BIOORGANIC CHEMISTRY
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2025
·
IF 4.7
Nan Li,Feng-xiang Pang,Yu-wan Zhou,Shou-chang Ding,Chuan-jian Shi,Rui-jia Wen,Yong-xin Mai,Xian-lin Wu,Jin-fang Zhang
Background Osteosarcoma (OS) is a malignant primary tumor in bone tissues, and Methotrexate (MTX) is widely used as a chemotherapeutic drug for OS in clinical treatment. However, MTX resistance is a major challenge for OS patients. Polydatin (PD) is an extract derived from Reynoutria japonica Houtt and has been identified as a potential agent for reversing chemotherapy resistance in cancer. We therefore wondered whether PD could alleviate MTX resistance in OS. Methods The effect of PD on MTX resistance was investigated. And H19 expression was examined in the PD-treated OS cells. The association between H19 and MTX resistance in osteosarcoma was investigated.The effects of H19 on MTX resistance in osteosarcoma were evaluated by cell proliferation, colony formation, ChIP and western blotting assays. In order to investigate the molecular mechanism of PD underlying methotrexate resistance in OS, the cell proliferation, colony formation, q-PCR and western blotting were examined. Results In the present study, PD was found to act as a novel MTX sensitizer, and significantly enhanced the suppressive effects of MTX on OS in vitro and in vivo . Mechanically, PD was demonstrated to suppress the expression of long non-coding RNA H19 as well as its binding protein histone methyltransferase Enhancer of zeste homolog 2 (EZH2), and thus reduced the trimethylation of histone H3K9 (H3K9me3) and K27 (H3K27me3). Furthermore, H19 knowndown increased the binding ability of H3K9me3 and H3K27me3 with the folate metabolism-related genes RFC-1 and PCFT's promoter, and influenced folate metabolism and MTX resistance. Conclusion In conclusion, our results indicated that PD alleviated MTX resistance in OS via the H19/H3K27me3/H3K9me3 mediated folate metabolism regulatory axis. The translational potential of this article The findings of this study validate the function of PD in alleviating MTX resistance, and provide the new insight into developing PD as a promising drug candidate for the MTX resistant OS patients.
研究领域:
肿瘤学
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分子生物学
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药理学
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产品关联
DOI
PubMed
高影响因子
IMMUNOPHARMACOLOGY AND IMMUNOTOXICOLOGY
·
2021
·
IF 2.73
Shengyu Sun,Yourui Zou,Shaocai Hao,Zhanfeng Niu,Liang Wu
Objective Polydatin has been used in the treatment of various inflammatory diseases. However, its role in the regulation of neuroinflammation has not been reported. In this study, we designed to investigate the anti-inflammatory effects of polydatin in LPS-stimulated BV2 microglia cells.Methods Inflammatory mediators TNF-α, IL-1β, NO, and PGE2 production were measured by ELISA. The protein of signaling pathways were detected by western blot analysis.Results The results showed that polydatin significantly ameliorated the production of TNF-α, IL-1β, NO, and PGE2 up-regulated by LPS. Polydatin also blocked LPS-induced NF-κB activation. In addition, PI3K and AKT, the up-stream molecules of NF-κB signaling pathway, were inhibited by the treatment of polydatin. Also, we found the formation of lipid rafts was inhibited by polydatin through attenuating the cholesterol content. Finally, polydatin was found to increase the expression of ABCA1 and ABCG1.Conclusion In conclusion, the results of the present study suggested that polydatin exhibited its anti-inflammatory effects in BV2 cells through disrupting lipid rafts, which subsequently inhibiting PI3K/AKT signaling pathway.
