Resveratrol and its relationship with human health

Resveratrol and its derivatives are mainly found in at least 72 plants from 21 families and 31 genera, including Vitis, Polygonum, Arachis, Veratrum, etc., including common medicinal plants such as Polygonum cuspidatum, Cassia, and Mulberry, as well as crops such as grapes and peanuts. The main sources of natural resveratrol are Polygonum cuspidatum and grapes. Resveratrol is easily absorbed orally and excreted through urine and feces after metabolism. In vitro and animal experiments have shown that resveratrol has antioxidant, anti-inflammatory, anti-cancer and cardiovascular protection effects. Exploring the relationship between resveratrol and human health is conducive to promoting the deep processing and utilization of resveratrol and improving human health.

01 Resveratrol inhibits neutrophils through the ERK signaling pathway to improve liver ischemia-reperfusion injury

Abstract

Hepatic ischemia-reperfusion injury (HIRI) is a major complication of liver surgery or transplantation, with a high mortality rate. Inflammation, especially neutrophil response, plays an important role in the HIRI process. In this study, it was found that resveratrol pre-intervention improved IRI-induced liver injury and neutrophil inflammatory response in the liver. In addition, RNA sequencing analysis showed that resveratrol inhibited neutrophil functions such as survival, cell cycle, migration and chemotaxis, oxidative stress, and secretion of proinflammatory cytokines. Resveratrol inhibited endothelin 1 autocrine signaling by inhibiting the ERK signaling pathway, thereby inhibiting oxidative stress and inflammatory response of neutrophils.

Conclusion

The experiment showed that pre-intervention with resveratrol could prevent IRI-induced liver injury. At the same time, it was also found that resveratrol could inhibit liver inflammatory response during HIRI by affecting neutrophils. The mechanism by which resveratrol regulates neutrophils is to inhibit the survival, cell cycle, migration chemotaxis, oxidative stress, cytokine secretion, and endothelin 1 autocrine function of neutrophils by inhibiting the ERK signaling pathway. These data provide more evidence for the immunomodulatory effect of resveratrol and enrich our understanding of immune strategies to improve HIRI.

02Resveratrol mitigates metabolism in human microglia

Abstract

In the past, the understanding of the role of microglia in neurodegenerative diseases has steadily increased. An increasing number of studies have shown that uncontrolled and persistent activation of microglia is associated with the progression of diseases such as Alzheimer's or Parkinson's diseases. Inflammatory activation of microglia is often accompanied by a shift in metabolism toward higher glucose consumption and aerobic glycolysis. In this study, the changes induced by the natural antioxidant resveratrol in a human microglial cell line were investigated. Resveratrol is well known for its neuroprotective properties, but little is known about its direct effects on human microglia. By analyzing various inflammatory, neuroprotective and metabolic aspects, it was observed that resveratrol can reduce inflammasome activity, increase insulin-like growth factor 1 release, reduce glucose uptake, reduce mitochondrial activity and attenuate cellular metabolism in 1HNMR-based whole-cell extract analysis. Therefore, this study mainly analyzes the effects of exogenous stressors such as lipopolysaccharide or interferon gamma on the metabolic profile of microglia. The focus of this study is on changes in metabolism in the absence of any exogenous stressors to demonstrate how resveratrol provides protection against persistent neuroinflammation.

Conclusion

The study shows how resveratrol can demonstrate the transformation of human HMC3 microglia to an anti-inflammatory phenotype by alleviating metabolism, reducing endogenous inflammasome activity, and increasing IGF-1 production. Recognizing the importance of M1/M2 dynamics and developing related drugs such as resveratrol will help shift to a state of reduced metabolism and reduced inflammation, which will help in the treatment of neurodegenerative diseases in the future.

03 Potential Mechanisms of Resveratrol in Preventing and Treating Mental Disorders

Abstract

There is increasing evidence that diet and nutrients have the potential to improve people's mental health and treat mental illness. Some studies have shown that resveratrol has therapeutic effects on mental illnesses such as major depression, bipolar disorder, Alzheimer's disease, and autism. In addition, resveratrol is known to produce multiple benefits through the regulation of multiple synergistic pathways, controlling oxidative stress, inflammation, and cell death. This review collects currently available animal and human research data and discusses the potential mechanisms of action of resveratrol in the prevention and treatment of psychiatric disorders.

Conclusion

This article reviews the research progress of resveratrol (RSV) in the treatment of psychiatric disorders such as MDD, BD, SZ, AD, and ASD in recent years. These psychiatric disorders have complex physiological pathologies, but there are also some common neurobiological changes, such as oxidative stress, neuroinflammation, and decreased neuroplasticity. RSV has been shown to have antioxidant and anti-inflammatory properties and is a good alternative for the treatment of these psychiatric disorders. However, despite the obvious protective effects of RSV in preclinical studies (mainly antioxidant and anti-inflammatory), the substance has not shown an overall effect on symptoms in clinical studies of any of the diseases described in this article. This literature review clearly shows that RSV cannot treat the psychiatric disorders described in this article alone. However, since oxidative stress, inflammation, and death signaling pathways are involved in this process, adjuvant supplementation of treatment may help slow the neuroprogression of psychiatric diseases. Therefore, clinical studies of RSV as an adjunctive therapy are needed to clarify this hypothesis.

