Rui Pan

Microbial secondary metabolites (MSMs) have played and continue to play a highly significant role in the drug discovery and development process. Genetically, MSM chemical structures are biologically synthesized by microbial gene clusters. Recently, however, the speed of new bioactive MSM discovery has been slowing down due to consistent employment of conventional cultivation and isolation procedure. In order to alleviate this challenge, a number of new approaches have been developed. The strategy of one strain many compounds (OSMAC) has been shown as a simple and powerful tool that can activate many silent biogenetic gene clusters in microorganisms to make more natural products. This review highlights important and successful examples using OSMAC approaches, which covers changing medium composition and cultivation status, co-cultivation with other strain(s), adding enzyme inhibitor(s) and MSM biosynthetic precursor(s). Available evidences had shown that variation of cultivation condition is the most effective way to produce more MSMs and facilitate the discovery of new therapeutic agents.

Background Increasing evidence suggests that many neurons may die through apoptosis in Alzheimer's disease (AD). Mitochondrial dysfunction has been implicated in this process of neuronal cell death. One promising approach for preventing AD is based upon anti-apoptosis to decrease death of nerve cells. In this study, we observed the memory improving properties of curcumin in mice and investigated the neuroprotective effect of curcumin in vitro and in vivo. Methods The mice were given AlCl3 orally and injections of D-galactose intraperitoneally for 90 days to establish the AD animal model. From day 45, the curcumin group was treated with curcumin for 45 days. Subsequently, the step-through test, neuropathological changes in the hippocampus and the expression of Bax and Bcl-2 were carried out to evaluate the effect of curcumin on the AD model mice. In cultured PC12 cells, AlCl3 exposure induced apoptosis. The MTT assay was used to measure cell viabilities; flow cytometric analysis to survey the rate of cell apoptosis; DNA-binding fluorochrome Hoechst 33258 to observe nuclei changes in apoptotic cells and Western blot analysis of Bax, Bcl-2 to investigate the mechanisms by which curcumin protects cells from toxicity. Results Curcumin significantly improved the memory ability of AD mice in the step-through test, as indicated by the reduced number of step-through errors (P <0.05) and prolonged step-through latency (P <0.05). Curcumin also attenuated the neuropathological changes in the hippocampus and inhibited apoptosis accompanied by an increase in Bcl-2 level (P <0.05), but the activity of Bax did not change (P >0.05). AlCl3 significantly reduced the viability of PC12 cells (P <0.01). Curcumin increased cell viability in the presence of AlCl3 (P <0.01). The rate of apoptosis decreased significantly in the curcumin group (P <0.05) when measured by flow cytometric analysis. Curcumin protected cells by increasing Bcl-2 level (P <0.05), but the level of Bax did not change (P >0.05). Conclusions This study demonstrates that curcumin improves the memory ability of AD mice and inhibits apoptosis in cultured PC12 cells induced by AlCl3. Its mechanism may involve enhancing the level of Bcl-2.

Longan (Dimocarpus longan Lour.) pericarp, the main by-product of aril and pulp processing, is abundant in phenolic compounds and worthy of further utilization. The present work firstly reported HPLC analysis and in vitro antioxidant evaluation of longan (cv. Shixia) pericarp-derived phenolics (LPPs), the purified longan pericarp extract (LPE), as well as their cytotoxic effect on lung cancer cell line, A549. The results indicated that the purified LPE had significant amounts of phenolics, with content of 57.8 ± 0.6 mg of gallic acid equivalents per gram of dry longan pericarp (mg GAE·g−1 DLP), which consisted of six phenolic compounds (A–F), including protocatechuic acid (A), isoscopoletin (B), quercetin (C), ellagic acid (D), corilagin (E), and proanthocyanidins C1 (F). Antioxidant assays showed that LPPs (10 μM) and LPE (1.0 mg·mL−1) had certain antioxidant activities, in which corilagin (E) possessed the best DPPH radical scavenging rate 71.8 ± 0.5% and •OH inhibition rate 75.9 ± 0.3%, and protocatechuic acid (A) exhibited the strongest Fe2+ chelating ability 36.4 ± 0.7%. In vitro cytotoxic tests suggested that LPPs had different effect on A549 cell line, in which corilagin (E) exhibited potent cytotoxicity with an IC50 value of 28.8 ± 1.2 μM. These findings were further confirmed by cell staining experiments.