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Evidence-based Complementary and Alternative Medicine · 2015 ·Vol. 2015 ·期 1 ·239749 · IF 1.88

Berberine Nanosuspension Enhances Hypoglycemic Efficacy on Streptozotocin Induced Diabetic C57BL/6 Mice

Zhiping Wang,Junbiao Wu,Qun Zhou,Yifei Wang,Tongsheng Chen

Berberine (Ber), an isoquinoline derivative alkaloid and active ingredient of Coptis, has been demonstrated to possess antidiabetic activities. However its low oral bioavailability restricts its clinical application. In this report, Ber nanosuspension (Ber-NS) composed of Ber and D- α -tocopheryl polyethylene glycol 1000 succinate (TPGS) was prepared by high pressure homogenization technique. Antidiabetic effects of Ber-NS relative to efficacy of bulk Ber were evaluated in streptozotocin (STZ) induced diabetic C57BL/6 mice. The particle size and zeta potential of Ber-NS were 73.1 ± 3.7 nm and 6.99 ± 0.17 mV, respectively. Ber-NS (50 mg/kg) treatment via oral gavage for 8 weeks resulted in a superior hypoglycemic and total cholesterol (TC) and body weight reduction effects compared to an equivalent dose of bulk Ber and metformin (Met, 300 mg/kg). These data indicate that a low dosage Ber-NS decreases blood glucose and improves lipid metabolism in type 2 diabetic C57BL/6 mice. These results suggest that the delivery of Ber as a nanosuspension is a promising approach for treating type 2 diabetes.

研究领域: 药剂学 · 药理学 · 分子药理学 · 药物递送系统 · 糖尿病研究 · 药物代谢 · 纳米医学
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CHEMICAL ENGINEERING JOURNAL · 2026 · IF 12.5

Cascaded catalytic amplification by a phenylboronate ester-based double-network hydrogel for synergistic eradication of multidrug-resistant bacteria and diabetic wound healing

Weiwei Zhang,Jiawen Shao,Xuanjun Zhang,Wanzhen Li,Longbao Zhu,Dongdong Sun,Lisandra L. Martin,Zuchun Zhao,Fei Ge

Glucose oxidase and CuS nanoparticles synergise with NIR photothermal therapy for antibacterial activity. • ROS-responsive GS 128 @HPQ hydrogel generates hydroxyl radicals to trigger controlled drug release. • GS 128 @HPQ hydrogel is self-healing, adhesive and mechanically stable for irregular wound treatment. • GS 128 @HPQ hydrogel accelerates diabetic infected wound healing with excellent biocompatibility. Diabetic chronic wounds are plagued by hyperglycemic microenvironments, multidrug-resistant (MDR) bacterial colonization and biofilm formation. In this study, glucose oxidase (GOx)/ 60 nm CuS nanoparticles were incorporated into an adhesive phenylboronic acid-modified, hyaluronic acid/quaternized chitosan (HA-PBA/QCS) dynamic boronate hydrogel (GS 128 @HPQ). GOx catalyzes glucose to generate H 2 O 2 , and CuS, under 808 nm near-infrared irradiation, acts as a Fenton-like catalyst to generate ·OH and also displays photothermal activity that elevates local temperatures to 45–65 °C in vitro, resulting in a synergistic antibacterial effect. The hydrogel has a porous structure with a pore size of approximately 50 μm, exhibits reactive oxygen species (ROS)-responsive drug release, possesses excellent mechanical properties including favorable rheological behavior, a tensile strength of 140 kPa, and self-healing capacity, and demonstrates adhesion properties ideal for wound dressing applications. In vitro, HA-PBA/QCS showed >98% MDR bacterial and more than 85% biofilm clearance. In diabetic mouse infected wound models, the wound area was <5% on Day21, with a > 70% downregulation of inflammation biomarkers IL-6/TNF-α and upregulation of VEGF/CD31, enables rapid re-epithelialization and collagen maturation, while the hydrogel has a hemolysis rate of less than 5%. This hydrogel provides a safe, efficient, and multifunctional platform for treating chronically infected diabetic wounds. Schematic diagram illustrating the synthesis pathway of the GS 128 @HPQ hydrogel and its application in diabetic wound repair through a combined chemo-photothermal antibacterial strategy. (Created in BioGDP). Download: Download high-res image (169KB) Download: Download full-size image

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INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES · 2026 · IF 8.7

Self-regulating and photothermal nanozyme enhanced hyaluronic acid/gelatin hydrogel with glucose triggered responsive release for diabetic wound healing

