Ethnopharmacological relevance Sanguisorba officinalis L., a traditional Chinese hemostatic herb, is described in classical texts as having the dual function of “cooling and tonifying the blood.” Modern clinical studies have confirmed its significant efficacy against myelosuppression induced by cancer therapy, notably in elevating platelet counts in patients. However, the specific active components responsible for this effect and their underlying mechanisms remain unelucidated. Aim of the study Building on the traditional hemostatic efficacy of Sanguisorba officinalis L., this study elucidates the effects and mechanisms of its active monomer, epigallocatechin (EGC), in promoting megakaryocyte differentiation and platelet production for the treatment of thrombocytopenia. Materials and methods In this study we evaluated the ability of EGC to promote megakaryocyte differentiation of model cells in vitro. Its hematopoietic effects in vivo were further assessed using zebrafish and mouse models of RIT. To pinpoint the core targets of EGC against RIT, we utilized network pharmacology, complemented by experimental validation with molecular biology techniques to elucidate its pro-hematopoietic mechanisms mediated through the estrogen receptor. Results EGC effectively enhanced megakaryocyte differentiation and platelet production in vitro and in vivo, without detectable toxicity. Integrated network pharmacology and molecular validation revealed ERα-mediated signaling as the primary mechanism underlying EGC’s activity. Mechanistically, EGC promoted megakaryocyte differentiation by activating ERα-mediated SRC/PI3K/AKT signaling and modulating hematopoietic transcription factors. Conclusions EGC promotes megakaryocyte differentiation via ERα-mediated activation of the SRC/PI3K/AKT pathway and subsequent regulation of hematopoietic transcription factors for the treatment of thrombocytopenia.

BackgroundMyocardial infarction (MI) remains a leading cause of cardiovascular mortality worldwide, underscoring the need for improved diagnostic and therapeutic strategies. Despite recent in clinical management, delayed diagnosis and complications such as adverse myocardial remodeling continue to compromise long-term outcomes. Identifying specific biomarkers and actionable therapeutic targets is therefore crucial for precision medicine in MI.MethodsWe integrated MI-related datasets from the Gene Expression Omnibus (GEO) database and performed differential expression analysis alongside weighted gene co-expression network analysis (WGCNA) to identify key differentially expressed genes (DEGs). Machine learning algorithms were applied to screen diagnostic hub genes and evaluate their diagnostic performance. Two-sample Mendelian randomization (MR) analysis, primarily utilizing the random-effects inverse-variance weighting assessed causal relationships between candidate genes and MI risk. Immune profiling was conducted via immune cell infiltration deconvolution and scRNA-seq analysis. Finally, wet-lab validation was performed using quantitative real-time PCR (RT-qPCR), Western blot, and immunohistochemistry in an in vivo animal model.ResultsOur analysis initially identified 15 key diagnostic genes. Through two-sample MR analysis, MYO6 exhibited a significant causal relationship with a reduced risk of MI. Immune infiltration analysis revealed significant enrichment of pro-inflammatory cells (neutrophils and monocytes) and a concomitant depletion of protective immune cells (resting natural killer cells and activated CD4 memory T cells) in MI patients. MYO6 expression correlated positively with protective immune cells and negatively with pro-inflammatory cells. Furthermore, scRNA-seq analysis showed that MYO6 was predominantly enriched in T cells and natural killer cells, potentially regulating their subset differentiation, inhibiting excessive intercellular communication, and promoting collagen-mediated tissue repair, thereby alleviating MI injury and enhancing plaque stability. In vivo experiments validated the successful establishment of the MI model, revealing that MYO6 was significantly downregulated at both the mRNA and protein levels in infarcted myocardium.ConclusionThrough multidimensional analysis of clinical transcriptomic data and experimental validation in animal models, we have identified MYO6 as a potential novel diagnostic biomarker for MI, while highlighting the role of immune homeostasis in disease progression and MYO6 regulation. These findings provide crucial insights for the molecular diagnosis and targeted therapy of MI.