研究领域:
药理学
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神经科学
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免疫学
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产品关联
DOI
PubMed
高影响因子
Food Bioscience
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2024
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IF 4.8
Zhengming Xu,Xi Zhu,Jiayi Lian,Yuan Guan,Zhengang Zhao
Exploiting efficient tyrosinase inhibitors and utilizing the inhibition mechanism are of great significance to avoid enzymatic browning in food and skin melanogenesis. Polydatin had excellent tyrosinase inhibitory activity in vitro with IC 50 value of 24.90 μM; however, it exhibited unsatisfactory inhibitory activity intracellularly, which was associated with poor cellular uptake. Fortunately, 6″- O -lauryl polydatin was green-efficiently synthesized by lipase-catalyzed acylation under microwave irradiation. 6″- O -lauryl polydatin exhibited superior mono-/diphenolase inhibitory activity within 100 μM than kojic acid, which had IC 50 of 221 μM. Neither polydatin nor 6″- O -lauryl polydatin bound to the catalytic site, but rather bound noncovalently to the allosteric site 2 of tyrosinase through hydrogen bonds and hydrophobic interactions according to molecular simulations, thereby inducing secondary structure unfolding and reducing tyrosinase activity. 6″- O -lauryl polydatin showed stronger anti-browning effects than polydatin in the natural storage of potato and apple pieces. Polydatin and kojic acid did not induce apoptosis, but 6″- O -lauryl polydatin inhibited human melanin A375 cell proliferation by stimulating ROS overproduction and regulating cell cycle and apoptotic pathways. In addition, lipophilic 6″- O -lauryl polydatin had greater cellular uptake though suffered from intracellular hydrolysis, and exerted better tyrosinase and melanogenesis inhibitory activity than polydatin and kojic acid based on mouse B16F10 melanoma cell model. The results suggested polydatin and 6″- O -lauryl polydatin were promising tyrosinase inhibitors for anti-browning in foods or cosmetics fields.
研究领域:
食品科学
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药学
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化妆品化学
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酶学
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产品关联
DOI
高影响因子
TROPICAL JOURNAL OF PHARMACEUTICAL RESEARCH
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2016
·Vol. 14
·期 12
·2217-2222
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IF 0.543
Yang Liu,Baogang Wang,Qian Zhang,Kunfeng Liu,Quanxi Wu
Purpose: To investigate the physicochemical properties and lipophilicity of polydatin-lecithin complex.Methods: The complex of polydatin-lecithin was prepared by solvent method. The physicochemical properties of the complex were investigated by ultraviolet-visible spectrometry (UV), infrared spectrometry (IR), differential scanning calorimetry (DSC), x ray diffractometry (XRD) and scanning electron microscopy (SEM). Its solubility in n-octanol at 25 °C was examined by high performance liquid chromatography (HPLC).Results: The UV and IR spectra of the complex showed an additive effect of polydatin-lecithin, in which the characteristic absorption of their respective peaks were retained. DSC and XRD results suggest that the complex mainly showed the presence of lecithin with the characteristic peaks for polydatin absent, while SEM demonstrated that polydatin was dispersed in lecithin. HPLC analysis found that the solubility of polydatin in n-octanol at 25 °C was enhanced from 0.41 mg/mL to 21.98 mg/mL by complexing with lecithin, indicating that the lipophilicity of polydatin was significantly improved.Conclusion: Polydatin and lecithin in the complex are combined by non-covalent bonds, and did not form a new compound. The lipophilicity of polydatin increased to 21.98 mg/mL from 0.41 mg/mL as a result of complexation.Keywords: Polydatin, Lecithin, Complex, Physicochemical property, Lipophilicity
研究领域:
药剂学
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化学
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DOI
高影响因子
European Review for Medical and Pharmacological Sciences
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2022
·Vol. 26
·期 12
·4392-4402
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IF 3.784
Yuan Y,Feng G,Yang J,Yang C,Tu YH
OBJECTIVE: Osteoporosis is a severe degenerative chronic metabolic bone disease associated with high fracture risk. Polydatin (PD), a major bioactive component of Polygonum cuspidatum, has antioxidant and anti-inflammatory effects. This study investigated the anti-osteoporotic activity of PD in ovariectomized (OVX) mice and elucidated its underlying molecular mechanisms. SUBJECTS AND METHODS: An osteoporosis mouse model was established using OVX mice. OVX mice were then administered 10 or 40 mg/kg of PD for 60 days. Micro-CT and three-point bending tests were used to determine the therapeutic activities of PD in OVX mice. H&E staining was used to determine whether PD induced hepatorenal toxicity. In addition, the cellular and molecular mechanisms underlying the functionality of PD were elucidated. RESULTS: Micro-CT results showed that compared to control mice, the bone mass of OVX mice was significantly reduced due to estrogen deficiency; however, PD administration significantly elevated bone mass. Furthermore, PD substantially improved the trabecular microstructure parameters of the femur and enhanced bone strength compared with OVX mice. Hepatorenal toxicity was not observed in liver and kidney samples stained with H&E. PD significantly increased the proliferation of pre-osteoblast MC3T3-E1 cells and upregulated the expression of osteogenic differentiation markers compared to those in controls, as determined by qRT-PCR and western blotting. CONCLUSIONS: PD exerted a significant anti-osteoporotic effect in OVX mice by promoting osteogenesis. PD has great potential as a therapeutic option for osteoporosis.
