scholarly journals Chinese Herbal Preparation SaiLuoTong Alleviates Brain Ischemia via Nrf2 Antioxidation Pathway–Dependent Cerebral Microvascular Protection

2021 ◽  
Vol 12 ◽  
Author(s):  
Xiao-Di Fan ◽  
Ming-Jiang Yao ◽  
Bin Yang ◽  
Xiao Han ◽  
Ye-Hao Zhang ◽  
...  

Stroke is one of the most devastating diseases worldwide. The Chinese herbal preparation SaiLuoTong (SLT) capsule showed outstanding therapeutic effects on stroke and its sequelae. The aim of this study was to further elucidate its therapeutic mechanism. We duplicated a permanent cerebral ischemia model in rats by MCAO and used SLT (33 and 16.5 mg/kg) to intervene. The results showed SLT dose dependently decreased infarction volumes, relieved neuron degeneration and loss, and ameliorated neurological functions, and the dose of 33 mg/kg had statistical significance (compared with the model group, p < 0.05); SLT of 33 mg/kg also significantly inhibited the elevation in brain water content and the loss in claudin-1 and occludin expressions; additionally, it significantly increased nucleus translocation of Nrf2, elevated the expression of HO-1, and raised the activity of SOD and content of GSH (compared with the model group, p < 0.05 or 0.01). These results testified SLT’s anti-brain ischemia effect and hint this effect may be related to the protection of brain microvascular endothelial cells (BMECs) that is dependent on the Nrf2 pathway. To further testify, we cultured hCMEC/D3 cells, duplicated OGD/R model to simulate ischemia, and used SLT (3.125, 6.25, and 12.5 mg/L) to treat. SLT dose dependently and significantly inhibited the drop in cell viabilities, and activated the Nrf2 pathway by facilitating Nrf2 nucleus translocation, and increasing HO-1 expression, SOD activity, and GSH content (compared with the model group, p < 0.05 or 0.01); last, the anti-OGD/R effects of SLT, including raising cell viabilities, inhibiting the elevation in dextran permeability, and preserving expressions of claudin-1 and occludin, were all abolished by Nrf2 siRNA interference. The in vitro experiment undoubtedly confirmed the direct protective effect of SLT on BMECs and the obligatory role of the Nrf2 pathway in it. Collectively, data of this study suggest that SLT’s therapeutic effect on brain ischemia is related to its Nrf2-dependent BMECs protection.

2021 ◽  
Author(s):  
Xiao-Di Fan ◽  
Ming-Jiang Yao ◽  
Bin Yang ◽  
Xiao Han ◽  
Guang-Rui Wang ◽  
...  

Abstract Background: Stroke is one of the most devastating diseases worldwide. Chinese herbal preparation SaiLuoTong capsule (SLT) showed outstanding therapeutic effects over stroke and its sequelae. This study is to elucidate the mechanism. Methods: We duplicated cerebral ischemia model in rats by permanent MCAO, and simulated ischemia injury in cultured hCMEC/D3 cells with oxygen and glucose deprivation/reoxia (OGD/R); we treated them with SLT. Brain infarction volumes and micromorphology were examined with TTC and HE stainings, respectively; neurological function injuries were valued with deficits scoring; brain water contents were measured with the wet-dry method; and expressions of claudin-1, occludin, Nrf2 and HO-1 were examined with western blot assay and immunohistochemstry or immunocytofluorescnce stainings; activities of SOD and contents of GSH were measured by colorimetric method; cell viabilities were measured by CCK8 method; cell monolayer permeabilities were assessed by FITC-dextran diffusion method. Results: SLT (33 mg/kg) significantly decreased infarction volumes, relieved neuron degenerations and neuron loss, and ameliorated neurological functions; SLT also significantly inhibited elevations in brain water content and decreases of claudin-1 and occludin expressions; additionally SLT significantly increased the nucleus translocation of Nrf2, elevated expression of HO-1, and raised activity of SOD and content of GSH (p<0.05 or 0.01, compared with the model group, in quantitative data). These testified SLT’s anti-stroke effect, and hint the possible key role of cerebral blood vascular endothelial cells (CBVEC) protection and Nrf2 pathway in SLT’s therapy. In hCMEC/D3 cells, SLT significantly inhibited the drop in cell viabilities; SLT also significantly facilitated the nucleus translocation of Nrf2, and increased the expression of HO-1, the activity of SOD, and the content of GSH (in comparison to the model group, p<0.05 or 0.01). Lastly, the anti-OGD/R effects of SLT in hCMEC/D3 cells, including raising cell viabilities, inhibiting the elevation in cell monolayer permeabilities, and preserving the expressions of claudin-1 and occludin, were all abolished by Nrf2 siRNA interference. These undoubtedly confirmed SLT’s protective effect on CBVEC and the obligatory role of Nrf2 pathway in it. Conclusion: SLT’s therapeutic effect on brain ischemia is related to its protection on CBVEC, which is dependent on the activation of Nrf2 pathway.


