1.The effect of Resveratrol and Octreotide on peritoneal adhesions in a rat model
The Malaysian Journal of Pathology 2018;40(2):153-160
Introduction: The aim of this study was to investigate the efficacy of resveratrol and octreotide, agents that are used to prevent intra-abdominal adhesions in experimental models, in preventing intraperitoneal adhesions when used alone or in combination. Materials and Methods: The study employed 28 young female Wistar albino rats weighing 250-300 grams. An experimental adhesion model was created in each rat using serosal abrasion and peritoneal excision. They were divided into four groups, each comprising seven rats: Group 1, adhesion induction only; Group 2, resveratrol administration only; Group 3, octreotide administration only; and Group 4, administration of resveratrol and octreotide combination. The rats were monitored under appropriate conditions for 14 days and then underwent laparotomy. Macroscopic intensity and extensiveness of adhesions and microscopic changes in the granulation tissue (cellular intensity, reticular and collagen fibers, capillaries, elastic and smooth muscle fibers, fibrosis) were evaluated and graded. Kruskal-Wallis and Mann-Whitney U-test were used in statistical analysis and the level of statistical significance was established as p <0.05. Results: There was no significant difference between the groups in terms of the intensity and extensiveness of macroscopic adhesions (p=0.377 and p=0.319). There was a statistically significant difference between the microscopic scores of the groups according to Zühlke’s classification (p=0.026). The Bonferroni correction used to test for the differences revealed that the rats in Group 1 achieved significantly higher scores than the rats in Group 3 (p=0.016). Conclusion: Octreotide showed higher efficiency compared to the control group in microscopic classification; however, the two agents were not superior to each other or their combination was not superior in preventing intra-abdominal adhesions.
Octreotide
;
resveratrol
2.Resveratrol promotes the survival and neuronal differentiation of hypoxia-conditioned neuronal progenitor cells in rats with cerebral ischemia.
Yao YAO ; Rui ZHOU ; Rui BAI ; Jing WANG ; Mengjiao TU ; Jingjing SHI ; Xiao HE ; Jinyun ZHOU ; Liu FENG ; Yuanxue GAO ; Fahuan SONG ; Feng LAN ; Xingguo LIU ; Mei TIAN ; Hong ZHANG
Frontiers of Medicine 2021;15(3):472-485
Hypoxia conditioning could increase the survival of transplanted neuronal progenitor cells (NPCs) in rats with cerebral ischemia but could also hinder neuronal differentiation partly by suppressing mitochondrial metabolism. In this work, the mitochondrial metabolism of hypoxia-conditioned NPCs (hcNPCs) was upregulated via the additional administration of resveratrol, an herbal compound, to resolve the limitation of hypoxia conditioning on neuronal differentiation. Resveratrol was first applied during the in vitro neuronal differentiation of hcNPCs and concurrently promoted the differentiation, synaptogenesis, and functional development of neurons derived from hcNPCs and restored the mitochondrial metabolism. Furthermore, this herbal compound was used as an adjuvant during hcNPC transplantation in a photothrombotic stroke rat model. Resveratrol promoted neuronal differentiation and increased the long-term survival of transplanted hcNPCs. 18-fluorine fluorodeoxyglucose positron emission tomography and rotarod test showed that resveratrol and hcNPC transplantation synergistically improved the neurological and metabolic recovery of stroke rats. In conclusion, resveratrol promoted the neuronal differentiation and therapeutic efficiency of hcNPCs in stroke rats via restoring mitochondrial metabolism. This work suggested a novel approach to promote the clinical translation of NPC transplantation therapy.
Animals
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Brain Ischemia/drug therapy*
;
Cell Differentiation
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Hypoxia
;
Neurons
;
Rats
;
Resveratrol/pharmacology*
3.Inhibitory Effect of Resveratrol on the Proliferation of Multiple Myeloma Cells and the Underlying Mechanism.