研究领域:
药理学
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骨科
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分子生物学
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内分泌学
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DOI
PubMed
高影响因子
ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS
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2017
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IF 3.165
Xinyi Zhao,Rui Li,Ying Liu,Xuehong Zhang,Min Zhang,Zhi Zeng,Limin Wu,Xuelin Gao,Tian Lan,Yiqing Wang
Reactive oxygen species (ROS) play a key role in chronic liver injury and fibrosis. Polydatin, a glucoside of resveratrol , has been shown to possess anti-oxidative bioactivity. It has been demonstrated that resveratrol has many therapeutic effects on liver disorders including liver fibrosis. Recent study showed that polydatin prevented acute liver injury after carbon tetrachloride (CCl 4 ) induction. However, the protective effects of polydatin on chronic liver injury and fibrosis has not been understood. Thus, we aimed to determine the roles of polydatin in chronic liver injury and fibrosis. Mice were induced by CCl 4 for 6 weeks to develop chronic liver injury and fibrosis. Mice were treated with polydatin for 3 and 6 weeks, respectively. After 6 week injection of CCl 4 , the levels of serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) were markedly increased. The hepatic expression of α-SMA, collagen deposition and macrophage filtration were also increased. Furthermore, hepatic 4-HNE production and NOX4 expression were also increased in CCl 4 -induced mice. In contrast, polydatin ameliorated impaired liver function and histology. Moreover, polydatin attenuated liver fibrosis and inflammation in mice induced by CCl 4 . Additionally, polydatin suppressed hepatic 4-HNE production and NOX4 expression. In conclusion, polydatin ameliorate chronic liver injury and fibrosis through inhibition of oxidative stress and inflammation.
研究领域:
药理学
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肝病学
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毒理学
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产品关联
DOI
PubMed
高影响因子
BIOMEDICINE & PHARMACOTHERAPY
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2016
·
IF 2.326
ZhenQiu Chen,QiuShi Wei,GuoJu Hong,Da Chen,Jiang Liang,Wei He,Mei Hui Chen
Bone marrow stromal cells (BMSCs) have proven to be useful for the treatment of numerous human diseases . However, the reparative ability of BMSCs is limited by their poor migration. Polydatin , widely used in traditional Chinese remedies, has proven to exert protective effects to BMSCs. However, little is known about its role in BMSCs migration. In this study, we studied the effects of polydatin on rat BMSCs migration using the scratch wound healing and transwell migration assays. Our results showed polydatin could promote BMSCs migration. Further experiments showed activation of ERK 1/2, but not JNK , was required for polydatin-induced BMSCs migration, suggesting that polydatin may promote BMSCs migration via the ERK 1/2 signaling pathways . Taken together, our results indicate that polydatin might be beneficial for stem cell replacement therapy by improving BMSCs migration.
