Background and purpose Liver fibrosis (LF) is a precursor to cirrhosis. Approved therapies remain limited and are restricted to specific etiologies, necessitating effective anti-LF interventions. Huaganjian decoction (HGJD) has long been used for chronic liver diseases. However, the mechanism of action and active components remain unclear. This study aimed to characterize anti-LF efficacy of HGJD and clarify its mechanism through a phenotype-component-target-pathway evidence chain. Methods and results The anti-LF efficacy of HGJD was first evaluated in CCl4-induced mouse LF and TGF-β1-stimulated hepatic stellate cell (HSC) activation models. HGJD alleviated hepatic injury and fibrotic remodeling, reduced collagen deposition, extracellular matrix accumulation, inflammatory mediators, and fibrogenic markers. It also suppressed HSC proliferation and migration while promoting apoptosis and cell-cycle arrest. The chemical composition of HGJD was profiled using UPLC-Q-Exactive MS/MS, and network pharmacology identified inflammation as a key hub, linking HGJD active compounds to fibrosis-related targets. Integrated metabolomics and transcriptomics converged on the reversal of a metabolism-inflammation imbalance. HGJD exerts multi-component synergistic effects to modulate pathological networks through a dual mechanism: by reducing adenosine levels, thereby removing a critical upstream metabolic trigger, and by directly inhibiting the signaling pathway. The dual mechanism, supported by loss-of-function, gain-of-function, and adenosine rescue experiments, allowed HGJD to inhibit HSC activation, reduce extracellular matrix accumulation-related protein expression and deposition, and promote fibrosis regression. Conclusion HGJD mitigates LF by reprogramming the metabolism-inflammation-fibrosis axis, centered on blockade of the NF-κB/NLRP3/IL-18 feed-forward circuit, providing a mechanistic rationale for its multi-component anti-LF potential.

Licorice (Glycyrrhiza spp.) has received extensive attention due to its remarkable medicinal value and dual medicinal and edible properties. In this study, gas chromatography-ion mobility spectrometry (GC-IMS) was employed to investigate volatile organic compounds (VOCs) in three typical processed licorice products, including stir-fried licorice (SFL), honey-fried licorice (HRL), and wine-fried licorice (WPL). A total of 143 signal peaks were detected, from which 112 compounds were successfully identified, predominantly belonging to aldehydes, alcohols, and ketones. Fingerprint analysis revealed that the three processed samples shared the same types of VOCs but differed in their contents. Principal component analysis (PCA) further confirmed a clear separation among the three processing treatments. The composition and content of VOCs act as crucial factors determining the flavor characteristics and sensory quality of processed licorice. Euclidean distance analysis and partial least squares discriminant analysis (PLS-DA) were performed to clarify the correlation characteristics of VOCs among differently processed licorice samples. The results identified that multiple flavor‑related differential volatile markers were closely associated with different processing methods. Unlike conventional GC‑MS, GC‑IMS requires no derivatization or complex sample preparation, enables separation of isomer and monomer/dimer signals, and provides high‑throughput volatile profiling - making it particularly suitable for differentiating processed herbal products. GC-IMS facilitates rapid and intuitive visualization of dynamic changes in volatile components during licorice processing, providing a new analytical tool and theoretical basis for process optimization, quality evaluation, and mechanism research on licorice processing.

Atherosclerosis and its complications significantly affect human health globally. The etiology of atherosclerosis is multifaceted, with current research focusing on abnormalities in lipid metabolism, immune cell activation, inflammation, and epithelial damage. Currently, highly effective preventive and therapeutic strategies for atherosclerosis remain lacking. Recent reports have indicated the anti-atherosclerotic effects of medicinal herbs from the Araliaceae family, including Panax ginseng C. A. Mey., Panax notoginseng, Panax quinquefolius L., and Panax japonicus. The pharmacological effects of these herbs on atherosclerosis include lipid metabolism, immune cell activation, inflammation, oxidative stress, endothelial function, cell proliferation and migration, angiogenesis, apoptosis, autophagy, and gut microbiota homeostasis. This review aims to comprehensively elucidate, summarize, and update the protective effects and underlying mechanisms of Araliaceae herbs against atherosclerosis.

