Sophocarpine Alleviates Isoproterenol-Induced Kidney Injury by Suppressing Inflammation, Apoptosis, Oxidative Stress and Fibrosis

Zhou, Wei; Fu, Yang Xin; Xu, Jinsong

doi:10.3390/molecules27227868

Cited by 7 publications

(8 citation statements)

References 31 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Similarly, TGF‐β1 has been shown to upregulate the phospho‐form Smad3 protein but not Smad3 in adult rat cardiac fibroblasts 39 . Indeed, isoproterenol treatment increases phosphorylated Smad3 protein levels but not Smad3 protein levels in heart and kidney tissues 8,40 …”

Section: Discussionmentioning

confidence: 99%

“…39 Indeed, isoproterenol treatment increases phosphorylated Smad3 protein levels but not Smad3 protein levels in heart and kidney tissues. 8,40 Picrosirius red staining and analysis of fibrosis-related genes (Col1a1 and Fn1) revealed that protocatechuic acid attenuated cardiac fibrosis. To identify the target genes of protocatechuic acid, RNA sequencing analysis was performed, and the expression of 10 genes was validated.…”

Section: Protocatechuic Acid Attenuates Kmo Overexpression-induced Hy...mentioning

confidence: 99%

See 1 more Smart Citation

Protocatechuic acid prevents isoproterenol‐induced heart failure in mice by downregulating kynurenine‐3‐monooxygenase

Bai

Han

Kee

et al. 2023

J Cellular Molecular Medi

View full text Add to dashboard Cite

Protocatechuic acid (3,4‐dihydroxybenzoic acid) prevents oxidative stress, inflammation and cardiac hypertrophy. This study aimed to investigate the therapeutic effects of protocatechuic acid in an isoproterenol‐induced heart failure mouse model and to identify the underlying mechanisms. To establish the heart failure model, C57BL/6NTac mice were given high‐dose isoproterenol (80 mg/kg body weight) for 14 days. Echocardiography revealed that protocatechuic acid reversed the isoproterenol‐induced downregulation of fractional shortening and ejection fraction. Protocatechuic acid attenuated cardiac hypertrophy as evidenced by the decreased heart‐weight‐to‐body‐weight ratio and the expression of Nppb. RNA sequencing analysis identified kynurenine‐3‐monooxygenase (Kmo) as a potential target of protocatechuic acid. Protocatechuic acid treatment or transfection with short‐interfering RNA against Kmo ameliorated transforming growth factor β1–induced upregulation of Kmo, Col1a1, Col1a2 and Fn1 in vivo or in neonatal rat cardiac fibroblasts. Kmo knockdown attenuated the isoproterenol‐induced increase in cardiomyocyte size, as well as Nppb and Col1a1 expression in H9c2 cells or primary neonatal rat cardiomyocytes. Moreover, protocatechuic acid attenuated Kmo overexpression–induced increases in Nppb mRNA levels. Protocatechuic acid or Kmo knockdown decreased isoproterenol‐induced ROS generation in vivo and in vitro. Thus, protocatechuic acid prevents heart failure by downregulating Kmo. Therefore, protocatechuic acid and Kmo constitute a potential novel therapeutic agent and target, respectively, against heart failure.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Protocatechuic Acid Attenuates Kmo Overexpression-induced Hy...mentioning

confidence: 99%

Protocatechuic acid prevents isoproterenol‐induced heart failure in mice by downregulating kynurenine‐3‐monooxygenase

Bai

Han

Kee

et al. 2023

J Cellular Molecular Medi

View full text Add to dashboard Cite

show abstract

“…Isoprenaline, at high doses, can reduce the glomular filtration rate due to an increase in pre and postglomerular resistance [28], thereby damaging the kidneys [120]. Thioacetamide, while being a reactive chemical primarily known for its liver effects, can also be toxic to the kidneys at high doses [13].…”

