Guhong injection mitigates myocardial ischemia/reperfusion injury by activating GST P to inhibit ASK1-JNK/p38 pathway

Chen, Haiyang; Zhou, Huifen; Yang, Jiehong; Wan, Haitong

doi:10.1016/j.phymed.2022.154603

Cited by 9 publications

(7 citation statements)

References 71 publications

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“…PK/PD studies deduced the concentration that produced effects, optimized the administered dose, as well as provided a scientific basis for the optimum administration regimen via investigating the three–dimensional relationship of concentration-effect-time [ 56 ]. Owing to the cardioprotective effect of GHI in vivo and in vitro has been affirmed in our previous research, we proceeded with PK/PD studies to supply guidelines for the clinical medication of GHI in treating MI/R injury [ 21 ]. In the present study, analytes with a negative coefficient in PLSR equations and four cardiac enzymes (i.e., CK-MB, cTn I, IMA, and α-HBDH) were respectively regarded as PK and PD indicators to fit PK/PD model.…”

Section: Discussionmentioning

confidence: 99%

“…They were reared in a specific pathogen-free sounding under approximately 50% humidity and 22 °C in Zhejiang Chinese Medical University Laboratory Animal Research Center (Laboratory animal use license: SYXK 2021–0012) with registration number of experimental animals: 20220411–04. The MI/R surgery in this article was consulted from our previous research [ 21 ]. In a nutshell, rats were firstly anesthetized by sodium pentobarbital (50 mg/kg, i.p.…”

Section: Methodsmentioning

confidence: 99%

“…), as well as in verapamil hydrochloride group was administered with verapamil hydrochloride (0.95 mg/kg) dissolved in physiological saline via tail vein. The administrated dosages of GHI and positive drug were converted from the clinical doses [ 21 , 23 ].…”

Section: Methodsmentioning

confidence: 99%

“…Although GHI, composed of N-acetyl-L-glutamine (NAG) and the aqueous extract of safflower ( C. tinctorius L.), has been attested to mitigate MI/R injury via improving oxidative stress to inhibit apoptosis by our previous study, the specific process of GHI in vivo is not revealed plenty [ 21 ]. Although our team explored the PK parameters of only two active ingredients of GHI in both cerebral ischemia/reperfusion rats and normal rats, we deemed that this research was incomplete [ 22 ].…”

Section: Introductionmentioning

confidence: 99%

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An auxiliary strategy of partial least squares regression in pharmacokinetic/pharmacodynamic studies: A case of application of guhong injection in myocardial ischemia/reperfusion rats

Chen,

Li,

Shao

et al. 2024

Journal of Food and Drug Analysis

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Guhong injection (GHI) has been applied in the therapy of cardio-cerebrovascular disease in clinic, but there is no report about the pharmacokinetic/pharmacodynamic (PK/PD) research on GHI treating myocardial ischemia/reperfusion (MI/R) injury in rats. In this study, eight compounds of GHI in plasma, including N-acetyl-L-glutamine (NAG), chlorogenic acid (CGA), hydroxysafflor yellow A (HSYA), p -coumaric acid ( p CA), rutin, hyperoside, kaempferol-3-O-rutinoside, and kaempferol-3-O-glucoside, were quantified by LC-MS/MS. We discovered that the values of t 1/2β , k 12 , V 2 , and CL 2 were larger than those of t 1/2α , k 21 , V 1 , and CL 1 for all compounds. The levels of four biomarkers, creatine kinase-MB (CK-MB), cardiac troponin I (cTn I), ischemia-modified albumin (IMA), and alpha-hydroxybutyrate dehydrogenase (α-HBDH) in plasma were determined by ELISA. The elevated level of these biomarkers induced by MI/R was declined to different degrees via administrating GHI and verapamil hydrochloride (positive control). The weighted regression coefficients of NAG, HSYA, CGA, and p CA in PLSR equations generated from The Unscrambler X software (version 11) were mostly minus, suggesting these four ingredients were positively correlated to the diminution of the level of four biomarkers. E max and ED 50 , two parameters in PK/PD equations that were obtained by adopting Drug and Statistics software (version 3.2.6), were almost enlarged with the rise of GHI dosage. Obviously, all analytes were dominantly distributed and eliminated in the peripheral compartment with features of rapid distribution and slow elimination. With the enhancement of GHI dosage, the ingredients only filled in the central compartment if the peripheral compartment was replete. Meanwhile, high-dose of GHI generated the optimum intrinsic activity, but the affinity of compounds with receptors was the worst, which may be caused by the saturation of receptors. Among the eight analytes, NAG, HSYA, CGA, and p CA exhibited superior cardioprotection, which probably served as the pharmacodynamic substance basis of GHI in treating MI/R injury.

