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Ecotoxicology and Environmental Safety Oct 2023Adverse reactions to traditional Chinese medicine have hindered the healthy development and internationalization process of the traditional Chinese medicine industry....
Adverse reactions to traditional Chinese medicine have hindered the healthy development and internationalization process of the traditional Chinese medicine industry. The critical issue that needs to be solved urgently is to evaluate the safety of traditional Chinese medicine systematically and effectively. Podophyllotoxin (PPT) is a highly active compound extracted from plants of the genus Podophyllum such as Dysosma versipellis (DV). However, its high toxicity and toxicity to multiple target organs affect the clinical application, such as the liver and kidney. Based on the concurrent effects of PPT's medicinal activity and toxicity, it would be a good example to conduct a systematic review of its safety. Therefore, this study revolves around the Toxicological Evidence Chain (TEC) concept. Based on PPT as the main toxic constituent in DV, observe the objective toxicity impairment phenotype of animals. Evaluate the serum biochemical indicators and pathological tissue sections for substantial toxic damage results. Using metabolomics, lipidomics, and network toxicology to evaluate the nephrotoxicity of PPT from multiple perspectives systematically. The results showed that PPT-induced nephrotoxicity manifested as renal tubular damage, mainly affecting metabolic pathways such as glycerophospholipid metabolism and sphingolipid metabolism. PPT inhibits the autophagy process of kidney cells through the PI3K/Akt/mTOR and Nrf2/HO1 pathways and induces the activation of oxidative stress in the body, thereby causing nephrotoxic injury. This study fully verified the feasibility of the TEC concept for the safety and toxicity evaluation of traditional Chinese medicine. Provide a research template for systematically evaluating the safety of traditional Chinese medicine.
Topics: Animals; Rats; Kidney; NF-E2-Related Factor 2; Phosphatidylinositol 3-Kinases; Podophyllotoxin; Proto-Oncogene Proteins c-akt; TOR Serine-Threonine Kinases; Podophyllum; Drugs, Chinese Herbal
PubMed: 37651795
DOI: 10.1016/j.ecoenv.2023.115392 -
Frontiers in Pharmacology 2023is a core Chinese herbal medicine for the treatment of diabetes and diabetic nephropathy (DN). It has been used for the treatment of diabetes for over 1,000 years.... (Review)
Review
is a core Chinese herbal medicine for the treatment of diabetes and diabetic nephropathy (DN). It has been used for the treatment of diabetes for over 1,000 years. Catalpol is the main active compound in Rehmannia roots. Current evidence suggests that catalpol exhibits significant anti-diabetic bioactivity, and thus it has attracted increasing research attention for its potential use in treating DN. However, no studies have systematically evaluated these effects, and its mechanism of action remains unclear. This study aimed to evaluate the effects of catalpol on DN, as well as to summarize its possible mechanisms of action, in DN animal models. We included all DN-related animal studies with catalpol intervention. These studies were retrieved by searching eight databases from their dates of inception to July 2022. In addition, we evaluated the methodological quality of the included studies using the Systematic Review Center for Laboratory animal Experimentation (SYRCLE) risk-of-bias tool. Furthermore, we calculated the weighted standard mean difference (SMD) with 95% confidence interval (CI) using the Review Manager 5.3 software and evaluated publication bias using the Stata (12.0) software. A total of 100 studies were retrieved, of which 12 that included 231 animals were finally included in this review. As compared to the control treatment, treatment with catalpol significantly improved renal function in DN animal models by restoring serum creatinine (Scr) ( = 0.0009) and blood urea nitrogen (BUN) ( < 0.00001) levels, reducing proteinuria ( < 0.00001) and fasting blood glucose (FBG) ( < 0.0001), improving kidney indices ( < 0.0001), and alleviating renal pathological changes in the animal models. In addition, it may elicit its effects by reducing inflammation and oxidative stress, improving podocyte apoptosis, regulating lipid metabolism, delaying renal fibrosis, and enhancing autophagy. The preliminary findings of this preclinical systematic review suggest that catalpol elicits significant protective effects against hyperglycemia-induced kidney injury. However, more high-quality studies need to be carried out in the future to overcome the methodological shortcomings identified in this review.
