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BACKGROUND: Neurological disorders constitute a growing worldwide concern due to the progressive aging of the population and the risky behavior they represent. Herbal medicines have scientific relevance in the treatment of these pathologies. One of these substances, Astragaloside IV (AS-IV), is the main active compound present in the root of Astragalus membranaceus (Fisch.) Bge, a Chinese medicinal herb with neuroprotective properties. OBJECTIVE: In the present study we performed a systematic review that sought to comprehend the neuroprotective effect presented by AS-IV in experimental models of neurological disorders. METHODS: This study is a systematic review, where an electronic search in United States National Library of Medicine (PubMed), Science Direct, Cochrane Library, Scientific Electronic Library Online (SciELO), Scopus, Web of Science, Medline via Proquest and Periodicos Capes databases covering the years between 2007 and 2017, using "Astragaloside IV" and "Neurodegenerative diseases"; "Astragaloside IV" and " Neurological disorders" as reference terms was made. RESULTS: A total of 16 articles were identified, in which the efficacy of AS-IV was described in experimental models of Parkinson's disease, Alzheimer's disease, cerebral ischemia and autoimmune encephalomyelitis, by improving motor deficits and/or neurochemical activity, especially antioxidant systems, reducing inflammation and oxidative stress. CONCLUSION: The findings of the present study indicate that the administration of AS-IV can improve behavioral and neurochemical deficits largely due to its antioxidant, antiapoptotic and antiinflammatory properties, emerging as an alternative therapeutic approach for the treatment of neurological disorders.

OBJECTIVE: To examine the efficacy of early intervention (4 weeks before pollen dispersal) with sphenopalatine ganglion (Xinwu acupoint) stimulation in patients with allergies after the onset of seasonal allergic rhinitis (SAR). METHODS: This is a prospective, randomized and unblinded half-open study. Forty-one SAR volunteers were randomly assigned to either the sphenopalatine ganglion (SPG) acupuncture plus supplementary acupuncture (SPG group) or the sham-SPG acupuncture plus supplementary acupuncture (SA group) stimulation 4 weeks before the onset of allergy season. The changes of the total nasal symptom score (TNSS) and the Rhinoconjunctivitis Quality of Life Questionnaire (RQLQ) scores were measured on the first week in the onset of allergy season. RESULTS: Four patients dropped out due to local hematoma and pain in the SPG and SA groups. The remaining 37 patients continued through to the end of the trial. After early intervention 4 weeks before the onset of allergy season, the sneezing, nasal congestion and itchiness scores in the first week of onset time were significantly lower in the SPG group than in the SA group patients ( 0.001). The RQLQ score obtained at the onset of symptoms indicated that symptoms were more significantly ameliorated in the SPG group than in the SA group (0.001). CONCLUSIONS: The results of this study confirmed that early intervention by sphenopalatine ganglion (Xinwu acupoint) stimulation can effectively improve the symptoms and the quality of SAR patients' daily lives.

BACKGROUND: Astragaloside IV (As), a bioactive tetracyclic triterpenoid saponin from Astragalus membranaceus, exhibits diverse pharmacological properties including anti-inflammatory, anticancer and immunomodulatory activities. However, its potential role as a targeted therapeutic agent for cisplatin sensitization in triple-negative breast cancer (TNBC) via the STING signaling pathway remains unexplored. PURPOSE: This study aimed to investigate the cisplatin-sensitizing potential of As in TNBC and elucidate its underlying molecular mechanisms. METHODS: Bioinformatic analysis identified key module genes from public databases using weighted gene co-expression network analysis (WGCNA), followed by feature selection via least absolute shrinkage and selection operator (LASSO) regression. Immune microenvironment characterization was performed using CIBERSORT deconvolution analysis. Potential targets of As in TNBC were systematically identified through multi-database mining, protein-protein interaction (PPI) network construction, pathway enrichment analysis and molecular docking simulations. Transcriptomic profiling revealed treatment-induced differentially expressed genes and enriched signaling pathways in murine tissues. The combinatorial anti-tumor efficacy was evaluated using orthotopic TNBC model (4T1 cell-derived) in vivo and 4T1, MDA-MB-231, and MCF-7 cell lines in vitro. Mechanistic validation was conducted through integrated in vivo and in vitro experiments. RESULTS: Integrated bioinformatics analysis (WGCNA, LASSO, and CIBERSORT) identified STING within a chemotherapy-sensitive module among six endoplasmic reticulum (ER)-associated gene co-expression networks. STING exhibited significant enrichment in antitumor immune pathways and correlated with heterogeneous immune cell infiltration. KEGG pathway analysis implicated immune/inflammatory signaling and DNA damage responses in the cisplatin-sensitizing effects of As. Molecular docking confirmed stable binding between As and STING (binding energy: -36.09 kcal/mol). In vivo, As synergistically enhanced cisplatin's tumor growth inhibition while mitigating cisplatin-induced toxicity, including weight loss, nephrotox

