Search

Glioblastoma (GBL) is one of the more malignant primary brain tumors; it is currently treated by a multimodality strategy including surgery, and radio- and chemotherapy, mainly consisting of temozolomide (TMZ)-based chemotherapy. Tumor relapse often occurs due to the establishment of TMZ resistance, with a patient median survival time of <2 years. The identification of natural molecules with strong anti-tumor activity led to the combination of these compounds with conventional chemotherapeutic agents, developing protocols for integrated anticancer therapies. Curcumin (CUR), resveratrol (RES), and its glucoside polydatin (PLD) are widely employed in the pharmaceutical and nutraceutical fields, and several studies have demonstrated that the combination of these natural products was more cytotoxic than the individual compounds alone against different cancers. Some of us recently demonstrated the synergistic efficacy of the sublingual administration of a new nutraceutical formulation of CUR+PLD in reducing tumor size and improving GBL patient survival. To provide some experimental evidence to reinforce these clinical results, we investigated if pretreatment with a combination of CUR+PLD can improve TMZ cytotoxicity on GBL cells by analyzing the effects on cell cycle, viability, morphology, expression of proteins related to cell proliferation, differentiation, apoptosis or autophagy, and the actin network. Cell viability was assessed using the MTT assay or a CytoSmart cell counter. CalcuSyn software was used to study the CUR+PLD synergism. The morphology was evaluated by optical and scanning electron microscopy, and protein expression was analyzed by Western blot. Flow cytometry was used for the cell cycle, autophagic flux, and apoptosis analyses. The results provide evidence that CUR and PLD, acting in synergy with each other, strongly improve the efficacy of alkylating anti-tumor agents such as TMZ on drug-resistant GBL cells through their ability to affect survival, differentiation, and tumor invasiveness. [ABSTRACT FROM AUTHOR]

Various materials have been used to promote human dental pulp stem cells (hDPSCs) differentiation to produce dentin bridge formation with less-than-optimal results. Polydatin (PD), a naturally present material with osteogenic properties can be a promising material in the pulp regeneration/repair process. The aim of this study was to evaluate the effect of (PD) on the viability and differentiation of human dental pulp stem cells. PD effect on hDPSCs in terms of cellular viability, alkaline phosphatase (ALP) production, and messenger RNAs (mRNA) of odontogenic markers production using quantitative reverse transcription polymerase chain reaction (RT-qPCR) were evaluated. In addition, mineral deposits were detected with Alizarin red stain. The viable hDPSCs in the presence of 0.01 μM and 0.1 μM PD were significantly higher than the control on days 3 and 7, respectively. In addition, ALP activity of hDPSCs was significantly increased with 0.01, 0.1, and 1 μM of PD. In addition, increased expression mRNAs of ALP, osteocalcin (OC), osteonectin (ON), osteopontin (OP), Runt-related transcription factor-2 (RUNX-2), dentin sialophosphoprotein (DSPP), and dentin matrix protein-1 (DMP-1) was observed after PD treatment, however, the difference was not statistically significant. Furthermore, increased size of mineral deposits was observed with PD. PD promoted the expression of markers associated with odontogenic differentiation and mineralized tissue deposition in hDPSCs. [ABSTRACT FROM AUTHOR]

Objective: This study aims to investigate the inhibitory effect of Polydatin (PD) on endoplasmic reticulum (ER) stress following subarachnoid hemorrhage (SAH) and to elucidate the underlying mechanisms. Methods: A standard intravascular puncture model was established to mimic SAH in mice. Neurological functions were assessed using neurological scoring, Grip test, and Morris water maze. Brain edema and Evans blue extravasation were measured to evaluate blood-brain barrier permeability. Western blot and quantitative real-time polymerase chain reaction (PCR) analyses were performed to examine protein and mRNA expressions related to ER stress. Terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) staining was used to detect cell apoptosis, and transmission electron microscopy was used to observe the ultrastructure of the endoplasmic reticulum. Results: The results indicated that PD significantly reduced brain edema and Evans blue extravasation after SAH, improving neurological function. Compared to the SAH group, the expression levels of ER stress-related proteins including glucose-regulated protein 78 (GRP78), phosphorylated protein kinase R-like endoplasmic reticulum kinase (p-PERK), phosphorylated eukaryotic initiation factor 2α (p-eIF2α), activating transcription factor 4 (ATF4), and C/EBP homologous protein (CHOP), were significantly lower in the PD-treated group. Moreover, PD significantly enhances the protein expression of Sirtuin 1 (SIRT1). Validation with sh-SIRT1 confirmed the critical role of SIRT1 in ER stress, with PD's inhibitory effect on ER stress being dependent on SIRT1 expression. Additionally, PD attenuated ER stress-mediated neuronal apoptosis and SAHinduced ferroptosis through upregulation of SIRT1. Conclusion: PD alleviates ER stress following SAH by upregulating SIRT1 expression, thereby mitigating early brain injury. The protective effects of PD are mediated through SIRT1, which inhibits ER stress and reduces neuronal apoptosis and ferroptosis. [ABSTRACT FROM AUTHOR]

Background/purpose: Various materials have been used to promote human dental pulp stem cells (hDPSCs) differentiation to produce dentin bridge formation with less-than-optimal results. Polydatin (PD), a naturally present material with osteogenic properties can be a promising material in the pulp regeneration/repair process. The aim of this study was to evaluate the effect of (PD) on the viability and differentiation of human dental pulp stem cells. Materials and methods: PD effect on hDPSCs in terms of cellular viability, alkaline phosphatase (ALP) production, and messenger RNAs (mRNA) of odontogenic markers production using quantitative reverse transcription polymerase chain reaction (RT-qPCR) were evaluated. In addition, mineral deposits were detected with Alizarin red stain. Results: The viable hDPSCs in the presence of 0.01 μM and 0.1 μM PD were significantly higher than the control on days 3 and 7, respectively. In addition, ALP activity of hDPSCs was significantly increased with 0.01, 0.1, and 1 μM of PD. In addition, increased expression mRNAs of ALP, osteocalcin (OC), osteonectin (ON), osteopontin (OP), Runt-related transcription factor-2 (RUNX-2), dentin sialophosphoprotein (DSPP), and dentin matrix protein-1 (DMP-1) was observed after PD treatment, however, the difference was not statistically significant. Furthermore, increased size of mineral deposits was observed with PD. Conclusion: PD promoted the expression of markers associated with odontogenic differentiation and mineralized tissue deposition in hDPSCs.

Background: Considering the complex pathological mechanisms behind spinal cord injury (SCI) and the adverse effects of present non-approved drugs against SCI, new studies are needed to introduce novel multi-target active ingredients with higher efficacy and lower side effects. Polydatin (PLD) is a naturally occurring stilbenoid glucoside recognized for its antioxidative and anti-inflammatory properties. This study aimed to assess the effects of PLD on sensory-motor function following SCI in rats. Methods: Following laminectomy and clip compression injury at the thoracic 8 (T8)-T9 level of the spinal cord, rats were randomly assigned to five groups: Sham, SCI, and three groups receiving different doses of PLD treatment (1, 2, and 3 mg/kg). Over 4 weeks, behavioral tests were done such as von Frey, acetone drop, hot plate, Basso-Beattie-Bresnahan, and inclined plane test. At the end of the study, changes in catalase and glutathione activity, nitrite level, activity of matrix metalloproteinase 2 (MMP2) and MMP9 as well as spinal tissue remyelination/neurogenesis, were evaluated. Results: The results revealed that PLD treatment significantly improved the behavioral performance of the animals starting from the first week after SCI. Additionally, PLD increased catalase, and glutathione levels, and MMP2 activity while reduced serum nitrite levels and MMP9. These positive effects were accompanied by a reduction in the size of the lesion and preservation of neuronal count. Conclusion: In conclusion, PLD showed neuroprotective effects in SCI rats by employing anti-inflammatory and antioxidant effects, through which improve sensory and motor function. [ABSTRACT FROM AUTHOR]

