• Nutrition Research and Practice
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• v.17 no.1
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• pp.164-173
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• 2023

BACKGROUND/OBJECTIVES: Hyperglycemia is a major cause of diabetes and diabetesrelated diseases. Sodium butyrate (NaB) is a short-chain fatty acid derivative that produces dietary fiber by anaerobic bacterial fermentation in the large intestine and occurs in foods, such as Parmesan cheese and butter. Butyrate has been shown to prevent obesity, improve insulin sensitivity, and ameliorate dyslipidemia in diet-induced obese mice. Therefore, this study examined the effects and mechanism of NaB on the secretion of inflammatory cytokines induced by high glucose (HG) in THP-1 cells. MATERIALS/METHODS: THP-1 cells were used as an in vitro model for HG-induced inflammation. The cells were cultured under normal glycemic or hyperglycemic conditions with or without NaB (0-25 μM). Western blotting and quantitative polymerase chain reaction were used to evaluate the protein and mRNA levels of nuclear factor-κB (NF-κB), interleukin-6, tumor necrosis factor-α, acetylated p65, acetyl CREB-binding protein/p300 (CBP/p300), and p300 using THP-1 cells. Histone acetyltransferase (HAT), histone deacetylase (HDAC), and pro-inflammatory cytokine secretion activity were analyzed using an enzyme-linked immunosorbent assay. RESULTS: HG significantly upregulated histone acetylation, acetylation levels of p300, NF-κB activation, and inflammatory cytokine release in THP-1 cells. Conversely, the NaB treatment reduced cytokine release and NF-κB activation in HG-treated cells. It also significantly reduced p65 acetylation, CBP/p300 HAT activity, and CBP/p300 gene expression. In addition, NaB decreased the interaction of p300 in acetylated NF-κB and TNF-α. CONCLUSIONS: These results suggest that NaB suppresses HG-induced inflammatory cytokine production through HAT/HDAC regulation in monocytes. NaB has the potential for preventing and treating diabetes and its related complications.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.12
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• pp.5001-5007
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• 2014

The acetyltransferase inhibitor garcinol, a polyisoprenylated benzophenone, is extracted from the rind of the fruit of Garcinia indica, a plant found extensively in tropical regions. Anti-cancer activity has been suggested but there is no report on its action via inhibiting acetylation against cell proliferation, cell cycle progression, and apoptosis-inhibtion induced by estradiol ($E_2$) in human breast cancer MCF-7 cells. The main purposes of this study were to investigate the effects of the acetyltransferase inhibitor garcinol on cell proliferation, cell cycle progression and apoptosis inhibition in human breast cancer MCF-7 cells treated with estrogen, and to explore the significance of changes in acetylation levels in this process. We used a variety of techniques such as CCK-8 analysis of cell proliferation, FCM analysis of cell cycling and apoptosis, immunofluorescence analysis of NF-${\kappa}B$/p65 localization, and RT-PCR and Western blotting analysis of ac-H3, ac-H4, ac-p65, cyclin D1, Bcl-2 and Bcl-xl. We found that on treatment with garcinol in MCF-7 cells, $E_2$-induced proliferation was inhibited, cell cycle progression was arrested at G0/G1 phase, and the cell apoptosis rate was increased. Expression of ac-H3, ac-H4 and NF-${\kappa}B$/ac-p65 proteins in $E_2$-treated MCF-7 cells was increased, this being inhibited by garcinol but not ac-H4.The nuclear translocation of NF-${\kappa}B$/p65 in $E_2$-treated MCF-7 cells was also inhibited, along with cyclin D1, Bcl-2 and Bcl-xl in mRNA and protein expression levels. These results suggest that the effect of $E_2$ on promoting proliferation and inhibiting apoptosis is linked to hyperacetylation levels of histones and nonhistone NF-${\kappa}B$/p65 in MCF-7 cells. The acetyltransferase inhibitor garcinol plays an inhibitive role in MCF-7 cell proliferation promoted by $E_2$. Mechanisms are probably associated with decreasing ac-p65 protein expression level in the NF-${\kappa}B$ pathway, thus down-regulating the expression of cyclin D1, Bcl-2 and Bcl-xl.