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Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

An auxiliary strategy of partial least squares regression in pharmacokinetic/pharmacodynamic studies: A case of application of guhong injection in myocardial ischemia/reperfusion rats

Chen,

Li,

Shao

et al. 2024

Journal of Food and Drug Analysis

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“…Thrombus‐induced ischaemia contributes to myocardial hypoxia; dissolution or removal of the thrombus results in reperfusion of the affected vessel (Kusakabe et al, 2023). The relatively high oxygen content from reinstating blood flow stimulates cardiomyocytes, disrupts mitochondrial function and brings about oxidative damage (Kusakabe et al, 2023; X. Yang, Wang, et al, 2023; S. Zhang, Yu, et al, 2023). I/R worsens the already poor myocardial status (J. Yang, Sundqvist, et al, 2023; X. Yang, Wang, et al, 2023).…”

Section: Aim2 Inflammasomes In Cardiovascular Diseases (Cvds)mentioning

confidence: 99%

The cytoplasmic sensor, the AIM2 inflammasome: A precise therapeutic target in vascular and metabolic diseases

Lin,

Wang,

Fang

et al. 2024

British J Pharmacology

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Cardio‐cerebrovascular diseases encompass pathological changes in the heart, brain and vascular system, which pose a great threat to health and well‐being worldwide. Moreover, metabolic diseases contribute to and exacerbate the impact of vascular diseases. Inflammation is a complex process that protects against noxious stimuli but is also dysregulated in numerous so‐called inflammatory diseases, one of which is atherosclerosis. Inflammation involves multiple organ systems and a complex cascade of molecular and cellular events. Numerous studies have shown that inflammation plays a vital role in cardio‐cerebrovascular diseases and metabolic diseases. The absent in melanoma 2 (AIM2) inflammasome detects and is subsequently activated by double‐stranded DNA in damaged cells and pathogens. With the assistance of the mature effector molecule caspase‐1, the AIM2 inflammasome performs crucial biological functions that underpin its involvement in cardio‐cerebrovascular diseases and related metabolic diseases: The production of interleukin‐1 beta (IL-1β), interleukin‐18 (IL-18) and N‐terminal pore‐forming Gasdermin D fragment (GSDMD‐N) mediates a series of inflammatory responses and programmed cell death (pyroptosis and PANoptosis). Currently, several agents have been reported to inhibit the activity of the AIM2 inflammasome and have the potential to be evaluated for use in clinical settings. In this review, we systemically elucidate the assembly, biological functions, regulation and mechanisms of the AIM2 inflammasome in cardio‐cerebrovascular diseases and related metabolic diseases and outline the inhibitory agents of the AIM2 inflammasome as potential therapeutic drugs.

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New insights into mechanism of ellagic acid alleviating arsenic-induced oxidative stress through MAPK/keap1-Nrf2 signaling pathway response, molecular docking and metabolomics analysis in HepG2 cells

Yu,

Xu,

Zhao

et al. 2024

Ecotoxicology and Environmental Safety

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Guhong injection mitigates myocardial ischemia/reperfusion injury by activating GST P to inhibit ASK1-JNK/p38 pathway

Cited by 9 publications

References 71 publications

An auxiliary strategy of partial least squares regression in pharmacokinetic/pharmacodynamic studies: A case of application of guhong injection in myocardial ischemia/reperfusion rats

An auxiliary strategy of partial least squares regression in pharmacokinetic/pharmacodynamic studies: A case of application of guhong injection in myocardial ischemia/reperfusion rats

The cytoplasmic sensor, the AIM2 inflammasome: A precise therapeutic target in vascular and metabolic diseases

New insights into mechanism of ellagic acid alleviating arsenic-induced oxidative stress through MAPK/keap1-Nrf2 signaling pathway response, molecular docking and metabolomics analysis in HepG2 cells

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