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The agricultural fumigant pesticide aluminum phosphide (AlP) is cardiotoxic. Water causes AlP to emit phosphine gas, a cardiac toxin that affects heart function and causes cardiogenic shock. AlP poisoning's high fatality rate is due to cardiotoxicity. This study examines how resveratrol reduces oxidative stress, mitochondrial activity, and apoptosis in human cardiac myocyte (HCM) cells. After determining the optimal doses of resveratrol using the MTT test, HCM cells were subjected to a 24-h treatment of resveratrol following exposure to AlP (2.36 μM). The levels of reactive oxygen species (ROS), superoxide dismutase (SOD) activity, mitochondrial swelling, mitochondrial cytochrome c release, and mitochondrial membrane potential (MMP) in HCM cells were investigated. Also, the expression of Bax and Bcl-2, caspace-3 activity, and apoptosis were assessed. The present investigation revealed that AlP substantially increased the level of ROS and decreased SOD activation, which were significantly modulated by resveratrol in a dose-dependent manner. Moreover, AlP induced an elevation of mitochondrial swelling, cytochrome c release, and MMP collapse. Co-administration of resveratrol significantly reduced above mitochondrial markers. AlP also significantly upregulated BAX and downregulated Bcl-2 expression, elevated caspace-3 activity, and apoptosis. Resveratrol co-administration was able to meaningfully modulate the mentioned parameters and finally reduce apoptosis. In conclusion, resveratrol, via its pleotropic properties, significantly demonstrated cytoprotective effects on HCM cytotoxicity induced by AlP. [ABSTRACT FROM AUTHOR]

(1) Background: Oxidative stress plays a pivotal role in the pathogenesis of various diseases, including neurodegenerative disorders, cardiovascular diseases, cancer, and diabetes, highlighting the pressing need for effective antioxidant interventions. (2) Methods: In this study, we aimed to develop and characterise two novel antioxidant formulations, F3 and F4, as therapeutic interventions for oxidative stress-related conditions. (3) Results: The physicochemical characterisation, preformulation analysis, formulation, preparation of filling powders for capsules, capsule content evaluation, and antioxidant activity assessment of the two novel antioxidant formulations were assessed. These formulations comprise a combination of well-established antioxidants like quercetin, biotin, coenzyme Q10, and resveratrol. Through comprehensive testing, the formulations' antioxidant efficacy, stability, and potential synergistic interactions were evaluated. (4) Conclusions: The findings underscore the promising potential of these formulations as therapeutic interventions for oxidative stress-related disorders and highlight the significance of antioxidant interventions in mitigating their progression. [ABSTRACT FROM AUTHOR]

Resveratrol has a protective effect on sepsis-induced acute kidney injury (AKI). Circ_0074371 has been confirmed to inhibit sepsis-induced AKI process, but whether resveratrol inhibits sepsis-induced AKI by regulating circ_0074371-related pathway remains unclear. In this study, lipopolysaccharide (LPS)-induced renal tubular epithelial cells (HK2) were used to mimic AKI cell models. Quantitative real-time PCR was used to detect relative expression of circ_0074371, microRNA (miR)-145-5p and inositol polyphosphate multikinase (IPMK). Cell proliferation and apoptosis were detected by cell counting kit 8 assay, EdU assay and flow cytometry. The levels of inflammation factors were measured by ELISA assay, and MDA level and SOD activity were examined to assess oxidative stress. Protein expression of IPMK was evaluated by western bolt analysis. The relationship between miR-145-5p and circ_0074371 or IPMK was confirmed by dual-luciferase reporter assay. It was showed that circ_0074371 was upregulated in AKI patients and LPS-induced HK2 cells, and silencing of circ_0074371 promoted proliferation and inhibited apoptosis, inflammation and oxidative stress in LPS-induced HK2 cells. In terms of mechanism, circ_0074371 sponged miR-145-5p to positively regulate IPMK. IPMK overexpression could reverse the relieving effect of circ_0074371 knockdown on LPS-induced HK2 cell injury. Moreover, resveratrol suppressed LPS-induced apoptosis, inflammation and oxidative stress in HK2 cells, and circ_0074371 overexpression also reversed the protective effect of resveratrol against LPS-induced cell injury. Our data suggested that resveratrol alleviated LPS-induced HK2 cell injury by inactivating the circ_0074371/miR-145-5p/IPMK axis. Highlights: Circ_0074371 knockdown alleviates LPS-induced HK2 cell injury; Circ_0074371 sponges miR-145-5p to regulate IPMK. Resveratrol relieves LPS-induced HK2 cell injury via circ_0074371-related pathway. [ABSTRACT FROM AUTHOR]

Inflammatory bowel disease (IBD) is a long-life disease with periods of recurrence and relief. Oxidative stress plays an important role in the pathogenesis of this disease. Recent years' studies in the field of IBD treatment mostly have focused on targeting cytokines and immune cell trafficking using antibodies and inhibitors, altering the composition of intestinal bacteria in the line of attenuation of inflammation using probiotics and prebiotics, and attenuating oxidative stress through antioxidant supplementation. Studies in animal models of IBD have shown that some polyphenolic compounds including curcumin, quercetin, resveratrol, naringenin, and epigallocatechin-3-gallate can affect almost all of the above aspects and are useful compounds in the treatment of IBD. Clinical studies performed on IBD patients have also confirmed the findings of animal model studies and have shown that supplementation with some of the above-mentioned polyphenolic compounds has positive effects in reducing disease clinical and endoscopic activity, inducing and maintaining remission, and improving quality of life. In this review article, in addition to a detailed reviewing the effects of the above-mentioned polyphenolic compounds on the events involved in the pathogenesis of IBD, the results of these clinical studies will also be reviewed. [ABSTRACT FROM AUTHOR]

Mulberry is a rapidly growing plant that thrives in diverse climatic, topographical, and soil types, spanning temperature and temperate countries. Mulberry plants are valued as functional foods for their abundant chemical composition, serving as a significant reservoir of bioactive compounds like proteins, polysaccharides, phenolics, and flavonoids. Moreover, these compounds displayed potent antioxidant activity by scavenging free radicals, inhibiting reactive oxygen species generation, and restoring elevated nitric oxide production induced by LPS stimulation through the downregulation of inducible NO synthase expression. Active components like oxyresveratrol found in Morus demonstrated anti-inflammatory effects by inhibiting leukocyte migration through the MEK/ERK signaling pathway. Gallic and chlorogenic acids in mulberry leaves (ML) powder-modulated TNF, IL-6, and IRS1 proteins, improving various inflammatory conditions by immune system modulation. As we delve deeper into understanding its anti-inflammatory potential and how it works therapeutically, it is crucial to refine the extraction process to enhance the effectiveness of its bioactive elements. Recent advancements in extraction techniques, such as solid–liquid extraction, pressurized liquid extraction, superficial fluid extraction, microwave-assisted extraction, and ultrasonic-assisted extraction, are being explored. Among the extraction methods tested, including Soxhlet extraction, maceration, and ultrasound-assisted extraction (UAE), UAE demonstrated superior efficiency in extracting bioactive compounds from mulberry leaves. Overall, this comprehensive review sheds light on the potential of mulberry as a natural immunomodulatory agent and provides insights into its mechanisms of action for future research and therapeutic applications. [ABSTRACT FROM AUTHOR]

High glucose concentrations result in oxidative stress, leading to damage of cellular constituents like DNA, proteins, and lipids, ultimately resulting in apoptosis. Resveratrol, a polyphenol phytoalexin, has been studied for its potential therapeutic effects on diabetes. This study investigated the influence of high glucose (HG) on HepG2 cells and assessed resveratrol's effect on high‐glucose‐induced oxidative stress and apoptosis. HepG2 cells were cultured for 48 and 72 h with high glucose (40 mM), low resveratrol (25 μM), high resveratrol (50 μM), high glucose + low resveratrol, and high glucose + high resveratrol. After exposure, oxidative and apoptosis‐related gene expression was evaluated using quantitative polymerase chain reaction (qPCR), and lactate dehydrogenase (LDH) release was measured using the supernatant. In HepG2 cells cultured with high glucose, all antioxidant enzymes (SOD, superoxide dismutase; GPx1, glutathione peroxidase 1; CAT, catalase; Nrf2, nuclear factor erythroid 2–related factor 2; and NQO1, NAD(P)H quinone oxidoreductase 1) were significantly reduced; however, when HepG2 cells were cultured with resveratrol (25 and 50 μM) and high glucose, the expression levels of all antioxidant enzymes were increased. The anti‐apoptotic gene (B‐cell lymphoma 2; Bcl2) and the DNA repair gene (Oxoguanine glycosylase‐1, OGG1) were significantly decreased following high glucose exposure to HepG2 cells. Surprisingly, the expression levels of Bcl2 and OGG1 were notably elevated after resveratrol treatment. Furthermore, high glucose levels increased the LHD release in HepG2 cells, whereas resveratrol treatment reduced the LDH release. Our results demonstrate that resveratrol provides protection against oxidative stress and apoptosis induced by high glucose in HepG2 cells. Hence, resveratrol shows potential as an effective approach to address the impaired antioxidant response resulting from elevated glucose levels commonly observed in diabetes and metabolic disorders. [ABSTRACT FROM AUTHOR]

