Showing papers by "Jae Sik Yu published in 2018"

Beneficial Effects of Bioactive Compounds in Mulberry Fruits against Cisplatin-Induced Nephrotoxicity

Abstract: Mulberry, the fruit of white mulberry tree (Morus alba L., Moraceae), is commonly used in traditional Chinese medicines as a sedative, tonic, laxative, and emetic. In our continuing research of the bioactive metabolites from mulberry, chemical analysis of the fruits led to the isolation of five compounds, 1-5. The compounds were identified as butyl pyroglutamate (1), quercetin 3-O-β-d-glucoside (2), kaempferol 3-O-β-d-rutinoside (3), rutin (4), and 2-phenylethyl d-rutinoside (5) by spectroscopic data analysis, comparing their nuclear magnetic resonance (NMR) data with those in published literature, and liquid chromatography-mass spectrometry analysis. The isolated compounds 1-5 were evaluated for their effects on anticancer drug-induced side effects by cell-based assays. Compound 1 exerted the highest protective effect against cisplatin-induced kidney cell damage. This effect was found to be mediated through the attenuation of phosphorylation of c-Jun N-terminal kinase, extracellular signal-regulated kinase, p38, mitogen-activated protein kinase, and caspase-3 in cisplatin-induced kidney cell damage.

Natalenamides A⁻C, Cyclic Tripeptides from the Termite-Associated Actinomadura sp. RB99.

Abstract: In recent years, investigations into the biochemistry of insect-associated bacteria have increased. When combined with analytical dereplication processes, these studies provide a powerful strategy to identify structurally and/or biologically novel compounds. Non-ribosomally synthesized cyclic peptides have a broad bioactivity spectrum with high medicinal potential. Here, we report the discovery of three new cyclic tripeptides: natalenamides A–C (compounds 1–3). These compounds were identified from the culture broth of the fungus-growing termite-associated Actinomadura sp. RB99 using a liquid chromatography (LC)/ultraviolet (UV)/mass spectrometry (MS)-based dereplication method. Chemical structures of the new compounds (1–3) were established by analysis of comprehensive spectroscopic methods, including one-dimensional (1H and 13C) and two-dimensional (1H-1H-COSY, HSQC, HMBC) nuclear magnetic resonance spectroscopy (NMR), together with high-resolution electrospray ionization mass spectrometry (HR-ESIMS) data. The absolute configurations of the new compounds were elucidated using Marfey’s analysis. Through several bioactivity tests for the tripeptides, we found that compound 3 exhibited significant inhibitory effects on 3-isobutyl-1-methylxanthine (IBMX)-induced melanin production. The effect of compound 3 was similar to that of kojic acid, a compound extensively used as a cosmetic material with a skin-whitening effect.

Tirucallane Triterpenoids from the Stems and Stem Bark of Cornus walteri that Control Adipocyte and Osteoblast Differentiations.

Abstract: Cornus walteri Wanger (Cornaceae) has been broadly used in traditional East Asian medicine for the treatment of various disorders, including skin inflammation and diarrhea. As part of our efforts to identify structurally and/or biologically new compounds from Korean medicinal plants, we have explored potentially new bioactive constituents from C. walteri. In the present study, seven triterpenoids (1–7) were isolated from C. walteri stems and stem bark. Compounds 1–3 were new tirucallane triterpenoids (cornusalterins N-P) and compounds 4–7 were isolated for the first time from C. walteri. The structures of the new compounds were determined based on 1D and 2D NMR spectroscopic data interpretations and HR-ESIMS, as well as a computational method coupled with a statistical procedure (DP4+). The regulatory effects of the isolated triterpenoids (1–7) on mesenchymal stem cell (MSC) differentiation to adipocytes and osteoblasts were examined in the C3H10T1/2 cell line. Although these compounds had little effect on MSC differentiation to osteoblasts, lipid droplet formation in adipocyte-differentiated MSCs decreased in the presence of the seven triterpenoids. Compounds 1 and 4 each had a relatively distinct correlation between dose and efficacy, showing adipogenesis suppression at higher concentrations. Our findings demonstrate that the active compounds 1 and 4 can exert beneficial effects in regulation of adipocyte differentiation.

Identification of bioactive heterocyclic compounds from mulberry and their protective effect against streptozotocin-induced apoptosis in INS-1 cells

Abstract: A phytochemical investigation of the MeOH extracts from mulberries (the fruit of Morus alba L.) led to the identification of six heterocyclic compounds (1‑6). These compounds were screened to detect whether they protected pancreatic INS‑1 cells from streptozotocin (STZ)‑induced cytotoxicity. Compound 3 was the most effective at preventing STZ‑induced cytotoxicity and the production of reactive oxygen species (ROS) in INS‑1 cells. In addition, compound 3 effectively prevented apoptosis induced by STZ in INS‑1 cells. Compound 3 also prevented STZ‑mediated cleavage of caspase‑8, caspase‑3 and poly (ADP‑ribose) polymerase and increased the expression of B‑cell lymphoma‑2 (Bcl‑2), an anti‑apoptotic Bcl‑2 family protein. In conclusion, the results of the present study indicate that compound 3 extracted from the fruit of M. alba was highly effective in preventing type 1 diabetes mellitus and may be a novel treatment option.

Biological Evaluation of a New Lignan from the Roots of Rice (Oryza sativa)

Abstract: LC/MS-based phytochemical analysis of an EtOH extract of the roots of rice (Oryza sativa; Gramineae), which takes a crucial role in the stable crop population in Asia, resulted in the isolation of a new lignan, oryzativol C (1), as a minor component The chemical structure of compound 1 was unambiguously confirmed using spectroscopic evidence (including 1D- and 2D-NMR data), HR-ESI-MS, and CD data analysis Considering the traditional medicinal efficacy of O sativa and its importance as a food crop, compound 1 was evaluated for effects on breast cancer cell lines (MDA-MB-231) and on glucose-stimulated insulin secretion in an INS-1 pancreatic β-cell line Compound 1 showed mild cytotoxicity toward the MDA-MB-231 Furthermore, compound 1 stimulated insulin secretion in INS-1 pancreatic β-cells without inducing cytotoxicity These results indicate that compound 1 is an active ingredient of O sativa that offers health benefits including inhibition of breast cancer cell proliferation and hyperglycemia control

The Inhibitory Effects of Cyclodepsipeptides from the Entomopathogenic Fungus Beauveria bassiana on Myofibroblast Differentiation in A549 Alveolar Epithelial Cells

Abstract: Pulmonary fibrosis (PF) is a chronic and fatal lung disease with few treatment options. Although the pathogenesis of PF is not clear, a chronic inflammatory response to continuous damage is considered the cause of pulmonary fibrosis. PF is characterized by excessive accumulation of extracellular matrix (ECM), therefore, inhibition of myofibroblast differentiation is a good therapeutic target for PF. As part of our continuing endeavor to explore biologically active metabolites from insect-associated microbes, we found that the MeOH extract of the culture broth from the entomopathogenic fungus Beauveria bassiana inhibited collagen induction and E-cadherin down-regulation. In order to identify active compounds, we carried out chemical analysis of the MeOH extract with the assistance of LC/MS-guided isolation approach, which led to the successful identification of four cyclodepsipeptides 1–4. Among the isolates, compound 2 showed inhibitory effects on myofibroblast differentiation induced by TGF-β1. Compound 2 inhibited induction of α-SMA and N-cadherin, which are myofibroblast markers, and blocked the accumulation of ECM proteins such as collagen and fibronectin. Overall these findings demonstrate that compound 2 can be used to attenuate pulmonary fibrosis by targeting myo- fibroblast differentiation.