Atherosclerosis seriously endangers human health. Quercetin has drawn attention for its potential anti-atherosclerotic pharmacological effects. This study aimed to comprehensively assess quercetin's effect and potential mechanism in treating atherosclerosis through a systematic review and meta-analysis. Preclinical studies published before 20 January 2025 were searched for in databases including PubMed, Embase, Web of Science, CNKI, Wanfang, and VIP. The CAMARADES list was used to assess the quality of the included studies. Stata 12 was applied for overall effect, sensitivity, subgroup, and publication bias analyses. Time-dose interval analyses were conducted to explore how quercetin dose and dosing cycle affect intervention effects. Finally, trial sequential analyses were performed using TSA 0.9 software. A total of 22 studies involving 421 animals were included, with a mean methodological quality score of 7.73/10. Meta-analysis showed that relative to the control group, quercetin reduced aortic plaque area, adjusted lipids (lowered TC, TG, and LDL-C and raised HDL-C), downregulated adhesion factors (e.g., VCAM-1) and pro-inflammatory factors (e.g., IL-1β and IL-6), upregulated anti-inflammatory factor IL-10 and antioxidant enzymes (SOD, CAT) while decreasing MDA content, and regulated atherosclerosis-related targets (e.g., LXRα, SIRT1, and mTOR). Subgroup analyses found model establishment time and quercetin administration time affected aortic lesion areas, TC, and TG. Time-dose analysis indicated quercetin had better ameliorative effects on atherosclerosis at 25-100 mg/kg with an 8-10-week intervention. Quercetin significantly improves atherosclerosis and inhibits its occurrence and progression through multiple pathways, such as regulating lipid metabolism, anti-inflammatory effects, and counteracting oxidative stress. Based on current evidence, quercetin is a potential therapeutic agent for treating atherosclerosis.

Ulcerative colitis (UC) is a persistent inflammatory bowel disease that poses an increasingly significant public health concern worldwide. Given the limited efficacy of current therapies, the development of novel treatment approaches has become increasingly urgent. Our previous investigation established that methyl gallate (MG) exhibits therapeutic potential for UC due to its effective anti-inflammatory properties. However, the low targeting specificity and high in vivo clearance rate of MG restrict its application. Herein, platelet membrane (PM) biomimetic MG-loaded liposome (PML) was firstly constructed to improve MG delivery and enable targeted UC therapy. Due to the PM cloaking, PML exhibited prolonged circulation time and enhanced targeting to damaged colon caused by UC. Moreover, the PM biomimetic liposome demonstrated higher uptake efficiency in inflammatory cells. In vitro and in vivo investigations consistently proved that PML exhibited significant anti-inflammatory activity. Additionally, intravenous administration of PML effectively reduced disease severity in UC mouse models and promoted the intestinal tissue repair. Besides, PML showed high erythrocyte compatibility and favorable biosafety in UC mice and zebrafish. Collectively, PML achieve enhanced MG delivery and may provide a novel precision therapy strategy for UC treatment.

Objective:To observe the effects of iron supplementation on a physiological pregnancy and on pregnancy following iron deficiency anemia (IDA) caused by low-iron diet. Method:Physiological pregnancy anemia and IDA-induced pregnancy rat models were established, and the effects of preventive iron supplementation with ferrous succinate tablets (Sulifei, SLF) and polysaccharide-iron complex (Niferex, LFN) on pregnancy ability, embryonic development, anemia indicators, and iron content and metabolic indicators were observed in the model rats. Result:Anemia markers and body iron content were decreased in physiological pregnancy rat model, accompanied by abnormal oxidative stress and iron metabolism. In post-IDA gestational rat model, these markers were even more severely aggravated. SLF and LFN intervention improved body iron content, oxidative stress, and iron metabolism-related markers in physiological pregnant rats, but did not improve anemia-related markers. After 6 weeks of pretreatment with SLF and LFN, some reproductive toxicity effects were observed. SLF and LFN intervention in post-IDA gestational rat model improved anemia markers, body iron content, and iron metabolism-related markers. There were no significant differences in reproductive parameters between the two groups. Fetal weight and the average crown-rump length per litter increased in the LFN group. Conclusion:Post-IDA gestation further exacerbates iron deficiency anemia. Prophylactic iron supplementation can significantly improve physiological iron deficiency and iron metabolism during pregnancy but cannot improve iron deficiency anemia. In contrast, iron supplementation can significantly improve iron deficiency anemia in post-IDA gestation. To prevent or treat pregnancy complicated by IDA, iron supplementation is recommended either before the onset of IDA or after pregnancy.