Section: Validation and Analysismentioning

confidence: 99%

Completion of the DrugMatrix Toxicogenomics Database using ToxCompl

Cong,

Patton,

Chao

et al. 2024

Preprint

View full text Add to dashboard Cite

The DrugMatrix Database contains systematically generated toxicogenomics data from short-term in vivo studies for over 600 chemicals. However, most of the potential endpoints in the database are missing due to a lack of experimental measurements. We present our study on leveraging matrix factorization and machine learning methods to predict the missing values in the DrugMatrix, which includes gene expression across eight tissues on two expression platforms along with paired clinical chemistry, hematology, and histopathology measurements. One major challenge we encounter is the skewed distribution of the available measured data, in terms of both tissue sources and values. We propose a method, ToxiCompl, that applies systematic hybrid sampling guided by Bayesian optimization in conjunction with low-rank matrix factorization to recover the missing values. ToxiCompl achieves good training and validation performance from a machine learning perspective. We further conduct an in-depth validation of the predicted data from biological and toxicological perspectives with a series of analyses. These include examining the connectivity pattern of predicted gene expression responses, characterizing molecular pathway-level responses from sets of differentially expressed genes, evaluating known transcriptional biomarkers of tissue toxicity, and characterizing predicted apical endpoints. Our analysis shows that the predicted expression, broadly speaking, aligns with what would be anticipated. For example, in most instances, our prediction offers a connectivity level comparable to that of measured data in connectivity analysis. Using Havcr1, a known transcriptional biomarker of kidney injury, we identify treatments that, based on the predicted expression data, manifest kidney toxicity in a manner that is mechanistically plausible and supported by the literature. Characterization of the predicted clinical chemistry data suggests that strong effects are relatively reliably predicted, while more subtle effects pose a greater challenge. In the case of histopathological prediction, we find a significant overprediction due to positivity bias in the measured data. Developing methods to deal with this bias is one of the areas we plan to target for future improvement. The main advantage of the ToxiCompl approach is that, in the absence of additional experimental data, it drastically extends the toxicogenomic landscape into a number of data-poor tissues, thereby allowing researchers to formulate mechanistic hypotheses about effects in tissues that have been underrepresented in the literature. All predicted DrugMatrix data, along with the measured data, is available to the public through an intuitive GUI interface that allows for retrieval and gene set analysis (https://rstudio.niehs.nih.gov/ complete_drugmatrix/). Importantly, a clear distinction is made between the measured and predicted data, so researchers are aware of the data source they are working with. All data streams, including gene expression, clinical chemistry, hematology, and histopathology, are made available. We anticipate that this data will facilitate mechanistic and toxicological hypothesis generation regarding chemical effects in a variety of understudied tissues.

show abstract

“…It has been shown that in a mouse model of isoproterenol (ISO)-induced kidney injury, sophocarpine could alleviate kidney injury by reducing the serum levels of serum creatinine (SCr) and blood urea nitrogen (BUN), inhibiting inflammatory cytokine release, preventing fibrosis, and reducing apoptosis and oxidative stress. The TLR-4/NF-κB, TGF-β1/Smad3, and Nrf2/HO-1 signaling pathways may participate in sophocarpine-mediated renal protection ( Zhou et al, 2022 ). Lupus nephritis is a complication of the autoimmune disease systemic lupus erythematosus ( Anders et al, 2020 ).…”

Section: Pharmacological Activitiesmentioning

confidence: 99%

“…This mechanism leads to a reduction in inflammatory factors within the body, alleviation of oxidative stress, and ultimately safeguards the liver and lungs from damage caused by relevant detrimental factors. In the context of kidney function, NF-κB serves as a pivotal pathway for sophocarpine in addressing isoproterenol (iso)-induced kidney injury ( Zhou et al, 2022 ) while also exhibiting potential in managing autoimmune disorders such as lupus nephritis. By diminishing the production of anti-dsDNA antibodies and reducing immune complex deposition within renal tissues, NF-κB significantly contributes to the therapeutic efficacy of sophocarpine treatment ( Li et al, 2018 ).…”

Section: Association Of Sophocarpine With Inflammatory Cytokines Nf-κ...mentioning

confidence: 99%

A review on the pharmacology, pharmacokinetics and toxicity of sophocarpine

Wei,

Xiao,

et al. 2024

Front. Pharmacol.

View full text Add to dashboard Cite

Sophocarpine is a natural compound that belongs to the quinolizidine alkaloid family, and has a long history of use and widespread distribution in traditional Chinese herbal medicines such as Sophora alopecuroides L., Sophora flavescens Ait., and Sophora subprostrata. This article aims to summarize the pharmacology, pharmacokinetics, and toxicity of sophocarpine, evaluate its potential pharmacological effects in various diseases, and propose the necessity for further research and evaluation to promote its clinical application. A large number of studies have shown that it has anti-inflammatory, analgesic, antiviral, antiparasitic, anticancer, endocrine regulatory, and organ-protective effects as it modulates various signaling pathways, such as the NF-κB, MAPK, PI3K/AKT, and AMPK pathways. The distribution of sophocarpine in the body conforms to a two-compartment model, and sophocarpine can be detected in various tissues with a relatively short half-life. Although the pharmacological effects of sophocarpine have been confirmed, toxicity and safety assessments and reports on molecular mechanisms of its pharmacological actions have been limited. Given its significant pharmacological effects and potential clinical value, further research and evaluation are needed to promote the clinical application of sophocarpine.

show abstract

Sophocarpine Alleviates Isoproterenol-Induced Kidney Injury by Suppressing Inflammation, Apoptosis, Oxidative Stress and Fibrosis

Cited by 7 publications

References 31 publications

Protocatechuic acid prevents isoproterenol‐induced heart failure in mice by downregulating kynurenine‐3‐monooxygenase

Protocatechuic acid prevents isoproterenol‐induced heart failure in mice by downregulating kynurenine‐3‐monooxygenase

Completion of the DrugMatrix Toxicogenomics Database using ToxCompl

A review on the pharmacology, pharmacokinetics and toxicity of sophocarpine

Contact Info

Product

Resources

About