Saposhnikoviae Radix (SR) may enhance the pharmacodynamics of Huangqi Chifeng Tang (HQCFT) in the treatment of cerebral infarction according to our previous research, but the underlying mechanism is unknown. Herein, an in vivo pharmacokinetic assay in rats and in vitro MDCK-MDR1 cell assays were used to investigate the possible mechanism of SR, its main components, and its interactions with Astragali Radix (AR) and Paeoniae Radix (PR). An ultrahigh-performance liquid chromatography-tandem mass spectrometry (UPLC‒MS/MS)-based analytical method for quantifying astragaloside IV (ASIV) and paeoniflorin (PAE) in microdialysis and transport samples was developed. The pharmacokinetic parameters of SR were determined using noncompartmental analyses CCK-8 assays were used to detect the cytotoxicity of ASIV, PAE, cimifugin (CIM), prim-o-glucosylcimifugin (POG) and their combinations. Moreover, drug transport was studied using MDCK-MDR1 cells. Western blotting was performed to measure the protein expression levels of P-GP and MRP1. Claudin-5, ZO-1, and F-actin expression was determined via immunohistochemical staining of MDCK-MDR1 cells. harmacokinetic studies revealed that, compared with those of Huangqi Chifeng Tang-Saposhnikoviae Radix (HQCFT-SR), the Tmax of ASIV increased by 11.11 %, and the MRT0-t and Tmax of PAE increased by 11.19 % and 20 %, respectively, in the HQCFT group. Transport studies revealed that when ASIV was coincubated with 28 μM CIM or POG, the apparent permeability coefficient (Papp) increased by 71.52 % and 50.33 %, respectively. Coincubation of PAE with 120 μM CIM or POG increased the Papp by 87.62 % and 60.95 %, respectively. Moreover, CIM and POG significantly downregulated P-gp and MRP1 (P < 0.05), inhibited the expression of Claudin-5, ZO-1, and F-actin (P < 0.05), and affected intercellular tight junctions (TJs). In conclusion, our study successfully established a selective, sensitive and reproducible UPLC‒MS/MS analytical method to detect drug‒drug interactions between SR, AR and PR in vivo and in vitro, which is beneficial for enhancing the therapeutic efficacies of AR and PR. Moreover, this study provides a theoretical basis for further res

Vericiguat (VER) is a novel soluble guanylate cyclase stimulator treating symptomatic chronic heart failure (HF), and it is a substrate of both transporters P-glycoprotein and breast cancer resistance protein (BCRP). Astragaloside IV (ASIV) is the main active ingredient in Radix Astragali (Huangqi), a traditional Chinese medicine widely used for HF treatment in China. ASIV's effect on the protein expression of P-glycoprotein and BCRP has been observed, its impact on VER metabolism remain uncertain. In the present study, male Sprague-Dawley rats were administered with 20 mg/kg ASIV and 1 mg/kg VER to study their pharmacokinetics. Blood samples were subject to liquid-liquid extraction, and riociguat was employed as the internal standard (IS). The analytical method involved a C18 column (XSelect® HSS T3 column, 2.1 × 100 mm, 2.5 μm) with a mobile phase of 0.1% formic acid and acetonitrile for gradient elution. The flow rate of the mobile phase was set at 0.2 mL/min, and 5 µL of the sample was used for analysis. The positive ion multi-response monitoring mode was utilized with a transition of m/z 427.4→109.1 for VER and m/z 423.3→109.1 for the IS. The method exhibited good linearity within the concentration range of 0.1 to 300 ng/mL (r = 0.9987), and all the validation processes were conducted in accordance with the requirements of biological analysis. The pharmacokinetic results revealed that ASIV did not significantly alter the main parameters of VER, except for Cmax, which decreased by 33.2% (P < 0.05). Overall, our study successfully established a selective, sensitive and repeatable ultra-high performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) analysis for detecting VER in rat plasma.

