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Diabetic nephropathy (DN) is a common and serious micro-vascular complication of diabetes and a leading cause of end-stage renal disease globally. This disease primarily affects middle-aged and elderly individuals, especially those with a diabetes history of over 10 years and poor long-term blood glucose control. Small ubiquitin-related modifiers (SUMOs) are a group of reversible post-translational modifications of proteins that are widely expressed in eukaryotes. SUMO proteins intervene in the progression of DN by modulating various signaling cascades, such as Nrf2-mediated oxidative stress, NF-κB, TGF-β, and MAPK pathways. Recent advancements indicate that natural products regulating SUMOylation hold promise as targets for intervening in DN. In a previous article published in 2022, we reviewed the mechanisms by which SUMOylation intervenes in renal fibrosis and presented a summary of some natural products with therapeutic potential. Therefore, this paper will focus on DN. The aim of this review is to elucidate the mechanism of action of SUMOylation in DN and related natural products with therapeutic potential, thereby summarising the targets and candidate natural products for the treatment of DN through the modulation of SUMOylation, such as ginkgolic acid, ginkgolide B, resveratrol, astragaloside IV, etc., and highlighting that natural product-mediated modulation of SUMOylation is a potential therapeutic strategy for the treatment of DN as a potential therapeutic strategy. [ABSTRACT FROM AUTHOR]

Bone marrow mesenchymal stem cells (BMECs)-derived exosomes (MSC-Exo) can improve acute myocardial infarction (AMI). Astragaloside IV (AS-IV) has also been reported to have cardioprotective pharmacological effects. However, it is not entirely clear whether AS-IV can improve AMI by inducing MSC-Exo. BMSCs and MSC-Exo were isolated and identified, and we also established the AMI rat model and the OGD/R model with H9c2 cells. After MSC-Exo or AS-IV-mediated MSC-Exo treatment, cell angiogenesis, migration, and apoptosis were evaluated by tube formation, wound healing, and TUNEL staining. The cardiac function of the rats was measured by echocardiography. The pathological changes and collagen deposition in rats were also assessed with Masson and Sirius red staining. The levels of α-SMA, CD31 and inflammatory factors were determined by immunohistochemistry and enzyme-linked immunosorbent assay (ELISA). In vitro, AS-IV-mediated MSC-Exo can significantly enhance the angiogenesis and migration of H9c2 cells induced by OGD/R, and significantly reduce their apoptosis. In vivo, AS-IV-mediated MSC-Exo can improve the cardiac function of rats, and attenuate pathological damage and collagen deposition in AMI model rats. In addition, AS-IV-mediated MSC-Exo can also promote angiogenesis and reduce inflammatory factors in rats with AMI. AS-IV-stimulated MSC-Exo can improve myocardial contractile function, myocardial fibrosis and angiogenesis, reduce inflammatory factors and induce apoptosis in rats after AMI. [ABSTRACT FROM AUTHOR]

Inflammation induced by angiotensin II (Ang II) is a key event in the progression of numerous cardiovascular diseases. Astragaloside IV (AS‐IV), a glycoside extracted from Astragalus membranaceus Bunge, has been shown to inhibit Ang II–induced inflammatory responses in vivo. However, the mechanisms underlying the beneficial effects are still unclear. This study investigated whether AS‐IV attenuates endothelial inflammation induced by Ang II via the activation of endothelial nitric oxide synthase (eNOS)/nitric oxide (NO) pathway. Human umbilical vein endothelial cells (HUVECs) were cultured in the presence of AS‐IV with or without the specific inhibitor of NOS or Ca2+‐ and phosphatidylinositol 3‐kinase (PI3K)/Akt‐dependent cascade prior to Ang II exposure. Incubation of HUVECs with AS‐IV enhanced NO production and eNOSser1177 phosphorylation. These responses were abrogated by the inhibition of NOS or Ca2+‐ and PI3K/Akt‐dependent pathway. In addition, preincubation of HUVECs with AS‐IV inhibited Ang II–induced cytokine and chemokine production, adhesion molecule expression, monocyte adhesion, and nuclear factor kappa B (NF‐κB) activation as evidenced by the attenuation of inhibitor of kappa B alpha phosphorylation and subsequent NF‐κB DNA binding. These effects of AS‐IV were abolished by the suppression of NOS or Ca2+‐ and PI3K/Akt‐dependent cascade. Our findings indicate that AS‐IV attenuates inflammatory responses triggered by Ang II possibly via the activation of Ca2+/PI3K/Akt/eNOS/NO pathway in endothelial cells. [ABSTRACT FROM AUTHOR]

Diabetic nephropathy (DN) is a common and serious micro-vascular complication of diabetes and a leading cause of end-stage renal disease globally. This disease primarily affects middle-aged and elderly individuals, especially those with a diabetes history of over 10 years and poor long-term blood glucose control. Small ubiquitin-related modifiers (SUMOs) are a group of reversible post-translational modifications of proteins that are widely expressed in eukaryotes. SUMO proteins intervene in the progression of DN by modulating various signaling cascades, such as Nrf2-mediated oxidative stress, NF-κB, TGF-β, and MAPK pathways. Recent advancements indicate that natural products regulating SUMOylation hold promise as targets for intervening in DN. In a previous article published in 2022, we reviewed the mechanisms by which SUMOylation intervenes in renal fibrosis and presented a summary of some natural products with therapeutic potential. Therefore, this paper will focus on DN. The aim of this review is to elucidate the mechanism of action of SUMOylation in DN and related natural products with therapeutic potential, thereby summarising the targets and candidate natural products for the treatment of DN through the modulation of SUMOylation, such as ginkgolic acid, ginkgolide B, resveratrol, astragaloside IV, etc., and highlighting that natural product-mediated modulation of SUMOylation is a potential therapeutic strategy for the treatment of DN as a potential therapeutic strategy. [ABSTRACT FROM AUTHOR]

SUMMARY: Astragaloside IV is a significant chemical component derived from the medicinal plant Astragalus membranaceus. Despite the characterization of several glycosyltransferases from A. membranaceus, the complete biosynthetic pathway of astragaloside IV has not been fully elucidated. In this study, we propose a biosynthetic pathway for astragaloside IV that involves a sequence of oxidation–reduction reactions. The biosynthesis pathway from cycloastragenol to astragaloside IV encompasses four key steps: C‐3 oxidation, 6‐O‐glucosylation, C‐3 reduction, and 3‐O‐xylosylation. We identified a hydroxysteroid dehydrogenase AmHSD1 from A. membranaceus. AmHSD1 catalyzes the C‐3 oxidation of cycloastragenol, yielding cycloastragenol‐3‐one, and the C‐3 reduction of cycloastragenol‐3‐one‐6‐O‐glucoside, resulting in cycloastragenol‐6‐O‐glucoside. Additionally, the glycosyltransferases AmGT8 and AmGT1, previously reported by our groups, were identified as catalyzing the 6‐O‐glucosylation and 3‐O‐xylosylation steps, respectively. Astragaloside IV was successfully synthesized in transient expression in Nicotiana benthamiana using the combination of AmHSD1, AmGT8 and AmGT1. These results support the proposed four‐step biosynthetic pathway and suggest that AmHSD1 probably plays a crucial role in the biosynthesis of astragaloside IV within A. membranaceus. [ABSTRACT FROM AUTHOR]

Increasing evidence suggests that endoplasmic reticulum stress (ER stress) and neuroinflammation are involved in the complex pathological process of traumatic brain injury (TBI). However, the pathological mechanisms of their interactions in TBI remain incompletely elucidated. Therefore, investigating and ameliorating neuroinflammation and ER stress post-TBI may represent effective strategies for treating secondary brain injury. Astragaloside IV (AS-IV) has been reported as a potential neuroprotective and anti-inflammatory agent in neurological diseases. This study utilized a mouse TBI model to investigate the pathological mechanisms and crosstalk of ER stress, neuroinflammation, and microglial cell morphology in TBI, as well as the mechanisms and potential of AS-IV in improving TBI. The research revealed that post-TBI, inflammatory factors IL-6, IL-1b, and TNF-a increased, microglial cells were activated, and the specific inhibitor of PERK phosphorylation, GSK2656157, intervened to alleviate neuroinflammation and inhibit microglial cell activation. Post-TBI, levels of ER stress-related proteins (p-PERK, p-eIF2a, ATF4, ATF6, and p-IRE1a) increased. Following AS-IV treatment, neurological dysfunction in TBI mice improved. Levels of p-PERK, p-eIF2a, and ATF4 decreased, along with reductions in inflammatory factors IL-6, IL-1b, and TNF-a. Changes in microglial/macrophage M1/M2 polarization were observed. Additionally, the PERK activator CCT020312 intervention eliminated the impact of AS-IV on post-TBI inflammation and ER stress-related proteins p-PERK, p-eIF2a, and ATF4. These results indicate that AS-IV alleviates neuroinflammation and brain damage post-TBI through the PERK pathway, offering new directions and theoretical insights for TBI treatment. [ABSTRACT FROM AUTHOR]

