Polydatin Treatment Research Articles

Cardioprotective effects of polydatin against myocardial injury in HFD/stz and high glucose-induced diabetes via a Caveolin 1-dependent mechanism

BackgroundDiabetic cardiomyopathy (DCM) is defined as cardiac dysfunction involving changes in structure, function, and metabolism in the absence of coronary artery disease, which eventually developed into heart failure. There is still a lack of effective drugs for the treatment of DCM, while the ameliorative effects of traditional herbs on DCM have been commonly reported. Polydatin (PD) is a glucoside derivative of traditional herbs of resveratrol, which has been shown to ameliorate the pathological development of DCM. However, the cardioprotective effect and mechanism of PD in the improvement of myocardial injury are still unclear. Aim of studyThis study aimed to investigate the cardio-protective role of PD on DCM and reveal the critical effect of Cav1 in PD’ regulation of DCM. Materials and methodsThe Cav1-/- and Cav1+/+mice and H9C2 cells were used to induce DCM models and then given PD treatment (150 mg/kg) or not. The cardiac functions of all mice were checked via echocardiography, and myocardial histological changes were measured by H&E, periodic acid-schiff (PAS) and Masson staining. The markers expression of heart fibrosis and inflammation, and hypertrophic factors were detected using western blotting. The NF-κB signaling activation was performed by confocal, immunohistochemical, Electrophoretic mobility shift assay (EMSA) and western blotting. ResultsHere, we found that PD significantly improved the cardiac function and injury of diabetic Cav1+/+ mice, and enhanced the expression of Cav1 in the cardiac tissues of diabetic Cav1+/+ mice and HG-induced H9C2 cells. Further investigation showed that when Cav1 was knocked down, PD no longer plays the cardioprotective effect and inhibits the NF-κB signaling pathway activation in HFD/stz-treated diabetic mice and HG-induced H9C2 cells. ConclusionThese results demonstrated that PD inhibited the hyperglycemia-induced myocardial injury and inflammatory fibrosis of DCM models in vivo and in vitro, and targeting Cav1 may provide a novel understanding the mechanism of the treatment of PD in DCM.

Polydatin, a potential NOX5 agonist, synergistically enhances antitumor activity of cisplatin by stimulating oxidative stress in non‑small cell lung cancer.

Non‑small cell lung cancer (NSCLC) is one of the major causes of cancer‑related death worldwide. Cisplatin is a front‑line chemotherapeutic agent in NSCLC. Nevertheless, subsequent harsh side effects and drug resistance limit its further clinical application. Polydatin (PD) induces apoptosis in various cancer cells by generating reactive oxygen species (ROS). However, underlying molecular mechanisms of PD and its effects on cisplatin‑mediated antitumor activity in NSCLC remains unknown. MTT, colony formation, wound healing analyses and flow cytometry was employed to investigate the cell phenotypic changes and ROS generation. Relative gene and protein expressions were evaluated by reverse transcription‑quantitative PCR and western blot analyses. The antitumor effects of PD, cisplatin and their combination were evaluated by mouse xenograft model. In the present study, it was found that PD in combination with cisplatin synergistically enhances the antitumor activity in NSCLC by stimulating ROS‑mediated endoplasmic reticulum stress, and the C‑Jun‑amino‑terminal kinase and p38 mitogen‑activated protein kinase signaling pathways. PD treatment elevated ROS generation by promoting expression of NADPH oxidase 5 (NOX5), and NOX5 knockdown attenuated ROS‑mediated cytotoxicity of PD in NSCLC cells. Mice xenograft model further confirmed the synergistic antitumor efficacy of combined therapy with PD and cisplatin. The present study exhibited a superior therapeutic strategy for some patients with NSCLC by combining PD and cisplatin.

PD protects Müller cells through the SIRT1/NLRP3 inflammasome pathway.

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. 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. 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. 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.

Effect of polydatin on the viability and odontogenic differentiation of human dental pulp stem cells: An in-vitro study

Background/purposeVarious 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 methodsPD 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. ResultsThe 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. ConclusionPD promoted the expression of markers associated with odontogenic differentiation and mineralized tissue deposition in hDPSCs.

