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Clerodendrum trichotomum has been reported to possess beneficial properties for human health, but its effects on metabolic syndrome have not been reported. In this study, we investigated the effect of C. trichotomum leaf extract (CT) on the metabolic derangements induced by a high-fructose (HF) diet. Sprague–Dawley rats were fed with a 46% carbohydrate diet (HC group), 60% high-fructose diet (HF group), or HF diet supplemented with CT (500 mg/kg of body weight/day, CT group) via drinking water for 16 weeks. Results showed that CT alleviated HF diet-induced insulin resistance, dyslipidemia, and hepatic steatosis In liver tissues, CT affected the signaling pathways of AMP-activated protein kinase, peroxisome proliferator-activated receptor α (PPARα), and sterol regulatory element binding protein 1. CT enriched the genes that were mainly involved in cytokine-cytokine receptor interaction, PPAR, PI3K-Akt signaling pathways, and fatty acid metabolism pathway. These results suggest that CT is a promising therapeutic against metabolic disorders.

Clerodendrum trichotomum is a folk medicine exhibiting anti-hypertension, anti-arthritis, and anti-rheumatism properties. However, little is known about whether the material might prevent hyperuricemia and associated inflammation. In this study, we explored whether C. trichotomum leaf extract (CTE) prevented hyperuricemia induced by potassium oxonate (PO) in mice. CTE (400 mg/kg body weight) significantly reduced the serum uric acid (UA), blood urea nitrogen (BUN), and serum creatinine levels and increased urine UA and creatinine levels. CTE ameliorated PO-induced inflammation and apoptosis by reducing the levels of relevant proteins in kidney tissues. Also, CTE ameliorated both UA-induced inflammatory response in RAW 263.7 cells and UA-induced cytotoxicity in HK-2 cells. In addition, liver transcriptome analysis showed that CTE enriched mainly the genes for mediating positive regulation of MAPK cascade and apoptotic signaling pathways. Together, the results show that CTE effectively prevents hyperuricemia and associated inflammation in PO-induced mice.

Polymethoxyflavones (PMFs) are flavonoids exclusively found in certain citrus fruits and have been reported to be beneficial to human health. Most studies have been conducted with PMFs isolated from citrus peels, while there is no study on PMFs isolated from leaves. In this study, we prepared a PMF-rich fraction (PRF) from the leaves of

Polymethoxyflavones (PMFs) are flavonoid compounds present in citrus plants that are proposed to be advantageous to human health. However, the advantageous effects of PMFs in the context of renal dysfunction are unclear. In this study, we made a PMF-rich fraction (PRF) from the leaves of Citrus sunki Hort ex. Tanaka and identified its components using liquid chromatography and mass spectrometry. We then investigated the effect of PRF—comprising 9 types of PMF—on renal dysfunction induced by unilateral ureteral obstruction (UUO) in mice. Animals were divided into four experimental groups ( n = 7 per group): I) sham-operated group (Sham); II) UUO group (UUO); III) UUO + Enalapril 0.1 mg/1 mL (UUO + Enap); IV) UUO + PRF 100 mg/kg/day (UUO + PRF). All mice were orally administered with the drugs once a day from 7 days before UUO to 1 week after UUO. After the experiments were over, serum and tissues were taken for biochemical and histological analysis. PRF promoted the recovery of body weight in the background of UUO. Biochemical and histological analysis revealed that PRF ameliorated UUO-induced renal dysfunction and moderately reversed inflammation and tubulointerstitial fibrosis. Further, PRF inhibited the expression of endothelial nitric oxide synthase (eNOS), inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), transforming growth factor-β (TGF-β), collagen I (Col-I), and collagen IV (Col-IV). These results suggest that PRF improves UUO-induced renal dysfunction by regulating the expression of inflammatory and fibrotic response-related genes.

CXCL16, as a chemotactic cytokine, promotes cancer proliferation, migration, and immune cell infiltration in tumor microenvironment. However, CXCL16 has been shown to play a conflicting role in breast cancer. The aim of this study was to investigate the therapeutic potential of CXCL16 in breast cancer. Breast cancer patients (n=1097) from the TCGA dataset were divided into two group according to the CXCL16 expressions, the CXCL16low (n=548) and the CXCLhigh (n=549) groups. Mean diagnostic ages were similar between groups (59 ± 13.5 vs 58 ± 12.9 years, P=0.233). The ratio of triple-negative breast cancer (TNBC) was significantly higher in the CXCLhigh than that of the CXCL16low groups (24.8 vs 6.8%, P Citation Format: Sun Wook Cho, Mi Gyeong Jang, Hyun Jin Sun, Han Sai Lee, Young Shin Song, Seong Keun Kim. CXCL16 as a potential therapeutic target of triple-negative breast cancer [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P5-05-08.

