Inflammatory macrophages in failing myocardium secrete CCL17, which targets CCR4 in immunosuppressive Tregs and inhibits the intracellular second messenger ARRB2-mediated cardiac chemotaxis. Traditional Chinese medicine (TCM) LuQi formula (LQF) is safe and effective in treating heart failure (HF). This study aims to elucidate the cardioprotective mechanism of LQF through its modulation of cardiac macrophages and Tregs.

In vivo, the HF mouse model was established via transverse aortic constriction (TAC), with the superagonistic anti-CD28 monoclonal antibody (CD28-SA)-induced Tregs expansion as a positive control. Proteomics analysis elucidated the core link of LQF in anti-HF. In vitro, bone marrow-derived macrophages (BMDMs) were isolated, and Naive CD4+T cells were sorted and stimulated to differentiate into Tregs. The pharmacological mechanism of LQF was confirmed through histological and molecular biology experiments.

Proteomics reveals that LQF modulates the immune microenvironment of failing myocardium. We revealed that LQF inhibited cardiac inflammatory macrophage infiltration and NF-κB (p50, p65)/CCL17 axis expression, and promoted cardiac Tregs recruitment against HF, with the comparable efficacy of CD-SA28-induced Tregs expansion. Mechanistically, LQF inhibited the NF-κB activator 1-induced NF-κB (p50, p65)/CCL17 axis overexpression, and JSH-23 (NF-κB Inhibitor) abolished NF-κB (p50, p65)/CCL17 axis expression in inflammatory macrophages. Furthermore, the inhibition of CCL17 expression in inflammatory macrophages by LQF was found to be mediated by NF-κB (p50, p65). LQF concentration-dependently promoted Tregs CD73/Foxp3 axis expression, enhancing Tregs immunosuppressive function. LQF activated CCR4-ARRB2 complex and CCR4/ARRB2 axis expression in Tregs. Although AZD2098 (CCR4 Inhibitor) blocked CCR4 expression and CCR4-ARRB2 complex, LQF promoted ARRB2-mediated Tregs cardiac chemotaxis independent of the CCR4. We revealed that NF-κB p50SEP337-CCL17, NF-κB p65SEP536-CCL17, and CCR4-ARRB2 highly bound subunit interface targets. Molecular docking analysis demonstrated that the LQF's active ingredients exhibit good binding affinity with the NF-κB (p50, p65) /CCL17 axis in macrophages and Foxp3 in Tregs.

LQF has the potential to enhance the cardiac immune microenvironment and effectively prevent and treat HF by modulating both innate and adaptive immune responses. It achieves this by inhibiting the infiltration of inflammatory macrophages, suppressing the NF-κB (p50, p65)/CCL17 axis, and promoting Tregs recruitment. The active ingredients of LQF provide valuable candidate compounds for developing new anti-HF drugs. Furthermore, CD-28SA-induced Tregs expansion showed cardioprotective effects in TAC-induced non-ischemic HF models.

In recent years, the use of traditional Chinese medicine (TCM) in the treatment of cancer has received widespread attention. Treatment of tumours using TCM can effectively reduce the side effects of anti-tumour drugs, meanwhile to improve the treatment efficacy of patients. However, most of the active ingredients in TCM, such as saponins, alkaloids, flavonoids, volatile oils, etc., have defects such as low bioavailability and poor solubility in clinical application, which seriously restrict the application of TCM. Meanwhile, the encapsulation of TCM into lipid nano-delivery systems for cancer therapy has received much attention. Lipid nano-delivery systems are obtained by using phospholipids as the base material and adding other auxiliary materials under a certain preparation process, including, for example, liposomes, solid lipid nanoparticles (SLNs), nanostructured lipid carriers (NLCs), microemulsions, and self-microemulsion drug delivery systems (SMEDDS), can resolve the application problems of TCM by improving the efficacy of active ingredients of TCM and reducing the toxicity of anti-tumour drugs. This paper focuses on the categories, development status, and research progress of lipid nano delivery system of TCM, aiming to provide a certain theoretical basis for further in-depth research and rational application of these systems.

Epigenetic modifications play a critical role in regulating gene expression under various physiological and pathological conditions. Epigenetic modifications reprogramming is a recognized hallmark of aging and a key component of the aging clock used to differentiate between chronological and biological age. The potential for prospective diagnosis and regulatory capabilities position epigenetic modifications as an emerging drug target to extend longevity and alleviate age-related organ dysfunctions. In the past few decades, numerous preclinical studies have demonstrated the therapeutic potential of natural products in various human diseases, including aging, with some advancing to clinical trials and clinical application. This review highlights the discovery and recent advancements in the aging clock, as well as the potential use of natural products as anti-aging therapeutics by correcting disordered epigenetic reprogramming. Specifically, the focus is on the imbalance of histone modifications, alterations in DNA methylation patterns, disrupted ATP-dependent chromatin remodeling, and changes in RNA modifications. By exploring these areas, new insights can be gained into aging prediction and anti-aging interventions.

This study investigated the effects of short-term exposure to flavonoids, specifically quercetin and taxifolin, on the transcriptomic responses of Chinese sucker (Myxocyprinus asiaticus) to validate their influence on gene expression related to immunity, antioxidant activity, and metabolism. Using transcriptomic data, we also analyzed their influence on relevant immune genes and examined the Chinese suckers' resistance to A. hydrophila. Oxidative stress, immune defense, and glucose metabolism of Chinese suckers were tested to assess potential enhancements. Significant alterations were observed in multiple immune-related Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways in the liver of Chinese suckers, notably the complement and coagulation cascades, degradation of aromatic compounds, and xenobiotic metabolism by cytochrome P450. The key immune markers such as UGT, MPO, C3, and C4 were highlighted in these pathways, underlining their importance in fish immunity. Additionally, oxidative stress related KEGG pathways were notably influenced after exposure to quercetin and taxifolin, displaying markers such as CYP3A, superoxide dismutase, GST, malondialdehyde, and catalase. Quercetin particularly affected the enzymatic activity of glucose oxidase, hexokinase, phosphofructokinase, and ATPase, which are enzymes related to stress responses in fish. Antimicrobial tests revealed that both flavonoids enhanced Chinese suckers' defense against A. hydrophila by bolstering oxidative stress resistance and immunity. These results provided valuable insights for using flavonoids to enhance fish immunity.

Myocarditis is one of the common causes of sudden death in adolescents, and autoimmune response and inflammation play an essential role in the development of myocarditis. Quercetin is a natural flavonoid compound with anti-inflammatory and cardioprotective effects. However, the mechanism of quercetin in autoimmune myocarditis remains unclear. This study observed that quercetin significantly improved cardiac function, inflammation and fibrosis in mice with experimental autoimmune myocarditis (EAM). In addition, Network pharmacology predicts the key target C/EBPβ and signalling pathway MAPK for quercetin treatment of autoimmune myocarditis. CESTA and DARTS experiments verified that quercetin and C/EBPβ have strong binding ability. It is shown that quercetin down-regulates MCP-1 expression in H9C2 cells by dephosphorylation of ERK1/2 and C/EBPβ. Specifically, quercetin reduced the binding of C/EBPβ to the MCP-1 promoter, resulting in decreased expression of MCP-1, which was associated with decreased ERK1/2 dependent phosphorylation at the C/EBPβ threonine 188 site. This inhibitory effect of quercetin could be further enhanced by the ERK1/2 inhibitor PD98059. The biological relevance of this regulatory network is demonstrated in EAM mice. In conclusion, these results illustrate the protective effect of quercetin against autoimmune myocarditis. A novel regulatory mechanism was revealed, namely the down-regulation of MCP-1 through the ERK1/2-C/EBPβ axis. This provides a new therapeutic strategy for autoimmune myocarditis.

