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Advanced Healthcare Materials · 2024 · IF 10

2D is Better: Engineering Polydopamine into Cationic Nanosheets to Enhance Anti-inflammatory Capability

Lulu Liu,Chenxin Lu,Zhenchao Tao,Zhengbao Zha,Hua Wang,Zhaohua Miao

Polydopamine nanomaterials have emerged as one of the most popular organic materials for management of oxidative stress-mediated inflammatory diseases. However, their current anti-inflammatory ability is still unsatisfied because of limited phenolic hydroxyl groups and oxidation reaction-medicated reactive oxygen and nitrogen species (RONS) scavenging. Herein, via fusing dimension engineering and surface charge engineering, we reported two-dimension (2D) cationic polydopamine nanosheets (PDA NSs) capable of scavenging multiple danger signals to enhance anti-inflammatory capability. Compared with conventional spherical polydopamine nanoparticles, 2D PDA NSs exhibited 3∼4-fold enhancement in RONS scavenging capability, which should be attributed to high specific surface area and abundant phenol groups of 2D ultrathin structure. To further enhance the anti-inflammatory ability, polylysine molecules were absorbed on the surface of PDA NSs to endow the scavenging capability of cell-free DNA (cfDNA), another typical inflammatory factor to exacerbate the pathogenesis of inflammation. Molecular mechanisms revealed that cationic PDA NSs could concurrently activate Keap1-Nrf2 and block TLR9 signaling pathway, achieving synergistical inflammation inhibition. As a proof of concept, cationic PDA NSs with RONS and cfDNA dual-scavenging capability effectively alleviated the inflammatory bowel disease in both delayed and prophylactic models, much better than the clinical drug 5-aminosalicylic acid. This article is protected by copyright. All rights reserved

CAS / MDL: 62-31-7 25988-63-0
研究领域: 材料科学 · 纳米技术 · 药学 · 炎症研究
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INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES · 2023 ·Vol. 24 ·期 19 ·14721 · IF 5.6

A Neutral Polysaccharide from Spores of Ophiocordyceps gracilis Regulates Oxidative Stress via NRF2/FNIP1 Pathway

Yue Wang,Shixiang Wei,Hui Lian,Lingling Tong,Linhui Yang,Bo Ren,Dongsheng Guo,He Huang

Ophiocordyceps gracilis(O. gracilis) is a parasitic fungus used in traditional Chinese medicine and functional foods. In this study, a neutral heteropolysaccharide (GSP-1a) was isolated from spores ofO. gracilis, and its structure and antioxidant capacities were investigated. GSP-1a was found to have a molecular weight of 72.8 kDa and primarily consisted of mannose (42.28%), galactose (35.7%), and glucose (22.02%). The backbone of GSP-1a was composed of various sugar residues, including →6)-α-D-Manp-(1→, →2,6)-α-D-Manp-(1→, →2,4,6)-α-D-Manp-(1→, →6)-α-D-Glcp-(1→, and →3,6)-α-D-Glcp-(1→, with some branches consisting of →6)-α-D-Manp-(1→ and α-D-Gal-(1→. In vitro, antioxidant activity assays demonstrated that GSP-1a exhibited scavenging effects on hydroxyl radical (•OH), 2,2′-azino-bis-3-ethylbenzothiazoline-6-sulfonic acid radical cation (ABTS•+), and 2,2-diphenyl-1-picrylhydrazyl radical (DPPH•). Moreover, GSP-1a was found to alleviate H2O2-induced oxidative stress in HepG2 cells by reducing the levels of reactive oxygen species (ROS) and malondialdehyde (MDA), while enhancing the activities of superoxide dismutase (SOD). Furthermore, GSP-1a upregulated the mRNA expression of antioxidant enzymes such asHo-1,Gclm, andNqo1, and regulated the NRF2/KEAP1 and FNIP1/FEM1B pathways. The findings elucidated the structural types of GSP-1a and provided a reliable theoretical basis for its usage as a natural antioxidant in functional foods or medicine.Keywords:Ophiocordyceps gracilis;spores;polysaccharide;structural characterization;antioxidant activity

