control) and normal saline (untreated control), respectively. Group E were given distilled water (normal controls). The adrenaline was injected intraperitoneally while the extract was given orally once daily for seven days. Results: Treatment with 100 and 200 mg/kg of the extract significantly reduced the elevated serum albumin, ALP, ALT, AST, chloride, sodium and creatinine, cholesterol and LDL concentrations compared with the untreated hypertensive rats. The bicarbonate level, WBC and RBC counts, mean cell hemoglobin and packed cell value were higher in rats treated with the extract compared with the untreated hypertensive rats. The mean cell value, HDL, triglyceride, urea, potassium, total and direct bilirubin concentrations in experimental groups were not significantly different from those in the controls (P<0.05). Conclusion: Our results suggest that treatment of the hypertensive rats with the extract of L. Hastata protects against renal, hepatic and cardiac damages, thus it could be considered as a natural anti-hypertensive agent. Further studies are required to identify the bioactive constituents and the mechanism(s) of action.


2019 ◽  
Vol 10 (4) ◽  
pp. 2755-2764
Author(s):  
Sumathi Rajamani ◽  
Gobinath Kalyanasundaram ◽  
Tamizharasi Sengodan ◽  
Sivakumar Thangavelu ◽  
Nikhitha K Shanmukhan ◽  
...  

Cisplatin (Cis-Diammineplatinum (II) dichloride/CIS) is one of the most potent chemotherapeutic agents widely used in treatment of various cancers. Naringenin (NAR), a natural flavonoid, protect against CIS-induced injury in rats without hampering CIS beneficial cytotoxic activity. Even though NAR exhibits therapeutic potency, clinical evolution of the molecule is embarrassed because of very less aqueous solubility which corresponds to low availability at the site of the tumor. In our former analysis, nanosuspension of naringenin (NARNS) was developed by the method of high-pressure homogenization. The study had been continued to evaluate the protective role of D-α-Tocopheryl polyethylene glycol succinate (TPGS) coated NARNS, against oxidative stress-induced hepato and nephrotoxicity in male Wistar rats upon CIS treatment. Induction of acute hepato and neprotoxicity was done by intraperitoneal injection (i.p) injection of CIS (7 mg/kg of body weight) and administration of NAR and NARNS. Administration of NARNS virtually suppressed CIS-induced and liver injury evidenced by a reduction of lipid peroxidation level, blood urea nitrogen, serum uric acid, creatinine and elevated enzymatic antioxidant activities of superoxide dismutase, catalase, and glutathione peroxidase in rats liver tissue. Histological studies substantiated the biochemical parameters. The study suggests that NARNS has strong hepato and nephroprotective effect compared to NAR.


2021 ◽  
Vol 12 ◽  
Author(s):  
Pasquale Filannino ◽  
Raffaella Di Cagno ◽  
Olimpia Vincentini ◽  
Daniela Pinto ◽  
Andrea Polo ◽  
...  

We compared raw bee-collected pollen (Raw-BCP), spontaneously fermented BCP (Unstarted-BCP), and BCP fermented with selected microbial starters (Started-BCP) to deepen whether fermentation may favorably affect the nutrients bioaccessibility and functional features of BCP. Under in vitro gastrointestinal batches, the highest serum-availability of phenolic compounds was found in Started-BCP, highlighting the positive effect exerted by selected microbial starters. The same effect was not found in spontaneously fermented BCP. In colon adenocarcinoma cell line-2 (Caco-2) cells stressed by a pro-inflammatory stimulus, the treatment with Started-BCP halted the increase of pro-inflammatory mediator’s level. Started-BCP counteracted efficiently the deleterious effects of inflammatory stimuli on the integrity of the Caco-2 cells monolayer and its barrier function. Started-BCP successfully counteracted the H2O2-induced intracellular accumulation of reactive oxygen species (ROS) in Caco-2 cells. A protective role against lipopolysaccharide (LPS)-induced inflammation was exerted by Started-BCP in human keratinocytes. The same protective effects on Caco-2 and keratinocyte cell lines were negligible after treatments with Raw-BCP or Unstarted-BCP.


2020 ◽  
Author(s):  
Zhiqiang Liu ◽  
Bolong Wang

Abstract Background: Jianghuang (JH) is a popular ingredient in blood-regulating traditional Chinese Medicine (TCM) that could be effective for the treatment of various diseases. We demonstrate the compatibility laws and system pharmacological mechanisms of the key formula containing JH by leveraging data mining of bioinformatics databases.Material/Methods: The compatibility laws of blood-regulating formulae containing JH from the Chinese Traditional Medicine Formula Dictionary were analyzed using a generalized rule induction (GRI) algorithm implemented. The putative target gene and miRNA were retrieved via a combination of the Arrowsmith knowledge discovery tool and FunRich 3.1.3. System pharmacological mechanisms are traced by their protein-protein interaction (PPI) network, and the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis was conducted using Uniprot, the Human Protein Atlas (HPA), STRING 11.0, and KOBAS 3.0.Results: We found that the JH-CX-DG formula (Ligusticum chuanxiong-Angelica sinensis) could represent a key formula containing JH in blood-regulating TCM formulae. The JH-CX-DG formula was observed to directly target AKT, TLR4, caspase-3, PI3K, mTOR, p38 MAPK, VEGF, iNOS, Nrf2, BDNF, NF-κB, Bcl-2, and Bax 13 targets and regulate targets through 13 miRNA. The PPI network and KEGG pathway enrichment analysis showed that the JH-CX-DG formula possess potential pharmacological effects including anti-inflammatory, improving microcirculation, and anti-tumor through the regulation of multiple pathways including PI3K/Akt, MAPK, Toll-like receptor, T cell receptor, EGFR, VEGFR, Apoptosis, HIF-1 (p < 0.05).Conclusion: The JH-CX-DG formula can exert beneficial pharmacological effects through multi-target and multi-pathway interactions. It can be effectively administered for the treatment of inflammatory diseases, microcirculation disorders, cardiovascular disease, and cancer. We found a new effective drug formula through analyzing the compatibility law and systemic pharmacological mechanism of JH. Our study provides a theoretical basis and directions for subsequent research on the JH-CX-DG formula.


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