Search Results (2,356)

Background/Objectives: Type 2 diabetes (T2D) is a chronic metabolic disorder closely linked to cardiovascular disease and obesity and notably influenced by lifestyle and dietary patterns. The Mediterranean diet has well-established benefits across multiple cardiometabolic risk factors, including those relevant to diabetes. This study aimed to investigate the degree to which adults with T2D adhere to a Mediterranean dietary pattern and to examine how such adherence relates to glycemic and lipidemic regulation. Methods: This cross-sectional study included 100 adults with T2D (54 men and 46 women). Adherence to the Mediterranean diet was assessed using the Mediterranean Diet Score (MDS). Demographic, anthropometric, lifestyle, and clinical data were collected, and glycemic and lipid parameters were analyzed. Associations between Mediterranean diet adherence and metabolic outcomes were examined using correlation analyses and multivariable regression models adjusted for relevant confounders. Results: Most participants showed low adherence to the Mediterranean diet. A significant inverse association was observed between Mediterranean diet adherence and hemoglobin A1c (HbA1c) levels, with individuals scoring ≤35 on the MDS demonstrating higher HbA1c levels. Similar trends were observed in the lowest tertile of adherence. Notably, each one-point increase in MDS predicted a 0.13% reduction in HbA1c. In multivariable regression analyses, Mediterranean diet adherence remained the strongest predictor of glycemic control, independent of age, body mass index (BMI), sex, smoking status, physical activity and the number of antidiabetic treatments. Higher adherence was also significantly associated with lower low-density lipoprotein cholesterol (LDL-C) and triglyceride (TG) levels, as well as higher high-density lipoprotein cholesterol (HDL) concentrations. Conclusions: Greater adherence to the Mediterranean diet is independently associated with improved glycemic regulation and a more favorable lipid profile in adults with T2D. These findings support the Mediterranean diet as a valuable non-pharmacologic strategy for optimizing metabolic outcomes in people with T2D. Full article

Plants from the Zingiberaceae family, particularly Zingiber officinale, Curcuma longa, and Alpinia galanga, are rich sources of bioactive compounds with documented antidiabetic and anti-inflammatory properties. This review summarizes current evidence on their phytochemical profiles and pathways relevant to metabolic regulation. Key compounds, including gingerols, shogaols, curcuminoids, and phenylpropanoids, support glucose homeostasis by enhancing insulin sensitivity, promoting Glucose Transporter Type 4 (GLUT4)-mediated glucose uptake, improving β-cell function, and modulating metabolic signaling pathways such as PI3K/Akt, AMPK, PPARγ, and NF-κB. Their potent antioxidant and anti-inflammatory activities further reduce oxidative stress and chronic low-grade inflammation, both central to the progression of type 2 diabetes and its complications. Evidence from selected clinical and experimental studies suggests that dietary supplementation with whole-rhizome preparations or standardized extracts (including formulation-enhanced products) may improve fasting blood glucose (FBG), glycated hemoglobin (HbA1c), lipid metabolism, and oxidative stress markers. Recent advances in delivery systems, including nanoemulsions, liposomes, and curcumin–piperine complexes, substantially enhance the bioavailability of poorly soluble phytochemicals, strengthening their therapeutic potential. Overall, Zingiberaceae plants emerge as promising natural supplements in nutritional and pharmacological strategies targeting diabetes. Further clinical research is required to refine dosage, confirm long-term efficacy, and support their integration into evidence-based metabolic interventions. Full article