Hepatotoxicity is a well-known adverse effect of many substances, with toxicity often resulting from interactions of drugs with other drug-like substances. With the increased availability of complementary and alternative medicines, including herbal medicines, the likelihood of adverse interactions between drugs and drug-like substances in herbs increases. However, the impact of potential herb-herb interactions is little understood. To assess the potential of two cytochrome P450 enzyme modulating phytochemicals common to many herbal medicines, atractylenolide I (ATR-I) and astragaloside IV (AST-IV), to interact with coumarin, another phytochemical common in many foods, a hepatocyte function model with a liver carcinoma cell line, HepG2, was exposed to these agents. To determine the effects of cytochrome P450 modulation by these phytochemicals certain cells were induced with rifampicin to induce cytochrome P450. Increasing concentrations of ATR-I combined with a fixed, nontoxic concentration of coumarin (200 µM), demonstrated significant additive interactions. 300 µM ATR-I produced a 31% reduction in cell viability (p < 0.01) with coumarin in rifampicin uninduced cells. In rifampicin-induced cells, ATR-I (100-300 µM) produced a significant reduction in cell viability (p < 0.01) with coumarin (200 µM). AST-IV with fixed coumarin (200 µM) showed 27% toxicity at 300 µM AST-IV in rifampicin uninduced cells (p < 0.05) and 30% toxicity in rifampicin induced cells (p < 0.05). However, when fixed coumarin and AST-IV were combined with increasing concentrations of ATR-I no further significant increase in toxicity was observed (p > 0.05). These results demonstrate the potential toxic interactive capabilities of common traditional Chinese herbal medicine phytochemicals and underline the potential importance of coumarin-mediated toxicity.

BACKGROND: Astragaloside IV (AST) and metoprolol are often used together to treat cardiovascular diseases, while the herb-drug interaction (HDI) between them is still unclear. OBJECTIVE: This study investigates the effect of AST on the pharmacokinetics of metoprolol in rats and its mechanism to predict the HDI. METHOD: First, IC50 value of AST on nine CYP450 enzymes in human liver microsomes (HLMs) was determined by the cocktail method. We explored the effect of AST on the pharmacokinetics of metoprolol (metabolized by CYP2D6) in vivo. Twelve male SD rats were equally divided into two groups, with or without pretreatment of AST (3 mg/kg/day) for 7 days, and they received metoprolol (27 mg/kg) by oral administration. Blood samples were determined using HPLC. Finally, the mechanism of AST was explored. RESULTS: AST exhibited a moderate inhibitory effect on CYP2D6 with IC50 value of 32.28 μM. The pharmacokinetic parameters of metoprolol were significantly altered by AST with the increase of AUC0-∞ (538.81 ± 51.41 to 1088.34 ± 86.46 μg*min/mL, P<0.05) and Cmax (6.21 ± 0.56 to 8.34 ± 0.87 μg/ml, P<0.05). The investigation of the mechanism showed AST to be an irreversible inhibitor of CYP2D6 with KI value of 2.9 μM and Kinact of 0.018 min-1, respectively. CONCLUSION: AST was found to increase the plasma exposure of metoprolol in rats. AST reduced the metabolism of metoprolol by inhibiting CYP2D6 activity. The HDI might enhance when metoprolol and AST will be applied in combination.

