Search Results (114)

Daidzin is a soy-derived isoflavone with reported anti-obesity effects; however, the biological activity of microbial-derived daidzin remains poorly understood. In this study, we investigated the anti-adipogenic and anti-obesity potential of microbial-derived daidzin (hereafter referred to as Eco-3) in both in vitro and in vivo models. Eco-3 significantly suppressed adipocyte differentiation and lipid accumulation in 3T3-L1 preadipocytes and human adipose-derived stem cells (hASCs) without inducing cytotoxicity. Mechanistically, Eco-3 reduced the expression of key adipogenic regulators, including PPAR-γ and C/EBP-α, and modulated lipid metabolism-related proteins such as FAS and perilipin A. In addition, Eco-3 activated AMPK signaling while inhibiting the STAT-3 and STAT-5 pathway. In zebrafish models, Eco-3 significantly reduced lipid accumulation under both normal and diet-induced obesity conditions, as demonstrated by LipidGreen2 and Oil Red O staining. Collectively, these findings suggest that Eco-3 exerts anti-obesity effects through coordinated regulation of adipogenesis and lipid metabolism. Full article

This study evaluated olive leaf extract (OLE) as a multifunctional dermocosmetic candidate for sebum-related and inflammatory responses relevant to oily and acne-prone skin using an axis-aligned in vitro panel: (i) sebocyte lipogenesis, (ii) inflammatory mediator production in keratinocytes, and (iii) fibroblast-mediated collagen gel contraction. In addition, supportive mechanistic evidence for the sebum-related effects of OLE was obtained by examining signaling proteins associated with sebocyte lipogenesis, including PPAR-γ and SREBP-1. As a result, OLE significantly inhibited linoleic acid-induced lipid accumulation in SEB-1 sebocytes without cytotoxicity. In HaCaT keratinocytes, OLE significantly reduced the production of pro-inflammatory cytokines, including IL-8, TNF-α, and PGE₂, induced by Cutibacterium acnes or UVB. In dermal fibroblast-containing collagen gels, OLE enhanced fibroblast-mediated gel contraction. Additionally, analysis of the main mechanisms of lipid inhibition using SEB-1 sebocytes revealed that OLE exerts a dual regulatory role in lipid synthesis and inflammation by downregulating AKT and ERK phosphorylation and inhibiting PPAR-γ and SREBP-1 expression. Furthermore, among the tested extracts, the 70% ethanol extract (OLE70) exhibited the strongest antioxidant activity, the greatest gel contraction response, and the highest content of oleuropein, a major bioactive phenolic compound derived from olive. Like OLE, oleuropein also showed sebum-regulatory activity by reducing lipid accumulation in SEB-1 sebocytes, an inhibitory effect on IL-8 expression in HaCaT keratinocytes, and an inhibitory effect on the expression of PPAR-γ and SREBP-1, which are involved in sebum secretion. Taken together, these findings suggest that OLE and its major phenolic constituent, oleuropein, may modulate sebum-related, inflammatory, oxidative, and dermal remodeling-associated responses in skin cell models. These results should be interpreted as exploratory and provide a basis for further mechanistic and translational investigation. Full article

Background: Postmenopausal women are at high risk of Alzheimer’s disease (AD) incidence and progression. Irisin, an exercise-induced myokine, has neuroprotective and antiaging effects against AD, especially in menopausal women suffering from insulin resistance (IR). For the first time, the novel role of irisin induced by melatonin (MTN) or/and physical exercise (PHE) was investigated in the current ovariectomized (OVX)/AD rat model by modulating brain neuroinflammation and IR-related markers. Methods: Fifty female Wistar rats were divided into five groups, with one representing a sham group. AD was induced in the other four bilateral OVX rat groups by daily intraperitoneal injection of D-galactose/AlCl₃ (60 and 10 mg/kg, respectively) for 42 days. Group III–V: Animals were exposed to MTN (10 mg/kg/day; i.p.), PHE, and a combination of these, respectively, in the final 14 days of the experiment. Results: The OVX/AD rats showed significant deterioration in learning, memory, neurochemical, and histopathological examinations, while the MTN or/and PHE treatments significantly increased serum and brain irisin, improving memory in a Y-maze assessment. Thus, hippocampal histopathological alterations and IR-related markers decreased. In addition, suppressed hippocampal amyloid-beta protein expression and neuroinflammatory content of tumor necrosis factor-alpha (TNF-α), p38 mitogen-activated protein kinase (p38 MAPK), and NOD-like receptor protein-3 (NLRP3) were associated with an increase in peroxisome proliferator-activated receptor-gamma (PPAR-γ) protein expression and insulin-like growth factor-1 content in hippocampal tissues, collectively suppressing glial fibrillary acidic protein (GFAP) content, leading to an increase in brain-derived neurotrophic factor expression. Conclusions: Irisin induction may serve as a novel avenue in AD/menopause treatment and prevention via modulating the TNF-α/p38 MAPK/PPAR-γ/NLRP3/GFAP pathway. Full article