• BMB Reports
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• v.47 no.9
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• pp.524-529
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• 2014

Oxidative stress and inflammation are common to many pathological conditions. Defense mechanisms protect cells from oxidative stress, but can become over-activated following injury and inflammation. NF-${\kappa}B$ and Nrf2 transcription factors regulate proinflammatory and antioxidant gene expression, respectively. Studies have shown that many natural dietary compounds regulate NF-${\kappa}B$ and Nrf2, preventing inflammation and oxidative stress. Here, we report major compounds of Prunella vulgaris var. lilacina such as rosmarinic acid, oleanolic acid, ursolic acid and caffeic acid as a potential therapeutic for oxidative stress and inflammation. The major compounds exhibited high anti-inflammatory activity, inhibiting NO, PGE2 production, NF-${\kappa}B$ expression and activating Nrf2 expression. In addition, we examined the effect of major compounds on MafK expression. Among the compounds, oleanolic acid significantly decreased MafK expression and MafK-mediated p65 acetylation. These findings suggest that oleanolic acid as NF-${\kappa}B$ inhibitors can potentially be used in therapeutic applications for the treatment of oxidative stress-induced diseases.

• Korean Journal of Food Science and Technology
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• v.22 no.6
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• pp.659-667
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• 1990

Starch acetates were prepared by conventional method, preheat treatment, and extrusion process through acetylation of corn starch with acetic anhydride and their physicochemical properties were investigated. The optimal conditions of the acetylation of starch by conventional method(CSA) was found that starch concentration was 30%, reaction temperature $35^{\circ}C$ and pH 8.5. With increasing the molar ratio of acetic anhydride to anhydrous glucose unit from 0.03 to 0.20, DS(Degree of substitution) value of corn starch acetate prepared at the optimum condition was increased from 0.019 to 0.080, while the acetylation efficiency was decreased from 31.6% to 20.5%. In the case of the preheated (gelatinized), then acetylated starch(PSA), DS value was increased from 0.027 to 0.04 at the fixed molar ratio of the acetic anhydride with increasing preheating temperature from $60^{\circ}C\;to\;90^{\circ}C$. The DS was low as 0.02 in the case of starch acetate prepared by extrusion process(WESA). The CSA and PSA showed lowering gelatinization temperature and enthalpy than raw corn starch with increasing DS. All of starch acetates showed the increased degree of transparency, the decreased lightness and the increased yellowness as compared to the raw corn starch. WESA showed lower apparent viscosity and more close to the characteristic of the Newtonian fluid than CSA and PSA. Intrinsic viscosity was reduced in CSA and WESA, although PSA has a slightly higher one than raw corn starch. The rate of retrogradation of the gels was retarded in all starch acetates.

• The Korean Journal of Physiology and Pharmacology
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• v.27 no.6
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• pp.533-540
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• 2023

Sweroside is a natural monoterpene derived from Swertia pseudochinensis Hara. Recently, studies have shown that sweroside exhibits a variety of biological activities, such as anti-inflammatory, antioxidant, and hypoglycemic effects. However, its role and mechanisms in high glucose (HG)-induced renal injury remain unclear. Herein, we established a renal injury model in vitro by inducing human renal tubular epithelial cell (HK-2 cells) injury by HG. Then, the effects of sweroside on HK-2 cell activity, inflammation, reactive oxygen species (ROS) production, and epithelial mesenchymal transition (EMT) were observed. As a result, sweroside treatment ameliorated the viability, inhibited the secretion of inflammatory cytokines (TNF-α, IL-1β, and VCAM-1), reduced the generation of ROS, and inhibited EMT in HK-2 cells. Moreover, the protein expression of SIRT1 was increased and the acetylation of p65 NF-kB was decreased in HK-2 cells with sweroside treatment. More importantly, EX527, an inhibitor of SIRT1, that inactivated SIRT1, abolished the improvement effects of sweroside on HK-2 cells. Our findings suggested that sweroside may mitigate HG-caused injury in HK-2 cells by promoting SIRT1-mediated deacetylation of p65 NF-kB.