Background/Objectives: Flavonoids are widely used as lead structures in drug discovery, and their pharmacological and metabolic properties are strongly influenced by structural features such as positional isomerism. This study aimed to compare the metabolic profiles and underlying mechanisms of two isoflavone-based positional isomers, ACF-02 (2-(4-hydroxy-3-methoxyphenyl)-6,7-dimethoxy-3-(4-methoxyphenyl)-4H-chromen-4-one) and ACF-03 (2-(3-hydroxy-4-methoxyphenyl)-6,7-dimethoxy-3-(4-methoxyphenyl)-4H-chromen-4-one). Methods: The metabolic pathways of synthetically prepared ACF-02 and ACF-03 were investigated using an in vitro incubation system with human liver microsomes (HLMs) supplemented with an NADPH-regenerating system, followed by liquid chromatography–high-resolution tandem mass spectrometry (LC–HRMS/MS) analysis. Metabolites were identified based on LC–HRMS/MS data and molecular networking-based node connectivity with the parent compounds. Major metabolites were further characterized by CYP phenotyping using recombinant CYP450 isoforms, and the potential for drug–drug interactions of ACF-03 was evaluated using a CYP probe substrate cocktail approach. Results: HLM incubation of ACF-02 and ACF-03 produced both hydroxylated and O-demethylated metabolites, with O-demethylation as the predominant pathway; notably, the most abundant O-demethylated metabolite differed in an isomer-dependent manner, occurring at the B₂ ring for ACF-02 and at the A ring for ACF-03, with distinct CYP isoform involvement. Molecular networking supported the relationships between the parent compounds and their metabolites, and both compounds exhibited relatively high metabolic stability with limited CYP inhibition. Conclusions: Despite differing only in the position of a single methyl substituent, ACF-02 and ACF-03 exhibited distinct isomer-dependent metabolic profiles. These findings demonstrate that even subtle positional isomerism can significantly influence metabolic behavior and should be carefully considered during lead optimization and drug design. Full article

Background: Chronic nonbacterial prostatitis (CNP), the major subset of chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS), imposes a substantial global burden yet lacks satisfactory therapies. Maizibizi Wan (MZBZ) has long been used clinically for prostatitis, but its pharmacodynamic substance basis and mechanisms remain unclear. Methods: Ultra-high-performance liquid chromatography–Q-Orbitrap high-resolution mass spectrometry (UHPLC-Q-Orbitrap-HRMS) coupled with Global Natural Products Social Molecular Networking (GNPS) molecular networking profiled MZBZ constituents and rat plasma–exposed prototype components and metabolites was used. Based on blood-absorbable components, network pharmacology predicted core targets/pathways; representative interactions were validated by molecular docking. A λ-carrageenan–induced CNBP rat model underwent histopathology (H&E), serum cytokine assays (TNF-α, IL-1β, IL-6/IL-17), immunohistochemistry (COX-2, TNF-α, MMP-9), and Western blotting (P-p65/p65, p-AKT/AKT, COX-2, TGF-β1, BCL2). Results: A total of 188 chemical constituents were identified in MZBZ (79 flavonoids, 38 organic acids, 30 alkaloids, 15 phenylpropanoids, 7 steroids, 4 phenylethanoid glycosides, 15 others). A total of 35 blood-absorbable components (18 prototype components, 17 metabolites) were identified, mainly involving Phase I oxidation and Phase II glucuronidation/sulfation. Network analysis yielded 54 core targets enriched in NF-κB and PI3K/AKT signaling and apoptosis. Docking indicated stable binding of key flavonoids to COX-2, NFKB1, TNF, IL-6, and BCL2. In vivo, MZBZ ameliorated prostatic inflammation, reduced serum TNF-α/IL-1β/IL-6/IL-17 (p < 0.05 or p < 0.01); decreased P-p65/p65, p-AKT/AKT, COX-2, and TGF-β1; and increased BCL2 in prostate tissue. Conclusions: MZBZ exerts anti-CNBP effects via multi-component synergy (prototypes + metabolites) that suppresses inflammatory cytokines, modulates apoptosis, and inhibits NF-κB and PI3K/AKT pathways. These findings provide a mechanistic basis and quality control cues for the rational clinical use of MZBZ. Full article

Endoperoxides constitute a distinctive class of highly oxygenated terpenoids defined by the presence of a cyclic peroxide (–O–O–) bond, a structural motif responsible for their pronounced chemical reactivity and diverse biological effects. Naturally occurring endoperoxide-containing terpenoids are broadly distributed across terrestrial and marine taxa, including higher plants, algae, fungi, and bryophytes, where they are believed to participate in chemical defense and ecological interactions. This review provides a comprehensive overview of naturally occurring endoperoxide terpenoids, focusing on their natural sources, structural diversity, and reported biological activities. Particular emphasis is placed on compounds exhibiting antiprotozoal and antitumor activities, exemplified by artemisinin and its derivatives, which remain cornerstone agents in antimalarial therapy and continue to attract interest for their anticancer potential. Structure–activity relationship (SAR) analysis, supported by computational prediction using the PASS (Prediction of Activity Spectra for Substances) platform, is employed to examine correlations between peroxide-containing frameworks and biological function. Comparative assessment of experimental data and predicted activity profiles identifies key structural features associated with antiprotozoal, antineoplastic, and anti-inflammatory effects. Collectively, this review highlights endoperoxides as a valuable and chemically distinctive class of bioactive natural products and discusses their promise and limitations as leads for further pharmacological development, particularly in light of their intrinsic reactivity and stability challenges. Full article

