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INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES · 2024 · IF 7.7

Immobilization β-glucosidase from Dictyoglomus thermophilum on UiO-66-NH2: An efficient catalyst for enzymatic synthesis of kinsenoside via reverse hydrolysis reaction

Xin Yuan,Jia-Hui Liao,Gui-Jia Du,Yi Hou,Song-Qing Hu

Kinsenoside is a rare and valuable glycoside with extensive bioactivities. However, the enzymatic synthesis of kinsenoside has been a challenging task due to the limited enzyme toolbox and unsatisfactory yield. Herein, the β-glucosidase from Dictyoglomus thermophilum (DtBGL) was heterologously expressed, purified and enzymatically characterized. The purified DtBGL was successfully immobilized on the metal-organic frameworks of UiO-66-NH 2 . The DtBGL@UiO-66-NH 2 was fully characterized using SEM, XRD, TGA and FTIR. The studies on enzymatic properties demonstrated that DtBGL@UiO-66-NH 2 exhibited increased catalytic activity and stability compared to the free DtBGL. Particularly, DtBGL@UiO-66-NH 2 could catalyze the synthesis of kinsenoside via the reverse hydrolysis reaction and the kinsenoside yield was 34.12 % under the optimized catalytic system, which was 1.9-fold higher compared with the free DtBGL. Moreover, DtBGL@UiO-66-NH 2 displayed good reusability with a kinsenoside yield of 27.02 % after reuse for 3 times. The present work not only identifies and characterizes a highly active β-glucosidase with reverse hydrolysis activity, but also proposes the immobilized enzyme as an effective catalyst for the industrial production of glycosides.

研究领域: 生物化学 · 酶学 · 生物催化 · 材料科学
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INTERNATIONAL IMMUNOPHARMACOLOGY · 2024 · IF 4.8

Fraxin (7-hydroxy-6-methoxycoumarin 8-glucoside) confers protection against ionizing radiation-induced intestinal epithelial injury in vitro and in vivo

Feng-Ling Tang,Li-Wei Xie,Lin-Feng Tang,Hai-Yan Lu,Rui-Qiu Zhu,Di-Fan Wang,Ye Tian,Shang Cai,Ming Li

The small intestine exhibits remarkable sensitivity to ionizing radiation (IR), which significantly hampers the effectiveness of radiotherapy in the treatment of abdominal and pelvic tumors. Unfortunately, no effective medications are available to treat radiation-induced intestinal damage (RIID). Fraxin (7-hydroxy-6-methoxycoumarin 8-glucoside), is a coumarin derivative extracted from the Chinese herb Cortex Fraxini. Several studies have underscored the anti-inflammatory, antibacterial, antioxidant, and immunomodulatory properties of fraxin. However, the efficacy of fraxin at preventing or mitigating RIID remains unclear. Thus, the present study aimed to investigate the protective effects of fraxin against RIID in vitro and in vivo and to elucidate the underlying mechanisms. The study findings revealed that fraxin markedly ameliorated intestinal injuries induced by 13 Gy whole abdominal irradiation (WAI), which was accompanied by a significant increase in the population of Lgr5 + intestinal stem cells (ISCs) and Ki67 + progeny. Furthermore, fraxin mitigated WAI-induced intestinal barrier damage, and reduced oxidative stress and intestinal inflammation in mice. Transcriptome sequencing of fraxin-treated mice revealed upregulation of IL-22, a pleiotropic cytokine involved in regulating the function of intestinal epithelial cells. Moreover, in both human intestinal epithelial cells and ex vivo cultured mouse intestinal organoids, fraxin effectively ameliorated IR-induced damage by promoting the expression of IL-22. The radioprotective effects of fraxin were partially negated in the presence of an IL-22-neutralizing antibody. In summary, fraxin is demonstrated to possess the ability to alleviate RIID and maintain intestinal homeostasis , suggesting that fraxin might serve as a strategy for mitigating accidental radiation exposure- or radiotherapy-induced RIID.

CAS / MDL: 524-30-1
研究领域: 放射生物学 · 药理学 · 分子生物学 · 免疫学 · 胃肠病学
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EXPERIMENTAL ANIMALS · 2026 · IF 2

Activation of autophagy through Sirt1/AMPK/mTOR mediates the protective effects of fraxin against insulin resistance and steatosis in rats

Yang LI,Xinchang FENG,Lingpeng ZHENG

Insulin resistance (IR) and hepatic steatosis are key pathological features of type 2 diabetes mellitus (T2DM). Fraxin, a natural flavonoid with potential metabolic regulatory properties, has been proposed to modulate metabolic disorders. This study aimed to investigate whether fraxin protects against IR and steatosis via Sirt1/AMPK/mTOR-mediated autophagy activation. A T2DM rat model was established using high-fat diet (HFD) feeding combined with streptozotocin (STZ) injection. Rats were treated with fraxin (25 or 50 mg/kg) for 4 weeks, followed by assessment of fasting blood glucose (FBG), insulin (FINS), HOMA-IR index, serum lipid profiles and liver function. Histopathological examination (H&E and Oil Red O staining) evaluated hepatic steatosis. BRL 3A cells exposed to palmitic acid (PA) were treated with fraxin (40 or 80 μM), and glucose uptake, lipid accumulation, and protein expression (IRS-1 phosphorylation, GLUT-2 translocation, autophagy markers and Sirt1/AMPK/mTOR pathway components) were analyzed. The specific autophagy inhibitor chloroquine (CQ) was used to verify whether the regulatory effects of fraxin were dependent on autophagy activation. Fraxin significantly reduced FBG, FINS, HOMA-IR, and dyslipidemia in diabetic rats. In PA-treated BRL 3A cells, fraxin enhanced glucose uptake, reduced lipid droplets, and restored IRS-1 phosphorylation and GLUT-2 membrane localization. Mechanistically, fraxin activated autophagy and modulated the Sirt1/AMPK/mTOR pathway, which were abolished by the Sirt1 inhibitor EX527. In conclusion, fraxin alleviates IR and hepatic steatosis in HFD/STZ-induced diabetic rats by activating autophagy through Sirt1/AMPK/mTOR pathway, suggesting its potential as a therapeutic agent for diabetes-associated metabolic disorders.

CAS / MDL: 524-30-1
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