Polydatin attenuated neuropathic pain and motor dysfunction following spinal cord injury in rats by employing its anti-inflammatory and antioxidant effects.

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. 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 3mg/kg). Over 4weeks, 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. 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. In conclusion, PLD showed neuroprotective effects in SCI rats by employing anti-inflammatory and antioxidant effects, through which improve sensory and motor function.

Protective effects of polydatin on ileum injury in mice exposed to aflatoxin B1

Aflatoxin B1 (AFB1) is an extremely hazardous food/feed pollutant, posing a serious threat to health of human and animals. Particularly, exposure to AFB1 provokes enterocytes oxidative stress and inflammation, which lead to intestinal damage. Polydatin (PD), a stilbenoid glucoside, is known to possess antioxidant and anti-inflammatory properties and is being investigated for use in various disorders. The present study was intended at investigating the protective efficacy of polydatin against AFB1-induced ileum damage in mice. Kunming male mice received oral gavage of AFB1 (300 μg/kg body weight/day) and PD (100 mg/kg body weight/day) for 18 days. The results showed that mice exposed to AFB1 exhibited the impaired morphology, the suppressed disaccharidase activities, the down-regulated mRNA expressions of tight junction protein genes, oxidative stress, inflammation and the up-regulated mRNA expressions of genes related to mitophagy in the ileum, whereas PD treatment reversed the AFB1-induced disruption of ileal structure, digestion, barrier function, redox and immune status. The findings of the present study suggested that PD may have a potential benefit in preventing AFB1-induced ileum damage.

Polydatin Alleviates Chronic Stress-Induced Depressive and Anxiety-like Behaviors in a Mouse Model.

We aimed to investigate whether polydatin could suppress stress-induced depression- and anxiety-like behaviors in a mouse model. Mice were divided into the control group, chronic unpredictable mild stress (CUMS) exposure group, and CUMS mice treated with polydatin group. Following CUMS exposure and polydatin treatment, mice were subjected to behavioral assays to assess depressive-like and anxiety-like behaviors. Synaptic function was determined by the levels of brain-derived neurotrophic factor (BDNF), postsynaptic density protein 95 (PSD95), and synaptophysin (SYN) in the hippocampus and cultured hippocampal neurons. The number and length of dendrites were assessed in cultured hippocampal neurons. Finally, we investigated the effect of polydatin on CUMS-induced inflammation and oxidative stress in the hippocampus by measuring inflammatory cytokine levels, oxidative stress markers such as reactive oxygen species, glutathione peroxidase, catalase, and superoxide dismutase, as well as components of the Nrf2 signaling pathway. Polydatin alleviated CUMS-induced depressive-like behaviors in forced swimming, tail suspension and sucrose preference tests, and anxiety-like behaviors in marble-burying and elevated plus maze tests. Polydatin increased the number and length of dendrites of cultured hippocampal neurons from mice exposed to CUMS and alleviated CUMS-induced synaptic deficits by restoring BDNF, PSD95, and SYN levels in vivo and in vitro. Importantly, polydatin inhibited CUMS-induced hippocampal inflammation and oxidative stress and suppressed the activation of NFκB and Nrf2 pathways. Our study suggests that polydatin may be an effective drug for the treatment of affective disorders through inhibiting neuroinflammation and oxidative stress. Our current findings warrant further study to investigate the potential clinical application of polydatin.

Polydatin Inhibits Hepatocellular Carcinoma Cell Proliferation and Sensitizes Doxorubicin and Cisplatin through Targeting Cell Mitotic Machinery.

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.

Polydatin protects against gouty nephropathy by inhibiting renal tubular cell pyroptosis.

To investigate the protective effect and mechanism of polydatin (PD) against gouty nephropathy (GN) in mice. 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. 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. 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.