Nan ZHOU ; Shu-Xing CAO ; Zhen-Zhen WANG ; Jian-Min LUO ; Xiao-Jun LIU ; Yin-Tao SHANG ; Lin YANG
Journal of Experimental Hematology 2023;31(4):1093-1099
OBJECTIVE:
To investigate the effect of resveratrol (RSV) on the proliferation of multiple myeloma (MM) cells and its molecular mechanism.
METHODS:
MM cells (MM1.S, RPMI-8226 and U266) were treated with different concentrations of RSV for 24-72 h. The effect of RSV on the proliferation of MM cells was detected by CCK-8 (cell counting kit-8) assay. RPMI-8226 cells were divided into RSV, miR-21 mimic, RSV+miR-21 mimic, miR-21 inhibitor and RSV+miR-21 inhibitor groups, and transfected with corresponding plasmids. The cell cycle distribution of each group was detected by flow cytometry with propidium iodide (PI) single staining. The cell apoptosis of each group was detected by AnnexinV-FITC/PE-PI double staining. The expression of miR-21 in MM cells treated with RSV and the expression of KLF5 mRNA in each group were detected by qRT-PCR. The expression of KLF5 protein in each group was detected by Western blot.
RESULTS:
RSV inhibited the proliferation and induced apoptosis of MM cells in a time- and dose-dependent manner. After the MM cells were treated with RSV, the number of cells in sub-G1 phase was increased, and that in G2/M phase was decreased. Moreover, RSV significantly downregulated the expression of miR-21 in MM cells, and the inhibitory effect of miR-21 mimic on KLF5 expression in MM cells was counteracted by RSV.
CONCLUSION
RSV may inhibit the proliferation and induce apoptosis of MM cells by inhibiting miR-21 and up-regulating KLF5 expression.
Humans
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Resveratrol/pharmacology*
;
Multiple Myeloma/metabolism*
;
Cell Proliferation
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Cell Line, Tumor
;
Apoptosis
;
MicroRNAs/genetics*
4.Resveratrol Modulates Bone Mineral Density and Bone Mineral Content in A Rat Model of Male Hypogonadism.
Hussein F SAKR ; Boudaka AMMAR ; Amira ALKHARUSI ; I AL-LAWATI ; Mahmoud ALKHATEEB ; Basim H ELESAWY
Chinese journal of integrative medicine 2023;29(2):146-154
OBJECTIVE:
To determine whether resveratrol (Res) can correct osteoporosis induced in a rat model of male hypogonadism.
METHODS:
Thirty-two rats were randomly divided into 4 groups, 8 in each group; 1) a control sham group: underwent a similar surgical procedure for induction of orchiectomy (ORCD) without ligation of any arteries or veins or removal of the testis and epididymis; 2) a control + Res-treated group (Con+Res): underwent sham surgery similar to the control, but was then treated with Res, as described below; 3) an ORCD-induced group: bilateral ORCD surgery as described above, and 4) a ORCD+Res-treated group: bilateral ORCD surgery followed by Res treatment. Res treatment began 4 weeks after ORCD and continued for 12 weeks. After 12 weeks, bone mineral density (BMD) and bone mineral content (BMC) were measured in the tibia and femur of each rat's right hind leg. Blood levels of bone turnover indicators such as deoxypyridinoline (Dpd), N-telopeptide of type I collagen (NTX I), alkaline phosphatase (ALP), and osteocalcin (OC), as well as receptor activator of nuclear factor kappa B (RANK) and osteoprotegerin (OPG) were assessed.
RESULTS:
ORCD significantly decreased BMD (P<0.01) and significantly increased bone resorption, manifested by increased RANK. In addition, it inhibited serum levels of OPG and OC. Res treatment after ORCD effectively increased serum levels of bone formation markers such as OPG and OC, compared with testisectomized rats (P<0.05).
CONCLUSION
Res could ameliorate bone loss induced by male hypogonadism, possible via restoration of the normal balance between RANK and OPG.
Rats
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Male
;
Animals
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Bone Density
;
Resveratrol/pharmacology*
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Osteoporosis
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Osteoprotegerin/pharmacology*
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Bone Remodeling
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Hypogonadism
;
RANK Ligand/pharmacology*
5.Resveratrol Prevents Vibrio vulnificus-Induced Sepsis by Attenuating Necroptosis.