研究领域: 药理学 · 生物化学 · 分子生物学 · 传统中药
✓ 已验证 产品关联 DOI PubMed 高影响因子
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JOURNAL OF THE SCIENCE OF FOOD AND AGRICULTURE · 2023 · IF 4.1

Identification of novel antioxidant collagen-peptides for preventing and treating H2O2-induced oxidative stress in HepG2 cells through in vitro and in silico approaches

Bowei Du,Chao Zhang,Guiya Deng,Shuai Zhang,Shiqi Wang,Yuepeng Guan,Yaqin Huang

Background Nowadays, the prevalence of oxidative stress-related chronic diseases is increasing. The identification of novel antioxidant collagen-peptides to counteract oxidative stress for individuals’ health have gained significant intention. Results In this study, the collagen-peptides with antioxidant activities were separated and identified by ion chromatography (IEC), reversed-phase high-performance liquid chromatography (RP-HPLC), and liquid chromatography-tandem mass spectrometry (LC-MS/MS). The identified antioxidant collagen-peptides were further screened by molecular docking for Keap1-targeted peptide inhibitors and their theoretical interaction mechanisms were investigated. Four novel antioxidant collagen-peptides, GPAGPIGPVG, GPAGPpGPIG, ISGPpGPpGPA and IDGRPGPIGPA with high binding affinity to Keap1 were selected. Molecular docking results demonstrated that the putative antioxidant mechanism of four antioxidant collagen-peptides contributed to their blockage of Keap1-Nrf2 interactions. The results of antioxidant activity of four antioxidant collagen-peptides proved that IDGRPGPIGPA exerted a high scavenging capacity to DPPH and ABTS free radicals, while GPAGPpGPIG improved the resistance of cells to hydrogen peroxide (H 2 O 2 ) induced oxidative damage by promoting the activation of intracellular antioxidant enzymes and the production of reduced glutathione in human hepatoma (HepG2) cells. Conclusion The antioxidant collagen-peptides (GPAGPIGPVG, GPAGPpGPIG, ISGPpGPpGPA and IDGRPGPIGPA) will be developed as the novel functional food for human health in the near future. This article is protected by copyright. All rights reserved.

CAS / MDL: 1898-66-4 28752-68-3
研究领域: 药理学 · 生物化学 · 分子生物学 · 细胞生物学 · 食品科学
✓ 已验证 产品关联 DOI PubMed 高影响因子
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FOOD AND CHEMICAL TOXICOLOGY · 2025 · IF 3.5

Involvement of the PINK1/Parkin signaling pathway in 4-vinylcyclohexene diepoxide-induced ovary toxicity in rats

Yue Che,Xiaozhu Wang,Qian Li,Xiyi Peng,Zhen Liu,Wenhui Xu,Mei Jing,Ting Wang,Jian Gao,Weiling Wang

A B S T R A C T Exposure to 4-vinylcyclohexene diepoxide (VCD) has been associated to reproductive toxicity, However, the dynamic ovarian function alterations over time in rats and the underlying mechanisms remain unclear. This study investigated the effects of VCD on ovarian function in female Sprague-Dawley (SD) rats on the 25, 60 and 135 days after VCD injection and discovered related mechanisms. Our results showed that VCD had little ovotoxicity on the 25 th day, as no significant changes were observed except for the reduction of preantral follicles. However, on the 60 th day and 135 th day, rats exhibited irregular estrous cycles, abnormal serum sex hormone levels, ovarian morphological damage, decreased primordial and preantral follicles, and increased atretic follicles. We further found that on the 60 th and 135 th day, VCD might exert ovotoxicity by decreasing antioxidant enzyme levels, inhibiting of the Kelch-like ECH-associated protein 1 (KEAP1)/nuclear factor erythroid 2-related factor 2 (NRF2) and PTEN-induced putative kinase 1 (PINK1)/E3 ubiquitin ligase (Parkin) signaling pathway. Interestingly, on the 25 th day, KEAP1/NRF2 and PINK1/Parking signaling pathway were activated. This study provided a wider application in using laboratory rodents as a model of ovarian failure and highlighted that VCD-induced ovotoxicity was linked to the regulation of the KEAP1/NRF2 and PINK1/Parkin signaling pathways.