This study focused on investigating the mechanism of the astragaloside IV-induced bone marrow mesenchymal stem cell exosome (AS-IV-MSC-exo)/microRNA(miR)-411/HIF-1α axis in affecting vascular neovascularization and protecting cardiac function in myocardial infarction (MI) mice. Exosomes (MSC-exo and AS-IV-MSC-exo) were separated by differential centrifugation and then characterized. MI mouse models were established by left anterior descending coronary artery ligation. Echocardiography was used to evaluate cardiac function. HE staining and Masson staining were performed to observe myocardial histopathology. Capillary density in the myocardium via immunohistochemistry and quantified the expression of vascular endothelial growth factor (VEGF) via RT-qPCR. The expression of miR-411 and HIF-1α was tested by RT-qPCR and western blot and the targeting relationship of miR-411 and HIF-1α was verified by bioinformatics website and dual luciferase reporter gene assay. Exosomes with lipid bi-layer membrane structure, expressing exosomal surface marker proteins, and being taken up by cardiomyocytes could be successfully isolated utilizing ultracentrifugation. Intramyocardial injection of MSC-exo could restore cardiac function, decrease myocardial pathological changes and collagen deposition, and promote neovascularization in MI mice; the effect of AS-IV-MSC-exo was more significant. The ability of AS-IV-MSC-exo to restore cardiac function, lower myocardial pathological changes and collagen deposition, and promote neovascularization in MI mice was diminished when miR-411 expression in AS-IV-MSC-exo was reduced. Mechanistically, miR-411 was found to target and inhibit HIF-1α expression. Overexpression of HIF-1α impaired the impact of AS-IV-MSC-exo on improving cardiac function and promoting neovascularization in MI mice. AS-IV-MSC-exo improves cardiac function and promoted neovascularization via the miR-411/HIF-1α axis, thereby ameliorating MI. [ABSTRACT FROM AUTHOR]

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Tubular injury and oxidative stress are involved in the pathogenesis of diabetic kidney disease (DKD). Astragaloside IV (ASIV) is a natural antioxidant. The effects and underlying molecular mechanisms of ASIV on DKD have not been elucidated. The db/db mice and high‐glucose‐stimulated HK2 cells were used to evaluate the beneficial effects of ASIV in vivo and in vitro. Succinylated proteomics was used to identify novel mechanisms of ASIV against DKD and experimentally further validated. ASIV alleviated renal dysfunction and proteinuria, downregulated fasting blood glucose, and upregulated insulin sensitivity in db/db mice. Meanwhile, ASIV alleviated tubular injury, oxidative stress, and mitochondrial dysfunction in vivo and in vitro. Mechanistically, ASIV reversed downregulated 17beta‐hydroxysteroid dehydrogenase type 10 (HSD17B10) lysine succinylation by restoring carnitine palmitoyl‐transferase1alpha (Cpt1a or CPT1A) activity in vivo and in vitro. Molecular docking and cell thermal shift assay revealed that ASIV may bind to CPT1A. Molecular dynamics simulations demonstrated K99 succinylation of HSD17B10 maintained mitochondrial RNA ribonuclease P (RNase P) stability. The K99R mutation of HSD17B10 induced oxidative stress and disrupted its binding to CPT1A or mitochondrial ribonuclease P protein 1 (MRPP1). Importantly, ASIV restored the interaction between HSD17B10 and MRPP1 in vivo and in vitro. We also demonstrated that ASIV reversed high‐glucose‐induced impaired RNase P activity in HK2 cells, which was suppressed upon K99R mutation of HSD17B10. These findings suggest that ASIV ameliorates oxidative stress‐associated proximal tubular injury by upregulating CPT1A‐mediated K99 succinylation of HSD17B10 to maintain RNase P activity. [ABSTRACT FROM AUTHOR]

Abstract This study investigated the therapeutic effects of astragaloside IV (AST) on spinocerebellar ataxia type 3 (SCA3), also known as Machado-Joseph disease (MJD), a neurodegenerative disorder. Human neuroblastoma SK-N-SH cells expressing mutant ataxin-3 protein with 78 CAG repeats (MJD78) were employed as an in vitro model. Protein expression analysis demonstrated that AST treatment reduced mutant ataxin-3 protein expression and aggregation by enhancing the autophagic process in MJD78 cells. Elevated oxidative stress levels in MJD78 cells were significantly reduced following AST treatment, which also enhanced antioxidant capacity, as evidenced by flow cytometry and antioxidant enzyme activity assays. Furthermore, AST treatment ameliorated mitochondrial dysfunction in MJD78 cells, including improvements in mitochondrial membrane potential, respiration, and mitochondrial dynamics. In conclusion, AST administration increased antioxidant capacity, reduced both cellular and mitochondrial oxidative stress, and improved mitochondrial quality control processes through fusion, fission, and autophagy. These mechanisms collectively reduced intracellular mutant ataxin-3 protein aggregation, thereby achieving therapeutic efficacy in the SCA3 model.

This study aimed to investigate the detrimental impact of cigarettes on lung cells and the potential effects of astragaloside IV on lung epithelial cell oxidative stress and pyroptosis. The research utilized cigarette smoke extract (CSE) to stimulate lung epithelial cells BEAS-2B, assessed cytotoxicity using the CCK-8 method, and measured changes in reactive oxygen species (ROS) and mitochondrial membrane potential with a probe method. Additionally, Seahorse XF24 was employed to analyze the impact of CSE on mitochondria in lung epithelial cells. Furthermore, LPS and cigarette combination-treated mice were created, alveolar damage was evaluated using HE staining, and changes in the key protein GSDMD of pyroptosis were detected using western blot (WB). The study also utilized the CCK-8 method to assess the potential toxic effects of astragaloside IV on lung epithelial cells, and the probe method to monitor changes in ROS and mitochondrial membrane potential. WB analysis was conducted to observe protein alterations in the TXNIP/NLRP3/GSDMD pathway. CSE concentration-dependently reduced cell activity, increased cellular ROS levels, and decreased mitochondrial membrane potential. CSE also decreases basal respiratory capacity, respiratory reserve capacity, and ATP production levels in cells. In LPS and cigarette combination-treated mice, cigarette smoke caused the alveolar septum to break and alveoli to enlarge, while increasing the expression of pyroptosis-related protein GSDMD. Astragaloside IV did not show significant cytotoxic effects within 48 h of treatment and could reduce CSE-induced ROS levels while increasing mitochondrial membrane potential. WB results indicated that astragaloside IV reduced the activation of the TXNIP/NLRP3/GSDMD signaling pathway in lung epithelial cells exposed to CSE. Our study demonstrates that CSE induces oxidative stress and impairs mitochondrial function in pulmonary epithelial cells, while astragaloside IV can potentially reverse these effects by inhibiting the TXNIP-NLRP3-GSDMD signaling pathway, thereby mitigating CSE-induced pulmonary disease and epithelial cell pyroptosis. [ABSTRACT FROM AUTHOR]

Abstract Immune checkpoint inhibitors (ICIs) are effective agents for tumor immunotherapy. However, their clinical effectiveness is unsatisfactory due to off-target effects and a suppressive immune microenvironment. This study developed a nanodrug delivery system for bladder cancer (BCa) using PCL-MPEG and PCL-PEG-CHO to synthesize internal hydrophobic and external hydrophilic micelles (PP) that encapsulated water-insoluble astragaloside IV (PPA). The aldehyde group on the surface of PPA reacted with the amino group of aPD-L1, allowing the decoration of this antibody on the surface of the micelles. The resultingPPA@aPD-L1effectively piggybacked astragaloside IV and aPD-L1 antibody. These findings suggest that PPA@aPD-L1 is relatively stable in circulation and efficiently binds to BCa cells with the aid of aPD-L1. Additionally, this strategy prolongs the drug’s retention time in tumors. Compared to PBS, PP, and PPA with PPA + aPD-L1 groups, PPA@aPD-L1significantly prolonged the survival of mice with BCa and reduced tumor volume. Mechanistic studies showed that PPA inhibited the NF-κB and STAT3 signaling pathways in tumor cells. Additionally, PPA@aPD-L1increased IFN-γ and decreased IL-10 expression in bladder tumors, affecting the number and type of intratumorally infiltrating T cells. Our study presents a simple and effective drug delivery system that combines herbal monomers with ICIs. It has demonstrated a potent ability to suppress tumor growth and holds potential for future applications.

Objective: To determine the main components of Astragalus membranaceus (Fisch.) Bge (A. membranaceus, Huang Qi), Astragaloside IV (AIV) and Astragalus polysaccharides (AP), to characterize their properties, evaluate their in vivo efficacy, and to analyze drug diffusion using dissolving microneedle (DMN) technology in vivo. Methods: Respectively, AIV- and AP-loaded DMNs comprising chitosan (CTS) and polyvinyl alcohol (PVA) were prepared via dual-mold forming. Their morphology, mechanical properties, in vivo solubility, and skin irritation characteristics were tested. In vivo efficacy was assessed in cyclophosphamide-induced immunosuppressed mice, in vivo diffusion of AIV and AP by DMNs and conventional methods was compared, and the rheological properties of AIV-CTS-PVA and AP-CTS-PVA mixtures were measured. Results: Subcutaneous dissolution and absorption of AIV-CTS-PVA and AP-CTS-PVA microneedles (MNs) at low doses (50%–17% of intraperitoneal AIV injection and 12%–4% of intravenous AP injection) reduced the spleen index and acid phosphatase activity in immunosuppressed mouse models, increased the thymus index, and achieved equivalent or better systemic therapeutic effects. Compared with injections, AIV and AP achieved controllable solid-liquid conversion through delivery with CTS-PVA MNs, resulting in highly localized aggregation within 48 h, reducing the initial explosive effect of the drug, and achieving stable and slow drug release. Conclusion: The present study enhances our understanding of the efficacy and remote effects of drug-loaded DMNs from a traditional Chinese medicine (TCM) perspective, thereby promoting the development of precise and efficient delivery of TCM and further expanding the drug-loading range and application scenarios for DMNs.

