Neuroprotective Mechanism of BNG-1 against Focal Cerebral Ischemia: A Neuroimaging and Neurotrophin Study

Chi, Nai‐Fang; Liu, Ho Ling; Yang, Jing‐Tang; Lin, Jainn-Jim; Liao, Shu Li; Peng, Bo; Lee, Yen Tung; Lee, Tsong Hai

doi:10.1371/journal.pone.0114909

Cited by 6 publications

(7 citation statements)

References 41 publications

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“…The BNG-1 has neuroprotective effect against ischemic injury which can be seen in animals receiving BNG-1 before as well as after middle cerebral artery (MCA) occlusion and has anti-thrombotic activity to inhibit arachidonic acid-induced platelet aggregation in vitro and prolong bleeding time in mice in vivo 20 . Our previous study using 7T MR neuroimaging and neurotrophin analyses in rat MCA occlusion model 22 found the neuroprotective effect of BNG-1 may act through recovery of cerebral hemodynamics, decrease of infarction size and edema, reduction of postischemic hyperperfusion injury and recovery of neurotrophn-3 and brain-derived neurotrophic factor.…”

Section: Introductionmentioning

confidence: 98%

Improved thrombolytic effect with focused ultrasound and neuroprotective agent against acute carotid artery thrombosis in rat

Lee

Yeh

Tsai

et al. 2017

Sci Rep

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Combination therapy with focused ultrasound (FUS) and a neuroprotective agent, BNG-1, was examined in an acute carotid thrombotic occlusion model using LED irradiation in rat to improve the thrombolytic effect of rt-PA. Seven treatment groups included (A) intravenous bolus injection of 0.45 mg/kg rt-PA, (B) intravenous bolus injection of 0.9 mg/kg, (C) sonothrombolysis with FUS alone, (D) oral administration of 2 g/kg BNG-1 for 7 days alone, (E) A + D, (F) A + C, and (G) A + C + D. Four comparison groups were made including (H) 0.45 mg/kg rt-PA 20% bolus +80% IV fusion + FUS, (I) 0.9 mg/kg rt-PA with 10% bolus + 90% intravenous fusion, (J) B + C, (K) B + D. At 7 days after carotid occlusion, small-animal carotid ultrasound and 7 T MR angiography showed the recanalization rate of ≤50% stenosis was 50% in group B and 83% in group I, but 0% in groups A and C and 17% in group D. Combination therapy improved recanalization rate to 50–63% in groups E and F, to 67–83% in groups J and K, and to 100% in groups G and H. Our study demonstrated combination therapy with different remedies can be a feasible strategy to improve the thrombolytic effect of rt-PA.

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Section: Introductionmentioning

confidence: 98%

Improved thrombolytic effect with focused ultrasound and neuroprotective agent against acute carotid artery thrombosis in rat

Lee

Yeh

Tsai

et al. 2017

Sci Rep

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“…The cAMP-dependent lipolysis in adipose tissues was shown to be activated by ROS and TNF-α 21 , 22 . Additionally, BNG-1 has previously been shown to be a non-specific inhibitor of artery cAMP-dependent PDEs including PDE-1 to -6 8 . The present results showed that the BNG-1 can exert a dual effect on the cAMP activities and PDE3B expression of target tissues and affect the oxidative stress status.…”

Section: Discussionmentioning

confidence: 99%

“…The Chinese medicinal formula BNG-1 is composed of a number of herbs, which are thought to be effective for the treatment of stroke. BNG-1 has been shown to exert its anti-inflammatory activity by suppression of different phosphodiesterases (PDEs) 8 . PDEs are known to hydrolyze both cAMP and cGMP to the inactive forms and are involved in cellular signaling transduction.…”

Section: Introductionmentioning

confidence: 99%

Effects of Chinese Medicinal Formula BNG-1 on Phosphodiesterase 3B Expression, Hepatic Steatosis, and Insulin Resistance in High Fat Diet-induced NAFLD Mice