Millions of people worldwide suffer from epilepsy, a persistent neurological illness characterized by recurring seizures. Despite advances in anti-epileptic medications, a significant number of patients continue to have insufficient seizure control and have side effects. Nanotechnology has emerged as a promising alternative for increasing medicine delivery and therapeutic effects in recent years. The anti-epileptic potential of nanoparticles produced from herbal medicines such as berberine-loaded zein/hyaluronic acid composite, Cannabis sativa extract-loaded nanoliposomes and nanostructured lipids, nanostructured lipid vehicle-carried safranal, and cryptolepine solid-lipid NPs is reviewed in this work, which makes use of the synergistic effects of nanotechnology and natural substances. The manuscript presents an overview of the mechanisms underlying the anti-epileptic effects of these nanoparticles, ranging from regulating neurotransmitter systems and ion channels to lowering oxidative stress and inflammation. Preclinical studies using animal models of epilepsy have shown that herbal medicine nanoparticles can reduce seizure activity, prolong seizure latency, and improve cognitive function. The findings presented in this manuscript highlight the remarkable potential of herbal medicine nanoparticles as a novel approach to the management of epilepsy. Continued research and development in this field have the potential to revolutionize epilepsy therapy and improve the quality of life for people suffering from this debilitating condition.

Quercetin is a natural product with multiple activities, which possesses a promising antitumor effect on malignancies. The involvement of proline 4-hydroxylase II (P4HA2) in collagen synthesis is crucial in the growth of tumor cells. Apoptosis is a programmed cell death requisite for the stability of the intracellular environment. However, the relationship between quercetin and cell apoptosis, as well as the impact of P4HA2 in this connection, has not yet been specified in hepatocellular carcinoma(HCC).

The present study used HCC cells to investigate how quercetin regulates P4HA2 and influences cell proliferation and apoptosis.

The outcomes reveal that quercetin can impede the viability and growth of HCC cells and generate cell apoptosis in a dose-dependent manner. Additionally, quercetin prompts downregulation of P4HA2, leading to cell apoptosis in HCC cells, and knocking down P4HA2 can enhance this effect. Furthermore, we pretreated HCC cells with inhibitors (Z-VAD-FMK, LY294002) or activators (740Y-P) and found that the PI3K/Akt/mTOR pathway was occupied with quercetin-induced cell apoptosis.

This investigation reveals that quercetin compels apoptosis in HCC cells by diminishing P4HA2 and restraining the PI3K/Akt/mTOR axis.

Psoriasis is an immune-mediated inflammatory skin disorder marked by excessive keratinocyte proliferation and inflammatory cell infiltration. Quercetin has shown a range of biological activities, highlighting its potential as a therapeutic agent for psoriasis.

This study aims to explore the mechanisms by which quercetin treats psoriasis.

An Imiquimod-induced psoriasis mouse model and a TNF-α-induced keratinocyte proliferation model were utilized, supplemented with quercetin and DAPT. The expression of K10, K14, Notch1, NICD, AKT and Glut1 in psoriatic lesions and normal skin was assessed. Techniques employed included hematoxylin-eosin staining, immunohistochemical staining, western blotting, quantitative polymerase chain reaction, cell counting kit-8 assay, flow cytometry, and enzyme-linked immunosorbent assay.

Notch1, AKT, and Glut1 were highly expressed in psoriasis. Quercetin induced keratinocyte apoptosis and inhibited the Notch signaling pathway, as well as the expression of AKT and Glut1. Inhibition of Notch signaling led to keratinocyte apoptosis and downregulation of the AKT and Glut1 expression. The results of network pharmacology and molecular docking are consistent with this.

This study provides the first evidence that quercetin induces keratinocyte apoptosis and promotes keratinocyte differentiation to treat psoriasis through the triple inhibition of the Notch and PI3K/AKT signaling pathways, as well as Glut1. The downregulation of the PI3K/AKT pathway and Glut1 is achieved partially via Notch inhibition. These findings suggest that quercetin could be a novel agent for improving psoriasis treatment, especially in patients exhibiting high expression of Notch1, AKT, and Glut1 in their skin lesions.

Quercetin as a flavonoid polyphenol in nature has shown great anti-obesity effects. Due to its poor stability in chemical structure and low intestinal absorption, the in vivo bioavailability of quercetin is considered to be the main challenge for applications. To achieve the oral quercetin administration, chitosan was successfully trimethylated (TMC) to coat the quercetin-loaded zein nanoparticles (Zein-Q), which were designed as the core-shell structure for enhancing the intestinal absorption in this study. TMC-Zein-Q was demonstrated to protect quercetin from degradation and showed the sustained-release effect in an in vitro drug release experiment. The nanoparticles were found to reversibly open tight junctions between intestinal epithelial cells and help to increase quercetin uptake via the paracellular pathway in Caco-2 cells. In addition, the delivery system also showed stronger intestinal permeability and mucoadhesion in vivo, which improved the bioavailability of quercetin in cellular and animal experiments. After 10 weeks of intervention, TMC-Zein-Q could effectively suppress weight gain, improve serum lipid levels, and ameliorate hepatic steatosis and glucose tolerance in high-fat diet (HFD) mice by mediating the AMPK pathway. Consequently, this work successfully constructed TMC-Zein-Q for oral quercetin delivery, providing a novel and feasible strategy for the treatment of obesity via the oral route.

Enzyme-based electrochemical biosensors have broad and significant applications in biomedical, environmental monitoring, and food safety fields. However, the application of natural enzymes is limited due to issues such as poor stability, complex preparation, and high cost. Single-atom nanozymes (SAzymes), with their unique catalytic properties and efficient enzyme-like activities, present a promising alternative in the field of electrochemical biosensing. Compared to traditional enzymes, SAzyme offer enhanced stability and controllability, making them particularly effective in complex detection environments. This work presents the first systematic review of the progress made since 2018 in the use of SAzymes as alternatives to natural enzymes in electrochemical biosensors, and presents the latest advancements in this area. The review begins with a discussion of various enzyme-like activities of single-atom materials, including peroxidase (POD)-like, oxidase (OXD)-like, catalase (CAT)-like, and superoxide dismutase (SOD)-like activities. It then explores the advantages of SAzymes in improving the performance of electrochemical biosensors from multiple perspectives. The review also summarizes the applications of SAzyme-based electrochemical sensors for reactive oxygen species (ROS), metabolites, neurotransmitters, and other analytes, highlighting specific examples to elucidate underlying catalytic mechanisms and understand fundamental structure-performance relationships. In the final section, the challenges faced by SAzyme-based electrochemical biosensing are discussed, along with potential solutions.