Objective: To investigate the improvement effect of polydatin on atherosclerotic (AS) plaque and endothelial inflammation in AS rats by inhibiting transforming growth factor β( TGF-β)/Smad signaling pathway. Methods: Sixty rats were randomly divided into blank control group, model control group, low, medium and high dose polydatin groups and positive control group, with 10 rats in each group. The rats in the normal control group were fed with ordinary feed, and the rats in the other groups were used to prepare AS rat models by feeding with high-fat feed and intraperitoneally injected with vitamin D3. The rats in the low-dose, mediumdose and high-dose polydatin groups were given 40, 80 and 160 mg/kg of polydatin by gavage every day, the rats in the positive control group were given 5 mg/kg of simvastatin by gavage every day, and the rats in the model control group and the blank control group were given the same amount of normal saline by gavage every day. After the administration, oil red O staining was used to observe the formation of AS plaque in the rat aorta; automatic biochemical analyzer was used to detect the levels of rat triglyceride (TG), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), and high-density lipoprotein cholesterol (HDL-C); enzyme-linked immunosorbent assay was used to detect the contents of tumor necrosis factor (TNF)-α, IL-6, IL-8, C-reactive protein (CRP), monocyte chemoattractant protein 1 (MCP-1), homocysteine (Hcy), intercellular adhesion molecule 1 (ICAM-1) and endothelin-1 (ET-1) in serum; Western blot was used to detect the protein expression levels of TGF-β1, Smad2/3 and p-Smad2/3 in rats. Results: Compared with blank control group, a large number of AS plaques appeared on the inner wall of the aorta in the model control group, the levels of TG, TC, LDL-C, TNF-α, IL-6, IL-8, CRP, MCP-1, Hcy, ICAM and ET-1 in the serum were significantly increased, the level of HDL-C was significantly reduced, and the expression of TGF-β1 protein and the of p-Smad2/3/Smad2/3 in aortic tissue were significantly increased (P<0.05). The plaque area on the inner wall of the aorta of AS rats was significantly reduced after the intervention of polydatin, the levels of TG, TC, LDL-C, TNF-α, IL-6, IL-8, CRP, MCP-1, Hcy, ICAM, and ET-1 in the serum were significantly reduced, the level of HDL-C was significantly increased, the expression of TGF-β1 protein and the p-Smad2/3/Smad2/3 in aortic tissue were significantly reduced (P<0.05), and the changes of the above indexes were all dose-dependent (P<0.05). The levels of TC, LDL-C and HDL-C in the positive control group were not significantly different from those in the high dose polydatin group (P> 0.05), while the other indexes were lower than those in the high dose polydatin group (P<0.05). Conclusion: Polydatin regulates blood lipids and reduces the expression of cellular inflammatory factors to reduce the formation of AS plaques and improve inflammation in AS rats, and the mechanism is related to the inhibition of the TGF-β/Smad signaling pathway. [ABSTRACT FROM AUTHOR]

Objective The aim of this study was to compare the interventional effects of polydatin given by different administration modes on experimental silicosis rats. Methods Fifty SPF SD rats were randomly divided into five groups, namely the control group, silica model group, polydatin inhalation group, polydatin gavage group, and polydatin intraperitoneal injection group. There were 10 rats in each group. Among them, the control group did not have any treatment, the model group was only treated with silica molding, and the other 3 groups were treated with polydatin via different administration methods after silica molding. The general condition of rats in each group and the lung coefficient of each group were observed at 28 days and 56 days after dust treatment. Paraffin sections of rat lung tissue were stained with hematoxylin-eosin (HE) and Masson staining. The kit was used to detect the content of hydroxyproline (HYP) and malondialdehyde (MDA) in the lung tissue of rats in each group, and the degree of lung inflammation and pulmonary fibrosis in each group of rats was evaluated. Results At day 56 after dust exposure, the lung coefficient of rats in the model group was significantly increased (P < 0.001) compared with the control group; compared with the model group, the lung coefficient of rats in the intraperitoneal injection group was decreased (P < 0.05). The results of HE staining of lung tissue of rats in each group showed that the alveolar wall was thin and the alveolar structure was normal in the control group on the 28th and 56th days, and no collapse was seen; compared with the control group on the 28th day, the alveolar wall of the rats in the 28th day model group was significantly thickened, the alveolar septum was widened, and a large number of inflammatory cells infiltrated the alveolar cavity; compared with the 28th day model group, the alveolar structure of each intervention group of polydatin was relatively normal. At day 56, compared with the control group, the alveolar wall of fibroblasts and fibroblast hyperplasia were further thickened in the model group; compared with the model group, the alveolar spacing in the intraperitoneal injection group, gavage group, and nebulized inhalation group was reduced. The Masson staining examination of rat lung tissue showed that, compared with the control group, the lung tissue of the model groups on the 28th and 56th days had blue cord -like collagen fiber hyperplasia. The results of collagen volume analysis showed that on the 28th and 56th days, the collagen volume integration number of the model group increased significantly compared with the control group; compared with the model group, the collagen volume fraction of all three groups of polydatin -treated rats decreased (P < 0.01). Such effects were observed to be more pronounced in rats with the intraperitoneal injection compared to those of the other two groups. On the 56th day after treatment, the content of HYP in the lung tissues in all treated groups increased compared with the control group (P < 0.05); compared with the model group, the content of hydroxyproline decreased in the intraperitoneal injection group, gavage group, and nebulized inhalation group (P < 0.05). On the 28th day after treatment, there was no significant difference in the concentration of malondialdehyde in the serum of each group (P = 0.140). On the 56th day after treatment, compared with the control group, the levels of MDA in the serum of the model group, the gavage group, and the aerosol inhalation group increased (P < 0.05); the content of MDA in the intraperitoneal injection group, gavage group, and nebulized inhalation group decreased (P < 0.05) compared with the model group, among which the MDA content in the intraperitoneal injection group had the best amelioration effect. Conclusions Polydatin, optimally administered by intraperitoneal injection, could effectively decelerate silicosis progression in SD rats, possibly via its anti-inflammatory and anti-fibrotic effects. [ABSTRACT FROM AUTHOR]

Polydatin is an active polyphenol displaying multifaceted benefits. Recently, growing studies have noticed its potential therapeutic effects on bone and joint disorders (BJDs). Therefore, this article reviews recent in vivo and in vitro progress on the protective role of polydatin against BJDs. An insight into the underlying mechanisms is also presented. It was found that polydatin could promote osteogenesis in vitro , and symptom improvements have been disclosed with animal models of osteoporosis, osteosarcoma, osteoarthritis and rheumatic arthritis. These beneficial effects obtained in laboratory could be mainly attributed to the bone metabolism-regulating, anti-inflammatory, antioxidative, apoptosis-regulating and autophagy-regulating functions of polydatin. However, studies on human subjects with BJDs that can lead to early identification of the clinical efficacy and adverse effects of polydatin have not been reported yet. Accordingly, this review serves as a starting point for pursuing clinical trials. Additionally, future emphasis should also be devoted to the low bioavailability and prompt metabolism nature of polydatin. In summary, well-designed clinical trials of polydatin in patients with BJD are in demand, and its pharmacokinetic nature must be taken into account. [ABSTRACT FROM AUTHOR]

Rheumatoid arthritis (RA) is a chronic and refractory autoimmune disease that primarily affects the synovium of diarthrodial joints. Inflammatory macrophages and fibroblast-like synoviocytes (FLS) in the synovial microenvironment produce pathogenic mediators such as cytokines and proteases that perpetuate immune-mediated inflammation and contribute to the destruction of cartilage and bone. Polydatin (PD), a natural active compound, has demonstrated potential anti-inflammatory and anti-arthritic effects. However, drug development and delivery of PD is still a great challenge owing to its low solubility, short half-life, and high dose requirement. In order to overcome these drawbacks, we developed a novel nanodrug system named HA-M@PB@Ag@PD NPs. This system is composed of hybrid membrane (M), hyaluronic acid (HA), Prussian blue nanoparticles (PB NPs), PD, and chitosan-silver (Chi-Ag). In vitro experiments demonstrated that HA-M@PB@Ag@PD NPs effectively cleared ROS, promoted the repolarization of inflammatory macrophages, and induced apoptosis of RA-FLS. Using a rat model of RA, HA-M@PB@Ag@PD NPs markedly suppressed joint inflammation, inhibited synovial hyperplasia, and protected joints against destruction of cartilage and bone. Moreover, HA-M@PB@Ag@PD NPs significantly improved the synovial microenvironment of arthritic rats by reducing the number of RA-FLS and inflammatory macrophages, and facilitating the repolarization of inflammatory macrophages.

