A Rationally Designed Prodrug for the Fluorogenic Labeling of Albumin and Theranostic Effects on Drug-Induced Liver Injury.

The development of small-molecular fluorogenic tools for the chemo-selective labeling of proteins in live cells is important for the evaluation of intracellular redox homeostasis. Dynamic imaging of human serum albumin (HSA), an antioxidant protein under oxidative stress with concomitant release of antioxidant drugs to maintain redox homeostasis, affords potential opportunities for disease diagnosis and treatment. In this work, we developed a nonfluorogenic prodrug named TPA-NAC, by introducing N-acetyl-l-cysteine (NAC) into a conjugated acceptor skeleton. Through combined thiol and amino addition, coupling with HSA results in fluorescence turn-on and drug release. It was reasoned that the restricted intramolecular motion of the probe under an HSA microenvironment after covalent bonding inhibited the nonradiative transitions. Furthermore, the biocompatibility and photochemical properties of TPA-NAC enabled it to image exogenous and endogenous HSA in living cells in a wash-free manner. Additionally, the released drug evoked upregulation of superoxide dismutase (SOD), which synergistically eliminated reactive oxygen species in a drug-induced liver injury model. This study provides insights into the design of new theranostic fluorescent prodrugs for chemo-selective protein labeling and disease treatments.

Novel isobavachalcone derivatives induce apoptosis and necroptosis in human non-small cell lung cancer H1975 cells.

In this study, seventeen isobavachalcone (IBC) derivatives (1-17) were synthesised, and evaluated for their cytotoxic activity against three human lung cancer cell lines. Among these derivatives, compound 16 displayed the most potent cytotoxic activity against H1975 and A549 cells, with IC50 values of 4.35 and 14.21 µM, respectively. Compared with IBC, compound 16 exhibited up to 4.11-fold enhancement of cytotoxic activity on human non-small cell lung cancer H1975 cells. In addition, we found that compound 16 suppressed H1975 cells via inducing apoptosis and necroptosis. The initial mechanism of compound 16 induced cell death in H1975 cells involves the increasing of Bax/Bcl-2 ratio and Cyt C protein level, down-regulating of Akt protein level, and cleaving caspase-9 and -3 induced apoptosis; the up-regulation of RIP3, p-RIP3, MLKL, and p-MLKL levels induced necroptosis. Moreover, compound 16 also caused mitochondrial dysfunction, thereby decreasing cellular ATP levels, and resulting in excessive reactive oxygen species (ROS) accumulation.

Semi-synthesis and in vitro anti-cancer effects evaluation of novel xanthohumol derivatives.

Xanthohumol (Xn) is a chalcone compound isolated from Humulus lupulus Linn., that has various biological activities. In this study, eight Xn derivatives were synthesized by Williamson, Mannich, Reimer-Tiemann, and Schiff base reactions, and evaluated for their in vitro cytotoxic activity against five human cancer cell lines (MDA-MB-231, MCF-7, CNE-2Z, SMMC-7721, and H1975). Among these compounds, 2-((E)-2,4-dihydroxy-5-((E)-3-(4-hydroxyphenyl)acryloyl)-6-methoxy-3-(3- methylbut-2-en-1-yl)benzylidene)hydrazine-1-carboximidamide (8) exhibited the most potent cytotoxic activity against the five cancer cells, with IC50 values ranging from 4.87 to 14.35 µM. Wound-healing and transwell assays showed that compound 8 inhibited the migration and invasion of MDA-MB-231 cells by down-regulation HIF-1α, MMP-2 and MMP-9 protein expression. We further demonstrated that compound 8 induced apoptosis of MDA-MB-231 cells by increasing of Bax/Bcl-2 ratio and down-regulation of Akt protein expression.

Semisynthesis and in Vitro Anti-cancer Effect of New Magnolol Derivatives on the Cell Proliferation, Apoptosis, Migration, and Invasion of Human Hepatocellular Carcinoma SMMC-7721 Cells.

Four new magnolol derivatives were synthesized and evaluated for their in vitro anti-cancer properties. Among these, compound 3 showed the most potent cytotoxic activity against the SMMC-7721, SUN-449, and HepG2 human hepatocellular carcinoma cell lines, with IC50 values of 3.39, 4.11, and 6.88 µM, respectively. Compound 3 also induced apoptosis of SMMC-7721 cells by down-regulating Bcl-2 and Akt protein levels, up-regulating of Bax protein level, and cleaving caspase-9 and -3. In addition, transwell assays showed that compound 3 significantly suppressed the migration and invasion of SMMC-7721 cells, which was confirmed based on the down-regulation of hypoxia inducible factor-1α (HIF-1α), matrix metalloproteinase-2 and -9 (MMP-2, and MMP-9) protein levels.