2021 ◽  
Vol 45 (2) ◽  
pp. 125-136
Author(s):  
Wang Fan ◽  
Fan Shendong ◽  
Cui Guangwei ◽  
Cheng Huaijin ◽  
Shi She ◽  
...  

Objectives: To study the mechanism of acupuncture manipulation (AM) based on the secretion function and morphological variation of fibroblasts in acupoint region.<br/> Methods: 40 rabbits were randomly divided to normal group (N), model group (M), needle retaining group (A), and acupuncture manipulation group (AM), each group consist of 10 rabbits. The animal model of Rabbits with Bacterium Endotoxin Induced Fever (BEIF) was established by intravenous injection of bacterial endotoxin. Groups A and AM were treated with 'Qu Chi'(LI11) acupuncture after modeling, and acupuncture manipulations were conducted in group AM. The serum heat factors IL-1β, IL-6, and TNF-α content were assayed conducted in group AM. The serum heat factors IL-1β, IL-6, and TNF-α content were assayed by Elisa after acupuncturet; the morphological changes of fibroblasts in acupoint area were observed by Vimentin staining; the fibroblasts of subcutaneous connective tissue in acupoint area were isolated and cultured in vitro, and the contents of PEG2, NO and ATP in supernatant were assayed.<br/> Results: There was no significant difference in fibroblasts cytomorphology among groups M, A, and N. Fibroblasts in group AM were stretched and aligned in almost one direction. Comparing with group N, the content of serum IL-1β, IL-6, and TNF-α was significantly higher in group M, along with higher NO and ATP content in the cell culture supernant; Comparing with group M, content of IL-6 and TNF-α was lower in group A, content of serum IL-1β, IL-6 and TNF-α was higher in group AM, along with higher PEG2, NO and ATP content in both groups, while group AM demonstrated more significant changes in the above indicators than group A.<br/> Conclusion: Acupuncture had therapeutic effects on BEIF rabbits, the application of acupuncture manipulation can further improve its therapeutic effects. The mechanism may be related to the influence on fibroblasts cytomorphology in acupoint region and facilitation of fibroblasts-derived PEG2, NO, and ATP, which together promote the acupoint vitality.


2020 ◽  
Vol 15 (3) ◽  
pp. 1934578X2090449
Author(s):  
Qi Zhou ◽  
Dong H. Yu ◽  
Na Zhang ◽  
Xiao Y. Wang ◽  
Ning Zhang ◽  
...  

Gouty arthritis (GA) is an inflammatory disease caused by the deposition of monosodium urate in the synovial membrane and cartilage due to a high concentration of uric acid in the blood. Dioscorea nipponica Makino is widely used in the clinic to treat GA. Total saponins are its main components and showed an anti-inflammatory effect on GA in a previous study. The mitogen-activated protein kinase (MAPK)-peroxisome proliferator-activated receptor γ (PPARγ) signaling pathway plays a key role during the onset of GA; however, little is known about its potential mechanism. Based on in vitro experiments, this study aims to determine the mechanism of total saponins from Dioscorea nipponica Makino (TDN) in treating GA by regulating the MAPK-PPARγ signaling pathway. Fibroblast-like synoviocytes were divided into 3 groups: the model group, which was given 10 µg/L IL-1β to induce proliferation; TDN group (10 µg/L IL-1β + 100 µg/L TDN); and indomethacin group (10 µg/L IL-1β + 100 µg/L indomethacin). Seventy-two hours after treatment, the real-time PCR method was used to detect the mRNA expression levels of extracellular signal regulated kinase 1/2 (ERK1/2), p-38, c-Jun N-terminal kinase (JNK), IKKα, c-Jun, MAPK phosphatase (MKP), vascular cell adhesion molecule 1 (VCAM1), intercellular adhesion molecule 1 (ICAM1), C-X-C motif chemokine ligand 1 (CXCL1), PPARγ, and Adipor2. The Western blot method was used to detect the protein expression of ERK1/2, p-ERK1/2, p-38, p-P38, JNK, p-JNK, IKKα, p-IKKα, c-Jun, p-c-Jun, MKP, p-MKP, VCAM1, ICAM1, CXCL1, PPARγ, and Adipor2. Compared with the model group, the TDN group displayed significantly increased mRNA expression of c-Jun, MKP, CXCL1, PPARγ, and Adipor2 and significantly decreased mRNA expression of ICAM1. Compared with the model group, the TDN group exhibited significantly increased protein expression of MKP and significantly decreased protein expression of p-ERK1/2, p-38, p-JNK, p-IKKα, p-c-Jun, VCAM1, ICAM1, and PPARγ. Our results indicated that TDN could treat GA by influencing the MAPK-PPARγ signaling pathway.


2013 ◽  
Vol 864-867 ◽  
pp. 472-476
Author(s):  
Nan Shen ◽  
Zhi Wei Li ◽  
Ying An ◽  
Xue Chen ◽  
Bo Xu ◽  
...  