CAS / MDL: 8008-74-0
研究领域: 生殖毒理学 · 分子生物学
✓ 已验证 产品关联 DOI PubMed 高影响因子
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FOOD RESEARCH INTERNATIONAL · 2025 · IF 8

Green preparation of low-molecular-weight galactomannan from Gleditsia sinensis and mechanistic investigation on ameliorating nonalcoholic fatty liver disease

Chi Feng,Xichuang Cheng,Mula Na,Fenglun Zhang,Jiufang Duan,Li Ji,Jianxin Jiang

Galactomannan comes from a wide range of plant resources and has some biological activities, but its bioavailability is limited due to its large molecular weight and complex structure. In this study, three degradation methods (H 2 O 2 , ultrasound, and β-mannanase) combined with ethanol fractional precipitation (25 %, 50 %, and 75 %) were used to degrade and separate Gleditsia sinensis galactomannans (GSG), and the physicochemical properties and biological activities of GSG after degradation were analyzed. Comprehensive comparison indicates that H 2 O 2 exhibits had a better degradation effect. After 4 h of degradation using 4 % H 2 O 2 , the yield of GSG precipitated with 50 % ethanol was 37.06 % (the yield of undigested GSG is 1.80 %). Simultaneously, the molecular weight (reduced from 225.25 to 36.87 kDa) and viscosity were significantly reduced under this condition, while the solubility was increased. In addition, the low-molecular-weight GSG (LGSG) obtained by 4 % H 2 O 2 /50 % ethanol showed the strongest free radical scavenging activity in vitro . Furthermore, the results of in vivo antioxidant assays showed that LGSG inhibited Aflatoxin B1-induced developmental toxicity by regulating gene expression in the Keap1 / Nrf2 pathway. LGSG also promoted Nrf2 -mediated expression of the lipid metabolism genes ppar-α and cpt1 , while suppressing expression of the fatty acid synthesis genes fas and scd-1 . Therefore, the liver recovered from lipid peroxidation induced nonalcoholic fatty liver disease (NAFLD). The present study introduces a method for green and efficient preparation of LGSG, indicates its potential as a nutritional product.

CAS / MDL: 7722-84-1
研究领域: 食品科学 · 生物化学 · 医学
✓ 已验证 产品关联 DOI PubMed 高影响因子
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CHEMICAL ENGINEERING JOURNAL · 2026 · IF 12.5

Chrysanthemum-derived carbon dots alleviate colitis by dual targeting and regulating Keap1/Nrf2 and NF-κB/NLRP3 signaling pathways

Yana Ma,Wen Luo,Weijia Zhu,Zhichao Deng,Shijun Xu,Hang Yuan,Wei-jun Fan,Quanjun Yao,Wei Yao,Ho-Young Song,Mingzhen Zhang,Jizhao Wang,Hongtao Hu

Oxidative stress, resulting from excessive reactive oxygen species (ROS), is critically involved in the development and progression of inflammatory diseases such as inflammatory bowel disease. Therefore, targeting ROS for the treatment of inflammation holds great potential, and the underlying mechanism is of great significance for clinical medication. In this work, carbon dots (C-dots) based on chrysanthemum as carbon source were obtained through a hydrothermal method. The as-prepared C-dots exhibited favorable ROS scavenging capacity and biocompatibility. The ROS level and the oxidative damage were reversed, the expression of proinflammatory factors was reduced, and the disrupted barrier was recovered by chrysanthemum-derived C-dots in the cellular inflammatory model. The anti-inflammatory effects were also validated in mice colitis model. Mechanistically, the chrysanthemum-derived C-dots regulated the Keap1/Nrf2 antioxidant signaling and inhibited the NF-κB/NLRP3 inflammasome-mediated inflammatory signaling, thereby restoring redox homeostasis and modulating the inflammatory microenvironment. Collectively, the C-dots from chrysanthemum with preferable biocompatibility hold a bright prospect in inflammation resolution through remodeling redox and inflammatory microenvironment.