Context: Puerarin and astragaloside IV (AS-IV) are sometimes used together for the treatment of disease in Chinese clinics, however, the drug-drug interaction between puerarin and AS-IV is still unknown.Objective: This study investigates the effects of puerarin on the pharmacokinetics of astragaloside IV in rats and clarifies its main mechanism.Materials and methods: The pharmacokinetic profiles of oral administration of astragaloside IV (20 mg/kg) in Sprague-Dawley rats, with or without pre-treatment of puerarin (100 mg/kg/day for 7 days) were investigated. The effects of puerarin on the transport and metabolic stability of AS-IV were also investigated using Caco-2 cell transwell model and rat liver microsomes.Results: The results showed that puerarin could significantly increase the peak plasma concentration (from 48.58 ± 7.26 to 72.71 ± 0.62 ng/mL), and decrease the oral clearance (from 47.5 ± 8.91 to 27.15 ± 9.27 L/h/kg) of AS-IV. The Caco-2 cell transwell experiments indicated that puerarin could decrease the efflux ratio of astragaloside IV from 1.89 to 1.26, and the intrinsic clearance rate of astragaloside IV was decreased by the pre-treatment with puerarin (34.8 ± 2.9 vs. 41.5 ± 3.8 μL/min/mg protein).Discussion and conclusions: These results indicated that puerarin could significantly change the pharmacokinetic profiles of astragaloside IV, via increasing the absorption of astragaloside IV or inhibiting the metabolism of astragaloside IV in rats.

Decreased chemosensitivity among tumor cells is often an obstacle in cisplatin (Cis) chemotherapy. Overexpression of multidrug resistance-associated protein 2 (MRP2) is a key mechanism underlying decreased Cis chemosensitivity and resistance. Astragaloside IV (AS IV) is an important component derived from the well-known traditional Chinese herb Astragalus membranaceus. The aim of this study was to explore the role of AS IV in enhancing the antitumor effect of Cis by suppressing MRP2 expression in HepG2 cells and H22 tumor-bearing mice. After co-treatment of HepG2 cells with Cis and AS IV, we assessed the effects on cell proliferation and apoptosis. Tumor growth and apoptosis assessment were performed to assess chemosensitivity in H22 tumor-bearing mice. We used western blotting, immunofluorescence assays, and immunohistochemistry assays to detect MRP2 expression in HepG2 cells, H22 tumor tissues and mouse kidney tissues. AS IV enhanced Cis chemosensitivity by increasing tumor cell apoptosis and slowing tumor growth in vitro and in vivo. MRP2 overexpression in tumor cells was induced by Cis, which contributes to decreased chemosensitivity and Cis resistance. Co-administration of AS IV suppressed MRP2 expression in tumor tissues, which might be an important mechanism for enhancing Cis chemosensitivity in hepatocellular carcinoma. Moreover, AS IV alleviated Cis-induced kidney injury in mice without changing MRP2 expression. In total, AS IV enhanced the antitumor effect of Cis against hepatocellular carcinoma by suppressing MRP2 expression in tumor cells. The results provide a new insight into the combined use of a chemotherapy drug and natural ingredients to treat cancer.

Context: It is common to combine two or more drugs in clinics in China. Triptolide (TP) has been used primarily for the treatment of inflammatory and autoimmune diseases. Astragaloside IV (AS-IV) has been applied with many other drugs, due to its various pharmacological effects. AS-IV and TP can be used together for the treatment of diseases in clinics in China.Objective: This study investigates the effects of astragaloside IV (AS-IV) on the pharmacokinetics of TP in rats and its potential mechanism.Materials and methods: The pharmacokinetics of orally administered triptolide (2 mg/kg) with or without AS-IV pre-treatment (100 mg/kg/day for 7 d) were investigated. Additionally, the effects of AS-IV on the transport of triptolide were investigated using the Caco-2 cell transwell model.Results: The results indicated that when the rats were pre-treated with AS-IV, the Cmax of triptolide decreased from 418.78 ± 29.36 to 351.31 ± 38.88 ng/mL, and the AUC0-t decreased from 358.83 ± 19.56 to 252.23 ± 15.75 μg/h/L. The Caco-2 cell transwell experiments indicated that AS-IV could increase the efflux ratio of TP from 2.37 to 2.91 through inducing the activity of P-gp.Discussion and conclusions: In conclusion, AS-IV could decrease the system exposure of triptolide when they are co-administered, and it might work through decreasing the absorption of triptolide by inducing the activity of P-gp.