PubMed: 37621314
DOI: 10.3389/fphar.2023.1192694 -
Journal of Drug Targeting Sep 2023Renal fibrosis, characterised by glomerulosclerosis and tubulointerstitial fibrosis, is a typical pathological alteration in the progression of chronic kidney disease... (Review)
Review
Renal fibrosis, characterised by glomerulosclerosis and tubulointerstitial fibrosis, is a typical pathological alteration in the progression of chronic kidney disease (CKD) to end-stage renal disease (ESRD). However, the limited and expensive options for treating renal fibrosis place a heavy financial burden on patients and healthcare systems. Therefore, it is significant to find an effective treatment for renal fibrosis. Ferroptosis, a non-traditional form of cell death, has been found to play an important role in acute kidney injury (AKI), tumours, neurodegenerative diseases, and so on. Moreover, a growing body of research suggests that ferroptosis might be a potential target of renal fibrosis. Meanwhile, mitophagy is a type of selective autophagy that can selectively degrade damaged or dysfunctional mitochondria as a form of mitochondrial quality control, reducing the production of reactive oxygen species (ROS), the accumulation of which is the main cause of renal fibrosis. Additionally, as a receptor of mitophagy, NIX can release beclin1 to induce mitophagy, which can also bind to solute carrier family 7 member 11 (SLC7A11) to block the activity of cystine/glutamate antitransporter (system Xc-) and inhibit ferroptosis, thereby suggesting a link between mitophagy and ferroptosis. However, there have been only limited studies on the relationship among mitophagy, ferroptosis and renal fibrosis. In this paper, we review the mechanisms of mitophagy, and describe how ferroptosis and mitophagy are related to renal fibrosis in an effort to identify potential novel targets for the treatment of renal fibrosis.
Topics: Humans; Mitophagy; Ferroptosis; Acute Kidney Injury; Cystine; Mitochondria
PubMed: 37607069
DOI: 10.1080/1061186X.2023.2250574 -
Journal of Hazardous Materials Oct 2023Phthalates (PAEs) are widely used for their excellent ability to improve plastic products. As an essential endocrine axis that regulates the reproductive system, whether... (Review)
Review
Phthalates (PAEs) are widely used for their excellent ability to improve plastic products. As an essential endocrine axis that regulates the reproductive system, whether dysfunction of the hypothalamic-pituitary-gonadal (HPG) axis is involved in reproductive toxicity mediated by environmental endocrine disruptors PAEs has become a hot topic of widespread concern. This study systematically reviewed the adverse effects of multiple PAEs on the HPG axis in different models and objectively discussed the possible underlying mechanisms. The abnormal release of gonadotropin-releasing hormone and gonadotropin, dysfunction of sex hormone receptors and steroid hormone synthesis, and general damage, including cell proliferation, oxidative stress, apoptosis, and autophagy have been confirmed to be involved in this process. Although it is widely established that PAEs induce HPG axis dysfunction, the specific mechanisms involved remain unclear. From a systematic review of relevant publications, it appears that the abnormal expression of peroxisome proliferator-activated, aryl hydrocarbon, and insulin receptors mediated by PAEs is key upstream event that induces these adverse outcomes; however, this inference needs to be further verified. Overall, this study aimed to provide reliable potential biomarkers for future environmental risk assessment and epidemiological investigation of PAEs.
Topics: Reproduction; Gonadotropin-Releasing Hormone; Gonads; Endocrine System; Gonadal Steroid Hormones
PubMed: 37557049
DOI: 10.1016/j.jhazmat.2023.132182 -
Heart Failure Reviews Jan 2024Iron overload increases the production of harmful reactive oxygen species in the Fenton reaction, which causes oxidative stress in the body and lipid peroxidation in the... (Review)
Review
Iron overload increases the production of harmful reactive oxygen species in the Fenton reaction, which causes oxidative stress in the body and lipid peroxidation in the cell membrane, and eventually leads to ferroptosis. Diabetes is associated with increased intracellular oxidative stress, inflammation, autophagy, microRNA alterations, and advanced glycation end products (AGEs), which cause cardiac remodeling and cardiac diastolic contractile dysfunction, leading to the development of diabetic cardiomyopathy (DCM). While these factors are also closely associated with ferroptosis, more and more studies have shown that iron-mediated ferroptosis is an important causative factor in DCM. In order to gain fresh insights into the functions of ferroptosis in DCM, this review methodically summarizes the traits and mechanisms connected with ferroptosis and DCM.