Abstract Background Astragaloside IV is a main medicinal active ingredient in Astragalus membranaceus Bge. var. mongholicus (Bge.) Hsiao, which is also the key biomarker of A. membranaceus quality. Ethylene has been well-documented to involve in secondary metabolites biosynthesis in plants. Nevertheless, how ethylene regulates astragaloside IV biosynthesis in A. membranaceus is still unclear. Therefore, in the present study different dosages and time-dependent exogenous application of ethephon (Eth) were employed to analyze astragaloside IV accumulation and its biosynthesis genes expression level in hydroponically A. membranaceus. Results Exogenous 200 µmol·L− 1Eth supply is most significantly increased astragaloside IV contents in A. membranaceus when compared with non-Eth supply. After 12 h 200 µmol·L− 1 Eth treatment, the astragaloside IV contents reaching the highest content at 3 d Eth treatment(P ≤ 0.05). Moreover, After Eth treatment, all detected key genes involved in astragaloside IV synthesis were significant decrease at 3rd day(P ≤ 0.05). However, SE displayed a significant increase at the 3rd day under Eth treatment(P ≤ 0.05). Under Eth treatment, the expression level of FPS, HMGR, IDI, SS, and CYP93E3 exhibited significant negative correlations with astragaloside IV content, while expression level of SE displayed a significant positive correlation. Conclusions These findings suggest that exogenous Eth treatment can influence the synthesis of astragaloside IV by regulating the expression of FPS, HMGR, IDI, SS, CYP93E3 and SE. This study provides a theoretical basis for utilizing molecular strategies to enhance the quality of A. membranaceus.

Abstract Background Astragaloside IV (AST-IV), as an effective active ingredient of Astragalus membranaceus (Fisch.) Bunge. It has been found that AST-IV inhibits the replication of dengue virus, hepatitis B virus, adenovirus, and coxsackievirus B3. Enterovirus 71 (EV71) serves as the main pathogen in severe hand-foot-mouth disease (HFMD), but there are no specific drugs available. In this study, we focus on investigating whether AST-IV can inhibit EV71 replication and explore the potential underlying mechanisms. Methods The GES-1 or RD cells were infected with EV71, treated with AST-IV, or co-treated with both EV71 and AST-IV. The EV71 structural protein VP1 levels, the viral titers in the supernatant were measured using western blot and 50% tissue culture infective dose (TCID50), respectively. Network pharmacology was used to predict possible pathways and targets for AST-IV to inhibit EV71 replication. Additionally, ultra-high performance liquid chromatography-high resolution mass spectrometry (UHPLC-HRMS) was used to investigate the potential targeted metabolites of AST-IV. Associations between metabolites and apparent indicators were performed via Spearman’s algorithm. Results This study illustrated that AST-IV effectively inhibited EV71 replication. Network pharmacology suggested that AST-IV inhibits EV71 replication by targeting PI3K-AKT. Metabolomics results showed that AST-IV achieved these effects by elevating the levels of hypoxanthine, 2-ketobutyric acid, adenine, nicotinic acid mononucleotide, prostaglandin H2, 6-hydroxy-1 H-indole-3- acetamide, oxypurinol, while reducing the levels of PC (14:0/15:0). Furthermore, AST-IV also mitigated EV71-induced oxidative stress by reducing the levels of MDA, ROS, while increasing the activity of T-AOC, CAT, GSH-Px. The inhibition of EV71 replication was also observed when using the ROS inhibitor N-Acetylcysteine (NAC). Additionally, AST-IV exhibited the ability to activate the PI3K-AKT signaling pathway and suppress EV71-induced apoptosis. Conclusion This study suggests that AST-IV may activate the cAMP and the antioxidant stress response by targeting eight key metabolites, including hypoxanthine, 2-ketobutyric acid, adenine, nicotinic acid mononucleotide, prostaglandin H2, 6-Hydroxy-1 H-indole-3-acetamide, oxypurinol and PC (14:0/15:0). This activation can further stimulate the PI3K-AKT signaling to inhibit EV71-induced apoptosis and EV71 replication. Graphical Abstract

Abstract Background Astragaloside IV (AS-IV) is one of the basic components of Astragali radix, that has been shown to have preventive effects against various diseases, including cancers. This study aimed to explore the role of AS-IV in hepatocellular carcinoma (HCC) and its underlying mechanism. Methods The cell viability, glucose consumption, lactate production, and extracellular acidification rate (ECAR) in SNU-182 and Huh7 cell lines were detected by specific commercial kits. Western blot was performed to analyze the succinylation level in SNU-182 and Huh7 cell lines. The interaction between lysine acetyltransferase (KAT) 2 A and phosphoglycerate mutase 1 (PGAM1) was evaluated by co-immunoprecipitation and immunofluorescence assays. The role of KAT2A in vivo was explored using a xenografted tumor model. Results The results indicated that AS-IV treatment downregulated the protein levels of succinylation and KAT2A in SNU-182 and Huh7 cell lines. The cell viability, glucose consumption, lactate production, ECAR, and succinylation levels were decreased in AS-IV-treated SNU-182 and Huh7 cell lines, and the results were reversed after KAT2A overexpression. KAT2A interacted with PGAM1 to promote the succinylation of PGAM1 at K161 site. KAT2A overexpression promoted the viability and glycolysis of SNU-182 and Huh7 cell lines, which were partly blocked following PGAM1 inhibition. In tumor-bearing mice, AS-IV suppressed tumor growth though inhibiting KAT2A-mediated succinylation of PGAM1. Conclusion AS-IV inhibited cell viability and glycolysis in HCC by regulating KAT2A-mediated succinylation of PGAM1, suggesting that AS-IV might be a potential and suitable therapeutic agent for treating HCC.

Astragaloside IV (AS-IV), a natural triterpenoid isolated from Astragalus membranaceus, has been used traditionally in Chinese medicine. Previous studies have highlighted its benefits against carcinoma, but its interaction with the gut microbiota and effects on adenomatous polyps are not well understood. This present study investigates the effects of AS-IV on colonic adenomatous polyp (CAP) development in high-fat-diet (HFD) fed A p c Min ∕ + mice. A p c Min ∕ + mice were fed an HFD with or without AS-IV or Naringin for 8 weeks. The study assessed CAP proliferation and employed 16S DNA-sequencing and untargeted metabolomics to explore correlations between microbiome and metabolome in CAP development. AS-IV was more effective than Naringin in reducing CAP development, inhibiting colonic proinflammatory cytokines (IL-1β, IL-6, and TNF-α), tumor associated biomarkers (c-Myc, Cyclin D1), and Wnt/β-catenin pathway proteins (Wnt3a, β-catenin). AS-IV also inhibited the proliferative capabilities of human colon cancer cells (HT29, HCT116, and SW620). Multiomics analysis revealed AS-IV increased the abundance of beneficial genera such as Bifidobacteriumpseudolongum and significantly modulated serum levels of certain metabolites including linoleate and 2-trans,6-trans-farnesal, which were significantly correlated with the number of CAP. Finally, the anti-adenoma efficacy of AS-IV alone was significantly suppressed post pseudoaseptic intervention in HFD-fed A p c Min ∕ + mice but could be reinstated following a combined with Bifidobacteriumpseudolongum transplant. AS-IV attenuates CAP development in HFD-fed A p c Min ∕ + mice by regulating gut microbiota and metabolomics, impacting the Wnt3a/β-catenin signaling pathway. This suggests a potential new strategy for the prevention of colorectal cancer, emphasizing the role of gut microbiota in AS-IV's antitumor effects. [ABSTRACT FROM AUTHOR]

Cerebral ischemia-reperfusion injury (IRI), occurring after blood supply restoration, contributes significantly to stroke-related deaths. This study explored the combined impact and mechanisms of astragaloside IV (AS-IV), hydroxysafflor yellow A (HSYA), and their combination in mitigating IRI. Male Sprague–Dawley (SD) rats were randomized to the Sham, MCAO, MCAO+AS-IV, MCAO+HSYA, and MCAO+AS-IV+HSYA groups. Neurological deficits and cerebral infarction were examined after restoring the blood supply to the brain. Pathomorphological changes in the cerebral cortex were observed via HE staining. IL-1β and IL-18 were quantified using ELISA. The expression of NF-κB and GSDMD in the ischemic cerebrum was analyzed using immunohistochemistry. The expression levels of NLRP3, ASC, IL-1β, Caspase-1, and GSDMD in the ischemic cerebrum were evaluated using Western blot. The MCAO+AS-IV, MCAO+HSYA, and MCAO+AS-IV+HSYA groups exhibited notably better neurological function and cerebral infarction compared with the MCAO group. The combined treatment demonstrated superior brain tissue injury alleviation. Reductions in NF-κB, GSDMD positive cells, and NLRP3/ASC/IL-1β/Caspase-1/GSDMD protein expression in the ischemic brain were significantly more pronounced with the combined therapy, indicating a synergistic effect in countering cerebral IRI via the NF-κB/NLRP3/Caspase-1/GSDMD pathway inhibition of cell pyroptosis-induced injury. [ABSTRACT FROM AUTHOR]

Acute kidney injury (AKI) is one of the most common clinical critical illnesses, with decreased glomerular filtration rate, retention of nitrogen products, water and electrolyte disorders, and acid–base imbalance as the main clinical manifestations. Presently, there is no effective treatment for acute kidney injury, but the main treatment is to cure the primary disease, remove risk factors, maintain acid–base and water–electrolyte balance, and undergo kidney replacement. However, the mortality rate is still high. Investigations and studies showed that the mortality rate of patients with acute kidney injury in the ICU is 5–80% [1]. In recent years, Chinese medicine has been widely used in acute kidney injury treatment due to its complete dialectical system and rich experience. Astragalus is a commonly used medicine in traditional Chinese medicine to treat acute kidney injury. Astragaloside IV is the main active component of traditional Chinese medicine, Astragalus membranaceus. This article summarizes the relevant studies on treating acute kidney injury with astragaloside IV. [ABSTRACT FROM AUTHOR]