Diabetic wounds are difficult to heal because of persistent oxidative stress and limited angiogenesis. However, traditional wound dressings cannot address these issues simultaneously. In this study, a thermosensitive chitosan (CS) hydrogel loaded with Thonningianin A (TA) nanoparticles (TA-NPs) was constructed. First, TA-NPs were developed via the nanoprecipitation technique. CS was subsequently combined with β‑sodium glycerophosphate (β-GP) to prepare a thermosensitive hydrogel matrix (CS/β-GP). Finally, composite hydrogels (TA-NPs@Gel) with antioxidant and angiogenesis-promoting properties were synthesized by incorporating TA-NPs into a CS/β-GP hydrogel matrix. Characterization revealed that the TA-NPs were uniformly spherical, with a particle size of 186.30 ± 1.15 nm and a zeta potential of -35.07 ± 0.61 mV. Scanning electron microscopy and Fourier transform infrared spectroscopy confirmed the successful integration of TA-NPs into the hydrogel matrix. Both in vitro and in vivo studies demonstrated that TA-NPs@Gel exhibited potent antioxidant and angiogenic effects, significantly accelerating wound healing in a diabetic mouse model. Network pharmacology predictions indicated that TA-NPs@Gel promoted diabetic wound healing through the HIF-1 signaling pathway. Overall, the integration of TA-NPs into a hydrogel system has broad therapeutic potential for the treatment of diabetic wounds.

[This corrects the article DOI: 10.3389/fnut.2025.1650536.].

Doxorubicin (DOX) is widely employed in anticancer therapy, but its clinical application is constrained by its cardiotoxic effects. Trillin, a bioactive compound derived from Trillium tschonoskii Maxim., has been identified as a natural antioxidant possessing cardioprotective properties. This study aimed to ascertain whether trillin can protect against DOX-induced cardiotoxicity (DIC) through its inherent antioxidant capabilities. In vivo studies, C57BL/6 mice were administered DOX (5 mg/kg i.p.) via intraperitoneal injection once weekly for a total of five consecutive weeks and received trillin (25, 50 and 100 mg/kg i.g.) through intragastric administration once daily for six weeks. In vitro studies, H9c2 cardiomyocytes were utilized to verify the protective efficacy of trillin (0.5, 1 and 2 μM) against DIC. Trillin significantly mitigated DOX-induced myocardial damage, which encompassed improvements in left ventricular function, reductions in serum cardiac enzymes levels, and diminution of heart cell vacuolation. Moreover, trillin effectively attenuated DIC while preserving the anticancer efficacy of DOX. Trillin also alleviated oxidative injury by elevating levels of SOD and GSH and reducing MDA levels. Additionally, trillin restored the expression of Nrf2 and HO-1 in mouse hearts and H9c2 cardiomyocytes treated with DOX. Trillin safeguarded against DIC by inhibiting oxidative stress via upregulation of the Nrf2/HO-1 pathway. These findings furnish evidence suggesting trillin may serve as a therapeutic agent for the prevention of DIC.

Chemotherapy- and radiotherapy-induced leukopenia is a common challenge in cancer treatment, with a significant dearth of effective therapeutic options. IL-23 receptor (IL-23R) signaling holds the potential for promoting neutrophil generation and maturation, yet the underlying mechanisms remain elusive. This study investigates the molecular mechanism and efficacy of Mulberroside C (MC) in alleviating leukopenia via IL-23R signaling. In vitro, flow cytometry, nitroblue tetrazolium reduction assay, and Giemsa staining were employed to evaluate MC's impact on neutrophil differentiation in NB4 and HL-60 cell lines. The antibacterial activity of MC was assessed using an agar plate assay. In vivo, leukopenia models induced by irradiation and cyclophosphamide were established in zebrafish and mice to determine MC's effect on neutrophil recovery. Mechanistic studies involved RNA sequencing, network pharmacology analysis, molecular docking, quantitative real-time PCR (qRT-PCR), and Western blotting to explore the associated signaling pathways. Cellular thermal shift assay (CETSA) and drug affinity responsive target stability (DARTS) were used to identify MC's targets. MC significantly enhanced neutrophil maturation in a dose-dependent manner, facilitating leukopenia recovery. Mechanistically, MC binds to IL-23R, upregulating G-CSF, GM-CSF, and RASGRP1 and activating the RAS/ERK signaling pathway. Notably, the upregulation of RASGRP1 by MC supports the generation of fully functional neutrophils, compared to those induced by G-CSF and GM-CSF alone. This study provides the first evidence that MC promotes neutrophil generation and antimicrobial activity through the IL-23R-mediated pathway, offering a promising therapeutic strategy for leukopenia.