Metabolic syndrome (MetS) is a cluster of risk factors that significantly increase the chances of developing heart disease, type 2 diabetes mellitus, stroke, and other cardiovascular complications. Since current anti-MetS medications like statins, angiotensin-converting enzyme inhibitors, β-blockers, insulin sensitizers and diuretics have been reported to cause unwanted side effects, researchers are exploring promising alternatives. One such alternative relies on the potential of spices and condiments, which have a long history of use in traditional medicine. Among them, Cinnamomum zeylanicum Blume stands out as a popular spice worldwide for its unique taste, aroma, and delicate sweetness compared to other cinnamon varieties. This narrative review aims to summarize the in vivo and clinical evidence concerning the efficacy of C. zeylanicum against MetS indices. Relevant articles from PubMed, Scopus and Google scholar databases were reviewed. In vivo results suggested that C. zeylanicum preparations (extracts, essential oil, crude powder, bioactive compounds, and biosynthesized nanoparticles) were remarkably efficient in ameliorating MetS indices, while the clinical data were less and with several methodological limitations. Further robust clinical studies are warranted to definitively establish C. zeylanicum as a promising functional food for mitigating MetS, potentially leading to its dietary integration as a natural approach to improve metabolic health. Please cite this article as: Adarthaiya S, Arivarasan VK. Potential of Cinnamomum zeylanicum for metabolic syndrome management: insights from in vivo and human studies. J Integr Med. 2025; Epub ahead of print.

Renal fibrosis represents the terminal pathological manifestation of most chronic kidney diseases, driving progressive loss of renal function. Natural products have emerged as promising therapeutic agents for preventing and ameliorating renal fibrosis due to their multi-target efficacy and favorable safety profiles. In this review, we conducted a comprehensive literature search on PubMed using the keywords "natural product" and "renal fibrosis" from 2004 to 2025, identifying 704 relevant articles. We systematically categorize and discuss the biological effects of key natural products and formulations with antifibrotic potential, focusing on five major classes: glycosides, flavonoids, phenolic compounds, anthraquinones, and terpenoids. Representative compounds from each category are highlighted for their mechanisms of action, including modulation of oxidative stress, inflammation, autophagy, and fibrosis signaling pathways. This review aims to provide a theoretical foundation for the development of natural product-based therapies to combat renal fibrosis, offering insights into their therapeutic potential and future research directions.

Obesity is a chronic metabolic disease, mainly caused by excessive/abnormal fat accumulation, as well as accompanied by endotoxemia and chronic inflammation. Quercetin, a natural flavonoid, may alleviate obesity by regulating gut microbiota and metabolites, but its exact mechanism for improving obesity is unknown.

The aim of this study was to investigate the effects of quercetin on high-fat diet (HFD)-induced obesity in mice. In particular, we focused on the regulatory effects of quercetin on gut microbiota and the tryptophan metabolite indole-3-propionic acid (IPA).

The C57BL/6J mice were subjected to a 20-week HFD feeding regimen with concurrent daily oral administration of quercetin or IPA. The body weight, fat accumulation, gut barrier function, and chronic inflammation were determined. Gut microbiota composition was analyzed by 16S rRNA sequencing and IPA levels were measured in serum and feces. In vitro experiments, Caco-2 cells were used to evaluate the effects of IPA and fecal dilutions from quercetin-treated mice on tight junction protein expression and aryl hydrocarbon receptor (AhR) activation.

Our results revealed that quercetin supplementation significantly mitigated obesity and chronic inflammation, and improved the disrupted gut barrier function through the actvation of AhR/interleukin 22 (IL-22) pathway. 16S rRNA sequencing revealed that quercetin treatment increased the abundance of Lactobacillus. Quercetin intervention increased the levels of IPA in the serum and feces of mice. IPA supplementation alleviated obesity and chronic inflammation, and enhanced intestinal barrier function through AhR activation. The findings were further corroborated by Caco-2 cell experiment, which indicated that the modulation of the dysregulated gut microbiota to change microbial metabolite IPA coordinated the improvement effect of quercetin on gut barrier disruption.

Quercetin supplementation alleviates obesity by restoring high-fat diet induced gut microbiota disorder, which elevates IPA level to activate AhR/IL-22 pathway, thereby enhancing intestinal barrier integrity and suppressing chronic inflammation.

Hepatic ischemia-reperfusion injury (IRI) is an inevitable adverse event following liver surgery, leading to liver damage and potential organ failure. Despite advancements, effective interventions for hepatic IRI remain elusive, posing a significant clinical challenge. The innate immune response significantly contributes to the pathogenesis of hepatic IRI by promoting an inflammatory cytotoxic cycle. We have reported that blocking GSDMD-induced pyroptosis in innate immunity cells protected hepatic IRI from inflammatory injury. However, the search for effective pyroptosis inhibitors continues.

This study aims to evaluate whether quercetin, a natural flavonoid, can inhibit GSDMD-induced pyroptosis and mitigate hepatic IRI.

We established the hepatic IRI murine model and cellular pyroptosis model to evaluate the efficacy of quercetin.

Quercetin effectively alleviated hepatic IRI-induced tissue necrosis and inflammation. We found that during hepatic IRI, the cleavage of GSDMD occurred in hepatic macrophages, but not in other non-parenchymal cells. Quercetin inhibited the cleavage of GSDMD in macrophages. Moreover, we found that quercetin blocked the ASC assembly to inhibit the formation of NLRP3 inflammasomes and AIM2 inflammasomes, suppressing macrophage pyroptosis. Co-immunoprecipitation experiments confirmed that quercetin inhibited the interaction between ASC and Caspase-8, which is the mechanism of ASC complex and inflammasome formation. Overexpression of Caspase-8 abolished the anti-pyroptosis effect of quercetin in NLRP3 and AIM2 inflammasome signaling. Furthermore, we found that the hepatoprotective activity of quercetin was reduced in myelocytic GSDMD-deficient mice.

Our findings suggest that quercetin has beneficial effects on hepatic IRI. Quercetin could attenuate hepatic IRI and target inhibition of macrophage pyroptosis via blocking Caspase-8/ASC interaction. We recommend that quercetin might serve as a targeted approach for the prevention and personalized treatment of hepatic IRI in perioperative patients.

Quercetin (Que) is a polyhydroxy flavonoid with strong inhibitory activity against cancer cells. However, the poor water solubility and low bioavailability of Que. limit its application in the functional food industry. In the present study, the nanoparticle loaded with Que. was prepared with whey isolate protein (WPI) stabilized by triphenylphosphonium bromide (TPP) and pectin (P) as wall materials. The formation mechanism, release of Que., and antitumor activity of nanoparticles were investigated. The results showed that the optimal ratio of WPI: TPP: Que.: P in the preparation of nanoparticles (WPI-TPP-Que-P) was 50:8:1:20 (w/w/w/w). The encapsulation rate of Que. in the WPI-TPP-Que-P was 82.64 % with a particle size of 261.7 nm and a zeta potential of -42.1 mV. Compared with WPI-TPP-Que, the retention rate of WPI-TPP-Que-P increased by 4.03 % after in vitro digestion. The release kinetic result indicated that WPI-TPP-Que-P release was dominated by non-Fickian diffusion. In addition, WPI-TPP-Que-P was taken in and achieved intracellular targeting to mitochondria and promoted apoptosis (apoptosis rate: 83.6 %) by decreasing mitochondrial membrane potential and IL-10 content and improving the content of TNF-α in HepG-2 cells. This study highlights the promising application of P-modified mitochondria-targeted nanocarriers for enhanced Que. delivery.

