Oxymatrine prevents the development of monocrotaline-induced pulmonary hypertension via regulation of the N, N-dimethyl-L-arginine metabolism pathways in rats

Dai, Guidong; Li, Benpeng; Xu, Yuping; Zeng, Z; Yang, Hong‐Yun

doi:10.1016/j.ejphar.2018.11.007

Cited by 14 publications

(5 citation statements)

References 33 publications

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“…Oxymatrine (OMT), an alkaloid that originates from the traditional Chinese herb Sophora flavescens Aiton, possesses numerous pharmacological properties, including anti-hepatic fibrosis (6), anti-inflammatory (7) and antitumor activities (8). The use of OMT in patients with cardiovascular diseases has attracted increasing attention, because studies have identified that OMT has a wide range of pharmacological properties, including activities against arrhythmia (9), shock (10) and hypertension (11). The nuclear factor erythroid-2-related factor 2 (Nrf2)/heme oxygenase-1 (HO-1) pathway and the Oxymatrine pretreatment protects H9c2 cardiomyocytes from hypoxia/reoxygenation injury by modulating the PI3K/Akt pathway phosphatidylinositol 3-kinase (PI3K)/Akt/glycogen synthase kinase-3β (GSK3β) pathway are important pathophysiological mechanisms that are relevant to I/R injury, and previous studies have shown that OMT attenuates I/R injury in the brain through the p-Akt/GSK3β/HO-1/Nrf2 signaling pathway (12)(13)(14).…”

Section: Introductionmentioning

confidence: 99%

Oxymatrine pretreatment protects H9c2 cardiomyocytes from hypoxia/reoxygenation injury by modulating the PI3K/Akt pathway

et al. 2021

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Ischemia-reperfusion (I/R) plays an important role in myocardial damage, which has been widely recognized as a key procedure in the cardiovascular disease. A hypoxia/reoxygenation (H/R) model was established using H9c2 cardiomyocytes to investigate the possible positive effect of oxymatrine (OMT), an alkaloid originating from the traditional Chinese herb Sophora flavescens Aiton, on cardiomyocytes exposed to H/R injury and the underlying molecular mechanisms. Cell viability was measured using the MTT assay, lactate dehydrogenase release measurements and hematoxylin and eosin staining. Oxidative stress was detected by measuring cellular malondialdehyde (MDA) content, as well as superoxide dismutase (SOD) and catalase (CAT) activities. Apoptosis was detected using TUNEL staining and flow cytometric analysis, and the underlying mechanism was investigated using reverse transcription-quantitative PCR and western blot analyses. The results revealed that OMT increased the viability of H9c2 cardiomyocytes exposed to H/R. The OMT pretreatment decreased the production of MDA by reactive oxygen species and increased the activities of SOD and CAT. Furthermore, the OMT pretreatment reduced the expression of Bax and caspase-3, while inducing Bcl-2 expression. In addition, the protective effect of OMT was shown to be associated with the PI3K/Akt signaling pathway, and the PI3K inhibitor LY294002 attenuated the effects of OMT on the H9c2 cardiomyocytes exposed to H/R. These findings indicate that OMT could be a potential therapeutic candidate for the treatment of myocardial ischemia/reperfusion injury.

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Section: Introductionmentioning

confidence: 99%

Oxymatrine pretreatment protects H9c2 cardiomyocytes from hypoxia/reoxygenation injury by modulating the PI3K/Akt pathway

et al. 2021

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“…In brain-related diseases, such as amyotrophic lateral sclerosis, cerebral ischemia/reperfusion injury, and Alzheimer’s disease, oxymatrine induces neuroprotective and memory impairment effects by influencing the PI3K/Akt/mTOR, PI3K/Akt/GSK3β, TLR4/NF-κB, and HMGB1/TLR4/NF-κB pathways. − In cardiopulmonary-related diseases, oxymatrine could ameliorate myocardial ischemia/reperfusion-induced acute lung injury in diabetic rats by inhibiting autophagy and endoplasmic reticulum stress and alleviating myocardial fibrosis induced by acute myocardial infarction via the TGF-β1-Smads pathway. − In a model of septic-shock-induced myocardial injury, oxymatrine reduced the severity of the infection and protected cardiomyocytes by inhibiting the TNF-α/p38 MAPK/caspase-3 and JAK2/STAT3 signaling pathways. , In an isoproterenol-induced heart failure rat model, oxymatrine attenuated the severity of heart failure by regulating the COX-2/PGI and DDAH/ADMA metabolism pathways. , Additionally, in a rat model of myocardial injury caused by chemotherapeutic drugs, such as doxorubicin, oxymatrine induced protective effects by partially inhibiting cardiac apoptosis and oxidative stress . In lung diseases, oxymatrine could attenuate hypoxia- and monocrotaline-induced pulmonary hypertension, bleomycin-induced pulmonary fibrosis, and acute lung injury by regulating the N(G), N(G)-dimethyl- l -arginine metabolism pathway, JNK, TGF-β/Smad signaling pathway. − …”