Polydatin ameliorates hepatic ischemia-reperfusion injury by modulating macrophage polarization

BackgroundPolydatin, a glucoside of resveratrol, has shown protective effects against various diseases. However, little is known about its effect on hepatic ischemia-reperfusion (I/R) injury. This study aimed to elucidate whether polydatin protects liver against I/R-induced injury and to explore the underlying mechanism. MethodsAfter gavage feeding polydatin once daily for a week, mice underwent a partial hepatic I/R procedure. Serum alanine aminotransferase (ALT)/aspartate aminotransferase (AST), hematoxylin-eosin (H&E) and TdT-mediated dUTP nick-end labeling (TUNEL) staining were used to evaluate liver injury. The severity related to the inflammatory response and reactive oxygen species (ROS) production was also investigated. Furthermore, immunofluorescence and Western blotting were used to detect macrophage polarization and the NF-κB signaling pathway in macrophages. ResultsCompared with the I/R group, polydatin pretreatment significantly attenuated I/R-induced liver damage and apoptosis. The oxidative stress marker (dihydroethidium fluorescence, malondialdehyde, superoxide dismutase and glutathione peroxidase) and I/R related inflammatory cytokines (interleukin-1β, interleukin-10 and tumor necrosis factor-α) were significantly suppressed after polydatin treatment. In addition, the result of immunofluorescence indicated that polydatin reduced the polarization of macrophages toward M1 macrophages both in vivo and in vitro. Western blotting showed that polydatin inhibited the pro-inflammatory function of RAW264.7 via down-regulating the NF-κB signaling pathway. ConclusionsPolydatin protects the liver from I/R injury by remodeling macrophage polarization via NF-κB signaling.

Polydatin Improves Sepsis-Associated Encephalopathy by Activating Sirt1 and Reducing p38 Phosphorylation.

Our previous study confirmed that polydatin (PD) can alleviate sepsis-induced multiorgan dysfunction (in the vascular endothelium, kidney, and small intestine) by activating Sirt1 and that PD protects against traumatic brain injury in rats via increased Sirt1 and inhibition of the p38-mediated mitogen-activated protein kinase (MAPK) pathway. We aim to investigate whether PD may also attenuate sepsis-associated encephalopathy (SAE). In this study, we constructed an SAE mouse model by cecal ligation and puncture (CLP) and measured Sirt1 protein activity, p38 phosphorylation, brain tissue pathological damage, pro-inflammatory cytokines (TNF-α, IL-1β, and IL-6), mitochondrial function (mitochondrial membrane potential, ATP content, and reactive oxygen species), neurological function, and animal survival time. Sirt1 selective inhibitor Ex527 and p38 inhibitor SB203580 were used to explore the possible mechanism of PD in SAE. We confirmed that PD inhibits neuroinflammation evidenced by reduced proinflammatory cytokines. In addition, PD protects mitochondria as demonstrated by restored mitochondrial membrane potential and adenosine triphosphate (ATP) content, and decreased reactive oxygen species (ROS) level. As we expected, p38 inhibition reduces neuroinflammation and mitochondrial damage. In contrast, Sirt1 inhibition aggravates cerebral cortex mitochondrial damage and neuroinflammation and promotes phosphorylation of p38. Mechanistically, PD treatment suppressed p38 phosphorylation and consequently reduced the neuroinflammatory response, and these effects were blocked by the Sirt selective inhibitor Ex527. This study, to the best of our knowledge, is the first to demonstrate that PD alleviates SAE, at least partially, by upregulating Sir1-mediated neuroinflammation inhibition and mitochondrial function protection.

Polydatin inhibits IL-1β-mediated chondrocyte inflammation and ameliorates cartilage degradation: Involvement of the NF-κB and Wnt/β-catenin pathways