The atmosphere's fine particulate matter (PM2.5) can enter the liver through the circulatory system, leading to hepatic inflammation and fibrosis. As a non-flavonoid polyphenolic compound, resveratrol (RES) has anti-oxidant, anti-inflammatory and hepatoprotective effects, but the molecular mechanisms of liver fibrosis induced by PM2.5 exposure are still limited. In this study, we established an in vitro cell model to investigate the intervention effect of RES with different concentrations (5 and 20 μmol/mL) on mouse hepatic stellate cells (mHSCs) injury induced by PM2.5 (100 μg/mL). We determined the cell viability in mHSCs after treatment with PM2.5 or/and RES for 24 h. We investigated the intracellular oxidative stress by detecting the changes in reactive oxygen species (ROS), malondialdehyde (MDA), superoxide dismutase (SOD) and lactate dehydrogenase (LDH) levels. We also measured the protein expressions of fibrosis-related genes (α-SMA, Collagen I and Collagen III) and key genes (SIRT1, NF-κB, NLRP3, Cleaved-Caspase1, IL-1β) in the NLRP3 pathway in mHSCs exposed to PM2.5 with or without RES. The results showed that (1) PM2.5 has cytotoxic effects on mHSCs, whereas RES (5 μmol/L and 20 μmol/L) inhibited PM2.5-induced cytotoxicity and LDH leakage; (2) RES effectively reduces ROS and MDA production caused by PM2.5 while concurrently enhancing SOD levels, thereby improving cellular anti-oxidant capacity; (3) the expression of α-SMA, Collagen I and Collagen III were notably downregulated in the PM2.5 plus RES treatment group compared to the PM2.5-exposed group; (4) RES significantly increased SIRT1 expression and decreased the expression of NF-κB, NLRP3, Cleaved-Caspase1 and IL-1β in mHSCs exposure to PM2.5 compared to the PM2.5 group. These results demonstrate that RES can up-regulate SIRT1 and mitigate PM2.5-induced fibrosis by suppressing oxidative stress in mHSCs and the SIRT1/NF–κB/NLRP3 pathway activated by PM2.5. [ABSTRACT FROM AUTHOR]

As the aging population continues to increase, aging-related inflammation, oxidative stress, and neurodegenerative diseases have become serious global health threats. Resveratrol, a star molecule in natural polyphenols, has been widely reported to have physiological activities such as anti-aging, anti-inflammatory, antioxidant, and neuroprotection. However, its poor water solubility, rapid metabolism, low bioavailability and poor targeting ability, which limits its application. Accordingly, a brain-targeted resveratrol liposome (ANG-RES-LIP) was developed to solve these issues. Experimental results showed that ANG-RES-LIP has a uniform size distribution, good biocompatibility, and a drug encapsulation rate of over 90%. Furthermore, in vitro cell experiments showed that the modification of the targeting ligand ANG significantly increased the capability of RES to cross the BBB and neuronal uptake. Compared with free RES, ANG-RES-LIP demonstrated stronger antioxidant activity and the ability to rescue oxidatively damaged cells from apoptosis. Additionally, ANG-RES-LIP showed the ability to repair damaged neuronal mitochondrial membrane potential. In vivo experiments further demonstrated that ANG-RES-LIP improved cognitive function by reducing oxidative stress and inflammation levels in the brains of aging model mice, repairing damaged neurons and glial cells, and increasing brain-derived neurotrophic factor. In summary, this study not only provides a new method for further development and application of resveratrol but also a promising strategy for preventing and treating age-related neurodegenerative diseases. [ABSTRACT FROM AUTHOR]

Malignant tumors are the second most common cause of death worldwide. More attention is being paid to the link between the body's impaired oxidoreductive balance and cancer incidence. Much attention is being paid to polyphenols derived from plants, as one of their properties is an antioxidant character: the ability to eliminate reactive oxygen and nitrogen species, chelate specific metal ions, modulate signaling pathways affecting inflammation, and raise the level and activity of antioxidant enzymes while lowering those with oxidative effects. The following three compounds, resveratrol, quercetin, and curcumin, are polyphenols modulating multiple molecular targets, or increasing pro-apoptotic protein expression levels and decreasing anti-apoptotic protein expression levels. Experiments conducted in vitro and in vivo on animals and humans suggest using them as chemopreventive agents based on antioxidant properties. The advantage of these natural polyphenols is low toxicity and weak adverse effects at higher doses. However, the compounds discussed are characterized by low bioavailability and solubility, which may make achieving the blood concentrations needed for the desired effect challenging. The solution may lie in derivatives of naturally occurring polyphenols subjected to structural modifications that enhance their beneficial effects or work on implementing new ways of delivering antioxidants that improve their solubility and bioavailability. [ABSTRACT FROM AUTHOR]

Thyroid cancer, particularly undifferentiated tumors, poses a significant challenge due to its limited response to standard therapies. The incidence of thyroid cancer, predominantly differentiated carcinomas, is on the rise globally. Anaplastic thyroid carcinoma (ATC), though rare, is highly aggressive and challenging to treat. Therefore, this study aimed to collect data and explore alternative treatments, focusing on the efficacy of photodynamic therapy (PDT) combined with natural compounds as well as the potential role of phytochemicals, including quercetin, kaempferol, apigenin, genistein, daidzein, naringenin, hesperitin, anthocyanidins, epigallocatechin gallate (EGCG), resveratrol, ellagic acid, ferulic acid, caffeic acid, curcumin, saponins, ursolic acid, indole-3-carbinol (I3C), capsaicin, and piperine in thyroid cancer treatment. PDT, utilizing sensitizers activated by tumor-directed light, demonstrates promising specificity compared to traditional treatments. Combining PDT with natural photosensitizers, such as hypericin and genistein, enhances cytotoxicity against thyroid carcinoma cells. This literature review summarizes the current knowledge on phytochemicals and their anti-proliferative effects in in vitro and in vivo studies, emphasizing their effectiveness and mechanism of action as a novel therapeutic approach for thyroid cancers, especially those refractory to standard treatments. [ABSTRACT FROM AUTHOR]

Resveratrol (3,5,4′-trihydroxystilbene, RSV) is a natural stilbene synthetized as trans -isomer in plants exposed to oxidative stress. In order to understand the mechanism involved during photosensitized degradation of trans -resveratrol, steady-state and time-resolved experiments were performed and compared with quantum-chemical calculations using density functional theory (DFT). Pterin (Ptr), a well-known photosensitizer, under UV-A radiation induces the oxidation of several biomolecules mainly through electron-transfer mechanisms. On the one hand, it was observed that trans -RSV participates in an energy-transfer pathway with Ptr triplet excited state (3Ptr*) forming 3 trans -RSV*, which dissipates the energy by isomerization to cis -RSV. On the other hand, RSV neutral radical (trans -RSV(-H)•) was detected in laser flash photolysis experiments, evidencing an electron-transfer mechanism. The electron-transfer from 3Ptr* to trans -RSV is a barely feasible reaction, however, more favorable is the formation of trans -RSV(-H)• in a reaction between trans -RSV and Ptr radical cation (Ptr•+), which is produced during irradiation. The combination of experimental and theoretical approaches evidences the capability of trans -RSV to undergo energy-transfer (feasible by DFT calculations) and/or one-electron transfer pathways with 3Ptr*. These findings reveal the mechanisms involved in the interaction of trans -RSV and pterin excited states and provide information on the antioxidant action of resveratrol during photosensitized oxidation of biomolecules. [Display omitted] • Resveratrol is a natural polyphenol synthesized against oxidative stress in plants. • Pterin excited states with the ability to oxidize biomolecules are deactivated by resveratrol. • Energy transfer from trans -resveratrol to pterin triplet excited state is feasible. • Resveratrol acts as electron donor to pterin triplet excited state. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Objective: Cadmium (Cd) is a well-known widespread environmental pollutant and is not rapidly excreted by the kidneys; instead, it accumulates and causes kidney damage. This study aimed to compare the effects of antioxidant curcumin and resveratrol on antioxidant defense in Cd-induced rat kidney tissue. Methods: In the study, 36 (200-250 gr) Wistar albino rats were divided into 6 (n=6) groups. Group 1: control; group 2: CdCl2; group 3: curcumin; group 4: CdCl2 + curcumin; group 5: resveratrol; group 6: CdCl2 + resveratrol. At the end of the experiment, malondialdehyde (MDA), total oxidant capacity (TOC), and total antioxidant capacity (TAC) activities were measured in kidney tissues. Results: In the CdCl2-treated group, oxidative stress index (OSI), TOC, and MDA levels increased compared with the control group, and TAC values decreased (p<0.05). In the case of resveratrol or curcumin administered with Cd, TAC levels increased, MDA levels, and OSI values decreased compared with the group administered only Cd (p<0.05). Conclusion: Both resveratrol and curcumin may have protective effects in the kidneys against CdCl2-induced oxidative damage. [ABSTRACT FROM AUTHOR]