BACKGROUND: Due to the multi-factorial etiology of hepatic fibrosis, multi-target therapeutics based on combinatory drugs is known to be a promising strategy for the disease. AIMS: The present study attempted to test the hypothesis that astragaloside IV combined with ferulic acid synergistically inhibits activation of hepatic stellate cells in vivo. METHODS: Bile duct-ligated rats were treated with astragaloside IV or/and ferulic acid for 28 days. Liver fibrosis was measured by histological examination. The oxidative stress-related biomarkers were measured with spectrophotometry. Expressions of mRNA and protein were measured by real-time PCR and Western blotting. RESULTS: Bile duct-ligated rat treatment with astragaloside IV and ferulic acid in combination resulted in synergistic alleviation of hepatic fibrosis. Simultaneously, activation of hepatic stellate cells was significantly inhibited by the combination therapy when compared with astragaloside IV or ferulic acid alone. Interestingly, astragaloside IV, but not ferulic acid, induced accumulation of Nrf2 in the nucleus, synthesized antioxidant enzymes through negative regulation of glycogen synthase kinase-3β, scavenged reactive oxygen species, and, in turn, suppressed hepatic stellate cells activation in bile duct-ligated rats. Conversely, ferulic acid, but not astragaloside IV, suppressed TGF-β1 and its receptors expression, which resulted in downregulation of Smad3 and Smad4. CONCLUSIONS: These findings suggest that the combination of astragaloside IV and ferulic acid synergistically induces deactivation of hepatic stellate cells through inhibition of the TGF-β pathway and activation of the Nrf2 pathway, and suggest that combination of astragaloside IV and ferulic acid is a promising candidate for the treatment of hepatic fibrosis.

ATP-binding cassette (ABC) transporters, such as P-glycoprotein (P-gp) and breast cancer resistance protein (BCRP), often reduce drug efficacy and are the major cause of drug resistance. Astragaloside IV (ASIV), one of the bioactive saponins isolated from Astragalus membranaceus, has been demonstrated to alleviate the progression of experimental autoimmune encephalomyelitis (EAE) in mice, an animal model for multiple sclerosis (MS). In the present study, we found for the first time that ASIV induced the upregulation of P-gp and BCRP in the central nervous system (CNS) microvascular endothelial cells of EAE mice. Further study disclosed that tariquidar, a P-gp inhibitor, could facilitate the penetration of ASIV into CNS. On bEnd.3 cells, a mouse brain microvascular endothelial cell line, tariquidar benefited the net uptake and transport of ASIV. Additional molecular docking experiment suggested that ASIV might be a potential substrate of P-gp. In EAE mice, tariquidar was demonstrated to enhance the efficacy of ASIV, as shown by attenuated clinical symptom and reduced incidence rate as well as mitigated inflammatory infiltration and decreased demyelination in the CNS. Collectively, our findings implicate that P-gp inhibitor can promote the therapeutic efficacy of ASIV on EAE mice, which may boost its clinical usage together with ASIV in the therapy of MS.

BACKGROUND: Skin aging results from intrinsic and extrinsic factors, including oxidative stress, ultraviolet (UV) radiation, and declining cellular functions. These factors lead to visible changes like rhytids, pigmentation, and loss of elasticity. Meanwhile, interest in plant-based skincare ingredients for skin aging has been increasing. OBJECTIVE: This systematic review investigates the anti-aging potential of Astragalus membranaceus, a botanical plant. The authors focused on its active components and their roles in dermal protection, antioxidant, anti-inflammatory, anti-aging properties, and telomere elongation. METHODS: A comprehensive PubMed search from 2015 to 2025 per PRISMA guidelines identified clinical and experimental studies assessing the anti-aging effects of Astragalus membranaceus. RESULTS: Bioactive compounds, including astragaloside IV, cycloastragenol, flavonoids, and polysaccharides, showed photoprotective effects, including reactive oxygen species (ROS) reduction, inflammatory signaling inhibition, mitochondrial preservation, and promotion of collagen synthesis. Elongation of telomeres under oxidative stress was also demonstrated with Astragaloside IV. Clinical trials showed improvements in skin hydration, tone, and wrinkle reduction. CONCLUSION: Astragalus membranaceus offers promise as a botanical anti-aging agent. Its effects on collagen, oxidative defense, and telomere preservation support its potential use in cosmeceuticals. However, further randomized trials are needed to confirm long-term efficacy and safety. &nbsp.