Immune checkpoint inhibitors (ICIs) are effective agents for tumor immunotherapy. However, their clinical effectiveness is unsatisfactory due to off-target effects and a suppressive immune microenvironment. This study developed a nanodrug delivery system for bladder cancer (BCa) using PCL-MPEG and PCL-PEG-CHO to synthesize internal hydrophobic and external hydrophilic micelles (PP) that encapsulated water-insoluble astragaloside IV (PPA). The aldehyde group on the surface of PPA reacted with the amino group of aPD-L1, allowing the decoration of this antibody on the surface of the micelles. The resultingPPA@aPD-L1effectively piggybacked astragaloside IV and aPD-L1 antibody. These findings suggest that PPA@aPD-L1 is relatively stable in circulation and efficiently binds to BCa cells with the aid of aPD-L1. Additionally, this strategy prolongs the drug's retention time in tumors. Compared to PBS, PP, and PPA with PPA + aPD-L1 groups, PPA@aPD-L1significantly prolonged the survival of mice with BCa and reduced tumor volume. Mechanistic studies showed that PPA inhibited the NF-κB and STAT3 signaling pathways in tumor cells. Additionally, PPA@aPD-L1increased IFN-γ and decreased IL-10 expression in bladder tumors, affecting the number and type of intratumorally infiltrating T cells. Our study presents a simple and effective drug delivery system that combines herbal monomers with ICIs. It has demonstrated a potent ability to suppress tumor growth and holds potential for future applications. [ABSTRACT FROM AUTHOR]

ObjectiveTo observe the intervention effect of caudal vein injection of astragaloside Ⅳ on renal ischemia- reperfusion injury in rats, and to explore the related mechanism based on the regulation of PI3K/AKT signaling pathway and autophagy. MethodsSixty healthy male SD rats were randomly divided into the astragaloside Ⅳ group, wortmannin group, model group, and control group, respectively. Ischemia-reperfusion injury models were made in the astragaloside Ⅳ group, wortmannin group and model group, while in the control group, we only dissociated the renal pedicle of both kidneys and underwent right nephrectomy without other treatment. Rats in the astragaloside Ⅳ group were injected with astragaloside Ⅳ 10 mg/kg at 5 min before reperfusion, while rats in the wortmannin group were injected with astragaloside Ⅳ 10 mg/kg and wortmannin 0. 6 mg/kg (PI3K specific inhibitor) at 5 min and 10 min before reperfusion, respectively. Rats in the control group and the model group were injected with equal volume of normal saline at the same time. Serum creatinine (Cr) and urea nitrogen (BUN) were detected at 24 h after reperfusion. Renal tissue was stained with HE to observe the pathological changes. We observed the apoptosis of renal cells and calculated the apoptosis index, and detected microtubule-associated protein light chain 3- Ⅱ(LC3), Beclin-1 and phosphorylated AKT (p-AKT) in renal tissues. ResultsThe levels of serum Cr and BUN in the astragaloside Ⅳ group, wortmannin group and model group were higher than those in the control group, while the levels of serum Cr and BUN in the model group, wortmannin group and astragaloside Ⅳ group decreased in turn( all P<0. 05). Compared with the model group, the pathological damage of renal tissue in the astragaloside Ⅳ group and wortmannin group was reduced, especially in the astragaloside Ⅳ group. Apoptosis index and the expression levels of LC3-Ⅱ, Beclin-1 and p-AKT protein in the renal tissues of the astragaloside Ⅳ group, wortmannin group and model group were higher than those in the control group, but the apoptosis index and the expression levels of LC3-Ⅱ and Beclin-1 protein in the model group, wortmannin group and astragaloside Ⅳ group decreased in turn, and the expression of p-AKT protein in wortmannin group was lower than that in astragaloside Ⅳ group (all P<0. 05). Conclusion Astragaloside Ⅳ intervention can alleviate renal ischemia-reperfusion injury in rats, and its mechanism may be related to regulating PI3K/AKT pathway and inhibiting autophagy. [ABSTRACT FROM AUTHOR]

Astragalus, as the most commonly used traditional Chinese medicinal herb, contains various active components, the most important of which are astragaloside IV, flavonoids, and polysaccharides.These components endow Astragalus with a variety of pharmacological effects such as immunity enhancement, anti-fatigue, anti-inflammatory, cardiovascular and cerebrovascular protection, visceral tissue protection, anti-cancer, anti-tumor, etc.The article reviews the physiological functions of the active components of Astragalus and their application in food, with the aim of providing theoretical references for the further development and application of Astragalus and its active components in the food industry. [ABSTRACT FROM AUTHOR]

The persistent restriction of airflow is a hallmark of chronic obstructive pulmonary disease. It includes alterations in lung tissue, emphysema, inflammation of the airways, and chronic bronchitis. Globally, chronic obstructive pulmonary disease is one of the leading causes of disability and death. Chronic obstructive pulmonary disease is categorized as lung distension, asthma syndrome and cough in traditional Chinese medicine, where the herb, Astragalus has tonic qualities, to bolster the body and ward off sickness. Astragalus has polysaccharides and saponins that lower inflammation, boost immunity, and lessen oxidative stress against chronic obstructive pulmonary disease. In order to aid in the development of novel chronic obstructive pulmonary disease treatments, this review focuses on the components and processes of Astragalus. [ABSTRACT FROM AUTHOR]

Cell senescence is intensively related to aging and neurodegenerative diseases. This study aimed to explore the effect and targets of Astragaloside IV against amyloid-beta-induced astrocyte senescence. Oligomerized amyloid-beta was prepared to culture with human astrocytes. The effects of Astragaloside IV were assessed based on SA-ß-gal staining analysis, senescence markers (p53, p16INK4, and p21WAF1), neurotrophic growth factor levels (qRT-PCR), and cell proliferation (CCK-8 kit). The targets for Astragaloside IV were predicted, and hsp90aa1 protein was verified using molecular docking. After hsp90aa1 overexpression, the effects of Astragaloside IV on amyloidbeta-induced astrocytes were assessed. Treatment of human amyloid-beta-induced astrocytes with Astragaloside IV can decrease the percentage of SA-ß-gal positive cells, downregulate the p53, p16INK4, and p21WAF1 levels, and increase the levels of neurotrophic growth factors (IGF-1 and NGF mRNA) and cell proliferation. Based on target prediction, hsp90aa1 was found to be a potential target of Astragaloside IV. Moreover, cellular experiments demonstrated that exogenously enhanced expression of hsp90aa1 overexpression suppressed the protective effect of Astragaloside IV on amyloid-beta-induced human astrocytes. The results presented here demonstrate that Astragaloside IV could confront amyloid-beta-induced astrocyte senescence via hsp90aa1, possibly opening new therapeutic avenues. [ABSTRACT FROM AUTHOR]

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This study used network pharmacology to forecast and evaluate effectiveness in controlling chronic atrophic gastritis, laying the groundwork for its inclusion in functional foods. The target genes of astragaloside IV that control chronic atrophic gastritis were gathered for this experiment from databases such as Swiss Target Prediction, PharmaMapper, OMIM, etc. The target gene was identified by taking intersections. Based on the STRING database, a protein-protein interaction (PPI) network was created. Based on the centrality of the intermediate number, the PPI network did topology analysis using Cytoscape software, and simulated potential molecular docking outcome with Autodock Vina software. GO and KEGG enrichment analysis was conducted on the bioinformatics online platform to screen out relevant signal pathways. In vitro experiments were conducted by inducing GES-1 cells (human gastric mucosal epithelial cells) with MNNG (1-methyl- 3-nitro-1-nitrosoguanidine) and treating them with astragaloside IV to detect cell viability and inflammatory factor secretion levels for validation. Finally, 53 potential targets were identified for the regulation of chronic atrophic gastritis by astragaloside IV, including 8 key genes. GO enrichment analysis showed that the vesicular cavity was the main site for biological processes to occur. The KEGG results indicated that proteoglycans in tumors were a key signaling pathway for astragaloside IV to regulate chronic atrophic gastritis. In vitro experiments found that astragaloside IV had a preventive and therapeutic effect on MNNG-induced cell damage, and could downregulate IL-6, IL-8, IL-1β, and TNF-α (P < 0.05). This study showed that astragaloside IV could operate as a functional factor for the prevention and treatment of chronic atrophic gastritis and could exercise its anti-chronic atrophic gastritis impact through many targets and pathways. [ABSTRACT FROM AUTHOR]

