BIOACTIVE FRACTION DLBS2411 FROM CINNAMOMUM BURMANNII, (NEES AND T. NEES) BLUME AS COLON AND GASTROPROTECTOR BY STIMULATING MUC5AC AND CYCLOOXYGENASE-2 GENE EXPRESSION

Objective: Mucus therapy is one of the therapies for gastric ulcer management aside from proton pump inhibitor (PPI) and H2-blocker medication. Bioactive fraction DLBS2411 which comes from Cinnamomum burmannii has been identified as a gastric acid anti-secretory agent by inhibiting the activity of hydrogen-potassium adenosine triphosphate (H+/K+ATPase). The study was aimed to evaluate the effect of DLBS2411 as a neuroprotective agent in gastric and colon by investigating its regulation on mucus related pathway.Methods: Total RNA was extracted from gastric and colon cells followed by quantitative real-time polymerase chain reaction (qPCR) analysis for mucus synthesis and mucosal blood flow gene expression. Protein expression of prostaglandin E2 (PGE2) and phosphorylation of IĸB kinase subunit alpha (IKKα) was analyzed with enzyme-linked immunosorbent assay (ELISA) kit and western blot. Measurement of nitric oxide (NO), which is related to mucosal blood flow, was also analyzed.Results: Treatment of DLBS2411 elevated phosphorylation of IKKα and activated nuclear factor-КB (NF-κB) which in turn stimulated mucus synthesis and mucosal blood flow. High level of NF-κB increased mucus synthesis pathway by promoting cyclooxygenase-2 (COX-2) and PGE2 expression, which increased the MUC5AC gene. Activation of NF-κB also increased production of NO, which stimulated mucosal blood flow.Conclusion: DLBS2411 is a promising candidate for gastric and colon mucus protection by increasing mucus synthesis and stimulating mucosal blood flow.Â

Forhidrol, a bioactive fraction of Phaleria macrocarpa (Scheff.) Boerl., increases reverse cholesterol transport pathway by down-regulation of cholesteryl ester transfer protein activity

Phaleria macrocarpa (Scheff.) Boerl. is one of the most popular medicinal plants in Indonesia. This plant has traditionally been used to lower cholesterol and control hypertension. This study was performed to examine the effect of Forhidrol, a bioactive fraction of P. macrocarpa (Scheff.) Boerl., to increase reverse cholesterol transport through the down-regulation of cholesteryl ester transfer protein (CETP) activity in hepatocellular carcinoma cell lines. Measurement of target genes including liver X receptor (LXR), sterol regulatory element-binding protein 1 (SREBP1), scavenger receptor class B type 1, low-density lipoprotein (LDL) receptor, apolipoprotein B, CYP11B1, CYP11B2, peroxisome proliferatoractivated receptor α (PPARα), peroxisome proliferator-activated receptor δ (PPARδ) and peroxisome proliferator-activated receptor γ (PPARγ) were done using realtime polymerase chain reaction assay. Secreted CETP and apolipoprotein A-1 were analyzed using western blot. CETP activity in vitro was measured using CETP inhibitor drug screening kit and triglyceride synthesis was measured using enzyme-linked immunosorbent assay. Forhidrol was found to significantly down-regulate CETP mRNA expression, as well as total CETP and cholesteryl esters transfer activity (P<0.05). It specifically reduced transcriptional level of regulatory genes of CETP promoter including SREBP-1 and LXR. Forhidrol also significantly increased PPARδ and PPARα expression (P<0.05) and slightly repressed triglycerides synthesis. In vivo study showed elevated high-density lipoprotein (HDL) levels in rabbits after 4-week treatment of Forhidrol at a dose of 37.5 mg/1.5 kg body weight compared to placebo. Conversely, LDL, triglyceride and CETP activity were decreased. Forhidrol increased HDL levels by reducing CETP-dependent transfer of cholesterol from HDL to LDL particles. Looking at possible side effects, Forhidrol apparently acted as a safe agent without negative effect towards blood pressure. These findings suggested that Forhidrol may be further developed as a potential anti-atherogenic drug

The light subunit of mushroom Agaricus bisporus tyrosinase:Its biological characteristics and implications

The light subunit of mushroom Agaricus bisporus tyrosinase (LSMT) is a protein of unknown function that was discovered serendipitously during the elucidation of the crystal structure of the enzyme. The protein is non-immunogenic and can penetrate the intestinal epithelial cell barrier, and thus, similar to its structural homologue HA-33 from Clostridium botulinum, may be potentially absorbable by the intestine. LSMT also shares high structural homology with the ricin-B-like lectin from the mushroom Clitocybe nebularis (CNL), which has been shown to display biological activity against leukemic cancer cells and dendritic cells. Therefore, we evaluated the biological activity of LSMT. An in vitro assay suggested that LSMT presentation to most of the cancer cell lines studied has a negligible effect on their proliferation. However, inhibition of cell growth and a slight stimulation of cell proliferation were observed with breast cancer and macrophage cells, respectively. LSMT appeared to be relatively resistant against proteolysis by trypsin and papain, but not bromelain. Challenges with gastric and intestinal juice suggested that the protein is resistant to gastrointestinal tract conditions. This is the first report on the biological characteristics and implication of LSMT. (C) 2017 Elsevier B.V. All rights reserved