Panax ginseng (Panax ginseng C.A. Meyer) is a classic herbal medicine widely utilized in dermatological management, yet its precise therapeutic mechanisms have only recently begun to be fully elucidated. This review systematically synthesizes the pharmacological roles of ginseng’s active components, including ginsenosides, polysaccharides, and gintonin, in maintaining skin homeostasis and treating various cutaneous pathologies. Emerging evidence suggests that the efficacy of ginseng extends beyond direct molecular interactions, exhibiting the distinct characteristics of "indirect pharmacology." Specifically, parent ginsenosides function primarily as natural prodrugs that require microbial biotransformation into high-affinity active metabolites, such as Compound K and Rh2, to exert potent therapeutic effects. Functionally, these components regulate skin health by mobilizing endogenous host defense systems, particularly through the activation of the Nrf2/ARE antioxidant pathway and the suppression of inflammatory cascades via the NF-κB, MAPK, and IL-1 signaling networks. Furthermore, they remodel the systemic microenvironment through the gut-skin axis, facilitating metabolic homeostasis to improve skin barrier function. Notably, biotransformation rates and ultimate therapeutic efficacy are highly dependent on individualized variables, such as host age, dietary patterns, and baseline disease states. This systemic regulation has demonstrated robust efficacy in intervening in complex pathologies, including atopic dermatitis, psoriasis, and skin cancer. Additionally, this article addresses the translational bottleneck of low bioavailability and evaluates recent advances in novel skin delivery systems, specifically those utilizing ginseng-derived exosomes. Collectively, this review provides a scientific framework for understanding the systemic actions of ginseng, supporting its development as a precision botanical therapy for dermatological applications.

BackgroundNeoadjuvant immunotherapy/targeted therapy combined with chemotherapy shows encouraging activity for oropharyngeal squamous cell carcinoma (OPSCC). However, evidence specific to tonsillar squamous cell carcinoma (TSCC) remains limited, particularly regarding the systematic relationships among radiological response, pathologic response, margin control, and voice and swallowing functional outcomes.MethodsThis single-arm, single-center study included patients with pathologically confirmed TSCC diagnosed between January 2024 and June 2025. Patients received triplet neoadjuvant therapy consisting of nimotuzumab, toripalimab, nab-paclitaxel, and carboplatin every 3 weeks for 2 cycles, followed by transoral radical tonsillectomy combined with radical cervical lymph node dissection. Radiologic response was assessed using Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1) and volumetric magnetic resonance imaging (MRI). Pathologic response, margin status, perioperative safety, adjuvant treatment, and functional outcomes were evaluated.ResultsTwenty patients achieved clinicopathologic downstaging after surgery. The primary-site pCR rate was 65.0%, nodal pCR was 60.0%, and overall ypT0N0 pCR was 45.0%. The objective radiological response (ORR) rate of the primary lesion was 100%, and 9 patients (45%) achieved a complete radiological response. Mean primary-tumor and dominant-node volume reductions were 76.18% and 72.59%, respectively. Both pre- and postneoadjuvant margins were negative in all patients, yielding R0 resection in all cases. Functional scores improved after neoadjuvant therapy, worsened transiently during radiotherapy, and generally recovered during follow-up.ConclusionsNimotuzumab plus toripalimab and chemotherapy produced high radiological and pathological response rates with reliable margin control in patients with locally advanced TSCC. Postneoadjuvant boundary assessment with intraoperative pathologic verification may support individualized resection planning, but routine resection of the primary lesion and cervical lymph node dissection remain necessary. Longer follow-up and prospective validation are required to confirm these results.Clinical trial registrationhttps://clinicaltrials.gov/study/, identifier NCT07353723.

