Background and purpose: Natural compounds obtained from marine organisms have received considerable attention as potential sources of novel drugs for treatment of human inflammatory diseases. Capnellene, isolated from the marine soft coralCapnella imbricate, 4,4,6a‐trimethyl‐3‐methylene‐decahydro‐cyclopenta[]pentalene‐2,3a‐diol (GB9) exhibited anti‐inflammatory actions on activated macrophagesin vitro. Here we have assessed the anti‐neuroinflammatory properties of GB9 and its acetylated derivative, acetic acid 3a‐hydroxy‐4,4,6a‐trimethyl‐3‐methylene‐decahydro‐cyclopenta[]pentalen‐2‐yl ester (GB10).Experimental approach: Effects of GB9 or GB10 on the expression of inducible nitric oxide synthase (iNOS), and cyclooxygenase‐2 (COX‐2) in interferon‐γ (IFN‐γ)‐stimulated mouse microglial BV2 cells were measured by Western blot. Thein vivoeffects of these compounds were examined in the chronic constriction injury (CCI) rat model of neuropathic pain, measuring thermal hyperalgesia, and microglial activation and COX‐2 protein in lumbar spinal cord, by immunohistochemistry.Key results: In BV2 cells, GB9 and GB10 inhibited the expression of iNOS and COX‐2, stimulated by IFN‐γ. Intrathecal administration of GB9 and GB10 inhibited CCI‐induced nociceptive sensitization and thermal hyperalgesia in a dose‐dependent manner. Intraperitoneal injection of GB9 inhibited CCI‐induced thermal hyperalgesia and also inhibited CCI‐induced activation of microglial cells and up‐regulation of COX‐2 in the dorsal horn of the lumbar spinal cord ipsilateral to the injury.Conclusion and implications: Taken together, these data indicate that the marine‐derived capnellenes, GB9 and GB10, had anti‐neuroinflammatory and anti‐nociceptive properties in IFN‐γ‐stimulated microglial cells and in neuropathic rats respectively. Therefore, capnellene may serve as a useful lead compound in the search for new therapeutic agents for treatment of neuroinflammatory diseases.

Targeting protein–protein interactions (PPIs) offers tantalizing opportunities for therapeutic intervention for the treatment of human diseases. Modulating PPI interfaces with organic small molecules has been found to be exceptionally challenging, and few candidates have been successfully developed into clinical drugs. Meanwhile, the striking array of distinctive properties exhibited by metal compounds renders them attractive scaffolds for the development of bioactive leads. Here, we report the identification of iridium(III) compounds as inhibitors of the H-Ras/Raf-1 PPI. The lead iridium(III) compound 1 exhibited potent inhibitory activity against the H-Ras/Raf-1 interaction and its signaling pathway in vitro and in vivo, and also directly engaged both H-Ras and Raf-1-RBD in cell lysates. Moreover, 1 repressed tumor growth in a mouse renal xenograft tumor model. Intriguingly, the Δ-enantiomer of 1 showed superior potency in the biological assays compared to Λ-1 or racemic 1. These compounds could potentially be used as starting scaffolds for the development of more potent Ras/Raf PPI inhibitors for the treatment of kidney cancer or other proliferative diseases.

Parkinson's disease (PD) is a neurodegenerative disease that is characterized by the progressive loss of dopaminergic (DA) neurons in the substantia nigra. However, current treatments for PD are mainly palliative. Recently, researchers discovered that neurotoxins can induce Parkinsonian-like symptoms in zebrafish. No study to date has investigated the characteristics of PD, such as neuroinflammation factors, oxidative stress, or ubiquitin dysfunction, in this model. Therefore, the current study was aimed at utilizing commonly used clinical drugs, minocycline, vitamin E, and Sinemet, to test the usefulness of this model. Previous studies had indicated that DA cell loss was greater with 6-hydroxydopamine (6-OHDA) than with other neurotoxins. Thus, we first challenged zebrafish with 6-OHDA immersion and found a significant reduction in zebrafish locomotor activity; we then reversed the locomotor disruptions by treatment with vitamin E, Sinemet, or minocycline. The present study also analyzed the mRNA expression of parkin, pink1, and cd-11b, because the expression of these molecular targets has been shown to result in attenuation in mammalian models of PD. Vitamin E, Sinemet, and minocycline significantly reversed 6-OHDA-induced changes of parkin, pink1, and cd-11b mRNA expression in zebrafish. Moreover, we assessed tyrosine hydroxylase (TH) expression to confirm the therapeutic effects of vitamin E tested on this PD model and established that vitamin E reversed the 6-OHDA-induced damage on TH expression. Our results provide some support for the validity of this in vivo Parkinson's model, and we hope that this model will be more widely used in the future.