Osteoarthritis (OA) is a highly prevalent chronic joint disease that involves extracellular matrix (ECM) degradation and articular cartilage inflammation. Polydatin (PD) can alleviate inflammatory reactions in numerous diseases. The present study aimed to investigate the chondroprotective and anti-inflammatory effects of PD on interleukin (IL)− 1β-treated chondrocytes in vitro and anterior cruciate ligament transection-induced rat OA models in vivo. Primary chondrocytes were isolated from SD rats and cultured. Only second-passage cells were used for subsequent experiments. Counting kit-8, quantitative real-time polymerase chain reaction, western blotting, enzyme-linked immunosorbent assay, and immunofluorescence were used to detect relevant indices. Rat OA models were established to obtain in vivo data. PD treatment decreased the production of nitric oxide (NO), prostaglandin E2 (PGE2), inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), tumor necrosis factor-α (TNF-α), and IL-6 during IL-1β-stimulated chondrocyte inflammation. Moreover, PD upregulated aggrecan and collagen II expression, whereas downregulated a disintegrin and metalloproteinase with thrombospondin motifs 5 (ADAMTS5) and matrix metalloproteinase-13 (MMP-13) expression on IL-1β-mediated chondrocytes. Additionally, PD reduced IL-1β-stimulated NF-κB and Wnt/β-catenin activation and nuclear translocation. The results of histological analysis and scoring revealed that OA in the rat models was effectively ameliorated by the intra-articular injection of PD. PD suppressed IL-1β-stimulated iNOS, COX-2, NO, and PGE2 production, TNF-α, IL-6, collagen X, MMP-13, and ADAMTS-5 expression, collagen II and aggrecan degeneration by inhibiting NF-κB and Wnt/β-catenin signaling in vitro. PD also mitigated OA progression in the rat models, thereby providing reliable data that PD could serve as a promising candidate for OA therapy.

Effect of polydatin on the proliferation and apoptosis of THP-1 cells and the mechanism

To explore the effect of polydatin on the proliferation and apoptosis of acute monocytic leukemia cell line THP-1 and the possible mechanism. After THP-1 cells were treated with polydatin at gradient concentrations for 24 hours and 48 hours, their proliferation was determined by CCK-8 assay, and half maximal inhibitory concentration (IC50) was calculated. Logarithmically growing THP-1 cells were divided into two groups, a polydatin treatment group (treated with IC50 of polydatin) and a blank control group (treated without polydatin solution), and incubated for 48 hours. Cell apoptosis and cell cycle were measured by flow cytometry. The expression levels of PI3K, AKT, p-AKT, mTOR, p-mTOR, p70 S6K, and p-p70 S6K proteins were measured by Western blotting. After treatment with polydatin, the proliferation of THP-1 cells was strongly inhibited, and the IC50 at 48 hours was 1 800 μmol/L. After treatment with 1 800 μmol/L polydatin solution for 48 hours, the apoptosis rate of THP-1 cells increased significantly compared with the blank control group (P<0.05). The cell cycle was arrested in the G0/G1 and S phases, with a significantly increased proportion of cells in the G0/G1 phase and a significantly decreased proportion of cells in the S phase, as compared with the blank control group (P<0.05). The expression levels of PI3K, AKT, p-AKT, mTOR, p-mTOR, p70 S6K, and p-p70 S6K proteins decreased significantly compared with the blank control group (P<0.05). Polydatin can effectively inhibit the proliferation, block the cell cycle, and induce the apoptosis of THP-1 cells, which may be related to inhibition of the PI3K/AKT/mTOR signaling pathway.

Antioxidant Activity and Mechanism of Resveratrol and Polydatin Isolated from Mulberry (Morus alba L.).

Natural stilbenes have unique physiological effects, such as anti-senile dementia, anti-cancer, anti-bacterial, lowering blood lipid, and other important biological functions, which have attracted great attention from scholars in recent years. In this study, two stilbene compounds, resveratrol (RES) and polydatin (PD), were isolated from Mulberry (Morus alba L.), and their antioxidant activity and mechanism were investigated. The results showed that the contents of RES and PD in mulberry roots were 32.45 and 3.15 μg/g, respectively, significantly higher than those in mulberry fruits (0.48 and 0.0020 μg/g) and mulberry branches (5.70 and 0.33 μg/g). Both RES and PD showed high antioxidant potential by DPPH, ABTS free-scavenging methods, and ORAC assay, and provided protection against oxidative damage in HepG2 cells by increased catalase (CAT) activity, superoxide dismutase (SOD) activity, and Glutathione (GSH) content, and decreasing generation of reactive oxygen species (ROS), lactate dehydrogenase (LDH) level, and malondialdehyde (MDA) content. Therefore, RES and PD treatment could be effective for attenuating AAPH-induced oxidative stress in HepG2 cells. This study will promote the development and application of stilbene compounds. Furthermore, the RES and PD could be used as antioxidant supplements in functional foods, cosmetics, or pharmaceuticals, contributing to health improvement.