Background: Human diseases remain a major global health challenge, requiring effective therapeutic strategies. Traditional Chinese medicine (TCM) has been widely used in clinical settings. Many natural compounds, such as flavonoids from TCM, exhibit diverse pharmacological activities. Alpinetin and pinocembrin are structurally related flavonoids. Alpinetin is derived from Zingiberaceae plants, and pinocembrin is extracted from wild marjoram (origanum vulgare) or other natural sources. They possess a wide range of pharmacological activities or biological effects, including anti-inflammatory, anti-tumor, liver and kidney protection, cardiovascular protection, and antibacterial activities. Methods: The present comparative review was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, using four major databases (PubMed, EMBASE, Web of Science, and Cochrane Library), as well as CNKI without language restrictions. Results: Pharmacokinetic studies reveal distinct absorption, metabolism, and excretion profiles. Alpinetin and pinocembrin undergo glucuronidation and interact with cytochrome P450 enzymes and transporters. However, alpinetin has demonstrated approximately 1.5-fold higher plasma exposure and slower clearance compared to pinocembrin. Mechanistically, alpinetin exerted therapeutic effects through modulation of the NF-κB/MAPK, PI3K/Akt, and PPAR-γ signaling pathways, resulting in a 2- to 3-fold reduction in pro-inflammatory cytokines. In contrast, pinocembrin exerted protective activity through the inhibition of HMGB1/TLR4 signaling, regulation of endoplasmic reticulum stress, and activation of Nrf2/HO-1, leading to a 1.8-fold increase in antioxidant enzyme activity. The minimum inhibitory concentrations were reduced by 2- to 4-fold against Gram-positive bacteria compared to alpinetin. Conclusions: These findings highlight the pharmacological potential of alpinetin and pinocembrin as promising candidates for the development of novel anti-tumor, anti-inflammatory, liver and kidney protection, cardiovascular protection, and antibacterial agents. However, research on the pharmacological actions of alpinetin and pinocembrin is still in the preclinical stage. Further research is required to validate their efficacy in clinical settings, especially for translation to clinical studies. This is critical to translating these natural flavonoids into effective therapeutic agents while addressing the regulatory challenges and pathways associated with botanical drugs in human diseases. Full article

Glehniae Radix, the dried root of Glehnia littoralis Fr. Schmidt ex Miq. (Apiaceae), exhibits diverse biological activities. However, research on the hypoglycemic effects of Glehniae Radix polysaccharides (GRPs), particularly in vivo studies clarifying their mechanisms of action, remains limited. This study aimed to verify the in vivo hypoglycemic activity of crude GRP in a diabetic model and to elucidate its mechanism. GRP was extracted by water extraction and ethanol precipitation, yielding an extraction rate of 38% and a polysaccharide content of 73.48%. Its hypoglycemic effects and mechanisms were investigated in female B6.BKS(D)-Leprdb/J (db/db) mice following daily administration of GRP at doses of 300 and 600 mg/kg for five consecutive weeks. Following GRP administration, mice in the CH group (600 mg/kg) exhibited a mean reduction in fasting blood glucose levels of approximately 40.7% and an improvement in insulin tolerance test (ITT) outcomes by about 28.4%. Additionally, GRP alleviated damage to the liver, kidney, and colon; decreased hepatic total cholesterol (TC) and triglycerides (TGs) by approximately 40.8% and 24.6%, respectively; and increased colonic Zonula Occludens-1 (ZO-1) expression by an average of 49.5%. Mechanistically, GRP significantly upregulated the expression of peroxisome proliferator-activated receptor-α (PPAR-α) and PPAR-γ in the liver, while also increasing the abundance of beneficial gut bacteria such as Alistipes and suppressing harmful bacteria including Escherichia-Shigella. Furthermore, GRP activated the galactose metabolism pathway and inhibited abnormal enrichment of the steroid biosynthesis pathway, collectively ameliorating glucose metabolic disorders in female db/db mice via the “gut microbiota–PPAR signaling axis”. In light of these results, GRP exerts significant in vivo hypoglycemic effects by modulating gut microbiota balance and activating the PPAR signaling pathway. Full article