Athamanta L. is a small genus of the Apiaceae family, comprising only sixteen species and subspecies, which are distributed in the Canary Islands, Central Europe, and the Mediterranean basin. Background/Objectives: Since the time of Dioscurides, the species of this genus have been reported to have had several ethnopharmacological activities, and some of them are also used currently. Athamanta sicula L., growing in Italy, Tunisia, Algeria, and Morocco, is the only species of this genus present in Sicily. To further explore the phytochemical profile and biological properties of this species, the present study focused on the essential oil (EO) extracted from the aerial parts of wild A. sicula populations collected in central Sicily. Methods: The chemical composition of the EO, obtained by hydrodistillation, was determined by GC–MS analysis. The presence of myristicin was confirmed by isolation and by ¹H-NMR spectroscopic characterization. Results: The EO and its main constituents have been tested for possible antimicrobial properties against several bacterial strains, showing MIC values in the of 15–30 mg/mL range, and the mechanism of action was further investigated, revealing membrane-targeting effects consistent with outer membrane permeabilization. In addition, antibiofilm activity (with up to ~80% inhibition of biofilm formation at sub-MICs), antioxidant potential (demonstrating dose-dependent radical scavenging activity), and biocompatibility with eukaryotic cells were assessed to provide a comprehensive pharmacological profile of A. sicula EO. Specifically, the most abundant constituent was myristicin (62.2%), the principal representative of the phenylpropanoid class (64.4%). Hydrocarbon monoterpenes represented the second class of the EO (27.4%), with β-phellandrene (12.2%) as the main compound. Conclusions: Myristicin emerged as the key contributor to the antimicrobial and antibiofilm activity of the EO. The obtained results highlight the relevance of A. sicula EO as a myristicin-rich essential oil with notable in vitro biological activity. Full article

Cutaneous melanoma is a highly aggressive skin cancer prone to relapse and metastasis. Surgery is often curative when combined with early screening and prevention. However, in recurrent or advanced disease, the development of new targeted and immune therapies has demonstrated promising clinical outcomes, although the acquisition of resistance limits their effectiveness. Thus, new therapeutic approaches are needed. Emerging data indicate that the Hedgehog (Hh) pathway, which is essential for embryonic development, is aberrantly reactivated in melanoma and may represent a promising therapeutic target. Here, we demonstrate its chronic up-modulation in a panel of patient-derived cell lines and, by investigating the underlying molecular mechanisms, we excluded mutations in the principal components of the pathway. We observed reduced PTCH1 and SUFU repressors expression and GLI2 upregulation as common melanoma features. At the same time, copious SHH release, the principal PTCH1 ligand, evidenced autocrine Hh signaling activation. Consistently, a tendency of greater level of this factor resulted higher in the blood of patients compared to controls, confirming the relevance of ligand-dependent trigger in melanoma. The therapeutic potential of inhibiting the Hh pathway is highlighted by the reduced proliferation and migration observed in the presence of clinically approved pharmacological Hh antagonists. Profiling inflammatory mediators revealed significant modulation upon treatment with SMO inhibitors, possibly affecting chemotactic and immune functions. Collectively, these findings provide deeper insight into the role of the Hh pathway in melanoma and support the potential repurposing of Hh inhibitors as therapeutic agents for melanoma. Full article

Ganoderma is a genus of medically significant fungi, that is used in traditional medicine and is increasingly incorporated into modern nutraceuticals and pharmaceuticals. Accurate species identification and product standardization remain major challenges due to morphological plasticity and cryptic diversity. This review articulates current advances in Ganoderma systematics, phylogenetics, and metabolomics, with an emphasis on molecular identification strategies and chemical profiling. Internal transcribed spacer (ITS) sequencing has substantially improved species delineation compared with morphology alone, but its resolving power is limited in closely related species complexes, necessitating complementary multilocus approaches. Advances in metabolomics, and LC-MS- and HPLC-based profiling of triterpenes and polysaccharides, have enhanced species discrimination, chemotaxonomic resolution, and quality control of commercial products. Integrating molecular barcoding with metabolomic fingerprints provides a more robust framework for classification, pharmacological evaluation, and standardization. This review also highlights significant geographic knowledge gaps, particularly in Africa, where molecular and metabolomic data remain scarce despite high species diversity. Full article