Objective:To explore effect of polydatin on ocular surface dysfunction and pathology in dry eye disease (DED) rats and its protective mechanism. Methods:Eighteen from 90 SD rats were randomly chosen as control group, and other rats were injected subcutaneously with scopolamine hydrobromide to establish DED model. After modeling, rats were separated into model group, 0.05%polydatin group, 0.5%polydatin group, 0.5%polydatin+U0126 [mitogen-activated protein kinase kinase (MEK) inhibitor group, with 18 rats in each group; each administration group was given corresponding doses of drugs for intervention, and rats in control group and model group were given same amount of normal saline. On the 7th, 14th, 21st, and 28th day of intervention, Schirmer test was performed to measure tear secretion amount of rats in each group, fluorescein staining was performed to measure tear film breakup time (BUT) and corneal damage of rats in each group; RT-qPCR was performed to measure mRNA expression of proinflammatory factors TNF-α, IFN-γ and IL-1β in cornea and conjunctival tissues; HE staining was performed to observe histopathological changes of cornea; PAS staining was performed to evaluate number of conjunctival goblet cells; Western blot was performed to detect expressions of MEK/extracellular regulatory protein kinase (ERK) pathway related proteins. Results:Compared with control group, tear secretion amount BUT and number of conjunctival goblet cells in model group were obviously reduced (P<0.05), corneal injury score, TNF- α, IFN- γ and IL-1β mRNA levels were obviously increased (P<0.05), corneal epithelial layer was thinned, a large number of inflammatory cell infiltration and new capillaries could be seen; compared with model group, tear secretion amount, BUT, number of conjunctival goblet cells, p-MEK1/2/MEK1/2 and p-ERK1/2/ERK1/2 in 0.05%polydatin group and 0.5%polydatin group were obviously increased (P<0.05), corneal injury score, TNF-α, IFN-γ and IL-1β mRNA levels were obviously reduced (P< 0.05), pathological damage of corneal tissue was obviously relieved; U0126 could significantly attenuate protective effects of polydatin on ocular surface dysfunction and pathological changes in DED rats. Conclusion:Polydatin may improve ocular surface dysfunction and pathology of DED rats induced by scopolamine by activating MEK/ERK pathway. [ABSTRACT FROM AUTHOR]

Copyright of Chinese Journal of Cancer Biotherapy is the property of Editorial Office of Chinese Journal of Cancer Biotherapy and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

BackgroundConsidering the complex pathological mechanisms behind spinal cord injury (SCI) and the adverse effects of present non-approved drugs against SCI, new studies are needed to introduce novel multi-target active ingredients with higher efficacy and lower side effects. Polydatin (PLD) is a naturally occurring stilbenoid glucoside recognized for its antioxidative and anti-inflammatory properties. This study aimed to assess the effects of PLD on sensory-motor function following SCI in rats.MethodsFollowing laminectomy and clip compression injury at the thoracic 8 (T8)-T9 level of the spinal cord, rats were randomly assigned to five groups: Sham, SCI, and three groups receiving different doses of PLD treatment (1, 2, and 3 mg/kg). Over 4 weeks, behavioral tests were done such as von Frey, acetone drop, hot plate, Basso-Beattie-Bresnahan, and inclined plane test. At the end of the study, changes in catalase and glutathione activity, nitrite level, activity of matrix metalloproteinase 2 (MMP2) and MMP9 as well as spinal tissue remyelination/neurogenesis, were evaluated.ResultsThe results revealed that PLD treatment significantly improved the behavioral performance of the animals starting from the first week after SCI. Additionally, PLD increased catalase, and glutathione levels, and MMP2 activity while reduced serum nitrite levels and MMP9. These positive effects were accompanied by a reduction in the size of the lesion and preservation of neuronal count.ConclusionIn conclusion, PLD showed neuroprotective effects in SCI rats by employing anti-inflammatory and antioxidant effects, through which improve sensory and motor function.

Glioblastoma (GBL) is one of the more malignant primary brain tumors; it is currently treated by a multimodality strategy including surgery, and radio- and chemotherapy, mainly consisting of temozolomide (TMZ)-based chemotherapy. Tumor relapse often occurs due to the establishment of TMZ resistance, with a patient median survival time of

Polygonum cuspidatum is a traditional medicinal plant enriched with resveratrol and polydatin. However, low temperatures reduce the medicinal component contents of P. cuspidatum, and prolonged low temperatures also affect the growth and survival of P. cuspidatum at the seedling stage. It is unclear whether a culturable endophytic fungus Serendipita indica is able to enhance P. cuspidatum's low-temperature tolerance and medicinal components. The objective of this study was to examine the biomass, leaf gas exchange, antioxidant enzyme activity, proline levels, medicinal constituent levels, and the expression of the resveratrol synthase (PcRS) and resveratrol-forming stilbene synthase 11 (PcRS11) genes of potted P. cuspidatum plants inoculated with S. indica at low temperatures (10 °C/6 °C, 12 h/12 h, day/night temperature). The six-week low-temperature treatment significantly reduced the root fungal colonization, biomass production, and leaf gas exchange variables, whereas S. indica inoculation significantly increased shoot and root biomass, photosynthetic rate, stomatal conductance, and transpiration rate at low temperatures. S. indica inoculation significantly increased superoxide dismutase and catalase activity as well as proline levels in leaves at low temperatures. The magnitude of root chrysophanol, emodin, polydatin, and resveratrol levels decreased by low temperatures was greater in uninoculated plants than in inoculated plants. Inoculation of S. indica, on the other hand, significantly increased the four medicinal component levels in roots at low temperatures, with a greater magnitude rise in chrysophanol, polydatin, and resveratrol at low temperatures than at suitable temperatures. The low-temperature treatment down-regulated the expression of PcRS and PcRS11 genes in roots, while S. indica up-regulated the expression of PcRS and PcRS11 genes at low temperatures. This implies that S. indica acts as a powerful microbial stimulant on P. cuspidatum to promote low-temperature resistance and medicinal component levels. [ABSTRACT FROM AUTHOR]

Purpose: Polydatin (PD) has widely pharmacological activities. However, the effects of PD on high glucose (HG)-induced Müller cells in diabetic retinopathy (DR) are rarely studied. Methods: The protective effects of PD were evaluated in HG-induced human retinal Müller cells. The levels of pro-angiogenic factors and pro-inflammatory factors were detected using the ELISA kits. The expressions of nucleotide-binding oligomerization domain-like receptor family pyrin domain-containing-3 (NLRP3) and sirtuin-1 (SIRT1) were determined by western blot. Results: PD inhibited proliferation and activation of HG-induced MIO-M1 cells. PD treatment reduced the levels of pro-angiogenic factors, pro-inflammatory factors, and oxidative stress, while these effects were attenuated by NLRP3 agonist ATP in HG-induced MIO-M1 cells. Furthermore, PD inhibited the activation of NLRP3 inflammasome by regulating the SIRT1 expression after HG stimulation, and knockdown of SIRT1 reversed the inhibition effects of PD on NLRP3 inflammasome, pro-angiogenic factors, pro-inflammatory factors, and oxidative stress in HG-induced MIO-M1 cells. Conclusion: PD may inhibit HG-induced Müller cells proliferation and activation and suppress pro-angiogenic factors, pro-inflammatory factors, and oxidative stress through the SIRT1/NLRP3 inflammasome pathway. In summary, PD treatment may be an effective therapeutic strategy for DR. [ABSTRACT FROM AUTHOR]

Polygonum Cuspidate (P. cuspidatum) is a traditional topical preparation of Chinese medicine. The aim of this study was to develop HPLC fingerprints for P. cuspidatum Powder and P. cuspidatum Ointment, as well as to determine the total stilbene and total anthraquinone contents in them. A XB-C18 column (250 mm 4.6 mm, 5 μm) was used with a mobile phase consisting of 0.1% phosphoric acid solution-acetonitrile and a gradient elution. The flow rate was 1.0 ml/min and the detection wavelength was 286 nm. The column temperature was 30 °C and injection volume was 10 μl. The similarity evaluation system for chromatographic fingerprint of traditional Chinese medicine (2012 edition) was employed to confirm the common peaks at 13 batches of samples and to assess the similarity. The study revealed that 20 common peaks were identified in both P. cuspidatum powder and P. cuspidatum ointment, with a similarity greater than 0.95. Amongst them, seven components were attributed and confirmed, which were identified as polydatin, resveratrol, emodin-8-glucoside, aloe-emodin, rhein, emodin and physcion. Under the established conditions of the chromatography, quantitative analysis of six components could be well separated, and had a good linearity and linear range, the precision, repeatability and stability were good. The method's efficacy in assessing the quality of P. cuspidatum powder and P. cuspidatum ointment is validated, and it can be employed for quality control purposes. [ABSTRACT FROM AUTHOR]

