TPN171H alleviates pulmonary hypertension via inhibiting inflammation in hypoxia and monocrotaline-induced rats

Zhao, Congke; Hu, Linlin; He, Xinkuai; Li, Lijun; Yin, Minghui; Tettey, Abraham Terkpertey; Wang, Yu; Shen, Jingshan; Tang, Siyuan; Wu, Chunhui; Li, Qianbin; Wang, Zhen; Li, Xiaohui

doi:10.1016/j.vph.2022.107017

Cited by 5 publications

(5 citation statements)

References 41 publications

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“…The Wound scratch assay was performed as previously described . HPASMCs were cultured in 6-well plates.…”

Section: Methodsmentioning

confidence: 99%

“…The Trans-well chamber was utilized to detect cell migration . A cell solution containing 1% FBS was added to the upper chamber, while a complete medium containing varying concentrations of compounds was added to the lower chamber.…”

Section: Methodsmentioning

confidence: 99%

“…The specific scheme of animal experiment was carried out according to our previously reports. ,, All animal procedures and protocols were approved by the Experimental Animal Welfare Ethics Committee and the Animal Management Committee of Hunan Normal University (IRB approval number: D2023050). Male Sprague–Dawley (SD) rats (160–180 g) were purchased from Hunan SJA Laboratory Animal Co., Ltd. (NO: SYXK (Xiang) 2015-0017).…”

Section: Methodsmentioning

confidence: 99%

“…The assays were conducted following the previously described protocol . Total proteins were extracted from tissues and cells using RIPA lysate (Beyotime, China), while nuclear and cytoplasmic proteins were extracted using the Nuclear Cytoplasmic Protein Extraction Kit (Solarbio, China) according to the manufacturer’s instructions.…”

Section: Methodsmentioning

confidence: 99%

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Discovery and Optimization of Hsp110 and sGC Dual-Target Regulators for the Treatment of Pulmonary Arterial Hypertension

Hu,

Zhao,

Tan

et al. 2024

J. Med. Chem.

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Currently, bifunctional agents with vasodilation and ameliorated vascular remodeling effects provide more advantages for the treatment of pulmonary arterial hypertension (PAH). In this study, we first screened the hit 1 with heat shock protein 110 (Hsp110) inhibition effect from our in-house compound library with soluble guanylate cyclase (sGC) activity. Subsequently, a series of novel bisamide derivatives were designed and synthesized as Hsp110/sGC dual-target regulators based on hit 1. Among them, 17i exhibited optimal Hsp110 and sGC molecular activities as well as remarkable cell malignant phenotypes inhibitory and vasodilatory effects in vitro. Moreover, compared to riociguat, 17i showed superior efficacy in attenuating pulmonary vascular remodeling and right ventricular hypertrophy via Hsp110 suppression in hypoxia-induced PAH rat models (i.g.). Notably, our study successfully demonstrated that the simultaneous regulation of Hsp110 and sGC dual targets was a novel and feasible strategy for PAH therapy, providing a promising lead compound for anti-PAH drug discovery.

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“…The Wound scratch assay was performed as previously described . HPASMCs were cultured in 6-well plates.…”

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

See 2 more Smart Citations

Discovery and Optimization of Hsp110 and sGC Dual-Target Regulators for the Treatment of Pulmonary Arterial Hypertension

Hu,

Zhao,

Tan

et al. 2024

J. Med. Chem.

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“…Mechanistically, PDE5 inhibitors exert protective effects on the cardiovascular system by activating protein kinase G (PKG), PKG-dependent hydrogen sulfide generation, nitric oxide expression, and glycogen synthase kinase-3β phosphorylation ( 64 – 66 ). In addition to hydrogen sulfide-mediated NLRP3 activation ( 38 , 39 ), the PDE-5 inhibitor TPN171H, an icariin derivative, displays significant anti-inflammatory activities via suppressing NLRP3 inflammasome-mediated pyroptosis via cathepsin B ( 67 – 69 ). These results indicate that PDE5 inhibitors provide cardioprotection against DCM by inhibiting NLRP3 inflammasome-mediated pyroptosis; however, direct evidence is still lacking.…”

Section: Clinical Diabetes Cardiomyopathy Therapies Targeting Pyroptosismentioning

confidence: 99%

Potential diabetic cardiomyopathy therapies targeting pyroptosis: A mini review

et al. 2022

Front. Cardiovasc. Med.

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Pyroptosis is primarily considered a pro-inflammatory class of caspase-1- and gasdermin D (GSDMD)-dependent programmed cell death. Inflammasome activation promotes the maturation and release of interleukin (IL)-1β and IL-18, cleavage of GSDMD, and development of pyroptosis. Recent studies have reported that NLRP3 inflammasome activation-mediated pyroptosis aggravates the formation and development of diabetes cardiomyopathy (DCM). These studies provide theoretical mechanisms for exploring a novel approach to treat DCM-associated cardiac dysfunction. Accordingly, this review aims to summarize studies that investigated possible DCM therapies targeting pyroptosis and elucidate the molecular mechanisms underlying NLRP3 inflammasome-mediated pyroptosis, and its potential association with the pathogenesis of DCM. This review may serve as a basis for the development of potential pharmacological agents as novel and effective treatments for managing and treating DCM.

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Avanafil as a Novel Therapeutic Agent Against LPS-Induced Acute Lung Injury via Increasing CGMP to Downregulate the TLR4-NF-κB-NLRP3 Inflammasome Signaling Pathway

Aydin

Magden

Uzunçakmak

et al. 2022

Lung

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TPN171H alleviates pulmonary hypertension via inhibiting inflammation in hypoxia and monocrotaline-induced rats

Cited by 5 publications

References 41 publications

Discovery and Optimization of Hsp110 and sGC Dual-Target Regulators for the Treatment of Pulmonary Arterial Hypertension

Discovery and Optimization of Hsp110 and sGC Dual-Target Regulators for the Treatment of Pulmonary Arterial Hypertension

Potential diabetic cardiomyopathy therapies targeting pyroptosis: A mini review

Avanafil as a Novel Therapeutic Agent Against LPS-Induced Acute Lung Injury via Increasing CGMP to Downregulate the TLR4-NF-κB-NLRP3 Inflammasome Signaling Pathway

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