Background: Astragaloside IV (AST-IV), as an effective active ingredient of Astragalus membranaceus (Fisch.) Bunge. It has been found that AST-IV inhibits the replication of dengue virus, hepatitis B virus, adenovirus, and coxsackievirus B3. Enterovirus 71 (EV71) serves as the main pathogen in severe hand-foot-mouth disease (HFMD), but there are no specific drugs available. In this study, we focus on investigating whether AST-IV can inhibit EV71 replication and explore the potential underlying mechanisms. Methods: The GES-1 or RD cells were infected with EV71, treated with AST-IV, or co-treated with both EV71 and AST-IV. The EV71 structural protein VP1 levels, the viral titers in the supernatant were measured using western blot and 50% tissue culture infective dose (TCID50), respectively. Network pharmacology was used to predict possible pathways and targets for AST-IV to inhibit EV71 replication. Additionally, ultra-high performance liquid chromatography-high resolution mass spectrometry (UHPLC-HRMS) was used to investigate the potential targeted metabolites of AST-IV. Associations between metabolites and apparent indicators were performed via Spearman's algorithm. Results: This study illustrated that AST-IV effectively inhibited EV71 replication. Network pharmacology suggested that AST-IV inhibits EV71 replication by targeting PI3K-AKT. Metabolomics results showed that AST-IV achieved these effects by elevating the levels of hypoxanthine, 2-ketobutyric acid, adenine, nicotinic acid mononucleotide, prostaglandin H2, 6-hydroxy-1 H-indole-3- acetamide, oxypurinol, while reducing the levels of PC (14:0/15:0). Furthermore, AST-IV also mitigated EV71-induced oxidative stress by reducing the levels of MDA, ROS, while increasing the activity of T-AOC, CAT, GSH-Px. The inhibition of EV71 replication was also observed when using the ROS inhibitor N-Acetylcysteine (NAC). Additionally, AST-IV exhibited the ability to activate the PI3K-AKT signaling pathway and suppress EV71-induced apoptosis. Conclusion: This study suggests that AST-IV may activate the cAMP and the antioxidant stress response by targeting eight key metabolites, including hypoxanthine, 2-ketobutyric acid, adenine, nicotinic acid mononucleotide, prostaglandin H2, 6-Hydroxy-1 H-indole-3-acetamide, oxypurinol and PC (14:0/15:0). This activation can further stimulate the PI3K-AKT signaling to inhibit EV71-induced apoptosis and EV71 replication. [ABSTRACT FROM AUTHOR]

Objective: Ovarian cancer has the highest mortality rate in women and it has a poor response rate to treatment due to its late diagnosis and is frequently resistant to currently used cisplatin-based treatment methods. Astragaloside IV (As-IV), a bioactive compound and natural tripeptide glycoside known as an antioxidant, has drawn attention in Chinese medicine for its healing properties. Many studies have shown that it has anti-inflammatory, antidiabetic, antitumoral, and anti-angiogenic properties. Materials and Methods: In our study, we first rendered ovarian cancer cells (OVCAR-3) resistant to cisplatin and then applied determined doses of As-IV (40 µg/mL) and (70 µg/mL) to OVCAR-3 cells and cisplatin-resistant ovarian cancer cells (OVCAR-3-CisR). The cell viability capacity, variation of BAX/BCL-2 gene expression, and regulation of the SDF-1/CXCR4 chemokine axis protein and their gene expressions were investigated. Results: According to the findings, As-IV administration suppressed metastasis by lowering the colony formation potential of cisplatin-resistant ovarian cancer and down-regulating the SDF-1/CXCR4 axis, and increasing the ratio of BAX/BCL-2 mRNA and protein levels due to BAX up-regulation and BCL-2 down-regulation. Conclusion: As a result, we showed that As-IV, used as an antioxidant, can be used as an effective anticancer agent to improve response to the currently used cisplatin-based treatment in cases of drug resistance in ovarian cancer. [ABSTRACT FROM AUTHOR]

Astragaloside IV (AST) has been confirmed to have antiasthmatic effects. However, the underline mechanism is unclear. The study aimed to explore the treatment mechanism of AST based on autophagy of memory T cells. AST treatment significantly decreased the number of T effector cells in asthma mice blood and the nude mice that received AST-treated TCMs had relieved inflammation compared with the untreated group; meanwhile, we found that AST significantly decreased the autophagy level and inhibited OX40/OX40L signal pathway of lymphocytes. The results highlighted that AST regulated autophagy to inhibit differentiation of effector T-cell phenotype. [ABSTRACT FROM AUTHOR]

Background: Astragaloside IV (AS‐IV) is the most active monomer in the traditional Chinese herbal medicine Radix Astragali, which has a wide range of antiviral, anti‐inflammatory, and antifibrosis pharmacological effects, and shows protective effects in acute lung injury. Methods: This study utilized the immunofluorescence, flow cytometry, enzyme‐linked immunosorbent assay, quantitative reverse transcription‐polymerase chain reaction, western blot, and hematoxylin and eosin staining methods to investigate the mechanism of AS‐IV in reducing viral pneumonia caused by influenza A virus in A549 cells and BALB/c mice. Results: The results showed that AS‐IV suppressed reactive oxygen species production in influenza virus‐infected A549 cells in a dose‐dependent manner, and subsequently inhibited the activation of nucleotide‐binding oligomerization domain‐like receptor thermal protein domain associated protein 3 inflammasome and Caspase‐1, decreased interleukin (IL) ‐1β and IL‐18 secretion. In BALB/c mice infected with Poly (I:C), oral administration of AS‐IV can significantly reduce Poly (I:C)‐induced acute pneumonia and lung pathological injury. Conclusions: AS‐IV alleviates the inflammatory response induced by influenza virus in vitro and lung flammation and structural damage caused by poly (I:C) in vivo. [ABSTRACT FROM AUTHOR]

Percutaneous coronary intervention (PCI) is the main treatment for patients with severe coronary vascular stenosis. However, In-stent neo-atherosclerosis (ISNA) is an important clinical complication in patients after PCI, which is mainly caused by a persistent inflammatory response and endothelial insufficiency. In the cardiovascular field, magnesium-based scaffolds stand out due to their properties. Magnesium plays a key role in regulating cardiovascular physiology. Magnesium deficiency can promote endothelial cell dysfunction, which contributes to the formation of atherosclerosis. Since astragaloside IV (AS‑IV) has been proven to have potent cardioprotective effects, we asked whether high levels of magnesium cooperate with AS‑IV might have effects on endothelial function and ISNA. We performed in vitro experiments on endothelial cells. Being treated with different concentrations of magnesium or/and AS-IV, the cell growth and migration were detected by CCK-8 and wound healing assay, respectively. The pro-inflammatory factors tumor necrosis factor α (TNF-α) and interleukin 6 (IL-6), adhesion molecule vascular cell adhesion molecule-1 (VCAM-1), and NF-kB were determined by qRT-PCR, ELISA kits or western blot. Results showed that high magnesium and AS-IV improved endothelial function, including promoting cell migration and decreasing the content of TNF-α, IL-6, VCAM-1, and NF-kB. With the supplement of AS-IV, additive magnesium maintains cell proliferation, migration, and function of endothelial cells. In conclusion, these findings suggest that high magnesium and AS‑IV could improve vascular endothelial dysfunction. Early detection and treatment for neo-atherosclerosis may be of great clinical significance for improving stent implantation efficacy and long-term prognosis. [ABSTRACT FROM AUTHOR]

BackgroundHeart failure with preserved ejection fraction (HFpEF) has grown to become the dominant form of heart failure worldwide. However, no unequivocally effective treatment for HFpEF has been identified in clinical trials. In this study, we report that Astragaloside IV (AS-IV) can be used to treat HFpEF.MethodsMice were fed on a high-fat diet and given 0.5 g/L L-NAME (in drinking water) for 10 weeks to establish the HFpEF model. After 10th weeks, the HFpEF mice were given 10 mg/kg empagliflozin, 10 mg/kg AS-IV, or 20 mg/kg AS-IV for 4 weeks. The echocardiography, blood pressure, hemodynamics, heart failure biomarkers, collagen deposition and fibrosis, histopathology, and inflammation in HFpEF mice were evaluated. Metabolic profiling based on NMR measurements was also performed. Myocardial glucose and fatty acid metabolism were evaluated.ResultsAS-IV improves cardiac function and myocardial remodeling in HFpEF mice. AS-IV attenuates systemic inflammatory infiltration and myocardial inflammation levels in HFpEF mice by decreasing the expression of plasma inflammatory markers GDF15, CRP, IL1RL1, and MCP-1, NLRP3, IL-1β, Caspase-1, and IL-6 in the myocardium of HFpEF mice. Metabolomic analysis suggested that AS-IV improved cardiac glucose and fatty acid metabolism in HFpEF mice. Further studies showed that AS-IV significantly improved Complex I activity, increased ATP production, and elevated plasma NAD + levels; AS-IV also significantly improved pyruvate dehydrogenase activity and decreased pyruvate and lactate accumulation, thereby improving glucose metabolism in the hearts of HFpEF mice.ConclusionThese results provide novel evidence that Astragaloside IV alleviates inflammation and improves myocardial metabolism in HFpEF mice.

Heatstroke is a condition caused by overheating of the body that leads to severe central nervous system dysfunction. Although there have been numerous studies on the pathological process of heatstroke, effective treatment methods are lacking. Astragaloside IV can protect the brain from inflammation and brain damage in various inflammation-related diseases, but it has not yet been used clinically for the treatment of heatstroke. Therefore, the aim of this study was to explore the neuroprotective effect of Astragaloside IV on heatstroke-induced central nervous system damage and its mechanism. Brain injury model under heatstroke was established using artificial climate simulation cabin. By scoring neurological deficits, performing histological and immunofluorescence staining of microglia, and detecting cytokine levels, we determined that Astragaloside IV alleviated brain injury and neuroinflammation. To further explore the potential molecular mechanism, RNA sequencing was performed to investigate the differences in the brain. The results revealed that the PI3K/AKT pathway is involved. In vitro experiments further confirmed that Astragaloside IV can abrogate the phenotypic changes in microglia induced by heatstroke. Moreover, Astragaloside IV promotes the polarization of M2 microglia by activating the PI3K/AKT pathway. In summary, these results indicate that Astragaloside IV alleviates neuroinflammation and brain injury induced by heatstroke through the PI3K/AKT pathway. Astragaloside IV is a commonly used therapeutic agent in the clinic, but its use in the treatment of heatstroke-induced brain injury has not been explored. This study reveals that Astragaloside IV may be a new therapeutic agent for the treatment of heatstroke-induced brain injury.

