基于分子指纹相似性的药物-药物网络

根据分子指纹相似性构建了FDA批准的小分子药物的药物-药物网络,结合药物ATC分类系统中定义的药物治疗功能信息,提出了一种基于网络的药物功能预测方法。预测了1 277个药物-治疗功能关系对,其中有59.44%得到了文献的证实;337个已知ATC分类的药物(占ATC药物的55.89%)的预测功能与已知功能相符;那些尚未有文献支持的药物-治疗功能关系对,很可能暗示了药物潜在的新功能。

Proteomic and bioinformatic analyses of possible targetrelated proteins of gambogic acid in human breast carcinoma MDA-MB-231 cells

Gambogic acid （GA） is an anticancer agent in phase IIb clinical trial in China but its mechanism of action has not been fully clarified. The present study was designed to search the possible target-related proteins of GA in cancer cells using proteomic method and establish possible network using bioinformatic analysis. Cytotoxicity and anti-migration effects of GA in MDA-MB-231 cells were checked using MTT assay, flow cytometry, wound migration assay, and chamber migration assay. Possible target-related proteins of GA at early （3 h） and late stage （24 h） of treatment were searched using a proteomic technology, two-dimensional electro- phoresis （2-DE）. The possible network of GA was established using bioinformatic analysis. The intracellular expression levels of vimentin, keratin 18, and calumenin were determined using Western blotting. GA inhibited cell proliferation and induced cell cycle arrest at G2/M phase and apoptosis in MDA-MB-231 cells. Additionally, GA exhibited anti-migration effects at non-toxic doses. In 2-DE analysis, totally 23 possible GA targeted proteins were found, including those with functions in cytoskeleton and transport, regulation of redox state, metabolism, ubiquitin-proteasome system, transcription and translation, protein transport and modification, and cytokine. Network analysis of these proteins suggested that cytoskeleton-related proteins might play important roles in the effects of GA. Results of Western blotting confirmed the cleavage of vimentin, increase in keratin 18, and decrease in calumenin levels in GA-treated cells. In summary, GA is a multi-target compound and its anti-cancer effects may be based on several target-related pro- teins such as cytoskeleton-related proteins.

Ginkgo biloba extracts attenuate lipopolysaccharide-induced inflammatory responses in acute lung injury by inhibiting the COX-2 and NF-κB pathways

In the present study, we analyzed the role of Ginkgo biloba extract in lipopolysaccharide（LPS）-induced acute lung injury （ALl）. ALI was induced in mice by intratracheal instillation of LPS. G. biloba extract （12 and 24 mg.kg^-1） and dexamethasone （2 mg.kg^-1）, as a positive control, were given by i.p. injection. The cells in the bronchoalveolar lavage fluid （BALF） were counted. The degree of animal lung edema was evaluated by measuring the wet/dry weight ratio. The superoxidase dismutase （SOD） and myelop- eroxidase （MPO） activities were assayed by SOD and MPO kits, respectively. The levels of inflammatory mediators, tumor necrosis factor-a, interleukin-1/3, and interleukin-6, were assayed by enzyme-linked immunosorbent assay. Pathological changes of lung tissues were observed by H＆E staining. The levels of NF-κB p65 and COX-2 expression were detected by Western blotting. Compared to the LPS group, the treatment with the G. biloba extract at 12 and 24 mg.kg ^-1 markedly attenuated the inflammatory cell numbers in the BALF, decreased NF-κB p65 and COX-2 expression, and improved SOD activity, and inhibited MPO activity. The histological changes of the lungs were also significantly improved. The results indicated that G biloba extract has a protective effect on LPS-induced acute lung injury in mice. The protective mechanism of G. biloba extract may be partly attributed to the inhibition of NF-κB p65 and COX-2 activation.