Sasa quelpaertensis Nakai is a dwarf bamboo grass suitable for food and health-related applications as it is a rich source of antioxidants. In this study, the leaves and culms of this plant were harvested from May to December, and the ethanol extracts of leaves (ESL) and culms (ESC), and the hot water extracts of leaves (HSL) and culms (HSC) were prepared. Extracts were evaluated for the seasonal changes in the content of p-coumaric acid, tricin, total phenolics (TP), and total flavonoids (TF) content; as well as for the antioxidant and anti-inflammatory activities. The p-coumaric acid in HSL and tricin contents in ESL rapidly decreased from June to October, and remained relatively constant until December. TP and TF contents in ESL were gradually increased from October and reached the highest level in December. The phenolic compounds (p-coumaric acid, tricin, TP and TF contents) in ESL showed an excellent correlation with antioxidant activities, indicating that ESL contained the highest levels of antioxidant and anti-inflammatory substances. Taken together, these results suggest that the optimal time to harvest this plant is from October to December.

In this study, trihydroxychalcone derivatives were synthesized and evaluated for their potential antidiabetic effects in a cell-culture system and a diabetic mouse model in vivo. Some of them increased fatty acid oxidation (FAO) in C2C12 myotubes without affecting the cell viability. In addition, some trihydroxychalcone derivatives, including chalcone 13, facilitated AMP-activated protein kinase (AMPK) activation. Chalcone 13 administration to high-fat diet (HFD)-induced diabetic mice improved glucose tolerance, increased muscle FAO, and reduced fat accumulation in the liver and skeletal muscles. These results suggest that some chalcone derivatives, particularly chalcone 13, might be potential therapeutic agents for the treatment of diabetes.

p-Coumaric acid (p-CA), a phenolic compound abundantly found in edible plants, was found to induce apoptosis in SNU-16 gastric cancer cells. However, the effects of p-CA on the microRNA expression pattern in SNU-16 cells have not been reported. The primary objective of this study was to investigate microRNA expression profiles in p-CA-treated SNU-16 cells. SNU-16 cells were treated with 1.5 mM p-CA for 48 h. High-throughput RNA sequencing was performed. The accuracy and validity of the RNA sequencing results were tested by real-time PCR. Gene Ontology (GO) enrichment and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses were performed using the differentially expressed microRNAs (DEMs). Thirty-two DEMs were identified between p-CA-treated and control cells, 9 of which were upregulated, and 23 downregulated. GO and KEGG pathway analyses of the target genes indicated that these genes were involved in a variety of biological functions and several cancer-related pathways. The miRNA interactive network analysis identified hsa-miR-125a-5p, hsa-miR-30a-5p, and hsa-miR-7-5p as the major nodes. Our findings indicated that p-CA exerted its anticancer effects in SNU-16 gastric cancer cells by modulating the expression of certain microRNAs, providing a better understanding of the anticancer properties of p-CA in gastric cancer cells.

Background: Increased dietary fructose consumption is closely associated with lipid and glucose metabolic disorders. Sasa quelpaertensis Nakai possesses various health-promoting properties, but there has been no research on its protective effect against fructose-induced metabolic dysfunction. In this study, we investigated the effects of S. quelpaertensis leaf extract (SQE) on metabolic dysfunction in high-fructose-diet-fed rats. Methods: Animals were fed a 46% carbohydrate diet, a 60% high-fructose diet, or a 60% high-fructose diet with SQE (500 mg/kg of body weight (BW)/day) in drinking water for 16 weeks. Serum biochemical parameters were measured and the effects of SQE on hepatic histology, protein expression, and transcriptome profiles were investigated. Results: SQE improved dyslipidemia and insulin resistance induced in high-fructose-diet-fed rats. SQE ameliorated the lipid accumulation and inflammatory response in liver tissues by modulating the expressions of key proteins related to lipid metabolism and antioxidant response. SQE significantly enriched the genes related to the metabolic pathway, namely, the tumor necrosis factor (TNF) signaling pathway and the PI3K-Akt signaling pathway. Conclusions: SQE could effectively prevent dyslipidemia, insulin resistance, and hepatic lipid accumulation by regulation of metabolism-related gene expressions, suggesting its role as a functional ingredient to prevent lifestyle-related metabolic disorders.