Ke Wei QIN ; Jian Fei LIU ; Cheng Lin WU ; Chen ZHANG ; Li Jun ZHOU
Biomedical and Environmental Sciences 2023;36(2):135-145
OBJECTIVE:
This study investigated how the natural phytophenol and potent SIRT1 activator resveratrol (RSV) regulate necroptosis during Vibrio vulnificus (V. vulnificus)-induced sepsis and the potential mechanism.
METHODS:
The effect of RSV on V. vulnificus cytolysin (VVC)-induced necroptosis was analyzed in vitro using CCK-8 and Western blot assays. Enzyme-linked immunosorbent assays and quantitative real-time polymerase chain reaction, western blot, and immunohistochemistry and survival analyses were performed to elucidate the effect and mechanism of RSV on necroptosis in a V. vulnificus-induced sepsis mouse model.
RESULTS:
RSV relieved necroptosis induced by VVC in RAW264.7 and MLE12 cells. RSV also inhibited the inflammatory response, had a protective effect on histopathological changes, and reduced the expression level of the necroptosis indicator pMLKL in peritoneal macrophages, lung, spleen, and liver tissues of V. vulnificus-induced septic mice in vivo. Pretreatment with RSV downregulated the mRNA of the necroptosis indicator and protein expression in peritoneal macrophages and tissues of V. vulnificus-induced septic mice. RSV also improved the survival of V. vulnificus-induced septic mice.
CONCLUSION
Our findings collectively demonstrate that RSV prevented V. vulnificus-induced sepsis by attenuating necroptosis, highlighting its potency in the clinical management of V. vulnificus-induced sepsis.
Animals
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Mice
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Necroptosis
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Resveratrol/therapeutic use*
;
Vibrio vulnificus
;
Sepsis/drug therapy*
;
Blotting, Western
6.Molecular mechanism of resveratrol combined with irinotecan in treatment of colorectal cancer.
Fang LI ; Rui-Yang YAN ; Kai-Yang LI ; Jue WANG ; Li WANG ; Hui SHEN ; Cai-Li HAN ; Min LIU
China Journal of Chinese Materia Medica 2023;48(8):2212-2221
This study aimed to investigate the mechanism of resveratrol(RES) combined with irinotecan(IRI) in the treatment of colorectal cancer(CRC). The targets of RES, IRI, and CRC were obtained from databases, and the targets of RES combined with IRI in the treatment of CRC were acquired by Venn diagram. The protein functional cluster analysis, GO and KEGG enrichment analyses were performed. In addition, the protein-protein interaction(PPI) network was constructed. The core target genes were screened out and the target-signaling pathway network was set up. IGEMDOCK was used to dock the core target gene molecules. Besides, the relationship between the expression level of key target genes and the prognosis and immune infiltration of CRC was analyzed. Based on the in vitro cell experiment, the molecular mechanism of RES combined with IRI in the treatment of CRC was explored and analyzed. According to the results, 63 potential targets of RES combined with IRI were obtained for CRC treatment. Furthermore, cluster analysis revealed that protein functions included 23% transmembrane signal receptors, 22% protein modifying enzymes, and 14% metabolite converting enzymes. GO analysis indicated that BPs were mainly concentrated in protein autophosphorylation, CCs in receptor complex and plasma membrane, and MFs in transmembrane receptor protein tyrosine kinase activity. Moreover, KEGG signaling pathways were mainly enriched in central carbon metabolism in cancer. The key targets of RES combined with IRI in the treatment of CRC were PIK3CA, EGFR, and IGF1R, all of which were significantly positively correlated with the immune infiltration of CRC. As shown by the molecular docking results, PIK3CA had the most stable binding with RES and IRI. Compared with the results in the control group, the proliferation ability and EGFR protein expression of CRC cells in the RES-treated group, the IRI-treated group, and the RES+IRI treated group significantly decreased. Moreover, the cell proliferation ability and EGFR protein expression level of CRC cells in the RES+IRI treated group were remarkably lower than those in the IRI-treated group. In conclusion, PIK3CA, EGFR, and IGF1R are the key targets of RES combined with IRI in CRC treatment. In addition, RES can inhibit the proliferation of CRC cells and improve IRI chemoresistance by downregulating the EGFR signaling pathway.