Topics: Humans; Diabetic Cardiomyopathies; Ferroptosis; MicroRNAs; Autophagy; Diastole; Reactive Oxygen Species; Diabetes Mellitus
PubMed: 37555989
DOI: 10.1007/s10741-023-10336-z -
Chinese Medicine Aug 2023Pulmonary fibrosis is a chronic progressive interstitial lung disease caused by a variety of etiologies. The disease can eventually lead to irreversible damage to the... (Review)
Review
Pulmonary fibrosis is a chronic progressive interstitial lung disease caused by a variety of etiologies. The disease can eventually lead to irreversible damage to the lung tissue structure, severely affecting respiratory function and posing a serious threat to human health. Currently, glucocorticoids and immunosuppressants are the main drugs used in the clinical treatment of pulmonary fibrosis, but their efficacy is limited and they can cause serious adverse effects. Traditional Chinese medicines have important research value and potential for clinical application in anti-pulmonary fibrosis. In recent years, more and more scientific researches have been conducted on the use of traditional Chinese medicine to improve or reduce pulmonary fibrosis, and some important breakthroughs have been made. This review paper systematically summarized the research progress of pharmacological mechanism of traditional Chinese medicines and their active compounds in improving or reducing pulmonary fibrosis. We conducted a systematic search in several main scientific databases, including PubMed, Web of Science, and Google Scholar, using keywords such as idiopathic pulmonary fibrosis, pulmonary fibrosis, interstitial pneumonia, natural products, herbal medicine, and therapeutic methods. Ultimately, 252 articles were included and systematically evaluated in this analysis. The anti-fibrotic mechanisms of these traditional Chinese medicine studies can be roughly categorized into 5 main aspects, including inhibition of epithelial-mesenchymal transition, anti-inflammatory and antioxidant effects, improvement of extracellular matrix deposition, mediation of apoptosis and autophagy, and inhibition of endoplasmic reticulum stress. The purpose of this article is to provide pharmaceutical researchers with information on the progress of scientific research on improving or reducing Pulmonary fibrosis with traditional Chinese medicine, and to provide reference for further pharmacological research.
PubMed: 37537605
DOI: 10.1186/s13020-023-00797-7 -
Antioxidants (Basel, Switzerland) Jul 2023Ethanol consumption triggers oxidative stress by generating reactive oxygen species (ROS) through its metabolites. This process leads to steatosis and liver... (Review)
Review
Ethanol consumption triggers oxidative stress by generating reactive oxygen species (ROS) through its metabolites. This process leads to steatosis and liver inflammation, which are critical for the development of alcoholic liver disease (ALD). Autophagy is a regulated dynamic process that sequesters damaged and excess cytoplasmic organelles for lysosomal degradation and may counteract the harmful effects of ROS-induced oxidative stress. These effects include hepatotoxicity, mitochondrial damage, steatosis, endoplasmic reticulum stress, inflammation, and iron overload. In liver diseases, particularly ALD, macroautophagy has been implicated as a protective mechanism in hepatocytes, although it does not appear to play the same role in stellate cells. Beyond the liver, autophagy may also mitigate the harmful effects of alcohol on other organs, thereby providing an additional layer of protection against ALD. This protective potential is further supported by studies showing that drugs that interact with autophagy, such as rapamycin, can prevent ALD development in animal models. This systematic review presents a comprehensive analysis of the literature, focusing on the role of autophagy in oxidative stress regulation, its involvement in organ-organ crosstalk relevant to ALD, and the potential of autophagy-targeting therapeutic strategies.
PubMed: 37507963
DOI: 10.3390/antiox12071425 -
Journal of Traditional Chinese Medicine... Aug 2023To evaluate the effectiveness and safety of Xuebijing injection (XBJ) on coronavirus disease 2019 (COVID-19) in patients. (Meta-Analysis)
Meta-Analysis
OBJECTIVE
To evaluate the effectiveness and safety of Xuebijing injection (XBJ) on coronavirus disease 2019 (COVID-19) in patients.
METHODS
Related studies on multiple biological databases and websites were searched up to December 11, 2021 without language and publication time restrictions. Review Manager V.5.3 and Stata 14 software were used for data analysis.