Another noteworthy point is that RSV seems to reduce drug side effects and residual symptoms of psychiatric disorders. RSV was found to improve sexual dysfunction in a preclinical study. Sexual dysfunction is a symptom of the psychiatric disorders described in this article (MDD, BD, SZ, ASD, and AD) and a side effect of the drugs used to treat these disorders. Therefore, natural substances that treat sexual dysfunction are essential to improve the quality of life of patients. RSV also improves metabolic parameters in animal models of depression, reducing LDL, total cholesterol, and triglycerides and increasing HDL in mice. The coexistence of metabolic syndrome in patients with psychiatric disorders is well described, so a substance that acts on these parameters may also improve their quality of life when treating symptoms of major depression, bipolar disorder, SZ, AD, and ASD.

04 Plasticity of resveratrol as a colorectal cancer sensitizer

Abstract

Despite the great success of modern medical treatment, colorectal cancer (CRC) remains one of the leading causes of cancer death worldwide. Chemotherapy as a monotherapy may cause significant side effects and chemoresistance, which may be related to multiple resistance-activating biological processes, including increased inflammation, cellular plasticity, multidrug resistance (MDR), suppression of the sentinel gene p53, and apoptosis. Tumor cells can evade the effectiveness of chemotherapeutic drugs and emphasize the need for cross-target therapeutic approaches that are not only pharmacologically safe but also capable of modulating multiple potent signaling pathways and sensitizing cancer cells to overcome resistance to standard drugs. In recent years, scientists have been searching for natural compounds that can be used as chemosensitizers in addition to traditional drugs for synergistic treatment of colorectal cancer. Resveratrol, a natural polyphenol phytoalexin found in various fruits and vegetables such as peanuts, berries, and red grapes, is one of the effective natural chemopreventive agents. Extensive in vitro and in vivo studies have shown that resveratrol interacts with standard drugs and is an effective chemosensitizer for CRC cells to chemotherapeutic drugs, thereby modulating multiple pathways, including transcription factors, epithelial-mesenchymal transition plasticity, proliferation, metastasis, angiogenesis, cell cycle, and apoptosis. The ability of resveratrol to alter multiple subcellular pathways may inhibit cancer cell plasticity and reverse chemoresistance, which is a key parameter to understand its anticancer effects. In this review, the focus is on the chemosensitizing properties of resveratrol in colorectal cancer and its potential importance as an additive for sustained treatment.

Conclusion

Based on comprehensive preclinical studies, resveratrol exerts chemoprotective and chemosensitizing effects through anti-plasticity, antioxidant, anti-inflammatory, and pro-apoptotic modes of action. In addition to its anticancer effects, resveratrol can also act as a mitigater of chemotherapy-induced toxicity in normal cells/tissues. Drug combination as an anticancer drug (targeting multiple mechanisms) improves its therapeutic efficacy and reduces chemoresistance effects through superposition and synergy.

In this article, it was found that the polyphenol resveratrol can not only be used for the prevention of CRC, but also can be used in combination with conventional chemotherapy. In addition, the molecular targets of chemoprevention resveratrol are similar to those currently used for the treatment of CRC, emphasizing the importance of clinical trials to verify its anticancer effectiveness and reliability in clinical settings. The use of resveratrol as a cancer chemoprotectant or chemosensitizer in combination with conventional chemotherapy drugs in CRC patients requires further in-depth clinical evaluation to clarify the differences between preclinical cancer research and clinical practice. These studies must include precise analysis of resveratrol's pharmacokinetic parameters in humans; finding adequate and safe doses of resveratrol when used as monotherapy and/or in combination with existing chemotherapy drugs; finding effective combinations of resveratrol and conventional chemotherapy drugs to resensitize cancers resistant to chemotherapy/radiotherapy; detailing the cellular targets of resveratrol and its effects on tumor-specific issues such as disease recurrence and treatment resistance; understanding how the specific individual characteristics of cancer patients affect the therapeutic efficacy, chemosensitization potential, and prognosis of resveratrol formulations in colorectal cancer patients undergoing treatment; evaluating advanced drug formulations and improved drug delivery technologies, such as nanotechnology, to specifically target tumor cells/tissues, which avoids possible off-target and side effects when resveratrol is used as monotherapy and/or in combination with existing chemotherapy drugs.

In summary, this review summarizes the chemosensitization of tumor cells to chemotherapeutic drugs by resveratrol from the perspective of cell plasticity, which has important implications for the adaptability of cells to the TME during tumor cell transformation and metastasis. This also provides new impetus for further research on cancer epigenetics and resveratrol-mediated inhibition of plasticity, strongly suggesting that resveratrol, as an active phytochemical, will play an important role in the prevention and treatment of CRC in the future.