Humans
;
Irinotecan
;
Colorectal Neoplasms/genetics*
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Resveratrol
;
Molecular Docking Simulation
;
ErbB Receptors/genetics*
7.Effect of resveratrol on PTEN expression and fibrosis of renal tubular epithelial cells in a high-glucose environment.
Lan SUN ; Xu-Xian WU ; Yu-Fen PENG
China Journal of Chinese Materia Medica 2021;46(18):4793-4799
This study explored the effects of resveratrol(Res) on the expression of phosphatase and tensin homolog deleted on chromosome ten(PTEN) and the fibrosis of rat renal tubular epithelial cells in a high-glucose environment and the possible mechanism underlying the fibrosis reduction. After the pretreatment of rat renal tubular epithelial cells(NRK-52 E) cultured in a high-glucose condition with Res or PTEN inhibitor SF1670, they were divided into several groups, i.e., normal glucose(NG), normal glucose + SF1670(NS), high glucose(HG), high glucose + SF1670(HS), high glucose + Res at different concentrations(5, 10, 25 μmol·L~(-1)). The expression and distribution of E-cadherin and α-SMA in renal tubular epithelial cells were observed by immunofluorescence cytochemistry. The protein expression levels of PTEN, E-cadherin, α-SMA, p-Akt~((Thr308)) and collagen Ⅳ were determined by Western blot. Real-time PCR was employed to detect the expression of PTEN mRNA. Compared with the NG group, the HG group witnessed the reduced expression of PTEN mRNA, PTEN protein and E-cadherin protein, but saw the increased expression of α-SMA, p-Akt~((Thr308)) and collagen Ⅳ proteins. Besides, with the increase in Res concentration, the expression levels of PTEN mRNA, PTEN protein and E-cadherin protein gradually increased, while those of α-SMA, collagen Ⅳ, p-Akt~((Thr308)) proteins gradually decreased in the Res groups, showing a dose-effect dependence, compared with the HG group. No distinct difference was found between the NS group and the NG group. The expression level of E-cadherin was even lower and those of α-SMA, p-Akt~((Thr308)), and collagen Ⅳ were higher in the HS group than in the HG group, with no marked difference shown in the two groups in terms of PTEN mRNA and protein. Although the PTEN inhibitor did not affect PTEN, the expression changes of the other proteins were opposite to the results after Res treatment and the fibrosis was aggravated, which suggested that SF1670 promoted the fibrosis by inhibiting PTEN, activating Akt and increasing the synthesis of collagen Ⅳ and other extracellular matrix. The results show that Res can antagonize the high glucose-mediated fibrosis of renal tubular epithelial cells. This may be achieved via the up-regulation of PTEN and the inhibition of PI3 K/Akt signaling pathway.
Animals
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Epithelial Cells
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Fibrosis
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Glucose
;
PTEN Phosphohydrolase/genetics*
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Rats
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Resveratrol/pharmacology*
8.Inhibit affection of resveratrol on the growth of Hep-2 cell line.
Yunchuan LI ; Yanwei XU ; Dan HUANG ; Linlin JIANG ; Kesen LI
Journal of Clinical Otorhinolaryngology Head and Neck Surgery 2007;21(24):1129-1131
OBJECTIVE:
To study the inhibitory effect of resveratrol on growth of human laryngeal cancer cell line, Hep-2.
METHOD:
Count cell number under microscope, MTT assay was used to determine the cell growth inhibitory rate. Soft agar colony forming experiment was performed to observe the proliferation ability, before or after resveratrol treatment.
RESULT:
Resveratrol was able to depress cell growth and inhibit cell proliferation.
CONCLUSION
Resveratrol strongly inhibit Hep-2 cell proliferation in a time- and dose-dependent manner.