[Display omitted] • RES can alleviate depressive behavior in PSD rats. • RES can reduce inflammation and oxidative stress in the brain tissue of PSD rats. • RES can ameliorate cognitive impairment in PSD rats. • RES can activate the Nrf2/HO-1 pathway in the brain tissue of PSD rats. • The repressed Nrf2/HO-1 pathway reverses the effect of RES on PSD rats. Post-stroke depression (PSD) is a prevalent mental health issue, and resveratrol (RES) has been implicated in its management. This study aimed to elucidate the impact of RES on PSD. A PSD rat model was established through middle cerebral artery occlusion and chronic unpredictable mild stress. Rats received RES via gavage, and depressive behaviors were evaluated through various measures. Cerebral infarction areas and brain tissue pathology were assessed using TTC and H&E staining. Levels of inflammatory factors (TNF-α/IL-1β/IL-6/IL-10), neurotransmitters (ACH/DA/5-HT/BDNF), and oxidative stress-related indicators (SOD/GSH-Px/MDA), along with the total Nrf2/C-Nrf2/N-Nrf2/HO-1 proteins, were analyzed. The role of the Nrf2/HO-1 pathway was investigated by co-treating rats with RES and either an Nrf2 pathway specific inhibitor (ML385) or activator (dimethyl fumarate). PSD rats exhibited depressive behaviors, disrupted neurotransmitter levels, and oxidative stress markers. RES treatment effectively alleviated these symptoms and activated the Nrf2/HO-1 pathway in PSD rat brain tissues. Co-administration of ML385 attenuated the beneficial effects of RES in PSD rats. Altogether, RES mitigates depressive behaviors, improves cognitive dysfunction, and reduces oxidative stress and inflammatory response in PSD rats. These effects are mediated through the activation of the Nrf2/HO-1 pathway, suggesting RES as a potential therapeutic agent for PSD-related cognitive impairment. [ABSTRACT FROM AUTHOR]

Chronic exposure to manganese (Mn) leads to its accumulation in the central nervous system (CNS) and neurotoxicity with not well-known mechanisms. We investigated the involvement of matrix metalloproteinase (MMP)-2 and -9 in Mn neurotoxicity in an in vivo model of rats treated through an intraperitoneal injection, for 4 weeks, with 50 mg/kg of MnCl2 in the presence or in the absence of 30 mg/kg of resveratrol (RSV). A loss of weight was observed in Mn-treated rats compared with untreated and RSV-treated rats. A progressive recovery of body weight was detected in rats co-treated with Mn and RSV. The analysis of brain homogenates indicated that RSV counteracted the Mn-induced increase in MMP-9 levels and reactive oxygen species production as well as the Mn-induced decrease in superoxide dismutase activity and glutathione content. In conclusion, Mn exposure, resulting in MMP-9 induction with mechanisms related to oxidative stress, represents a risk factor for the development of CNS diseases. [ABSTRACT FROM AUTHOR]

Stilbenes are phytoalexins, and their biosynthesis can occur through a natural route (shikimate precursor) or an alternative route (in microorganism cultures). The latter is a metabolic engineering strategy to enhance production due to stilbenes recognized pharmacological and medicinal potential. It is believed that in the human body, these potential activities can be modulated by the regulation of the nuclear factor erythroid derived 2 (Nrf2), which increases the expression of antioxidant enzymes. Given this, our review aims to critically analyze evidence regarding E-stilbenes in human metabolism and the Nrf2 activation pathway, with an emphasis on inflammatory and oxidative stress aspects related to the pathophysiology of chronic and metabolic diseases. In this comprehensive literature review, it can be observed that despite the broad number of stilbenes, those most frequently explored in clinical trials and preclinical studies (in vitro and in vivo) were resveratrol, piceatannol, pterostilbene, polydatin, stilbestrol, and pinosylvin. In some cases, depending on the dose/concentration and chemical nature of the stilbene, it was possible to identify activation of the Nrf2 pathway. Furthermore, the use of some experimental models presented a challenge in comparing results. In view of the above, it can be suggested that E-stilbenes have a relationship with the Nrf2 pathway, whether directly or indirectly, through different biological pathways, and in different diseases or conditions that are mainly related to inflammation and oxidative stress. [ABSTRACT FROM AUTHOR]

This review aims to analyze the emerging number of studies on biological media that describe the unexpected effects of different natural bioactive antioxidants. Hormetic effects, with a biphasic response depending on the dose, or activities that are apparently non-dose-dependent, have been described for compounds such as resveratrol, curcumin, ferulic acid or linoleic acid, among others. The analysis of the reported studies confirms the incidence of these types of effects, which should be taken into account by researchers, discarding initial interpretations of imprecise methodologies or measurements. The incidence of these types of effects should enhance research into the different mechanisms of action, particularly those studied in the field of basic research, that will help us understand the causes of these unusual behaviors, depending on the dose, such as the inactivation of the signaling pathways of the immune defense system. Antioxidative and anti-inflammatory activities in biological media should be addressed in ways that go beyond a mere statistical approach. In this work, some of the research pathways that may explain the understanding of these activities are revised, paying special attention to the ability of the selected bioactive compounds (curcumin, resveratrol, ferulic acid and linoleic acid) to form metal complexes and the activity of these complexes in biological media. [ABSTRACT FROM AUTHOR]

Resveratrol (RSV) is a natural polyphenol compound found in various plants that has been shown to have potential benefits for preventing aging and supporting cardiovascular health. However, the specific signal pathway by which RSV protects the aging heart is not yet well understood. This study aimed to explore the protective effects of RSV against age‐related heart injury and investigate the underlying mechanisms using a D‐galactose‐induced aging model. The results of the study indicated that RSV provided protection against age‐related heart impairment in mice. This was evidenced by the reduction of cardiac histopathological changes as well as the attenuation of apoptosis. RSV‐induced cardioprotection was linked to a significant increase in antioxidant activity and mitochondrial transmembrane potential, as well as a reduction in oxidative damage. Additionally, RSV inhibited the production of pro‐inflammatory cytokines such as interleukin‐1β (IL‐1β) and tumor necrosis factor‐α (TNF‐α). Furthermore, the expression of toll‐like receptor 4 (TLR4), nuclear factor kappa‐B p65 (NF‐κB p65), and notch 1 protein were inhibited by RSV, indicating that inhibiting the Notch/NF‐κB pathway played a critical role in RSV‐triggered heart protection in aging mice. Moreover, further data on intestinal function demonstrated that RSV significantly increased short‐chain fatty acids (SCFAs) in intestinal contents and reduced the pH value in the feces of aging mice. RSV alleviated aging‐induced cardiac dysfunction through the suppression of oxidative stress and inflammation via the Notch/NF‐κB pathway in heart tissue. Furthermore, this therapeutic effect was found to be associated with its protective roles in the intestine. [ABSTRACT FROM AUTHOR]

BACKGROUND: In recent years, it has been found that some traditional Chinese medicine monomers can alleviate oxidative stress and apoptosis of the skin flap, promote vascular regeneration of the skin flap and prevent skin flap necrosis by activating autophagy. OBJECTIVE: To review the research progress of traditional Chinese medicine monomer regulating autophagy in preventing flap necrosis. METHODS: The Chinese and English key words were “traditional Chinese medicine (TCM), autophagy, skin flaps”. The first author searched the relevant articles published in CNKI and PubMed databases from January 2010 to October 2022. A total of 196 articles were retrieved in the preliminary screening and then screened according to the inclusion and exclusion criteria. The quality assessment was conducted by reading the literature titles and abstracts. Finally, 55 articles were summarized. RESULTS AND CONCLUSION: (1) The regulation of autophagy is mediated by AMPK/mTOR, PI3K/AKT and other signaling pathways. Activation of autophagy can alleviate the oxidative stress and apoptosis of the flap, promote the regeneration of blood vessels in the flap, and prevent flap necrosis. (2) Terpenoids (Betulinic acid, Andrographolide, Notoginseng Triterpenes, Catalpa), phenolic compounds (Resveratrol, Curcumin, Gastrodin), phenolic acids (Salvianolic acid B) and steroid compounds (Pseudoginsenoside F11) in traditional Chinese medicine monomers can alleviate oxidative stress and apoptosis of skin flap by regulating related signaling pathways to activate autophagy, promote skin flap angiogenesis and promote skin flap survival. (3) Studying the research progress of traditional Chinese medicine monomer to prevent flap necrosis by regulating autophagy can provide a reference and theoretical basis for traditional Chinese medicine to prevent flap necrosis and promote flap healing in the clinic. [ABSTRACT FROM AUTHOR]

Background: Using inulin can enhance resveratrol's effects by improving the intestinal microbiome and the stability of resveratrol. Objectives: We aimed to investigate the effect of therapeutic intervention with combined inulin and resveratrol on kidney function in diabetic rats. Methods: Diabetic model was induced by intraperitoneal injection of streptozotocin. Afterward, rats were divided into 6 groups: control, diabetic without treatment, diabetic treated with insulin, diabetic treated with resveratrol, diabetic treated with inulin, and diabetic treated with a combination of inulin and resveratrol. After 10 wk, the creatinine, urea, insulin, urinary proteins, and inflammatory and oxidative stress markers were evaluated. Pathologic changes were examined in kidney tissues. Results: Renal dysfunction, accompanied by increased inflammation and oxidative stress, was observed. Our results showed that treatment with resveratrol and inulin had antidiabetic effects and was associated with reduced renal dysfunction, oxidative stress, and kidney inflammation. In addition, it was observed that combined treatment with inulin and resveratrol outperformed monotherapies in improving kidney function and reducing oxidative stress and inflammation. Conclusions: Treatment with resveratrol and inulin can have renoprotective effects by improving oxidative stress and inflammation in kidney tissues. Therefore, employing these 2 compounds is suggested as an inexpensive and available method for diabetic nephropathy. [ABSTRACT FROM AUTHOR]