Background/Objectives: This study examined the metabolic, oxidative, immunological, and histomorphological effects of the multicomponent fermented biological product derived from camel milk, Inullact-Fito, in comparison to metformin in a rat model of alloxan-induced diabetes resulting from insulin insufficiency. The model was chosen as an experimental system that replicates pancreatic β-cell damage induced by oxidative stress rather than insulin resistance. Methods: Alloxan-induced diabetes was used to evaluate metabolic, oxidative, immunological, and histomorphological alterations. Metformin was utilized as a pharmacological comparator. Blood glucose levels, circulating insulin concentrations, markers of oxidative stress and lipid peroxidation, immunoglobulin levels, CD4⁺/CD8⁺ T cell balance, and pancreatic histostructure were assessed. Results: Alloxan administration led to substantial hyperglycemia, oxidative stress, immunological imbalance, and structural damage to pancreatic tissue. Following therapy with Inullact-Fito, blood glucose levels reduced dramatically (from 21.9 ± 0.22 to 9.85 ± 0.10 mmol/L, p < 0.05), circulating insulin concentrations were largely corrected, oxidative stress and lipid peroxidation markers decreased. Immunological evaluation revealed decreased serum immunoglobulin M and IgG levels (p < 0.05) and partial normalization of the CD4⁺/CD8⁺ T cell balance. Metformin showed comparative effects; however, its activity in this model is limited by its primary mechanism related to insulin resistance. Conclusions: Overall, the data reveal that Inullact-Fito combines metabolic, antioxidant, and immunomodulatory actions under experimental oxidative and metabolic stress conditions. Further research using models of insulin resistance and type 2 diabetes, as well as long-term clinical trials, is needed to fully evaluate the therapeutic potential, safety profile, and translational importance of this fermented dairy product as a functional nutritional intervention. Full article

Obesity has reached epidemic proportions, driven by energy imbalance and limited capacity for adaptive thermogenesis. Brown (BAT) and beige adipose tissues dissipate energy through non-shivering thermogenesis (NST), primarily via uncoupling protein-1 (UCP1), making them attractive targets for increasing energy expenditure (EE). The canonical β-adrenergic pathway robustly activates NST in rodents through β3 adrenoceptors; however, translational success in humans has been limited by low β3 expression, off-target cardiovascular effects, and the emerging dominance of β2-mediated signaling in human BAT. Consequently, attention has shifted to non-adrenergic and UCP1-independent mechanisms that offer greater tissue distribution and improved safety profiles. This review examines a broad spectrum of alternative receptors and pathways—including GPRs, TRP channels, TGR5, GLP-1R, thyroid hormone receptors, estrogen receptors, growth hormone, BMPs, sirtuins, PPARs, and interleukin signaling—as well as futile substrate cycles (Ca²⁺, creatine, and glycerol-3-phosphate) that sustain thermogenesis in beige adipocytes and skeletal muscle. Pharmacological agents (natural compounds, peptides, and small molecules) and non-pharmacological interventions (cold exposure, exercise, diet, and time shift) targeting these pathways are critically evaluated. We highlight the translational gaps between rodent and human studies, the promise of multimodal therapies combining low-dose adrenergic agents with non-adrenergic activators, and emerging strategies such as sarco/endoplasmic reticulum calcium ATPase protein (SERCA) modulators and tissue-specific delivery. Ultimately, integrating adrenergic and non-adrenergic approaches holds the greatest potential for safe, effective, and sustainable obesity management. Full article

Interstitial lung diseases (ILDs) encompass a heterogeneous group of disorders characterized by varying degrees of inflammation and fibrosis. Despite advances in understanding the pathogenesis, therapeutic options remain limited, particularly for patients with progressive phenotypes. Current international guidelines for idiopathic pulmonary fibrosis (IPF) and progressive pulmonary fibrosis (PPF) emphasize the need for antifibrotic strategies and call for novel pharmacological interventions targeting key molecular pathways involved in fibrogenesis. This review provides a comprehensive overview of the most promising emerging pharmacological agents for ILDs, with particular attention to their mechanisms of action, efficacy, and safety profiles as reported in recent preclinical and clinical studies. The recent approval of Nerandomilast and the ongoing phase III trials of other agents mark a pivotal transition toward a new generation of antifibrotic therapies, aiming to achieve more effective disease control and improved patient outcomes. In view of an enlargement of active drugs aiming at controlling the disease with different mechanisms, the Authors underline the need for a “precision medicine” model to be applied to each ILD phenotyped patient, mirroring what already happens for other respiratory diseases. Full article