Chemoselective Fluorogenic Bioconjugation of Vicinal Dithiol-Containing Proteins for Live Cellular Imaging via Small Molecular Conjugate Acceptors.

To develop small molecular fluorogenic tools for the chemoselective labeling of vicinal dithiol-containing proteins (VDPs) in live cells is important for studying intracellular redox homeostasis. With this research, we developed small molecule-based fluorescent probes, achieving selective labeling of VDPs through thiol-thiol substitutions on bisvinylogous thioester conjugated acceptors (IDAs). Initially, IDAs demonstrated its ability to bridge vicinal cysteine-sulfhydryls on a peptide as a mimic. Then, the peptide complex could be decoupled to recover the original peptide-SH in the presence of dithiothreitol. Furthermore, fluorometric signal amplification of the fluorescent probes occurred with high sensitivity, low limit of detection, and selectivity toward vicinal dithiols on reduced bovine serum albumin, as an example of real world VDPs. More importantly, the probes were utilized successfully for labeling of endogenous VDPs at different redox states in live cells. Thus, the bisvinylogous thioester-based receptor as a functional probe represents a new platform for uncovering the function of VDPs in live cells.

Visualizing Drug Release from a Stimuli-Responsive Soft Material Based on Amine-Thiol Displacement.

In this research, we developed a photoluminescent platform using amine-coupled fluorophores, generated from a single conjugate acceptor containing bis-vinylogous thioesters. Based on the experimental and computational results, the fluorescence turn-on mechanism was proposed to be charge separated induced energy radiative transition for the amine-coupled fluorophore, while the sulfur-containing precursor was not fluorescent since the energy internal conversion occurred through vibrational 2RS- (R represents alkyl groups) as energy acceptor(s). Further utilizing the conjugate acceptor, we establish a new fluorogenic approach via a highly cross-linked soft material to selectively detect cysteine under neutral aqueous conditions. Turn-on fluorescence emission and macroscopic degradation occurred in the presence of cysteine as the stimuli, which can be visually tracked due to the generation of an optical indicator and the cleavage of linkers within the matrix. Furthermore, a novel drug delivery system was constructed, achieving controlled release of sulfhydryl drug (6-mercaptopurine) which was tracked by photoluminescence and high-performance liquid chromatography. The photoluminescent molecules developed herein are suitable for visualizing polymeric degradation, making them suitable for additional "smart" material applications.

Expression level of miR-383-5p in colorectal cancer patients following neoadjuvant chemotherapy and its clinical significance in the prognosis.

BACKGROUND: This study aimed to detect expression level of microRNA-383-5p (miR-383-5p) in colorectal cancer (CRC) patients following chemotherapy and its potential influence on the prognosis in CRC. METHODS: A total of 150 CRC patients treated in The First Affiliated Hospital of Heilongjiang University of Chinese Medicine from June 2016 to July 2019 were included. All patients were preoperatively treated with neoadjuvant chemotherapy. Serum levels of miR-383-5p in CRC patients before and after neoadjuvant chemotherapy were detected by reverse transcriptase-polymerase chain reaction (RT-PCR). Univariable and multivariate unconditioned Cox hazard analyses were conducted to assess risk factors for prognosis in CRC patients. The prognostic value of miR-383-5p in CRC was examined by depicting Kaplan-Meier curves. RESULTS: Overexpression of miR-383-5p could enhance the sensitivity of neoadjuvant chemotherapy in CRC patients. Its level was closely related to differentiation, TNM staging, lymphatic metastasis and vascular infiltration in CRC. Cox hazard analyses demonstrated that stage III+IV, lymphatic metastasis, vascular invasion and low serum level of miR-383-5p were risk factors for prognosis in CRC patients. High level of miR-383-5p was favorable to the overall survival in CRC. CONCLUSIONS: MiR-383-5p is lowly expressed in serum of CRC patients. Upregulation of miR-383-5p is beneficial to the therapeutic efficacy of neoadjuvant chemotherapy and the prognosis in CRC.