Na Yang,Lingling Tang,Huanghe Zeng,Xiaoxiao Wang,Li Huang,Hui Zhang,Xuan Zheng,Zhengyun Ren,Jie Weng,Haopeng Zhang,Tailin Guo

Healing of diabetic wounds is severely hindered by a persistent vicious cycle of bacterial infection and metabolic disorders. Pathological microenvironments, characterized by high glucose levels and excessive reactive oxygen species (ROS), exacerbate chronic inflammation and impede the transition of macrophages toward a pro-healing phenotype. To address these challenges, we developed a multi-stimuli-responsive composite hydrogel platform (GHFA/Cu@TA) by integrating fulvic acid (FA) and copper-tannic acid nanozymes (Cu@TA NPs) into a dynamic covalent network composed of methacrylated gelatin (GelMA) and phenylboronic acid-modified hyaluronic acid (HA-PBA). This platform implements a self-feedback mechanism to restore metabolic homeostasis: glucose-triggered release of Cu@TA NPs effectively scavenges microenvironmental ROS to drive tissue microenvironment remodeling, thereby decelerating responsive hydrogel degradation upon homeostasis normalization to ensure synchronized on-demand drug delivery. Intelligently released FA promotes M2 macrophage polarization to reshape the immune microenvironment, while Cu@TA NPs achieve photothermal biofilm eradication under near-infrared (NIR) light. This “metabolic sensing-feedback regulation-homeostasis reconstruction” strategy offers a distinct therapeutic framework for addressing diabetic wound and contributes to the rational design of bioactive dressings with stimuli responsiveness.

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Small · 2026 · IF 11.8

Engineering EVs Via ZnBGs-Integrated 3D Dynamic Culture for Type II Diabetic Pressure Ulcer Therapy

Zhipeng Sun,Yilin Ding,Xiaolin Chen,Zilin Wu,Yue Huang,Huitong Luo,Xiaodong Cao

Pressure ulcers (PUs) under type II diabetic conditions pose a significant clinical challenge due to damage to the vascular and neural networks, a situation further complicated by sustained mechanical pressure resulting from prolonged patient immobility. While engineered extracellular vesicles (EVs) hold therapeutic potential, conventional production methods face limitations such as rapid drug inactivation, compromised EV structural integrity, and poor scalability. Metal-doped bioactive glass (mBGs) extract induces cellular phenotypic changes through continuous ion release and nanoparticle mineralization, employing a non-genetic, non-destructive approach that preserves the integrity of EVs and enables more stable, directed functional induction. To further facilitate scalable manufacturing without compromising directed functional induction, we coupled ZnBGs extract with 3D dynamic cell culture technology for enhanced EVs production. The resulting 3D-ZnBG-EVs significantly increased protein yield and demonstrated enhanced angiogenic and neurogenic functions, which are mediated via the PI3K-AKT-HIF-1α axis. In a Sprague-Dawley (SD) rat model of type II diabetic pressure ulcers, ZnBG-EVs significantly improved vascular and neural repair, extracellular matrix deposition, collagen maturation, and overall wound closure. This integrated strategy provides a scalable, function-directed platform for EVs-based PUs therapy.

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FITOTERAPIA · 2026 · IF 2.9

Systematic investigation of a Fraxinus mandshurica seed-derived iridoid glucoside fraction as a novel functional ingredient with anti-diabetic potential

Wei Zhou,Haoyu Li,Quan Guo,Shanshan Zhang,Lu Bai,Yu Zhang,Mengjiao Wang,Naisheng Bai,Sen Guo