Fibroblasts play a fundamental role in maintaining tissue architecture, regulating repair processes, and adapting to metabolic and inflammatory stress. Increasing evidence indicates that endogenous bioelectrical states contribute to gene expression regulation and cellular homeostasis. In this study, we investigated the effects of Radio Electric Asymmetric Conveyer (REAC) Metabolic Optimization–Inside Blue Zone (MO-IBZ) treatment on key regulators of stress response and metabolic control in human foreskin fibroblasts (HFF-1). Cells were exposed to nine standardized REAC MO-IBZ sessions, and changes in gene and protein expression were evaluated. Quantitative RT-PCR revealed a significant downregulation of SIRT1 and an upregulation of PPAR-γ expression in treated cells compared with untreated controls. These findings indicate molecular changes involving stress-responsive and metabolic regulatory pathways; however, they should be interpreted primarily as transcriptional signatures, as no direct functional stress-response or metabolic assays were performed. Immunofluorescence analysis showed visually increased expression of mTOR, IGF-1 receptor, and cytochrome c in REAC-treated fibroblasts, supporting a qualitative indication of activation of pathways associated with anabolic signaling, mitochondrial function, and metabolic efficiency. Taken together, these findings indicate that REAC MO-IBZ induces a coordinated molecular profile compatible with changes in cellular metabolic regulatory capacity. Within the framework of current bioelectrical literature, these changes may plausibly reflect broader regulatory adaptations; however, the present work does not provide direct measurements of bioelectrical parameters, functional metabolic activity, or epigenetic regulation, and therefore such interpretations remain speculative. These results provide descriptive mechanistic evidence supporting further investigation of REAC-based bioelectrical modulation as a potential strategy to influence cellular pathways involved in metabolic balance and tissue repair, encouraging future studies incorporating direct bioelectrical, epigenetic, and functional analyses. Full article

Medium- and long-chain fatty acids (MLFAs) are increasingly recognized not only as metabolic substrates but also as precursors of diverse bioactive metabolites generated through host and microbial transformations. Recent advances in analytical chemistry and microbiome research have revealed that gut microorganisms catalyze extensive modifications of dietary MLFAs—producing hydroxylated, conjugated, and keto-fatty acids with enhanced potency toward host receptors. These metabolites exhibit dual activity on classical metabolic receptors, including FFAR1/4 and PPARα/γ, as well as ectopically expressed chemosensory receptors such as olfactory receptors (ORs) and bitter taste receptors (TAS2Rs). This expanded receptor landscape establishes a previously unrecognized chemosensory–metabolic axis that integrates dietary signals, microbial metabolism, and host physiology. Microbial MLFA derivatives such as 10-hydroxyoctadecenoic acid and conjugated linoleic acid regulate incretin secretion, adipogenesis, macrophage polarization, and intestinal barrier function through coordinated activation of FFARs and PPARs. Concurrently, dicarboxylic acids such as azelaic acid activate Olfr544 to modulate lipolysis, ketogenesis, GLP-1 release, and feeding behavior. TAS2Rs also sense oxidized lipids, linking lipid metabolism to immune regulation and enteroendocrine signaling. Collectively, these pathways highlight the microbiome as a metabolic transducer that converts dietary lipids into signaling molecules influencing endocrine, immune, and gut–brain circuits. Understanding the mechanisms governing MLFA bioconversion and receptor engagement provides new opportunities for therapeutic and nutritional intervention. Targeting ORs and TAS2Rs, engineering probiotics to enhance beneficial FA-derived metabolites, and developing receptor-selective synthetic analogs represent promising strategies. Future progress will require integrative approaches combining physiology, biochemistry, metabolomics, and microbial genomics to elucidate receptor specificity and host variability. Full article