Obesity and obesity-related metabolic diseases are causally linked to inflammatory activation. Proinflammatory macrophage infiltration and NOD-like receptor pyrin domain containing 3 (NLRP3) inflammasome activation contribute to chronic inflammation and insulin resistance. Alleviating inflammatory responses is a reliable method to restore insulin sensitivity and reduce the severity of metabolic syndrome. Solanesol, rich in anti-inflammatory foods (potato, tomato, eggplant, chili peppers), has demonstrated anti-inflammatory properties, but whether it plays a beneficial role in obesity-induced chronic inflammation remains poorly understood. In this study, we investigated the effects of solanesol on the NLRP3 inflammasome and inflammatory responses both in vitro and in high-fat diet (HFD)-fed mice. We found that oral administration of solanesol reduced weight gain, insulin resistance, and inflammation in epididymal white adipose tissue (eWAT) in both HFD-fed obese mice and mice concurrently treated with a HFD. This effect was involved with reducing macrophage inflammation and inactivating the NLRP3 inflammasome by reducing the K+ efflux and reactive oxygen species (ROS) production in macrophages. Solanesol also reprogrammed the phenotype of inflammatory macrophages. Taken together, our study suggests that solanesol may be a promising candidate for treating obesity and obesity-related metabolic diseases.

Inflammation represents a critical immune response triggered by cellular activities and inflammatory mediators following tissue damage. It plays a central role in the pathological progression of diverse diseases, including psychiatric disorders, cancer, and immunological conditions, rendering it an essential target for therapeutic intervention. Periodontitis, a prevalent oral inflammatory disease, is a leading cause of tooth loss and poses significant health challenges globally. Traditionally, inflammatory diseases such as periodontitis have been treated with systemic administration of synthetic chemicals. However, recent years have witnessed challenges, including drug resistance and microbial dysbiosis associated with these treatments. In contrast, natural products derived from Chinese medicine offer numerous benefits, such as high safety profiles, minimal side effects, innovative pharmacological mechanisms, ease of extraction, and multiple targets, rendering them viable alternatives to conventional antibiotics for treating inflammatory conditions. Numerous effective anti-inflammatory natural products have been identified in traditional Chinese medicine (TCM), including alkaloids, flavonoids, terpenoids, lignans, and other natural products that exhibit inhibitory effects on inflammation and are potential therapeutic agents. Several studies have confirmed the substantial anti-inflammatory and immunomodulatory properties of these compounds. This comprehensive review examines the literature on the anti-inflammatory effects of TCM-derived natural products from databases such as PubMed, Web of Science, and CNKI, focusing on terms like "inflammation", "periodontitis", "pharmacology", and "traditional Chinese medicine". The analysis systematically summarizes the molecular pharmacology, chemical composition, and biological activities of these compounds in inflammatory responses, alongside their mechanisms of action. This research seeks to deepen understanding of the mechanisms and biological activities of herbal extracts in managing inflammatory diseases, potentially leading to the development of promising new anti-inflammatory drug candidates. Future applications could extend to the treatment of various inflammatory conditions, including periodontitis.

"Jiedu Tongluo Tiaoying Formula" (JDTLTYF) is a kind of traditional Chinese medicine (TCM) prescription for treating hyperthyroidism, which can effectively improve the condition of patients. The main active ingredients of JDTLTYF were collected from the traditional Chinese medicine systems pharmacology (TCMSP) database, and the target was predicted. Genes related to hyperthyroidism were identified using DisGeNET, GeneCards, and Online Mendelian Inheritance in Man (OMIM) databases. Protein-protein interaction (PPI) network and interaction network of "formula-herb-active ingredient-target genes" was constructed. Mass spectrometry was used to identify the components. The binding of key components to the target was verified by molecular docking and molecular dynamics (MD) simulations. A hyperthyroidism mouse model was established by using levothyroxine sodium tablets, and the hormone and expression levels of inflammatory factors were examined by ELISA and Western blot. The key genes of JDTLTYF in the treatment of hyperthyroidism were TNF and AKT1. The results of mass spectrometry also showed that quercetin was one of the main components. The results of molecular docking and MD simulation showed that the binding-free energy between AKT1 and quercetin was the lowest, and the binding was stable. In vivo experimental results showed that gastric lavage with JDTLTYF could target AKT1 and TNF-α, effectively alleviate the pathological features of hyperthyroidism in mice, and reduce inflammation response. This study elucidated the key small molecule compounds and their action targets of JDTLTYF in the treatment of hyperthyroidism. It provides a direction for the development of new drugs for clinical hyperthyroidism.NEW & NOTEWORTHY Based on the network pharmacology and molecular dynamics (MD) simulation, this study elucidated the key small molecule compounds and their action targets of JDTLTYF Chinese herbal prescription (debark peony root, common selfheal fruit-spike, figwort root, thunberg fritillary bulb, and oyster shell) in the treatment of hyperthyroidism, preliminarily analyzed its molecular mechanism, and provided a reference direction for subsequent cell experiments.

Global health is increasingly challenged by the growing prevalence of obesity and its associated complications. Quercetin, one of the most important dietary flavonoids, is being explored as an effective therapy for obesity with its mechanism remains understudied. Here in this study, it is demonstrated that quercetin intervention significantly reverses obesity-related phenotypes through reshaping the overall structure of microbiota, especially boosting colonization of the beneficial gut commensal Akkermansia muciniphila (A. muciniphila). Enrichment of A. muciniphila leads to generate more indole-3-lactic acid (ILA) to upregulate the expression of 12α-hydroxylase (CYP8B1) via fat mass and obesity-associated protein (FTO)/ N6-methyladenosine (m6A)/YTHDF2 manner, thereby facilitating cholesterol converts to cholic acid (CA). CA in turn drastically suppresses lipid accumulation via activating the farnesoid X receptor (FXR) in adipose tissue. This work introduces a novel therapeutic target for addressing obesity and expands upon the current limited understanding of the mediator function of m6A modifications in microorganism-influenced bile acid (BA) metabolism.

Non-alcoholic fatty liver disease (NAFLD) is a progressive disease. Without effective interventions, NAFLD can gradually develop to non-alcoholic steatohepatitis, fatty liver fibrosis, liver cirrhosis and even hepatocellular carcinoma. It is still to investigate the precise molecular mechanism behind the pathophysiology of NAFLD. Triggering receptor expressed on myeloid cells 2 (TREM2) can sense tissue injury and mediate immune remodeling, thereby inducing phagocytosis, lipid metabolism, and metabolic transfer, promoting cell survival and combating inflammatory activation. NAFLD might develop as a result of TREM2's regulatory role. We here briefly summarize the biological characteristics of TREM2 and its functions in the disease progression of NAFLD. Moreover, we propose to broaden the therapeutic strategy for NAFLD by targeting TREM2.