研究领域:
药理学
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细胞生物学
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干细胞研究
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DOI
PubMed
高影响因子
CHEMICAL ENGINEERING JOURNAL
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2025
·
IF 13.2
Binke Wang,Xinyu Qi,Ruping Yang,Xu Xu,Shiyao Li,Chunli Zhang,Haitao Yu
Liver cancer is one of the most prevalent and deadly malignancies worldwide, with limited effective therapeutic strategies. Although doxorubicin (DOX) is widely used as a frontline chemotherapeutic agent, its severe cardiotoxicity and lack of tumor selectivity significantly limited its clinical applications. Polydatin (PLD), a natural antioxidant and anticancer compound, has shown promise as an adjuvant for reducing DOX-induced cardiotoxicity, yet its poor bioavailability hinders its therapeutic potential. To improve the therapeutic efficacy of DOX while reducing systemic toxicity, we developed a hyaluronic acid (HA)-functionalized cubosome-based nanosystem co-loaded with DOX and PLD (1:3 ratio), i.e. HA 3% -D/P-CUBS + , to specifically target tumor sites with enhanced antitumor efficiency and alleviated DOX-induced cardiotoxicity. HA 3% -D/P-CUBS + significantly improved drug internalization and induced apoptosis in hepatocellular carcinoma cells (HepG-2 and HUH-7). Meanwhile, HA 3% -D/P-CUBS + protected normal hepatocytes (HL-7702 and AML-12) and reduced oxidative stress in cardiomyocytes (H9C2 cells). Notably, HA 3% -D/P-CUBS + inhibited in vivo tumor growth of 94 % without causing damage to vital organs, leading to improved survival rates. Moreover, it also mitigated DOX-induced oxidative stress by restoring the balance between oxidative and antioxidant systems. These findings highlight HA 3% -D/P-CUBS + as a promising and synergistic nanomedicine for targeted live cancer therapy, providing new insights into combination chemotherapy with enhanced safety and efficacy.
研究领域:
肿瘤学
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纳米医学
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药剂学
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分子药理学
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转化医学
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氧化应激
✓ 已验证
产品关联
DOI
高影响因子
JOURNAL OF THERMAL ANALYSIS AND CALORIMETRY
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2025
·
IF 3.1
Wu Chuan Chao,Ye You Wen,Cheng Zhao Yang,Li Yu qi,Liu Yan,Wu Hai Xia,Wu Jian Rong,Liu Qing Tao,Huang Yi Na
Polydatin (PD) possesses a variety of pharmacological activities, but its poor aqueous solubility, stability, and bioavailability limit its application. To improve PD’s water solubility, PD/β-CD inclusion complexes were prepared by solution stirring method and characterized by infrared spectroscopy, X-ray diffraction spectroscopy, nuclear magnetic resonance hydrogen spectroscopy, and molecular docking. The results showed that PD and β-CD successfully generated an inclusion complex with a 1:1 host–guest ratio and a stabilization constant of 4362 M −1 . To further explore the beneficial potential, the antioxidant capacity of PD/β-CD after digestion and the pattern of change during digestion were evaluated in stages by simulated digestion and simulated fermentation in vitro. The simulated digestion process hardly changed the total sugar and reducing sugar contents ( P > 0.05). During the simulated fermentation process, the pH value kept decreasing, and the short-chain fatty acid content in the fermentation products increased significantly ( P < 0.05), with the acetic acid content showing the highest increment (1.90 ± 0.35 g L −1 ). In addition, at the phylum level, PD/β-CD inclusion significantly increased the relative abundance of Firmicutes and Actinomycetes and significantly decreased the relative abundance of Proteobacteria , relative to the β-CD group. At the genus level, beneficial bacteria such as Bifidobacterium and Lactobacillus proliferated in the PD/β-CD group, and the relative abundance of potentially pathogenic bacteria such as Streptococcus , and Escherichia-Shigella was significantly reduced. The experimental results indicated that PD/β-CD inclusion complexes were a potential prebiotic with high potential in the field of medicine and health care.
研究领域:
药学
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营养生物化学
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微生物学
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药物递送系统
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产品关联
DOI
高影响因子
PROCESS BIOCHEMISTRY
·
2016
·
IF 2.529
Zhao-Yu Wang,Yan-Hong Bi,Rong-Ling Yang,Xiang-Jie Zhao,Ling Jiang,Cheng-Xin Ding,Shang-Yong Zheng
Efficient lipase-mediated research work was successfully exploited for synthesizing potential 6″- O -acyl-polydatin prodrugs in biomass-derived 2-methyltetrahydrofuran (2-MeTHF). The results of the enzyme recognitions of nine acyl donors evidently demonstrated that the position and number of the C C double bond in acyl chains profoundly influenced the behavior of the enzyme, which could be attributable to the resonance effect between the double bond and carbonyl group. Further investigations showed that introducing various acyl groups into the polydatin apparently enhanced its pH stability and 1-octanol-water partition coefficient (log P ). With regard to the human cervical cancer siHa cell apoptosis by a flow cytometry assay, the lipophilic 6″- O -sorboyl-polydatin exhibited improved apoptosis-inducing capability than the parent drug. The presence of the more lipophilic sorboyl chain in the acylated derivative could account for this.
