Therapeutic Effects Of Resveratrol Research Articles

Does Resveratrol Improve Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD)?

Metabolic dysfunction-associated steatotic liver disease (MASLD) is influenced by a variety of factors, including environmental and genetic factors. The most significant outcome is the alteration of free fatty acid and triglyceride metabolism. Lipotoxicity, impaired autophagy, chronic inflammation, and oxidative stress, as well as coexisting insulin resistance, obesity, and changes in the composition of gut microbiota, are also considered crucial factors in the pathogenesis of MASLD. Resveratrol is a polyphenolic compound that belongs to the stilbene subgroup. This review summarises the available information on the therapeutic effects of resveratrol against MASLD. Resveratrol has demonstrated promising antisteatotic, antioxidant, and anti-inflammatory activities in liver cells in in vitro and animal studies. Resveratrol has been associated with inhibiting the NF-κB pathway, activating the SIRT-1 and AMPK pathways, normalizing the intestinal microbiome, and alleviating intestinal inflammation. However, clinical studies have yielded inconclusive results regarding the efficacy of resveratrol in alleviating hepatic steatosis or reducing any of the parameters found in MASLD in human patients. The lack of homogeneity between studies, low bioavailability of resveratrol, and population variability when compared to animal models could be the reasons for this.

A short treatment with resveratrol after a renal ischaemia-reperfusion injury prevents maladaptive repair and long-term chronic kidney disease in rats.

Acute kidney injury (AKI) often triggers physiological processes aimed at restoring renal function and architecture. However, this response can become maladaptive, leading to nephron loss and fibrosis. Although the therapeutic effects of resveratrol (RSV) are well established, its impact after AKI and for subsequent chronic kidney disease (CKD) remains unclear. This study assessed whether transient administration of RSV following ischaemia-reperfusion injury (IRI) could prevent the progression to CKD. Forty-one male Wistar rats were assigned randomly to sham surgery, bilateral renal ischaemia for 30min (IR) or IR+RSV. The RSV treatment commenced 24h after IRI and continued for 10days. The rats were studied for either 10days or 5months, after which kidney function and structure were evaluated. Mitochondrial homeostasis, oxidant defence and renal inflammation state were also evaluated. Despite having the same severity of AKI, rats receiving RSV for 10days after IRI exhibited significant improvement in kidney histological injury and reduced inflammation, although renal haemodynamic recovery was less pronounced. Resveratrol effectively prevented the elevation of tubular injury-related molecules and profibrotic signalling with reduced myofibroblast proliferation. Furthermore, RSV substantially improved the antioxidant response and mitochondrial homeostasis. After 5months, RSV prevented the transition to CKD, as evidenced by the prevention of progressive proteinuria, renal dysfunction and tubulointerstitial fibrosis. This study demonstrates that a brief treatment with RSV following IRI is enough to prevent maladaptive repair and the development of CKD. Our findings highlight the importance of the early days of reperfusion, indicating that maladaptive responses can be reduced effectively following severe AKI. KEY POINTS: Physiological processes activated after acute kidney injury (AKI) can lead to maladaptive responses, causing nephron loss and fibrosis. Prophylactic renoprotection with resveratrol (RSV) has been described in experimental AKI, but its impact after AKI and for subsequent chronic kidney disease (CKD) remains unclear. In this study, we found that histological tubular injury persists 10days after ischaemia-reperfusion injury and contributes to a failed repair phenotype in proximal tubular cells. Short-term RSV intervention influenced the post-ischaemic repair response and accelerated tubular recovery by reducing oxidative stress and mitochondrial damage. Furthermore, RSV targeted inflammation and profibrotic signalling during the maladaptive response, normalizing both processes. Resveratrol effectively prevented AKI-to-CKD transition even 5 months after the intervention. The study serves as a proof of concept, proposing RSV as a valuable candidate for further translational clinical studies to mitigate AKI-to-CKD transition.

Therapeutic effects of resveratrol on epigenetic mechanisms in age-related diseases: A comprehensive review.