✓ 已验证 DOI 高影响因子
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FOOD RESEARCH INTERNATIONAL · 2025 · IF 8

Antioxidant potential of peptides from poultry hemoglobin via probiotic-assisted hydrolysis: Deciphering mechanisms at the cellular level and through molecular dynamics simulations

Wei Cui,Yong Xie,Yinghui Zhang,Xinlian Su,Tianqi Cui,Xingguang Chen,Zhaoming Wang,Feiran Xu,Hui Zhou,Baocai Xu

Achieving the therapeutic goal of treating diseases by effectively controlling the excessive accumulation of intracellular free radicals is still very challenging, which motivates researchers to develop efficient novel antioxidant peptides from sustainable resources continuously. This study first pioneered a probiotic-assisted enzymatic hydrolysis of hemoglobin, which obtained 149 peptides. Two antioxidant peptides were rapidly screened using advanced molecular dynamics simulation techniques, revealing their molecular interaction mechanisms with Keap1. It was found that GLWGKV occupied six binding sites for Keap1 to form hydrogen bonds with Nrf2, whereas LIVYPW occupied two binding sites, and the binding free energy of GLWGKV to Keap1 was lower binding more stable. Cellular experiments confirmed that GLWGKV up-regulated the expression of related proteins and increased antioxidant enzyme activities, thereby attenuating H 2 O 2 -induced oxidative damage in Caco-2 cells. This research increases the economic added value of animal blood and demonstrates its great potential for development in functional foods.

CAS / MDL:
研究领域: 食品科学 · 生物化学 · 细胞生物学
✓ 已验证 产品关联 DOI PubMed 高影响因子
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NEUROSCIENCE · 2025 · IF 2.8

Formononetin attenuates LPS-induced neuroinflammation and depressive-like behaviors by regulating the Keap1/Nrf2/HO-1 pathway in the hippocampus

Siqi Quan,Mengyuan Li,Zhouli Yue,Hui Liu,Shuaijun Peng,Roujia Guo,Xiaoyan Fang,Yucheng Li

Neuroinflammation and oxidative stress are major pathogenic drivers of depression, with the Keap1/Nrf2/HO-1 pathway serving as a key regulator of both processes. Formononetin (FMN) is a naturally occurring isoflavone with anti-inflammatory and antioxidant activities; however, its potential to exert antidepressant effects through activation of this pathway has not been investigated. In this study, lipopolysaccharide (LPS, 1 mg/kg, i.p.) was used to induce neuroinflammation and depressive-like behaviors in mice, and FMN (20 or 40 mg/kg) was administered for seven days prior to LPS challenge. FMN dose-dependently alleviated LPS-induced behavioral deficits, including reduced sucrose preference, decreased locomotor activity, and prolonged immobility in the tail suspension test. Hematoxylin-eosin (HE) and Nissl staining revealed that FMN markedly attenuated LPS-induced hippocampal neuronal damage. FMN also inhibited microglial activation, as evidenced by reduced Iba-1 expression, decreased NF-κB phosphorylation, and downregulation of both mRNA and protein levels of pro-inflammatory cytokines, including IL-1β, TNF-α, and IL-6. Furthermore, LPS-induced lipid peroxidation was significantly attenuated, as indicated by lower levels of 4-hydroxynonenal (4-HNE). Molecular docking suggested a potential direct interaction between FMN and Keap1, while Western blot analysis confirmed that FMN downregulated Keap1 and upregulated Nrf2 and HO-1 protein expression. Collectively, these findings demonstrate that FMN alleviates LPS-induced neuroinflammation and depressive-like behaviors, likely through activating the Keap1/Nrf2/HO-1 pathway, supporting its potential as a preventive candidate for inflammation-associated depression.

CAS / MDL: 75-80-9
研究领域: 神经药理学 · 分子生物学 · 精神病学 · 炎症研究 · 氧化应激
✓ 已验证 产品关联 DOI PubMed 高影响因子
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Food Bioscience · 2026 · IF 6.2

Valorization of Pinus koraiensis Nut Skin Byproducts: Polyphenols Alleviate Doxorubicin-Induced Cardiotoxicity via the Nrf2/Keap1-Mediated Oxidative Stress Response