With the intensification of population aging, aging-related diseases are attracting more and more attention, thus, the study of aging mechanisms and anti-aging drugs is becoming increasingly urgent. Resveratrol is a potential candidate as an anti-aging agent, but its low bioavailability limits its application in vivo. In this work, a 4-hydroxy-3′-trifluoromethoxy-substituted resveratrol derivative (4–6), owing to its superior cell accumulation, could inhibit NO production in an inflammatory cell model, inhibit oxidative cytotoxicity, and reduce ROS accumulation and the population of apoptotic cells in an oxidative stress cell model. In D-galactose (D-gal)-stimulated aging mice, 4–6 could reverse liver and kidney damage; protect the serum, brain, and liver against oxidative stress; and increase the body's immunity in the spleen. Further D-gal-induced brain aging studies showed that 4–6 could improve the pathological changes in the hippocampus and the dysfunction of the cholinergic system. Moreover, protein expression related to aging, oxidative stress, and apoptosis in the brain tissue homogenate measured via Western blotting also showed that 4–6 could ameliorate brain aging by protecting against oxidative stress and reducing apoptosis. This work revealed that meta-trifluoromethoxy substituted 4–6 deserved to be further investigated as an effective anti-aging candidate drug. [ABSTRACT FROM AUTHOR]

One of the most important side effects of Doxorubicin (DOX), a chemotherapeutic agent, is nephrotoxicity. The purpose of this study is to determine whether different doses of natural polyphenol Resveratrol (RSV) show antioxidative, anti-inflammatory or antiapoptotic effects in kidney tissue in DOX-induced nephrotoxicity and to detect how nephrin and OTULIN levels are affected in this process. A total of six equal groups made up of the 42 Sprague-Dawley rats utilized in the study (n = 7) were randomly assigned. Except for the control group (no treatment), all treatments were given intraperitoneally to the DOX (15 mg/kg), DOX + RSV I (15 mg/kg DOX+ 1 mg/kg/day RSV), DOX + RSV II (15 mg/kg DOX+ 5 mg/kg/day RSV), RSV I and RSV II groups. Kidney tissues taken from rats sacrificed on the fifteenth day were analyzed biochemically, histologically and immunohistochemically. Accordingly, it was determined that nephrin and OTULIN levels decreased in kidney tissue in DOX-induced nephrotoxicity. Furthermore, DOX caused oxidative stress, inflammation, and apoptosis, as well as histopathological changes in kidney tissue. However, it was observed that DOX-induced changes were regulated by RSV application. RSV was demonstrated to have antioxidant, anti-inflammatory and anti-apoptotic properties in dose-dependent DOX-induced nephrotoxicity. RSV may exert nephroprotective effects by modulating DOX-induced altered nephrin and OTULIN levels. [ABSTRACT FROM AUTHOR]

Reactive oxygen species are a group of cellular molecules that stand as double-edged swords, their good and bad being discriminated by a precise balance. Several metabolic reactions in the biological system generate these molecules that interact with cellular atoms to regulate functions ranging from cell homeostasis to cell death. A prooxidative state of the cell concomitant with decreased clearance of such molecules leads to oxidative stress, which contributes as a prime pathophysiological mechanism in various diseases including renal disorders, such as acute kidney injury. However, targeting the generation of oxidative stress in renal disorders by an antioxidant, resveratrol, is gaining considerable therapeutic importance and is known to improve the condition in preclinical studies. This review aims to discuss molecular mechanisms of oxidative stress in acute kidney injury and its amelioration by resveratrol. The major sources of data were PubMed and Google Scholar, with studies from the last five years primarily included, with significant earlier data also considered. Mitochondrial dysfunction, various enzymatic reactions, and protein misfolding are the major sources of reactive oxygen species in acute kidney injury, and interrupting these loci of generation or intersection with other cellular components by resveratrol can mitigate the severity of the condition. [ABSTRACT FROM AUTHOR]

The use of antioxidants for semen preservation prevents oxidative damage caused by reactive oxygen species (ROS). One of the most promising natural antioxidants is resveratrol, a phytoalexin derived from plants, grapes, berries, peanuts and red wine. To evaluate the effect of resveratrol on the quality and redox status of cryopreserved bovine semen. Five bulls were subjected to electroejaculation to obtain 15 ejaculates. Each ejaculate was extended with a tris‐egg yolk‐glycerol‐based medium and divided into six aliquots supplemented with 0 (control), 10, 20, 30, 40 and 50 μM of resveratrol. Semen was frozen with liquid nitrogen vapours. Post‐thawing, motility and kinetics were evaluated using a computer‐assisted sperm analysis (CASA) system, membrane integrity using the hypoosmotic test (HOST), morphology by staining with eosin–nigrosin, sperm vitality by fluorescence microscopy with the SYBR14/IP probes. Total antioxidant capacity (TAC) was evaluated using the ABTS•+ assay and ROS was evaluated using spectrofluorimetry with the H2DCFDA probe. For the statistical analysis linear models were adjusted and means were compared using the Tukey test. All concentrations of resveratrol reduced post‐thawed motility and kinetics of sperm. Supplementation with 40 and 50 μM of resveratrol reduced sperm kinetics, and between 30 and 50 μM of resveratrol alterations in the sperm membrane and morphology were observed. However, using resveratrol at 50 μM increased TAC and at 20 μM, it reduced ROS production of cryopreserved bovine semen. Resveratrol appears to have a dose‐dependent effect in which higher doses produce greater sperm alterations, however, it can increase semen TAC during freezing. It is concluded that resveratrol can increase antioxidant capacity and reduce ROS production in cryopreserved bovine semen. However, its use between 10 and 50 μM reduces post‐thawing semen quality. [ABSTRACT FROM AUTHOR]

Vitis vinifera L. (grapevine) is a perennial plant of the Vitaceae family that is widely used to produce grapes and wines. Grape seed oil is rich in fatty acids such as linoleic acid (65–75%), vitamin E (50 mg), and phytosterols in addition to phenolic compounds, such as catechins (414 mg), epicatechins (130.4 mg), and gallic acid (77 µg), shows promise as a nutritional compound and is outstanding as a therapeutic substance with active properties for health, detected mainly by in vitro studies, as well as some in vivo studies. The benefits of consuming this oil include modulating the expression of antioxidant enzymes, anti-atherosclerotic and anti-inflammatory effects, and protection against oxidative cell damage and some types of cancer. However, experimental findings confirm that therapeutic functions remain scarce; thus, more studies are needed to determine the mechanisms of action involved in the indicated therapeutic qualities. [ABSTRACT FROM AUTHOR]

Objective: NAD(P)H: Quinone oxidoreductase1 (NQO1) plays a crucial role in cellular defense against oxidative stress. Overexpression of NQO1 is linked to various cancer pathways. Despite its potential, the actual mechanisms to inhibit NQO1 and increase the efficacy of standard therapeutic options are not yet established. Resveratrol is an anti-cancer polyphenol found in dietary products and red wine. The objective of this investigation is to employ in silico methods to explore how resveratrol interacts with NQO1. Materials and Methods: Docking analysis of resveratrol against NQO1 was performed using Glide. The most efficiently docked complex was characterized and analyzed by measuring intermolecular (IM) hydrogen (H)-bonds and binding energy values, additional hydrophobic, and electrostatic interactions. IM interaction between complexed protein and compound was demonstrated using LigPlot+ and the Schrödinger ligand interaction module. Molecular dynamics tools were employed to examine the physical movement of molecules to evaluate how macromolecular structures relate to their functions. Results: The results of this investigation depicted a strong affinity of resveratrol againstNQO1followed byMDsimulations (NQO1- resveratrol complex-binding energy: -2.847kcal/mol). Resveratrol's robust binding affinity through docking and molecular dynamic simulations highlights a significant change around 90 ns. The H-bonds number was inversely linked with the resveratrol-NQO1 complex stability. The NQO1-Resveratrol complex displayed dynamic motion, as revealed by porcupine projections, indicating alterations in its movement and flexibility. Conclusion: The present in silico analysis suggests a possible alteration in resveratrol's orientation in the protein binding pocket. The findings encourage further investigation, including validation using in vitro and in vivo assays. [ABSTRACT FROM AUTHOR]

HIV suppression in brain viral reservoirs, especially macrophages, and microglia is critical to suppress HIV neuropathogenesis and subsequently HIV-associated neurocognitive disorders (HAND). Since most antiretroviral therapy (ART) drugs do not achieve optimal therapeutic concentrations in the brain and can cause neurotoxicity, an alternative/adjuvant therapy is needed to suppress HIV neuropathogenesis. In this study, our objectives were to examine the anti-HIV, antioxidant, and anti-inflammatory potential of resveratrol (RES) and its synthetic analogs 4-(E)-{(p-tolylimino)-methylbenzene-1,2-diol} (TIMBD) and 4-(E)-{(4-hydroxyphenylimino)-methylbenzene,1,2-diol} (HPIMBD) in HIV-infected macrophages. We used HIV replication (viral load), oxidative stress (reactive oxygen species and antioxidant enzymes), and inflammatory response (pro- and anti-inflammatory cytokines/chemokines) assays to achieve the objectives of the study. Our results showed that RES and its analogs HPIMBD and TIMBD at 25 µM concentration significantly decrease HIV replication in both primary monocyte-derived macrophages and U1-differentiated macrophages. Moreover, RES and its analogs do not induce any cytotoxicity for up to 3 days in these cells. Further, treatment with RES and TIMBD (25 µM) also reduced the levels of reactive oxygen species without affecting the expression of antioxidant enzymes, SOD1, and catalase in U1 macrophages. Besides, RES and HPIMBD treatment inhibited the proinflammatory cytokines and chemokines in U1 macrophages, which was associated with decreased levels of anti-inflammatory cytokines. Importantly, our western blot experiments show that RES also decreases cellular proinflammatory cytokine IL-1β, which is usually elevated in both myeloid and neuronal cells upon HIV infection. Taken together, our results suggest that RES and/or its analogs are important adjuvants that may be used not only to suppress HIV but also oxidative stress and inflammation in brain viral reservoirs. [ABSTRACT FROM AUTHOR]