To investigate the effect and mechanism of polydatin on bleomycin (BLM)‐induced pulmonary fibrosis in a mouse model. The lung fibrosis model was induced by BLM. The contents of TNF‐α, LPS, IL‐6 and IL‐1β in lung tissue, intestine and serum were detected by ELISA. Gut microbiota diversity was detected by 16S rDNA sequencing; R language was used to analyse species composition, α‐diversity, β‐diversity, species differences and marker species. Mice were fed drinking water mixed with four antibiotics (ampicillin, neomycin, metronidazole, vancomycin; antibiotics, ABx) to build a mouse model of ABx‐induced bacterial depletion; and faecal microbiota from different groups were transplanted into BLM‐treated or untreated ABx mice. The histopathological changes and collagen I and α‐SMA expression were determined. Polydatin effectively reduced the degree of fibrosis in a BLM‐induced pulmonary fibrosis mouse model; BLM and/or polydatin affected the abundance of the dominant gut microbiota in mice. Moreover, faecal microbiota transplantation (FMT) from polydatin‐treated BLM mice effectively alleviated lung fibrosis in BLM‐treated ABx mice compared with FMT from BLM mice. Polydatin can reduce fibrosis and inflammation in a BLM‐induced mouse pulmonary fibrosis model. The alteration of gut microbiota by polydatin may be involved in the therapeutic effect. [ABSTRACT FROM AUTHOR]

Skeletal muscle atrophy severely impacts one's quality of life. The effects and mechanism of polydatin on skeletal muscle atrophy are unclear. This study investigated the effects and mechanism of polydatin on TNF-α-induced skeletal muscle cells. The skeletal muscle cell atrophy model was established by inducing C2C12 cells with TNF-α. Cell viability, IL-1β levels and cell apoptosis were assessed. The mRNA and protein expression levels of apoptosis-related proteins were measured. Meanwhile, the binding of polydatin to AKT was analyzed by molecular docking. TNF-α reduced cell fusion and viability while up-regulated IL-1β level and promoted cell apoptosis. TNF-α activated AKT, NF-κB, and p38 MAPK signaling pathways. Polydatin reversed these effects induced by TNF-α, with a low concentration being more effective. Polydatin was predicted to bind to GLY162, PHE161, GLU198, THR195 and GLU191 sites of AKT protein through van der Waals force and conventional hydrogen bonds. Overexpression of AKT led to increased phosphorylation levels of AKT, p38, and p65 proteins, as well as IL-1β levels and cell apoptosis. Polydatin inhibited TNF-α-induced apoptosis of C2C12 cells by regulating NF-κB and p38 MAPK signaling pathways through AKT. This suggests that polydatin shows promise as a new drug for the treatment of skeletal muscle atrophy. [ABSTRACT FROM AUTHOR]

AIM: To investigate the effect of scutellarin combined with polydatin on pulmonary and bronchial injury induced by lipopolysaccharide （LPS） combined with smoking in rats and its mechanism. METHODS: Male SD rats were randomly divided into control group, model group, Huangqin Jingye-Huzhang decoction （5 g/kg） group, scutellarin （40 mg/kg） group, polydatin （60 mg/kg） group, scutellarin+polydatin （20 mg/kg+30 mg/kg, 40 mg/kg+60 mg/kg and 80 mg/kg+120 mg/kg） groups, and Guilong Kechuanning tablet （1 g/kg） group, with 10 rats each group. Chronic bronchitis model was established in 90 rats. The levels of interleukin-1β（ IL-1β）, IL-6, IL-17A, IL-10 and tumor necrosis factor-α （TNF-α） in bronchoalveolar lavage fluid （BALF） and serum were measured by ELISA, and the levels of superoxide dismutase （SOD） and malondialdehyde （MDA） in lung tissues were detected using kits. Protein content and cell counts in BALF were determined. Wet/dry（ W/D） mass ratio of the right lung was estimated, and HE staining was used to observe the pathological changes of pulmonary and bronchial tissues and score the lung tissue injury. The mRNA expression of phosphatidylinositol 3-kinase （PI3K）, protein kinase B （PKB/AKT） and mammalian target of rapamycin （mTOR） was detected by RT-qPCR. The protein levels of p-PI3K, PI3K, p-AKT, AKT, p-mTOR and mTOR were detected by Western blot. RESULTS: Compared with control group, the levels of IL-1β, IL-6, protein, leukocytes and neutrophils in BALF, the levels of IL-17A and TNF-α in serum, the content of MDA in lung tissues and the W/D mass ratio of the right lung in model group were significantly increased （P<0. 01）, while the content of IL-10 in serum and the activity of SOD in lung tissue were significantly decreased（ P<0. 01）. The protein levels of p-PI3K, p-AKT and p-mTOR were significantly up-regulated （P<0. 01）. Compared with model group, the levels of IL-1β, IL-6, protein, white blood cells and neutrophils in BALF, the levels of IL-17A and TNF-α in serum, the content of MDA in lung tissues and the W/D mass ratio of the right lung in scutellarin+polydatin （20 mg/kg+30 mg/kg, 40 mg/kg+60 mg/kg and 80 mg/kg+120 mg/kg） groups were significantly lower than those in model group（ P<0. 01 or P<0. 05）, while the content of IL-10 in serum and the activity of SOD in lung tissue were significantly increased （P<0. 01）. The pulmonary and bronchial inflammatory response was alleviated, and the injury was obviously attenuated. The protein levels of p-PI3K, p-AKT and p-mTOR were significantly down-regulated （P<0. 01）. CONCLUSION: Scutellarin combined with polydatin protects pulmonary and bronchial tissues against the injury induced by LPS combined with smoking in rats. The mechanism may be related to inhibiting the activation of PI3K/AKT/mTOR pathway, reducing oxidative stress and inhibiting inflammatory factors such as IL-17A, TNF-α, IL-1β and IL-6. [ABSTRACT FROM AUTHOR]

Background: Acquired radio-resistance and the undesired normal tissue radiation injuries seriously discount the therapeutic effect of lung cancer radiotherapy. In this study, we aimed to explore the role and potential mechanism of polydatin in simultaneously decreasing radioresistance and radiation injuries. Methods: The tumor-bearing model of nude mice was used to investigate the tumor inhibition of polydatin on lung cancer and its effect on radiosensitivity, and the effect of polydatin on B cell infiltration in cancerous tissue was investigated. In addition, we performed systemic radiotherapy on BABL/C mice and evaluated the protective effect of polydatin on radiation injury by the Kaplan–Meier survival curve. Moreover, the regulation of polydatin on proliferation and apoptosis of A549 cells was also investigated in vitro. Results: In this study, it is first found that polydatin inhibits the growth and promotes the radiosensitivity of lung cancer while reducing the radiation damage of the healthy tissue. Further, it is evidenced that the major mechanism relies on its regulation on body's immune function, and in particular, the inhibition of radiation-induced B cell infiltration in tumor tissue. Conclusion: These findings show that in addition to tumor inhibition, polydatin also promotes the sensitivity and reduces the adverse reactions of radiotherapy, making itself a promising candidate for boosting lung cancer radiotherapy efficacy. [ABSTRACT FROM AUTHOR]

Three different types of solid dispersions based on polyvinyl polymers and related copolymers (Kollidon® VA64, Soluplus® and Kollicoat IR®) comprising polydatin-rich Polygoni cuspidati extract were prepared by hot melt extrusion. The systems were characterized using X-ray powder diffraction, infrared spectroscopy as well as by polydatin release and in vitro permeability. Mucoadhesive tablets were prepared from the extrudates based on Kollidon® VA64 and Soluplus® to obtain a suitable pharmaceutical form, where (hydroxypropyl)methyl cellulose was added as a mucoadhesive agent. The tablets were evaluated in terms of the kinetics of polydatin release as well as their mucoadhesive properties. The best tabletability properties, polydatin release profile and adequate mucoadhesive properties were obtained by the formulation containing the Kollidon® VA64-based extrudate, which makes it an excellent prototype for enhancing the release of poorly water-soluble compounds. [ABSTRACT FROM AUTHOR]

Background: Oxidative stress and inflammatory responses are critical factors in calcium oxalate (CaOx) crystal-induced renal injury. Reactive oxygen species (ROS) are usually produced in the cytoplasm and mitochondria and trigger the priming and activation of the NLRP3 inflammasome, thereby regulating cytokines and inflammation. Polydatin is a plant rhizome extract with anti-inflammatory, antioxidant, and antitumor effects. However, it remains not clear whether and how these pathophysiological processes exists in CaOx crystal-induced renal inflammatory injury. Methods: Here, we measured the expression of the NLRP3 inflammasome, IL-18, IL-1β, intracellular and mitochondrial ROS (mtROS) levels and relevant morphological changes in treated renal tubular epithelial cells (TECs) and stone-forming rats. The study further explored the action of intracellular ROS and mtROS on these inflammatory damage, and the beneficial effects and pathway of polydatin. Results: We verified that CaOx crystal-induced cytoplasmic ROS and mtROS upregulation promoted the priming and activation of the NLRP3 inflammasome, thereby stimulating IL-18/1β maturation and activation. Polydatin can relieve oxidative stress and inflammatory damage by decreasing ROS. We further demonstrated that mtROS is the main target for polydatin to exert the NLRP3 inflammasome-regulating function. The inhibition of mtROS can effectively relieve the inflammatory damage to TECs and kidney caused by CaOx crystal. Conclusion: These findings provide new insight into the relationship between mitochondrial damage and inflammation in nephrolithiasis and show that polydatin-mediated anti-inflammatory and antioxidative protection is a therapeutic strategy for, but not limited to, crystalline nephropathy.