Purpose: To evaluate the efficacy, durability and safety of intravitreal faricimab versus aflibercept over 48 weeks in patients with neovascular age-related macular degeneration (nAMD) from the LUCERNE China subpopulation. Design: LUCERNE (NCT03823300) was a phase 3 global, double-masked, active comparator-controlled trial. The China subpopulation comprised patients from mainland China, Taiwan and Hong Kong. Methods: Treatment-na & iuml;ve patients aged >= 50 years with nAMD were randomized 1:1 to receive faricimab 6.0 mg up to every 16 weeks (Q16W) based on prespecified disease criteria after four initial Q4W doses or aflibercept 2.0 mg Q8W after three initial Q4W doses. The primary endpoint was mean change from baseline in best- corrected visual acuity (BCVA) averaged over weeks 40 to 48. Anatomical, durability and safety outcomes were also evaluated. Results: The China subpopulation comprised 119 patients (faricimab: n = 59, aflibercept: n = 60). At weeks 40 to 48, adjusted mean (95% confidence interval [CI]) BCVA letter gains from baseline were +9.7 (7.4 to 12.0) and +9.8 (7.5 to 12.1) with faricimab and aflibercept, respectively. Central subfield thickness was reduced from baseline by weeks 40 to 48 in both arms, with an adjusted mean (95% CI) change of-145.4 mu m (-156.2 to-134.6) and-156.5 mu m (-167.3 to-145.7) for faricimab and aflibercept, respectively. By week 48, 87.3% of the patients were on extended >= Q12W faricimab dosing. Faricimab was well tolerated with no new safety signals. Conclusions: Faricimab up to Q16W showed durable efficacy in the LUCERNE China subpopulation, consistent with global findings. Faricimab may reduce treatment burden for patients with nAMD in China, without compromising efficacy.

BackgroundBerberine (BBR) is widely used to treat gastrointestinal diseases. However, the pharmacological mechanism of action of BBR in anti-chronic atrophic gastritis (CAG) remains unclear. This study aimed to investigate the mechanism of action of BBR in CAG by integration of molecular biology and multi-omics studies strategy.MethodsThe CAG model was established by alternating drinking water of 0.1% ammonia and 20 mmol/L sodium deoxycholate, accompanied by an irregular diet. Serum biochemical indices including PGI, PGII, GAS-17, IL-6, IL-1β, and TNF-α were analyzed. HE and AB-PAS staining were employed to assess pathological damage in gastric tissue. The underlying molecular mechanism of BBR in CAG treatment was explored via the integration of network pharmacology, transcriptomics, widely targeted metabolomics and intestinal flora analysis. Finally, relevant key targets and pathway were verified.ResultsThe results showed that BBR exerted therapeutic effects in improving CAG via alleviating inflammation response, maintaining the gastric mucosal barrier’s integrity and repairing gastric mucosal tissues. Network pharmacology showed that the treatment of CAG by BBR mainly involved in inflammatory response, apoptosis, angiogenesis and metabolic processes. Furthermore, 234 different expression genes were identified in the gastric tissue transcriptome, which were mainly involved in biological processes such as cell adhesion, angiogenesis, apoptosis, cell migration and lipids metabolism by regulating the MAPK signaling pathway. Metabolomics results showed that 125 differential metabolites were also identified, while the pathways were mainly involved in D-glutamine and D-glutamate metabolism, and tyrosine metabolism, etc. Integrating transcriptomics and metabolomics analyses indicated that BBR directly regulated Carnitine C3:0, LPC (0:0/20:3), L-Glutamic Acid and FFA (15:0) by acting on SLC25A20, PNLIPRP1, PLA2G4C, GSR, GFPT2, GCLM, CTPS1, ACSL1, ACOT4 and ACOT2. 16S rRNA sequencing revealed that BBR could restore the balance of gut microbiota dysbiosis by significantly regulating the relative abundance of unclassified_Muribaculaceae and Lactobacillus_johnsonii.ConclusionThis study demonstrated that BBR alleviates CAG through the regulation of the MAPK signaling pathway, metabolic disorders and gut microbiota dysbiosis, thereby revealing the complex mechanism of BBR in relation to alleviating CAG from multiple levels and perspectives.