Recently, various studies have shown that epigenetic changes are associated with aging and age-related diseases. Both animal and human models have revealed that epigenetic processes are involved in aging mechanisms. These processes happen at multiple levels and include histone modification, DNA methylation, and changes in noncoding RNA expression. Consequently, changes in the organization of chromatin and DNA accessibility lead to the regulation of gene expression. With increasing awareness of the pivotal function of epigenetics in the aging process, researchers' attention has been drawn to how these epigenetic changes can be modified to prevent, stop, or reverse aging, senescence, and age-related diseases. Among various agents that can affect epigenetic, polyphenols are well-known phytochemicals found in fruits, vegetables, and plants. Polyphenols are found to modify epigenetic-related mechanisms in various diseases and conditions, such as metabolic disorders, obesity, neurodegenerative diseases, cancer, and cardiovascular diseases. Resveratrol (RSV) is a member of the stilbene subgroup of polyphenols which is derived from various plants, such as grapes, apples, and blueberries. Therefore, herein, we aim to summarize how RSV affects different epigenetic processes to change aging-related mechanisms. Furthermore, we discuss its roles in age-related diseases, such as Alzheimer's, Parkinson's, osteoporosis, and cardiovascular diseases.

Effect of resveratrol on herpesvirus encephalitis: Evidences for its mechanisms of action

BackgroundHerpes simplex virus type 1 (HSV-1)-induced herpes simplex encephalitis (HSE) has a high mortality rate in clinically immunocompromised patients, while recovered patients often experience neurological sequelae due to neuroinflammation. Nucleoside drugs and nucleoside analogues such as acyclovir and ganciclovir are mainly used in clinical treatment, and the emergence of resistant viral strains makes the development of new anti-herpesvirus encephalitis drugs urgent. Resveratrol is a multifunctional, plant-derived bioactive compound and its antiviral potential is attracting much attention. PurposeThis study aimed to investigate the anti-HSV-1 mechanism of resveratrol in microglial cells and in the HSE mouse model. MethodsThe antiviral effect of resveratrol on HSV-1 infection was investigated by plaque assay, virus titer, immunofluorescence, Western blot and time-of-addition assay. The influence of resveratrol on stimulator of interferon gene (STING)/Nuclear Factor kappa B (NF-κB) signaling pathway-mediated neuroinflammation was examined by Western blot, RT-qPCR and ELISA. The interaction between resveratrol and STING/heat shock protein 90 beta (HSP90β) was evaluated by molecular modeling, co-immunoprecipitation, and drug affinity responsive target stability assay. The therapeutic effect of resveratrol on HSE was evaluated in the HSE mouse model by analyzing weight loss, neurodegenerative symptoms and histopathological scores. ResultsResveratrol inhibited the early process of HSV-1 infection, and interfered with the STING/NF-κB signaling pathway to attenuate HSV-1-induced neuroinflammation and microglial M1 polarization, independent of its classical target Sirtuin1. Mechanistically, resveratrol completely bound to Glu515 and Lys491 of HSP90β, thus disrupting the HSP90β-STING interaction and promoting STING degradation. Resveratrol also significantly alleviated viral encephalitis and neuroinflammation caused by HSV-1 in the HSE mouse model. ConclusionResveratrol acted as a non-classical HSP90β inhibitor, binding to the STING-HSP90β interaction site to promote STING degradation and attenuate HSV-1-induced encephalitis and neuroinflammation. These findings suggest the alternative strategy of targeting HSP90β and resveratrol-mediated inhibition of HSP90β as a potential antiviral approach.

Therapeutic Effect of Resveratrol and its Novel Formulations on Lung Cancer: Focus on Biological Aspects and Underlying Pathways.

Lung cancer is a leading cause of mortality and morbidity worldwide. Due to significant advances in therapeutic strategies, patients' survival and life quality have been improved, however there is still an urgent requirement for developing more effective therapeutic methods. Resveratrol, a natural polyphenol with numerous biological potentials, has been widely studied. It has shown therapeutic potetial in various diseases including neurodegenerative diseases, cardiovascular disorders, and cancers through the regulation of key cellular signaling such as apoptosis, as well as molecular pathways such as microRNA modulation. It has been reported that resveratrol acts as an anticancer agent against lung cancer in vivo and in vitro. Resveratrol could combat against lung cancer by modulating various molecular targets and signaling pathways involved in oxidative stress, inflammation, apoptosis and autoghagy and also microRNAs expression. Moreover, novel delivery systems and analogs have recently been introduced to promote the anticancer impacts of resveratrol. In this article, we review current evidence on the anticancer effects of resveratrol and its novel formulations in the treatment of lung cancer with a focus on underlying mechanisms.