AIM: From the perspective of regulating mitochondrial complex I activity by DJ-1 protein, this study aims to explore the mechanism of DJ-1-mediated resveratrol (RES) preconditioning in protecting against oxidative stress injury induced by myocardial ischemia-reperfusion (I/R) in rats. METHODS: After intramyocardial injection of lentivirus carrying DJ-1 shRNA (sh-DJ-l) or negative control (NC) shRNA, the myocardial I/R model was constructed by ligating the left anterior descending branch of the rat coronary artery. Sprague-Dawley (SD) rats were randomly divided into 6 groups: sham group, I/R group, RES+I/R group, NC+RES+I/R group, sh-DJ-1+RES+I/R group, and IACS-010759 (mitochondrial complex I inhibitor)+RES+I/R group, with 10 rats in each group. The rats in RES treatment groups were given RES (20 mg/kg) via gavage for 7 d prior to the myocardial I/R modeling, once daily. Moreover, the rats in sham and I/R groups received an equivalent volume of normal saline via gavage. Myocardial infarction area and cardiac function were assessed by TTC staining and echocardiography, respectively. The MitoSOX fluorescent probe was used to detect levels of mitochondrial reactive oxygen species (ROS) in the myocardium. The levels of malondialdehyde (MDA), superoxide dis-mutase (SOD) and lactate dehydrogenase (LDH) in the serum were detected using kits. Western blot and co-immunoprecipitation assays were used to observe the interaction between DJ-1 and the two subunits, ND-1 and NDUFA4, of the mitochondrial complex I. RESULTS: Compared with I/R group, RES pretreatment significantly reduced the myocardial infarction area, mitochondrial ROS levels, serum LDH activity, and serum MDA content (P<0. 01). It also elevated left ventricular ejection fraction, left ventricular fractional shortening and serum SOD activity (P<0. 01). Pretreatment with RES increased the expression and mitochondrial translocation of DJ-1 (P<0. 01), promoted the interaction between DJ-1 and ND-1/NDUFA4, which in turn protected the activity of mitochondrial complex I (P<0. 01). However, when the expression of DJ-1 was suppressed, the protective effects of RES against myocardial I/R injury were significantly inhibited compared with RES+I/R group (P<0. 05 or P<0. 01). CONCLUSION: Pretreatment with RES increases the expression and mitochondrial translocation of DJ-1, and facilitates the interaction of DJ-1 with ND1 and NDUFA4 subunits of mito-chondrial complex I, thus preserving the activity of mitochondrial complex I and attenuating myocardial I/R-induced oxidative stress damage. [ABSTRACT FROM AUTHOR]

Background: This study aimed to investigate the combined effects of resveratrol (RES) and saroglitazar (SARO) on a high-fat diet (HFD)-induced non-alcoholic fatty liver disease (NAFLD) in a rat model. Methods: In this animal study, rats were treated with RES, SARO, or a combination of both. Male rats were fed with an HFD to induce nonalcoholic steatohepatitis (NASH) and then divided into 4 groups: RES treatment, SARO treatment, combined RES and SARO treatment, and no treatment. Various parameters were measured, including body and liver weight, liver enzymes, gene expression of inflammatory markers and reactive oxygen species (ROS), protein expression levels of transforming growth factor-beta (TGF-β) and p-Smad3, and liver histology. Results: The combination of RES and SARO significantly reduced blood and hepatic lipids, attenuated weight gain, and decreased inflammatory cytokine production in a NAFLD study. The combination diminished hepatic lipid accumulation, oxidative stress, and TGF-β1 expression, suggesting antifibrotic effects. Histological evaluations showed antisteatotic and antifibrotic outcomes of the combined treatment. Improved glycemic index, blood lipids, and reduced NASH indicators (i.e., aspartate aminotransferase [AST] and alanine aminotransferase [ALT]) were observed after 6 weeks. The treatment also decreased ROS and NOX family expression, lessening oxidative stress. The inhibition of the TGF-β-Smad3 pathway in HFD-induced rats resulted in reduced NASH(P< 0.05). Conclusions: The results indicated that the group receiving the combination of RES and SARO showed a more efficient reduction in fibrosis and steatosis in the NASH model induced by an HFD than the groups receiving RES or SARO alone. [ABSTRACT FROM AUTHOR]

Tacrolimus (TAC) is a potent and well-tolerated immunosuppressive drug, but serious side effects including nephrotoxicity and hepatotoxicity have been reported. Ursodeoxycholic acid (UDCA) and resveratrol (RSV) exhibit hepatoprotective effects in liver diseases. We investigated the hepatoprotective effect of UDCA and RSV against TAC induced hepatotoxicity. We divided 40 male rats into five equal groups: A) control group, B) TAC group, C) TAC + UDCA group, D) TAC + RSV group, E) TAC + UDCA + RSV group. We administered 0.5 mg/kg TAC once daily, 25 mg/kg UDCA twice daily and 10 mg/kg RSV once daily. The drugs in the experimental groups were given by gavage from the first day of the study and continued for 21 days. Histopathologic and biochemical analyses were performed on day 22. In group B, serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), tumor necrosis factor-alpha (TNF), interleukin-1 (IL-1), interleukin-6 (IL-6), total oxidative status (TOS) and malondialdehyde (MDA) levels were higher compared to group A, and catalase (CAT), superoxide dismutase (SOD) levels and total antioxidant status (TAS) were lower compared to group A. Severe cellular swelling, degeneration and focal necrosis were more evident in group B than in groups C–E. Histopathological improvement was observed in groups C–E, where UDCA and RSV were combined, compared to group B. We found that UDCA and RSV, together or separately, protected the liver against oxidative stress damage caused by TAC. [ABSTRACT FROM AUTHOR]

The control of oxidative stress with natural active substances could limit the development of numerous pathologies. Our objective was to study the antiradical effects of resveratrol (RSV), ε-viniferin (VNF), and vitisin B (VB) alone or in combination, and those of a standardized stilbene-enriched vine extract (SSVE). In the DPPH-, FRAP-, and NO-scavenging assays, RSV presented the highest activity with an IC50 of 81.92 ± 9.17, 13.36 ± 0.91, and 200.68 ± 15.40 µM, respectively. All binary combinations resulted in additive interactions in the DPPH- and NO-scavenging assays. In the FRAP assay, a synergic interaction for RSV + VNF, an additive for VNF + VB, and an antagonistic for RSV + VB were observed. The ternary combination of RSV + VNF + VB elicited an additive interaction in the DPPH assay and a synergic interaction in the FRAP- and NO-scavenging assays. There was no significant difference between the antioxidant activity of the SSVE and that of the combination of RSV + VNF. In conclusion, RSV presented the highest effects, followed by VNF and VB. The interactions revealed additive or synergistic effects, depending on the combination of the stilbenes and assay. [ABSTRACT FROM AUTHOR]

Indoxyl sulfate (IS) is a uremic toxin produced by the gut microbiota that commonly accumulates in patients with chronic kidney disease (CKD) and can be harmful. Resveratrol is a polyphenol with properties that attenuate oxidative stress and inflammation. This study aims to evaluate the effect of resveratrol against the damage caused by IS in RAW 264.7 murine macrophages. Cells were treated with 0, 250, 500 and 1000 μmol/L of IS, in the presence of 50 μmol/L of resveratrol. The mRNA and protein expressions of erythroid-related nuclear factor 2 (Nrf2) and nuclear factor kappa-B (NF-κB) were measured using rt-PCR and Western blot analysis, respectively. Malondialdehyde (MDA) and reactive oxygen species (ROS) levels were also analyzed. As a result, it was demonstrated that resveratrol induces the activation of the Nrf2 pathway that enhances cytoprotective response. IS upregulated the NF-κB expression and downregulated the Nrf2 expression. In contrast, resveratrol treatment significantly reduced the MDA and ROS production and inhibited the IS-induced expression of NF-κB in macrophage-like RAW 264.7. In conclusion, resveratrol can mitigate inflammation and oxidative stress caused by uremic toxins produced by the gut microbiota, such as IS. [Display omitted] • Indoxyl sulfate (IS) is a uremic toxin produced by the gut microbiota. • IS is accumulated in chronic kidney disease (CKD) patients and can be harmful. • Resveratrol is a polyphenol found in foods and exerts antioxidant and anti-inflammatory activities. • IS upregulated the inflammation and oxidative stress in macrophage-like RAW 264.7 cells. • Resveratrol treatment significantly reduced the inflammation and oxidative stress induced by IS in macrophage-like RAW 264.7. [ABSTRACT FROM AUTHOR]