Efficient Co-production of Docosahexaenoic Acid Oil and Carotenoids in Aurantiochytrium sp. Using a Light Intensity Gradient Strategy.

Aurantiochytrium is a promising source of docosahexaenoic acid (DHA) and carotenoids, but their synthesis is influenced by environmental stress factors. In this study, the effect of different light intensities on the fermentation of DHA oil and carotenoids using Aurantiochytrium sp. TZ209 was investigated. The results showed that dark culture and low light intensity conditions did not affect the normal growth of cells, but were not conducive to the accumulation of carotenoids. High light intensity promoted the synthesis of DHA and carotenoids, but caused cell damage, resulting in a decrease of oil yield. To solve this issue, a light intensity gradient strategy was developed, which markedly improved the DHA and carotenoid content without reducing the oil yield. This strategy produced 30.16 g/L of microalgal oil with 15.11 g/L DHA, 221 µg/g astaxanthin, and 386 µg/g ß-carotene. This work demonstrates that strain TZ209 is a promising DHA producer and provides an efficient strategy for the co-production of DHA oil together with carotenoids.

Two new alkaloids produced by Dothideomycetes sp. BMC-101 isolated from the Magnolia grandiflora.

AbstactA total of 16 fungal strains were isolated from fresh leaves and flowers of Magnolia grandiflora and the EtOAc extracts of them were assayed for antitumor activities. Among these, the fungus Dothideomycetes sp. BMC-101 with broad spectrum inhibition was selected for further study. Four alkaloids (1-4) including two new compounds (2-(hydroxyimino)-3-phenylpropanoyl)-L-phenylalanine (1) and 8-Acetyl-bisdethiobis(methylsulfanyl)apoaranotin (4)) were isolated from Dothideomycetes sp. BMC-101. The structure of 1 was characterized with an oxime moiety formed by the condensation of two phenylalanines. To our knowledge, this is the first report on a fungal phenylalanine derivative with an oxime moiety.

Isobavachalcone Induces Multiple Cell Death in Human Triple-Negative Breast Cancer MDA-MB-231 Cells.

Standardized treatment guidelines and effective drugs are not available for human triple-negative breast cancer (TNBC). Many efforts have recently been exerted to investigate the efficacy of natural compounds as anticancer agents owing to their low toxicity. However, no study has examined the effects of isobavachalcone (IBC) on the programmed cell death (PCD) of human triple-negative breast MDA-MB-231 cancer cells. In this study, IBC substantially inhibited the proliferation of MDA-MB-231 cells in concentration- and time-dependent manners. In addition, we found that IBC induced multiple cell death processes, such as apoptosis, necroptosis, and autophagy in MDA-MB-231 cells. The initial mechanism of IBC-mediated cell death in MDA-MB-231 cells involves the downregulation of Akt and p-Akt-473, an increase in the Bax/Bcl-2 ratio, and cleaved caspases-3 induced apoptosis; the upregulation of RIP3, p-RIP3 and MLKL induced necroptosis; as well as a simultaneous increase in LC3-II/I ratio induced autophagy. In addition, we observed that IBC induced mitochondrial dysfunction, thereby decreasing cellular ATP levels and increasing reactive oxygen species accumulation to induce PCD. These results suggest that IBC is a promising lead compound with anti-TNBC activity.

Isolation, identification, and pathogenicity of a ALV-K strain from Chinese indigenous chicken breed.

Subgroup K avian leukosis virus (ALV-K) is a new subgroup of avian leukosis virus (ALV) first identified in Chinese indigenous chickens in recent years. In this study, an ALV-K strain was isolated from Luhua chicken in Shandong province, China, and designated SD20LH01. The full-length genomic sequence of SD20LH01 was 7491 bp, which had the highest homology with ALV-K reference strains GDFX0601, GDFX0602 and GDFX0603. The nucleotide homology of env gene of SD20LH01 with reference strains of subgroup A, B, C, D, E, and J was ranged from 57.1 to 93.2%, while 94.1 to 99.4% with other ALV-K reference strains. The nucleotide difference of SD20LH01 mainly clustered with gp85 gene and U3 sequence when compared with the reference strain of ALV-K. In order to investigate the pathogenicity of SD20LH01, SPF chicken embryos were infected by yolk sac inoculation, and 1-day-old chickens were infected by intraperitoneal inoculation of SD20LH01. The results showed that yolk sac inoculation of SD20LH01 could induce persistent viremia, growth retardation and reduce the immune response to NDV and AIV-H9 vaccines. However, intraperitoneal inoculation in 1-day-old chickens could only induce a low level of viremia. In addition, no tumors were found in infected chickens during the animal experiments. This study enriched the genomic sequence data of ALV-K isolated in Chinese indigenous chickens, and laid a foundation for further study on the pathogenesis and prevention of ALV-K.