ETHNOPHARMACOLOGICAL RELEVANCE: Myocardial fibrosis (MF),characterized by excessive extracellular matrix (ECM) remodeling, represents a central pathological process in progressive cardiovascular diseases and drives cardiac functional impairment.Contemporary anti-fibrotic therapies face limitations due to inadequate target specificity and systemic toxicity, whereas bioactive compounds derived from traditional Chinese medicine (TCM) offer novel multi-target therapeutic strategies for MF reversal. AIM OF THE STUDY: This review synthesizes evidence on molecular mechanisms by which TCM compounds modulate fibrotic signaling networks, providing translational insights for precision anti-fibrotic interventions. MATERIALS AND METHODS: Following PRISMA guidelines,we systematically searched major scientific databases (PubMed, Web of Science, Embase, Cochrane Library, CNKI) from January 2000 to September 2025 using predefined keywords: myocardial fibrosis, traditional Chinese medicine, bioactive compounds, and herbal pharma cology. Eligible experimental studies elucidating mechanistic pathways were analyzed to map chemical constituents, pharmacological actions, and pathway interactions. RESULTS: TCM-derived compounds including tanshinone IIA and astragaloside IV demonstrate anti-MF efficacy by suppressing fibroblast activation and collagen deposition through coordinated modulation of TGF-β1/Smad, MAPK, and NF-κB pathways, correlating with reduced MF severity and improved cardiac function. CONCLUSION: TCM bioactives exhibit unique therapeutic potential by remodeling the fibrotic microenvironment through multi-modal signaling pathways, overcoming limitations of single-target approaches.Current constraints include insufficient validation in dynamic disease models and interspecies pharmacokinetic variability.Future research should prioritize integrating organ-on-a-chip systems with spatial metabolomics. To bridge current translational gaps, future studies must converge cutting-edge technologies: (1) Organ-on-a-chip platforms simulating human cardiac microenvironments; (2) Spatial metabolomics mapping compound distribution; and (3) AI-driven screening to construct predictive comp

BACKGROUND: Astragaloside IV (AS-IV), a key monomeric compound extracted from the traditional Chinese medicine Astragalus membranaceus, has demonstrated significant therapeutic potential in cancer treatment. Hepatocellular carcinoma (HCC), as a malignant tumor posing severe threats to global health, is characterized by high incidence and mortality rates, imposing substantial burdens on patients, families, and society. Numerous studies have demonstrated that AS-IV exhibits significant inhibitory effects on HCC. However, the precise underlying mechanisms remain unclear. Therefore, this systematic review provides a comprehensive summary of current research findings. METHODS: This systematic review comprehensively evaluates the molecular mechanisms of AS-IV in HCC through extensive literature retrieval from five authoritative databases, encompassing studies published from their inception to March 2025. RESULTS: A total of 172 potentially relevant articles were retrieved through database search. After screening, a total of 16 articles finally met the qualification criteria. CONCLUSION: Current evidence indicates that AS-IV exerts crucial therapeutic effects in HCC through multiple pathways: inhibiting tumor cell proliferation, migration, and invasion; inducing apoptosis; modulating immune responses; reducing drug resistance while enhancing chemosensitivity; and suppressing angiogenesis. However, large-scale, well-designed multicenter randomized controlled trials are warranted to establish more robust clinical evidence, thereby solidifying the foundation for AS-IV's broader application in HCC therapeutics. © 2025. The Author(s).