Protective effects of resveratrol on the ethanol-induced disruption of retinogenesis in pluripotent stem cell-derived organoids.

Prenatal alcohol exposure-induced fetal alcohol syndrome (FAS) can lead to serious maldevelopment in many organ systems, including the eyes. In the present study, the effects of alcohol exposure on early development of the human retina and the therapeutic effects of resveratrol on alcohol-induced neural retinal damage were observed for the first time in an in vitro retinal organoid model. We report that the number of proliferating and apoptotic cells decreased and increased, respectively, following ethanol treatment. In addition, the number of PAX6+ cells and migrating TUJ1+ cells decreased after ethanol exposure. However, pretreatment with resveratrol prevented all of these negative effects. Using RNA sequencing and immunofluorescence, we identified activation of the PI3K-AKT signalling pathway as the possible mechanism through which resveratrol protects the retina from alcohol-induced damage. These results suggest that while ethanol exposure can restrict the growth of the human retina and impede the development of specific retinal cells, pretreatment with resveratrol may be a feasible method for preventing these effects.

Therapeutic Effect of Resveratrol and Gamma-GlutamylCysteine in Azathioprine Drug-Induced Hepatotoxicity

Therapeutic Effect of Resveratrol and Gamma-GlutamylCysteine in Azathioprine Drug-Induced Hepatotoxicity

Therapeutic Effect of Resveratrol and Gamma-GlutamylCysteine in Azathioprine Drug-Induced Hepatotoxicity

Therapeutic Effect of Resveratrol and Gamma-GlutamylCysteine in Azathioprine Drug-Induced Hepatotoxicity

Resveratrol accelerates wound healing by inducing M2 macrophage polarisation in diabetic mice

Context The reduction in M2 macrophage polarisation plays a major role during diabetic wound healing. Resveratrol (RSV) can promote the polarisation of M2 macrophages and accelerate diabetic wound healing. However, the specific mechanism by which RSV regulates M2 macrophage polarisation to promote diabetic wound healing is unclear. Objective This study evaluated the effectiveness of RSV on diabetic wound healing and analysed the underlying mechanisms. Materials and methods STZ-induced C57/B6 mice were used as a diabetic mice model for a period of 15 days. RSV (10 μmol/L) was injected around the wound to evaluate the effect of RSV on the healing process of diabetic wounds. The human monocyte line THP-1 was used to evaluate the effects of RSV (10 μmol/L) on polarisation of M2 macrophages and the secretion of pro-inflammatory factors. Results In vivo, RSV significantly increased diabetic wound healing (p < 0.05) and make the regenerated skin structure more complete. And it promoted the expression of α-SMA and Collagen I (p < 0.05). Moreover, RSV reduced the secretion of inflammatory factors (TNF-α, iNOS and IL-1β) (p < 0.05) and promoted M2 macrophage polarisation by increasing Arg-1 and CD206 expression (p < 0.01). In vitro, RSV promoted the polarisation of M2 macrophages (p < 0.001) and reduced the secretion of pro-inflammatory factors (TNF-α, IL-6 and IL-1β) (p < 0.05). The therapeutic effects of RSV were all significantly reversed with LY294002 (p < 0.01). Discussion and conclusions RSV has the positive effects on promoting the acceleration and quality of skin wound healing, which provides a scientific basis for clinical treatment in diabetic wound.

Resveratrol Ameliorates High Altitude Hypoxia-Induced Osteoporosis by Suppressing the ROS/HIF Signaling Pathway.