Wild ginseng (WG) and forest-grown cultivated ginseng (CG) are two chemotypically distinct forms of Panax ginseng Meyer with markedly different therapeutic and economic value. Providing industry with an objective, rapid screening tool is therefore essential. Existing identification methods are destructive, subjective, and slow, so a non-invasive alternative is needed. We captured short-wave NIR hyperspectral images (900-1700 nm) of 170 authenticated ginsengs and extracted 1140 representative spectra (577 WG, 563 CG). After Savitzky-Golay smoothing, Multiplicative Scatter Correction, and Local Standard Normal Variate normalization, a Genetic Algorithm (GA) combined with Decision-Tree (DT) importance ranking retained 216 informative wavelengths, which trained a 200-tree Random Forest (RF) classifier. On a 10% test set (114 spectra), the RF achieved 93.86% overall accuracy, correctly identifying 100% of WG and 87.5% of CG samples and outperforming Linear Discriminant Analysis (83.3%), K-Nearest Neighbours (84.2%), and PLS-DA (83.3%). Learning-curve diagnostics confirmed that training accuracy (100%) and test accuracy (approximate to 94%) converge, indicating minimal overfitting. The end-to-end workflow processes a ginseng in under two minutes, can be embedded in handheld hyperspectral image sensors for in-field inspection, and offers a transferable template for other high-value medicinal plants.

Chinese yam (Dioscorea polystachya) is an edible plant in China, known for its nutritional properties. In this study, Chinese yam protein extract (CYCSE) was extracted using cold-soaking extraction, and systematically evaluated for its composition, structural characteristics, physicochemical properties, and potential in protecting male reproductive function. Liquid chromatography-tandem mass spectrometry identified 22 proteins in CYCSE, with two dioscorin isoforms showing the highest peptide coverage (76-78%). The extract comprised proteins primarily below 90 kDa, rich in glutamate, aspartate, and arginine residues. Structurally, CYCSE exhibited characteristic protein ultraviolet and infrared absorption peaks, a high beta-sheet content, a stable tertiary conformation, and high thermal stability (denaturation temperature 86.7 degrees C). Physicochemical properties showed that CYCSE has high solubility, water- and oil-holding capacity, emulsifying activity, and foaming stability. In vivo studies demonstrated that CYCSE significantly ameliorated glycolipid metabolic disorders, enhanced erectile function, and repaired cavernous damage in diabetic rats with erectile dysfunction. Mechanistically, CYCSE enhanced the NO/cGMP signaling pathway by activating the PI3K/Akt/eNOS axis in penile tissue. It also suppressed oxidative stress and inflammation by inhibiting the TXNIP/NLRP3 signaling pathway. These findings highlight the potential of CYCSE as a functional food ingredient for improving male reproductive health.

BACKGROUND Tangwang formula (TWF), a traditional Chinese medicine, has been shown to delay the progression of diabetic retinopathy (DR) over the past 20 years. However, the potential therapeutic mechanisms and effective components of TWF remain unclear. AIM To investigate the effective components of TWF and elucidate the mechanism underlying TWF treatment for DR. METHODS The chemical ingredients of TWF were detected using high-pressure liquid chromatography. Network pharmacology and molecular docking were applied to identify the targets and pathways associated with TWF and DR. A DR mouse model was established by streptozotocin to evaluate the therapeutic effect of TWF in vivo. High glucose treatment was used to induce injury in mouse retinal endothelial cells (mRECs) to verify the mechanism of TWF in vitro. The 16S ribosomal RNA sequencing and untargeted metabolomics were performed to detect intestinal bacteria and fecal metabolites in DR mice. RESULTS Eight important active constituents were identified by high-pressure liquid chromatography. Network pharmacology results showed that Bcl2 and Casp3 were key targets between TWF and DR. Isorhamnetin-3-O-neohespeidoside, naringenin, ononin, and calycosin-7-O-beta-D-glucoside from TWF had strong affinities with Bcl2 and Casp3. TWF significantly reduced random blood glucose, inhibited the levels of proinflammatory factors in DR mice and mRECs, and alleviated retinal damage by downregulating the expressions of vascular endothelial growth factor and receptor advanced glycation end products, and upregulating the expressions of zonula occludens-1 and RBP-3. TWF inhibited the apoptosis in mouse retinal tissues and mRECs. Analysis of intestinal bacteria and metabolites revealed that TWF increased the richness and evenness of intestinal microbiota and improved fecal metabolic profiles in DR mice. Importantly, seven genus bacteria were closely correlated with amino acids, fatty acids, glycerophosphocholine, and bile acid, which could participate in ameliorating retinal injury. CONCLUSION These findings suggest that TWF may ameliorate retinal damage in DR mice via anti-inflammatory and anti-apoptotic activities, which may be associated with modulation of the intestinal microbiota and metabolic profiles.