研究领域:
药物化学
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癌症研究
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酶学
·
有机合成
✓ 已验证
产品关联
DOI
高影响因子
Food & Function
·
2022
·Vol. 13
·期 13
·7302-7319
·
IF 6.317
Li-Ming Yu,Xue Dong,Ning Li,Hui Jiang,Ji-Kai Zhao,Yin-Li Xu,Deng-Yue Xu,Xiao-Dong Xue,Zi-Jun Zhou,Yu-Ting Huang,Qiu-Sheng Zhao,Zhi-Shang Wang,Zong-Tao Yin,Hui-Shan Wang
Polydatin has attracted much attention as a potential cardioprotective agent against ischemic heart disease and diabetic cardiomyopathy. However, the effect and mechanism of polydatin supplementation on alcoholic cardiomyopathy (ACM) are still unknown. This study aimed to determine the therapeutic effect of polydatin against ACM and to explore the molecular mechanisms with a focus on SIRT6–AMP-activated protein kinase (AMPK) signaling and mitochondrial function. The ACM model was established by feeding C57/BL6 mice with an ethanol Lieber–DeCarli diet for 12 weeks. The mice received polydatin (20 mg kg−1) or vehicle treatment. We showed that polydatin treatment not only improved cardiac function but also reduced myocardial fibrosis and dynamin-related protein 1 (Drp-1)-mediated mitochondrial fission, and enhanced PTEN-induced putative kinase 1 (PINK1)–Parkin-dependent mitophagy in alcohol-treated myocardium. Importantly, these beneficial effects were mimicked by SIRT6 overexpression but abolished by the infection of recombinant serotype 9 adeno-associated virus (AAV9) carrying SIRT6-specific small hairpin RNA. Mechanistically, alcohol consumption induced a gradual decrease in the myocardial SIRT6 level, while polydatin effectively activated SIRT6–AMPK signaling and modulated mitochondrial dynamics and mitophagy, thus reducing oxidative stress damage and preserving mitochondrial function. In summary, these data present new information regarding the therapeutic actions of polydatin, suggesting that the activation of SIRT6 signaling may represent a new approach for tackling ACM-related cardiac dysfunction.
研究领域:
药理学
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心脏病学
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分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Advances in Experimental Medicine and Biology
·
2016
·
IF 1.953
Jin Ju,Li Yan,Zhang Xiuli,Chen Tongsheng,Wang Yifei,Wang Zhiping
Cellular damage such as oxidation and lipid peroxidation, and DNA damage induced by free-radicals like reactive oxygen species, has been implicated in several diseases. Radicals generated by 2,2-azobis (2-amidino-propane) dihydrochloride (AAPH) are similar to physiologically active ones. In this study we found that polydatin, a resveratrol natural precursor derived from many sources, has the capacity of free radical scavenging and antioxidative damage. Using free radical scavenging assays, the IC 50 values of polydatin were 19.25 and 5.29 μg/ml with the DPPH and the ABTS assay, respectively, and 0.125 mg ferrous sulfate/1 mg polydatin with the FRAP assay. With the AAPH-induced oxidative injury cell model assay, polydatin showed a strong protective effect against the human liver tumor HepG2 cell oxidative stress damage. These results indicate that the antioxidant properties of polydatin have great potential for use as an alternative to more toxic synthetic antioxidants as an additive in food, cosmetics and pharmaceutical preparations for the treatment of oxidative diseases. Keywords Free radical scavenging Polydatin Antioxidation AAPH
研究领域:
药理学
·
生物化学
✓ 已验证
DOI
PubMed
高影响因子
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