Post-translational modification (PTM) is an essential mechanism for enhancing the functional diversity of proteins and adjusting their signaling networks. The reversible conjugation of ubiquitin (Ub) and ubiquitin-like proteins (Ubls) to cellular proteins is among the most prevalent PTM, which modulates various cellular and physiological processes by altering the activity, stability, localization, trafficking, or interaction networks of its target molecules. The Ub/Ubl modification is tightly regulated as a multi-step enzymatic process by enzymes specific to this family. There is growing evidence that the dysregulation of Ub/Ubl modifications is associated with various diseases, providing new targets for drug development. In this review, we summarize the recent progress in understanding the roles and therapeutic targets of the Ub and Ubl systems in the onset and progression of human diseases, including cancer, neurodegenerative disorders, and heart diseases.

We examined the potential of tannic acid (TA) as a novel histone acetyltransferase inhibitor (HATi) and demonstrated that TA prevents non-alcoholic fatty liver disease (NAFLD) by inhibiting HAT activity. The anti-HAT activity of TA was examined using HAT activity assays. An in vitro NAFLD model was generated by treating HepG2 cells with oleic and palmitic acids. Male C57BL/6J mice were fed a control diet (CD) or Western diet (WD) with or without supplementation with either 1% or 3% TA (w/w) for 12 weeks. Finally, the possibility of interacting p300 and TA was simulated. TA suppressed HAT activity both in vitro and in vivo. Interestingly, TA abrogated occupancy of p300 on the sterol regulatory element in the fatty acid synthase and ATP-citrate lyase promoters, eventually inducing hypoacetylation of H3K9 and H3K36. Furthermore, TA decreased acetylation at lysine residues 9 and 36 of histone H3 protein and that of total proteins. Consequently, TA decreased the mRNA expression of lipogenesis-related genes and attenuated lipid accumulation in vivo. We observed that NAFLD features, including body weight, liver mass, fat mass, and lipid profile in serum, were improved by TA supplementation in vivo. Finally, we demonstrated the possibility that TA directly binds to p300 through docking simulation between ligand and protein. Our findings demonstrate that TA, a novel HATi, has potential application for the prevention of NAFLD.

Diabetes is a metabolic syndrome characterized by inadequate blood glucose control and is associated with reduced quality of life and various complications, significantly shortening life expectancy. Natural phytochemicals found in plants have been traditionally used as medicines for the prevention of chronic diseases including diabetes in East Asia since ancient times. Many of these phytochemicals have been characterized as having few side effects, and scientific research into the mechanisms of action responsible has accumulated mounting evidence for their efficacy. These compounds, which may help to prevent metabolic syndrome disorders including diabetes, act through relevant intracellular signaling pathways. In this review, we examine the anti-diabetic efficacy of several compounds and extracts derived from medicinal plants, with a focus on AMP-activated protein kinase (AMPK) activity.

Context: Boehmeria nivea (Linn.) Gaudich (Urticaceae), a natural herb, has a long history of treating several diseases including wound healing. However, the anti-inflammatory effect of B. nivea has not been investigated. Objective: We investigated whether the 70% ethanol extract of B. nivea (Ebn) can exert anti-inflammatory activity. Several phenolic compounds of extracts were determined to provide further information on the correlation between anti-inflammatory effects and phenolic compounds. Materials and methods: We prepared a 70% ethanol extract of B. nivea leaves and evaluated its anti-inflammatory activity (200, 400, 800, 1200 µg/mL) by measuring the secretions of nitric oxide (NO), tumor necrosis factor alpha (TNF-α) and interleukin 6 (IL-6), which were stimulated by lipopolysaccharide (LPS) in RAW264.7 macrophages. The total phenolic compounds were determined by the Folin–Ciocalteu method and major compounds were determined by HPLC. Results: Ebn was able to abolish the LPS-induced secretions of NO, TNF-α and IL-6. It also decreased the protein levels (IC₅₀ = 186 µg/mL) of LPS-induced inducible nitric oxide synthase (iNOS). The LPS stimulated p38, JNK and ERK phosphorylations significantly more than the controls. Surprisingly, although Ebn reduced p38 and JNK phosphorylations, it did not influence ERK phosphorylation. We found that Ebn revealed several major compounds such as chlorogenic acid (1.96 mg/100 g), rutin (46.48 mg/100 g), luteolin-7-glucoside (11.29 mg/100 g), naringin (1.13 mg/100 g), hesperidin (23.69 mg/100 g) and tangeretin (1.59 mg/100 g). Discussion and conclusion: Boehmeria nivea exerts an anti-inflammatory effect on macrophages by inhibiting p38 and JNK, suggesting that it may be used as a functional ingredient against inflammation.

Few studies have examined the relationship of protein intake by food source with metabolic syndrome in Korean adults, even though animal food intake has increased. This study examined the association between plant and animal protein intake and metabolic syndrome among middle-aged Korean adults. A total of 13,485 subjects aged 30–64 years were selected from the 2013–2018 Korea National Health and Nutrition Examination Survey. Protein intake was assessed using 24-h dietary recall data and divided into quintiles. Men had a higher percentage of energy intake from animal protein (7.4%) than plant protein (6.9%). Men in the highest quintile group of animal protein intake had a higher prevalence of abdominal obesity (OR: 1.30, 95% CI: 1.00–1.70), reduced high-density lipoprotein cholesterol (HDL-C) (OR: 1.43, 95% CI: 1.07–1.90), and elevated fasting glucose (OR: 1.32, 95% CI: 1.01–1.74), after adjusting for covariates. Furthermore, stronger associations of animal protein intake with abdominal obesity were shown in men who consumed less than estimated energy requirements (OR: 1.60, 95% CI: 1.11–2.31). Plant protein intake was negatively associated with increased blood pressure in men. Neither animal nor plant protein intakes were significantly associated with any of the metabolic syndrome risk factors in women. The results imply that lower animal protein intake may be a beneficial factor for metabolic syndrome management in middle-aged Korean men.