S.W.A. Himaya

Paeonol from Hippocampus kuda Bleeler suppressed the neuro-inflammatory responses in vitro via NF-κB and MAPK signaling pathways.

Inflammation has recently been implicated as a critical mechanism responsible for neurodegenerative diseases. In this study, paeonol (1-(2-hydroxy-4-methoxyphenyl)ethanone) isolated from the sea horse Hippocampus kuda Bleeler was studied as an agent to suppress LPS induced activation of BV-2 microglial and RAW264.7 macrophage cells. The results obtained showed that paeonol significantly suppressed LPS induced release of pro-inflammatory products such as nitric oxide (NO), prostaglandin E2 (PGE(2)), and cytokines; tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β) and interleukin-6 (IL-6). Furthermore, the compound down regulated the protein and gene expression levels of inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), TNF-α, IL-1β and IL-6 in both cell lines. Molecular signaling pathway studies showed that paeonol inhibited the translocation of nuclear factor-κB (NF-κB) p65 and p50 subunits to the nucleus by blocking IKKα/β (IκB kinase α/β) mediated degradation of IκBα. Moreover, it suppressed the phosphorylation of mitogen activated protein kinase (MAPK) pathway molecules; c-Jun N-terminal kinases (JNK) and p38 in both cell lines. Collectively these results indicate that paeonol blocked the LPS stimulated inflammatory responses in BV-2 and RAW264.7 cells via modulating MAPK and NF-κB signaling pathways. Therefore, paeonol could be a promising candidate to be used in neuro-inflammatory therapy.

Triterpene glycosides from sea cucumbers and their biological activities.

Triterpenoid glycosides are abundantly present in sea cucumbers, which are responsible for the toxicity of these echinoderms. More than 100 triterpenoid glycosides have been isolated in the past 20 years and those are grouped into four main structural categories considering their aglycone structure: 3β-hydroxyholost-9(ll)-ene aglycone skeleton, 3β-hydroxyholost-7-ene skeleton, other holostane type aglycones and nonholostane aglycone. Most of the triterpenoid glycosides are found to be possessing potential biological activities. Among the biological activities, anticancer activity and antiviral activity are the most widely studied areas. In this communication, we have presented a general view of the structural characteristics of triterpenoid glycosides and their major biological activities. The structural significance and the application limitations of triterpene glycosides are also discussed.

Sea cucumber, Stichopus japonicus ethyl acetate fraction modulates the lipopolysaccharide induced iNOS and COX-2 via MAPK signaling pathway in murine macrophages

The sea cucumber Stichopus japonicus is an important food and traditional medicine in Asian countries. However, ethyl acetate solvent fraction of S. japonicus (SCEA-F) is largely unknown for its anti-inflammatory activity and related molecular mechanisms. In this study, effect of SCEA-F on inflammation was investigated in LPS stimulated RAW264.7 cells. SCEA-F significantly inhibited the productions of NO and PGE(2) by inhibiting iNOS and COX-2 at their protein and gene levels. The production and the gene transcription of pro-inflammatory cytokines are also inhibited. The responsible molecular signaling for these inhibitory actions was found to be through suppression of the phosphorylation of MAPK molecules; ERK and p38 MAPK. These results indicate that SCEA-F inhibits LPS-induced inflammatory response via blocking of MAPK signaling pathway in murine macrophages, thus demonstrated its in vitro anti-inflammatory potential. Therefore it could be suggested that SCEA-F could be effectively used in functional food preparations.

Triterpenoids of Marine Origin as Anti-Cancer Agents

Triterpenoids are the most abundant secondary metabolites present in marine organisms, such as marine sponges, sea cucumbers, marine algae and marine-derived fungi. A large number of triterpenoids are known to exhibit cytotoxicity against a variety of tumor cells, as well as anticancer efficacy in preclinical animal models. In this review efforts have been taken to review the structural features and the potential use of triterpenoids of marine origin to be used in the pharmaceutical industry as potential anti-cancer drug leads.

Peptide Isolated from Japanese Flounder Skin Gelatin Protects against Cellular Oxidative Damage

Gelatin was extracted from the skin of Japanese flounder ( Palatichtys olivaceus ) and was subjected to enzymatic hydrolysis. The peptic hydrolysate resulted in a potent antioxidative peptide Gly-Gly-Phe-Asp-Met-Gly (582 Da), which bears +12.61 kcal/mol hydrophobicity. The antioxidative potential of the peptide was characterized by analyzing the protective effect of the peptide on reactive oxygen species (ROS)-mediated intracellular macromolecule damage. It was found that the peptide is a potent scavenger of intracellular ROS, thereby protecting the radical-mediated damage of membrane lipids, proteins, and DNA. Moreover, the peptide is capable of upregulating the expression of inherent antioxidative enzymes, superoxide dismutase-1, glutathione, and catalase. Collectively, it can be concluded that Japanese flounder skin, a processing byproduct of filleting, can be effectively used to produce a bioactive peptide with potent antioxidant capacity.

Fumigaclavine C from a marine-derived fungus Aspergillus fumigatus induces apoptosis in MCF-7 breast cancer cells.