Mycoplasma pneumoniae (MP) is one of the main pathogens causing community acquired pneumonia (CAP) in children and adults. Previous pharmacological and clinical studies have shown that Polydatin (PD) exerts anti-inflammatory action by conferring protective benefit in MP pneumonia. However, the mechanism underlying the of PD on MP infection remains unclear. It was found that PD alleviated MP-induced injury by inhibiting caspase-1/gasdermin D (GSDMD)-mediated epithelial pyroptosis. The results demonstrated that PD inhibited the transformation of GSDMD to N-terminal gasdermin-N (GSDMD-N) by decreasing caspase-1 activation, as well as suppressed the formation and secretion of interleukin-1β (IL-1β) and interleukin-18 (IL-18), reversed Na, K-ATPase reduction, and suppressed LDH release both in vitro and vivo. Taken together, epithelial pyroptosis in BEAS‐2B cells and lung injury in mice were prevented by PD. In conclusion, PD suppressed pulmonary injury triggered by MP infection, by inhibiting the caspase-1/GSDMD-mediated epithelial pyroptosis signaling pathway. Thus, PD may be regarded as a potential therapy for MP-induced inflammation.

Objective To investigate the effect of polydatin on fracture healing in rats with osteoporotic fracture and its effect on silent information regulator 1 (SIRT)/forkhead transcription factor O1 (FoxO1) signaling pathway. Methods A rat model of osteoporotic fracture was established, and 48 rats with successful modeling were randomly divided into model group, polydatin low (30 mg/kg), high (60 mg/kg) dose groups, and alendronate sodium (0.5 mg/kg) group. Another 12 rats were taken as control group to construct the fracture model of the same site. After modeling, the rats in each group were given the corresponding drugs by gavage once a day for 8 weeks. Fracturehealing score and bone mineral density (BMD) at fracture site were performed in rats; enzyme linked immunosorbent assay was used to measure the serum levels of C-telopeptide of type I collagen (CTX-I), osteocalcin (OC), tumor necrosis factor-a (TNF-α), interleukin-1ẞ (IL-1ẞ); HE staining was used to observe the pathological changes of bone tissue; the mRNA levels of SIRT1 and Fox01 in bone tissue were detected by fluorescence quantitative PCR; Western blot was used to detect the protein levels of SIRT1 and Fox01 in bone tissue. Results Compared with model group, the pathological changes of bone tissue in thepolydatin low and high dose groups were gradually alleviated, the fracture healing score, BMD at the fracture site, the levels of OCin serum, and mRNA and protein levels of SIRT1 and Fox01 in bone tissue were increased successively, CTX- I, TNF-α, IL-1ẞ levels was decreased successively (P<0.05); there were no significant differences in bone pathological changes and various indexes between alendronate sodium group and polydatin high dose group (P>0.05). Conclusion Polydatin can reduce inflammatory response, improve BMD and promote fracture healing in rats with osteoporotic fracture, and its mechanism may be related to the activation of SIRT1/Fox01 signaling pathway. [ABSTRACT FROM AUTHOR]

Effective and non-invasive inspection method toward viscosity is expected to ease the burden of continued increased health problems worldwide. Herein, we proposed that viscosity is one of the most important markers in the liquid microenvironment. Then, a natural product was further developed from resveratrol derivate, polydatin, as an activatable molecular sensor for monitoring liquid micro-environmental viscosity alterations for metamorphic extent determination. This natural molecular sensor was constructed by the single double bond alternating conjugate structure, which can rotate freely in the low viscosity media, and in the highly viscous media, bright fluorescent signals are specifically activated (around 383 nm, 53-fold), endowing the natural sensor with the capacity to avoid autofluorescence from the additives and achieving high signal-to-noise ratio imaging. With the lower detection limit 1.125 cP, the sensor polydatin exhibits higher viscosity sensitive coefficient (0.60), and 75.5 nm of Stokes shift was found in the distilled water. Afterward, polydatin achieved non-invasively identifying the thickening effects of food thickeners. In addition, the capability of polydatin to evaluate the deterioration extent of liquids with viscosity as a robust marker was explored. It was found that the viscosity level in microenvironments is highly dependent on the liquid food metamorphic period. The fluorescent intensity increment and viscosity value changes were fitted into a linear equation. We expected that this approach would reinvigorate the fluorescent analytical methods toward liquid safety inspection. [ABSTRACT FROM AUTHOR]

Objective: To investigate the effect of polydatin treatment on postoperative cognitive dysfunction, hippocampal oxidative stress and neuroinflammation in aged mice. Methods: C57BL/6J male aged mice, 18 months old, weighing 24-28 g, were randomly divided into 4 groups: sham operation group (Sham group), postoperative cognitive dysfunction group (POCD group), low-dose polydatin group (PD1 group), high-dose polydatin group (PD2 group). The mice in the Sham group received only chloral hydrate anesthesia without surgery; the mice in the POCD group received abdominal surgery to prepare the POCD model; mice in PD1 group underwent abdominal surgery and received intraperitoneal injection of 25 mg/kg polydatin immediately, 24 h and 48 h after surgery; mice in PD2 group underwent abdominal surgery and received intraperitoneal injection of 50 mg/kg polydatin immediately, 24 h and 48 h after surgery. From postoperative day 5 to postoperative day 9, Morris water maze test was used to evaluate postoperative cognitive function. Western blot was used to determine the protein expression levels of Nrf2, HO-1, HMGB1, and Iba-1 in the hippocampus. The concentration of reactive oxygen species (ROS), malondialdehyde (MDA) as well as superoxide dismutase (SOD) in the hippocampus were detected to reflect the postoperative hippocampal oxidative stress level. Methods: (1) Compared with the Sham group, the mice in the POCD group had a longer escape latency (P<0.05), decreased platform crossing times and time spent in the target quadrant (P<0.05), reduced expression levels of Nrf2 and HO-1 proteins (P<0.05), increased oxidative products ROS and MDA (P<0.05), decreased activity of antioxidant enzyme SOD (P<0.05), and elevated protein expression levels of Iba-1 and HMGB1(P<0.05); (2) Compared with POCD group, mice in PD1 group and PD2 group had shorter escape latency (P<0.05), increased platform crossing times and time spent in the target quadrant (P<0.05), elevated expression levels of Nrf2 and HO-1 proteins(P<0.05), reduced ROS and MDA(P<0.05), improved SOD activity(P<0.05), and decreased protein expression levels of Iba-1 and HMGB1 (P<0.05). Conclusions: Polydatin can alleviate postoperative cognitive impairment in aged mice, and reduce postoperative hippocampal oxidative stress and neuroinflammation. Its mechanism may be related to the activation of Nrf2/HO-1 signaling pathway. [ABSTRACT FROM AUTHOR]

Osteoporosis and osteoarthritis are common clinical aging-related bone metabolism disease, and their incidence gradually increases with age. Polydatin is a natural polyphenol and non-flavonoid compound present in the traditional Chinese medicine Polygonum cuspidatum, and it has attracted much attention because of its strong role in regulating bone metabolism and stimulating blood vessel formation. In this research, we summarize relevant literature that published at home or abroad, which contents about the characteristics of pharmacokinetic, pharmacological mechanisms and targets of polydatin in the prevention and treatment of osteoporosis and osteoarthritis. It is expected to provide more clues for the follow-up research on the prevention and treatment of aging-related bone metabolism diseases, and to supply more scientific theoretical basis for the development and utilization of polydatin. [ABSTRACT FROM AUTHOR]

