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Food Interactions, Sirtuins, Genes, Homeostasis, and General Discussion
Published in Chuong Pham-Huy, Bruno Pham Huy, Food and Lifestyle in Health and Disease, 2022
Chuong Pham-Huy, Bruno Pham Huy
In tumorigenesis (cancer development), Sirt1 seems to play a contradictory role, acting as both a tumor promoter and tumor suppressor (70, 73, 87, 95–98). Sirt1 was the first sirtuin family member to be discovered and is still the most studied. Its biological role in cancer has been studied extensively, yet there are conflicting results regarding the association between the two, as Sirt1 is known to suppress or promote cancer depending on its cellular content or type (97). It is similar to survivin, a protein of the inhibitor of apoptosis family. As tumor suppressor, sirtuin1 inhibits oncogenes and oncoproteins. Sirt1 knockdown accelerated tumor xenograft formation by HCT116 cells, whereas Sirt1 overexpression inhibited tumor formation (70). High Sirt1 levels were also detected in normal colon mucosa and benign adenomas; and Sirt1 overexpression was observed in about 25% of stage I/II/III colorectal adenocarcinomas but rarely found in advanced stage IV tumors (70). On the other hand, up-regulated Sirt1 has been described in cancer cell lines as well as in tissue samples from patients with human lung cancer, prostate cancer, colon carcinoma, and chronic lymphocytic leukemia cells (70). These results raise the possibility that inhibition of Sirt1 might suppress cancer cell proliferation. However, reduced Sirt1 levels have been also reported in breast cancer and hepatic cell carcinoma compared with their normal controls, while slight increase or no change of Sirt1 levels were detected in other tumors (70).
ENZOGENOL Pine Bark Extract
Published in Dilip Ghosh, Pulok K. Mukherjee, Natural Medicines, 2019
Bioactivities of the compounds present in ENZOGENOL have been studied from different plant sources and in many different model systems, offering a number of mechanisms, other than anti-oxidant effects, by which ENZOGENOL may be influencing human physiology. Only a few particularly interesting studies are mentioned here. Proanthocyanidins (PACs) from grape-seeds were shown in healthy rats to significantly increase hepatic nicotinamide adenine dinucleotide (NAD+) content in a dose-dependent manner by specifically modulating hepatic concentrations of the major NAD+ precursors as well as the mRNA levels of the genes encoding the enzymes involved in the cellular metabolism of NAD+. Sirtuin 1 (Sirt1) gene expression was also significantly upregulated. The increase in both the NAD+ availability and Sirt1 mRNA levels, in turn, resulted in the hepatic activation of SIRT1, which was significantly associated with improved protection against hepatic triglyceride accumulation. This data indicates that PAC consumption may benefit liver lipid profiles via modulation of NAD+ levels and SIRT1 activity (Aragonès et al. 2016). These may be another part of the mechanisms by which ENZOGENOL normalizes hepatic liver profiles in diabetic rats as described above (mouse diabetes trial).
Polyphenols and Cancer Immunology
Published in Spyridon E. Kintzios, Maria G. Barberaki, Evangelia A. Flampouri, Plants That Fight Cancer, 2019
Resveratrol also induces apoptosis through a p53-mediated mechanism or activation of the CD95 signaling pathway which enhances CD95L expression or activates caspase-3 activity and decreases the mitochondrial transmembrane potential (Falchetti et al. 2001, Shimizu et al. 2006, Cui et al. 2010). It has also been shown that resveratrol selectively induces programmed death of tumor cells, simultaneously inhibiting this process in healthy cells (Wright 2013). In the presence of resveratrol, the release of pro-inflammatory cytokines and chemokines is reduced, among others through up-regulation of the sirt1 gene encoding the sirtuin 1 protein, also known as NAD-dependent deacetylase sirtuin-1. This process is followed by inhibition of the activity of protein kinase C and NF-κB and nuclear translocation. Sirt1 is a resveratrol receptor involved in peripheral T-cell tolerance. The consequences of sirt1 expression include decreased acetylation of c-Jun, blockage of its translocation into the nucleus, and inhibited activation of T-cells (Rieder et al. 2012, Zou et al. 2013).