Protective Role of Combined Polyphenols and Micronutrients against Influenza A Virus and SARS-CoV-2 Infection In Vitro.

Polyphenols have been widely studied for their antiviral effect against respiratory virus infections. Among these, resveratrol (RV) has been demonstrated to inhibit influenza virus replication and more recently, it has been tested together with pterostilbene against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. In the present work, we evaluated the antiviral activity of polydatin, an RV precursor, and a mixture of polyphenols and other micronutrients, named A5+, against influenza virus and SARS-CoV-2 infections. To this end, we infected Vero E6 cells and analyzed the replication of both respiratory viruses in terms of viral proteins synthesis and viral titration. We demonstrated that A5+ showed a higher efficacy in inhibiting both influenza virus and SARS-CoV-2 infections compared to polydatin treatment alone. Indeed, post infection treatment significantly decreased viral proteins expression and viral release, probably by interfering with any step of virus replicative cycle. Intriguingly, A5+ treatment strongly reduced IL-6 cytokine production in influenza virus-infected cells, suggesting its potential anti-inflammatory properties during the infection. Overall, these results demonstrate the synergic and innovative antiviral efficacy of A5+ mixture, although further studies are needed to clarify the mechanisms underlying its inhibitory effect.

Polydatin protects neuronal cells from hydrogen peroxide damage by activating CREB/Ngb signaling.

Oxidative stress-induced neuronal cell death contributes significantly to the physiological processes of a number of neurological disorders. Polydatin (PD) has been reported to protect against Alzheimer's disease (AD), ischemic stroke and traumatic brain injury. However, the underlying neuroprotective mechanisms remain to be elucidated. The current study suggested that PD activates AKT/cAMP response element-binding protein (CREB) signaling and induces neuroglobin (Ngb) to protect neuronal cells from hydrogen peroxide (H2O2) in vitro. PD inhibited the H2O2-induced neuronal cell death of primary mouse cortical neurons and N2a cells. Functional studies showed that PD attenuated H2O2-induced mitochondrial dysfunction and mitochondrial reactive oxygen species production. Mechanistically, PD was verified to induce the phosphorylation of AKT and CREB and increase the protein level of Ngb. The luciferase assay results showed that Ngb transcriptional activity was activated by CREB, especially after PD treatment. It was further indicated that PD increased the transcription of Ngb by enhancing the binding of CREB to the promoter region of Ngb. Finally, Ngb knockdown largely attenuated the neuroprotective role of PD against H2O2. The results indicated that PD protected neuronal cells from H2O2 by activating CREB/Ngb signaling in neuronal cells, indicating that PD has a neuroprotective effect against neurodegenerative diseases.

Polydatin Inhibits Cell Viability, Migration, and Invasion Through Suppressing the c-Myc Expression in Human Cervical Cancer.

Polydatin, an active ingredient from the roots of Polygonum cuspidatum, is considered to have protective effects on the cardiovascular system and liver. In this study, we demonstrated that polydatin has antitumor activity against human cervical cancer. Polydatin efficiently inhibited cervical cancer cell proliferation by regulating cell cycle-related proteins including p21, p27, CDK2, CDK4, Cyclin D1, and Cyclin E1. Furthermore, polydatin suppressed cell invasion and migration by regulating epithelial–mesenchymal transition (EMT) markers, including E-cadherin, N-cadherin, Snail and Slug. The c-Myc, as a proto-oncogene, is considered to be closely associated with the proliferation and metastasis of tumor cells. After polydatin treatment, the protein expression of c-Myc showed a significant decrease. Based on these data, we overexpressed c-Myc in cervical cancer cells and observed that the overexpression of c-Myc rescued the inhibitory effect of polydatin on cell proliferation and metastasis. These results indicated that polydatin can inhibit cell proliferation and metastasis through suppressing the c-Myc expression in human cervical cancer.