This study showed the protective effect of polydatin (PD), which has an antioxidant activity against oxidative stress in mice caused by aflatoxin B1 (AFB1). In this study, 36 male Swiss albino mice were divided equally into 6 groups: 0.2 mL of FTS was administered to the control group, 0.2 mL of olive oil to the second group, and 0.75 mg/kg AFB1 to the third group by intragastric gavage every day for 28 days. The fourth, fifth, and sixth groups were administered 50, 100, and 200 mg/kg PD and 0.75 mg/kg AFB1 intragastrically for 28 days, respectively. AFB1 administration increased plasma aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, blood urea nitrogen, creatinine, and malondialdehyde levels in blood and tissue samples but decreased the level of glutathione and the activities of superoxide dismutase and catalase. On the other hand, it was determined that PD applications depending on the increasing doses brought these levels closer to normal. In addition, AFB1 administration increased the amount of ssDNA and liver COX-2, TNF-α, IL-6, NFκB, and Cyp3a11 mRNA expression levels; on the other hand, it decreased the IL-2 mRNA expression level. In contrast, increasing doses of PD application regulated the amount of ssDNA and these mRNA expression levels. Additionally, histopathological damage was observed in the liver and kidney tissues of the AFB1 group, while PD applications in a dose-dependent manner improved these damages. As a result, it was determined that PD reduced AFB1-induced oxidative stress, DNA damage, and inflammation and exhibited a protective effect on tissues in mice. [ABSTRACT FROM AUTHOR]

Aims The study is aimed at understanding the novel molecular mechanisms governing drug resistance in the opportunistic fungi belonging to the genus Candida. Methods and results This is a multipronged study wherein different assays like drug susceptibility and whole cell proteome analysis, stress tolerance assay, measurement of total internal glycerol content, western blot analysis, reactive oxygen species (ROS) measurement, glucose uptake, lactate production, ATP generation, and NADPH measurements were made. The study reveals an incidence of different species of Candida in the northern most part of India (Kashmir valley). Resistant isolates, mostly resistant to azoles were reported across all the species. The study revealed a difference in resistance mechanisms between Candida albicans and C. glabrata clinical isolates. Further, such resistance mechanism (in the case of C. albicans) was mostly mediated by Hexokinase 2 (Hxk2) and Glucose-6-phosphate dehydrogenase (G6pd). Increased expression of Hxk2 was associated with increased glucose uptake, more lactate production, and more ATP generation in drug-resistant C. albicans. At the same time, increased G6pd expression was responsible for the increased production of NADPH, which imparts a better ROS scavenging potential. While in C. glabrata the resistance was linked with glycerol metabolism, where the drug-resistant isolate tends to accumulate more glycerol as an osmolyte in response to external stresses. This glycerol accumulation was found to be triggered by the HOG1-MAPK pathway. Conclusion The study concludes that, like various human malignant tumors, there is a strong correlation between drug resistance and aberrant cellular metabolism in the opportunistic fungi belonging to the genus Candida. [ABSTRACT FROM AUTHOR]

Triple-negative breast cancer (TNBC) has been clearly recognized as a heterogeneous tumor with the worst prognosis among the subtypes of breast cancer (BC). The advent and application of current small-molecule drugs for treating TNBC, as well as other novel inhibitors, among others, have made treatment options for TNBC more selective. However, there are still problems, such as poor patient tolerance, large administration doses, high dosing frequency, and toxic side effects, necessitating the development of more efficient and less toxic treatment strategies. High expression of Nrf2, a vital antioxidant transcription factor, often promotes tumor progression, and it is also one of the most effective targets in BC therapy. We found that in MDA-MB-231 cells and SUM159 cells, brusatol (BRU) combined with polydatin (PD) could significantly inhibit cell proliferation in vitro, significantly downregulate the expression of Nrf2 protein as well as the expression of downstream related target genes Heme Oxygenase-1 (HO-1) and NAD(P)H dehydrogenase, quinone 1 (NQO1), and promote reactive oxygen species (ROS) levels to further strengthen the anti-tumor effect. Furthermore, we discovered in our in vivo experiments that by reducing the drug dosage three times, we could significantly reduce tumor cell growth while avoiding toxic side effects, providing a treatment method with greater clinical application value for TNBC treatment. [ABSTRACT FROM AUTHOR]

Polydatin (PD), a natural product derived from Polygonum cuspidatum, has anti‐inflammatory and antioxidant effects and has significant benefits in treating allergic diseases. However, its role and mechanism in allergic rhinitis (AR) have not been fully elucidated. Herein, we investigated the effect and mechanism of PD in AR. AR model was established in mice with OVA. Human nasal epithelial cells (HNEpCs) were stimulated with IL‐13. HNEpCs were also treated with an inhibitor of mitochondrial division or transfected with siRNA. The levels of IgE and cellular inflammatory factors were examined by enzyme linked immunosorbent assay and flow cytometry. The expressions of PINK1, Parkin, P62, LC3B, NLRP3 inflammasome proteins, and apoptosis proteins in nasal tissues and HNEpCs were measured by Western blot. We found that PD suppressed OVA‐induced epithelial thickening and eosinophil accumulation in the nasal mucosa, reduced IL‐4 production in NALF, and regulated Th1/Th2 balance. In addition, mitophagy was induced in AR mice after OVA challenge and in HNEpCs after IL‐13 stimulation. Meanwhile, PD enhanced PINK1‐Parkin‐mediated mitophagy but decreased mitochondrial reactive oxygen species (mtROS) production, NLRP3 inflammasome activation, and apoptosis. However, PD‐induced mitophagy was abrogated after PINK1 knockdown or Mdivi‐1 treatment, indicating a key role of the PINK1‐Parkin in PD‐induced mitophagy. Moreover, mitochondrial damage, mtROS production, NLRP3 inflammasome activation, and HNEpCs apoptosis under IL‐13 exposure were more severe after PINK1 knockdown or Mdivi‐1 treatment. Conclusively, PD may exert protective effects on AR by promoting PINK1‐Parkin‐mediated mitophagy, which further suppresses apoptosis and tissue damage in AR through decreasing mtROS production and NLRP3 inflammasome activation. [ABSTRACT FROM AUTHOR]

This study investigated the ability of PVP/HPβCD-based electrospun nanofibers to enhance the dissolution rate of poorly soluble polydatin and resveratrol, the main active components of Polygoni cuspidati extract. To make a solid unit dosage form that would be easier to administer, extract-loaded nanofibers were ground. SEM examination was used to analyze the nanostructure of the fibers, and the results of the cross-section of the tablets showed that they had maintained their fibrous structure. The release of the active compounds (polydatin and resveratrol) in the mucoadhesive tablets was complete and prolonged in time. Additionally, the possibility of staying on the mucosa for a prolonged time has also been proven for both tablets from PVP/HPβCD-based nanofibers and powder. The appropriate physicochemical properties of the tablets, along with the proven antioxidant, anti-inflammatory, and antibacterial properties of P. cuspidati extract, highlight the particular benefits of the mucoadhesive formulation for use as a drug delivery system for periodontal diseases. [ABSTRACT FROM AUTHOR]

Radon exposure is significantly associated with lung cancer. Radon concentration is currently reduced mainly by physical methods, but there is a lack of protective drugs or biochemical reagents for radon damage. This study aimed to explore the protective effect of polydatin (PD) on the radon-exposed injury. The results showed that PD can significantly reduce ROS level, raise SOD activity, weaken the migration ability, increase E-cad, and decrease mesenchymal cell surface markers (FN1, Vimentin, N-cad, α-SMA, and Snail) in radon-exposed epithelial cells. In vivo, PD increased the mice weight, promoted SOD activity, and decreased MDA content, the number of bullae, pulmonary septum thickness, lung collagenous fibers, and mesenchymal cell surface markers. Furthermore, PD inhibited p-PI3K, p-AKT, and p-mTOR expression. Compared with directly adding PD on radon-exposed cells, adding PD before and after radon exposure could more obviously improve the adhesion of radon-exposed cells, significantly alleviate the migration ability, and more significantly reduce mesenchyme markers and p-AKT and p-mTOR. These results indicate that PD can reduce oxidative stress, weaken epithelial-mesenchymal transition (EMT) and lung fibrosis in radon-exposed cells/mice, and have good radiation protection against radon injury. The mechanism is related to the inhibition of the PI3K/AKT/mTOR pathway. [ABSTRACT FROM AUTHOR]