Cadmium (Cd) is an important environmental pollutant that can enter the body and inflict kidney damage. Quercetin (Que) is a natural flavonoid compound that can alleviate kidney damage in Cd-treated rats, but the specific mechanism is unclear. Herein, 24 male Sprague-Dawley rats were divided into four groups, namely the control, Cd, Cd + Que, and Que groups. Four weeks later, the rats were anesthetized with ether and were euthanized; then, their blood was collected and their kidneys were removed. Renal function markers were measured. Kidney tissue structure was observed by HE staining, cell apoptosis was detected by the TUNEL method, and mRNA and protein expression levels in the IRE1α-XBP1 apoptosis signaling pathway were analyzed by RT-PCR and Western blotting. Results showed that the Cd treatment group exhibited decreased renal dysfunction and pathologic injury. Cd-induced tissue damage and cell apoptosis and significantly increased the mRNA and protein expression levels (p < 0.01) related to the IRE1α-XBP1 signaling pathway. Compared with the Cd group, the Cd + Que group exhibited increased renal dysfunction. Conversely, kidney tissue damage and renal cell apoptosis decreased, and the mRNA and protein expression levels of IRE1α and XBP1 significantly decreased (p < 0.01). Cd treatment inflicted renal damage. Therefore, Que can restore the kidney tissue damage and alleviate the cell apoptosis caused by Cd through the inhibition of the IRE1α-XBP1 signaling pathway.

Hyperuricemia is associated with several metabolic and cardiovascular disorders, and traditional treatments, such as xanthine oxidase (XO) inhibitors, often have limitations, such as severe hypersensitivity reactions or ineffectiveness in achieving target serum urate levels in some patients. Quercetin, a naturally occurring flavonoid, has shown potential as a hypouricemic agent through XO inhibition.

This study aims to evaluate the potential hypouricemic effect of Quercetin Phytosome™ (QP) supplementation across three cohort studies involving healthy adults with various metabolic health profiles, exploring its potential as a safe, effective intervention for hyperuricemia.

Clinical data collected in various clinics in Italy between September 2021 and April 2024 under real-life clinical settings from three distinct cohort studies, were analyzed. Cohort 1 consisted of 164 healthy participants (87 QP-treated, 77 probiotic Streptococcus salivarius (S. salivarius) K12-treated) who were monitored for 90 days. Cohort 2 included 22 mildly hyperuricemic adults with metabolic disorders receiving QP, while Cohort 3 comprised 64 obese adults with hypercholesterolemia, further divided into moderately hyperuricemic QP-treated group (n = 20), a moderately hyperuricemic Berberine Phytosome™ and monacolins (BM)-treated group (n = 22), and a normouricemic BM-treated group (n = 22). QP was administered at 400 mg of quercetin daily in all cohorts. Primary endpoints were reductions in serum uric acid levels, while secondary outcomes included effects on lipid profile, glycemia, liver enzymes, and treatment tolerability.

In Cohort 1, QP significantly reduced uric acid levels by 15.2% in males and 13.8% in females, with no significant changes observed in the probiotic group. Cohort 2 showed a significant 13.1% reduction in uric acid (p < 0.01) and a concurrent 10.2% reduction in triglycerides (p < 0.05). In Cohort 3, QP led to a 13.7% decrease in uric acid and a 20.8% reduction in triglycerides (p < 0.01), with no significant uric acid changes in the BM-treated group. QP was well tolerated across all cohorts, with minimal, transient side effects.

QP supplementation demonstrates a significant hypouricemic effect. Additionally, triglyceride-lowering benefits were evident, particularly in metabolically compromised individuals (Cohorts 2 and 3), where these effects were statistically significant. With high tolerability, these findings highlight Quercetin Phytosome™'s potential as a safe adjunctive therapy for hyperuricemia management, meriting further investigation in larger, randomized trials to confirm its efficacy and safety.

clinicaltrials.gov, identifier NCT06652035.

Lipopolysaccharide (LPS) is a large amphipathic glycoconjugate molecule in the cell wall of Gram-negative bacteria. This bacterial endotoxin binds to toll-like receptor 4 (TLR4) and stimulates the inflammatory reactions and oxidative stress. The current paper presents the protective effects of natural compounds against LPS-induced injuries. The relevant findings were extracted from PubMed, Web of Science, Scopus, and Google Scholar databases from the beginning of 2005 until the end of September 2023 were employed. The results of in vitro and in vivo studies indicated that thymoquinone, crocin, carvacrol, and quercetin effectively attenuated LPS-induced damages via lowering the level of inflammatory cytokines and free radicals. These natural compounds could also amplify the antioxidant defense against LPS by increasing the activity of antioxidant enzymes such as superoxide dismutase (SOD) and catalase (CAT). In addition, a part of the protective effects of these phytochemicals against detrimental impacts of LPS is attributed to their ability to downregulate the TLR4 expression and to inhibit the NF-κB signaling pathway. Briefly, the protective effects of natural compounds mentioned in current review against LPS-caused damages mainly are mediated by their anti-inflammatory and antioxidant activities.

The rapid development of nanotechnology has resulted in the widespread use of nanoparticles (NPs) in various sectors due to their unique properties and diverse applications. However, the increased exposure of humans to NPs raises concerns about their potential negative impact on human health and the environment. The pathways through which NPs exert adverse effects, including inflammation and oxidative stress, are primarily influenced by their size, shape, surface charge, and chemistry, underscoring the critical need to comprehend and alleviate their potential detrimental impacts. In this context, the natural flavonoid quercetin is a promising candidate for counteracting the toxicity induced by NPs due to its anti-inflammatory and antioxidant properties. This review provides an overview of the existing literature on quercetin's protective effects against NPs-induced toxicity, highlighting its therapeutic benefits and mechanisms of action, focusing on its ability to alleviate oxidative stress, inflammation, and cellular damage caused by various types of NPs. Insights from both in vitro and in vivo studies demonstrate the effectiveness of quercetin in preserving cellular function, modulating apoptotic pathways, and maintaining tissue integrity in the presence of NPs. The potential of quercetin as a natural therapeutic agent against NPs-induced toxicity provides valuable insights for safer use of NPs in various daily applications.

The ovary is a crucial gonadal organ that supports female reproductive and endocrine functions. Ovarian aging can result in decreased fertility and dysfunction across multiple organs. Research has demonstrated that cellular senescence in various cell types within the ovary can trigger a decline in ovarian function through distinct stress responses, resulting in ovarian aging. This review explores how cellular senescence may contribute to ovarian aging and reproductive failure. Additionally, we discuss the factors that cause ovarian cellular senescence, including the accumulation of advanced glycation end products, oxidative stress, mitochondrial dysfunction, DNA damage, telomere shortening, and exposure to chemotherapy. Furthermore, we discuss senescence in six distinct cell types, including oocytes, granulosa cells, ovarian theca cells, immune cells, ovarian surface epithelium, and ovarian endothelial cells, inside the ovary and explore their contribution to the accelerated ovarian aging. Lastly, we describe potential senotherapeutics for the treatment of ovarian aging and offer novel strategies for ovarian longevity.