et al. 2018

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Background: Chinese medicinal formula BNG-1, a non-specific inhibitor of phospho-diesterases (PDEs), can be considered as a potential anti-inflammatory agent. The present study was aimed at determining the effects of BNG-1 on the development of non-alcoholic fatty liver disease (NAFLD) in mice.Design and Methods: Male CD1 mice were randomly divided into seven groups, the control Con (4) and Con (8)+saline groups were fed a standard control diet for four or eight weeks; the experimental HFD (4) and HFD (8)+saline groups were fed a high fat diet for four or eight weeks; the HFD (8)+LBNG, HFD (8)+MBNG, and HFD (8)+HBNG groups received a high fat diet along with low, moderate or high doses of BNG-1 (0.026, 0.035, and 0.052g/30g body weight) which was administered for the last four weeks of an eight-week experimental period. After the end of experiment, blood and tissue samples were taken and analyzed.Results: Mice in the HFD (4) group had higher levels of alanine aminotransferase (ALT), plasma and hepatic triglyceride and cholesterol, and homeostasis model assessment-estimated insulin resistance (HOMA-IR) compared with mice in the Con (4) group. Mice receiving the high fat diet along with the BNG-1 supplement had decreased body weight gains and lower visceral fat weights compared with the HFD (8)+saline group. They had also significantly reduced levels of abnormal ALT and HOMA-IR, and improved blood lipid profile. BNG-1-treated mice exhibited reduced hepatic lipid accumulation, lower oxidative stress, and decreased expression of pro-inflammatory cytokines (TNF-α and IL-1β). Furthermore, BNG-1 treatment resulted in down-regulation of hepatic cyclic-AMP dependent PDE3B and up-regulation of PDE3B expression in epididymis adipose tissue.Conclusions: BNG-1 mediated changes in PDE3B expression along with reduction in oxidative stress and inflammation. BNG-1 may ameliorate insulin resistance and hepatic steatosis in the NAFLD mouse model.

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“…As described in detail previously [ 20 ], inhalation of a nitrous oxide/oxygen/isoflurane mixture (70%/30%/1.5%) was used to anesthetize the rats before MRI. After exposing the inguinal area, a biomedical silicone catheter (external diameter of 0.64 mm) was cannulated into left femoral vein to administer MR contrast agent.…”

Section: Methodsmentioning

confidence: 99%

The Protective Effect of Human Umbilical Cord Blood CD34+ Cells and Estradiol against Focal Cerebral Ischemia in Female Ovariectomized Rat: Cerebral MR Imaging and Immunohistochemical Study

et al. 2016

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Human umbilical cord blood derived CD34+ stem cells are reported to mediate therapeutic effects in stroke animal models. Estrogen was known to protect against ischemic injury. The present study wished to investigate whether the protective effect of CD34+ cells against ischemic injury can be reinforced with complemental estradiol treatment in female ovariectomized rat and its possible mechanism. Experiment 1 was to determine the best optimal timing of CD34+ cell treatment for the neuroprotective effect after 60-min middle cerebral artery occlusion (MCAO). Experiment 2 was to evaluate the adjuvant effect of 17β-estradiol on CD34+ cell neuroprotection after MCAO. Experiment 1 showed intravenous infusion with CD34+ cells before MCAO (pre-treatment) caused less infarction size than those infused after MCAO (post-treatment) on 7T magnetic resonance T2-weighted images. Experiment 2 revealed infarction size was most significantly reduced after CD34+ + estradiol pre-treatment. When compared with no treatment group, CD34+ + estradiol pre-treatment showed significantly less ADC reduction at 2 h and 2 d, less CBF reduction at 2 h and less hyperperfusion at 2 d. The immunoreactivity of c-Fos, c-Jun and GFAP was attenuated, and BDNF showed significant recovery from 2 h to 2 d after MCAO, especially after CD34+ + estradiol pre-treatment. The present study suggests pre-treatment with CD34+ cells with complemental estradiol can be most protective against ischemic injury, which may act through stabilization of cerebral hemodynamics and normalization of the expressions of immediate early genes and BDNF.

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Neuroprotective Mechanism of BNG-1 against Focal Cerebral Ischemia: A Neuroimaging and Neurotrophin Study

Cited by 6 publications

References 41 publications

Improved thrombolytic effect with focused ultrasound and neuroprotective agent against acute carotid artery thrombosis in rat

Improved thrombolytic effect with focused ultrasound and neuroprotective agent against acute carotid artery thrombosis in rat

Effects of Chinese Medicinal Formula BNG-1 on Phosphodiesterase 3B Expression, Hepatic Steatosis, and Insulin Resistance in High Fat Diet-induced NAFLD Mice

The Protective Effect of Human Umbilical Cord Blood CD34+ Cells and Estradiol against Focal Cerebral Ischemia in Female Ovariectomized Rat: Cerebral MR Imaging and Immunohistochemical Study

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