Synthesis and biological evaluation of nitric oxide (NO)-hydrogen sulfide (H 2 S) releasing derivatives of ( S )-3- n -butylphthalide as potential antiplatelet agents

Wang, Xiaoli; Wang, Zhaoya; Ling, Jingjing; Zhang, Yihua; Yin, Jian

doi:10.1016/s1875-5364(17)30021-3

Cited by 14 publications

(15 citation statements)

References 27 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Compared with the vehicle group, the initial (4h) hemorrhage volume of the NBP group appeared a little bit larger than that of the vehicle group, but there was no statistically significant difference. Previous study showed that NBP has antiplatelet effects, and antiplatelet medicines may increase the risk of intracerebral hemorrhage [34][35][36]. This was consistent with our results.…”

Section: Agingsupporting

confidence: 93%

“…Therefore, for the future treatment of ICH, further animal studies that focus on the molecular mechanism by selective blockade of the ICH relative pathway are necessary. Finally, previous studies showed that NBP could significantly inhibit platelet activation and might be an effective antiplatelet drug for ischemic stroke [34][35][36]. Therefore, future preclinical and translational studies are also needed to address the safety effects of NBP for the treatment ICH.…”

Section: Agingmentioning

confidence: 99%

See 1 more Smart Citation

L-3-n-butylphthalide attenuates inflammation response and brain edema in rat intracerebral hemorrhage model

Zeng

Gong

2020

Aging

View full text Add to dashboard Cite

L-3-n-butylphthalide(NBP), a compound found in Apium graveolens Linn seed extracts, has a therapeutic effect on acute ischemic stroke. The pathological inflammatory pathways and consequent brain edema in intracerebral hemorrhage (ICH) share some similar characteristics with ischemic stroke. We hypothesized that NBP has anti-inflammatory and therapeutic effects on rats with ICH. ICH was induced by an infusion of bacterial collagenase type IV into the unilateral striatum of anesthetized rats. The therapeutic effect of NBP was measured by assessing neurological function, brain water content, blood-brain barrier permeability, and expression of tumor necrosis factor-alpha (TNF-α) and matrix metalloproteinase-9 (MMP-9) around the hematoma 48 hours after surgery. Magnetic resonance imaging was performed 4 and 48 hours after ICH induction, and ICH-induced injured area volumes were measured using T2-weighted images. The NBP treatment group performed better in the neurological function test than the vehicle group. Moreover, in comparison with the vehicle group, NBP group showed a lower expanded hematoma volume, brain water content, blood-brain barrier permeability, and TNF-α/ MMP-9 expression level. Our results indicate that NBP attenuates inflammation and brain edema in rat ICH model. Therefore, our findings also provide a potential therapeutic strategy for the treatment of ICH with NBP.

show abstract

Section: Agingsupporting

confidence: 93%

Section: Agingmentioning

confidence: 99%

L-3-n-butylphthalide attenuates inflammation response and brain edema in rat intracerebral hemorrhage model

Zeng

Gong

2020

Aging

View full text Add to dashboard Cite

show abstract

“…Another class of nitric oxide-hydrogen sulfide-releasing hybrids is based on a modified (S)-3-n-butylphthalide core (Wang et al, 2016d). From a series of molecules, compound NOSH-NBP-5 was found to release moderate amounts of NO and H 2 S and displayed significantly inhibitory effects on platelet aggregation in vitro.…”

Section: No/h 2 S Hybrid Donorsmentioning

confidence: 99%

International Union of Basic and Clinical Pharmacology. CII: Pharmacological Modulation of H₂S Levels: H₂S Donors and H₂S Biosynthesis Inhibitors

2017

View full text Add to dashboard Cite

Over the last decade, hydrogen sulfide (HS) has emerged as an important endogenous gasotransmitter in mammalian cells and tissues. Similar to the previously characterized gasotransmitters nitric oxide and carbon monoxide, HS is produced by various enzymatic reactions and regulates a host of physiologic and pathophysiological processes in various cells and tissues. HS levels are decreased in a number of conditions (e.g., diabetes mellitus, ischemia, and aging) and are increased in other states (e.g., inflammation, critical illness, and cancer). Over the last decades, multiple approaches have been identified for the therapeutic exploitation of HS, either based on HS donation or inhibition of HS biosynthesis. HS donation can be achieved through the inhalation of HS gas and/or the parenteral or enteral administration of so-called fast-releasing HS donors (salts of HS such as NaHS and NaS) or slow-releasing HS donors (GYY4137 being the prototypical compound used in hundreds of studies in vitro and in vivo). Recent work also identifies various donors with regulated HS release profiles, including oxidant-triggered donors, pH-dependent donors, esterase-activated donors, and organelle-targeted (e.g., mitochondrial) compounds. There are also approaches where existing, clinically approved drugs of various classes (e.g., nonsteroidal anti-inflammatories) are coupled with HS-donating groups (the most advanced compound in clinical trials is ATB-346, an HS-donating derivative of the non-steroidal anti-inflammatory compound naproxen). For pharmacological inhibition of HS synthesis, there are now several small molecule compounds targeting each of the three HS-producing enzymes cystathionine--synthase (CBS), cystathionine--lyase, and 3-mercaptopyruvate sulfurtransferase. Although many of these compounds have their limitations (potency, selectivity), these molecules, especially in combination with genetic approaches, can be instrumental for the delineation of the biologic processes involving endogenous HS production. Moreover, some of these compounds (e.g., cell-permeable prodrugs of the CBS inhibitor aminooxyacetate, or benserazide, a potentially repurposable CBS inhibitor) may serve as starting points for future clinical translation. The present article overviews the currently known HS donors and HS biosynthesis inhibitors, delineates their mode of action, and offers examples for their biologic effects and potential therapeutic utility.

