Narirutin-Rich Celluclast Extract from Mandarin (Citrus unshiu) Peel Alleviates High-Fat Diet-Induced Obesity and Promotes Energy Metabolism in C57BL/6 Mice.

Mandarin peel, a main by-product from the processing of citrus juice, has been highlighted for its various bioactivities and functional ingredients. Our previous study proved the inhibitory effects of Celluclast extract from mandarin peel (MPCE) on lipid accumulation and differentiation in 3T3-L1 adipocytes. Therefore, the current study aimed to evaluate the anti-obesity effect of MPCE in high-fat diet (HFD)-induced obese mice. The high-performance liquid chromatography (HPLC) analysis exhibited that narirutin and hesperidin are the main active components of MPCE. Our current results showed that MPCE supplementation decreased adiposity by reducing body and organ weights in HFD-induced obese mice. MPCE also reduced triglyceride (TG), alanine transaminase (ALT), aspartate transaminase (AST), and leptin contents in the serum of HFD-fed mice. Moreover, MPCE significantly inhibited hepatic lipid accumulation by regulating the expression levels of proteins associated with lipid metabolism, including sterol regulatory element-binding protein (SREBP1c), fatty acid synthase (FAS), and acetyl-CoA carboxylase (ACC). Furthermore, MPCE administration significantly inhibited both adipogenesis and lipogenesis, with modulation of energy metabolism by activating 5' adenosine monophosphate-activated protein kinase (AMPK) and lipolytic enzymes such as hormone-sensitive lipase (HSL) in the white adipose tissue (WAT). Altogether, our findings indicate that MPCE improves HFD-induced obesity and can be used as a curative agent in pharmaceuticals and nutraceuticals to alleviate obesity and related disorders.

Radio-protective effects of Thymus quinquecostatus Celak extract in mice.

Thymus quinquecostatus Celak (TQC) is an aromatic herb, that possesses a wide range of biological properties. In the present study, we investigated the radio-protective effect of TQC water extract (TQCW) in gamma ray-exposed splenocytes, a peripheral immune cell and mice. Our results showed that the treatment with TQCW dose-dependently increased the viability of splenocytes. TQCW significantly increased the proliferation of splenocytes by reducing the production of intracellular reactive oxygen species (ROS) in 2 Gy-exposed splenocytes. Moreover, TQCW enhanced the hemopoietic system as increasing the number of endogenous spleen colony-forming units, and the number and the proliferation of splenocytes in 7 Gy-exposed mice. These results suggest that TQCW protects mice by enhancing the splenocytes proliferation and hemopoietic systems following exposure to gamma rays.

Ishige okamurae Celluclast extract ameliorates non-alcoholic fatty liver in high-fructose diet-fed mice by modulation of lipid metabolism and gut microbiota composition.

Recently, a new mechanism has revealed that gut microbiota plays a pivotal role in metabolizing fructose to acetate that facilitates hepatic lipogenesis. Therefore, our study investigated the role of microbiome on abnormal lipid synthesis in the presence of fructose and identified attenuating effects of Ishige okamurae Celluclast extract (IOCE) against fructose-induced fatty liver. The results indicated that oral administration of IOCE (150 and 300 mg/kg/day for 12 weeks) significantly reduced both gut microbiota-mediated and -non-mediated hepatic lipogenesis simultaneously triggered by fructose metabolism. IOCE reduced hepatic triglyceride accumulation and expression levels of key enzymes for glucolipid metabolism. In addition, IOCE regulated fatty acid synthesis, ß-oxidation, and improved hepatic inflammation. Furthermore, IOCE inhibited direct fructose-to-acetate conversion and altered the compositions of gut microbiota. These findings suggest that IOCE might serve as a potential prebiotic dietary supplement by ameliorating fatty liver through dual regulation of classical lipogenic pathway and gut microbiota.

Structure Characterization and Antihypertensive Effect of an Antioxidant Peptide Purified from Alcalase Hydrolysate of Velvet Antler.