This systematic review and meta-analysis were conducted to evaluate the therapeutic efficacy of Astragaloside IV (As-IV) in ischemic heart disease based on the preclinical evidence and to correlate the cardioprotective effect with various available mechanisms. This systematic review and meta-analysis were conducted based on the results of a thorough literature search in databases of published papers, such as PubMed, Embase, and Google Scholar. A total of 18 studies that met the inclusion/exclusion criteria were included. The meta-analysis has shown the significant therapeutic efficacy of As-IV on ischemic heart disease. As-IV has decreased the myocardial infarction size, the left ventricular weight indices, the left ventricular internal diameter in systole, and the left ventricular internal diameter in diastole. As-IV has decreased the level of the third type of collagen and the decreased activity of creatine kinase and lactate dehydrogenase. Also, As-IV has markedly decreased the rate of apoptosis and the expression of the proapoptotic markers such as caspase-3 and Bax. The left ventricular systolic pressure, as well as the arterial shortening edge and the ejection fraction, has increased. The levels of the antiapoptotic protein Bcl-2 increased. In addition, As-IV has a powerful anti-inflammatory influence by inhibiting the main markers of inflammation, such as TLR4, IL-1, TNF-α, and TGF-β. As-IV has also caused an effect on angiogenesis by increasing the VEGF level. The results have revealed the As-IV, as a decent universal medicine for ischemic heart disease because of its variety of actions and effectiveness. © 2025 The Author(s). Journal of Biochemical and Molecular Toxicology published by Wiley Periodicals LLC.

ETHNOPHARMACOLOGICAL RELEVANCE: Apoptosis of renal tubular epithelial cells (RTECs) is a critical pathological feature of diabetic kidney disease (DKD), a primary contributor to end-stage renal disease (ESRD). Traditional Chinese medicine (TCM) has shown potential in modulating RTECs apoptosis and alleviating DKD progression, making it a promising area for further investigation. AIM OF THE STUDY: This study aims to summarize the apoptotic pathways implicated in DKD, analyze existing research on the effects of TCM monomers and compounds on RTECs apoptosis, and elucidate the molecular mechanisms underlying these effects. Additionally, this study emphasizes the significant role of TCM in mitigating DKD progression. MATERIALS AND METHODS: Relevant literature was systematically retrieved from ancient Chinese medicine texts and modern scientific databases, including CNKI, Web of Science, and PubMed, using keywords such as "Traditional Chinese Medicine", "Diabetic Kidney Disease", "Diabetic Nephropathy", "Renal Tubular Epithelial Cells", and "Apoptosis". The collected information was synthesized and analyzed. RESULTS: This review systematically analyzed 187 relevant studies, focusing on the mechanisms and clinical applications of 16 TCM monomers and 20 TCM compounds in DKD treatment. Key bioactive compounds, such as berberine, astragaloside IV, and tanshinone IIA, have demonstrated renoprotective effects by mitigating oxidative stress and inflammation, as well as regulating critical signaling pathways, including PI3K/Akt, NF-κB, and TGF-β/Smad, to suppress RTECs apoptosis and decelerate DKD progression. Additionally, several TCM compounds have shown significant efficacy in clinical studies, reducing proteinuria and enhancing renal function, thereby reinforcing the therapeutic potential of TCM in DKD management. CONCLUSIONS: RTECs apoptosis is a critical pathological feature of DKD. TCM exhibits significant therapeutic potential by intervening in this process through multiple pathways. This study highlights the ability of TCM to exert anti-apoptotic and renoprotective effects by modulating oxidative stress, inflammatory responses, and multiple cellular signaling pathway

CONTEXT: Myocardial fibrosis is a common manifestation of end-stage cardiovascular disease, but there is a lack of means to reverse fibrosis. Astragaloside IV (AS-IV), the major active component of Astragalus membranaceus Fisch. ex Bunge Fabaceae, possesses diverse biological activities that have beneficial effects against cardiovascular disease. OBJECTIVE: This systematic review aims to summarize the anti-fibrosis effect of AS-IV in animal models (rats or mice only) and its underlying mechanisms, and provide potential directions for the clinical use of AS-IV. METHODS: PubMed, EMBASE, Web of Science, CNKI, Wanfang database, and SinoMed were searched from inception to 31 December 2024. The following characteristics of the included studies were extracted and summarized: animal model, route of administration, dose/concentration, measurement indicators, and potential mechanisms. The quality of the included studies was assessed used a 10-item scale from SYRCLE. RESULTS AND CONCLUSION: AS-IV represents a promising multi-target candidate for myocardial fibrosis treatment in the 24 eligible studies included in the analysis. This systematic review is the first to comprehensively evaluate the anti-fibrosis mechanisms of AS-IV across heterogeneous cardiovascular disease animal models, including myocardial infarction, hypertension, ischemia-reperfusion injury, and myocarditis. The underlying mechanisms of the anti-fibrosis effects of AS-IV may include collagen metabolism, anti-apoptosis, anti-inflammation and, pyroptosis, antioxidants, improving mitochondrial function, regulating senescence, etc. Current evidence remains preclinical, with critical gaps in toxicological profiles, human safety thresholds, and clinical adverse reaction data. Future research must integrate robust toxicological evaluations, optimized combination therapies, and adaptive clinical trials to validate translational potential.