Cell Cycle
;
drug effects
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Cell Line, Tumor
;
Cell Proliferation
;
drug effects
;
Dose-Response Relationship, Drug
;
Humans
;
Resveratrol
;
Stilbenes
;
pharmacology
9.Network pharmacology-based study of the therapeutic mechanism of resveratrol for Alzheimer's disease.
Yingyan FANG ; Zhenhong SU ; Wenxia SI ; Yuancheng LIU ; Jie LI ; Peng ZENG
Journal of Southern Medical University 2021;41(1):10-19
OBJECTIVE:
To investigate the therapeutic mechanism of resveratrol (RES) for Alzheimer's disease (AD) in light of network pharmacology.
METHODS:
We searched PubChem, BATMAN-TCM, Genecards, AD, TTD, String 11.0, AlzData, SwissTargetPrediction, Metascape and other databases for the therapeutic targets of RES and human AD-related targets. The intersection was determined using Venny 2.1 to obtain the therapeutic targets of RES for AD. The protein-protein interaction (PPI) network was constructed, the gene ontology (GO) was enriched and the Kyoto Encyclopedia of Genes and Genomes pathway (KEGG pathway) were analyzed. Cytoscape 3.7.1 software was used to construct a target-signaling pathway network of RES in the treatment of AD. Molecular docking verification was carried out on SwissDock (http://www.swissdock.ch/docking). We examined a 293Tau cell model of AD for changes in protein levels of pS396, pS199, Tau5, CDK5, glycogen synthase kinase 3β (GSK3β) and p-GSK3β in response to RES treatment using Western blotting.
RESULTS:
We obtained 182 targets of RES, 525 targets related to AD, and 36 targets of RES for AD treatment, among which 34.6% of the targets were protein-modifying enzymes, 27.7% were metabolite invertase, 13.8% were gene-specific transcriptional regulators, and 10.3% were transporters. The core key targets of RES in the treatment of AD included INS, APP, ESR1, MMP9, IGF1R, CACNA1C, MAPT (microtubule- associated protein Tau), MMP2, TGFB1 and GSK3B. Enrichment analysis of GO biological process suggested that the biological function of RES in AD treatment mainly involved the response to β-amyloid protein, positive regulation of transferase activity, the transmembrane receptor protein tyrosine kinase signaling pathway, regulation of behavior, learning or memory, aging, and transmembrane transport. KEGG pathway enrichment analysis showed that the most significantly enriched signaling pathways were AD pathway, PI3K-AKT signaling pathway, cGMP-PKG signaling pathway, and MAPK signaling pathway. Molecular docking results showed that RES had strong binding with ESR1, GSK3B, MMP9, IGF1R, APP and INS. In the cell model of AD, treatment with 50 μmol/L RES for 12 h significantly reduced the levels of pS396 and pS199 by regulating CDK5 and GSK3β activity (
CONCLUSIONS
RES produces therapeutic effects on AD by acting on multiple targets and affecting multiple signaling pathways and improves AD-associated pathologies
Alzheimer Disease/genetics*
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Drugs, Chinese Herbal/therapeutic use*
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Humans
;
Molecular Docking Simulation
;
Phosphatidylinositol 3-Kinases
;
Resveratrol/pharmacology*
10.Resveratrol inhibits Ca
Mikio MARUMO ; Kazumi EKAWA ; Ichiro WAKABAYASHI
Environmental Health and Preventive Medicine 2020;25(1):70-70
BACKGROUND:
Resveratrol has been shown to inhibit platelet aggregation. However, the mechanism for this action of resveratrol remains to be clarified. The purpose of this study was to elucidate the Ca
METHODS:
Ca
RESULTS:
Thapsigargin-induced Ca
CONCLUSIONS
The results suggest that resveratrol inhibits thrombin-induced platelet aggregation through decreasing Ca
Antioxidants/administration & dosage*
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Calcium/physiology*
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Humans
;
Platelet Aggregation/drug effects*
;
Platelet Aggregation Inhibitors/pharmacology*
;
Resveratrol/pharmacology*
;
Signal Transduction/drug effects*