Metabolomics Reveals Rubiadin Accumulation and the Effects of Methyl Jasmonate Elicitation in Damnacanthus major Calli.

Callus suspension techniques have been considered attractive for improving bioactive metabolite productivity; methyl jasmonate (MeJA) is a widely used elicitor for stimulating synthetic pathways. In this study, a multivariate analysis-based metabolomics approach was employed to investigate the primary and specialized metabolites in the leaves, unelicited calli, and 100 or 200 µM MeJA elicited calli of Damnacanthus major. Rubiadin, a powerful anthraquinone with various therapeutic properties, was only identified in D. major calli, accumulating in a MeJA elicitation concentration-dependent manner. Callus cultures also contained high levels of amino acids, sugars, and phenolic compounds, indicating energy metabolism and metabolic adaptation responses for proliferation and stabilization. Regarding MeJA application, elicited calli contained higher amounts of quinic acid, kaempferol, and glucose with lower amounts of sucrose and raffinose than those in the unelicited control, which were closely related to protective mechanisms against MeJA. Moreover, excessive elicitation increased the asparagine, fructose, and raffinose levels and decreased the glucose and sucrose levels, which was ascribed to increased activation of the aminoacyl-tRNA biosynthesis pathway and wider utilization of glucose than of fructose after sucrose degradation. These results will be useful for optimizing plant cell culture techniques to achieve high production rates for valuable specialized metabolites.

Immature Persimmon (Diospyros kaki Thunb.) Ethanol Extract Ameliorates High-Fat Diet-Induced Obesity by Modulating Lipid Metabolism.

In this study, immature persimmon (Diospyros kaki Thunb.) ethanol extract was administered to an obese animal model fed a high-fat diet to measure weight change, adipose tissue weight, serum lipid level, and expression level of adipose-related genes to evaluate its efficacy. Administration of D. kaki ethanol extract (DKE) (100 and 500 mg/kg/d) decreased the body weight gain, adipose tissue weight, and serum triglyceride levels in mice fed a high-fat diet. Furthermore, it improved the leptin and adiponectin levels in the blood as well as gene expression in the liver. It also inhibited the expression of sterol regulatory element-binding protein-1c, inhibiting the production of triglyceride biosynthetic enzyme fatty acid synthesis and acetyl-CoA carboxylase, and decreased the expressions of peroxisome proliferator-activated receptor γ and CCAAT/enhancer-binding proteins that induce adipocyte differentiation. Therefore, these data suggest that DKE exerts beneficial effects on high-fat diet-induced obesity by modulating lipid metabolism in mice fed a high-fat diet.

Extracts of Citrus Juice Processing Wastes Induce Weight Gain and Decrease Serum Glucose in Sprague-Dawley Rats.

In this study, the safety and functionality of using citrus juice processing waste (CJPW) was confirmed. Large quantities of CJPW are generated on Jeju Island and cause environmental problems. CJPW extract (2,000 mg/kg) was administered intragastrically to male and female Sprague-Dawley (SD) rats for 14 days and the rats were analyzed. No general signs of toxicity were observed in SD rats administered CJPW extract. Feed intake did not differ between experimental and control animals. However, male and female rats administered CJPW extract had greater weight gain (102.9±5.53% and 114.15±6.89%, respectively) compared with the control animals. Higher weight gain was found in male and female experimental animals, but the difference was only significant in female animals. Serum analyses indicated that total protein and albumin, indicators of nutritional status, were significantly increased in animals administered CJPW. Further, serum glucose values were lower in male and female rats treated with CJPW (91.6±9.02% and 69.9±4.11%, respectively) compared with the controls; again, the difference was significant only for female animals. From the results of this study, CJPW can be considered as a safe material that does not induce toxicity in experimental animals. Therefore, CJPW is a potential raw material that can be used as a supplement in animal feed to help improve weight gain and achieve serum glucose con-trol.

Clinical Evidence of Effects of Green Mandarin (Putgyul) Extract on Skin Aging: A Randomized, Double Blind, Placebo-Controlled Study.

Green mandarins are widely consumed unripe as mandarin oranges (Citrus unshiu Marcov.), which exhibit anti-inflammatory and anti-wrinkle effects by inhibiting the production of inflammatory cytokines and matrix metalloproteinase. A randomized, double-blind, placebo-controlled clinical study was performed to verify the skin improvement efficacy and safety of green mandarin extract (PTE). For the standardization of PTE, narirutin was set as a marker compound, and PTE with a constant narirutin content was prepared for the study. After randomizing subjects with periorbital wrinkles, they were orally administered PTE (300 mg/day) or a placebo for 12 weeks. Periorbital wrinkles were measured using PRIMOSCR SF. Skin elasticity, moisture content, transepidermal water loss, and gloss were also measured. In the study results, the depth, volume, and skin roughness of the periorbital wrinkles were significantly improved compared to the control group (p = 0.011, 0.009, and 0.004, respectively). The survey confirmed that the skin condition improved after PTE consumption for 12 weeks. No adverse reactions associated with PTE were observed during the study period. Thus, the results demonstrate that PTE effectively improves UV-induced skin wrinkles. Therefore, it is considered that PTE has sufficient value as a functional food ingredient that can prevent skin aging.