Clay-hydrochar composites return to cadmium contaminated paddy soil: Reduced Cd accumulation in rice seed and affected soil microbiome.

Excess cadmium (Cd) in rice precipitated by Cd contamination in paddy soils is a global human health threat and rational response is urgently needed. In this study, attapulgite-modified hydrochar (CA) and the montmorillonite-modified hydrochar (CM) were utilized in Cd-contaminated paddy soils at 0.5% (w/w) and 1% (w/w) application rates to investigate the effects of these clay-hydrochar composites on rice growth and soil Cd availability. The results show that the utility of CA and CM resulted in a significant increase in rice yield, especially at 1% application rate, which extended rice yield by 46.7-50.0% compared to 0.5% application rate. This is related to the Cd fixation and nutrient sequestration of the acidic functional groups on the surface of CA and CM. Additionally, CA-1% and CM-1% reduced the Cd concentration in rice seeds by 26.9-28.1% relative to the control. Notably, CA-1% showed the capacity to passivate Cd at the early stage of rice transplanting, lowering the proportion of Cd in the ion exchange state by 41.6% compared to the control, and this passivation effect persisted until the late stage of transplanted rice. The soil microbial community consequences showed that CA and CM did not significantly change the horizontal composition of the soil bacterial phylum and species diversity, indicating that CA and CM had excessive soil microbial adaptability. Moreover, results of correlation and Canonical Correspondence Analysis confirm that microbial genera responded significantly to the soil Cd morphologies, revealing the importance of CA and CM in the remediation of Cd-contaminated soils by influencing microorganisms. Our findings provide clay-hydrochar composites as a low-cost approach to effectively mitigate soil Cd contamination and improve the security and quality of rice.

Anti-Cancer Properties of Ginkgolic Acids in Human Nasopharyngeal Carcinoma CNE-2Z Cells via Inhibition of Heat Shock Protein 90.

Ginkgo biloba L. has been used in traditional Chinese medicine (TCM) for thousands of years. However, the anti-cancer properties of ginkgolic acids (GAS) isolated from G. biloba have not been investigated in human nasopharyngeal carcinoma cells. In this study, GAS exhibited an inhibitory effect on the ATPase activity of heat shock protein 90 (Hsp90) and anti-proliferative activities against four human cancer cell lines, with IC50 values ranging from 14.91 to 23.81 µg·mL-1. In vivo experiments confirmed that GAS inhibited tumor growth in CNE-2Z cell-xenografted nude mice with low hepatotoxicity. We further demonstrated that GAS suppressed migration and invasion and induced the apoptosis of CNE-2Z cells by inducing the degradation of Hsp90 client proteins (MMP-2, MMP-9, Her-2, c-Raf, Akt, and Bcl-2). Together, GAS are new Hsp90 inhibitors by binding to Hsp90 (hydrogen bond and hydrophobic interaction). Thus, GAS from G. biloba might represent promising Hsp90 inhibitors for the development of anti-nasopharyngeal carcinoma agents.

Effect of metal decoration on sulfur-based gas molecules adsorption on phosphorene.

Based on first-principles calculation, the adsorption of sulfur-based gas molecules (H2S, SO2, SO3) on various metal-decorated phosphorenes is researched systematically. Eleven metals (Li, Na, K, Rb, Cs, Ca, Sr, Ba, Ni, La, Tl) which can avoid the formation of clusters on the phosphorene are considered. Noticeably, all metal decorations can enhance the adsorption strength of phosphorene to sulfur-based gas molecules except for H2S on Tl-decorated phosphorene. Meanwhile, the adsorption energy (Eads) shows the trend of Eads(H2S) < Eads(SO2) < Eads(SO3) for the same metal decoration case. In addition, some metal-decorated phosphorene systems exhibit intriguing magnetic and electrical variation after sulfur-based gas molecule adsorptions, indicating that these systems are promising to be candidates for the detection and removal of sulfur-based gas molecules.

Semi-Synthesis and In Vitro Anti-Cancer Evaluation of Magnolol Derivatives.