Hypoxia at high-altitude leads to osteoporosis. Resveratrol (RES), as an antioxidant, has been reported to promote osteoblastogenesis and suppress osteoclastogenesis. However, the therapeutic effect of RES against osteoporosis induced by high-altitude hypoxia remains unclear. Thus, this study was intended to investigate the potential effects of RES on high-altitude hypoxia-induced osteoporosis both in vivo and in vitro. Male Wistar rats were given RES (400 mg/kg) once daily for nine weeks under hypoxia, while the control was allowed to grow under normoxia. Bone mineral density (BMD), the levels of bone metabolism-related markers, and the changes on a histological level were measured. Bone marrow-derived mesenchymal stem cells (BMSCs) and RAW264.7 were incubated with RES under hypoxia, with a control growing under normoxia, followed by the evaluation of proliferation and differentiation. The results showed that RES inhibited high-altitude hypoxia-induced reduction in BMD, enhanced alkaline phosphatase (ALP), osteocalcin (OCN), calcitonin (CT) and runt-related transcription factor 2 (RUNX2) levels, whereas it reduced cross-linked carboxy-terminal telopeptide of type I collagen (CTX-I) levels and tartrate-resistant acid phosphatase (TRAP) activity in vivo. In addition, RES attenuated histological deteriorations in the femurs. In vitro, RES promoted osteoblastogenesis and mineralization in hypoxia-exposed BMSCs, along with promotion in RUNX2, ALP, OCN and osteopontin (OPN) levels, and inhibited the proliferation and osteoclastogenesis of RAW264.7. The promotion effects of RES on osteoblastogenesis were accompanied by the down-regulation of reactive oxygen species (ROS) and hypoxia inducible factor-1α (HIF-1α) induced by hypoxia. These results demonstrate that RES can alleviate high-altitude hypoxia-induced osteoporosis via promoting osteoblastogenesis by suppressing the ROS/HIF-1α signaling pathway. Thus, we suggest that RES might be a potential treatment with minimal side effects to protect against high-altitude hypoxia-induced osteoporosis.

Resveratrol from Dietary Supplement to a Drug Candidate: An Assessment of Potential.

Resveratrol (RVT) is a well known phyto-chemical and is widely used in dietary supplements and botanical products. It shows a wide range of pharmacological/beneficial effects. Therefore, it can be a potential candidate to be developed as phyto-pharmaceutical. Multiple diseases are reported to be treated by the therapeutic effect of RVT since it has antioxidant, anti-cancer activity and anti-inflammatory activities. It also has a major role in diabetes, arthritis, cardiac disorder and platelet aggregation etc. The major requirements are establishments regarding safety, efficacy profile and physicochemical characterization. As it is already being consumed in variable maximum daily dose, there should not be a major safety concern but the dose needs to be established for different indications. Clinical trials are also being reported in different parts of the world. Physicochemical properties of the moiety are also well reported. Moreover, due to its beneficial effect on health it leads to the development of some intellectual property in the form of patents.

Therapeutic Effects of Resveratrol in Inflammatory Bowel Diseases: Shedding Light on the Role of Cellular and Molecular Pathways

Therapeutic Effects of Resveratrol in Inflammatory Bowel Diseases: Shedding Light on the Role of Cellular and Molecular Pathways

Hepatoprotective and therapeutic effects of resveratrol: A focus on anti-inflammatory and antioxidative activities.

Being the most essential organ in the body, the liver performs critical functions. Hepatic disorders, such as alcoholic liver disease, hepatic steatosis, liver fibrosis, nonalcoholic fatty liver disease, hepatocellular carcinoma, and hepatic failure, have an impact on the biochemical and physiological functions of the body. The main representative of the flavonoid subgroup of flavones, resveratrol (RES), exhibits suitable pharmacological activities for treating various liver diseases, such as fatty hepatitis, liver steatosis, liver cancer, and liver fibrosis. According to various studies, grapes and red wine are good sources of RES. RES has various health properties; it is anti-inflammatory, anti-apoptotic, antioxidative, and hepatoprotective against several hepatic diseases and hepatoxicity. Therefore, we performed a thorough research and created a summary of the distinct targets of RES in various stages of liver diseases. We concluded that RES inhibited liver inflammation essentially by causing a significant decrease in the expression of various pro-inflammatory cytokines like TNF-α, IL-1α, IL-1β, and IL-6. It also inhibits the transcription factor nuclear NF-κB that brings about the inflammatory cascade. RES also inhibits the PI3K/Akt/mTOR pathway to induce apoptosis. Additionally, it reduces oxidative stress in hepatic tissue by markedly reducing malondialdehyde (MDA) and nitric oxide (NO) contents and significantly increasing the levels of catalase (CAT), superoxide dismutase (SOD), and reduced hepatic glutathione (GSH), in addition to aspartate aminotransferase (AST) and alanine aminotransferase (ALT), against toxic chemicals like CC14, As2O3, and TTA. Due to its antioxidant, anti-inflammatory, and anti-fibrotic properties, RES reduces liver injury markers. RES is safe natural antioxidant that provides pharmacological rectification of the hepatoxicity of toxic chemicals.