Effects of Sargassum horneri and Ulva australis Extracts on Body Weight and Serum Glucose Levels of Sprague-Dawley Rats.

This study investigated the safety and functionality of a functional additive for humans and animals from Sargassum horneri (SH) and Ulva australis (UA) waste for recycling marine refuse generated in large quantities in Jeju. Sprague-Dawley rats were orally administered functional additives at 2,000 mg/kg to assess 14-day repeated dose toxicity of the two extracts. For female rats, weight gain after administration of SH was 66.2±18.8% vs. controls. Male rats administered UA showed weight gain of 92.3±8.0% vs. controls. SH and UA significantly decreased serum glucose levels in male rats compared with controls (79.8±11.10% and 76.1±9.67%, respectively). Similarly, significant decrease in serum glucose levels were shown for female rats after administration of SH and UA (79.2±1.58% and 82.8±3.21%, respectively). Furthermore, rats showed significant differences vs. controls in several serological parameters after receiving extracts, however results remained within the normal range. Thus, the SH and UA extracts were considered safe substances that may be used as functional additives to help reduce body weight and serum glucose.

Anti-Arthritis Effect through the Anti-Inflammatory Effect of Sargassum muticum Extract in Collagen-Induced Arthritic (CIA) Mice.

(1) Background: Rheumatoid arthritis is a chronic autoimmune disease that causes progressive articular damage and functional loss. It is characterized by synovial inflammation that leads to progressive cartilage destruction. For this reason, research on functional foods that reduce the inflammatory response are under progress. (2) Methods: We focused on the anti-inflammatory effects of Sargassum muticum, and confirmed the effect of the extract on the collagen-induced arthritis (CIA) DBA/1J mice model. (3) Results: The extract was given at concentrations of 50, 100, and 200 mg/kg, and the arthritis score and edema volume of the experimental group were significantly different from the CIA group. The level of interleukin (IL)-6, tumor necrosis factor (TNF)-α, and interferon (IFN)-γ were determined in serum and lymphocytes. The expression of these cytokines in the serum remarkably decreased from S. muticum extract (SME)100 mg/kg, and decreased from SME 200 mg/kg in lymphocytes. Also, immunohistochemical analysis of IL-6 and TNF-α in the joints revealed that the inflammatory response was noticeably lower when treated with S. muticum extract. (4) Conclusions: This study provides results of the experiment of S. muticum extract treatment in a mouse model. The treatment was found to contribute to the alleviation of edema and symptoms by reducing the expression of inflammatory cytokines. It was concluded that it may be a useful substance to help in the mitigation of arthritis symptoms.

Anti-inflammation effects of 8-oxo-9-octadecenoic acid isolated from Undaria peterseniana in lipopolysaccharide-stimulated macrophage cells.

The aim of this study was to investigate the anti-inflammatory activity of 8-oxo-9-octadecenoic acid (OOA) isolated from Undaria peterseniana by examining its ability to inhibit the lipopolysaccharide (LPS)-induced production of inflammatory mediators in RAW 264.7 macrophage cells. We found that OOA significantly suppressed the LPS-induced production of nitric oxide (NO) and inflammatory cytokines. OOA downregulated the LPS-induced expression of inducible nitric oxide synthase and cyclooxygenase-2 proteins. With respect to proinflammatory signaling pathways, OOA inhibited LPS-induced mitogen-activated protein kinase signaling by inhibiting the phosphorylation of c-Jun N-terminal kinase (JNK) and extracellular signal-regulated kinase (ERK). Moreover, OOA inhibited LPS-induced nuclear factor (NF)-κB signaling by reducing the phosphorylation of IκB-α and p50 proteins. These results indicate that OOA significantly reduces proinflammatory signaling, which results in reduced expression of cytokines and proinflammatory mediators. Taken together, these results suggest that OOA has potent anti-inflammatory effects and could be considered an effective anti-inflammatory agent.

Anti-Photoaging Effect of Jeju Putgyul (Unripe Citrus) Extracts on Human Dermal Fibroblasts and Ultraviolet B-induced Hairless Mouse Skin.