• BMB Reports
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• v.50 no.5
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• pp.275-280
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• 2017

Herpes simplex virus type 1 ICP27 is a multifunctional protein responsible for viral replication, late gene expression, and reactivation from latency. ICP27 interacts with various cellular proteins, including Daxx. However, the role of interaction between ICP27 and Daxx is largely unknown. Since Daxx is known to repress $NF-{\kappa}B$ activity, there is a possibility that ICP27 may influence the inhibitory effect of Daxx on $NF-{\kappa}B$ activity. In this study, we tested whether ICP27 affects the $NF-{\kappa}B$ activity through its interaction with Daxx. Interestingly, ICP27 enhanced the Daxx-mediated repression of $NF-{\kappa}B$ activity. In addition, we found that sumoylation of Daxx regulates its interaction with p65. ICP27 binds to Daxx, inhibits Daxx sumoylation, and enhances p65 deacetylation induced by Daxx. Consequently, ICP27 represses the $NF-{\kappa}B$ activity, by elevating the inhibitory effect of Daxx on $NF-{\kappa}B$ activity through desumoylation of Daxx.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.11
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• pp.4539-4543
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• 2014

Since the epigenetic alteration in tumor cells can be reversed by the dietary polyphenol quercetin (Q) or butyrate (B) with chemopreventive activity, suggesting that Q or B can be used for chemopreventive as well as therapeutic agent against tumors. In this study the polyphenol flavonoid quercetin (Q) or sodium butyrate (B) suppressed human esophageal 9706 cancer cell growth in dose dependent manner, and Q combined with B (Q+B) could further inhibit Eca9706 cell proliferation than that induced by Q or B alone, compared with untreated control group (C) in MTT assay. The reverse expressions of global DNMT1, $NF-{\kappa}Bp65$, HDAC1 and Cyclin D1 were down-regulated, while expressions of caspase-3 and $p16INK4{\alpha}$ were up-regulated, compared with the C group in immunoblotting; the down-regulated HDAC1-IR (-immunoreactivity) with nuclear translocation, and up-regulated E-cadherin-IR demonstrated in immunocytochemistry treated by Q or B, and Q+B also displayed further negatively and positively modulated effects compared with C group. The order of methylation specific (MS) PCR of $p16INK4{\alpha}$: C>B/Q>Q+B group, while the order of E-cadherin expression level was contrary, Q+B>Q/B>C group. Thus, Q/B, especially Q+B display reverse effect targeting both altered DNA methylation and histone acetylation, acting as histone deacetylase inhibitor mediated via epigenetic-$NF-{\kappa}B$ cascade signaling.

• BMB Reports
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• v.54 no.10
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• pp.534-539
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• 2021

IL-10⁺ regulatory B (Breg) cells play a vital role in regulating the immune responses in experimental autoimmune encephalomyelitis, colitis, and contact hypersensitivity (CHS). Several stimulants such as lipopolysaccharide (LPS), CD40 ligand, and IL-21 spur the activation and maturation of IL-10⁺ Breg cells, while the epigenetic mechanism for the IL-10 expression remains largely unknown. It is well accepted that the histone acetylation/deacetylation is an important mechanism that regulates the expression of IL-10. We found that entinostat, an HDAC inhibitor, stimulated the induction of IL-10⁺ Breg cells by LPS in vitro and the formation of IL-10⁺ Breg cells to suppress CHS in vivo. We further demonstrated that entinostat inhibited HDAC1 from binding to the proximal region of the IL-10 expression promoter in splenic B cells, followed by an increase in the binding of NF-κB p65, eventually enhancing the expression of IL-10 in Breg cells.