The increased generation of reactive oxygen species (ROS) by mitochondria under stress conditions leads to lipid peroxidation (LPO) as a consequence of the ROS interactions with polyunsaturated fatty acids in the lipid bilayer of cell membranes, causing their damage. It was assumed that chemical preparations that reduce the excessive ROS generation by mitochondria should exhibit protecting properties under oxidative-stress conditions. In this context, the antioxidants resveratrol (RSV) and 2-ethyl-6-methyl-3-hydroxypyridine N-acetylcysteinate (NAC-3-HP) were examined as potential chemical protectors upon the exposure to stress, able to maintain the functional state of mitochondria. [ABSTRACT FROM AUTHOR]

Background: We aimed to investigate the ability of resveratrol carbon dots (RES C-Dots) to protect SHSY5Y cells from oxido-inflammatory stress and apoptosis caused by 6-hydroxydopamine (6-OHDA). Materials and Methods: In vitro PD model was generated in SH-SY5Y cells by administering of 200 µM 6- OHDA for 24 hours. Different concentrations of RES C-Dots (12.5, 25, and 50 µg/mL) were applied to the cells 30 minutes before administration of 6-OHDA. Results: We observed that application of RES C-Dots prevented cell death induced by 6-OHDA and maintained cell viability. As expected, RES C-Dots prevented oxidative damage induced by 6-OHDA - by strengthening the total amount of antioxidants and lowering the total amount of oxidants in SH-SY5Y cells. Similarly, RES C-Dots markedly alleviated the secretion of inflammatory factors (TNF-α and IL-1β) promoted by 6-OHDA. Furthermore, RES C-Dots prevented apoptosis induced by 6-OHDA by suppressing caspase-3 mRNA expression level. Conclusions: RES C-Dots rescued SH-SY5Y cells from 6-OHDA- induced damage by modulating the oxidoinflammatory and apoptotic response. This report indicates enounces that RES- synthesised C-Dots may have promising curative potential for PD. [ABSTRACT FROM AUTHOR]

Multiple myeloma (MM) is a cancer of plasma cells in the bone marrow characterized by bone lesions, hypercalcemia, anemia, and renal failure. Bortezomib (BTZ), a common treatment for MM, is a proteasome inhibitor that induces apoptosis in MM cells. However, high doses of BTZ can be very toxic, signifying a need for a synergistic drug combination to improve treatment efficacy. Resveratrol (RES), a phenolic compound found in grapes, has been shown to inhibit MM cell growth. We sought to identify a synergistic combination of BTZ with a RES derivative and analyze the effects on reducing viability and inducing apoptosis in human MM cells. BTZ as well as RES and its derivatives pinostilbene (PIN) and piceatannol (PIC) decreased MM cell viability in a dose- and time-dependent manner and increased expression of cleaved proapoptotic proteins poly(ADP-ribose) polymerase 1 (PARP1) and caspase-3 in a dose-dependent manner. The combination of 5 nM BTZ and 5 μM PIN was identified to have synergistic cytotoxic effects in MM RPMI 8226 cells. MM RPMI 8226 cells treated with this combination for 24 h showed increased cleaved PARP1 and caspase-3 expression and higher percentages of apoptotic cells versus cells treated with the individual compounds alone. The treatment also showed increased apoptosis induction in MM RPMI 8226 cells co-cultured with human bone marrow stromal HS-5 cells in a Transwell model used to mimic the bone marrow microenvironment. Expression of oxidative stress defense proteins (catalase, thioredoxin, and superoxide dismutase) in RPMI 8226 cells were reduced after 24 h treatment, and cytotoxic effects of the treatment were ameliorated by antioxidant N-acetylcysteine (NAC), suggesting the treatment impacts antioxidant levels in RPMI 8226 cells. Our results suggest that this combination of BTZ and PIN decreases MM cell viability synergistically by inducing apoptosis and oxidative stress in MM cells. [ABSTRACT FROM AUTHOR]

Objectives: Madecassoside (MAD) is a triterpenoid constituent of Centella asiatica (L.) Urb., an ethnomedical tropical plant, extracts of which were shown to reduce blood glucose in experimental diabetes. This study examines MAD for its anti-hyperglycaemic effects and tests the hypothesis that it reduces the blood glucose in experimentally induced diabetic rats by protecting the β-cells. Methods: Diabetes was induced using streptozotocin (60 mg/kg, i.v.) followed by nicotinamide (210 mg/kg, intraperitoneal (i.p.)). MAD (50 mg/kg) was administered orally for 4 weeks, commencing 15 days after induction of diabetes; resveratrol (10 mg/kg) was used as a positive control. Fasting blood glucose, plasma insulin, HbA1c, liver and lipid parameters were measured, along with antioxidant enzymes and malondialdehyde as an index of lipid peroxidation; histological and immunohistochemical studies were also undertaken. Key findings: MAD normalized the elevated fasting blood glucose levels. This was associated with increased plasma insulin concentrations. MAD alleviated oxidative stress by improving enzymatic antioxidants and reducing lipid peroxidation. Histopathological examination showed significant recovery of islet structural degeneration and an increased area of islets. Immunohistochemical staining showed increased insulin content in islets of MAD-treated rats. Conclusions: The results demonstrate an antidiabetic effect of MAD associated with preservation of β-cell structure and function. Graphical Abstract [ABSTRACT FROM AUTHOR]

Radiotherapy, which is routinely used to treat a wide range of oncological disorders, primarily affects the malignant tissue in the targeted area, but also have negative effects in the surrounding tissues. Pelvic radiotherapy causes early and late effects on the colon and rectum. Resveratrol (RVT) has been revealed to have a number of pharmacological effects in a variety of experimental models and clinical circumstances, therefore it has piqued the interest of scientists in recent years. In this study, we aimed to investigate the potential protective effects of resveratrol (RVT), a strong antioxidant, anti-inflammatory and anti-mutagenic agent, against toxicity of colonic and rectal tissues seen in the early and late stages after pelvic radiation. The treatment durations of the current study were designed as one week and ten weeks interval by following radiation exposure. Sprague Dawley rats were divided into 5 groups (8 animals/group) as the control, radiation-early effects (Rd-E), radiation-late effects (Rd-L), and RVT-treated Rd-E (Rd-E+RVT) and RVT-treated Rd-L (Rd-L+RVT) groups. İonizing radiation was performed to the pelvic area that covers colon and rectum in single fraction of 20 Gy in a linear accelerator using with 6 MV photon energy. RVT was orally administered (10 mg/kg/day) immediately following the radiation exposure and continued daily for 1 and 10 weeks for early and late groups, respectively. Pelvic radiation caused a significant decrease in glutathione level, while malondialdehyde levels, myeloperoxidase activity and 8-hydroxydeoxyguanosine were increased in both Rd-E and Rd-L groups in the colon and rectum tissues. Additionally, light microscopic evaluations (H&E staining) revealed degeneration of epithelium and inflammatory cell infiltration in the colonic and rectal tissues in radiation groups. RVT treatment reversed all conducted biochemical parameters and ameliorated histomorphological changes following early and late effects of pelvic radiation in tissues. In conclusion, resveratrol may be a candidate as a radioprotector for normal tissues during and after radiotherapy. [ABSTRACT FROM AUTHOR]

Several shreds of evidence have supported the growth-inhibitory effect of resveratrol in breast cancer. Owing to the low efficiency, we aimed to fabricate an ACN nanoparticle containing resveratrol to target the proliferation of breast cancer cells. Resveratrol encapsulation was characterized using spectrophotometry, FTIR, and SEM. The cytotoxicity and antioxidant activities of compounds were evaluated by MTT, NO, FRAP, and qRT-PCR assays on MCF7 and SKBr3 cells. Our result found that the encapsulation efficiency was 87%, the particle size was 200 ± 15 nm, and the zeta potential was 31 ± 0.4 mV. The prepared RES + ACN had controlled in vitro release. RES + ACN nanoparticle showed a significantly increased cytotoxicity in both cell lines. The reduced level of NO and enhance antioxidative content in both cells, especially the MCF7, were in line with increased expression of Nrf2 and SOD as well as more apoptotic effect. Decreased growth and increased expression of Nrf2 in MCF7 compared to SKBr3 cells proved that the upregulation of Nrf2 by nanoresveratrol is likely contributed to its relationship with ER/PR signaling factors, albeit its precise mechanism is needed to be more elucidated. [ABSTRACT FROM AUTHOR]

Introduction: Hydrogen sulfide (H2S), known as a third gasotransmitter, is a signaling molecule that plays a regulatory role in physiological and pathophysiological processes. Decreased H2S levels were reported in inflammatory respiratory diseases such as asthma, chronic obstructive pulmonary disease, and pulmonary hypertension. H2S donors or drugs that increase H2S have emerged as novel treatments for inflammatory respiratory diseases. We previously showed that resveratrol (RVT) causes vascular relaxation and antioxidant effects by inducing H2S production. In the current study, we synthesized a new molecule Cpd2, as an RVT analog. We examined the effect of Cpd2 and its precursor chalcone compound (Cpd1) on H2S formation under both healthy and oxidative stress conditions in the lung, as well as vascular relaxation in the aorta. Methods: Cpd2 synthesized from Cpd1 with microwaved in basic conditions. H2S formation was measured by H2S biosensor in the mice lungs under both healthy and pyrogallol-induced oxidative stress conditions in the presence/absence of H2S synthesis inhibitor aminooxyacetic acid (AOAA). The effect of compounds on vascular tonus is investigated in mice aorta by DMT myograph. Results: RVT and Cpd2 significantly increased l-cysteine (l-cys) induced-H2S formation in the lung homogenates of healthy mice, but Cpd1 did not. Superoxide anion generator pyrogallol caused a decrease in H2S levels in mice lungs and Cpd2 restored it. Inhibition of Cpd2-induced H2S formation by AOAA confirmed that Cpd2 increases endogenous H2S formation in both healthy and oxidative stress conditions. Furthermore, we found that both Cpd1 and Cpd2 (10−8–10−4 M) caused vascular relaxation in mice aorta. Discussion and Conclusion: We found that Cpd2, a newly synthesized RVT analog, is an H2S-inducing molecule and vasorelaxant similar to RVT. Since H2S has antioxidant and anti-inflammatory effects, Cpd2 has a potential for the treatment of respiratory diseases where oxidative stress and decreased H2S levels are present. [ABSTRACT FROM AUTHOR]