Ganoderma lucidum is a fungus of medicinal importance; however, its quality differs according to origin. Moreover, multi-class classification remains a major challenge for standard machine-learning algorithms. To address this issue, this study establishes an origin identification framework for Ganoderma lucidum based on hyperspectral imaging technology. The SMOTE-TomekLinks hybrid sampling method is adopted to balance imbalanced sample distribution, and grid search is utilized for hyperparameter optimization. Three machine learning algorithms including support vector machine, random forest and extreme gradient boosting are selected for comparative modeling. Experimental results demonstrate that the support vector machine achieves the optimal comprehensive recognition performance among all models. It obtains a classification accuracy above 0.87 and an average F1-score exceeding 0.85 with favorable stability. The proposed data processing strategy effectively improves the origin identification accuracy of imbalanced samples. This study verifies the superiority of hybrid sampling combined with hyperspectral feature extraction in geographical traceability, and provides a feasible technical reference for origin discrimination of Ganoderma lucidum and other medicinal herbs.

BACKGROUND Dendrobium officinale (D. officinale ) is a traditional Chinese herb that has been studied extensively for its medicinal properties, including gastrointestinal protection, anti-aging effects, and antioxidant properties. However, the molecular mechanisms by which D. officinale delays aging have not been fully elucidated. AIM To investigate the effects of D. officinale extract (DOE) on extending healthy lifespan through the maintenance of intestinal homeostasis, and to explore its intervention window, molecular mechanism, and key components. METHODS Based on evaluation systems using human MRC-5 cells, Caenorhabditis elegans , and Drosophila melanogaster , the optimal spatiotemporal intervention window for DOE was determined. Its effects on aging-related markers and stress resistance were assessed. (16S) rDNA sequencing, bioinformatics, immunofluorescence staining, reintroduction of dominant strains, and in vivo gene knockdown strategies were applied to identify and validate potential targets. RESULTS We determined that midlife is the optimal intervention window for DOE to extend healthy lifespan. Intervention at this stage delayed the age-related decline in health indicators, including motor and intestinal functions as well as oxidative stress. Mechanistically, DOE remodeled the gut microbiota in a sex-specific microbe host pairing, favoring Acetobacter pomorum in females and Lactobacillus plantarum in males, which differentially regulated glucose and lipid metabolism in both sexes. This remodeling modulated the insulin/insulin-like growth factor-1 signaling pathway, thereby activating the Keap1 -Nrf2 -antioxidant response element antioxidant signaling pathway. The enhanced antioxidant defense ultimately contributed to the prolonged healthy lifespan. In addition, D. officinale polysaccharide was identified as a potential core component of DOE’s pharmacological activity. CONCLUSION DOE regulated the microbiota-InR -Nrf2 axis to counteract oxidative stress, thereby maintaining intestinal function and extending healthy lifespan. These findings provide a molecular basis for the discovery of new antioxidants and anti-aging agents.