Moringa oleifera, widely recognized as the horseradish tree or drumstick tree, is classified within the Moringaceae family, which comprises 13 species predominantly distributed across tropical and subtropical regions. The plant possesses a variety of therapeutic, nutritional, and beneficial health properties, including its potential to enhance the immune system. The present work provides extensive bibliographic research addressing the chemical composition of Moringa oleifera and its immunomodulatory properties with a focus on the cellular and molecular mechanisms involved in the regulation of immune function, which is crucial in unchecked cell proliferation and metastasis. The chemical composition of Moringa oleifera, including kaempferol, chlorogenic acid, quercetin, and niazimicin, varies between different biological parts of the plant (seeds, leaves, roots, and stems). The presence of these various chemical compounds contributes to the plant’s effect on the immune response via different pathways. Several studies indicate that Moringa oleifera mitigates inflammation by suppressing key pro-inflammatory mediators, such as TNF-α, IL-1β, inducible nitric oxide synthase (iNOS), prostaglandin E2 (PGE-2), and cyclooxygenase-2 (COX-2), while simultaneously enhancing anti-inflammatory mediators through activation of PPAR-γ. Furthermore, the immunomodulatory properties and possible application in health promotion and disease prevention, especially in cancer therapy, are discussed. Studies indicate that Moringa oleifera can modulate the tumor microenvironment (TME) by reducing Treg polarization, enhancing NK cell cytotoxicity, and prompting the proliferation and clonal expansion of CD8⁺ and CD4⁺ T lymphocytes. Together, Moringa oleifera could be considered for the treatment of conditions related to immune dysregulation, such as cancer. Full article

Insulin resistance, dyslipidemia, hypertension, and visceral adiposity are the leading causes of the growing worldwide health burden associated with metabolic syndrome, obesity, and cardiovascular diseases (CVDs). Despite the “obesity paradox,” which emphasizes the varied cardiovascular outcomes among obese people, obesity is now acknowledged as an active contributor to cardiometabolic dysfunction through endocrine, inflammatory, and metabolic pathways. Growing evidence indicates that nutrition is a key determinant of cardiometabolic risk, highlighting the need to understand diet-mediated mechanisms linking adipose tissue to cardiac function. Adipokines, including adiponectin, leptin, TNF-α, and resistin, which regulate systemic inflammation, metabolic homeostasis, and myocardial physiology, are secreted by adipose tissue, which is no longer thought of as passive energy storage. Its heterogeneous phenotypes, white, brown, and beige adipose tissue, exhibit distinct metabolic profiles that influence cardiac energetics and inflammatory status. Nutrient-driven transitions between these phenotypes further underscore the intricate interplay between diet, adipose biology, and cardiac metabolism. Central nutrient-sensing pathways, including mTOR, AMPK, SIRT1, PPAR-γ, and LKB1, integrate macronutrient and micronutrient signals to regulate adipose tissue remodeling and systemic metabolic flexibility. These pathways interact with hormonal mediators such as insulin, leptin, and adiponectin, forming a complex regulatory network that shapes the adipose-cardiac axis. This review synthesises current knowledge on how nutrient inputs modulate adipose tissue phenotypes and signaling pathways to influence cardiac function. By elucidating these mechanisms, we highlight emerging opportunities for precision nutrition and targeted therapeutics to restore metabolic balance, strengthen cardiac resilience, and reduce the burden of cardiometabolic disease. Full article

Citri grandis exocarpium (Citri grandis) has been consumed by human beings for fifteen hundred years. It is commonly consumed as a health drink and dietary supplement in China. However, its nutritional and healthcare functions are still not fully understood. Objective: Our previous study found that oral administration of Citri grandis extract can significantly decrease the blood lipid levels of hyperlipidemic mice fed a high-fat diet. The aim of this study was to confirm the preventative effects of Citri grandis extract against atherosclerosis. Methods: Atherosclerotic lesion models were induced in HUVECs and apoE^−/− C57BL/6J mice. ApoE^−/− mice fed a high-fat diet were orally administered Citri grandis extract (0.4, 0.8, and 1.6 g/kg/d BW) and Simvastatin (1 mg/kg/d BW) on the first day of model establishment. After a 16-week treatment, serum samples and aorta and liver tissues were collected. Observation of pathological changes in aortic and liver tissues was performed using a light microscope with oil red O, H&E, Masson’s trichrome staining, and TEM. Biochemical detection was employed to determine the serum levels of TC, TG, LDL-C, and HDL-C as well as the activities of AST and ALT. In addition, expression studies of TGF-β, PI3K, AKT1, PPAR-γ, LXR-α, and ABCA1 were performed via qPCR and Western blot analysis. Results: Compared with cholesterol-induced HUVECs, Citri grandis extract significantly enhanced cell viability, attenuated the morphological changes in HUVECs, and reduced LDH release. Furthermore, after treatment with Citri grandis extract, the levels of TC, TG, and LDL-C significantly decreased in the atherosclerosis model apoE^−/− mice after 16 weeks, and aortic plaque, lipid deposition, and endothelial injury were obviously ameliorated. The mRNA and protein expression of TGF-β, PPAR-γ, LXR-α, and ABCA1 in aortic and liver of atherosclerosis apoE^−/− mice were upregulated (p < 0.05, p < 0.01), while those of PI3K and Akt1 were suppressed (p < 0.05, p < 0.01). Conclusions: Citri grandis extract can significantly decrease the high circulating lipid levels and the liver lipid deposition of high-fat-diet-fed apoE^−/− mice and reduce aorta lipid accumulation and atherosclerotic plaques by regulating the expression of TGF-β1, PI3K, AKT1, PPAR-γ, LXR-α, and ABCA1. Citri grandis extract can be used as a healthcare dietary supplement for the prevention of abnormal lipid metabolism and atherosclerosis. Full article