The aim of this study was to investigate the relationship between the chemical composition and antioxidant activity of roasted jinpi extract (RJE) under various roasting conditions (e.g., 100–155 °C). The total phenolic contents, flavonoid content, and antioxidant activities in RJE increased with increased roasting temperature, and the highest efficacy was observed at 155 °C. The narirutin and hesperidin contents in RJE reached 15.32 and 11.50 mg/g, respectively, under this optimal temperature (155 °C). The roasting process caused the Maillard reaction to occur which increased the amounts of 2,4-diamino-5-(3′,4′-dichlorophenyl)-6-methyl pyrimidine (DDMP) and 5-hydroxymethlyfurfural (5-HMF) but decreased the total sugar content in RJE. Among the compounds contained in RJE, DDMP had the strongest diethylene glycol, 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging activity, which was determined by DPPH-HPLC analysis. These results suggest that roasting jinpi under optimal conditions increases the amount of phenolics and flavonoids and thereby enhances the antioxidant activity of jinpi.

It has been reported that various plant species may enhance the elimination of fatigue-related metabolites. However, relatively few studies have directly addressed the potential anti-fatigue effects. The objective of this study was to investigate the anti-fatigue potential of a hot water extract of Sasa quelpaertensis Nakai leaf (SQH) in male ICR mice. The animals were divided into three groups. The normal control (NC) group was administered saline without exercise every day for 7 days. The exercise control (EC) and exercise with SQH (ES) groups were administered saline and SQH (50 mg/kg of body weight), respectively, every day for 7 days and underwent swimming exercise. RNA sequencing technology was used to analyze the transcriptome profiles of muscle. Swimming times were prolonged in the ES group compared with the EC group. The ES group had higher blood glucose and lower blood lactate levels, and higher muscular glycogen and lower muscular lactate levels, compared with the EC group. The groups did not differ in histopathological parameters of the muscle and liver, but muscle cell sizes were smaller in the EC group than in the ES and NC groups. RNA sequencing analysis revealed that SQH administration regulated genes associated with energy-generating metabolic pathways in skeletal muscle. These results suggest that SQH exerts anti-fatigue properties by balancing various biological systems and helping maintain the basic harmonious pattern of the body.

Mature osteoblasts have three fates: as osteocytes, quiescent lining cells, or osteoblasts that undergo apoptosis. However, whether intermittent parathyroid hormone (PTH) can modulate the fate of mature osteoblasts in vivo is uncertain. We performed a lineage-tracing study using an inducible gene system. Dmp1-CreERt2 mice were crossed with Rosa26R reporter mice to obtain targeted mature osteoblasts and their descendants, lining cells or osteocytes, which were detected using X-gal staining. Rosa26R:Dmp1-CreERt2(+) mice were injected with 0.25 mg 4-OH-tamoxifen (4-OHTam) on postnatal days 5, 7, 9, 16, and 23. In a previous study, at 22 days after the last 4-OHTam, most LacZ+ cells on the periosteal surface were inactive lining cells. On day 25 (D25), the mice were challenged with an injection of human PTH (1-34, 80 μg/kg) or vehicle daily for 10 (D36) or 20 days (D46). We evaluated the number and thickness of LacZ+ osteoblast descendants in the calvaria and tibia. In the vehicle group, the number and thickness of LacZ+ osteoblast descendants at both D36 and D46 significantly decreased compared to D25, which was attenuated in the PTH group. In line with these results, PTH inhibited the decrease in the number of LacZ+/osteocalcin-positive cells compared to vehicle at both D36 and D46. As well, the serum levels of sclerostin decreased, as did the protein expression of sclerostin in the cortical bone. These results suggest that intermittent PTH treatment can increase the number of periosteal osteoblasts by preventing mature osteoblasts from transforming into lining cells in vivo.