Recently, interest in food-derived bioactive peptides as promising ingredients for the prevention and improvement of hypertension is increasing. The purpose of this study was to determine the structure and antihypertensive effect of an antioxidant peptide purified from velvet antler in a previous study and evaluate its potential as a various bioactive peptide. Molecular weight (MW) and amino acid sequences of the purified peptide were determined by quadrupole time-of-flight electrospray ionization mass spectroscopy. The angiotensin I-converting enzyme (ACE) inhibition activity of the purified peptide was assessed by enzyme reaction methods and in silico molecular docking analysis to determine the interaction between the purified peptide and ACE. Also, antihypertensive effect of the purified peptide in spontaneously hypertensive rats (SHRs) was investigated. The purified antioxidant peptide was identified to be a pentapeptide Asp-Asn-Arg-Tyr-Tyr with a MW of 730.31 Da. This pentapeptide showed potent inhibition activity against ACE (IC50 value, 3.72 µM). Molecular docking studies revealed a good and stable binding affinity between purified peptide and ACE and indicated that the purified peptide could interact with HOH2570, ARG522, ARG124, GLU143, HIS387, TRP357, and GLU403 residues of ACE. Furthermore, oral administration of the pentapeptide significantly reduced blood pressure in SHRs. The pentapeptide derived from enzymatic hydrolysate of velvet antler is an excellent ACE inhibitor. It might be effectively applied as an animal-based functional food ingredient.

Ishophloroglucin A, a potent PTP1B inhibitor isolated from brown alga Ishige okamurae inhibits adipogenesis in 3T3-L1 adipocytes.

Ishophloroglucin A (IPA) is one of the most abundant and active compounds in Ishige okamurae and is known to be a potential therapeutic candidate for the improvement of metabolic diseases. However, IPA on the inhibitory effects of protein tyrosine phosphatase 1B (PTP1B) and adipogenesis have not been determined. In this study, we investigated the effects of IPA on the inhibition of PTP1B, the effects on adipogenesis, and its mechanisms of action in 3 T3-L1 adipocytes. The IC50 value of IPA against PTP1B was 0.43 µM, which evidenced the higher inhibition activity than that of ursolic acid, a known PTP1B inhibitor. For further insight, we predicted the 3D structure of PTP1B and used a docking algorithm to simulate the binding between PTP1B and IPA. Molecular docking studies revealed a high and stable binding affinity between IPA and PTP1B and indicated that the IPA could interacts with the amino acid residues located in a region to the active site of PTP1B. Further studies showed that IPA concentrations between 6.25 µM and 25 µM dose-dependently attenuated adipogenesis, which was accompanied by a reduction in adipogenesis-related factors, including PPARγ, C/EBPα, SREBP-1c, and FABP4. Our findings suggested that IPA may be a promising natural compound for the treatment of obesity and related diseases.

Diphlorethohydroxycarmalol inhibits melanogenesis via protein kinase A/cAMP response element-binding protein and extracellular signal-regulated kinase-mediated microphthalmia-associated transcription factor downregulation in α-melanocyte stimulating hormone-stimulated B16F10 melanoma cells and zebrafish.

Diphlorethohydroxycarmalol (DPHC) is a marine polyphenolic compound derived from brown alga Ishige okamurae. A previously study has suggested that DPHC possesses strong mushroom tyrosinase inhibitory activity. However, the anti-melanogenesis effect of DPHC has not been reported at cellular level. The objective of the present study was to clarify the melanogenesis inhibitory effect of DPHC and its molecular mechanisms in murine melanoma cells (B16F10) and zebrafish model. DPHC significantly inhibited tyrosinase activity and melanin content dose-dependently in α-melanocyte stimulating hormone (α-MSH)-stimulated B16F10 cells. This polyphenolic compound also suppressed the expression of phosphorylation of cAMP response element-binding protein (CREB) by attenuating phosphorylation of cAMP-dependent protein kinase A, resulting in decreased MITF expression levels. Furthermore, DPHC downregulated MITF protein expression levels by promoting the phosphorylation of extracellular signal-regulated kinase. It also inhibited tyrosinase, tyrosinase-related protein 1 (TRP-1), and TRP-2 in α-MSH stimulated B16F10 cells. In in vivo studies using zebrafish, DPHC also markedly inhibited melanin synthesis in a dose-dependent manner. These results demonstrate that DPHC can effectively inhibit melanogenesis in melanoma cells in vitro and in zebrafish in vivo, suggesting that DPHC could be applied in fields of pharmaceutical and cosmeceuticals as a skin-whitening agent. Significance of study: The present study showed for the first time that DPHC could inhibit a-MSH-stimulated melanogenesis via PKA/CREB and ERK pathway in melanoma cells. It also could inhibit pigmentation in vivo in a zebrafish model. This evidence suggests that DPHC has potential as a skin whitening agent. Taken together, DPHC could be considered as a novel anti-melanogenic agent to be applied in cosmetic, food, and medical industry.