Targeting neuroinflammation: The therapeutic potential of ω-3 PUFAs in substance abuse.

Substance abuse is a chronic relapsing disorder that results in serious health and socioeconomic issues worldwide. Addictive drugs induce long-lasting morphologic and functional changes in brain circuits and account for the formation of compulsive drug-seeking and drug-taking behaviors. Yet, there remains a lack of reliable therapy. In recent years, accumulating evidence indicated that neuroinflammation was implicated in the development of drug addiction. Findings from both our and other laboratories suggest that ω-3 polyunsaturated fatty acids (PUFAs) are effective in treating neuroinflammation-related mental diseases, and indicate that they could exert positive effects in treating drug addiction. Thus, in the present review, we summarized and evaluated recently published articles reporting the neuroinflammation mechanism in drug addiction and the immune regulatory ability of ω-3 PUFAs. We also sought to identify some of the challenges ahead in the translation of ω-3 PUFAs into addiction treatment.

Curcumin: From a controversial "panacea" to effective antineoplastic products.

BACKGROUND: Curcumin, a controversial "panacea," has been broadly studied. Its bioactivities including antioxidant, anti-inflammatory, and especially antineoplastic activities have been documented. However, due to its extensive bioactivities, some scientists hold a skeptical point of view toward curcumin and described curcumin as a "deceiver" to chemists. The objective of this study was to explore curcumin's another possibility as a potential supplementary leading compound to cancer treatments. METHODS: Literature searches were conducted using electronic databases. Search terms such as "curcumin," "curcumin analogues," and so on were used. The literatures were collected and summarized. In this article, reported targets of curcumin are reviewed. The limitations of a curcumin as a therapeutic anticancer product including low bioavailability and poor targeting are mentioned. Furthermore, modified curcumin analogues and antitumor mechanisms are listed and discussed in the aspects of cell death and tumor microenvironment including angiogenesis, tissue hypoxia status, and energy metabolism. RESULTS: Several possible modification strategies were presented by analyzing the relationships between the antitumor activity of curcumin analogues and their structural characteristics, including the introduction of hydrophilic group, shortening of redundant hydrocarbon chain, the introduction of extra chemical group, and so on. CONCLUSIONS: From our perspective, after structural modification curcumin could be more effective complementary product for cancer therapies by the enhancement of targeting abilities and the improvement of bioavailability.

Onychin inhibits proliferation of vascular smooth muscle cells by regulating cell cycle.

AIM: To investigate the effects of onychin on the proliferation of cultured rat artery vascular smooth muscle cells (VSMCs) in the presence of 10% new-born calf serum (NCS). METHODS: Rat VSMCs were incubated with onychin 150 micromol/L or genistein 10 micromol/L in the presence of 10% NCS for 24 h. The proliferation of VSMCs was measured by cell counting and MTS/PMS colorimetric assays. Cell cycle progression was evaluated by flow cytometry. Retinoblastoma (Rb) phosphorylation, and expression of cyclin D1 and cyclin E were measured by Western blot assays. The tyrosine phosphorylation of ERK1/2 was examined by immunoprecipitation techniques using anti-phospho-tyrosine antibodies. RESULTS: The proliferation of VSMCs was accelerated significantly in the presence of 10% NCS. Onychin reduced the metabolic rate of MTS and the cell number of VSMCs in the presence of 10% NCS in a dose-dependent manner. Flow cytometry analysis revealed that the G1-phase fraction ratio in the onychin group was higher than that in the 10% NCS group (85.2% vs 70.0%, P<0.01), while the S-phase fraction ratio in the onychin group was lower than that in 10% NCS group (4.3% vs 16.4%, P<0.01). Western blot analysis showed that onychin inhibited Rb phosphorylation and reduced the expression of cyclin D1 and cyclin E. The effects of onychin on proliferation, the cell cycle and the expression of cyclins in VSMCs were similar to those of genistein, an inhibitor of tyrosine kinase. Furthermore immunoprecipitation studies showed that both onychin and genistein markedly inhibited the tyrosine phosphorylation of ERK1/2 induced by 10% NCS. CONCLUSION: Onychin inhibits the proliferation of VSMCs through G1 phase cell cycle arrest by decreasing the tyrosine phosphorylation of ERK1/2, and the expression of cyclin D1 and cyclin E, and sequentially inhibiting Rb phosphorylation.