Section: Discussionmentioning

confidence: 99%

Study on Oxymatrine-Based Research from 2001 to 2022: A Bibliometric Analysis

Lan,

Chen,

Duan

et al. 2024

ACS Omega

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Oxymatrine is a quinolizidine alkaloid mainly derived from Kushen; it possesses various therapeutic effects, such as organ-and tissue-protective, anticancer, and antiviral effects. The research directions for oxymatrine remain broad. In order to explore the overall status of oxymatrine-based research, we carried out a bibliometric analysis to summarize the oxymatrine-based, English-written studies published in the past 22 years. In total, 267 studies were included, most of which were original. The number of annual studies slowly increased with some fluctuations. Other than China, 11 different countries conducted studies on oxymatrine; the variety in the country of origin of these publications is presented as a recently increasing trend. Many affiliates and researchers have participated in oxymatrine-based research. Various treatment mechanisms involving different oxymatrine pathways have led to research in a wide range of fields, being published in numerous journals. Two particularly popular research fields related to oxymatrine involved anticancer and anti-inflammation. From this research, we concluded that with increasing and continuous in-depth studies, more therapeutic effects and mechanisms will be elucidated, and oxymatrine may present as a viable option for the treatment of additional diseases.

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“…Oxymatrine, an active alkaloid derived from the traditional Chinese herb Sophora alopecuroides was found to protect against hypoxia- and monocrotaline-induced PAH ( Zhang et al, 2014 ). The mechanism behind the protective effect of Oxymatrine in monocrotaline-induced PAH is likely to be through the reduction of pulmonary ADMA levels even though it did not affect the level of DDAH1 ( Dai et al, 2019 ).…”

Section: Ongoing Pharmaceutical Research On Nitric Oxide Pathway and Its Implication In Pulmonary Arterial Hypertensionmentioning

confidence: 99%

Therapy for Pulmonary Arterial Hypertension: Glance on Nitric Oxide Pathway

Tettey

Jiang

et al. 2021

Front. Pharmacol.

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Pulmonary arterial hypertension (PAH) is a severe disease with a resultant increase of the mean pulmonary arterial pressure, right ventricular hypertrophy and eventual death. Research in recent years has produced various therapeutic options for its clinical management but the high mortality even under treatment remains a big challenge attributed to the complex pathophysiology. Studies from clinical and non-clinical experiments have revealed that the nitric oxide (NO) pathway is one of the key pathways underlying the pathophysiology of PAH. Many of the essential drugs used in the management of PAH act on this pathway highlighting its significant role in PAH. Meanwhile, several novel compounds targeting on NO pathway exhibits great potential to become future therapy medications. Furthermore, the NO pathway is found to interact with other crucial pathways. Understanding such interactions could be helpful in the discovery of new drug that provide better clinical outcomes.

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Oxymatrine prevents the development of monocrotaline-induced pulmonary hypertension via regulation of the N, N-dimethyl-L-arginine metabolism pathways in rats

Cited by 14 publications

References 33 publications

Oxymatrine pretreatment protects H9c2 cardiomyocytes from hypoxia/reoxygenation injury by modulating the PI3K/Akt pathway

Oxymatrine pretreatment protects H9c2 cardiomyocytes from hypoxia/reoxygenation injury by modulating the PI3K/Akt pathway

Study on Oxymatrine-Based Research from 2001 to 2022: A Bibliometric Analysis

Therapy for Pulmonary Arterial Hypertension: Glance on Nitric Oxide Pathway

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