The effect of resveratrol on toxicity caused by cisplatin in rats with experimentally created diabetes by streptozotocin

Aim: In our study, the therapeutic effect of resveratrol against the toxicity of cisplatin in rats with experimental diabetes mellitus with streptozotocin was investigated.&#x0D; Material and Method: 64 rats were used in the study. 8 groups were randomly formed, with 8 rats in each group. Group 1 was determined as the control group. Group 2 (STZ) was injected with 60 mg/kg streptozotocin intraperitoneally (ip) on the first day to induce diabetes. Group 3 (RES) was given 100 mg/kg of resveratrol orally every day. Group 4 (SIS), a single dose of cisplatin 7 mg/kg (ip) was administered 3 days later. Group 5 (STZ+RES), group 6 (STZ+SIS), group 7 (RES+SIS) and group 8 (STZ+SIS+RES) were determined.&#x0D; Results: While there was weight gain in the control and RES groups during the experiment, the STZ and STZ + SIS groups showed a significant decrease in body weights of the rats. In the groups given streptozotocin and cisplatin together with resveratrol, there was no decrease in body weight, but a small increase was observed. In groups with increased blood glucose values with streptozotocin, these values were found to have dropped significantly with resveratrol. The TAS level has increased significantly in groups RES, STZ+RES, SIS+RES and STZ+SIS+RES according to the control group; no significant difference has been found in the other groups compared to the control group. While the AST level was significantly higher in the STZ, SIS and STZ+SIS groups compared to the control group, the ALT level was found to be significantly higher in the STZ and STZ+SIS groups compared to the control group. Creatinine was found to be significantly higher in SIS, STZ+SIS, RES+SIS and STZ+SIS+RES groups compared to the control group. The SIS group and RES+SIS and STZ+SIS+RES groups were compared, the decrease in the RES+SIS and STZ+SIS+RES groups was statistically significant. QT (ms) values increased significantly in the STZ and STZ+SIS groups compared to the control group, but there was no significant difference in the other groups. According to the control group, the heart rate per minute was found to be significantly lower in the STZ and STZ+SIS groups.&#x0D; Conclusion: As a result, it was seen that the use of resveratrol would be effective in reducing the increased glucose levels in the treatment of diabetes and in the treatment of possible complications.

Therapeutic Effects of Sirtuin 1 Activator on Glaucoma Mice and the Regulation Mechanism of Mitogen-Activated Protein Kinase Pathway

The study focused on the therapeutic effects of resveratrol, sirtuin 1 (Sirt1) activator, on glaucoma, and its influence on mitogen-activated protein kinase (MAPK) pathway. Specifically, C57BL/6 mice were used and the glaucoma mouse model was established by intraperitoneal injection of N-methyl-D-aspartate (NMDA). According to different treatment methods, they were randomly rolled into 3 groups: control group (no treatment), model group (glaucoma mouse model), and resveratrol (Res) group (intraperitoneal injection of 20 mg/kg resveratrol solution on the basis of model group). The intraocular pressure was measured, and Sirt1 mRNA and protein expression was detected using reverse transcription-polymerase chain reaction (RT-PCR) and Western blot. Subsequently, hematoxylin-eosin staining was used to observe histopathological morphology, the immunofluorescence labeling was used to identify retinal survival ganglia, and Terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling assay (TUNEL) and Western blot were for apoptotic cells determination and the expression of c-Jun N-terminal kinase (JNK), extracellular regulated protein kinase (ERK), and p38 protein in mitogen-activated protein kinase (MAPK) pathway, respectively. The model group showed lower intraocular pressure, Sirt1 mRNA and protein expression, number of survival retinal ganglion cells (RGCs), and thinner retina versus the control group (P &lt; 0.05), but number of apoptotic RGCs and the phosphorylation levels of the three kinds of protein were higher (P &lt; 0.05), and it exhibited no notable difference from the Res group (P &gt; 0.05). Also, compared with the control group, the number of survival RGCs in the Res group was reduced (P &lt; 0.05), but no notable difference was noted in the retinal thickness, the number of apoptotic RGCs, and the phosphorylation levels of the three kinds of protein (P &gt; 0.05). In conclusion, resveratrol, the Sirt1 activator, can inhibit RGCs apoptosis through the MAPK signaling pathway and improve the pathological manifestations of glaucoma animal models, thus playing a protective role of the retina.