Objective:To screen the Chinese herbal medicine with anti-pulmonary fibrosis, to provide reference for further study on anti-drug pulmonary fibrosis. Methods By complement lysis test, oleinic acid model of rats and paraquat model of mice were made as pulmonary fibrosis animal model to screen the medicine activity. Results in vitro, Cangzhu and Tinglizi had great significance in inhibition of RBC hemolysis; in vivo, compared with Control group, Hyp content of lung tissues in animal model groups had statistical significance; compared with model group, Hyp content of therapy groups had statistical significance, pathological lesion was reduced. Conclusion Extracts of Cangzhu and Tinglizi has certain resistance to pulmonary fibrosis activity.


2016 ◽  
Vol 11 ◽  
pp. S98-S105
Author(s):  
Tao Xu ◽  
Na Zhao ◽  
Jing-Dong Liu ◽  
Mo Xiao-Mei ◽  
Hui Zhang ◽  
...  

In this study, we observed the therapeutic effects of acupuncture and investigated the underlying molecular mechanisms by constructed a hypoxic-ischemic encephalopathy (HIE) animal model. In the electroacupuncture group, mTOR expression increased since 1d, and continued to rise till the 21st day. All of the differences were significantly (p<0.05 vs the model group). Meanwhile, mTOR expression was analyzed by Western blotting. There was statistical significance between the model group and the electroacupuncture group in the four time periods (p<0.05). The results provide evidence that electroacupuncture treatment protected cortical neurons against HIE-induced neuronal damage and degenerative changes in rats, which is in association with activation of mTOR both at the mRNA level and protein level. Therefore, electroacupuncture may become a potential therapeutic strategy for HIE of newborn. 


2021 ◽  
Vol 10 (3) ◽  
pp. 386
Author(s):  
Yuji Inagaki ◽  
Jun-ichi Kido ◽  
Yasufumi Nishikawa ◽  
Rie Kido ◽  
Eijiro Sakamoto ◽  
...  

Gan-Lu-Yin (GLY), a traditional Chinese herbal medicine, shows therapeutic effects on periodontitis, but that mechanism is not well known. This study aims to clarify the precise mechanism by investigating the inhibitory effects of GLY extracts on osteoclastogenesis in vitro and on bone resorption in periodontitis in vivo. RAW264.7 cells are cultured with soluble receptor activator of nuclear factor-kappa B (sRANKL) and GLY extracts (0.01–1.0 mg/mL), and stained for tartrate-resistant acid phosphatase (TRAP) to evaluate osteoclast differentiation. Experimental periodontitis is induced by placing a nylon ligature around the second maxillary molar in rats, and rats are administered GLY extracts (60 mg/kg) daily for 20 days. Their maxillae are collected on day 4 and 20, and the levels of alveolar bone resorption and osteoclast differentiation are estimated using micro-computed tomography (CT) and histological analysis, respectively. In RAW264.7 cells, GLY extracts significantly inhibit sRANKL-induced osteoclast differentiation at a concentration of more than 0.05 mg/mL. In experimental periodontitis, administering GLY extracts significantly decreases the number of TRAP-positive osteoclasts in the alveolar bone on day 4, and significantly inhibits the ligature-induced bone resorption on day 20. These results show that GLY extracts suppress bone resorption by inhibiting osteoclast differentiation in experimental periodontitis, suggesting that GLY extracts are potentially useful for oral care in periodontitis.


2001 ◽  
Vol 120 (5) ◽  
pp. A384-A384
Author(s):  
L MOLLISON ◽  
L TOTTEN ◽  
C HOVELL ◽  
K THAYNE ◽  
C CONNELLY ◽  
...  

1976 ◽  
Vol 35 (01) ◽  
pp. 049-056 ◽  
Author(s):  
Christian R Klimt ◽  
P. H Doub ◽  
Nancy H Doub

SummaryNumerous in vivo and in vitro experiments, investigating the inhibition of platelet aggregation and the prevention of experimentally-induced thrombosis, suggest that anti-platelet drugs, such as aspirin or the combination of aspirin and dipyridamole or sulfinpyrazone, may be effective anti-thrombotic agents in man. Since 1971, seven randomized prospective trials and two case-control studies have been referenced in the literature or are currently being conducted, which evaluate the effects of aspirin, sulfinpyrazone, or dipyridamole in combination with aspirin in the secondary prevention of myocardial infarction. A critical review of these trials indicates a range of evidence from no difference to a favorable trend that antiplatelet drugs may serve as anti-thrombotic agents in man. To date, a definitive answer concerning the therapeutic effects of these drugs in the secondary prevention of coronary heart disease is not available.


1989 ◽  
Vol 51 (5) ◽  
pp. 1003-1013 ◽  
Author(s):  
Hiromi KOBAYASHI ◽  
Masamitsu ISHII ◽  
Tsukasa TANII ◽  
Takeshi KOHNO ◽  
Toshio HAMADA

Sign in / Sign up

Export Citation Format

Share Document