Preclinical data suggest that cannabidiol (CBD) and Δ9-tetrahydrocannabinol (THC) modulate inflammatory pathways (e.g., NLRP3, NF-κB, and PPAR-γ), but clinical translation into consistent changes in circulating biomarkers remains ambiguous. Two reviewers independently screened the studies, extracted data, and assessed risk of bias with RoB-2. Random-effects meta-analyses (RevMan 5.4.1) formed standardized mean differences (SMD) or mean differences (MD) as appropriate. The certainty of evidence was graded by means of GRADE. Thirteen studies satisfied inclusion criteria; meta-analyses were feasible for IL-6 (four studies, n ≈ 129 per arm), IL-8 (two studies, n ≈ 78 per arm), IL-10 (two studies, n ≈ 92 per arm), and TNF-α (three studies, n ≈ 105 per arm). Pooled estimates favored CBD but were trivial and imprecise: IL-6 SMD −0.17 (95% CI −0.56 to 0.23; p = 0.41; I² = 55%); IL-8 SMD −0.30 (95% CI −0.62 to 0.01; p = 0.06; I² = 0%); IL-10 SMD −0.10 (95% CI −0.83 to 0.63; p = 0.79; I² = 81%); and TNF-α SMD −0.09 (95% CI −0.45 to 0.27; p = 0.62; I² = 33%). Individual trials reported reductions in biomarkers in high-exposure or diseased populations. GRADE ratings were as follows: IL-6 very low, IL-8 moderate, IL-10 low, and TNF-α moderate. Current RCT evidence demonstrates inconsistent, often trivial effects of phytocannabinoid interventions on circulating inflammatory biomarkers. Full article

Plant-derived vesicles (PDVs) represent an emerging class of naturally bioformulated nanocarriers with potential nutraceutical and therapeutic applications. In this study, the multifunctional biological activity of PDVs obtained from Eruca sativa leaves (arugula leaf vesicles, ALVs) was investigated both in vitro and in vivo. In differentiated Caco-2 and HepG2 cells, ALVs exhibited significant antioxidant activity, being rich in polyphenols and organic acids, by reducing intracellular reactive oxygen species (ROS) and modulating key metabolic regulators. ALVs upregulated SREBP-2, LDLR, and phosphorylated AMPK and Akt, leading to enhanced LDL and glucose uptake, while downregulating FASN and PPAR-γ, thereby reducing lipid accumulation. In mice fed a high-fat and high-fructose (HFHF) diet, ALV supplementation improved glucose tolerance and decreased total cholesterol, LDL, and hepatic injury biomarkers (ALT, AST, and LDH) without inducing toxicity. These findings demonstrate that ALVs exert hypocholesterolemic, hypoglycemic, and lipid-lowering effects through coordinated modulation of AMPK/Akt pathways. Overall, ALVs emerge as safe, multifunctional nanovesicles capable of counteracting oxidative stress and metabolic dysfunction, highlighting their potential as innovative bioactive ingredients for functional foods or nutraceutical formulations targeting metabolic syndrome. Full article