Therapeutic Effects of Resveratrol on Ischemia-Reperfusion Injury in the Nervous System.

Resveratrol is a phenol compound produced by some plants in response to pathogens, infection, or physical injury. It is well-known that resveratrol has antioxidant and protective roles in damages potentially caused by cancer or other serious disorders. Thus, it is considered as a candidate agent for the prevention and treatment of human diseases. Evidence has confirmed other bioactive impacts of resveratrol, including cardioprotective, anti-tumorigenic, anti-inflammatory, phytoestrogenic, and neuroprotective effects. Ischemia-reperfusion (IR) can result in various disorders, comprising myocardial infarction, stroke, and peripheral vascular disease, which may continue to induce debilitating conditions and even mortality. In virtue of chronic ischemia or hypoxia, cells switch to anaerobic metabolism, giving rise to some dysfunctions in mitochondria. As the result of lactate accumulation, adenosine triphosphate levels and pH decline in cells. This condition leads cells to apoptosis, necrosis, and autophagy. However, restoring oxygen level upon reperfusion after ischemia by producing reactive oxygen species is an outcome of mitochondrial dysfunction. Considering the neuroprotective effect of resveratrol and neuronal injury that comes from IR, we focused on the mechanism(s) involved in IR injury in the nervous system and also on the functions of resveratrol in the protection, inhibition, and treatment of this injury.

Resveratrol Reverses Social Deficits and Metabolic Dysfunction of Mice Model for Negative Symptoms of Schizophrenia

The negative symptoms of schizophrenia without effective therapeutic agents seriously affect the quality of life. Studies investigating the neurobiological mechanisms of the negative symptoms of schizophrenia failed to provide a unanimous conclusion, but generally accepted to be related to the prefrontal cortex (PFC). Resveratrol is a kind of natural plant polyphenol and has a potential role in negative symptoms treatment for its neuroprotective effects. To investigate the metabolic mechanism of the negative symptoms and the therapeutic effect of resveratrol on it, we analyzed the metabolic changes in the PFC of MK-801-induced schizophrenia model using ex vivo 1H nuclear magnetic resonance spectroscopy. And then, after chromic administration of resveratrol, we tested the social interaction behaviors of the schizophrenia model and analyzed the metabolic changes in the PFC. Our results showed that the levels of alanine (Ala), glutamate (Glu), tautine (Tau), glynine (Gly), choline (Cho), and valine (Val) are significantly decreased compared to control animals. The social deficits of MK-801-treated mice are improved after resveratrol administration. And the levels of Glu, Gly, and Cho were reversed after the treatment of resveratrol. In conclusion, our results suggest that the negative symptoms are associated with decreased concentration of Ala, Glu, Tau, Gly, Cho, Val in PFC and the social deficits could be recovered by resveratrol treatment, as well as the levels of Glu, Gly, and Cho in PFC.

Resveratrol can enhance osteogenic differentiation and mitochondrial biogenesis from human periosteum-derived mesenchymal stem cells

BackgroundOsteoporosis is a metabolic bone disorder that leads to low bone mass and microstructural deterioration of bone tissue and increases bone fractures. Resveratrol, a natural polyphenol compound, has pleiotropic effects including anti-oxidative, anti-aging, and anti-cancer effects. Resveratrol also has roles in increasing osteogenesis and in upregulating mitochondrial biogenesis of bone marrow-derived mesenchymal stem cells (BM-MSCs). However, it is still unclear that resveratrol can enhance osteogenic differentiation or mitochondrial biogenesis of periosteum-derived MSCs (PO-MSCs), which play key roles in bone tissue maintenance and fracture healing. Thus, in order to test a possible preventive or therapeutic effect of resveratrol on osteoporosis, this study investigated the effects of resveratrol treatments on osteogenic differentiation and mitochondrial biogenesis of PO-MSCs.MethodsThe optimal doses of resveratrol treatment on PO-MSCs were determined by cell proliferation and viability assays. Osteogenic differentiation of PO-MSCs under resveratrol treatment was assessed by alkaline phosphatase activities (ALP, an early biomarker of osteogenesis) as well as by extracellular calcium deposit levels (a late biomarker). Mitochondrial biogenesis during osteogenic differentiation of PO-MSCs was measured by quantifying both mitochondrial mass and mitochondrial DNA (mtDNA) contents.ResultsResveratrol treatments above 10 μM seem to have negative effects on cell proliferation and viability of PO-MSCs. Resveratrol treatment (at 5 μM) on PO-MSCs during osteogenic differentiation increased both ALP activities and calcium deposits compared to untreated control groups, demonstrating an enhancing effect of resveratrol on osteogenesis. In addition, resveratrol treatment (at 5 μM) during osteogenic differentiation of PO-MSCs increased both mitochondrial mass and mtDNA copy numbers, indicating that resveratrol can bolster mitochondrial biogenesis in the process of PO-MSC osteogenic differentiation.ConclusionTaken together, the findings of this study describe the roles of resveratrol in promoting osteogenesis and mitochondrial biogenesis of human PO-MSCs suggesting a possible application of resveratrol as a supplement for osteoporosis and/or osteoporotic fractures.