Due to changes in diet and lifestyle, the prevalence of intestinal diseases has been increasing annually. Current treatment methods exhibit several limitations, including adverse reactions and drug resistance, necessitating the development of new, safe, and effective therapies. Astragali Radix, a natural medicine utilized for over two millennia, offers unique advantages in treating intestinal ailments due to its multi-component and multi-target properties. This study aims to review the effective components of Astragali Radix that provide intestinal protection and to explore its pharmacological effects and molecular mechanisms across various intestinal diseases. This will provide a comprehensive foundation for using Astragali Radix in treating intestinal diseases and serve as a reference for future research directions. The active components of Astragali Radix with protective effects on the intestines include astragaloside (AS)-IV, AS-III, AS-II, astragalus polysaccharide (APS), cycloastagenol, calycosin, formononetin, and ononin. Astragali Radix and its active components primarily address intestinal diseases such as colorectal cancer (CRC), inflammatory bowel disease (IBD), and enterocolitis through mechanisms including anti-inflammatory actions, antioxidative stress responses, anti-proliferation and invasion activities, regulation of programmed cell death, immunoregulation, restoration of the intestinal epithelial barrier, and modulation of the intestinal microbiota and its metabolites. Consequently, Astragali Radix demonstrates significant intestinal protective activity and represents a promising natural treatment for intestinal diseases. However, the pharmacological actions and mechanisms of some active components in Astragali Radix remain unexplored. Moreover, further comprehensive toxicological and clinical studies are required to ascertain its safety and clinical effectiveness.

Programmed cell death protein-1 (PD-1) inhibitors are increasingly utilized in the treatment of lung cancer (LC). Combination therapy has recently gained popularity in treating LC. This study aimed to assess the efficacy of combining Astragaloside IV (AS-IV) and anti-PD-1 in LC. C57BL/6J mice were subcutaneously injected with Lewis lung carcinoma (LLC) cells. After 3 weeks, the animals were sacrificed, and the tumors were harvested for analysis. Ki-67 immuno-labeling and TUNEL assay were used for evaluating cell proliferation and apoptosis in tumor tissues. In addition, anti-cleaved caspase 3 was used for immunolabelling of apoptotic cells. Immune cell infiltration (macrophages and T cells) and gene expression in tumor tissues were also investigated by using immunofluorescence staining. Compared to treatment with anti-PD-1 or AS-IV, the combination of AS-IV and anti-PD-1 notably reduced tumor volume and weight of LLC-bearing mice. Additionally, the combination treatment strongly induced the apoptosis and suppressed the proliferation in tumor tissues through inactivating PI3K/Akt and ERK signaling pathways, compared to single treatment group. Moreover, the combination treatment elevated levels of the M1 macrophage marker mCD86, reduced levels of the M2 macrophage marker mCD206, as well as upregulated levels of the T cell activation marker mCD69 in tumor tissues. Collectively, the combination treatment effectively inhibited tumor growth in LLC mice through promoting M1 macrophage polarization and T cell activation. These findings showed that combining AS-IV with anti-PD-1 therapy could be a promising therapeutic approach for LC.

Astragaloside IV(AS-IV), the main active ingredient of Astragalus, has been used as a treatment for heart failure with favorable effects, but its molecular mechanism has not been fully elucidated. Network pharmacological analysis and molecular docking revealed that Heat shock transcription factor 1 (HSF1) is a potential target of AS-IV. We designed cellular and animal experiments to investigate the role and intrinsic molecular mechanisms of AS-IV in ameliorating pressure overload-induced heart failure. In cellular experiments, Myocardial microvascular endothelial cells (MMVECs) were cultured in isolation and stimulated by adding high and low concentrations of AS-IV, and a cell model with down-regulation of HSF1 expression was constructed by using siRNA technology. Changes in the expression of key molecules of HSF1/VEGF signaling pathway and differences in tube-forming ability were detected in different groups of cells using PCR, WB and tube-forming assay. In animal experiments, TAC technology was applied to establish a pressure overload-induced heart failure model in C57 mice, postoperative mice were ingested AS-IV by gavage, and adenoviral transfection technology was applied to construct a mouse model with down-regulation of HSF1 expression.Small animal ultrasound for cardiac function assessment, MASSON staining, CD31 immunohistochemistry, and Western blotting (WB) were performed on the mice. The results showed that AS-IV could promote the expression of key molecules of HSF1/VEGF signaling pathway, enhance the tube-forming ability of MMVECs, increase the density of myocardial capillaries, reduce myocardial fibrosis, and improve the cardiac function of mice with TAC.AS-IV could modulate the HSF1/VEGF signaling pathway to promote the angiogenesis and improve the pressure overload-induced heart failure.

Abstract Background Prostate cancer (PCa) is becoming the most common malignancy in men worldwide. We investigated the effect of astragaloside IV combined with PESV on the gut microbiota and metabolite of PCa mice and the process of treating PCa. Methods Nude mice were genetically modified to develop tumors characteristic of PCa. The treatment of PCa mice involved the administration of a combination of astragaloside IV and peptides derived from scorpion venom (PESV). Feces were collected for both 16 S rDNA and metabolic analysis. Fecal supernatant was extracted and used for fecal transplantation in PCa mice. Tumor development was observed in both PCa mice and nude mice. Tumor histopathology was examined, and the expression of inflammatory factors and the AGE-RAGE axis in PCa tissues were analyzed. Results PCa mice treated with Astragaloside IV in combination with PESV showed a significant reduction in tumor volume and weight, and stabilization of gut microbiota and metabolites. At the Genus level, significant differences were observed in Porphyromonas, Corynebacterium, Arthromitus and Blautia, and the differential metabolites were PA16_016_0, Astragaloside+, Vitamin A acid, Nardosinone, a-Nortestoster, D-Pantethine, Hypoxanthine, Pregnenolone, cinnamic acid, Pyridoxa, Cirtruline and Xanthurenate. There was a correlation between gut microbiota and metabolites. After the fecal transplantation, tumor growth was effectively suppressed in the PCa mice. Notably, both the mRNA and protein levels of the receptor for advanced glycation end products (RAGE) were significantly decreased. Furthermore, the expression of inflammatory factors, namely NF-κB, TNF-α, and IL-6, in the tumor tissues was significantly attenuated. Conversely, upregulation of RAGE led to increased inflammation and reversed tumor growth in the mice. Conclusion Astragaloside IV combined with PESV could treat PCa by intervening in gut microbiota composition and metabolite by targeting RAGE.

Childhood asthma, a common chronic childhood disease, leads to high mortality and morbidity in the world. Airway smooth muscle cells (ASMCs) is a group of multifunctional cells that has been found to be correlated with the pathogenesis of asthma. Astragaloside IV (AS-IV) is a compound extracted from Astragalus membranaceus, which has the anti-asthmatic effect. However, the role of molecular mechanisms regulated by AS-IV in the biological processes of ASMCs in asthma remains unclear. Our current study aims to investigate the downstream molecular mechanism of AS-IV in modulating the aberrant proliferation and pyroptosis of ASMCs in asthma. At first, we determined that the viability of ASMCs could be efficiently suppressed by AS-IV treatment (200 μM). Moreover, AS-IV promoted the pyroptosis and suppressed PDGF-BB-induced aberrant proliferation. Through mechanism investigation, we confirmed that AS-IV could suppress high mobility group box 1 (HMGB1) expression and prevent it from entering the cytoplasm. Subsequently, AS-IV blocked the interaction between HMGB1 and advanced glycosylation end product-specific receptor (RAGE) to inactivate NF-κB pathway. Finally, in vivo experiments demonstrated that AS-IV treatment can alleviate the lung inflammation in asthma mice. Collectively, AS-IV alleviates asthma and suppresses the pyroptosis of AMSCs through blocking HMGB1/RAGE axis to inactivate NF-κB pathway.

The pathogenesis of membranous nephropathy (MN) involves podocyte injury that is attributed to inflammatory responses induced by local immune deposits. Astragaloside IV (AS-IV) is known for its robust anti-inflammatory properties. Here, we investigated the effects of AS-IV on passive Heymann nephritis (PHN) rats and TNF-α-induced podocytes to determine the underlying molecular mechanisms of MN. Serum biochemical parameters, 24-h urine protein excretion and renal histopathology were evaluated in PHN and control rats. The expression of tumor necrosis factor receptor associated factor 6 (TRAF6), the phosphorylation of nuclear factor kappa B (p-NF-κB), the expression of associated proinflammatory cytokines (TNF-α, IL-6 and IL-1β) and the ubiquitination of TRAF6 were measured in PHN rats and TNF-α-induced podocytes. We detected a marked increase in mRNA expression of TNF-α, IL-6 and IL-1β and in the protein abundance of p-NF-κB and TRAF6 within the renal tissues of PHN rats and TNF-α-induced podocytes. Conversely, there was a reduction in the K48-linked ubiquitination of TRAF6. Additionally, AS-IV was effective in ameliorating serum creatinine, proteinuria, and renal histopathology in PHN rats. This effect was concomitant with the suppression of NF-κB pathway activation and decreased expression of TNF-α, IL-6, IL-1β and TRAF6. AS-IV decreased TRAF6 levels by promoting K48-linked ubiquitin conjugation to TRAF6, which triggered ubiquitin-mediated degradation. In summary, AS-IV averted renal impairment in PHN rats and TNF-α-induced podocytes, likely by modulating the inflammatory response through the TRAF6/NF-κB axis. Targeting TRAF6 holds therapeutic promise for managing MN.