RESULTS
Seven studies were finally included. The Metaanalysis showed that compared with the routine treatment alone, XBJ combined with the routine treatment can reduce the 28day mortality ( = 0.3, 95% : 0.12, 0.74), Creactive protein ( = -12.8, 95% : -23.13, 3.46), erythrocyte sedimentation rate ( = -9.32, 95% : -14.66, -3.98) and interleukin-6 (S = -0.6, 95% : -1.04, -0.17) levels and increase the leukocyte ( = 0.73, 95% : 0.42, 1.04) and lymphocyte count ( = 0.18, 95% : 0.07, 0.29) in peripheral blood; additionally, it has no obvious side effects ( = 1.11, 95% : 0.65, 1.9). There was no evidence that the XBJ combined therapy can improve the nucleic acid conversion rate and computed tomography improvement rate of COVID19 patients.
CONCLUSIONS
Preliminary evidence suggests that XBJ combined with routine treatment seems to be more effective than routine treatment for patients with COVID19. Limited by the number and quality of included papers, this finding still needs further validation by more studies.
Topics: Humans; COVID-19; Drugs, Chinese Herbal; Injections
PubMed: 37454247
DOI: 10.19852/j.cnki.jtcm.20230517.002 -
Journal of Thermal Biology May 2023Exposure to cold promotes cardiac remodeling, characterized by deleterious effects on structure and function, contributing to increased mortality from cardiovascular... (Review)
Review
Exposure to cold promotes cardiac remodeling, characterized by deleterious effects on structure and function, contributing to increased mortality from cardiovascular diseases. The mechanisms associated with these changes are poorly understood. This review gathers the literature data on the main alterations and mechanisms associated with the adverse cardiac structural and functional remodeling induced by cold exposure in mice. Original studies were identified by searching PubMed, Scopus, and Embase databases from January 1990 to June 2022. This systematic review was conducted in accordance with the criteria established by PRISMA and registered in PROSPERO (CRD42022350637). The risk of bias was evaluated by the SYRCLE. Eligible studies included original papers published in English that evaluated cardiac outcomes in mice submitted to short- or long-time cold exposure and had a control group at room temperature. Seventeen original articles were included in this review. Cold exposure induces pathological cardiac remodeling, characterized by detrimental structural and functional parameters, changes in metabolism and autophagy process, and increases in oxidative stress, inflammation, and apoptosis. In addition, Nppa, AT1, Fbp3, BECN, ETA, and MT, appear to play fundamental roles in regulating cardiac remodeling. We suggest that strategies that seek to minimize the CVD risk and adverse effects of cold exposure should target these agents.
Topics: Mice; Animals; Ventricular Remodeling; Heart; Cold Temperature; Oxidative Stress; Apoptosis
PubMed: 37321023
DOI: 10.1016/j.jtherbio.2023.103598 -
Fitoterapia Jul 2023Oxymatrine (OMT), was identified as a quinolizidine alkaloid, which was one of the major matrine-type alkaloids extracted from Sophora medicinal plants. Growing studies... (Review)
Review
Oxymatrine (OMT), was identified as a quinolizidine alkaloid, which was one of the major matrine-type alkaloids extracted from Sophora medicinal plants. Growing studies revealed that OMT has a wide range of beneficial pharmacological values, consisting of anticancer, antidiabetic, antivirus, and antiinflammtion, as well as the protective activities to the brain, liver, heart, lung, vascular, gastrointestinal, bone, kidney, and skin organs. Various in vitro and in vivo models of pharmacological actions were recorded in regard to the usage of alkaloidal OMT. Mechanisms underlying anticancer activity of this compound may have been possibly involved anti-proliferation, invasion, migration, angiogenesis, epithelial-mesenchymal transition of cells, autophagy, especially apoptotic cell deaths. OMT could reduce hyperglycemia and hyperlipemia in a high-fat diet and streptozotocin-stimulated diabetic mice by improving insulin secretion and sensitivity. OMT suppressed gastric ulcer via gastric inflammatory and oxidative inhibitions, and pro-apoptotic actions. It turns out that OMT is relatively safe for cell and animal experiments. In this study, we offer a systematic review of natural occurrence, pharmacological potentials, possible mechanisms of action, pharmacokinetics, and bioavailability. Clinical research with OMT is needed to extensively elucidate its health potential benefits.
Topics: Mice; Animals; Diabetes Mellitus, Experimental; Molecular Structure; Alkaloids; Matrines; Quinolizines
PubMed: 37295753
DOI: 10.1016/j.fitote.2023.105565