Microplastics and nanoplastics (MNPs) are emerging environmental contaminants that have received significant attention in recent years. Currently, there are more studies on the toxic effects of MNPs exposure on animals (especially aquatic organisms and mammals), but data on the reduction of toxic effects caused by MNPs exposure are still very limited. Lactic acid bacteria (LAB), recognized as safe food-grade microorganisms, possess the capability to bioconjugate harmful substances. In this experiment, we chose lactic acid bacteria (LAB) with different binding capacities to MNPs in vitro to intervene in MNPs-exposed mice to investigate the reducing effect on the toxicity caused by MNPs exposure. Our study showed that LAB with a high intercalation capacity with MNPs in vitro were more effective in alleviating the toxicity caused by MNPs exposure. Notably, Lactobacillus plantarum DT22, despite its low inter-adsorption with MNPs, played a pivotal role in upregulating the relative expression of tight junction proteins and modulating the intestinal microbiota. Thus, LAB strains' mitigation of MNPs toxicity extends beyond bio-binding; their capacity to repair the damaged gut environment is also crucial. LAB strains are proposed as a dietary intervention to reduce MNPs-induced toxicity.

Throughout the recent decades, obesity has become a serious health problem that raises the risk of several diseases, including cancer, diabetes, hypertension, heart disease, neurological musculoskeletal disorders, and Non-alcoholic fatty liver disease. Some strategies, such as dietary interventions, calorie restriction (CR), and the use of antioxidant compounds, have been proposed to improve quality of life in relation to obesity. The goal of this study was to characterize the effects of CR and quercetin (QUER) on obesity-induced oxidative stress (OS). Thirty 8-week-old male BALB/c mice were divided into 5 groups of six mice each: normal diet, high-fat diet (HFD), HFD + CR, HFD + QUER (15 mg kg-1, IP), and HFD + QUER + CR. CR was applied as two fasting days with an interval of two days in a week. Catalase (CAT), Paraxonase 1 (PON1) and adiponectin (APN) were decreased in the HFD group, while the combination of QUER and CR increased these parameters. Treatment with QUER and CR improved Alanine transaminase and Alkaline Phosphatase enzyme activity and also the amount of leptin and insulin. Moreover, combined QUER and CR also reduced triacylglycerol (TAG), total cholesterol and TAG droplets in hepatocytes. Decreased OS was associated with the higher expression of NAD(P)H Quinone Oxidoreductase 1(NQO1) and reduced hepatic vacuoles in QUER and CR-HFD treated groups. In conclusion, these findings suggest that the combination of QUER and CR might exert protective impacts on obesity through alleviating OS and the regulation of metabolism.

Food supplements are used for a variety of purposes, one of which is weight reduction. As excess weight is a long-term condition, some supplements are expected to be used for long periods of time. The long-term use of these dietary supplements makes it highly likely that they will be combined with medications, increasing the risk of food supplement-drug interactions, which are not always known or disclosed, and can lead to serious health problems, as has been observed. This article discusses some of the compounds used as food supplements for weight reduction (green tea extract, Garcinia cambogia, chitosan, quercetin and resveratrol) and the interactions they may cause with some drugs such as: dextromethorphan, buspirone, diclofenac, irinotecan, 5-fluorouracil, cytochrome P450 inducers and inhibitors, statins, orlistat, warfarina, acenocoumarol, fluoxetine, valproate, quetiapine, carbamazepine. This information is expected to be useful for healthcare professionals to detect and intervene on food supplement-drug interactions to ensure the optimization of therapy and patient safety.

Ulcerative colitis (UC) is a chronic inflammatory condition of the intestinal tract in which mucosal healing is a crucial measure of therapeutic efficacy. Quercetin, a flavonoid prevalent in various foods and traditional Chinese medicines, exhibits notable pharmacological properties, including antioxidant and anti-inflammatory activities. Consequently, it warrants investigation to determine its potential therapeutic effects on UC. The objective of this study was to investigate the effects and underlying mechanisms of quercetin in a murine model of UC.

A comprehensive approach integrating network predictions with transcriptomic analyses was employed to identify the potential targets and enriched pathways associated with quercetin in UC. Subsequently, the effects of quercetin on pathological morphology, inflammatory mediators, and mucosal barrier-associated proteins, as well as the identified potential targets and enriched pathways, were systematically investigated in a murine model of dextran sulfate sodium (DSS)-induced UC.

Network analyses identified CXCL8 and its receptors, CXCR1 and CXCR2, as primary target genes for therapeutic intervention in UC. Further validation through transcriptomic analysis and immunofluorescence staining demonstrated significant upregulation of the CXCL8-CXCR1/2 axis in the intestinal tissues of patients with UC. Experimental investigations in animal models have shown that quercetin markedly alleviates DSS-induced symptoms in mice. This effect includes the restoration of colonic crypt architecture, normalization of goblet cell structure and density, reduction of inflammatory cell infiltration, and decreased concentrations of inflammatory mediators. Quercetin enhanced the expression of tight junction (TJ) proteins, including ZO-1, MUC2 (Mucin 2), and occludin, thereby preserving the integrity of the intestinal mucosal barrier. Additionally, it significantly diminished the levels of IL-17A, NF-κB, CXCL8, CXCR1, and CXCR2 in the colonic tissues of mice with UC.

The ameliorative effects of quercetin on colon tissue damage in DSS-induced UC mice were significant, possibly due to its ability to inhibit the CXCL8-CXCR1/2 signaling axis. These findings provide a solid foundation for the clinical application and pharmaceutical advancement of quercetin.

Granulosa cell (GC) apoptosis, ferroptosis, and other programmed cell death processes are markers of follicular aging. Quercetin has been shown to reduce ferroptosis, however, its effects on ferroptosis in poultry remains unexplored. Our preliminary study identified ferroptosis in aging ovaries. Therefore, in the present study, 540-day-old Mountain Plum-blossom chickens were fed with quercetin supplementation at varying doses (0.2, 0.4, and 0.6 g/kg), and examined its molecular effects on GC ferroptosis using an in vitro Erastin-induced model.

The results showed that quercetin supplementation significantly increased egg production, which confirmed its potential to alleviate ferroptosis in chicken ovarian tissue. The in vitro experiment revealed that quercetin and Fer-1 (positive control) mitigated Erastin-induced ferroptosis in GCs. Further, transcriptome analysis revealed that quercetin modulated key genes such as acyl-CoA synthetase long-chain family member 4 (ACSL4), solute carrier family 7 member 11 (SLC7A11), and transferrin receptor (TFRC), involved in ferroptosis regulation. The results further showed that quercetin also reduced Erastin-induced apoptosis and inflammation by modulating the expression of genes and proteins related to apoptosis and inflammatory factors (NF-κB, TNF-α, IL-6, and IL-10).

Taken together, the results showed that quercetin improves egg production performance in chickens and mitigates ovarian ferroptosis in aging hens, and inhibits Erastin-induced ferroptosis, inflammation, and apoptosis in GCs. These findings revealed the protective role of quercetin in poultry ovarian tissue and its cellular mechanisms against detrimental factors in poultry production.