F. mandshurica seeds improve glucose/lipid metabolism and hepatorenal protection in T2DM mice. • F. mandshurica seeds modulate gut microbiota modulation: reducing Firmicutes/Bacteroidetes ratio and enriching Lactobacillus . • Iridoids are identified as the core bioactive components responsible for the anti-diabetic effects. • The anti-diabetic mechanism involves the regulation of AGE-RAGE and TNF signaling pathways. Fraxinus mandshurica (Oleaceae, Fraxinus ) seeds serve as food and condiments in traditional American and European diets. This study provides the first systematic evaluation of the therapeutic effects of F. mandshurica seed extract on T2DM. This study evaluated the effects of F. mandshurica seed extract on glucose-lipid metabolism, hepatorenal function, and gut microbiota in an HFD/STZ-induced T2DM mouse model. Through UPLC-Q-TOF-MS chemical characterization and phytochemical analysis, combined with network pharmacology and molecular docking techniques, potential active components and their corresponding targets were predicted. Critically, the predicted activity of 18 iridoid monomers was confirmed by evaluating their ability to enhance glucose consumption in L02 cells. F. mandshurica seed extract significantly reduced body weight, TC, TG, and blood glucose levels, improved insulin sensitivity and glucose tolerance, and alleviated hepatorenal injury. Additionally, it regulated the gut microbiota by reducing the Firmicutes/Bacteroidetes ratio. Network pharmacology analysis identified AGE-RAGE and TNF signaling as core anti-diabetic pathways. Key active components, including bisandrographolide A, ligstroside, reptoside, oleuropein, fraxoside, koaburside, and mudanpioside D, were identified and selected for molecular docking. The results indicate that these active components form stable ligand-receptor complexes with target proteins (HRAS, MAPK1, HSP90AA1, MMP9 and AKT1) via hydrogen bonds, hydrophobic interactions, π-π stacking and salt bridges. Finally, 18 iridoid glucosides from the F. mandshurica seed were shown to promote glucose consumption, with efficacy ranging from 7.27% to 71.52%. This study reveals that F. mandshurica seeds and their characteristic iridoid components possess promising prospects as candidates for developing natural anti-diabetic therapeutics. Download: Download high-res image (218KB) Download: Download full-size image

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Bioengineering-Basel · 2026 ·Vol. 13 ·期 7 ·792 · IF 4.4

Adhesive Hydrogel Loaded with Sulfonated Chitosan Promotes Oral Mucosal Defect Repair in Diabetic Rats

Xiaohui Zhang,Gaopeng Wang,Shuwen Ding,Chenyang Luo,Jing Wang

Diabetic oral mucosal wounds exhibit impaired healing and require biomaterials with strong wet adhesion, favorable biocompatibility, and adequate mechanical stability. In this study, an in situ photocurable adhesive hydrogel (ATDS) based on sulfonated chitosan was developed for diabetic oral mucosal wound repair. ATDS exhibited a tensile strength of 50 kPa, an elongation at break of 320%, and an adhesive strength of 0.605 MPa, while also displaying a porous microstructure without obvious cytotoxicity. Compared with hyaluronic acid (HA) gel, which was completely lost by day 3, ATDS provided more durable wound coverage in the oral environment. In a diabetic rat model of oral mucosal defect, ATDS significantly accelerated wound closure, with wounds nearly completely healed by day 6, promoted re-epithelialization as early as day 3, and increased epidermis thickness by approximately 50% compared with the control group. In addition, ATDS enhanced angiogenesis and reduced the expression of the inflammatory cytokines TNF-α and IL-1β. Collectively, these findings demonstrate that ATDS effectively promotes diabetic oral mucosal wound healing through its barrier-protective, pro-angiogenic, and anti-inflammatory effects, highlighting its potential as a promising biomaterial for oral tissue engineering and regenerative applications.

CAS / MDL: 18883-66-4 79-06-1
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CHEMICAL ENGINEERING JOURNAL · 2026 · IF 12.5

Triphasic sequential gas delivery via a photo-instructive hydrogel for enhanced diabetic skin wound healing

Jingwen Dong,Junjie Zhou,Shuguang Huang,Junmei Mu,Ye Tian,Zhifei Ding,Yihui Li,Aiping Wang,Zhanwei Zhou,Zeyu Xu,Minjie Sun

Near infrared light-triggered three-dimensional adaptive release in depth, time and dose for the treatment of diabetic foot ulcers. • A triphasic sequential NO release hydrogel achieves antibacterial, angiogenic and remodeling effects. • Triphasic sequential strategy for adapting NO dosage enhances the NO metabolic microenvironment at the wound condition, ultimately expediting wound healing. Diabetic foot ulcer (DFU) requires spatiotemporal coordinated modulation of the inflammatory response and tissue regeneration process, which is still the bottleneck. Here, a triphasic-sequential hydrogel was explored to tackle the infection treatment and tissue regeneration in DFU. The PDA@B6/L-Arg hydrogel was loaded with near infrared-responsive polydopamine nanoparticles, carrying the nitric oxide (NO) donors for different healing stages. Upon exposure to laser irradiation, 1) the PDA@B6/L-Arg hydrogel rapidly released a substantial amount of nitric oxide (NO) (μM) from N , N ′-di-sec-butyl-N,N′-dinitroso-1,4-phenylenediamine (BNN6), thereby synergistically achieving effective anti-bactericidal and anti-inflammatory effects; 2) L-Arg, as the substrate for nitric oxide synthases NOS, provided the support for deep angiogenesis; 3) the hydrogel degraded, allowing the released L-Arg to penetrate the wound and promote additional extracellular matrix remodeling. Compared to non-sequential NO therapy, PDA@B6/L-Arg hydrogel exhibited spatiotemporal modulation, enhancing the biofilm inhibition and angiogenesis. Furthermore, PDA@B6/L-Arg hydrogel, as a reactive oxygen species-scavenging agent, simultaneously attenuating inflammatory to improve the healing efficiency of chronic wounds, achieving 97.9% closure of infected wounds. It offers a promising therapeutic option for managing diabetic foot ulcers.