Ultraviolet (UV) radiation stimulates the expression of matrix metalloproteinases (MMPs) and inflammatory cytokines. These signaling pathways participate in the degradation of the extracellular matrix and induce inflammatory responses that lead to photoaging. This study evaluated the antioxidant activity and the effect on MMPs and procollagen of putgyul extract in vitro. The anti-photoaging activity of putgyul extracts was estimated in vivo using hairless mice (HR-1). The putgyul extracts reduced MMP-1 production and increased the content of procollagen type I carboxy-terminal peptide in human dermal fibroblasts. Ultravilot-B (UVB)-induced expression of inflammatory cytokines and MMPs was detected in mice, and putgyul extracts suppressed the expression. These results suggest that putgyul extract inhibits photoaging by inhibiting the expression of MMPs that degrade collagen and inhibiting cytokines that induce inflammatory responses. The mouse model also demonstrated that oral administration of putgyul extracts decreased wrinkle depth, epidermal thickness, collagen degradation, and trans-epidermal water loss, and increased ß-glucosidase activity on UVB exposed skin. Putgyul extract protects against UVB-induced damage of skin and could be valuable in the prevention of photoaging.

Sasa quelpaertensis and p-coumaric acid attenuate oleic acid-induced lipid accumulation in HepG2 cells.

In this study, we examined the effects of Jeju dwarf bamboo (Sasa quelpaertensis Nakai) extract (JBE) and p-coumaric acid (CA) on oleic acid (OA)-induced lipid accumulation in HepG2 cells. JBE and CA increased the phosphorylation of AMP-activated protein kinase (AMPK), and acetyl-CoA carboxylase (ACC) and the expression of carnitine palmitoyl transferase 1a (CPT1a) in OA-treated HepG2 cells. Additionally, these compounds decreased sterol regulatory element-binding protein-1c (SREBP-1c), fatty acid synthase (FAS), and OA-induced lipid accumulation, suggesting that JBE and CA modulate lipid metabolism in HepG2 cells via the AMPK activation pathway.

Sasa quelpaertensis Nakai extract and its constituent p-coumaric acid inhibit adipogenesis in 3T3-L1 cells through activation of the AMPK pathway.

In this study, we investigated the effects of Sasa quelpaertensis Nakai extract (SQE) and its main constituent, p-coumaric acid, on adipogenesis in 3T3-L1 cells. SQE markedly inhibited adipogenesis by downregulating the expression of CCAAT/enhancer-binding protein α (C/EBPα), peroxisome proliferator-activated receptor γ (PPARγ), sterol regulatory element-binding protein-1c (SREBP-1c), and aP2. It also decreased the expression of fatty acid synthase (FAS) and adiponectin mRNAs in differentiating adipocytes. SQE increased AMP-activated protein kinase (AMPK) and acetyl-CoA carboxylase (ACC) phosphorylation during the early phase of MDI-induced differentiation, suggesting that SQE exerted its anti-adipogenic effect via AMPK activation at an early stage of the differentiation process. p-Coumaric acid suppressed adipogenesis by attenuating the expression of C/EBPα, PPARγ, and SREBP-1c during the late phase of MDI-induced differentiation. In addition, p-coumaric acid increased the phosphorylation of AMPK and ACC, and the expression of carnitine palmitoyl transferase-1 (CPT-1) mRNA, in fully differentiated adipocytes, indicating that it promotes fatty acid ß-oxidation via AMPK signaling. Taken together, our data suggest that SQE and p-coumaric acid might have the anti-obesitic effects via AMPK pathway in 3T3-L1 cells.

p-Coumaric acid modulates glucose and lipid metabolism via AMP-activated protein kinase in L6 skeletal muscle cells.

p-Coumaric acid (3-[4-hydroxyphenyl]-2-propenoic acid) is a ubiquitous plant metabolite with antioxidant, anti-inflammatory, and anticancer properties. In this study, we examined whether p-coumaric acid modulates glucose and lipid metabolism via AMP-activated protein kinase (AMPK) in L6 skeletal muscle cells. p-Coumaric acid increased the phosphorylation of AMPK in a dose-dependent manner in differentiated L6 skeletal muscle cells. It also increased the phosphorylation of acetyl-CoA carboxylase (ACC) and the expression of CPT-1 mRNA and PPARα, suggesting that it promotes the ß-oxidation of fatty acids. Also, it suppressed oleic acid-induced triglyceride accumulation, and enhanced 2-NBDG uptake in differentiated L6 muscle cells. Pretreatment with compound C inhibited AMPK activation, reduced ACC phosphorylation and 2-NBDG uptake, and increased triglyceride accumulation. However, p-coumaric acid counterbalanced the inhibitory effects of compound C. Taken together, these results suggest that p-coumaric acid modulates glucose and lipid metabolism via AMPK activation in L6 skeletal muscle cells and that it has potentially beneficial effects in improving or treating metabolic disorders.

