Briarane-Related Diterpenoids from Octocoral Briareum stechei

A known polyoxygenated briarane, briaexcavatolide P (1), was isolated from a Formosan octocoral Briareum stechei. Moreover, the same species B. stechei, collected from Okinawan waters, yielded three chlorine-containing briaranes, including two new compounds, briastecholides B (2) and C (3) as well as a known analogue, briarenol R (4). The structures of 1–4 were established using spectroscopic methods. In addition, briarane 1 demonstrated anti-inflammatory activity in lipo-polysaccharide-induced RAW 264.7 mouse macrophage cells by suppressing the expression of inducible nitric oxide synthase (iNOS) protein.

Enhancement of the Immunostimulatory Effect of Phosphodiester CpG Oligodeoxynucleotides by an Antiparallel Guanine-Quadruplex Structural Scaffold

Guanine-quadruplex-based CpG oligodeoxynucleotides (G4 CpG ODNs) have been developed as potent immunostimulatory agents with reduced sensitivity to nucleases. We designed new monomeric G4 ODNs with an antiparallel topology using antiparallel type duplex/G4 ODNs as robust scaffolds, and we characterized their topology and effects on cytokine secretion. Based on circular dichroism analysis and quantification of mRNA levels of immunostimulatory cytokines, it was found that monomeric antiparallel G4 CpG ODNs containing two CpG motifs in the first functional loop, named G2.0.0, could maintain antiparallel topology and generate a high level of immunostimulatory cytokines in RAW264 mouse macrophage-like cell lines. We also found that the flanking sequence in the CpG motif altered the immunostimulatory effects. Gc2c.0.0 and Ga2c.0.0 are monomeric antiparallel G4 CpG ODNs with one cytosine in the 3′ terminal and one cytosine/adenine in the 5′ terminal of CpG motifs that maintained the same resistance to degradation in serum as G2.0.0 and improved interleukin-6 production in RAW264 and bone marrow-derived macrophages. The immunostimulatory activity of antiparallel G4 CpG ODNs is superior to that of linear natural CpG ODNs. These results provide insights for the rational design of highly potent CpG ODNs using antiparallel G4 as a robust scaffold.

Immunomodulatory Activity of Phyllanthus maderaspatensis in LPS-Stimulated Mouse Macrophage RAW 264.7 Cells

Phyllanthus species (Family Euphorbiaceae) has been used in traditional medicine of several countries as a cure for numerous diseases, including jaundice and hepatitis. This study is an attempt to evaluate the immunomodulatory activity of various fractions, column eluents of ethyl acetate fraction, and their polyphenols. Phyllanthus maderaspatensis were standardized using high-performance liquid chromatography to identify and quantify polyphenols, and purification of polyphenols was carried out using vacuum liquid chromatography. Subsequently, we tested various fractions, column eluents of ethyl acetate fraction, and polyphenols in vitro to assess their impact on nitric oxide (NO) production in LPS-stimulated mouse macrophage RAW 264.7 cells. The ethyl acetate fraction (100 μg mL−1) had a more significant stimulatory effect on LPS-stimulated NO production by the RAW 264.7 cells. We found that the ethyl acetate fraction contains a high amount of catechin, quercetin, ellagic acid kaempferol, and rutin, which are responsible for immunomodulation. The ethyl acetate fraction at concentrations of 25 and 50 μg mL−1 had a significant inhibitory effect and 100 μg mL−1 had a more significant stimulatory effect when compared with the LPS control. The percentage of inhibition by LPS control ranged from zero percentage, kaempferol ranged from 45.4% at 50 μg mL−1 to 41.88% at 100 μg mL−1, catechin ranged from 50% at 50 μg mL−1 to 35.28% at 100 μg mL−1, rutin ranged from 36.2% at 50 μg mL−1 to 47.44% at 100 μg mL−1, gallic acid ranged from 28.4% at 50 μg mL−1 to 50.9% at 100 μg mL−1, ellagic acid ranged from 45.12% at 50 μg mL−1 to 38.64% at 100 μg mL−1, and purified quercetin ranged from 26.2% at 50 μg mL−1to 45.48% at 100 μg mL−1. As NO plays an important role in the immune function, polyphenols’ treatment could modulate several aspects of host defense mechanisms owing to the stimulation of the inducible nitric oxide synthase.