Magnolol (MAG), a biphenolic neolignan, has various biological activities including antitumor effects. In this study, 15 MAG derivatives were semi-synthesized and evaluated for their in vitro anticancer activities. From these derivatives, compound 6a exhibited the best cytotoxic activity against four human cancer cell lines, with IC50 values ranging from 20.43 to 28.27 µM. Wound-healing and transwell assays showed that compound 6a significantly inhibited the migration and invasion of MDA-MB-231 cells. In addition, Western blotting experiments, performed using various concentrations of 6a, demonstrated that it downregulates the expression of HIF-1α, MMP-2, and MMP-9 in a concentration-dependent manner. Overall, these results suggest that substituting a benzyl group having F atoms substituted at the C2 position on MAG is a viable strategy for the structural optimization of MAG derivatives as anticancer agents.

LINGO-1 regulates Wnt5a signaling during neural stem and progenitor cell differentiation by modulating miR-15b-3p levels.

BACKGROUND: Manipulation of neural stem and progenitor cells (NSPCs) is critical for the successful treatment of spinal cord injury (SCI) by NSPC transplantation, since their differentiation into neurons and oligodendrocytes can be inhibited by factors present in inflamed myelin. In this study, we examined the effects of LINGO-1 on spinal cord-derived NSPC (sp-NSPC) differentiation, the underlying mechanisms of action, and the functional recovery of mice after transplantation of manipulated cells. METHODS: sp-NSPCs were harvested from female adult C57/BL6 mice after SCI induced with an NYU impactor. These cells were infected with lentiviral vectors containing LINGO-1 shRNA sequence or a scrambled control and transplanted into SCI mice. Tuj-1- and GFAP-positive cells were assessed by immunofluorescence staining. Wnt5a, p-JNK, JNK, and ß-catenin expression was determined by Western blot and RT-qPCR. miRNAs were sequenced to detect changes in miRNA expression. Motor function was evaluated 0-35 days post-surgery by means of the Basso Mouse Scale (BMS) and by the rotarod performance test. RESULTS: We discovered that LINGO-1 shRNA increased neuronal differentiation of sp-NSPCs while decreasing astrocyte differentiation. These effects were accompanied by elevated Wnt5a protein expression, but unexpectedly, no changes in Wnt5a mRNA levels. miRNA-sequence analysis demonstrated that miR-15b-3p was a downstream mediator of LINGO-1 which suppressed Wnt5a expression. Transplantation of LINGO-1 shRNA-treated sp-NSPCs into SCI mice promoted neural differentiation, wound compaction, and motor function recovery. CONCLUSIONS: LINGO-1 shRNA promotes neural differentiation of sp-NSPCs and Wnt5a expression, probably by downregulating miR-15b-3p. Transplantation of LINGO-1 shRNA-treated NSPCs promotes recovery of motor function after SCI, highlighting its potential as a target for SCI treatment.

The Effect of Hispidulin, a Flavonoid from Salvia plebeia, on Human Nasopharyngeal Carcinoma CNE-2Z Cell Proliferation, Migration, Invasion, and Apoptosis.

Nasopharyngeal carcinoma (NPC) is a common malignant head and neck tumor. Drug resistance and distant metastasis are the predominant cause of treatment failure in NPC patients. Hispidulin is a flavonoid extracted from the bioassay-guided separation of the EtOH extract of Salvia plebeia with strong anti-proliferative activity in nasopharyngeal carcinoma cells (CNE-2Z). In this study, the effects of hispidulin on proliferation, invasion, migration, and apoptosis were investigated in CNE-2Z cells. The [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide] (MTT) assay and the colony formation assay revealed that hispidulin could inhibit CNE-2Z cell proliferation. Hispidulin (25, 50, 100 µM) also induced apoptosis in a dose-dependent manner in CNE-2Z cells. The expression of Akt was reduced, and the expression of the ratio of Bax/Bcl-2 was increased. In addition, scratch wound and transwell assays proved that hispidulin (6.25, 12.5, 25 µM) could inhibited the migration and invasion in CNE-2Z cells. The expressions of HIF-1α, MMP-9, and MMP-2 were decreased, while the MMPs inhibitor TIMP1 was enhanced by hispidulin. Moreover, hispidulin exhibited potent suppression tumor growth and low toxicity in CNE-2Z cancer-bearing mice at a dosage of 20 mg/kg/day. Thus, hispidulin appears to be a potentially effective agent for NPC treatment.