Anti-obesity properties of a Sasa quelpaertensis extract in high-fat diet-induced obese mice.

This study explores the anti-obesity properties of a Sasa quelpaertensis leaf extract (SQE) in high-fat diet (HFD)-induced obese C57BL/6 mice and mature 3T3-L1 adipocytes. SQE administration with HFD for 70 d significantly decreased the body weight gain, adipose tissue weight, and serum total cholesterol and triglyceride levels in comparison with the HFD group. SQE administration also reduced the serum levels of glutamic oxaloacetic transaminase, glutamic pyruvic transaminase and lactate dehydrogenase, and the accumulation of lipid droplets in the liver, suggesting a protective effect against HFD-induced hepatic steatosis. SQE administration restored the HFD-induced decreases with phosphorylation of AMP-activated protein kinase (AMPK) and acetyl-CoA carboxylase (ACC) in epididymal adipose tissue. SQE also induced AMPK phosphorylation in mature 3T3-L1 adipocytes. These results suggest that SQE exerted an anti-obesity effect on HFD-induced obese mice by activating AMPK in adipose tissue and reducing lipid droplet accumulation in the liver.

Sinensetin attenuates LPS-induced inflammation by regulating the protein level of IκB-α.

Sinensetin is one of the polymethoxyflavones (PMFs) having five methoxy groups on the basic benzo-γ-pyrone skeleton with a carbonyl group at the C(4) position. We investigated in this study the anti-inflammatory activity of sinensetin in lipopolysaccharide (LPS)-stimulated RAW 264.7 cells. Sinensetin showed anti-inflammatory activity by regulating the protein level of inhibitor κB-α (IκB-α).

Petalonia binghamiae extract and its constituent fucoxanthin ameliorate high-fat diet-induced obesity by activating AMP-activated protein kinase.

In this study, we investigated the antiobesity properties of Petalonia binghamiae extract (PBE) in mice in which obesity was induced with a high-fat diet (HFD). PBE administration (150 mg/kg/day) for 70 days decreased body weight gain, adipose tissue weight, and the serum triglyceride level in mice fed a HFD. PBE reduced serum levels of glutamic pyruvic transaminase and glutamic oxaloacetic transaminase as well as the accumulation of lipid droplets in the liver. PBE restored the HFD-induced decrease in phosphorylation of AMP-activated protein kinase (AMPK) and acetyl-CoA carboxylase (ACC) in epididymal adipose tissue. PBE increased the phosphorylation of AMPK and ACC and decreased the expression of SREBP1c in mature 3T3-L1 adipocytes. In addition, we further explored the active compound responsible for AMPK activation by PBE in 3T3-L1 adipocytes. Fucoxanthin isolated from PBE increased the phosphorylation of AMPK and ACC with increasing LKB1 phosphorylation in mature 3T3-L1 adipocytes. Taken together, these data suggest that PBE (or fucoxanthin) exert improving effects on HFD-induced obesity by promoting ß-oxidation and reducing lipogenesis.

Immature Citrus sunki peel extract exhibits antiobesity effects by ß-oxidation and lipolysis in high-fat diet-induced obese mice.

The peel of Citrus sunki HORT. ex TANAKA has been widely used in traditional Asian medicine for the treatment of many diseases, including indigestion and bronchial asthma. In this study, we investigated the antiobesity activity of immature C. sunki peel extract (designated CSE) using high-fat diet (HFD)-induced obese C57BL/6 mice and mature 3T3-L1 adipocytes. In the animal study, body weight gain, adipose tissue weight, serum total cholesterol, and triglyceride in the CSE-administered group decreased significantly compared to the HFD group. Also, CSE supplementation reduced serum levels of glutamic pyruvic transaminase, glutamic oxaloacetic transaminase, and lactate dehydrogenase. Moreover, it significantly decreased the accumulation of fatty droplets in liver tissue, suggesting a protective effect against HFD-induced hepatic steatosis. Dietary supplementation with CSE reversed the HFD-induced decrease in the phosphorylation levels of AMP-activated protein kinase (AMPK) and acetyl-CoA carboxylase (ACC), which are related to fatty acid ß-oxidation, in the epididymal adipose tissue. Also, CSE increased AMPK and ACC phosphorylation in mature 3T3-L1 adipocytes. CSE also enhanced lipolysis by phosphorylation of cAMP-dependent protein kinase (PKA) and hormone-sensitive lipase (HSL) in mature 3T3-L1 adipocytes. These results suggest that CSE had an antiobesity effect via elevated ß-oxidation and lipolysis in adipose tissue.