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Bioactive Cadinane-type Compounds from the Soft Coral Sinularia scabra
Jyh-Horng Sheu,Jui-Hsin Su,Chiung-Yao Huang,Po-Ju Li,Yi Lu,Zhi-Hong Wen,Yao-Haur Kao 대한약학회 2012 Archives of Pharmacal Research Vol.35 No.5
Two new cadinane-type sesquiterpenoids, scabralins A (1) and B (2) were obtained from the soft coral Sinularia scabra. Metabolite 1 was shown to exhibit moderate to weak cytotoxicity against MCF-7, WiDr, Daoy, and HEp 2 cancer cell lines. Also, incubation with 10 μM compound 1 significantly inhibited the accumulation of the pro-inflammatory inducible nitric oxide synthase protein in lipopolysaccharide-stimulated RAW264.7 macrophage cells.
Anti-inflammatory Cembranoids from the Formosan Soft Coral Sinularia discrepans
Yi Lu,Huey-Jen Su,Yung-Husan Chen,Zhi-Hong Wen,Jyh-Horng Sheu,Jui-Hsin Su 대한약학회 2011 Archives of Pharmacal Research Vol.34 No.8
A new cembranoid, discrepanolide A (1), along with four known cembranoids 2-5 were isolated from the Formosan soft coral Sinularia discrepans. The structures of these compounds were determined by analysis of spectroscopic data and by comparison of NMR data with those of known compounds. None of these compounds were found to be cytotoxic towards a limited panel of cancer cell lines. Compounds 3-5 were found to display significant in vitro anti-inflammatory activity in LPS-stimulated RAW264.7 macrophage cells by inhibiting the expression of the iNOS protein. Compound 5 also significantly inhibited the accumulation of pro-inflammatory COX-2 protein.
Kok-Tong Tan,Yu-Hung Shih,Jiny Yin Gong,Xiang Zhang,Chiung-Yao Huang,Jui-Hsin Su,Jyh-Horng Sheu,Chi-Chen Lin The Korean Society of Pharmacology 2023 The Korean Journal of Physiology & Pharmacology Vol.27 No.4
Dihydroaustrasulfone alcohol (DA), the synthetic precursor of a natural compound (austrasulfone) isolated from the coral species Cladiella australis, has shown cytotoxic effects against cancer cells. However, it is unknown whether DA has antitumor effects on nasopharyngeal carcinoma (NPC). In this study, we determined the antitumor effects of DA and investigated its mechanism of action on human NPC cells. The MTT assay was used to determine the cytotoxic effect of DA. Subsequently, apoptosis and reactive oxygen species (ROS) analyses were performed by using flow cytometry. Apoptotic and PI3K/AKT pathway-related protein expression was determined using Western blotting. We found that DA significantly reduced the viability of NPC-39 cells and determined that apoptosis was involved in DA-induced cell death. The activity of caspase-9, caspase-8, caspase-3, and PARP induced by DA suggested caspase-mediated apoptosis in DA-treated NPC-39 cells. Apoptosis-associated proteins (DR4, DR5, FAS) in extrinsic pathways were also elevated by DA. The enhanced expression of proapoptotic Bax and decreased expression of antiapoptotic BCL-2 suggested that DA mediated mitochondrial apoptosis. DA reduced the expression of pPI3K and p-AKT in NPC-39 cells. DA also reduced apoptosis after introducing an active AKT cDNA, indicating that DA could block the PI3K/AKT pathway from being activated. DA increased intracellular ROS, but N-acetylcysteine (NAC), a ROS scavenger, reduced DA-induced cytotoxicity. NAC also reversed the chances in pPI3K/AKT expression and reduced DA-induced apoptosis. These findings suggest that ROS-mediates DA-induced apoptosis and PI3K/AKT signaling inactivation in human NPC cells.
Han-Chun Hung,Chien-Wei Feng,Yen-You Lin,Chun-Hong Chen,Kuan-Hao Tsui,Wu-Fu Chen,Chieh-Yu Pa,Jyh-Horng Sheu,Chun-Sung Sung,Zhi-Hong Wen 생화학분자생물학회 2018 Experimental and molecular medicine Vol.50 No.-
Atopic dermatitis (AD) is a chronic inflammatory skin disease, and its prevalence is increasing. AD usually elicits skin barrier dysfunction, dry skin and itching. As the mechanisms of AD remain unknown, there is an urgent need to find effective therapies. Because of the diversity and complexity of marine environments, the discovery of drugs from marine organisms as novel therapeutic agents for human diseases has seen renewed interest. Dihydroaustrasulfone alcohol (WA-25), the synthetic precursor of austrasulfone, which is a natural product isolated from a Formosan soft coral, has been shown to possess many therapeutic effects in our previous studies. However, the detailed mechanisms and therapeutic effects of WA-25 on AD are incompletely understood. We performed in vitro and in vivo studies to examine the effects of WA-25 on AD. We showed that WA-25 blocks inflammation and oxidative stress. Simultaneously, we also found that WA-25 reduces the AD scores and AD-induced transepidermal water loss (TEWL), scratching behavior, and alloknesis. WA-25 is more effective in cases of AD than are the drugs that are currently used clinically. Importantly, we also found that when nucleophosmin (NPM) was inhibited or when its expression was reduced, the anti-inflammatory and anti-AD effects of WA-25 were blocked. These data suggest that NPM plays dual roles in inflammation and AD. Overall, these results suggest that WA-25 is a potential anti-inflammatory and AD therapeutic agent that is modulated by NPM.