Hepatointestinal diseases seriously reduce the quality of life of affected individuals and pose a heavy burden on the society.Currently,there are some anti-hepatointestinal disease drugs in use;however,they have limitations.Paeoniflorin(PF)is a single terpenoid glycoside extracted from the roots of Paeonia lactiflora Pall.and Paeonia veitchii Lynch.It is a widely prescribed Chinese herbal medicine for the treatment of liver and intestinal diseases and has multipathway and multitarget characteristics.This review aimed to systematically summarize the pharmacological effects of PF on hepatointestinal diseases and its mechanisms of action.Regarding liver disease,PF shows remarkable anti-inflammatory,antioxidant,anti-apoptosis,and bile acid metabolism effects through the regulation of silent information regulator sirtuin 1/farnesol X receptor(FXR),high mobility group box 1/toll-like receptor 4,insulin receptor substrates/protein kinase B(Akt)/glycogen synthase kinase-3 β,and phosphoinositide 3-kinase/Akt signaling pathways.In addition,it plays an anti-fibrosis role through the transforming growth factor(TGF)-β1/Smads and liver X receptors/signal transducer and activator of transcription 3 pathways.PF can prevent the invasion and metastasis of hepatocellular carcinoma cells by inhibiting the expression of the TGF-β1/Smads and mitogen-activated protein kinase/extracellular regulated protein kinases signaling pathways.Regarding intestinal diseases,PF exerts mitochondrial protection and macrophage regulation and has anti-inflammatory and antioxidant effects through the regulation of the muramyl dipeptide/nucleotide-binding oligomerization domain 2,mammalian target of rapamycin/hypoxia inducible factor-1α,and liver kinase B1/AMP-activated protein kinase pathways.In addition,it is involved in liver-intestinal axis interaction through the regulation of FXR,bile acids,and intestinal flora.This review provides a solid foundation for the utilization of PF in hepatointestinal disease treatment.Further research and development of new dosage forms will extend its application in the field of hepatointestinal protection.

Recent evidence suggests that ferroptosis, an iron-facilitated cell death with excessive lipid peroxidation, is a critical mechanism underlying doxorubicin (DOX)-induced cardiotoxicity (DIC). Although dioscin has been reported to improve acute DIC, direct evidence is lacking to clarify the role of dioscin in chronic DIC and its potential mechanism in cardiac ferroptosis. In this study, we used chronic DIC rat models and H9c2 cells to investigate the potential of dioscin to mitigate DIC by inhibiting ferroptosis. Our results suggest that dioscin significantly improves chronic DIC-induced cardiac dysfunction. Meanwhile, it significantly inhibited DOX-induced ferroptosis by reducing Fe2+ and lipid peroxidation accumulation, maintaining mitochondrial integrity, increasing glutathione peroxidase 4 (GPX4) expression, and decreasing acyl-CoA synthetase long-chain family 4 (ACSL4) expression. Through transcriptomic analysis and subsequent validation, we found that the anti-ferroptotic effects of dioscin are achieved by regulating the nuclear factor-erythroid 2-related factor 2 (Nrf2)/GPX4 axis and Nrf2 downstream iron metabolism genes. Dioscin further downregulates nicotinamide adenine dinucleotide phosphate oxidase 4 (NOX4) and upregulates expression of frataxin (FXN) and ATP-binding cassette B8 (ABCB8) to limit mitochondrial Fe2+ and lipid peroxide accumulation. However, Nrf2 inhibition diminishes the anti-ferroptotic effects of dioscin, leading to decreased GPX4 expression and increased lipid peroxidation. This study is a compelling demonstration that dioscin can effectively reduce DIC by inhibiting ferroptosis, which is dependent on the Nrf2/GPX4 pathway modulation.