STAT3 signaling statuses determine the fate of resveratrol-treated anaplastic thyroid cancer cells.

Anaplastic thyroid cancer/ATC is highly lethal malignancy without reliable chemotherapeutic drug. Resveratrol possesses anti-ATC activities but encounters resistance in some cases due to certain unknown reason(s). Because signal transducer and activator of transcription/STAT3 signaling is critical for ATC cell survival and the main molecular target of resveratrol, its roles in determining the fates of resveratrol-treated ATC cells were investigated here. Human THJ-11T, THJ-16 and THJ-21T ATC cell lines were treated by 100 μM resveratrol and their growth, statuses of STAT3 signaling and STAT3-related gene expression were examined. The relevance of STAT3 activation with resveratrol resistance was elucidated using STAT selective inhibitor AG490. Leukemia inhibitory factor/LIF expression and phosphorylated-STAT3/p-STAT3 nuclear translocation in ATC tissues were immunohistochemically analyzed. Resveratrol inhibited proliferation, p-STAT3 nuclear translocation as well as LIF and STAT3 expression of THJ-16T and THJ-21T but not THJ-21T cells which showed LIF upregulation and more frequent p-STAT3 nuclear translocation. AG490 significantly prevent p-STAT3 nuclear translocation, and reversed the resveratrol tolerance of THJ-11T cells. Immonohistochemical staining revealed 14.3% (4/28) of LIF and 3.6% (1/28) of p-STAT3 detection in noncancerous ATC-surrounding tissues, which increased to 89.5% (17/19) and 52.6% (10/19) respectively among ATC specimens. The correlative analysis indicated the relevance of LIF expression and STAT3 activation (r= 0.825; P< 0.01). The status of STAT3 activation and LIF expression are closely correlated with the therapeutic effect of resveratrol on ATCs. Frequent LIF upregulation and STAT3 activation are the unfavorable factors of ATCs and the potential targets of anti-ATC therapy.

Exploring the Comparative Efficacy of Metformin and Resveratrol in the Management of Diabetes-associated Complications: A Systematic Review of Preclinical Studies.

Food-derived bioactive compounds such as resveratrol are increasingly explored for their protective effects against metabolic complications. Evidence supports the strong antioxidant properties and therapeutic effects of resveratrol in managing diabetes and its associated complications. However, evidence informing on the comparative or combination effects of this natural compound with an accomplished and well-characterized antidiabetic agent like metformin has not been revised. Thus, we conducted a comprehensive systematic search of the major electronic databases which included MEDLINE, Cochrane Library, and EMBASE. The cumulative evidence strongly supports the comparative effects of metformin and resveratrol in ameliorating diabetes-associated complications in preclinical settings. In particular, both compounds showed strong ameliorative effects against hyperglycemia, dyslipidemia, insulin resistance, a pro-inflammatory response, and lipid peroxidation in various experimental models of diabetes. Enhancing intracellular antioxidant capacity in addition to activating NAD-dependent deacetylase sirtuin-1 (SIRT1) and AMP-activated protein kinase (AMPK) are the prime mechanisms involved in the therapeutic effects of these compounds. Of interest, preclinical evidence also demonstrates that the combination treatment with these compounds may have a greater efficacy in protecting against diabetes. Thus, confirmation of such evidence in well-organized clinical trials remains crucial to uncover novel therapeutic strategies to manage diabetes and its linked complications.