Qidong Xue,Kangning Li,Jie Mi,Dekun Cheng,Ruijie Liu,Ming Chang

Doxorubicin (Dox)-induced cardiotoxicity is a major dose-limiting adverse effect of chemotherapy and is closely linked to oxidative stress and impaired endogenous antioxidant defenses. Food-derived polyphenols that reinforce cellular redox resilience may therefore offer a safe adjuvant strategy. Pinus koraiensis nut skin (PNS), an underutilized nut-processing residue, is rich in polyphenols, yet its bioactive profile and cardioprotective mechanism remain insufficiently defined. Here, we optimized the extraction of PNS polyphenols (PNSP), profiled its phytochemical composition, and investigated its protective effects against Dox-induced cardiomyopathy (DIC). Under optimized conditions, PNSP exhibited strong in vitro antioxidant capacity. UPLC-Q-TOF-MS tentatively identified 26 phytochemicals dominated by procyanidins and flavonoids. In a zebrafish DIC model, post-treatment with PNSP (10 – 40 μg/mL) dose-dependently rescued cardiac dysfunction. Notably, 40 μg/mL PNSP restored heart rate from 112.00 ± 24.28 to 157.00 ± 13.98 beats/min and reduced ROS accumulation. Mechanistically, PNSP reactivated endogenous antioxidant enzymes (SOD, GSH-Px) by activating the Nrf2/Keap1 signaling pathway. Procyanidin C1 and the Pinus -specific flavonoid pinobanksin 3-acetate were identified as key ligands that competitively occupy the Keap1 Kelch pocket, thereby facilitating Nrf2 nuclear translocation. This non-covalent, competitive activation mechanism was robustly validated by molecular docking, stable Keap1 protein expression, and enhanced ARE-luciferase reporter activity. Collectively, these findings identify PNSP as a food-relevant Nrf2 activator with potential to mitigate chemotherapy-associated cardiotoxicity, highlighting its potential as a high-value functional food ingredient.

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Antioxidants · 2020 ·Vol. 9 ·期 9 ·783 · IF 5.014

Hippuric Acid Promotes Renal Fibrosis by Disrupting Redox Homeostasis via Facilitation of NRF2–KEAP1–CUL3 Interactions in Chronic Kidney Disease

Bowen Sun,Xifan Wang,Xiaoxue Liu,Longjiao Wang,Fazheng Ren,Xiaoyu Wang,Xiaojing Leng

Chronic kidney disease (CKD) is characterized by the accumulation of protein-bound uremic toxins (PBUTs), which play a pathophysiological role in renal fibrosis (a common pathological process resulting in CKD progression). Accumulation of the PBUT hippuric acid (HA) is positively correlated with disease progression in CKD patients, suggesting that HA may promote renal fibrosis. Oxidative stress is the most important factor affecting PBUTs nephrotoxicity. Herein, we assessed the ability of HA to promote kidney fibrosis by disrupting redox homeostasis. In HK-2 cells, HA increased fibrosis-related gene expression, extracellular matrix imbalance, and oxidative stress. Additionally, reactive oxygen species (ROS)-mediated TGFβ/SMAD signaling contributed to HA-induced fibrotic responses. HA disrupted antioxidant networks by decreasing the levels of nuclear factor erythroid 2-related factor 2 (NRF2), leading to ROS accumulation and fibrotic responses, as evidenced by NRF2 activation and knockdown. Moreover, NRF2 levels were reduced by NRF2 ubiquitination, which was regulated via increased interactions of Kelch-like ECH-associated protein 1 with Cullin 3 and NRF2. Finally, renal fibrosis and redox imbalance promoted by HA were confirmed in rats. Importantly, sulforaphane (NRF2 activator) reversed HA-promoted renal fibrosis. Thus, HA promotes renal fibrosis in CKD by disrupting NRF2-driven antioxidant system, indicating that NRF2 is a potential therapeutic target for CKD.Keywords:hippuric acid;protein-bound uremic toxin;renal fibrosis;oxidative stress;antioxidation;NRF2;NRF2 ubiquitination

CAS / MDL: 133407-82-6
研究领域: 肾病学 · 药理学 · 分子生物学
✓ 已验证 产品关联 DOI PubMed 高影响因子
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Food & Function · 2023 · IF 6.1

High-sulfated derivative of polysaccharide from Ulva pertusa improves Adriamycin-induced nephrotic syndrome by suppressing oxidative stress