Interleukins, a diverse family of cytokines produced by various cells, play crucial roles in immune responses, immunoregulation, and a wide range of physiological and pathological processes. In the context of megakaryopoiesis, thrombopoiesis, and platelet function, interleukins have emerged as key regulators, exerting significant influence on the development, maturation, and activity of megakaryocytes (MKs) and platelets. While the therapeutic potential of interleukins in platelet-related diseases has been recognized for decades, their clinical application has been hindered by limitations in basic research and challenges in drug development. Recent advancements in understanding the molecular mechanisms of interleukins and their interactions with MKs and platelets, coupled with breakthroughs in cytokine engineering, have revitalized the field of interleukin-based therapeutics. These breakthroughs have paved the way for the development of more effective and specific interleukin-based therapies for the treatment of platelet disorders. This review provides a comprehensive overview of the effects of interleukins on megakaryopoiesis, thrombopoiesis, and platelet function. It highlights the potential clinical applications of interleukins in regulating megakaryopoiesis and platelet function and discusses the latest bioengineering technologies that could improve the pharmacokinetic properties of interleukins. By synthesizing the current knowledge in this field, this review aims to provide valuable insights for future research into the clinical application of interleukins in platelet-related diseases.

Stimulating erythropoiesis is essential in the treatment of various types of anemia. Sheng Xue Ning (SXN) is commonly used in China as an iron supplement to treat iron deficiency anemia, renal anemia, and anemia in pregnancy. This research reports a novel effect of SXN in enhancing the proliferation of hematopoietic stem/progenitor cell (HSPC) to promote erythropoiesis in the bone marrow, which is distinct from conventional iron supplements that primarily aid in the maturation of red blood cells. Employing a model of hematopoietic dysfunction induced by X-ray exposure, we evaluated the efficacy of SXN in restoring hematopoietic function. SXN significantly promoted the recovery of peripheral erythroid cells and enhanced the proliferation and differentiation of Lin−/c-KIT+/Sca-1+ HSPC in mice exposed to X-ray irradiation. Our results showed that SXN elevated the expression of stem cell factor (SCF) and activated the SCF/c-KIT/PI3K/AKT signaling pathway, facilitating the proliferation and differentiation of HSPC. In vitro, SXN markedly enhanced the proliferation of bone marrow nucleated cell (BMNC) and the colony-forming capacity of BFU-E, CFU-E, and CFU-GM, while also elevating the expression of proteins involved in the SCF/c-KIT/PI3K/AKT pathway in BMNC. Additionally, SXN enhanced the proliferation and differentiation of mesenchymal stem cell (MSC) and increased SCF secretion. In conclusion, SXN demonstrates the capacity to enhance erythropoiesis by upregulating SCF expression, thereby promoting HSPC proliferation and differentiation via the SCF/c-KIT/PI3K/AKT pathway. SXN may offer a new strategy for improving the activity of HSPC and promoting erythropoiesis in the treatment of hematopoiesis disorders.

Primary immune thrombocytopenia (ITP) is an acquired autoimmune disorder characterized by the destruction of platelets. Although it was long believed that the critical role of autoantibodies in platelet destruction, primarily through the Fc-dependent platelet clearance pathway, recent findings indicate that the significance of the Fc-independent platelet clearance pathway mediated by hepatocytes, thus shedding light on a previously obscure aspect of ITP pathogenesis. Within this context, the desialylation of platelets has emerged as a pivotal biochemical marker. Consequently, targeting platelet desialylation emerges as a novel therapeutic strategy in the pathogenesis of ITP. Notably, prevailing research has largely focused on antiplatelet antibodies and the glycosylation-associated mechanisms of platelet clearance, while comprehensive analysis of platelet desialylation remains scant. In response, we retrospectively discuss the historical progression, inducing factors, generation process, and molecular regulatory mechanisms underlying platelet desialylation in ITP pathogenesis. By systematically evaluating the most recent research findings, we contribute to a comprehensive understanding of the intricate processes involved. Moreover, our manuscript delves into the potential application of desialylation regulatory strategies in ITP therapy, heralding novel therapeutic avenues. In conclusion, this manuscript not only fills a critical void in existing literature but also paves the way for future research by establishing a systematic theoretical framework. By inspiring new research ideas and offering insights into the development of new therapeutic strategies and targeted drugs, our study is poised to significantly advance the clinical management of ITP.