AbstractBackground: Atherosclerosis (AS) is a chronic inflammatory vascular disease characterized by lipid deposition, macrophage inflammatory activation, and foam cell formation. Macrophage metabolic reprogramming is closely associated with persistent plaque inflammation and disease progression. HuaBan Decoction (HBD), a traditional Chinese medicine formula, has shown clinical efficacy in AS; however, whether it exerts anti-atherosclerotic activity by regulating the macrophage metabolic-inflammatory axis remains unclear.Purpose: This study aimed to investigate the anti-atherosclerotic effects of HBD and to clarify whether HBD regulates macrophage immunometabolic remodeling through the PKM2-related pathway.M ethods: Public transcriptomic datasets, single-cell RNA-sequencing data, machine-learning-based screening, and clinical samples were integrated to identify macrophage polarization-associated metabolic targets in AS. The anti-atherosclerotic effects of HBD were evaluated in high-fat diet-fed ApoE-/- mice and ox-LDL-induced macrophage foam cells. Histological staining, immunofluorescence, flow cytometry, qRT-PCR, western blotting, targeted metabolomics, mitochondrial function assays, UHPLC-HRMS, molecular docking, molecular dynamics simulations, SPR analysis, and functional validation of candidate constituents were performed to assess the pharmacological effects and underlying mechanisms of HBD.Results: PKM2 was identified as a candidate immunometabolic node linking macrophage glycolytic reprogramming, inflammatory polarization, and AS progression. HBD reduced plaque burden, improved plaque stability, inhibited macrophage lipid accumulation and inflammatory activation, and promoted M2-like macrophage polarization. Mechanistically, HBD alleviated metabolic disturbances, restrained PKM2-associated glycolytic activation, reduced dimeric PKM2 accumulation and nuclear translocation, and preserved mitochondrial function. Curcumenol, magnoflorine, and berberrubine were further identified and functionally validated as candidate PKM2-binding constituents of HBD.Conclusion: HBD may attenuate AS progression by modulating PKM2-associated macrophage immunometabolic remodeling. These findings provide mechanistic evidence for the anti-atherosclerotic activity of HBD and support its potential use for stabilizing

ETHNOPHARMACOLOGICAL RELEVANCE:In terms of anti-aging, ginseng has the effect of "lightning the body and prolonging the life" since ancient times. Although Panax ginseng Meyer (ginseng) has demonstrated anti-aging associations in experimental studies, clinical validation of its impact on telomere length and nicotinamide adenine dinucleotide (NAD+)/Nicotinamide adenine dinucleotide (NADH) ratio in healthy middle-aged individuals remains lacking. AIM OF THE STUDY:Exploratory hypothesis-generating study on the association of ginseng on the telomere lengths and NAD+/NADH ratio of middle-aged adults. METHODS:This study enrolled overweight middle-aged adults aged 45-50 years (Body mass index, BMI >24 kg/m2), involving two cohorts: high-dose short-term (6 g/day, 7 days; n = 20) and low-dose long-term (3 g/day, 28 days; n = 30), then they were followed up at 21 or 28 days after the completion of medication, respectively. Blood samples were collected before and after supplementation, and follow-up period. The primary outcomes: leukocyte telomere length and the NAD+/NADH ratio. The secondary outcomes: protection of telomeres 1 (POT1) expression, nicotinamide phosphoribosyltransferase (NAMPT) activities of peripheral blood mononuclear cells (PBMCs), reactive oxygen species (ROS), malondialdehyde (MDA), advanced glycation end-products (AGEs) and lactic acid (LA) levels. and scores on clinical scales [e.g., Pittsburgh sleep quality index (PSQI), Ascertain dementia 8 (AD8), Fatigue scale-14 (FS-14), International index of erectile function-5 (IIEF-5), and Kupperman index)]. RESULTS:The high-dose and low-dose groups showed a significant association with increased telomere length, POT1 expression, NAD+/NADH ratio, and NAMPT activity. The two cohorts also showed a significant association with reduced levels of ROS, MDA, AGEs, and LA, as well as improved scores on all clinical scales. Furthermore, the beneficial effects of the above indicators persisted during the follow-up period. CONCLUSIONS:Ginseng supplementation is associated with telomere elongation and an increased NAD+/NADH ratio in middle-aged adults, and exerts beneficial effects on human overall health by improving potential biomarkers of aging.