SCREENING FOR VIETNAMESE PLANT EXTRACTS WITH POTENTIAL BENEFIT FOR ANTI OSTEOCLASTOGENESISH

Bone's homeostasis is only achieved when there is a balance between bone formation and bone resorption. A metabolic disorder of bone-resorbing osteoclasts can lead to osteoporosis. Long-term use of anti-osteoporosis drugs can lead to undesirable side effects so traditional herbal can be a potential source of alternative medicine. In the present study, forty one Vietnamese plants (seventy methanol extracts) were screened for osteoclastogenesis inhibitory activities on RAW264.7 mouse macrophage cells. For the first time, 29 extracts from 24 species showed potential as effective inhibitors of osteoclastogenesis.

Anti-Inflammatory Effects of Heat-Processed Artemisia capillaris Thunberg by Regulating IκBα/NF-κB Complex and 15-PGDH in Mouse Macrophage Cells

Growing evidence suggests that dietary nutrients in herbs and plants are beneficial in improving inflammatory disorders. Artemisia capillaris Thunberg (AC) is a traditional herbal medicine widely used in East Asia to treat pain, hepatotoxicity, and inflammatory disorders. Heat processing is a unique pharmaceutical method used in traditional herbal medicine to enhance the pharmacological effects and safety of medicinal plants. This study demonstrates the anti-inflammatory effects of heat-processed AC (HPAC) in lipopolysaccharide- (LPS-) treated mouse macrophage cells. HPAC reduced LPS-induced inflammatory mediators such as IL-6, IL-1β, TNF-α, NO, and PGE2 in RAW 264.7 cells. Interestingly, 15-PGDH appears to play a pivotal role rather than COX-2 and mPGES-1 when HPAC regulated PGE2 levels. Meanwhile, HPAC showed anti-inflammatory effects by blocking IκBα phosphorylation and NF-κB nuclear translocalization. Also, we found that HO-1 upregulation was mediated by the mitogen-activated protein kinase (MAPK) pathways in HPAC-treated RAW 264.7 cells. And, in RAW 264.7 cells challenged with LPS, HPAC restored HO-1 expression, leading to NF-κB inhibition. Through further experiments using specific MAPK inhibitors, we found that, in response to LPS, the phosphorylated IκBα and activated NF-κB were attenuated by p38 MAPK/HO-1 pathway. Therefore, HPAC targeting both the IκBα/NF-κB complex and 15-PGDH may be considered as a potential novel anti-inflammatory agent derived from a natural source.

Cembranoids from Octocoral Lobophytum crassum (von Marenzeller, 1886)

Two cembranoids, including a new compound, lobocrassin I (1), as well as a known analogue, lobohedleolide (2), were obtained by solvent extraction from octocoral Lobophytum crassum. This study employed a spectroscopic approach to establish the structures of these two cembranoids, and utilized single-crystal X-ray diffraction analysis to determine their absolute configurations. The results of biological activity assays demonstrated that cembranoid 2 exhibited bioactivity against the protein expressions of inducible nitric oxide synthase (iNOS) lipopolysaccharide (LPS)-treated RAW 264.7 mouse macrophage cells.

Briarenols W–Z: Chlorine-Containing Polyoxygenated Briaranes from Octocoral Briareum stechei (Kükenthal, 1908)

Briareum stechei is proven to be a rich source of 3,8-cyclized cembranoids (briarane) with a bicyclo[8.4.0] carbon core. In the present study, four previously unreported briaranes, briarenols W–Z (1–4), along with solenolide A (5), briarenolide M (6), briaexcavatolide F (7), and brianolide (8), were isolated and characterized through spectroscopic analysis, and the absolute configuration of 8 was corroborated by a single-crystal x-ray diffraction analysis. Briaranes 2 and 5 were found to induce significant inflammatory activity in lipopolysaccharide (LPS)-induced RAW 264.7 mouse macrophage cells by enhancing the expression of the inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) proteins.