The pathogenesis of type 2 diabetes mellitus (T2DM) is closely associated with mitochondrial functions in insulin-responsive tissues. The mitochondrial proteome, compared with the mitochondrial genome, which only contains 37 genes in humans, can provide more comprehensive information for thousands of mitochondrial proteins regarding T2DM-associated mitochondrial functions. However, T2DM-associated protein signatures in insulin-responsive tissues are still unclear. Here, we performed extensive proteome profiling of mitochondria from skeletal muscles in nine T2DM patients and nine nondiabetic controls. A comparison of the mitochondrial proteomes identified 335 differentially expressed proteins (DEPs) between T2DM and nondiabetic samples. Functional and network analyses of the DEPs showed that mitochondrial metabolic processes were downregulated and mitochondria-associated ER membrane (MAM) processes were upregulated. Of the DEPs, we selected two (NDUFS3 and COX2) for downregulated oxidative phosphorylation and three (CALR, SORT, and RAB1A) for upregulated calcium and protein transport as representative mitochondrial and MAM processes, respectively, and then confirmed their differential expression in independent mouse and human samples. Therefore, we propose that these five proteins be used as a potential protein profile that is indicative of the dysregulation of mitochondrial functions in T2DM, representing downregulated oxidative phosphorylation and upregulated MAM functions., Type 2 diabetes: Different mitochondrial protein profile in skeletal muscle Diabetes alters the mitochondrial proteins in insulin-responsive tissues. Sehyun Chae from the Daegu Gyeongbuk Institute of Science and Technology, South Korea, and coworkers characterized the proteins found within the mitochondria of skeletal muscle tissues isolated from nine people with type 2 diabetes and nine non-diabetic controls. They identified 335 proteins that were expressed at significantly different levels in tissues from the two groups. Of these, several involved in energy metabolism were at lower levels in the diabetic cohort, while several involved in communication between the mitochondria and the endoplasmic reticulum, a neighboring celllular organelle, were at higher levels. The researchers confirmed this pattern for five specific proteins in mouse models of diabetes and in human samples. These proteins could form the basis of a diagnostic test for diabetes-associated mitochondrial dysfunction.

The peel of Citrus sunki is a rich source of polymethoxyflavones (PMFs). In this study, a PMF-rich fraction (PRF) was obtained from the peels of C. sunki by hot-water extraction and subsequent fractionation with n -hexane. Six PMFs and two demethylated PMFs were isolated by semi-preparative HPLC, and their structures were identified by 1 H NMR and 13 C NMR. To define the synergistic effects of PRF, the PRF and its eight individual components were assessed for antiproliferative activity using HL-60 cells. The PRF showed greater growth inhibitory activity ( IC 50 value = 25.14 μg/ml), compared with its individual components. Flow cytometric analysis confirmed that the PRF significantly increased the percentage of sub-G 1 cells (30.1% at 25 μg/ml). Our study provides an efficient method for preparing a PRF for use as a functional food ingredient.

Sasa quelpaertensis Nakai leaves contain a mixture of polysaccharides, amino acids, and polyphenols, which mediate various biological activities. For efficient utilization of its leaf, we reported the preparation procedure for phytochemical-rich extract (PRE) using the leaf residue, which was by-product of hot water extraction. This study was undertaken to evaluate the effects of PRE and its major constituent, p-coumaric acid,on the growth of several human cancer cell lines (MKN-74, MKN-45, SNU-1, SNU-16, and HL-60). The ethyl acetate fraction of PRE and p-coumaric acid significantly inhibited the proliferation of MKN-74 and HL-60 cells, respectively, and induced cell apoptosis, down-regulated Bcl-2 and poly (ADP-ribose) polymerase levels, and upregulated those of Bax and caspase-3. These results show the potential utility of S. quelpaertensis Nakai leaves in cancer prevention.

Oxidative stress plays a critical role in the pathogenesis of inflammation (Winrow et al., 1993), which is a physiological response that protects the body from stimuli including infections and tissue injury. The magnitude of the inflammatory response is crucial, and insufficient responses result in immunodeficiency, which can lead to infection and cancer. Excessive responses cause morbidity and mortality from diseases such as rheumatoid arthritis, Crohn’s disease, atherosclerosis, diabetes, Alzheimer’s disease, multiple sclerosis, and cerebral and myocardial ischemia (Tracey, 2002). Inflammation is associated with a wide range of inflammatory mediators that initiate inflammatory responses, recruit and activate other cells to the site of inflammation, and subsequently resolve the inflammation (Gallin & Snyderman, 1999). The expression of pro-inflammatory mediators such as cytokines, chemokines, adhesion molecules, iNOS, and COX-2 involves nuclear factor-κB (NF-κB) (Baeuerle & Baltimore, 1996; Hayden & Ghosh, 2004). Mitogen-activated protein kinases (MAPKs) pathways are also reportedly stimulated by inflammatory mediators (Guha & Mackman, 2001).