The Protective Activity of Penehyclidine Hydrochloride against Renal Ischemia/Reperfusion-Mediated NLRP3 Inflammasome Activation is Induced by SIRT1
Published in Journal of Investigative Surgery, 2022
Zhaohui Liu, Yanli Meng, Qianjie Wei, Yu Miao, Lili Yu, Yuqing Li, Bing Zhang
Recent studies have shown that an inflammatory response-related multiprotein complex (inflammasome) plays a key role in AM-induced innate immunity [12, 13]. Several inflammasomes, including pyrin domain-containing protein 1 (NLRP1), NLRP2, NLRP3, absent in melanoma 2 (AIM2), and ice protease-activating factor (IPAF), have been identified [14]. Of these, NLRP3 has been extensively studied— it plays a crucial role in inflammatory cytokines production and inflammation response [15]. Reportedly, the cleavage of procaspase-1 into caspase-1 activates the NLRP3 inflammasome and induces the production of proinflammatory cytokines such as interleukin (IL)-1β and IL-18 [15]. In AMs, rI/R promotes the IL-1β and NLRP3 inflammasome production [11]. The sirtuin family of proteins comprising seven proteins plays important roles in the cellular response to metabolic, inflammatory, and oxidative stressors [16]. It has been shown that sirtuin 1 (SIRT1), a member of the sirtuin family of proteins, plays an important role in cellular inflammation regulation [17]. Several studies have shown that SIRT1 mediates the inflammatory response by regulating the activation of the NLRP3 inflammasome [18]. For example, Peng et al. demonstrated that the high activity of SIRT1 decreases the NLRP3 inflammasome activation [19]. Wang et al. have shown that in vascular endothelial cells, SIRT1 inhibits inflammatory response partly through the regulation of NLRP3 inflammasome [20].
British Journal of Biomedical Science in 2021. What have we learned?
Published in British Journal of Biomedical Science, 2021
Rheumatoid arthritis (RA) is characterized by an autoimmune response, resulting in chronic inflammation and destruction of the synovial membrane. It is an insidious disease, lacking specific clinical signs and symptoms and therefore frequently not diagnosed at an early stage. Rheumatoid factor (RF) and more recently anti-cyclic citrulline polypeptide (anti-CCP) and anti-mutant citrulline vimentin (anti-MCV) are the most commonly used serum markers to aid in the diagnosis. However, additional markers with greater sensitivity and specificity, would be useful. Sirtuin-1 is a deacetylase, responsible for deacetylating a range of proteins to include histone, non-histones and it is also involved in regulating cell energy metabolism, inflammation and oxidative stress. In addition, there is evidence from in vitro and animal studies that sirtuin-1 is involved in immune regulation. Again in Issue 4, Li et al [28] compare the value of measuring sirtuin-1 levels, anti-CCP and anti-MCV in cases of RA. The authors find sirtuin-1 to be elevated in RA and to have great specificity than the other markers tested.
Protection against experimental cisplatin-induced optic nerve toxicity using resveratrol: A rat model study
Published in Cutaneous and Ocular Toxicology, 2021
Sümeyye Burcu Agcayazi, Adem Ugurlu, Turgay Ucak, Nurdan Gamze Tasli, Yucel Karakurt, Erel Icel, Ferda Keskin Cimen, Halis Süleyman
Resveratrol is a natural polyphenol with antioxidant and anti-inflammatory properties6,7. Resveratrol activates Sirtuin 1 (SIRT1), which is a member of sirtuin family that deacetylates numerous protein targets and exerts anti-oxidant effects through this mechanism8,9. The protective role of resveratrol against ageing and cardiovascular diseases has been shown in previous studies10–13. Resveratrol improves mitochondrial functions and exhibits antioxidant activities7,14–16. By scavenging ROS and modulating the effects of endogenous antioxidant enzymes, resveratrol exerts cytoprotective and neuroprotective functions in many disorders17–20. The long-term dietary intake of resveratrol has been determined to be protective against retinal ganglion cell loss after optic nerve injury16,19. However, there is limited data concerning the effects of resveratrol on oxidative stress-induced optic nerve damage.