Screening of highly effective mixed natural antioxidants to improve the oxidative stability of microalgal DHA-rich oil.

Docosahexaenoic acid (DHA)-rich oil sourced from microalgae can easily become oxidized. The objective of this work was to screen the optimal natural antioxidant mixture for protecting DHA-rich oil. Different natural antioxidants, encompassing tea polyphenols, natural vitamin E, rosemary extract, licorice root antioxidant, ascorbyl palmitate and lecithin were tested individually and in combination in an accelerated oxidation process. Three antioxidants namely natural vitamin E, rosemary extract and ascorbyl palmitate with synergistic effects were chosen, and their concentrations were further optimized using response-surface methodology. The highest antioxidants activity of 16.1740 was obtained with a combination of 0.0224% vitamin E, 0.0259% rosemary extract and 0.0166% ascorbyl palmitate, which prolonged the time until oxidation induction to 20.21 days. The mixed natural antioxidants showed a similar antioxidant effect to 0.02% tert-butylhydroquinone and was better than 0.02% butylated hydroxyanisole. These data indicate that the mixed natural antioxidants optimized in this work can be directly applied in the protection of commercial microalgal DHA-rich oil.

Paeoniflorin inhibited nod-like receptor protein-3 inflammasome and NF-κB-mediated inflammatory reactions in diabetic foot ulcer by inhibiting the chemokine receptor CXCR2.

Diabetic foot ulcer (DFU) is an invariably common complication of diabetes, characterized by delayed wound healing process and increased inflammation. Evidence has indicated that paeoniflorin exerts an anti-inflammatory effect in diabetic retinopathy. The current work was aimed to investigate the effect of paeoniflorin on inflammation and wound healing in DFU. DFU rat models by streptozotocin and skin biopsy punch, as well as high glucose-treated human immortalized keratinocytes (HaCaT) were established. Levels of blood glucose, wound contraction and proinflammatory cytokine were detected after paeoniflorin administration. Several essential targets associated with the NF-κB and Nod-like receptor protein-3 (NLRP3) signaling pathways were examined. Results showed markedly down-regulation of interleukin (IL)-1ß, IL-18 and tumor necrosis factor-alpha in paeoniflorin-treated DFU rats. Paeoniflorin decreased the expression levels of chemokine receptor CXCR2, nuclear NF-κB and p-IκB (Ser36), as well as increased IκB level. Histological analysis and immunostaining showed lower inflammatory cells with decreased NLRP3 and cleaved caspase-1 levels following paeoniflorin treatment. Further in vitro evidence confirmed that paeoniflorin efficiently inhibited NLRP3 and NF-κB-mediated inflammation in DFU by inhibiting CXCR2. These findings are suggestive of greatly attenuated wound inflammation and better wound healing in paeoniflorin-treated DFU rats. Our study demonstrates that paeoniflorin is a potential therapeutic agent for DFU.

Paeoniflorin accelerates foot wound healing in diabetic rats though activating the Nrf2 pathway.

As one of the most frequent diabetic complications, diabetic foot ulcer (DFU) can cause limb ischemia or even amputation. Paeoniflorin (PF) has been reported to possess many kinds of biological functions, such as antioxidant and anti-inflammatory effects. However, the role of PF in DFU remains unknown. In this study, streptozotocin (STZ)-induced diabetic rat models and high glucose (HG)-treated Human immortalized keratinocytes (HaCaT) cells were established. Histological analysis, immunohistochemistry, Electrophoretic mobility shift assay, MTT assay, TUNEL assay, oxidative stress analysis, ELISA assay and western blot were used to investigate the role and underlying mechanisms of PF on healing in DFU. Our results showed that the STZ-induced diabetic rats had delayed wound healing compared with the normal rats, exhibited by intense oxidative DNA damage, low vascular endothelial growth factor (VEGF) and transforming growth factor ß1 (TGF-ß1) expression, as well as increased apoptosis. PF treatment activated the expression of nuclear factor-E2-related factor 2 (Nrf2) and improved wound healing in DFU rats. Our in vitro experiments confirmed that PF accelerated wound healing through the Nrf2 pathway under hyperglycemic conditions, with alleviated oxidative stress, increased cell proliferation and migration, decreased apoptosis, and increased the expression of VEGF and TGF-ß1. Our study demonstrates the therapeutic benefits of PF in diabetic wound healing, which provides a reference for future clinical trials using PF in DFU treatment.