The in-hospital mortality rate in acute myocardial infarction (AMI) remains high despite the undoubted achievements in treatment of this disease achieved in the last 40 years. The dangerous complications of AMI remain cardiac microvascular injury (CMI) and intramyocardial hemorrhage (IMH). IMH is a widespread pathology that occurs in 42 - 57% of patients with ST-segment elevation myocardial infarction and percutaneous coronary intervention. IMH is associated with larger infarct size and contractile dysfunction. IMH is accompanied by inflammation. The appearance of IMH is depending on the duration of ischemia and requires reperfusion of the heart. IMH is accompanied by contractile dysfunction and adverse remodeling of the heart. The most likely cause of IMH is CMI. Pretreatment with ATL-146e, melatonin, tanshinone IIA, relaxin, empagliflozin, dapagliflozin, and astragaloside IV can mitigate I/R-induced CMI. CMI is accompanied by an increase in the myocardial and plasma proinflammatory cytokine levels and also the downregulation of tight junction proteins in cardiac vascular endothelial cells. However, there is no convincing evidence that proinflammatory cytokines trigger CMI. An increase in the proinflammatory cytokine levels and CMI could be two independent processes.

Erratum in Biomed Pharmacother. 2023 Oct 27:115787. doi: 10.1016/j.biopha.2023.115787. Astragaloside IV (AS-IV), a traditional Chinese medicine, is often used to treat cancer. Colorectal cancer imposes a heavy burden on patients and society. It is essential to update the clinical evidence supporting AS-IV in the treatment of colorectal cancer. The purpose of this review is to systematically evaluate the molecular pathway and safety of AS-IV in colorectal cancer. 7 databases were queried for Jan 2012-Dec 2022. A total of 37 related articles were retrieved. 8 papers were included to evaluate the role of AS-IV in colorectal cancer and make a review. AS-IV plays vital roles in colorectal cancer, especially in the suppression of proliferation, inducing tumor cell apoptosis, increasing immune function and reducing drug resistance. Furthermore, AS-IV has been proved to regulate many signaling pathways, which are usually affected by most cancers. However, a large-scale and well-designed multicenter randomized controlled study ensures that the safety and optimal dose of AS-IV will be determined in the future.

Astragaloside IV (ASIV) is the essential active component of astragalus that has diverse biological activities. Previous research has suggested its potentially beneficial effects on diabetic nephropathies. However, its effects and protective mechanism remain unclear. In this study, we conducted a preclinical systematic review to evaluate the efficacy and potential mechanisms of ASIV in reducing kidney damage in diabetes mellitus (DM) models. Studies were searched from nine databases until January 2020. A random-effects model was used to calculate combined standardised mean difference estimates and 95 % confidence intervals. Risk of bias of studies was assessed using the Systematic Review Center for Laboratory Animal Experimentation risk of bias tool 10-item checklist. RevMan 5.3 software was used for statistical analysis. Twenty-three studies involving 562 animals were included in the meta-analysis. Studies quality scores ranged from 2 to 5. The ASIV group induced a marked decrease in serum creatinine (P < 0.00001), blood urea nitrogen (P < 0.00001), 24-h urine protein (P < 0.00001) and pathological score (P < 0.001) compared with the control group. The determined potential mechanisms of ASIV action were relieving oxidative stress, delaying renal fibrosis, anti-apoptosis and anti-inflammatory action. We conclude that ASIV exerts renal protective effects in animals with DM through multiple signalling pathways.