Two previously undescribed highly oxygenated cembrane-type diterpenes, namely sarcocraol A (1) and sarcocraol B (2), along with five known compounds (3–7), have been isolated from the soft coral Sarcophyton crassocaule collected off Ximao Island in the South China Sea. Their structures were determined through comprehensive spectroscopic analysis, QM-NMR calculations, TDDFT-ECD computation, X-ray diffraction analysis, and by comparison with literature data. Plausible biosynthetic pathways for these compounds were also proposed. All compounds were evaluated for peroxisome proliferator-activated receptors (PPARs) transcriptional activity using luciferase assay. The bioassay results demonstrated that compound 1 exhibits selective PPAR-γ agonistic activity. Furthermore, it promoted glucose uptake in HepG2 cells by 1.18-, 1.45-, and 1.90-fold at concentrations of 2.5, 5, and 10 μM, respectively, whereas rosiglitazone (10 μM) produced a 2.47-fold increase over the induced control. Compound 1 at 10 μM induced mild lipid accumulation in 3T3-L1 cells, showing a 1.63-fold increase relative to the control, which was much lower than the 3.28-fold increase observed in rosiglitazone (10 μM) group indicating its potential antidiabetic properties. These findings suggested that compound 1 could be a promising lead for the development of antidiabetic agents. Full article

Background/Objectives: Coumarin-based compounds exhibit diverse pharmacological properties, and 4-methylcoumarin (4MC) has emerged as a promising scaffold for drug development. However, its anti-obesity mechanisms remain insufficiently understood. This study aimed to evaluate the anti-adipogenic potential of 4MC derivatives in 3T3-L1 preadipocytes and to elucidate their underlying molecular mechanisms. Methods: 3T3-L1 preadipocytes were treated with structurally diverse 4MC derivatives. Lipid accumulation was analyzed using Oil Red O staining, cell viability by MTT assay, and the expression of adipogenic proteins by Western blotting. Molecular docking and molecular dynamics simulations were performed to predict the interactions between lead compounds and key adipogenic regulators. Results: Among the tested derivatives, 6,7-dihydroxy-4-methylcoumarin (6,7DH-4MC) markedly inhibited lipid accumulation in a dose-dependent manner without cytotoxicity. It suppressed the expression of major adipogenic transcription factors (PPAR-γ, C/EBPα, SREBP-1c) and FABP4. Additionally, 6,7DH-4MC inhibited ERK1/2 and p38 MAPK phosphorylation while activating AMPK. It also reduced CREB phosphorylation, indicating suppression of early adipogenesis. Computational analyses revealed stable binding of 6,7DH-4MC within the active sites of multiple adipogenic regulators, supporting its pleiotropic mode of action. Conclusions: 6,7DH-4MC exerts potent anti-adipogenic effects by modulating key adipogenic signaling pathways and transcriptional networks. These findings highlight 6,7DH-4MC as a promising lead compound for anti-obesity drug development, warranting further in vivo studies. Full article

This study addressed the optimal magnesium (Mg) requirement for juvenile largemouth bass (Micropterus salmoides) and assessed the effects of dietary Mg supplementation on growth performance, nutrient metabolism, and alleviation of heat stress in it. In this study, six diets with varying Mg levels (1.01, 1.26, 1.78, 2.24, 2.35, and 2.51 g/kg), designated as MG1, MG2, MG3, MG4, MG5, and MG6, respectively, were formulated using MgSO₄·7H₂O as the Mg source. These diets were fed to juvenile M. salmoides (initial body weight 2.27 ± 0.02 g) for 8 weeks. The growth performance of the MG4 group was significantly improved. In addition, Plasma GLU, LDL-C, and TG levels were significantly reduced in the MG4 group, while plasma HDL-C levels were increased. In terms of gene expression, glut2, g6pdh, ppar-γ, fas, elovl2, acc, and igf-1 were significantly upregulated in the MG4 and MG5 groups, while g6pase and ppar-α were significantly downregulated in the MG5 group. In the heat stress test, MG4 group exhibited enhanced antioxidant capacity, as evidenced by decreased plasma MDA levels and increased CAT activity, coupled with enhanced gill Na⁺/K⁺-ATPase activity. Gene expression results also showed that il-10 and bcl-2 were significantly upregulated in the MG4 group, while nf-κb, ifn-γ, il-8, tnf-α, casp3, casp8, bax, jnk2 and ask1 were significantly downregulated. Furthermore, the results of TUNEL immunofluorescence labeling analysis showed that the apoptotic index was significantly decreased in the MG2-MG6 groups. Overall, appropriate dietary Mg levels promoted growth performance, improved glucose metabolism, and induced lipid deposition in juvenile M. salmoides. Notably, Mg reduced oxidative damage by enhancing antioxidant enzyme activity, thereby modulating heat stress-induced Antioxidant–Inflammatory–Apoptotic of juvenile M. salmoides. Based on quadratic regression analysis of SGR and FCR, the optimal Mg requirement for juvenile M. salmoides was 2.04, and 2.15 g/kg, respectively. Full article