Polydatin alleviates traumatic brain injury: Role of inhibiting ferroptosis

Secondary injury is the main cause of high mortality and poor prognosis of TBI, which has recently been suggested to be related to ferroptosis. Polydatin, a monocrystalline compound extracted from the rhizome of Polygonum, has been shown to exert potential neuroprotective effects. However, its role and mechanism in the secondary injury of TBI has not been elucidated. In this study, the inhibition of Polydatin on ferroptosis was observed both in the hemoglobin treated Neuro2A cells in vitro and in TBI mouse model in vivo, characterized by reversion of accumulation or deposition of free Fe2+, increased content of MDA, decreased activity of key REDOX enzyme GPx4, cell death and tissues loss. Although Polydatin corrected the increased mRNA levels of ferroptosis signaling molecules GPX4, SLC7A11, PTGS2, and ATP5G3 after TBI, TBI and Polydatin treatment had no significant effect on their protein expression. Notably, Polydatin could completely reverse the decrease of GPx4 activity after TBI in vivo and in vitro, and the effect was stronger than that of the classical ferroptosis inhibitor FER-1 in vitro. Further, Polydatin has been shown to reduce the severity of acute neurological impairment and significantly improve subacute motor dysfunction in TBI mice. Our findings provided translational insight into neuroprotection with Polydatin in TBI by inhibiting ferroptosis mainly depending on the maintenance of GPx4 activity.

Polydatin Protects Bovine Mammary Epithelial Cells Against Zearalenone-Induced Apoptosis By Inhibiting Oxidative Responses and Endoplasmic Reticulum Stress.

Zearalenone (ZEA) is a mycotoxin of the Fusarium genus that can cause endoplasmic reticulum (ER) stress and Apoptosis in bovine mammary epithelial cells (MAC-T). Polydatin (PD), a glycoside purified from Polygonum cuspidatum, has antioxidant properties. This study aimed to explore whether PD can alleviate ZEA-induced damage on bovine mammary epithelial cells (MAC-T). We found that incasing the concentration of ZEA (0, 7.5, 15, 30, 60, 90, 120, and 240 μM) gradually decreased the cell viability. PD treatment alone at 5, 10, and 20 μM did not affect cell viability. Follow-up studies then applied 30 μM of ZEA and 5 μM of PD to treat cells; the results showed that the ZEA + PD treatment group effectively reduced cell oxidative damage compared with the ZEA treatment group. The qPCR analysis showed that ZEA treatment significantly up-regulated the expression of ER stress-related genes, relative to the control. However, adding PD significantly down-regulated the expression of ER stress-related genes. The cell apoptosis detection results showed that, compared with the ZEA treatment group, the ZEA + PD treatment group down-regulated the Bax gene and up-regulated the Bcl-2 gene expressions, which reduced the cell apoptosis rate and Caspase-3 activity. Taken together, these results indicate that PD reduces ZEA-induced apoptosis by inhibiting oxidative damage and ER stress.

Polydatin-Induced Direct and Bystander Effects in A549 Lung Cancer Cell Line

Polydatin, a natural analogue of resveratrol, has many biological activities. The better bioavailability of polydatin than resveratrol makes it an ideal candidate for therapy. Polydatin has protective effects against various diseases (cardiovascular, neurological, inflammatory, etc.) including cancer. However, its mechanism of action has not been fully established. Therefore, the present study was initiated to explore the mechanism/s associated with chemotherapeutic effects of polydatin in in vitro using lung cancer A549 cells. The effects of polydatin on cell proliferation and metastasis were assessed using various parameters like MTT, colony formation, DNA damage, apoptosis, and wound healing. Polydatin treatment reduced the proliferation of A549 cells by inducing DNA damage and cell cycle arrest in a concentration-dependent manner. The inhibition of cell proliferation was induced by dual mechanism of senescence and apoptosis. Proteins involved in various pathways were studied using western blotting and immunocytochemistry. Interestingly, senescent and apoptotic cells induced a differential bystander response (proliferative/toxic) in naïve A549 cells. Our results show that polydatin can induce both senescence and apoptosis in A549 cells in a concentration-dependent manner and the differential bystander effects induced by polydatin are regulated by mTOR pathway.