The cognitive functions of people over 60 years of age have been diminished, due to the structural and functional changes that the brain has during aging. The most evident changes are at the behavioral and cognitive level, with decreased learning capacity, recognition memory, and motor incoordination. The use of exogenous antioxidants has been implemented as a potential pharmacological option to delay the onset of brain aging by attenuating oxidative stress and neurodegeneration. Resveratrol (RSVL) is a polyphenol present in various foods, such as red fruits, and drinks, such as red wine. This compound has shown great antioxidant capacity due to its chemical structure. In this study, we evaluated the effect of chronic RSVL treatment on oxidative stress and cell loss in the prefrontal cortex, hippocampus, and cerebellum of 20‐month‐old rats, as well as its impact on recognition memory and motor behavior. Rats treated with RSVL showed an improvement in locomotor activity and in short‐ and long‐term recognition memory. Likewise, the concentration of reactive oxygen species and lipid peroxidation decreased significantly in the group with RSVL, coupled with an improvement in the activity of the antioxidant system. Finally, with the help of hematoxylin and eosin staining, it was shown that chronic treatment with RSVL prevented cell loss in the brain regions studied. Our results demonstrate the antioxidant and neuroprotective capacity of RSVL when administered chronically. This strengthens the proposal that RSVL could be an important pharmacological option to reduce the incidence of neurodegenerative diseases that affect older adults. [ABSTRACT FROM AUTHOR]

Osteoarthritis (OA) of the knee is characterized by progressive deterioration and loss of articular cartilage with associatedstructural and performance changes in the entire joint, and current treatments for OA only aim to relieve symptoms, rather than to prevent or reverse disease progression. Recently, treatments targeting "early osteoarthritis" (EOA) have attracted attention. However, during EOA stage, chondrocytes may change behaviors to express pro‐inflammatory cytokines and free radicals, which would cause detrimental effects to the synovial cavity and further cartilage wear. In this study, we combined resveratrol (Res) and Bletilla striata polysaccharide (BSP) as anti‐inflammatories and antioxidants to diffuse free radicals and to alleviate inflammation from the synovial cavity both short term and long term. The current study introduced a new method for harvesting BSP from as‐received Bletilla striata to achieve high yields, shortened extraction times, and maintained structure/functions. In addition, it combined Res and home‐extracted BSP (Res‐BSP) to alleviate oxidative stress and inflammation in a Lipopolysaccharide (LPS)‐induced OA model. The gene expressions of inflammatory genes iNOs, IL‐1β, IL‐6, and MMP‐13 were upregulated 5.7‐fold, 6.5‐fold, 8.6‐fold, and 4.5‐fold, respectively on OA‐like chondrocytes and the gene expressions were significantly downregulated to 3.3‐fold, 2.1‐fold, 4.9‐fold, and 0.1‐fold, respectively, once OA‐like chondrocytes were treated with Res‐BSP (p < 0.05, compared with OA‐like chondrocytes). The gene expressions of chondrogenic genes TGFβ1, SOX9, and type II collagen were downregulated by 0.8‐fold, 2.2‐fold, and 0.8‐fold, respectively, based on the control group as a baseline. While it was significantly upregulated by 3.4‐fold, 0.32‐fold, and 0.4‐fold, respectively, once OA‐like chondrocytes were treated with Res‐BSP. (p < 0.05, compared with OA‐like chondrocytes). Finally, we elucidated the role of Res‐BSP in EOA in suppressing COX‐2 and activating p‐Smad 2/3 and p‐Erk1/2. We believe that the combination of Res and BSP has great potential as an alternative therapeutic strategy for EOA treatment in future. [ABSTRACT FROM AUTHOR]

Resveratrol is a polyphenol found naturally in fruits and plants. Recently, studies in humans and animal models have suggested beneficial properties of this polyphenol, such as improvements to metabolic and lipid profiles, along with antioxidant, anti-inflammatory and anti-proliferative effects. In the urogenital tract (UGT), resveratrol has also been tested clinically and experimentally as a therapeutic drug in several diseases; however, the translational efficacy of resveratrol, especially in UGT, is still a matter of debate. In the present review, we address the pre-clinical efficacy of resveratrol in UGT-related dysfunctions, focusing on lower urinary tract symptoms, non-cancerous prostatic disease (benign prostatic hyperplasia and prostatitis) and erectile dysfunction. In vitro studies indicate that resveratrol reduces inflammatory markers and oxidative stress, and improves endothelial function in UGT organs and cells isolated from humans and animals. Despite displaying low oral bioavailability, in vivo administration of resveratrol largely improves erectile dysfunction, benign prostatic hyperplasia, prostatitis and voiding impairments, as evidenced in different animal models. Resveratrol also acts as a microbiota modulator, which may explain some of its beneficial effects in vivo. In contrast to the large amount of pre-clinical data, there are insufficient clinical trials to establish resveratrol treatment efficacy in human UGT-related diseases. In summary, we provide an overview of the in vivo and in vitro efficacy of resveratrol in animal and human UGT dysfunctions, which may support future clinical trials. [ABSTRACT FROM AUTHOR]

The aim of this study was to investigate the effects of resveratrol against fumonisin B1 (FB1)-induced liver toxicity, as, to the best of our knowledge, these effects have not been investigated yet, even though the toxic effects and mechanisms of FB1 and the antioxidative effects of resveratrol are well known. 40 BALB/c mice were divided into control, FB1, resveratrol, and FB1+resveratrol groups. Control received saline for 14 days. The FB1 group received 2.25 mg/kg FB1 every other day for 14 days. The resveratrol group received 10 mg/kg resveratrol for 14 days. The FB1+resveratrol group received 2.25 mg/kg FB1 every other day and 10 mg/kg resveratrol every day for 14 days. All administrations were peritoneal. Alanine aminotransferase (ALT), aspartate aminotransferase (AST), total sialic acid (TSA) levels were analysed in serum samples, while total antioxidant status (TAS) and total oxidant status (TOS) were measured in the liver. Additionally, the liver tissue was examined for histopathological changes. AST, ALT, and TSA were significantly higher in the FB1 group than control. Resveratrol countered FB1 effects for all parameters, including TOS and TAS. Liver histology showed FB1-induced hyperaemia, infiltrations, and megalokaryosis in some hepatocytes. No pathological findings were detected in the control, resveratrol, or FB1+resveratrol group. Our findings confirm resveratrol's protective effect against liver damage and oxidative stress caused by FB1. In addition, they suggest that increased serum TSA levels can be used as a biomarker of FB1-induced hepatotoxicity. [ABSTRACT FROM AUTHOR]

Individuals born after intrauterine growth restriction (IUGR) are at risk of developing cardiovascular diseases (CVDs). Endothelial dysfunction plays a role in the pathogenesis of CVDs; and endothelial colony-forming cells (ECFCs) have been identified as key factors in endothelial repair. In a rat model of IUGR induced by a maternal low-protein diet, we observed an altered functionality of ECFCs in 6-month-old males, which was associated with arterial hypertension related to oxidative stress and stress-induced premature senescence (SIPS). Resveratrol (R), a polyphenol compound, was found to improve cardiovascular function. In this study, we investigated whether resveratrol could reverse ECFC dysfunctions in the IUGR group. ECFCs were isolated from IUGR and control (CTRL) males and were treated with R (1 μM) or dimethylsulfoxide (DMSO) for 48 h. In the IUGR-ECFCs, R increased proliferation (5′-bromo-2′-deoxyuridine (BrdU) incorporation, p < 0.001) and improved capillary-like outgrowth sprout formation (in Matrigel), nitric oxide (NO) production (fluorescent dye, p < 0.01), and endothelial nitric oxide synthase (eNOS) expression (immunofluorescence, p < 0.001). In addition, R decreased oxidative stress with reduced superoxide anion production (fluorescent dye, p < 0.001); increased Cu/Zn superoxide dismutase expression (Western blot, p < 0.05); and reversed SIPS with decreased beta-galactosidase activity (p < 0.001), and decreased p16ink4a (p < 0.05) and increased Sirtuin-1 (p < 0.05) expressions (Western blot). No effects of R were observed in the CTRL-ECFCs. These results suggest that R reverses long-term ECFC dysfunctions related to IUGR. [ABSTRACT FROM AUTHOR]