Aflatoxin B1 (AFB1) is a toxic food/feed pollutant, exerting extensive deleterious impacts on the liver. Oxidative stress and inflammation are considered to be vital contributors to AFB1 hepatotoxicity. Polydatin (PD), a naturally occurring polyphenol, has been demonstrated to protect and/or treat liver disorders caused by various factors through its antioxidant and anti-inflammatory properties. However, the role of PD in AFB1-induced liver injury is still elusive. Therefore, this study was designed to investigate the protective effect of PD on hepatic injury in mice subjected to AFB1. Male mice were randomly divided into three groups: control, AFB1 and AFB1-PD groups. The results showed that PD protected against AFB1-induced hepatic injury demonstrated by the reduced serum transaminase activity, the restored hepatic histology and ultrastructure, which could be attributed to the enhanced glutathione level, the reduced interleukin 1 beta and tumor necrosis factor alpha concentrations, the increased interleukin 10 expression at transcriptional level and the up-regulated mRNA expression related to mitophagy. In conclusion, PD could alleviate AFB1-induced hepatic injury by reducing oxidative stress, inhibiting inflammation and improving mitophagy. [ABSTRACT FROM AUTHOR]

Gout is a metabolic disease that seriously affects people's health. Polydatin, a stilbene compound isolated from Polygonum cuspidatum, has attracted much attention because of its rich biological activity and high safety. This study aimed to investigate the therapeutic effect and mechanism of polydatin on hyperuricemia (HUA) combined with gouty arthritis (GA). The results showed that polydatin reduced the levels of uric acid and inflammatory cytokines, indicating that polydatin had the effect of reducing uric acid and anti-GA. Then the inhibitors of ABCG2, NLRP3 inflammasome and NF-κB pathway (Ko143, MCC950 and QNZ) were used to demonstrate that polydatin played a role in reducing uric acid and anti-GA via regulating urate transporters, NLRP3 inflammasome and NF-κB pathway. Taken together, these results provided evidence that polydatin might be used as a potential functional ingredient for the synchronous treatment of HUA and GA.

Polygonum cuspidatum is a traditional medicinal plant enriched with resveratrol and polydatin. However, low temperatures reduce the medicinal component contents of P. cuspidatum, and prolonged low temperatures also affect the growth and survival of P. cuspidatum at the seedling stage. It is unclear whether a culturable endophytic fungus Serendipita indica is able to enhance P. cuspidatum’s low-temperature tolerance and medicinal components. The objective of this study was to examine the biomass, leaf gas exchange, antioxidant enzyme activity, proline levels, medicinal constituent levels, and the expression of the resveratrol synthase (PcRS) and resveratrol-forming stilbene synthase 11 (PcRS11) genes of potted P. cuspidatum plants inoculated with S. indica at low temperatures (10 °C/6 °C, 12 h/12 h, day/night temperature). The six-week low-temperature treatment significantly reduced the root fungal colonization, biomass production, and leaf gas exchange variables, whereas S. indica inoculation significantly increased shoot and root biomass, photosynthetic rate, stomatal conductance, and transpiration rate at low temperatures. S. indica inoculation significantly increased superoxide dismutase and catalase activity as well as proline levels in leaves at low temperatures. The magnitude of root chrysophanol, emodin, polydatin, and resveratrol levels decreased by low temperatures was greater in uninoculated plants than in inoculated plants. Inoculation of S. indica, on the other hand, significantly increased the four medicinal component levels in roots at low temperatures, with a greater magnitude rise in chrysophanol, polydatin, and resveratrol at low temperatures than at suitable temperatures. The low-temperature treatment down-regulated the expression of PcRS and PcRS11 genes in roots, while S. indica up-regulated the expression of PcRS and PcRS11 genes at low temperatures. This implies that S. indica acts as a powerful microbial stimulant on P. cuspidatum to promote low-temperature resistance and medicinal component levels.

IntroductionPolydatin is a biologically active compound found in mulberries, grapes, and Polygonum cuspidatum, and it has uric acid-lowering effects. However, its urate-lowering effects and the molecular mechanisms underlying its function require further study.MethodsIn this study, a hyperuricemic rat model was established to assess the effects of polydatin on uric acid levels. The body weight, serum biochemical indicators, and histopathological parameters of the rats were evaluated. A UHPLC-Q-Exactive Orbitrap mass spectrometry-based metabolomics approach was applied to explore the potential mechanisms of action after polydatin treatment.ResultsThe results showed a trend of recovery in biochemical indicators after polydatin administration. In addition, polydatin could alleviate damage to the liver and kidneys. Untargeted metabolomics analysis revealed clear differences between hyperuricemic rats and the control group. Fourteen potential biomarkers were identified in the model group using principal component analysis and orthogonal partial least squares discriminant analysis. These differential metabolites are involved in amino acid, lipid, and energy metabolism. Of all the metabolites, the levels of L-phenylalanine, L-leucine, O-butanoylcarnitine, and dihydroxyacetone phosphate decreased, and the levels of L-tyrosine, sphinganine, and phytosphingosine significantly increased in hyperuricemic rats. After the administration of polydatin, the 14 differential metabolites could be inverted to varying degrees by regulating the perturbed metabolic pathway.ConclusionThis study has the potential to enhance our understanding of the mechanisms of hyperuricemia and demonstrate that polydatin is a promising potential adjuvant for lowering uric acid levels and alleviating hyperuricemia-related diseases.

Polydatin (PD) is a natural compound with anticancer activities, but the underlying mechanisms remain largely unclear. To understand how PD inhibited hepatocellular carcinoma (HCC), we studied PD treatments in HCC HepG2 and SK-HEP1 cells, and normal liver HL-7702 cells. PD selectively blocked the proliferation of HCC cells but showed low toxicity in normal cells, while the effects of doxorubicin (DOX) and cisplatin (DDP) on HCC and normal liver cells were opposite. In the cotreatment studies, PD synergistically improved the inhibitory activities of DOX and DDP in HCC cells but alleviated their toxicity in HL-7702 cells. Furthermore, RNA-seq studies of PD-treated HepG2 cells revealed multiple altered signaling pathways. We identified 1679 Differentially Expressed Genes (DEGs) with over a 2.0-fold change in response to PD treatment. Integrative analyses using the DEGs in PD-treated HepG2 cells and DEGs in a TCGA dataset of HCC patients revealed five PD-repressed DEGs regulating mitotic spindle midzone formation. The expression of these genes showed significantly positive correlation with poor clinical outcomes of HCC patients, suggesting that mitotic machinery was likely a primary target of PD. Our findings improve the understanding of PD's anticancer mechanisms and provide insights into developing effective clinical approaches in HCC therapies. [ABSTRACT FROM AUTHOR]

Oral squamous cell carcinoma (OSCC) is one of the most prevailing and aggressive head and neck cancers, featuring high morbidity and mortality. The available conventional treatments suffer from several adverse effects and are often inefficient in terms of their survival rates. Thus, seeking novel therapeutic agents and adjuvants is of the utmost importance for modern society. Natural polyphenolic compounds have recently emerged as promising chemopreventive and anticancer agents. Specifically, the natural compound resveratrol (RSV) has recently gained momentum for this purpose. RSV is useful for treating OSCC due to its antiproliferative, antimetastatic, and proapoptotic effects. Additionally, RSV acts against tumor cells while synergically cooperating with chemotherapeutics, overcoming drug resistance phenomena. Despite these wide-spectrum effects, there are few specific investigations regarding RSV's effects against OSCC animal models that consider different routes and vehicles for the administration of RSV. Interestingly, an injectable RSV-loaded liposome-based formulation was proven to be effective against both in vitro and in vivo OSCC models, demonstrating that the development of RSV-loaded drug delivery systems for systemic and/or loco-regional applications may be the turning point in oral cancer treatment, leading to benefits from both RSV's properties as well as from targeted delivery. Given these premises, this review offers a comprehensive overview of the in vitro and in vivo effects of RSV and its main derivative, polydatin (PD), against OSCC-related cell lines and animal models, aiming to guide the scientific community in regard to RSV and PD use in the treatment of oral precancerous and cancerous lesions. [ABSTRACT FROM AUTHOR]