Yuzhou Wan,Kexu Chen,Shaopeng Wang,Lin Liu,Xiaoqian Wang,Bo Zhang,Lin Hu,Shunmei Liu,Tingting Zhao,Huimin Qi

Nephrotic syndrome (NS) is characterized by proteinuria, hyperlipidemia, and hypoalbuminemia. Ulva pertusa, a green seaweed, is a nutritional supplement. In this study, the high-sulfated derivative of Ulva pertusa polysaccharide (HU) was prepared by combining U pertusa polysaccharide with chlorosulfonic acid. The NS rat model was established by tail vein single injection of Adriamycin (6.0 mg/kg). Normal rats were used as the control group. NS rat models were treated with HU or U (173 mg/kg/day). After treatment for 6 weeks, we assessed urine protein, renal function, and blood lipids, and observed morphology and histologic injury of the kidney and glomerular microstructure. Furthermore, we detected antioxidant enzyme activity and expression level of the Keap1/Nrf2 signaling pathway to explore the potential mechanism of HU. Results showed that HU not only alleviated hyperlipidemia and hypoalbuminemia, but also reduced urine protein by inhibiting podocyte detachment, thickening of the glomerular basement membrane, and expression of kidney fibrosis markers (collagens Ⅰ and Ⅳ). In addition, HU enhanced antioxidant enzyme activity (GSH-Px, CAT, SOD) in both serum and the kidney, which may be due to upregulating the expression of Nrf2 and downregulating the expression of Keap1. In conclusion, HU appears to be effective in attenuating NS in rats through suppressing oxidative stress by regulating the Keap1/Nrf2 signaling pathway.

CAS / MDL: 25316-40-9
研究领域: 药理学 · 肾病学 · 分子生物学
✓ 已验证 产品关联 DOI PubMed 高影响因子
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Frontiers in Physiology · 2025 · IF 3.4

The multi-protective role of dietary betaine in largemouth bass (Micropterus salmoides): coordinating antioxidant, inflammatory, and metabolic homeostasis under high-fat diet stress

Yi-Jia Liu,Jian Guo,Chang-Da Li,Si-Yin Han,Lu Cai

Introduction Intensive aquaculture frequently utilizes high-fat diets (HF) as a cost-effective strategy, yet this practice often induces hepatic steatosis, oxidative stress, and chronic inflammation in carnivorous fish. Betaine, a natural methyl donor, has shown potential as a functional feed additive, but its comprehensive protective mechanisms under HF stress remain to be fully elucidated. Methods Juvenile largemouth bass (Micropterus salmoides) were fed one of four isonitrogenous diets for 8 weeks: a normal-fat control (Control), a high-fat diet (HF), and two high-fat diets supplemented with 0.5% (HFB0.5) or 1.0% (HFB1) betaine. Growth performance, digestive enzyme activities, serum biochemical parameters, hepatic antioxidant capacity, and the expression of genes related to antioxidant defense, lipid metabolism, and inflammation were analyzed. Results The HF group exhibited significantly impaired growth, digestive function, and antioxidant capacity, along with elevated lipid peroxidation, dyslipidemia, and pro-inflammatory cytokine expression. Betaine supplementation restored growth performance and feed efficiency to control levels, ameliorated digestive enzyme activities (particularly enhancing lipase), and activated the hepatic Nrf2-Keap1 pathway, upregulating antioxidant genes (nrf2, sod1, cat, gpx, ho-1, gr) and enhancing enzyme activities. Betaine also improved serum lipid profiles, upregulated genes related to fatty acid oxidation (pparα, cpt-1) and lipolysis (lpl, hsl), suppressed lipogenic genes (srebp-1, fas), and rebalanced inflammatory cytokines by reducing tnf-α and il-1β while increasing tgf-β1 and il-10. Discussion Dietary betaine effectively counteracts HF-induced metabolic stress in M. salmoides through coordinated multi-pathway regulation. It enhances antioxidant defense, reprograms hepatic lipid metabolism toward catabolism, and restores inflammatory homeostasis. These findings underscore betaine’s role as a multi-functional feed additive capable of mitigating HF-related metabolic disorders and promoting overall health in carnivorous fish aquaculture.

CAS / MDL: 107-43-7
✓ 已验证 产品关联 DOI PubMed 高影响因子
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