Recently, much attention has been given to discovering natural compounds as potent anti-cancer candidates. In the present study, the anti-cancer effects of fumigaclavine C, isolated from a marine-derived fungus, Aspergillus fumigatus, was evaluated in vitro. In order to investigate the impact of fumigaclavine C on inhibition of proliferation and induction of apoptosis in breast cancer, MCF-7 cells were treated with various concentrations of fumigaclavine C, and fumigaclavine C showed significant cytotoxicity towards MCF-7 cells. Anti-proliferation was analyzed via cell mobility and mitogen-activated protein kinase (MAPK) signaling pathway. In addition, fumigaclavine C showed potent inhibition on the protein and gene level expressions of MMP-2, -9 in MCF-7 cells which were manifested in Western blot and reverse transcription polymerase chain reaction (RT-PCR) results. The apoptosis induction abilities of the fumigaclvine C was studied by analyzing the expression of apoptosis related proteins, cell cycle analysis, DNA fragmentation and molecular docking studies. It was found that fumigaclavine C fragmented the MCF-7 cell DNA and arrested the cell cycle by modulating the apoptotic protein expressions. Moreover, fumigaclavine C significantly down-regulated the NF-kappa-B cell survival pathway. Collectively, data suggest that fumigaclavine C has a potential to be developed as a therapeutic candidate for breast cancer.

Tyrosol exerts a protective effect against dopaminergic neuronal cell death in in vitro model of Parkinson’s disease

Experimental evidence suggests that tyrosol [2-(4-hydroxyphenyl)ethanol] exhibits potent protective activities against several pathogeneses. In this study, we evaluated the protective effect of tyrosol against 1-methyl-4-phenylpyridinium (MPP(+))-induced CATH.a neuron cell death. Tyrosol dose-dependently protected CATH.a cells from MPP(+)-induced cell death and the protection was more apparent after prolong incubation (48h). The data showed that tyrosol treatment suppressed the reduction of phospho-tyrosine hydroxylase level in CATH.a cells. Further, the compound repressed MPP(+)-induced depletion of mitochondrial membrane potential (Δψm) and thereby maintained intracellular ATP production in the cell. The cellular signalling pathway studies revealed that tyrosol protected CATH.a cells from MPP(+)-induced apoptotic signalling, most likely via activation of PI3K/Akt signalling pathway along with up-regulation of anti-oxidative enzymes (SOD-1 and SOD-2) and DJ-1 protein in the cell. Collectively, present study demonstrates that tyrosol significantly protects dopaminergic neurons from MPP(+)-induced degradation, and reveals potential neuroprotective mechanism of tyrosol.

Neoechinulin A suppresses amyloid-β oligomer-induced microglia activation and thereby protects PC-12 cells from inflammation-mediated toxicity

A pathological hallmark of Alzheimers disease (AD), aggregation and deposition of amyloid-β peptides, has been recognized as a potent activator of microglia-mediated neuroinflammation and neuronal dysfunction. Therefore, downregulation of microglial activation has a significant therapeutic demand. In this study, focus was given to evaluate the ability of neoechinulin A, an indole alkaloid isolated from marine-derived Microsporum sp., to attenuate microglial activation by oligomeric amyloid-β 1-42 (Aβ42). Neoechinulin A treatment significantly inhibited the generation of reactive oxygen and nitrogen species in Aβ42-activated BV-2 microglia cells. In addition, we found that neoechinulin A significantly suppressed the production of neurotoxic inflammatory mediator tumour necrosis factor-α (TNF-α), interleukin-1β (IL-1β), interleukin-6 (IL-6), and prostaglandin E2 (PGE2) in activated BV-2 cells. Moreover, the treatment downregulated the protein and gene expressions of inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), TNF-α, IL-1β and IL-6. Further, activated microglia-mediated apoptosis of PC-12 pheochromocytoma cells was significantly repressed by neoechinulin A. The molecular mechanism studies suggested that neoechinulin A may block the phosphorylation of mitogen-activated protein kinase (MAPK) molecule p38, apoptosis signal-regulating kinase 1 (ASK-1) and nuclear translocation of nuclear factor-κB (NF-κB) p65 and p50 subunits. Regulation of these signalling pathways have most probably contributed to the anti-inflammatory activity of neoechinulin A. Collectively, these results suggest that with further studies neoechinulin A have a potential to be developed as a modulator of neuroinflammatory process in AD.

Medicinal Effects of Phlorotannins from Marine Brown Algae

Brown seaweeds are popular and abundant food in East Asia and also well known for their medicinal effects due to presence of active phenolic constituents. Phlorotannins, the major phenolic group of brown algae, have extensively investigated for their vast array of bioactivities such as antioxidant, anti-inflammatory, anticancer, and antidiabetic. They possess promising activity in both in vitro and in vivo systems showing promising potential to further develop as therapeutic agents. In this chapter, attempts have taken to examine and categorize the reports available on active phlorotannins which have shown strong bioactivities.

1-(5-bromo-2-hydroxy-4-methoxyphenyl)ethanone [SE1] suppresses pro-inflammatory responses by blocking NF-κB and MAPK signaling pathways in activated microglia

Unregulated activation of microglia is a key risk factor contributes to neurodegenerative diseases and suppression of this phenomenon is considered as a potential therapeutic target. The compound isolated from sea horse Hippocampus kuda Bleeler; 1-(5-bromo-2-hydroxy-4-methoxyphenyl)ethanone [SE1] was characterized for its ability in suppressing LPS mediated activation of murine BV-2 cells. Despite the presence of various active molecular groups in the structure, SE1 has not well explored for its biological activities. The outcome of this study clearly indicated that SE1 inhibited the production of inflammatory mediators; nitric oxide, prostaglandin E(2) and pro-inflammatory cytokines. Furthermore, it inhibited the protein and gene expression levels of inducible nitric oxide synthase, cyclooxygenase-2, tumor necrosis factor-α, interleukin-1β and interleukin-6. The responsible signaling mechanisms leading to these inhibitions were identified as SE1 mediated blocking of phosphorylation of mitogen activate protein kinase (MAPK) molecules; C-jun-N-terminal kinase (JNK), p38 and nuclear translocation of nuclear factor-κB (NF-κB) p65 and p50 subunits. These results suggest that SE1 has the potential to be further developed as therapeutic against neuro-inflammation.