Wheat peptides reduce oxidative stress and inhibit NO production through modulating μ-opioid receptor in a rat NSAID-induced stomach damage model

Non-steroidal anti-inflammatory drugs(NSAIDs) induce tissue damage and oxidative stress in animal models of stomach damage. In the present study, the protective effects of wheat peptides were evaluated in a NSAID-induced stomach damage model in rats. Different doses of wheat peptides or distilled water were administered daily by gavage for 30 days before the rat stomach damage model was established by administration of NSAIDs(aspirin and indomethacin) into the digestive tract twice. The treatment of wheat peptides decreased the NSAID-induced gastric epithelial cell degeneration and oxidative stress and NO levels in the rats. Wheat peptides significantly increased the superoxide dismutase(SOD) and glutathione peroxidase(GPx) activities and decreased i NOS activity in stomach. The m RNA expression level of μ-opioid receptor was significantly decreased in wheat peptides-treated rats than that in in the control rats. The results suggest that NSAID drugs induced stomach damage in rats, wchih can be prevented by wheat peptides. The mechanisms for the protective effects were most likely through reducing NSAID-induced oxidative stress.

A new ursane-type triterpenoid saponin from the aerial parts of Clematoclethra scandens subsp. actinidioides

A new ursane-type triterpenoid saponin, 2a,3a,24-trihydroxyurs-12,20（30）-dien-28-oic acid fl-D-glucopyranosyl ester （1）, together with six known triterpenoid saponins, was isolated and characterized from the aerial parts of Clematoclethra scandens subsp. actinidioides.

Siderochelins with anti-mycobacterial activity from Amycolatopsis sp. LZ149

Three new compounds, namely siderochelins D （2）, E （3）, and F （4）, together with one known siderochelin A （1）, were isolated from Amycolatopsis sp. LZ149 and elucidated by spectroscopic analyses includinglD- and 2D-NMR and X-ray single crystal diffraction. Compounds 1-3 showed antibacterial activity against Mycobacterium smegmatis.

“Omics” in pharmaceutical research: overview, applications, challenges, and future perspectives

In the post-genomic era, biological studies are characterized by the rapid development and wide application of a series of "omics" technologies, including genomics, proteomics, metabolomics, transcriptomics, lipidomics, cytomics, metallomics, ionomics, interactomics, and phenomics. These "omics" are often based on global analyses of biological samples using high through-put analytical approaches and bioinformatics and may provide new insights into biological phenomena. In this paper, the development and advances in these omics made in the past decades are reviewed, especially genomics, transcriptomics, proteomics and metabolomics; the applications of omics technologies in pharmaceutical research are then summarized in the fields of drug target discovery, toxicity evaluation, personalized medicine, and traditional Chinese medicine; and finally, the limitations of omics are discussed, along with the future challenges associated with the multi-omics data processing, dynamics omics analysis, and analytical approaches, as well as amenable solutions and future prospects.

In silico target fishing for the potential bioactive components contained in Huanglian Jiedu Tang(HLJDD) and elucidating molecular mechanisms for the treatment of sepsis

The present study was designed to target fish for potential bioactive components contained in a Huang Lian Jie Du decoction(HLJDD) and identify the underlying mechanisms of action for the treatment of sepsis at the molecular level. he bioactive components database of HLJDD was constructed and the sepsis-associated targets were comprehensively investigated. The 3D structures of the PAFR and TXA2 R proteins were established using the homology modelling(HM) method, and the molecular effects for sepsis treatment were analysed by comparing the bioactive components database and the sepsis targets using computational biology methods. The results of the screening were validated with biological testing against the human oral epidermal carcinoma cell line KB in vitro. We found that multiple bioactive compounds contained in the HLJDD interacted with multiple targets. We also predicted the promising compound leads for sepsis treatment, and the first 28 compounds were characterized. Several compounds, such as berberine, berberrubine and epiberberine, dose-dependently inhibited PGE2 production in human KB cells, and the effects were similar in the presence or absence of TPA. This study demonstrates a novel approach to identifying natural chemical compounds as new leads for the treatment of sepsis.

Absolute configuration of podophyllotoxone and its inhibitory activity against human prostate cancer cells

Podophyllotoxone(1) was isolated from the roots of Dysosma versipellis. The structure was determined by spectroscopic analysis in combination with single-crystal X-ray analysis. The absolute configuration of compound 1 was assigned based on the Flack parameter. It showed significant inhibitory activities against human prostate cancer cells PC3 and DU145 with IC50 values being 14.7 and 20.6 μmol·L-1, respectively. It also arrested the cells at G2/M phase. Tubulin polymerization assay showed that it inhibited the tubulin polymerization in a dose-dependent manner, and molecular docking analysis revealed a different binding mode with tubulin as compared with those known tubulin inhibitors.