Objective To explore the effects of astragaloside on neural dysfunction and neuronal apoptosis of traumatic brain injury (TBI) in rats through Fas/FasL signaling pathway. Methods Fifty rats were randomly divided into 5 groups: the sham operation group, the model group, the astragaloside group (20 mg/kg), the Fas silencing group [4 µg Fas small interfering RNA (siRNA) lentiviral vector] and the astragaloside+Fas silencing group (20 mg/kg astragaloside+4 µg Fas siRNA lentiviral vector). Each group consisted of 10 rats. Except the sham operation group, the other groups of rats were established TBI rat model. Each group was received medication intervention according to the corresponding dosage, once a day, for 7 days. Water maze test was used to detect the nerve function defect in rats. Fluorescence quantitative PCR was used to detect expression levels of Fas and FasL messenger RNA (mRNA) in brain tissue. Hematoxylin-eosin, β-tubulin III (Tuj1) immunofluorescence and TUNEL staining were used to observe pathological changes, neuronal activity and apoptosis of brain tissue, respectively. Western blot assay was used to detect expression levels of Fas/FasL pathway, Caspase-3, Bcl-2 associated X protein (Bax) and B lymphoblastoma-2 (Bcl-2) protein in brain tissue. Results Compared with the sham operation group, the cell gap was increased and degeneration was obvious in brain tissue in the model group. The escape latency of rats on days 1-5, neuronal apoptosis rate, Caspase-3, Bax protein, Fas, FasL mRNA and protein levels were increased (P＜0.05). The number of times crossing platforms, the number of Tuj1 positive cells and Bcl-2 protein were decreased (P＜0.05). Compared with the model group, in the astragaloside group and the Fas silencing group, the cell gap in brain tissue was narrowed and degeneration was reduced, the escape latency of rats on days 1-5, neuronal apoptosis rate, Caspase-3, Bax protein, Fas, FasL mRNA and protein levels were decreased, and the number of crossing platforms, the number of Tuj1 positive cells and Bcl-2 protein level were increased (P＜0.05). There were no significant differences in pathological changes of brain and the above indexes between the astragaloside group and the Fas silencing group (P＞0.05). Compared with the astragaloside group and the Fas silencing group, the pathological damage of brain tissue of rats was further reduced in the astragaloside+Fas silencing group, neuronal apoptosis rate, Caspase-3, Bax protein, Fas, FasL mRNA and protein levels were decreased, and the number of Tuj1 positive cells and Bcl-2 protein were increased (P＜0.05). Conclusion Astragaloside may reduce nerve function deficit and neuronal apoptosis in TBI rats by inhibiting Fas/FasL signaling pathway mediated apoptosis pathway. [ABSTRACT FROM AUTHOR]

Background: Prostate cancer (PCa) is becoming the most common malignancy in men worldwide. We investigated the effect of astragaloside IV combined with PESV on the gut microbiota and metabolite of PCa mice and the process of treating PCa. Methods: Nude mice were genetically modified to develop tumors characteristic of PCa. The treatment of PCa mice involved the administration of a combination of astragaloside IV and peptides derived from scorpion venom (PESV). Feces were collected for both 16 S rDNA and metabolic analysis. Fecal supernatant was extracted and used for fecal transplantation in PCa mice. Tumor development was observed in both PCa mice and nude mice. Tumor histopathology was examined, and the expression of inflammatory factors and the AGE-RAGE axis in PCa tissues were analyzed. Results: PCa mice treated with Astragaloside IV in combination with PESV showed a significant reduction in tumor volume and weight, and stabilization of gut microbiota and metabolites. At the Genus level, significant differences were observed in Porphyromonas, Corynebacterium, Arthromitus and Blautia, and the differential metabolites were PA16_016_0, Astragaloside+, Vitamin A acid, Nardosinone, a-Nortestoster, D-Pantethine, Hypoxanthine, Pregnenolone, cinnamic acid, Pyridoxa, Cirtruline and Xanthurenate. There was a correlation between gut microbiota and metabolites. After the fecal transplantation, tumor growth was effectively suppressed in the PCa mice. Notably, both the mRNA and protein levels of the receptor for advanced glycation end products (RAGE) were significantly decreased. Furthermore, the expression of inflammatory factors, namely NF-κB, TNF-α, and IL-6, in the tumor tissues was significantly attenuated. Conversely, upregulation of RAGE led to increased inflammation and reversed tumor growth in the mice. Conclusion: Astragaloside IV combined with PESV could treat PCa by intervening in gut microbiota composition and metabolite by targeting RAGE. [ABSTRACT FROM AUTHOR]

Many people around the world suffer from neurodegenerative diseases associated with cognitive impairment. As life expectancy increases, this number is steadily rising. Therefore, it is extremely important to search for new treatment strategies and to discover new substances with potential neuroprotective and/or cognition-enhancing effects. This study focuses on investigating the potential of astragaloside IV (AIV), a triterpenoid saponin with proven acetylcholinesterase (AChE)-inhibiting activity naturally occurring in the root of Astragalus mongholicus, to attenuate memory impairment. Scopolamine (SCOP), an antagonist of muscarinic cholinergic receptors, and lipopolysaccharide (LPS), a trigger of neuroinflammation, were used to impair memory processes in the passive avoidance (PA) test in mice. This memory impairment in SCOP-treated mice was attenuated by prior intraperitoneal (ip) administration of AIV at a dose of 25 mg/kg. The attenuation of memory impairment by LPS was not observed. It can therefore be assumed that AIV does not reverse memory impairment by anti-inflammatory mechanisms, although this needs to be further verified. All doses of AIV tested did not affect baseline locomotor activity in mice. In the post mortem analysis by mass spectrometry of the body tissue of the mice, the highest content of AIV was found in the kidneys, then in the spleen and liver, and the lowest in the brain. [ABSTRACT FROM AUTHOR]

Background: Astragaloside IV has emerged as a pharmaceutical monomer with great medical applications and potential. Astragaloside IV has many effects such as improving myocardial ischemia, cerebral ischemia–reperfusion injury, anti‐inflammatory, analgesic, antiviral, promoting lymphocyte proliferation, and antitumor effects. However, there are few bibliometric studies on astragaloside IV. Objectives: We aim to visualize the hotspots and trends in astragaloside IV research through bibliometric analysis to further understand the future development of basic and clinical research. Methods The articles and reviews on astragaloside IV were screened from the Web of Science Core Collection, and knowledge maps were generated using CiteSpace software. Bibliometric analysis was performed on 971 articles published from 1998 to 2022. Results: The number of articles on astragaloside IV increased yearly. These publications came from 42 countries/regions, with China being the largest. The primary research institutions were Shanghai University of Traditional Chinese Medicine and Guangzhou University of Traditional Chinese Medicine. Journal of Ethnopharmacology was the most studied journal and co‐cited journal. A total of 473 authors were included, among which Hongxin Wang had the highest number of publications and Zhang Wd had the highest total citation frequency. After analysis, the most common keywords are astragaloside IV, expression, and oxidative stress. Cardiovascular disease, cerebral ischemia, cancer, and kidney disease are current and developing research fields. Conclusion: This study used bibliometrics and visualization methods to analyze the research hotspots and trends of astragaloside IV. Astragaloside IV on ischemia–reperfusion injury, cancer, and tumor may become the focus of future research. [ABSTRACT FROM AUTHOR]

Objectives: Astragaloside IV (AST IV) and ligustrazine (Lig), the main ingredients of Astragali Radix and Chuanxiong Rhizoma respectively, have demonstrated significant benefits in treatment of cerebral ischemia ‐reperfusion injury (CIRI); however, the mechanisms underlying its benificial effects remain unclear. SUMO‐1ylation and deSUMO‐2/3ylation of dynamin‐related protein 1 (Drp1) results in mitochondrial homeostasis imbalance following CIRI, which subsequently aggravates cell damage. This study investigates the mechanisms by which AST IV combined with Lig protects against CIRI, focusing on the involvement of SUMOylation in mitochondrial dynamics. Methods: Rats were administrated AST IV and Lig for 7 days, and middle cerebral artery occlusion was established to mimic CIRI. Neural function, cerebral infarction volume, cerebral blood flow, cognitive function, cortical pathological lesions, and mitochondrial morphology were measured. SH‐SY5Y cells were subjected to oxygen–glucose deprivation/reoxygenation (OGD/R) injury. Mitochondrial membrane potential and lactic dehydrogenase (LDH), reactive oxygen species (ROS), and adenosine triphosphate (ATP) levels were assessed with commercial kits. Moreover, co‐immunoprecipitation (Co‐IP) was used to detect the binding of SUMO1 and SUMO2/3 to Drp1. The protein expressions of Drp1, Fis1, MFF, OPA1, Mfn1, Mfn2, SUMO1, SUMO2/3, SENP1, SENP2, SENP3, SENP5, and SENP6 were measured using western blot. Results: In rats with CIRI, AST IV and Lig improved neurological and cognitive functions, restored CBF, reduced brain infarct volume, and alleviated cortical neuron and mitochondrial damage. Moreover, in SH‐SY5Y cells, the combination of AST IV and Lig enhanced cellular viability, decreased release of LDH and ROS, increased ATP content, and improved mitochondrial membrane potential. Furthermore, AST IV combined with Lig reduced the binding of Drp1 with SUMO1, increased the binding of Drp1 with SUMO2/3, suppressed the expressions of Drp1, Fis1, MFF, and SENP3, and increased the expressions of OPA1, Mfn1, Mfn2, SENP1, SENP2, and SENP5. SUMO1 overexpression promoted mitochondrial fission and inhibited mitochondrial fusion, whereas SUMO2/3 overexpression suppressed mitochondrial fission. AST IV combined with Lig could reverse the effects of SUMO1 overexpression while enhancing those of SUMO2/3 overexpression. Conclusions: This study posits that the combination of AST IV and Lig has the potential to reduce the SUMO‐1ylation of Drp1, augment the SUMO‐2/3ylation of Drp1, and thereby exert a protective effect against CIRI. [ABSTRACT FROM AUTHOR]