We extracted turmeric volatile oil (TVO) from turmeric using supercritical CO₂ extraction for potential allergic rhinitis (AR) therapy. The volatile components of TVO were analyzed using gas chromatography mass spectrometry and gas chromatography-ion migration spectrometry. The pharmacological effects of TVO on ovalbumin (OVA)-induced AR in mice were evaluated through pathological markers, microbiomics, metabolomics, and proteomics. An inflammatory model using human mast cells (HMCs) was established to assess whether TVO could mitigate inflammation. TVO effectively alleviated AR symptoms in OVA-sensitized mice and reduced inflammation in lipopolysaccharide- and interferon-γ-treated HMCs. TVO suppressed the inflammatory cytokine production, restored the nasal microbiota composition, and regulated serum metabolic profiles. Proteomic analysis using four-dimensional data-independent acquisition indicated that the mitogen-activated protein kinase (MAPK) and transcription factor nuclear factor-κB (NF-κB) signaling pathways are involved in TVO’s anti-inflammatory mechanism. Accordingly, TVO inhibited the activation of MAPK and NF-κB pathways in the OVA mouse model and the inflammatory HMCs model. Jun N-terminal kinase and Relb were identified as key mediators in the therapeutic action of TVO, with Relb knockdown enhancing its anti-inflammatory effect, suggesting that TVO has potential as a therapeutic agent for alleviating AR.

In this study, a GH51 α-l-arabinofuranosidase (Cabf51) from Cellulosimicrobium sp. TH-20 was recombinantly expressed, characterized, and functionally analyzed. The Cabf51 exhibited optimal activity at pH 7.0 and 60 °C with arabinofuranose-induced activation. The recombinant enzyme selectively hydrolyzed the arabinofuranosyl residue at the C-20 position of ginsenoside Rc (G-Rc) and compound Mc1 (C-Mc1) to produce ginsenoside Rd (G-Rd) and ginsenoside F2 (G-F2), respectively. The kcat/Km values of Cabf51 for pNP-Araf, C-Mc1, and G-Rc were 102.32, 27.49, and 14.75 s-1 mM-1, respectively. Structural analysis of the Cabf51-ligand complex revealed a novel substrate selectivity mechanism for GH51 arabinofuranosidases toward ginsenosides. The three-dimensional structure of Cabf51 indicated the presence of a semi-open groove that gradually narrowed from the protein surface toward the interior. Gatekeeper residues (Trp178 and Lys309) were key determinants of substrate binding. The hierarchical architecture of the catalytic channel of Cabf51 functioned as a geometrically driven selective filter, with the narrow binding pocket preventing the accommodation of larger ginsenosides. This unique structural feature enabled Cabf51 to recruit Asn72 as an auxiliary catalytic residue. The Asn72 anchored G-Rc or C-Mc1 and stabilized the hydrogen bond network, thereby effectively driving the hydrolytic process to completion. These findings enhanced our understanding of the catalytic mechanism of GH51 family arabinofuranosidases and provided a theoretical foundation for the development of more efficient and versatile enzymes to accelerate ginsenoside biotransformation.

IntroductionGinsenosides, the primary bioactive constituents of ginseng, are widely recognized as popular natural products with anti-aging properties. However, they generally exhibit poor oral bioavailability. Moreover, existing pharmacokinetic studies have predominantly focused on young animal models, leaving a critical gap in understanding how aging alters the absorption, distribution, metabolism, and excretion of these compounds. This study aims to elucidate the multi-component pharmacokinetics and tissue distribution profiles of total ginsenosides following oral administration in both young and aging mice.MethodsThe validity of the aging mouse model was first confirmed through a series of physiological evaluations. A multiple reaction monitoring (MRM) technique was then employed to conduct comparative pharmacokinetic and tissue distribution analyses of 15 targeted ginsenosides after oral administration in young and aging mice.ResultsAging mice exhibited significantly higher systemic exposure (AUC) and markedly reduced clearance rates compared to their young counterparts. Tissue distribution analysis revealed the highest accumulation of ginsenosides in the liver, followed by the heart, kidneys, spleen, lungs, testes, and brain, confirming the liver as the primary metabolic site.DiscussionThese findings demonstrate that aging increases systemic exposure, prolongs half-lives, and enhances tissue accumulation of ginsenosides. This study provides essential scientific evidence for the rational clinical application and dosage optimization of ginseng in aging populations.