Background: Osteoarthritis (OA) is a prevalent degenerative joint disease often causing functional disability. Current therapies provide only temporary relief and can cause adverse effects that frequently result in pain and disability. Current pharmacological options offer only temporary symptom relief and may cause adverse effects. Piper sarmentosum (PS), a plant traditionally used for its medicinal properties, has demonstrated antioxidant and anti-inflammatory activities that may counteract OA-related degeneration. This study provides preliminary insight into the therapeutic potential of PS aqueous extract in human OA chondrocytes. Methods: Compounds in the PS aqueous extract were profiled using liquid chromatography–tandem mass spectrometry (LC-MS/MS). Primary human OA chondrocytes (HOCs) were treated with 0.5, 2, and 4 µg/mL of PS aqueous extract for 72 h. Key OA-related parameters were assessed, including anabolic markers (sulfated glycosaminoglycan (sGAG), collagen type II (COL II), aggrecan core protein (ACP), SRY-box transcription factor 9 (SOX9)), catabolic markers (matrix metalloproteinase (MMP) 1, MMP13, cyclooxygenase 2 (COX2)), oxidative stress (nitric oxide (NO) production, inducible NO synthase (iNOS) expression), and inflammatory responses (interleukin (IL) 6). Gene expression was quantified using qPCR, and protein levels were evaluated using the colorimetric method, immunocytochemistry, and Western blot. Results: A total of 101 compounds were identified in the extract, including vitexin, pterostilbene, and glutathione—bioactives known for antioxidant, anti-inflammatory, and chondroprotective functions. PS-treated chondrocytes maintain healthy polygonal morphology. PS aqueous extract significantly enhanced anabolic gene expression (COL2A1, ACP, SOX9) and sGAG production, while concurrently suppressing COX2 expression and NO synthesis. Additionally, PS aqueous extract reduced COX2 and iNOS protein levels, indicating inhibition of the NO signaling pathway. Catabolic activity was attenuated, and inflammatory responses were partially reduced. Conclusions: PS aqueous extract exhibits promising chondroprotective, antioxidant, and anti-inflammatory effects in human OA chondrocytes, largely through the suppression of NO-mediated catabolic signaling. The presence of multiple bioactive compounds supports its mechanistic potential. These findings highlight PS aqueous extract as a potential therapeutic candidate for OA management. Further ex vivo and in vivo studies are warranted to validate its efficacy and clarify its mechanism in joint-tissue environments. Full article

Background: The traditional formula Liqi Yangyin (LQYY) has shown clinical and preclinical efficacy for depression with constipation, yet its molecular mechanisms remain incompletely defined. This study aimed to elucidate its mechanisms using an integrative approach. Methods: Constituents of LQYY were profiled by UPLC-MS/MS and integrated with network pharmacology and molecular docking to identify brain-accessible components and putative targets. A chronic unpredictable mild stress (CUMS) model was used for experimental validation. Outcomes included behavioral tests (sucrose preference test, open field test, and forced swimming test), gastrointestinal indices, including fecal water content, time of first black stool, and intestinal propulsion rate, histopathology of the prefrontal cortex (PFC) and colon, TUNEL staining, NeuN immunofluorescence, Western blotting, and qRT-PCR. Results: LQYY attenuated CUMS-induced weight loss and depressive-like behaviors and improved intestinal transit metrics. It reduced neuronal apoptosis in the PFC and ameliorated colonic injury. Mechanistically, docking and enrichment analyses highlighted hub targets (STAT3, AKT1, ESR1, IL-6, TNF, TP53) and the JAK/STAT pathway. In vivo, LQYY decreased IL-6, TNF-α, ESR1, TP53, and STAT3, and increased AKT1 in the PFC and colon; it also reduced the TUNEL-positive rate and restored NeuN labeling, upregulated Bcl-2, and downregulated p-JAK2/JAK2 and p-STAT3/STAT3 ratios, and the expression of Bax and cleaved-caspase-3 in the PFC, consistent with the suppression of pro-inflammatory and apoptotic signaling. Conclusions: LQYY exerts antidepressant and pro-motility effects in CUMS mice by modulating JAK2/STAT3-centered networks and inhibiting neuronal apoptosis, thus supporting a multi-component, multi-target strategy for treating depression with constipation, and providing a defined molecular hypothesis for future investigation. Full article