show abstract

“…Therefore, for the future treatment of ICH, further animal studies that focus on the molecular mechanism by selective blockade of the NBP pathway are necessary. Finally, previous studies showed that NBP could significantly inhibit platelet activation and might be an effective antiplatelet drug for ischemic stroke [33][34][35]. Therefore, future studies are also needed to address the safety, mg/-dependent effects, and treatment initiation of NBP for ICH.…”

Section: Discussionmentioning

confidence: 99%

L-3-n-butylphthalide protect the neuro by reducing inflammation and brain edema in rat intracerebral hemorrhage model

Zeng

Gong

2019

Preprint

View full text Add to dashboard Cite

Background：Previous studies have shown that L-3-n-butylphthalide(NBP), which is a compound found in Apium graveolens Linn seed extracts, could have neuroprotective effects on acute ischemic stroke through anti-inflammation and by reducing brain edema. The pathological inflammatory pathways and consequent brain edema in intracerebral hemorrhage (ICH) share some characteristics with ischemic stroke. Methods：We hypothesized that NBP has anti-inflammatory and therapeutic effects on rats with ICH. ICH was induced by an infusion of bacterial collagenase type IV into the unilateral striatum of anesthetized rats. The therapeutic effect of NBP was measured by assessing neurological function, brain water content, blood-brain barrier permeability, and expression of tumor necrosis factor-alpha (TNF-α) and matrix metalloproteinase-9 (MMP-9) around the hematoma 48 hours after surgery. Magnetic resonance imaging (MRI) was performed 4 and 48 hours after ICH induction, and ICH-induced injured area volumes were measured using T2-weighted images. Results： The NBP treatment group performed better in the neurological function test than the vehicle group. Moreover, in comparison with the vehicle group, NBP group showed a lower expanded hematoma volume, brain water content, blood-brain barrier permeability, and TNF-α/ MMP-9 expression level. Conclusions：Our results suggested that NBP have a neuroprotective effect by reducing inflammation and brain edema in rat ICH model. Therefore, our findings also show the potential for clinical application of NBP in the treatment of ICH.

show abstract

Synthesis and biological evaluation of nitric oxide (NO)-hydrogen sulfide (H 2 S) releasing derivatives of ( S )-3- n -butylphthalide as potential antiplatelet agents

Cited by 14 publications

References 27 publications

L-3-n-butylphthalide attenuates inflammation response and brain edema in rat intracerebral hemorrhage model

L-3-n-butylphthalide attenuates inflammation response and brain edema in rat intracerebral hemorrhage model

International Union of Basic and Clinical Pharmacology. CII: Pharmacological Modulation of H₂S Levels: H₂S Donors and H₂S Biosynthesis Inhibitors

L-3-n-butylphthalide protect the neuro by reducing inflammation and brain edema in rat intracerebral hemorrhage model

Contact Info

Product

Resources

About

Synthesis and biological evaluation of nitric oxide (NO)-hydrogen sulfide (H 2 S) releasing derivatives of ( S )-3- n -butylphthalide as potential antiplatelet agents

Cited by 14 publications

References 27 publications

L-3-n-butylphthalide attenuates inflammation response and brain edema in rat intracerebral hemorrhage model

L-3-n-butylphthalide attenuates inflammation response and brain edema in rat intracerebral hemorrhage model

International Union of Basic and Clinical Pharmacology. CII: Pharmacological Modulation of H2S Levels: H2S Donors and H2S Biosynthesis Inhibitors

L-3-n-butylphthalide protect the neuro by reducing inflammation and brain edema in rat intracerebral hemorrhage model

Contact Info

Product

Resources

About

International Union of Basic and Clinical Pharmacology. CII: Pharmacological Modulation of H₂S Levels: H₂S Donors and H₂S Biosynthesis Inhibitors