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Advanced Healthcare Materials · 2026 · IF 11

Lipase-Activated MnO2 Nanoflowers for Precise Biofilm Imaging and Oxygen-Enhanced Sonodynamic Therapy to Promote Diabetic Wound Healing

Dongqiu Li,Bingyi Xu,Feifei Ren,Jiajing Yu,Yan Tong,Shiwu Deng,Hezhong Jiang

Diabetic wound healing is substantially impaired by biofilm infections, oxidative stress, and persistent hypoxia, which present major challenges for timely diagnosis and treatment. In this study, theranostic nanoparticles (NPs) were engineered to facilitate lipase-triggered biofilm theranostics and accelerate wound healing. Theranostic Mn-TC NPs were prepared by grafting a fluorescent sonosensitizer, meso-tetra (4-carboxyphenyl) porphine (TCPP), onto manganese dioxide (MnO 2 ) nanoflowers, quenching the fluorescence emissions of TCPP. Upon encountering biofilms in vivo, the elevated lipase hydrolyzes ester linkages within the Mn-TC NPs, liberating TCPP to restore its fluorescence emission and enabling the real-time visualization of biofilm-infected wounds. MnO 2 nanoflowers offer abundant reaction sites for TCPP grafting while enhancing the catalysis of hydrogen peroxide to generate oxygen. The boosted oxygen evolution promoted the sonodynamic therapy effect of ultrasound-activated TCPP, achieving 94.0% reduction in biofilm biomass and 99.9% bacterial clearance. Engineering NPs accelerate wound healing by simultaneously eradicating biofilms, modulating inflammatory states, enhancing collagen deposition, and promoting angiogenesis. This study presents a novel theranostic strategy for biofilm-triggered visual imaging and an antibiotic-free therapy for diabetic wounds.

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MOLECULAR PHARMACEUTICS · 2026 · IF 4.9

pH-Responsive Resveratrol Liposomes Targeting Sigma1 Receptor Attenuate Renal Fibrosis by Remodeling the Renal Microenvironment

Ning Yang,Yule Song,Junliang Song,Jian Qin,Mingwei Fu,Feng Yao,Huan Xu

Renal fibrosis (RF), a critical pathogenic mechanism in chronic kidney disease (CKD), now has exceedingly few therapeutic alternatives. This study presents a new sigma1 receptor (σ1R)-targeted nanodelivery system utilizing the natural polyphenolic medicine resveratrol (Res) as a therapeutic agent, addressing its low bioavailability and inadequate targeting properties, thereby providing a significant advancement in the treatment of RF. We engineered and produced a multifunctional material, aminoethyl anisamide-poly(2-ethyl-2-oxazoline)-cholesterol hemisuccinate (APC)-with benefits including active targeting, prolonged circulation, and pH sensitivity. In vitro investigations demonstrated that in the high glucose-induced HK-2 cell fibrosis model, the absorption efficiency of APC-modified liposomes was markedly enhanced, effectively suppressing the expression of fibrotic and inflammatory factors. In two typical animal models of RF, namely diabetic nephropathy and glomerulonephritis, APC@Res demonstrated therapeutic advantages, including modulation of the TGF-β1/Smad3 signaling pathway to impede fibrosis, a notable reduction in oxidative stress levels, enhanced renal function parameters, and diminished expression of inflammatory and fibrotic markers. This study innovatively employs the renal microacidic environment and sigma1 targeting to develop an effective delivery system, offering a novel treatment strategy for reversing RF.

