Anti-Obesity Effects of Polymethoxyflavone-Rich Fraction from Jinkyool (Citrus sunki Hort. ex Tanaka) Leaf on Obese Mice Induced by High-Fat Diet.

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 Citrus sunki Hort ex. Tanaka (Jinkyool) and investigated whether the PRF could improve metabolic decline in obese mice induced by a high-fat diet (HFD) for 5 weeks. The HFD-induced obese mice were assigned into HFD, OR (HFD + orlistat at 15.6 mg/kg of body weight/day), and PRF (HFD + 50, 100, and 200 mg/kg of body weight/day) groups. Orlistat and PRF were orally administered for 5 weeks. At the end of the experiment, the serum biochemical parameters, histology, and gene expression profiles in the tissues of each group were analyzed. The body weight gain of the obese mice was significantly reduced after orlistat and PRF administration for 5 weeks. PRF effectively improved HFD-induced insulin resistance and dyslipidemia. Histological analysis in the liver demonstrated that PRF decreased adipocyte size and potentially improved the liver function, as it inhibited the incidence of fatty liver. PRF activated AMP-activated protein kinase (AMPK), acetyl-CoA carboxylase (ACC), and hormone-sensitive lipase (HSL) in HFD-induced obese mice. Moreover, liver transcriptome analysis revealed that PRF administration enriched genes mainly related to fatty-acid metabolism and immune responses. Overall, these results suggest that the PRF exerted an anti-obesity effect via the modulation of lipid metabolism.

Clerodendrum trichotomum extract improves metabolic derangements in high fructose diet-fed rats.

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.

Sasa quelpaertensis Leaf Extract Ameliorates Dyslipidemia, Insulin Resistance, and Hepatic Lipid Accumulation in High-Fructose-Diet-Fed Rats.

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.

Prevention of Hyperuricemia by Clerodendrum trichotomum Leaf Extract in Potassium Oxonate-Induced Mice.

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.

Effects of p-coumaric acid on microRNA expression profiles in SNU-16 human gastric cancer cells.

BACKGROUND: 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. OBJECTIVES: The primary objective of this study was to investigate microRNA expression profiles in p-CA-treated SNU-16 cells. METHODS: 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). RESULTS: 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. CONCLUSIONS: 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.

Sasa quelpaertensis leaf extract mitigates fatigue and regulates the transcriptome profile in mice.

INTRODUCTION: 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. OBJECTIVE: 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. METHODS: 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. RESULTS: 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. CONCLUSION: These results suggest that SQH exerts anti-fatigue properties by balancing various biological systems and helping maintain the basic harmonious pattern of the body.

A mitochondrial proteome profile indicative of type 2 diabetes mellitus in skeletal muscles.

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.

Intermittent PTH treatment can delay the transformation of mature osteoblasts into lining cells on the periosteal surfaces.

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.