Objective To explore the influence of resveratrol (RES) on H2O2-induced ferroptosis in A549 cells by regulating nuclear factor E2-related factor 2 (Nrf2)-glutathione peroxidase 4 (GPX4) pathway. Methods Human alveolar epithelial cells A549 were randomly grouped into the control group, the H2O2 group, the RES low (RES-L, 50 µmol/L), the RES medium (RES-M, 100 µmol/L) and the RES high (RES-H, 150 µmol/L) concentration groups, the ML385 (Nrf2 inhibitor, 2 µmol/L ML385) group and the RES-H+ML385 (150 µmol/L RES+2 µmol/L ML385) group. Except for the control group, the other groups were treated with H2O2, and then intervened with corresponding doses of drugs and inhibitors. After the intervention, MTT method was performed to determine the viability of A549 cells in each group. The kit was applied to measure intracellular iron content. ELISA method was performed to measure levels of oxidative stress in A549 cells, including malondialdehyde (MDA), superoxide dismutase (SOD) and reduced glutathione (GSH). Transmission electron microscopy was applied to observe mitochondrial structure. Western blot assay was performed to measure the protein expression levels of Nrf2, GPX4 and heme oxygenase 1 (HO-1) in A549 cells. Results Compared with the control group, mitochondrial morphology was seriously damaged in the H2O2 group, and cell viability, SOD and GSH contents, and the Nrf2, GPX4 and HO-1 protein expression were significantly decreased, and the iron ion and MDA content were significantly increased (P＜0.05). Compared with the H2O2 group, with the increase of the RES concentration, the mitochondrial morphological damage of A549 cells was improved, the cell viability, SOD and GSH contents, and the Nrf2, GPX4 and HO-1 protein expression gradually increased, while the iron ion and MDA content gradually decreased (P＜0.05). However, the mitochondrial damage of A549 cells was aggravated in the ML385 group, and cell viability, SOD and GSH contents, and the Nrf2, GPX4 and HO-1 protein expression were significantly decreased, and iron ion and MDA content were significantly increased (P＜0.05). ML385 was able to reverse the protective effect of RES on H2O2-induced A549 cells. Conclusion RES can reduce the level of oxidative stress in A549 cells induced by H2O2 and inhibit ferroptosis, which may be related to the activation of Nrf2-GPX4 signaling pathway. [ABSTRACT FROM AUTHOR]

Doxorubicin (DOX) is an anthracycline antibiotic with a chemotherapeutic effect and has well-known cardiotoxic side effects. This study aimed to determine potential cardioprotective mechanisms of different doses of resveratrol (RES) in a DOX-induced cardiotoxic rat model. In the study, 42 Sprague–Dawley male rats were randomly divided into six groups (n = 7). The control group (n = 7) was given only ad libitum feed and water; the DOX group (n = 7) was administered DOX intraperitoneally (i.p) at a dose of 15 mg/kg at the beginning of the experiment. The DOX + RES I (n = 7) and DOX + RES II (n = 7) groups were administered RES i.p at doses of 1 mg/kg/day and 5 mg/kg/day, respectively, after administering 15 mg/kg DOX. The RES I (n = 7) and RES II (n = 7) groups were administered RES i.p at doses of 1 mg/kg/day and 5 mg/kg/day, respectively. Cardiac tissues collected upon completion of experimental procedures were used for biochemical, histopathological, and immunohistochemical evaluations. It was determined that RES administration may have an antiapoptotic effect by regulating apoptotic protein activities and an antioxidant effect by regulating oxidative stress parameters in DOX-induced cardiotoxicity. It was also observed that RES may regulate the levels of Meteorin-Like (MTRNL), which plays a role in energy metabolism, and the immunoreactivity of the transient receptor potential melastatin 2 (TRPM2) channel, which has a role in cellular ion homeostasis. RES may improve cardiac tissue damage by showing antiapoptotic and antioxidant effects against DOX-induced cardiotoxicity. Furthermore, MTRNL and TRPM2 ion channels may play a role in DOX-induced cardiotoxicity. [ABSTRACT FROM AUTHOR]

Introduction: Sodium fluoride (NaF) is a double-edged weapon against human health. We are exposed to it from different sources and it is proved to have a neurotoxic effect. Resveratrol (RES) is a naturally occurring polyphenolic compound that possesses powerful antioxidant and anti-inflammatory activities. Aim of the Work: The purpose of this study was to examine the histopathological and oxidative effects of NaF on rats' cerebellar cortex and the defensive role of RES. Material and Methods: In this study, 40 adult male albino rats were utilized. The rats were placed randomly into four groups, each with 10 animals. Rats in Group I (Control negative group) did not receive any drugs. Group II: (Control positive group) rats received 30 mg/kg of RES. Group III (Treated group): rats received 10 mg/kg B.W of NaF. Group IV (Protected group): rats received 10 mg/kg and 30 mg/kg of NaF and RES respectively. The doses were conducted once daily for a period of 30 days. Cerebella were obtained at the end and processed. Results: NaF was found to disrupt the mean levels of oxidative stress biomarkers in addition to light microscope studies that showed marked disturbances of the cerebellar cortex layers. There were extensive morphometric and statistical changes. There was a highly significant increase in the mean area percent of glial fibrillary acidic protein (GFAP) as well as a highly significant increase in the mean area percent of inducible nitric oxide synthase (iNOS) in the treated group when compared to the control and protected groups. Co-administration of RES with NaF protected against such changes. Conclusion: Adult male albino rats' cerebellar cortex architecture was substantially changed by exposure to NaF, both histologically and biochemically. The use of RES in combination with NaF guarded against the neurotoxicity of NaF. [ABSTRACT FROM AUTHOR]

Age-related macular degeneration (AMD) is one of the most commonly occurring ocular diseases worldwide. This degenerative condition affects the retina and leads to the loss of central vision. The current treatments are focused on the late stage of the disease, but recent studies have highlighted the importance and benefits of preventive treatments and how good dietary habits can reduce the risk of progression to an advanced form of the disease. In this context, we studied whether resveratrol (RSV) or a polyphenolic cocktail, red wine extract (RWE), are able to prevent the initiating events of AMD (i.e., oxidative stress and inflammation) in human ARPE-19 retinal pigment epithelial (RPE) cells and macrophages. This study highlights that RWE and RSV can prevent hydrogen peroxide (H2O2) or 2,2′-Azobis(2-methylpropionamidine) dihydrochloride (AAPH)-induced oxidative stress and can subsequently prevent DNA damage via the inhibition of the ATM (ataxia telangiectasia-mutated)/Chk2 (checkpoint kinase 2) or Chk1 signaling pathways, respectively. Moreover, ELISA assays show that RWE and RSV can prevent the secretion of proinflammatory cytokines in RPE cells and in human macrophages. Interestingly, RWE exhibits a greater protective impact compared to RSV alone, even though RSV was more concentrated when used alone than in the red wine extract. Our results suggest that RWE and RSV may have potential interest as preventive nutritional supplementations against AMD. [ABSTRACT FROM AUTHOR]

The Kelch-like ECH associated protein 1 (Keap1)/nuclear factor erythroid 2-related factor 2 (Nrf2)/antioxidant response elements (ARE) signaling pathway is considered a master regulator of the cellular response against oxidative stress. Numerous studies have investigated the role of Keap1/Nrf2/ARE in the different stages of cancer development. A comprehensive literature search using the Google Scholar, PubMed and Science Direct databases was performed to retrieve information related to the cancer protective role of 21 selected dietary polyphenols via modulation of Keap1/Nrf2/ARE and interconnected signaling pathways/proteins (MAPK/ERK1/2, PI3K/Akt, PKD, JNKs, AMPK, NF-κB). Information on the anti-inflammatory and cytoprotective effects caused by the selected dietary polyphenols following Keap1/Nrf2/ARE modulation was also collected. The majority of the studies analyzed in this review demonstrated the cancer protective role of the selected polyphenols mostly in-vitro. Limited work was performed in-vivo and only one of the selected polyphenols was subjected to a clinical trial. It is hoped that this review will encourage further in-vivo studies to confirm the cancer protective role of methyleugenol, carnosol, and catechin, as well as further clinical trials to unambiguously establish whether the consumption of dietary polyphenols impacts on the incidence and progression of cancers in humans. [ABSTRACT FROM AUTHOR]

Objectives: Periodontitis is closely associated with kidney disease and reactive oxygen species (ROS) involvement. Mitochondria are the primary source of both endogenous ROS and renal energy. We investigated whether resveratrol (RSV) prevents renal injury and mitochondrial dysfunction in periodontitis rats. Methods: Thirty male Wistar rats were divided into control, experimental periodontitis (Ep) and Ep‐RSV groups. To induce periodontitis, a steel ligature was placed on the cervix of the bilateral first maxillary molars. RSV (50 mg/kg/day) to the Ep‐RSV group and vehicle to the Ep and control groups were gavaged. After 8 weeks, alveolar bone loss, pocket depth, gingival blood index and tooth mobility were assessed. Oxidative stress parameters, mitochondrial structure, mitochondrial membrane potential (MMP), mitochondrial ROS, adenosine triphosphate (ATP), sirtuin 1 (SIRT1) and peroxisome proliferator‐activated receptor‐γ coactivator‐1α (PGC‐1α) were analysed in renal. Renal function and histology were also evaluated. Results: Compared with the control group, the Ep group showed renal structural destruction, elevated oxidative stress levels, mitochondrial structure destruction, MMP loss, mitochondrial ROS accumulation, ATP reduction, and decreased SIRT1 and PGC‐1α levels. RSV prevented these destruction (p < 0.05). However, there was no significant impairment in renal function (p > 0.05). Conclusions: Periodontitis induces mitochondrial dysfunction in renal tissues. Resveratrol exerts a preventive effect on periodontitis‐induced kidney injury by preventing mitochondrial dysfunction. [ABSTRACT FROM AUTHOR]