Objective: To investigate the protective effect and mechanism of polydatin (PD) against gouty nephropathy (GN) in mice. Methods: Twenty‐four mice were randomly divided into three groups: the control group (no treatment), the GN group (300 mg/kg hypoxanthine + 150 mg/kg potassium oxonate), and the GN + PD group (300 mg/kg hypoxanthine + 150 mg/kg potassium oxonate + 50 mg/kg PD). Histological changes in the kidneys and the levels of uric acid (UA), blood urea nitrogen (BUN), and serum creatinine (SCr) in the sera were measured. In addition, the expression of gasdermin D (GSDMD) protein in renal tubular epithelial cells, and the expression of NOD‐like receptor protein 3 (NLRP3), GSDMD, and caspase‐1 proteins in the kidney tissues were determined by immunohistochemistry, immunofluorescence, and Western blot. Results: In vitro, PD inhibited the expression of NLRP3, caspase‐1, and GSDMD and protected the renal tubular epithelial cells from pyroptosis. In vivo, PD treatment significantly ameliorated the pathological changes in kidney tissue, and reversed the decrease of serum UA and BUN in GN model mice. The expression of NLRP3, GSDMD, and caspase‐1 proteins was also decreased in the PD‐treated GN mice. Conclusion: The results suggest that PD has a protective effect on mice with GN, which may be related to the downregulation of NLRP3, GSDMD, and caspase‐1 proteins and the inhibition of renal tubular epithelial cells pyroptosis. [ABSTRACT FROM AUTHOR]

Copyright of Food Research & Development is the property of Food Research & Development Editorial Department and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Polygoni Cuspidati Rhizoma et Radix (Huzhang in Chinese), refers to the root and rhizome of Polygonum cuspidatum Sieb. et Zucc. Huzhang is commonly used in clinical practice for the prevention and treatment of diabetes and its complications, but its active components and regulatory mechanisms have not yet been thoroughly analyzed. The network pharmacology combined with multi-omics analysis will be employed to dissect the substance basis and action mechanism of Huzhang in exerting its anti-diabetic activity. This study employed phenotypic indicators for baseline assessment, followed by integrated analysis using network pharmacology, metabolomics, transcriptomics, and qPCR technology to elucidate the active components and pharmacological mechanisms of Huzhang. The analysis of network pharmacology revealed that polydatin is a potential active component responsible for the anti-T2DM pharmacological effects of Huzhang. In vivo experimental results demonstrated that polydatin significantly regulates blood glucose, lipid levels, liver function, and liver pathological damage in diabetic rats. Analysis results from transcriptomics, metabolomics, and qPCR validation showed that polydatin comprehensively regulates glucose and lipid metabolism in T2DM by modulating bile acid metabolism, fatty acid oxidation, and lipogenesis. Polydatin is a key component of Huzhang in treating T2DM, and its regulatory mechanisms are diverse, indicating significant development potential. [Display omitted] [ABSTRACT FROM AUTHOR]

• tFNA prevents kidney stone recurrence but does not mitigate kidney injury. • tFNA-P reduce both the kidney stones recurrence and kidney injury. • tFNA-P achieved its therapeutic effects by inhibiting ferroptosis. Kidney stone diseases present a serious global health challenge characterized by the development of solid mineral crystals within the renal system. Although conventional surgical treatments exhibit effectiveness, they are constrained by limitations such as recurrence and adverse effects, along with no efficient pharmacotherapeutic options. Our investigation investigated potential of Tetrahedral Framework Nucleic Acids (tFNAs) as a drug carrier, synergistically combining them with Polydatin to formulate an innovative dual therapeutic approach for recurrent kidney stone disease. By the precise delivery offered by tFNAs, Polydatin was effectively transported to the kidney. Experimental results demonstrated the substantial therapeutic impacts in inhibiting kidney stone formation and alleviating tubular injury. Bioinformatic analysis, complemented by both in vitro and in vivo experiments, conclusively elucidated that these effects could be achieved by the regulating ferroptosis. In summary, our study is created a dual-targeted nanoparticle that exhibits multifaceted therapeutic benefits in preventing kidney stone formation, holding potential for future translation into clinical practice. [ABSTRACT FROM AUTHOR]

Reynoutria japonica Houtt is a medicinal plant renowned for its diverse pharmacological properties, including heat-clearing, toxin-removing, blood circulation promotion, blood stasis removal, diuretic action, and pain relief. The plant is commonly utilized in Traditional Chinese Medicine (TCM), and its major bioactive constituents consist of polydatin (PD) and resveratrol (RES). To summarize the relevant targets of PD in various oxidative stress-related diseases through the activation of Silence information regulator1 (SIRT1). Furthermore, elucidating the pharmacological effects and signaling mechanisms to establish the basis for PD's secure clinical implementation and expanded range of application. Literature published before November 2023 on the structural analysis and pharmacological activities of PD was collected using online databases such as Google Scholar, PubMed, and Web of Science. The keywords were "polydatin", "SIRT1" and "oxidative stress". The inclusion criteria were research articles published in English, including in vivo and in vitro experiments and clinical studies. Non-research articles such as reviews, meta-analyses, and letters were excluded. PD has been found to have significantly protective and curative effects on diseases associated with oxidative stress by regulating SIRT1-related targets including peroxisome proliferator-activated receptor γ coactivator 1-alpha (PGC-1α), nuclear factor erythroid2-related factor 2 (Nrf2), high mobility group box 1 protein (HMGB1), NOD-like receptor thermal protein domain associated protein 3 (NLRP3), p38/p53, as well as endothelial nitric oxide synthase (eNOs), among others. Strong evidence suggests that PD is an effective natural product for treating diseases related to oxidative stress. PD holds promise as an effective treatment for a wide range of diseases, with SIRT1-mediated oxidative stress as its potential pathway. [Display omitted] [ABSTRACT FROM AUTHOR]

[Display omitted] • HA-M@PB@Ag@PD NPs were developed for effective treatment of rheumatoid arthritis, in which polydatin and chitosan-silver were successfully loaded onto prussian blue nanoparticles. • HA-M@PB@Ag@PD NPs synergistically promoted the repolarization of inflammatory macrophages and induced apoptosis of RA fibroblast-like synoviocytes in vitro. • HA-M@PB@Ag@PD NPs exhibited significantly prolonged circulation time and accumulation in the arthritic joints in vivo. • HA-M@PB@Ag@PD NPs demonstrated pronounced anti-arthritic effects and significantly improved the synovial microenvironment of arthritic rats. Rheumatoid arthritis (RA) is a chronic and refractory autoimmune disease that primarily affects the synovium of diarthrodial joints. Inflammatory macrophages and fibroblast-like synoviocytes (FLS) in the synovial microenvironment produce pathogenic mediators such as cytokines and proteases that perpetuate immune-mediated inflammation and contribute to the destruction of cartilage and bone. Polydatin (PD), a natural active compound, has demonstrated potential anti-inflammatory and anti-arthritic effects. However, drug development and delivery of PD is still a great challenge owing to its low solubility, short half-life, and high dose requirement. In order to overcome these drawbacks, we developed a novel nanodrug system named HA-M@PB@Ag@PD NPs. This system is composed of hybrid membrane (M), hyaluronic acid (HA), Prussian blue nanoparticles (PB NPs), PD, and chitosan-silver (Chi-Ag). In vitro experiments demonstrated that HA-M@PB@Ag@PD NPs effectively cleared ROS, promoted the repolarization of inflammatory macrophages, and induced apoptosis of RA-FLS. Using a rat model of RA, HA-M@PB@Ag@PD NPs markedly suppressed joint inflammation, inhibited synovial hyperplasia, and protected joints against destruction of cartilage and bone. Moreover, HA-M@PB@Ag@PD NPs significantly improved the synovial microenvironment of arthritic rats by reducing the number of RA-FLS and inflammatory macrophages, and facilitating the repolarization of inflammatory macrophages. [ABSTRACT FROM AUTHOR]

The present study was conducted to evaluate the effects of chronic bisphenol A (BPA) exposure and the possible protective effects of polydatin (PD) on different organs, oxidant-antioxidant status and spermatological parameters in male Wistar rats. Male Wistar rats (2 to 3 months old) were randomly divided into 5 groups (n = 6). Group 1 was the control (daily 0.5ml distilled water). Groups 2, 3, 4 and 5 daily received 0.5 ml olive oil (OO), 25 mg/kg bisphenol A in 0.5 olive oil (BPA), 150 mg/kg polydatin (PD), and a mixture of 25 mg/kg bisphenol A in 0.5 olive oil + 150 mg/kg polydatin (BPA-PD), respectively, daily for 45 days. BPA had negative effects on percent abnormal sperm and Hypo-osmotic swelling-Eosin (HE) test (P