Immunotherapy has brought hope to many breast cancer patients, but not all patients benefit from it. Quercetin (Qu), a natural product found in various sources, has anti-inflammatory and anti-tumor properties. We conducted a review of the pharmacological research of Qu in regulating anti-tumor immunity in vivo and in vitro. Qu can directly regulate the local tumor microenvironment (TME) by enhancing the activity of immune cells which includes promoting the infiltration of T cells and natural killer (NK) cells, inhibiting the recruitment of myeloid-derived suppressor cells and tumor-associated macrophages. Additionally, Qu inhibits anaerobic glycolysis in tumor cells, thereby reducing the production and transport of lactic acid. It also suppresses tumor angiogenesis by targeting the vascular endothelial growth factor (VEGF) pathway and the vitamin D pathway. Furthermore, Qu can enhance the efficacy of immunotherapy for breast cancer by modulating the systemic microenvironment. This includes inhibiting obesity-related chronic inflammation to decrease the production of inflammatory factors, regulating the composition of intestinal microbiota, and intervening in the metabolism of intestinal flora. At the same time, we also address challenges in the clinical application of Qu, such as low absorption rates and unknown effective doses. In conclusion, we highlight Qu as a natural immunomodulator that enhances immune cell activity and has the potential to be developed as an adjunct for breast cancer.

Diabetic peripheral neuropathy (DPN) results in an enormous burden and reduces the quality of life for patients. Considering there is no specific drug for the management of DPN, traditional Chinese medicine (TCM) has increasingly drawn attention of clinicians and researchers around the world due to its characteristics of multiple targets, active components, and exemplary safety.

To summarize the current status of TCM in the treatment of DPN and provide directions for novel drug development, the clinical effects and potential mechanisms of TCM used in treating DPN were comprehensively reviewed.

Existing evidence on TCM interventions for DPN was screened from databases such as PubMed, the Cochrane Neuromuscular Disease Group Specialized Register (CENTRAL), and the Chinese National Knowledge Infrastructure Database (CNKI). The focus was on summarizing and analyzing representative preclinical and clinical TCM studies published before 2023.

This review identified the ameliorative effects of about 22 single herbal extracts, more than 30 herbal compound prescriptions, and four Chinese patent medicines on DPN in preclinical and clinical research. The latest advances in the mechanism highlight that TCM exerts its beneficial effects on DPN by inhibiting inflammation, oxidative stress and apoptosis, endoplasmic reticulum stress and improving mitochondrial function.

TCM has shown the power latent capacity in treating DPN. It is proposed that more large-scale and multi-center randomized controlled clinical trials and fundamental experiments should be conducted to further verify these findings.

Ulcerative colitis (UC) is an idiopathic, relapsing inflammatory disorder of the colonic mucosa. Pyroptosis contributes significantly to UC. However, the molecular mechanisms of UC remain unexplained. Herein, using transcriptome data and animal experimental validation, we sought to explore pyroptosis-related molecular mechanisms, signature genes, and potential drugs in UC. Gene profiles (GSE48959, GSE59071, GSE53306, and GSE94648) were selected from the Gene Expression Omnibus (GEO) database, which contained samples derived from patients with active and inactive UC, as well as health controls. Gene Set Enrichment Analysis (GSEA), Weighted Gene Co-expression Network Analysis (WGCNA) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were performed on microarrays to unravel the association between UC and pyroptosis. Then, differential expressed genes (DEGs) and pyroptosis-related DEGs were obtained by differential expression analyses and the public database. Subsequently, pyroptosis-related DEGs and their association with the immune infiltration landscape were analyzed using the CIBERSORT method. Besides, potential signature genes were selected by machine learning (ML) algorithms, and then validated by testing datasets which included samples of colonic mucosal tissue and peripheral blood. More importantly, the potential drug was screened based on this. And these signature genes and the drug effect were finally observed in the animal experiment. GSEA and KEGG enrichment analyses on key module genes derived from WGCNA revealed a close association between UC and pyroptosis. Then, a total of 20 pyroptosis-related DEGs of UC and 27 pyroptosis-related DEGs of active UC were screened. Next, 6 candidate genes (ZBP1, AIM2, IL1β, CASP1, TLR4, CASP11) in UC and 2 candidate genes (TLR4, CASP11) in active UC were respectively identified using the binary logistic regression (BLR), least absolute shrinkage and selection operator (LASSO), random forest (RF) analysis and artificial neural network (ANN), and these genes also showed high diagnostic specificity for UC in testing sets. Specially, TLR4 was elevated in UC and further elevated in active UC. The results of the drug screen revealed that six compounds (quercetin, cyclosporine, resveratrol, cisplatin, paclitaxel, rosiglitazone) could target TLR4, among which the effect of quercetin on intestinal pathology, pyroptosis and the expression of TLR4 in UC and active UC was further determined by the murine model. These findings demonstrated that pyroptosis may promote UC, and especially contributes to the activation of UC. Pyroptosis-related DEGs offer new ideas for the diagnosis of UC. Besides, quercetin was verified as an effective treatment for pyroptosis and intestinal inflammation. This study might enhance our comprehension on the pathogenic mechanism and diagnosis of UC and offer a treatment option for UC.

Over the past few decades, significant research has been conducted on tissue-engineered constructs for cartilage repair. However, there is a growing interest in addressing subchondral bone repair along with cartilage regeneration. This study focuses on a bilayer tissue engineering scaffold loaded with icariin (ICA) and quercetin (QU) for simultaneous treatment of knee joint cartilage and subchondral bone defects. The cytotoxicity of dual-layer scaffolds loaded with ICA and QU was assessed through live/dead cell staining. Subsequently, these dual-layer scaffolds loaded with ICA and QU were implanted into cartilage and subchondral bone defects in Sprague-Dawley (SD) rats. The repair effects were evaluated through macroscopic observation, computed tomography, and immunohistochemistry. After 12 weeks of implantation of dual-layer scaffolds loaded with ICA and QU into the cartilage and bone defects of SD rats, better repair effects were observed in both cartilage and bone defects compared to the blank control group. We found that the dual-layer tissue-engineered scaffold loaded with ICA and QU had excellent biocompatibility and could effectively repair articular cartilage and subchondral bone injuries, showing promising prospects for clinical applications.

Endometriosis is a condition that can cause significant pain and discomfort for women, and the clinical and surgical treatments available have variable efficacy and can have adverse effects. These drawbacks often lead to poor adherence and therapeutic failure. Consequently, there has been increasing interest in the use of nutritional supplements as an adjuvant therapy for endometriosis. To facilitate clinical decision-making in managing women with endometriosis, a narrative review of clinical studies was conducted to investigate the effects of oral nutritional supplements on endometriosis-related pain. A literature search of the English-language PubMed/MEDLINE database was performed using appropriate keywords to identify clinical studies involving oral nutritional supplements and reporting on endometriosis-related pain. This narrative review included 20 studies published between 2013 and 2023, comprising 12 randomized controlled trials, six non-comparative trials, and two observational studies. The studies investigated the effects of various nutritional supplements on endometriosis-related pain, including vitamins, fatty acids, probiotics, medicinal plants, and bioactive compounds. A significant decrease in endometriosis-related pain was found in three out of five studies on vitamins, four out of six studies on fatty acids, one study on probiotics, two studies on medicinal plants, and five out of six studies on bioactive compounds. These nutritional supplements exhibited diverse biological activities, such as anti-inflammatory, antioxidant, antiproliferative, and antiangiogenic effects, all of which are relevant for managing endometriosis. These findings suggest that oral nutritional supplements could be included as part of a multidisciplinary treatment for endometriosis to decrease pain and enhance overall medical treatment.