Fresh Dendrobium officinale juice (FDOJ) changes color from green to purple after processing; however, the mechanism behind this is unknown. In this study, untargeted and targeted metabolomics were used to analyze pigment-related metabolites. The results showed that the content of delphinidin-type anthocyanin more than doubled in FDOJ after processing. Correlation analysis revealed that major substances in the anthocyanin biosynthesis pathway, including phenylalanine, cinnamic acid, and naringenin chalcone, changed with processing. We speculate that accumulation of anthocyanins during processing occurs through de novo anthocyanin biosynthesis starting from phenylalanine, and the addition of phenylalanine traced that the enhancement of enzyme activity promoted the accumulation of anthocyanins. This potential mechanism for development of the purple color in FDOJ provides theoretical guidance for quality control of FDOJ during processing.

BACKGROUND:Huanglian ointment, recorded in the 'Medical Canon of the Golden Mirror', is traditionally used to treat nasal sores and damp-heat conditions. Allergic rhinitis (AR) is a common immune-mediated disease. However, the mechanism by which the supercritical extract of Huanglian ointment (HLGSE) relieves AR remains unclear. PURPOSE:This study aimed to investigate the effects of HLGSE on AR and its underlying mechanisms. METHODS:Huanglian ointment was extracted by various methods, and the resulting extracts were screened for activity in HMC-1 and RAW264.7 inflammatory models. Optimal extraction conditions were identified through orthogonal design, and extract composition was analyzed by GC-MS, GC-IMS, and E-nose. HLGSE's anti-inflammatory efficacy was then validated in vivo and in vitro. RESULTS:HLGSE was the most effective extract, rich in esters, ketones, and alcohols. In vitro and in vivo, HLGSE reduced inflammation and alleviated AR in BALB/c mice. We combined network pharmacology, 16S rRNA gene sequencing, four-dimensional data-independent acquisition (4D-DIA) proteomics, and metabolomics. 16S rRNA sequencing identified Firmicutes, Bacteroidetes, Actinobacteria, and Proteobacteria as the predominant phyla; proteomics revealed key signaling pathways, including cGMP-PKG, cAMP, MAPK, NF-κB, and PI3K; and metabolomics characterized the major metabolic pathways. HLGSE modulated MAPK and NF-κB signaling pathway. Gain- and loss-of-function experiments further indicated that RelB modulation altered NF-κB-associated inflammatory responses in LPS- and IFN-γ-stimulated HMC-1 cells. CONCLUSION:This is the first study to combine GC-MS, GC-IMS, and E-nose to characterize HLGSE's components. HLGSE can remodel the nasal microbiota, serum metabolites, and nasal mucosal proteins and suppress the MAPK and NF-κB signaling pathways, potentially alleviating AR.

Despite advances in alternative proteins, it remains unclear whether novel plant proteins can achieve high nutritional digestibility, safety, and meat-like flavor. Therefore, this study evaluates hemp seed protein as a meat substitute through comparison with other alternative proteins and beef. Nutritional analyses (amino/fatty acid composition, in vivo/in vitro digestibility) showed that Hemp seed protein meet patties (HSMP) are abundant in essential amino acids and unsaturated fatty acids, with higher protein digestibility-corrected amino acid score (PDCAAS), metabolic amino acid digestibility (MAAD) and true ileal digestibility (TID) than plant-based protein meet patties (PPMPs). Safety evaluations (sensitization, storage stability) indicated low IgG/IgE reactivity and robust pH/carbonylation stability for HSMP. Sensory evaluation combined with GC-IMS showed that the flavor of HSMP is most similar to beef depending on 1,8-eucalyptol, octanal, and 2-ethyl-3,5-dimethylpyrazine. In summary, this study confirms that HSMP is a valid alternative food protein source and provides methodological insights to improve product applicability.