Background: In recent years, diabetic kidney disease (DKD) has emerged as a prominent factor contributing to end-stage renal disease. Tubulointerstitial inflammation and lipid accumulation have been identified as key factors in the development of DKD. Earlier research indicated that Astragaloside IV (AS-IV) reduces inflammation and oxidative stress, controls lipid accumulation, and provides protection to the kidneys. Nevertheless, the mechanisms responsible for its protective effects against DKD have not yet been completely elucidated. Purpose: The primary objective of this research was to examine the protective properties of AS-IV against DKD and investigate the underlying mechanism, which involves CD36, reactive oxygen species (ROS), NLR family pyrin domain containing 3 (NLRP3), and interleukin-1β (IL-1β). Methods: The DKD rat modelwas created by administering streptozotocin alongwith a high-fat diet. Subsequently, the DKD rats and palmitic acid (PA)-induced HK-2 cells were treated with AS-IV. Atorvastatin was used as the positive control. To assess the therapeutic effects of AS-IV on DKD, various tests including blood sugar levels, the lipid profile, renal function, and histopathological examinationswere conducted. The levels of CD36,ROS, NLRP3, Caspase-1, andIL-1β were detected usingwestern blot analysis, PCR, and flow cytometry. Furthermore, adenovirus-mediated CD36 overexpression was applied to explore the underlying mechanisms through in vitro experiments. Results: In vivo experiments demonstrated that AS-IV significantly reduced hyperglycemia, dyslipidemia, urinary albumin excretion, and serum creatinine levels in DKD rats. Additionally, it improved renal structural abnormalities and suppressed the expression of CD36, NLRP3, IL-1β, TNF-a, and MCP-1. In vitro experiments showed that AS-IV decreased CD36 expression, lipid accumulation, and lipid ROS production while inhibiting NLRP3 activation and IL-1β secretion in PA-induced HK-2 cells. Conclusion: AS-IV alleviated renal tubule interstitial inflammation and tubule epithelial cell apoptosis in DKD rats by inhibiting CD36-mediated lipid accumulation and NLRP3 inflammasome activation. [ABSTRACT FROM AUTHOR]

BACKGROUND: In the initial stage of multiple sclerosis, central immune cells activate and release a large number of inflammatory factors, causing white matter demyelination and even involving gray matter neurons. The equilibrium of differentiation between different subsets of CD4+ T cells plays an important role in the progression of experimental autoimmune encephalomyelitis. The previous results of the research group showed that the active ingredient astragalus glycoprotein in astragalus can regulate the immune response in experimental autoimmune encephalomyelitis mice, and whether it has a regulatory effect on the differentiation of T cell subsets has not been determined. OBJECTIVE: To explore the therapeutic effects and immune regulatory mechanisms of astragaloside IV on experimental autoimmune encephalomyelitis mice. METHODS: Female C57BL/6 mice were divided into the normal control group, experimental autoimmune encephalomyelitis disease model group, and astragaloside IV treatment group (n=8 per group). Myelin oligodendrocyte glycoprotein peptides 35-55 were used for experimental autoimmune encephalomyelitis model induction in the last two groups. On day 10 to 28 after immunization, the astragaloside IV treatment group was treated with 40 mg/kg per day astragaloside IV intragastrically. Body weight and clinical scores of mice in each group were recorded from the immunization day to the 28th day. On the 28th day after immunization, the mouse spinal cord was taken and made into frozen sections for hematoxylin-eosin staining and Lux fast blue staining to observe pathological changes in the spinal cord. Percentage of splenic T cell subsets was detected using flow cytometry. Western blot assay was used to determine the protein expression of interferon-γ, interleukin-17 and interleukin-6 in the spinal cord. Levels of interferon-γ, interleukin-17, interleukin-6 and interleukin-4 in supernatants of cultured splenocytes were determined by ELISA. RESULTS AND CONCLUSION: (1) Compared with the experimental autoimmune encephalomyelitis disease model group, astragaloside IV could reduce the degree of weight loss in experimental autoimmune encephalomyelitis mice (P < 0.05), ameliorate clinical symptoms (P < 0.05), inhibit the infiltration of inflammatory cells and alleviate myelin loss (P < 0.01, P < 0.05). (2) Compared with the experimental autoimmune encephalomyelitis disease model group, astragaloside IV could inhibit the proportion of CD4+ T cell subsets expressing interferon-γ (P < 0.001) and interleukin-17 (P < 0.001), but increase percentages of CD4+ interleukin-10+ (P < 0.001) and CD4+ transforming growth factor-β+ (P < 0.01) T cell subsets. (3) Astragaloside IV could inhibit the expression of interferon-γ (P < 0.05, P < 0.01), interleukin-17 (P < 0.05, P < 0.05), and interleukin-6 (P < 0.05, P < 0.05) in the spinal cord and spleen, and up-regulate the expression of interleukin-4 (P < 0.01) in spleen. (4) These findings confirm that astragaloside IV alleviates clinical symptoms in experimental autoimmune encephalomyelitis mice, which may be related to regulating the splenic T cell subsets, therefore, inhibiting the infiltration of inflammatory cells into the center and reducing the demyelination. [ABSTRACT FROM AUTHOR]

AIM: To observe the effect of icariin-astragaloside IV-puerarin mixture (Yin-Huang-Ge mixture, YHG) on cognitive function and ferroptosis amino acid metabolism pathway in hepcidin (HAMP) knockout APPswe/ PS1dE9 (APP/PS1 HAMP-/-) mice. METHODS: The mice were divided into 7 groups: negative control (C57BL/6 mice) group, APP/PS1 group, APP/PS1 HAMP-/- group, APP/PS1+YHG group, APP/PS1 HAMP-/-+YHG group, APP/PS1+de-ferasirox (DFX) group, and APP/PS1 HAMP-/- +DFX group, with 6 mice in each group. The YHG and DFX were administered intragastrically, while the mice in C57 group, APP/PS1 group and APP/PS1 HAMP-/- group were given intragastric administration of distilled water, once a day for 2 months. The iron content in mouse brain tissues was detected by tissue iron kit. The morphological changes of the mitochondria in hippocampal neurons were observed by transmission electron microscopy. Morris water maze was used to detect the learning and memory ability of the mice. The content of neuronal nuclear antigen (NeuN) in mouse brain tissues was detected by immunofluorescence staining. The expression of glutathione (GSH) in mouse brain tissues was detected by biochemical kit. The expression levels of glutamate-cysteine ligase catalytic subunit (GCLC) and glutamatase 2 (GLS2) in mouse brain tissues were detected by Western blot. RESULTS: Compared with C57BL/6 mice, the brain iron content of APP/PS1 mice was significantly incr eased (P<0. 01), the mitochondria were seriously damaged, the learning and memory ability was significantly decreased (P<0. 05), the brain neurons were seriously damaged (P<0. 01), and the expression levels of GSH, GCLC and GLS2 were significantly decreased (P<0. 01). Compared with APP/PS1 mice, the brain iron content of APP/PS1 HAMP-/- mice was significantly increased (P<0. 01), the mitochondria were seriously damaged, the learning and memory ability was significantly decreased (P<0. 05), the brain neurons were seriously damaged (P<0. 01), and the expression levels of GSH, GCLC and GLS2 were significantly decreased (P<0. 05). After treatment with YHG and DFX, the brain iron content was significantly decreased (P<0. 01), the mitochondrial damage was alleviated, the learning and memory ability was significantly increased (P<0. 05), the brain neuron damage was alleviated (P<0. 01), and the expression levels of GSH, GCLC and GLS2 were significantly increased (P<0. 05). CONCLUSION: The YHG can improve the cognitive function of APP/PS1 HAMP-/- mice, and its mechanism may be related to the regulation of ferroptosis amino acid metabolism and the enhancement of antioxidant capacity. [ABSTRACT FROM AUTHOR]

Pulmonary Fibrosis (PF) is a fatal lung disease with complicated pathogenesis. Astragaloside IV (ASV) has been discovered to alleviate PF progression, and the potential molecular mechanism of ASV in the development of PF need to be further clarified. Bleomycin (BLM) was used to construct PF in vivo model. Expression levels of circ_0008898, miR‐211‐5p, high mobility group protein B1 (HMGB1), alpha smooth muscle Actin (α‐SMA) and Collagen I were examined by Quantitative real time polymerase chain reaction (qRT‐PCR) and western blot. Cell survival was analyzed using Cell Counting Kit‐8 (CCK‐8) and EdU (5‐ethynyl‐2′‐deoxyuridine) assay. The invasion abilities were investigated by transwell assay. The levels of inflammatory factors were tested via using Enzyme‐linked immunosorbent assay (ELISA). The relationship between circ_0008898 or HMGB1 and miR‐211‐5p was identified by dual‐luciferase reporter assay. The results showed that ASV attenuated BLM‐induced pulmonary fibrosis in vivo. In vitro study, ASV alleviated TGF‐β1‐induced fibrogenesis in HFL1 cells. Circ_0008898 was increased in TGF‐β1‐induced HFL1 cells. ASV‐induced impacts were abrogated by circ_0008898 overexpression in TGF‐β1‐induced HFL1 cells. Mechanistically, circ_0008898 competitively bound to miR‐211‐5p to increase the expression of its target HMGB1. MiR‐211‐5p deficiency rescued ASV‐mediated effects in TGF‐β1‐induced HFL1 cells. In addition, HMGB1 overexpression partially overturned circ_0008898 interference‐induced impacts in HFL1 cells upon TGF‐β1 treatment. In conclusion, our work manifested that ASV hindered PF process by mediating the circ_0008898/miR‐211‐5p/HMGB1 network. [ABSTRACT FROM AUTHOR]