Results of artificial insemination (AI) are affected by changes in sperm quality and the function throughout collection and preservation procedures. Proteome and metabolome alterations of sperm treated with the different procedures in goat, however, aren't fully understood. To this end, we sought to investigate the impacts of rectal probe electrostimulation (EE) and artificial vagina (AV) semen collection methods on the quality and the cryotolerance of goat sperm, with additional focus on proteomic and metabolomic analyses. Semen samples were collected from Yunshang black goats and categorized into four groups: fresh sperm collected via AV (XAZ), fresh sperm collected via EE (XEZ), frozen sperm post-AV collection (DAZ) and frozen sperm post-EE collection (DEZ). Four comparisons (XAZ vs. XEZ, DAZ vs. XAZ, DEZ vs. XEZ, DAZ vs. DEZ) were performed, respectively. This study first evaluated sperm motility, acrosome integrity, plasma membrane integrity, mitochondrial activity, and reactive oxygen species (ROS) levels. The results indicated that there were no significant differences in fresh sperm quality parameters between the EE and AV methods. However, notable differences emerged post-cryopreservation. Specifically, the AV method proved more advantageous in preserving the motility, integrities of acrosome and plasma membrane, mitochondrial activity of frozen sperm compared to the EE method. Through the multi-omics approaches, a total of 210 differentially abundant proteins (DAPs) related to sperm characteristics and function were identified across the four comparations. Moreover, 32 differentially abundant metabolites (DAMs) were detected. Comprehensive bioinformatics analysis underscored significant molecular pathways in the co-enrichment of DAPs and DAMs, particularly focusing on the citrate cycle, ROS, oxidative phosphorylation, and glycine, serine, and threonine metabolism etc. We elucidated the differential impacts of AV and EE collection methods on the quality and cryotolerance of goat semen from omics perspectives, which offer a critical foundation for further exploration into optimizing semen collection and cryopreservation techniques in goat breeding program.

Apocynum pictum (A. pictum) honey is rich in effective ingredients including flavonoids, terpenes, and alkaloids that are beneficial to human health. In this study, widely targeted metabolomics were used to detect the plant-derived secondary metabolites of the same batch of A. pictum honey from 2022 to 2024, in order to explore whether storage time changes the quality of A. pictum honey, especially the content of plant-derived secondary metabolites with important health benefits. The results showed that storage time had no significant effect on the content of sugars, proteins, and other major components in A. pictum honey. At the same time, we also found that although storage time had an impact on the content of some secondary metabolites such as flavonoids in A. pictum honey, the changes in the content of the characteristic active ingredient, hyperoside, in A. pictum honey were not significant. These findings suggest that storage time has a minimal impact on the quality of A. pictum honey. This study provides a theoretical basis for the rational storage of A. pictum honey.

Fagopyrum dibotrys is an important wild food and feed germplasm resource. It has high nutritional and medicinal value and is rich in natural products, including flavonoids, phenolic acids, coumarins, and alkaloids. Endophytic fungi in F. dibotrys have emerged as valuable sources of natural products. However, studies on the biological activity and chemical composition of these endophytic fungi remain limited.

In this paper, a new method to obtain natural active ingredients by fermentation of endophytic fungi from medicinal plants was proposed. Then the antioxidant and pathogenic activities of the endophytic fungi extracts were determined in vitro. In addition, secondary metabolites produced by endophytic fungi with medicinal activity were analyzed by high performance liquid chromatography-tandem mass spectrometry (LC-MS).

Among the 95 endophytic fungal strains in F. dibotrys, four strains with high phenol yields were selected by reaction: Alternaria alstroemeriae (J2), Fusarium oxysporum (J15), Colletotrichum karsti (J74), and Colletotrichum boninense (J61). Compared with those of various extracts, the ethyl acetate fractions of A. alstroemeriae (J2), F. oxysporum (J15), and C. boninense (J61) exhibited superior antioxidant and antibacterial properties. The results indicated that the fungal extract was an excellent natural antioxidant and might be a potential antibacterial agent. The DPPH free radical clearance of A. alstroemeriae was 94.96 ± 0.004%. These findings indicated that A. alstroemeriae had strong antioxidant activity. In addition, the extract of A. alstroemeriae had good antibacterial activity against Escherichia coli and Staphylococcus aureus, with MICs of 0.5 and 0.05 mg/mL, respectively. The chemical constituents of the ethyl acetate extract from A. alstroemeriae were further analyzed by liquid chromatography-mass spectrometry (LC-MS). We noted that A. alstroemeriae can create a variety of medicinal substances that have high value in medicine, such as caffeic acid (884.75 ng/mL), 3-phenyllactic acid (240.72 ng/mL) and norlichexanthone (74.36 ng/mL).

In summary, many valuable active substances and medicinal substances can be obtained through the study of endophytic fungi of F. dibotrys.

Myocardial ischemia/reperfusion injury (MI/RI) can lead to impaired cardiac function. Quercetin (Que) has a positive effect and improves MI/RI. Sirtuin-3 (Sirt3) is a deacetylase that ameliorates oxidative stress and is associated with MI/RI. This study aimed to investigate the molecular mechanism by which Que protects cardiac function against MI/RI through the Sirt3 signaling pathway.

We conducted experiments by constructing hypoxia/reoxygenation (H/R) cardiomyocytes and MI/RI rat models. H9C2 cells were transfected with siRNA-Sirt3. Cardiomyocyte apoptosis was examined by TUNEL and Western blotting. The oxidative stress index was also determined. Mitochondrial reactive oxygen species (ROS) activity assays, ATP assays and mitochondrial membrane potential assays were performed. Evans Blue/TTC staining was used to examine surviving myocardial tissue.

In the constructed H/R cells and MI/RI animal models, it was found that myocardial cell apoptosis increased (Bcl-2 expression was downregulated; Bax and cleaved caspase-3/8/9 expression were upregulated). In addition, oxidative stress levels increased (MDA levels increased; SOD, CAT, GSH-Px levels decreased), myocardial tissue was damaged (LDH, CK content increased), Sirt3 expression was downregulated, acetylation levels of superoxide dismutase 2 (SOD2) increased (AC-SOD2), and mitochondrial ROS increased. Que treatment alleviated the effects of MI/RI on cardiomyocytes and rats. Sirt3 expression and activity were upregulated, SOD2 acetylation was decreased, and mitochondrial ROS production was reduced by Que treatment. After Sirt3 was knocked down, we found that AC-SOD2 expression was upregulated and mitochondrial ROS were increased in H/R cardiomyocytes, further increased the degree of injury, while Que treatment attenuated the effect of Sirt3 knockdown on H/R cardiomyocytes.

Que inhibits cardiomyocyte apoptosis, reduces oxidative stress levels, protects mitochondrial function and prevents the impairment of cardiac function during MI/RI via the Sirt3/SOD2/mitochondrial ROS pathway.