Flavonoids, a class of polyphenol secondary metabolites, are presented broadly in plants and diets. They are believed to have various bioactive effects including anti-viral, anti-inflammatory, cardioprotective, anti-diabetic, anti-cancer, anti-aging, etc. Their basic structures consist of C6-C3-C6 rings with different substitution patterns to produce a series of subclass compounds, and correlations between chemical structures and bioactivities have been studied before. Given their poor bioavailability, however, information about associations between structure and biological fate is limited and urgently needed. This review therefore attempts to bring some order into relationships between structure, activity as well as pharmacokinetics of bioactive flavonoids.

Alzheimer's disease (AD) is a progressive brain disease, for which there is no effective drug therapy at present. Ginsenoside Rg1 (G-Rg1) and G-Rg2 have been reported to alleviate memory deterioration. However, the mechanism of their anti-AD effect has not yet been clearly elucidated. Ultra performance liquid chromatography tandem MS (UPLC/MS)-based metabolomics was used to identify metabolites that are differentially expressed in the brains of AD mice with or without ginsenoside treatment. The cognitive function of mice and pathological changes in the brain were also assessed using the Morris water maze (MWM) and immunohistochemistry, respectively. The impaired cognitive function and increased hippocampal Aβ deposition in AD mice were ameliorated by G-Rg1 and G-Rg2. In addition, a total of 11 potential biomarkers that are associated with the metabolism of lysophosphatidylcholines (LPCs), hypoxanthine, and sphingolipids were identified in the brains of AD mice and their levels were partly restored after treatment with G-Rg1 and G-Rg2. G-Rg1 and G-Rg2 treatment influenced the levels of hypoxanthine, dihydrosphingosine, hexadecasphinganine, LPC C 16:0, and LPC C 18:0 in AD mice. Additionally, G-Rg1 treatment also influenced the levels of phytosphingosine, LPC C 13:0, LPC C 15:0, LPC C 18:1, and LPC C 18:3 in AD mice. These results indicate that the improvements in cognitive function and morphological changes produced by G-Rg1 and G-Rg2 treatment are caused by regulation of related brain metabolic pathways. This will extend our understanding of the mechanisms involved in the effects of G-Rg1 and G-Rg2 on AD.

Chronic high doses of morphine inhibit the growth of various human cancer cell lines. However, the mechanisms by which such high‐dose morphine inhibits cell proliferation and induces cell death are not fully understood. Here we show that c‐Jun N‐terminal kinase (JNK) plays a pivotal role in high‐dose morphine‐induced apoptosis of SH‐SY5Y cells in a mitochondria‐dependent manner. Activation of JNK by morphine led to reactive oxygen species (ROS) generation via the mitochondrial permeability transition pore, because the mPTP inhibitor cyclosporin A significantly inhibited ROS generation. ROS in turn exerted feedback regulation on JNK activation, as shown by the observations that cyclosporin A and the antioxidant N‐acetylcysteine significantly inhibited the phosphorylation of JNK induced by morphine. ROS‐amplified JNK induced cytochrome c release and caspase‐9/3 activation through enhancement of expression of the proapoptotic protein Bim and reduction of expression of the antiapoptotic protein Bcl‐2. All of these effects of morphine could be suppressed by the JNK inhibitor SP600125 and N‐acetylcysteine. The key role of the JNK pathway in morphine‐induced apoptosis was further confirmed by the observation that decreased levels of JNK in cells transfected with specific small interfering RNA resulted in resistance to the proapoptotic effect of morphine. Thus, the present study clearly shows that morphine‐induced apoptosis in SH‐SY5Y cells involves JNK‐dependent activation of the mitochondrial death pathway, and that ROS signaling exerts positive feedback regulation of JNK activity.