Glucagon-like peptide-1 (GLP-1) receptor agonists and sodium–glucose cotransporter-2 (SGLT2) inhibitors have reshaped pharmacological management of type 2 diabetes, but emerging safety signals suggest a possible association with intestinal obstruction. Because many candidates for these agents already harbor risk factors for ileus and bowel obstruction, clarifying agent- and dose-specific gastrointestinal safety is clinically important. We aimed to re-evaluate the risk of intestinal obstruction across individual GLP-1 receptor agonists and SGLT2 inhibitors, with particular attention to dose stratification. We systematically searched eight databases through 21 January 2025 to identify randomized controlled trials (RCTs) comparing GLP-1 receptor agonists or SGLT2 inhibitors with placebo or active comparators in adults. The primary outcome was incident intestinal obstruction (small or large bowel). A frequentist random-effects network meta-analysis estimated odds ratios (ORs) with 95% confidence intervals (CIs) across drugs and dose tiers; Bayesian models and surface under the cumulative ranking (SUCRA) metrics were used for sensitivity analyses and treatment ranking. Risk of bias and certainty of evidence were assessed with standard Cochrane and GRADE-adapted tools. Fifty RCTs (47 publications; 192,359 participants) met inclusion criteria. Overall, canagliflozin use was associated with a higher incidence of intestinal obstruction than control therapies (OR 2.56, 95% CI 1.01–6.49), corresponding to an absolute risk difference of 0.15% and a number needed to harm of 658. High-dose canagliflozin (300 mg/day) showed the clearest signal (OR 3.42, 95% CI 1.08–10.76). In contrast, liraglutide was associated with a lower risk of intestinal obstruction (OR 0.44, 95% CI 0.24–0.81), with an absolute risk reduction of 0.34% and a number needed to treat of 295. No other GLP-1 receptor agonist or SGLT2 inhibitor demonstrated a statistically significant increase in obstruction risk. Frequentist and Bayesian analyses yielded concordant estimates and rankings. From a randomized-trial perspective, intestinal obstruction risk is not elevated for most GLP-1 receptor agonists and SGLT2 inhibitors. A dose-dependent safety signal was observed only for high-dose canagliflozin, whereas liraglutide may confer a protective effect. These findings refine gastrointestinal safety profiles for modern antidiabetic agents and may inform perioperative bowel management, drug selection, and dose optimization in patients at risk for ileus or adhesive obstruction. Full article

Background: Beauveria bassiana infection of silkworm forms Bombyx Batryticatus (BB). It is a medicinal material with significant pharmacological potential. While artificial diet feeding improves the production efficiency of BB, it might alter host metabolism, consequently affecting its bioactive components and efficacy. To address this, we conducted a metabolomics analysis of BB reared under different feeding conditions; Methods: UPLC-MS/MS was employed to conduct metabolomic analysis of BB under three rearing conditions: all instars mulberry leaf feeding (MF), all instars artificial diet feeding (AF), and mixed feeding (AMF). The sample collection time was selected as the time when silkworms died after infection (D0), and the fifth day after death (D5), which is the time when fungus produces biologically active secondary metabolites to reach a stable state; Results: Compared to MF, AF did not significantly alter the levels of the index component induced by B. bassiana infection—beauvericin. Moreover, the overall metabolic profile differences between the two groups decreased at the later stage (D5). Specifically, the average Pearson correlation between these groups was 0.659 ± 0.102, and the first two principal components of PCA explained 49.6% of the total variance. This suggests a reduction in the differences in their pharmacological active components. KEGG enrichment analysis revealed that AF promoted the accumulation of certain flavonoids (e.g., apigenin, luteolin), but, overall, the biosynthesis of flavone and flavonol is suppressed. Additionally, several metabolites, including N,N′-diferuloylputrescine, N-methyl-4-aminobutyric acid, and 3,4-dimethoxyphenylacetic acid, were identified to be significantly positively correlated with artificial diet supplementation; Conclusions: This study reveals metabolic differences in BB under different rearing methods at the metabolomic level, providing a scientific basis for evaluating the quality of this medicinal material. Full article