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JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY · 2026 · IF 6.7

Polysaccharide from Ribes nigrum L. Ameliorates Diabetic Kidney Injury in Mice by Modulating the GUDCA/GPBAR1 Axis through the Remodeling of the Gut Microbiota

Ruijiao Zhu,Liuxin Li,Meimei Zhao,Boya Zhang,Ziyi Zhang,Mengcong Li,Lu Yu,Ziwei Song,Ning Gu

Diabetic nephropathy (DN) is a major microvascular complication of diabetes, requiring effective therapies. This study showed polysaccharide from Ribes nigrum L. (blackcurrant polysaccharides (BCP)) exerted therapeutic effects in high-fat diet/streptozotocin-induced diabetic mice, improving glucose homeostasis and alleviating renal inflammation and fibrosis. 16S rRNA sequencing revealed BCP altered gut microbiota and notably enriched Akkermansia muciniphila, which was validated via fecal microbiota transplantation and exogenous A. muciniphila administration. Combined 16S rRNA sequencing and metabolomic analysis identified a positive correlation between A. muciniphila and glycoursodeoxycholic acid (GUDCA). Exogenous A. muciniphila supplementation significantly increased the level of serum GUDCA in DN mice. Elevated GUDCA activated the bile acid receptor GPBAR1 in the kidney, suppressing NF-κB/NLRP3 inflammasome and TGF-β-mediated fibrosis. BCP improves renal outcomes by regulating bile acid metabolism through gut microbiota modulation, supporting its potential as a novel dietary strategy for DN.

CAS / MDL: 18883-66-4 64480-66-6
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iScience · 2026 · IF 4.5

A Platelet-Rich Plasma-Loaded Chitosan-Based Hydrogel for Promoting Type 2 Diabetes Wound Healing

Na Wang,Huirui Zhu,Dongkun Li,Xuena Wang,Ziyan Zhang,Bao Chai,Meining Li,Tao Gong

Hard-healing or non-healing diabetic wounds feature complex pathogenesis, posing significant challenges to clinical treatment. Platelet-rich plasma (PRP) is rich in various growth factors and possesses significant therapeutic potential, while its clinical application is largely limited by the rapid release of these bioactive factors. In this study, a multifunctional hydrogel dressing (GACP@PRP) based on PRP was fabricated for the promotion of type 2 diabetes wound healing via the physical cross-linking of graphene oxide-silver nanoparticles (GO-Ag NPs),chitosan (CS), and poly(N-isopropylacrylamide) (PNIPAM). The wound dressing possesses injectability, self-healing, favorable porosity, water absorption, moisture retention, adhesiveness, antibacterial and hemostatic functionalities. Moreover, the GACP@PRP hydrogel protects PRP to sustain growth factors release, promote cell proliferation and migration, which significantly accelerated wound healing rate in SD rats full-thickness skin defect model. Together with its great biocompatibility and biosafety, GACP@PRP meets the multiple functional requirements of diabetic wound dressing and is promising for clinical diabetic wounds management.

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Frontiers in Pharmacology · 2026 · IF 5.4

Nervonic acid confers neuroprotection in a zebrafish model of diabetic neuropathy by promoting myelin repair and metabolic modulation

Huan Ge,Mingzhu Dai,Qinwen Wang,Bingbing Cao,Ximin Zhu,Jie Guo,Tao Zhang,Shasha Wang,Yiqiao Xu,Lushan Yu

Introduction Diabetic neuropathy (DN) is one of the most common and debilitating complications of type 2 diabetes mellitus (T2DM), yet effective therapeutic strategies remain limited. Nervonic acid (NA) is recognized for its neuroprotective and anti-inflammatory properties. However, its role in DN has not been fully elucidated. In this study, we investigated the protective effects of NA against T2DM-induced DN using a zebrafish model and explored the underlying molecular mechanisms. Methods T2DM was induced in zebrafish larvae through a high-fat, high-glucose diet combined with a low dose of streptozotocin. Larvae were subsequently treated with NA at concentrations of 125, 250, or 500 μg/mL. Motor function, myelin integrity, neutrophil infiltration, and reactive oxygen species (ROS) levels were evaluated using fluorescence imaging and histological staining. Gene expression analysis was performed by quantitative real-time PCR. Metabolomics coupled with KEGG enrichment analysis was applied to identify NA-regulated metabolic pathways. Results NA significantly preserved myelin integrity, reduced neutrophil infiltration, and lowered ROS levels in DN zebrafish. Expression of myelin-related genes ( mbpa and mpz ) was upregulated, while pro-inflammatory cytokines were downregulated following NA treatment. Metabolomic profiling revealed that NA reversed diabetes-associated dysregulation in purine metabolism, energy metabolism, vitamin B6 pathways, and redox homeostasis. Key metabolites including guanosine monophosphate, adenosine triphosphate, pyridoxal 5′-phosphate, and L-glutathione were markedly restored toward normal levels. Discussion These findings demonstrate that NA confers robust neuroprotection in DN by alleviating inflammation and oxidative stress, preserving neuronal structure and function, and reprogramming key metabolic pathways.

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