Ethnopharmacological relevanceIron is an essential micronutrient for maintaining physiological activities, especially for highly active cardiomyocytes. Inappropriate iron overload or deficiency has a significant impact on the incidence and severity of cardiovascular diseases (CVD). Iron overload exerts potentially deleterious effects on doxorubicin (DOX) cardiomyopathy, atherosclerosis, and myocardial ischemia-reperfusion injury (MI/RI) by participating in lipid peroxides production. Notably, iron overload-associated cell death has been defined as a possible mechanism for ferroptosis. At present, some traditional herbal medicines and extracts have been included in the study of regulating iron overload and the subsequent therapeutic effect on CVD.Aim of the studyTo give an outline of iron metabolism and ferroptosis in cardiomyocytes and to focus on herbal medicines and extracts to prevent iron overload in CVD.Materials and methodsLiterature information was systematically collected from ScienceDirect, PubMed, Google Scholar, Web of Science, China National Knowledge Infrastructure, WanFang data, as well as classic books and clinical reports.ResultsAfter understanding the mechanism of iron overload on CVD, this paper reviews the therapeutic function of various herbal medicines in eliminating iron overload in CVD. These include Chinese herbal compound prescriptions (Salvia miltiorrhiza injection, Gegen Qinlian decoction, Tongxinluo, Banxia-Houpu decoction), plant extracts, phenylpropanoids, flavonoids, terpenoids, and polyphenols. Among them, flavonoids are considered to be the most promising compounds because of their prominent iron chelation. Mechanically, these herbal medicines act on the Nrf2 signaling pathway, AMPK signaling pathway, and KAT5/GPX4 signaling pathway, thereby attenuating iron overload and lipid peroxidation in CVD.ConclusionOur review provides up-to-date information on herbal medicines that exert cardiovascular protective effects by modulating iron overload and ferroptosis. These herbal medicines hold promise as a template for preventing iron overload in CVD.

Objectives: Thrombocytopenia is a disease in which the number of platelets in the peripheral blood decreases. It can be caused by multiple genetic factors, and numerous challenges are associated with its treatment. In this study, the effects of alnustone on megakaryocytes and platelets were investigated, with the aim of developing a new therapeutic approach for thrombocytopenia. Methods: Random forest algorithm was used to establish a drug screening model, and alnustone was identified as a natural active compound that could promote megakaryocyte differentiation. The effect of alnustone on megakaryocyte activity was determined using cell counting kit-8. The effect of alnustone on megakaryocyte differentiation was determined using flow cytometry, Giemsa staining, and phalloidin staining. A mouse model of thrombocytopenia was established by exposing mice to X-rays at 4 Gy and was used to test the bioactivity of alnustone in vivo. The effect of alnustone on platelet production was determined using zebrafish. Network pharmacology was used to predict targets and signaling pathways. Western blotting and immunofluorescence staining determined the expression levels of proteins. Results: Alnustone promoted the differentiation and maturation of megakaryocytes in vitro and restored platelet production in thrombocytopenic mice and zebrafish. Network pharmacology and western blotting showed that alnustone promoted the expression of interleukin-17A and enhanced its interaction with its receptor, and thereby regulated downstream MEK/ERK signaling and promoted megakaryocyte differentiation. Conclusions: Alnustone can promote megakaryocyte differentiation and platelet production via the interleukin17A/interleukin-17A receptor/Src/RAC1/MEK/ERK signaling pathway and thus provides a new therapeutic strategy for the treatment of thrombocytopenia.