2015 Vol. 13, No. 1

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Network pharmacology:A new approach to unveiling Traditional Chinese Medicine
WU Xiao-Ming, WU Chun-Fu
2015, 13(1): 1-2.
Traditional Chinese medicine (TCM) has thousandsyears of history in using herbal formulae (Fang-Ji in Chinese) that consist of many medicinal herbs for holistic treatment of various disorders. Due to the complex nature rooted in both medicinal herbs and human body, the mechanisms of actions for most TCMs remain unclear, especially for those clinically effective herbal formulae. With the advent of the big data era in the biomedical and biopharmaceutical research and development, network pharmacology is coming as a systematic approach to shifting the current one target, one drug paradigm in drug discovery and development. The network pharmacology approach is capable of describing complex interactions among biological systems, drugs, and diseases from a network perspective, sharing a similar holistic thinking of TCM.
“Omics” in pharmaceutical research:overview, applications, challenges, and future perspectives
YAN Shi-Kai, LIU Run-Hui, JIN Hui-Zi, LIU Xin-Ru, YE Ji, SHAN Lei, ZHANG Wei-Dong
2015, 13(1): 3-21.
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.
Wheat peptides reduce oxidative stress and inhibit NO production through modulating μ-opioid receptor in a rat NSAID-induced stomach damage model
YIN Hong, CAI Hui-Zhen, WANG Shao-Kang, YANG Li-Gang, SUN Gui-Ju
2015, 13(1): 22-29.
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 iNOS activity in stomach. The mRNA expression level of -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.
In silico target fishing for the potential bioactive components contained in Huanglian Jiedu Tang (HLJDD) and elucidating molecular mechanisms for the treatment of sepsis
MA Shi-Tang, FENG Cheng-Tao, DAI Guo-Liang, SONG Yue, ZHOU Guo-Liang, ZHANG Xiao-Lin, MIAO Cheng-Gui, YU Hao, JU Wen-Zheng
2015, 13(1): 30-40.
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 TXA2R 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.
Proteomic and bioinformatic analyses of possible targetrelated proteins of gambogic acid in human breast carcinoma MDA-MB-231 cells
LI Dong, SONG Xiao-Yi, Yue Qing-Xi, CUI Ya-Jun, LIU Miao, FENG Li-Xing, WU Wan-Ying, JIANG Bao-Hong, YANG Min, QU Xiao-Bo, LIU Xuan, GUO De-An
2015, 13(1): 41-51.
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 electrophoresis (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 proteins 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
YAO Xin, CHEN Nan, MA Chun-Hua, TAO Jing, BAO Jian-An, CHENG Zong-Qi, CHEN Zu-Tao, MIAO Li-Yan
2015, 13(1): 52-58.
In the present study, we analyzed the role of Ginkgo biloba extract in lipopolysaccharide(LPS)-induced acute lung injury (ALI). ALI was induced in mice by intratracheal instillation of LPS. G. biloba extract (12 and 24 mgkg-1) and dexamethasone (2 mgkg-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 myeloperoxidase (MPO) activities were assayed by SOD and MPO kits, respectively. The levels of inflammatory mediators, tumor necrosis factor-, interleukin-1, and interleukin-6, were assayed by enzyme-linked immunosorbent assay. Pathological changes of lung tissues were observed by HE staining. The levels of NF-B 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 mgkg-1 markedly attenuated the inflammatory cell numbers in the BALF, decreased NF-B 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-B p65 and COX-2 activation.
Absolute configuration of podophyllotoxone and its inhibitory activity against human prostate cancer cells
LI Juan, FENG Juan, LUO Cheng, Herman Ho-Yung Sung, JIANG Ren-Wang
2015, 13(1): 59-64.
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 molL-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.
A new ursane-type triterpenoid saponin from the aerial parts of Clematoclethra scandens subsp. actinidioides
XIAO Shi-Ji, CHEN Fang, DING Li-Sheng, ZHOU Yan
2015, 13(1): 65-68.
A new ursane-type triterpenoid saponin, 2,3,24-trihydroxyurs-12,20(30)-dien-28-oic acid -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
LU Chun-Hua, YE Fang-Wen, SHEN Yue-Mao
2015, 13(1): 69-72.
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 including1D- and 2D-NMR and X-ray single crystal diffraction. Compounds 1-3 showed antibacterial activity against Mycobacterium smegmatis.
Cause and control of Radix Ophiopogonis browning during storage
WANG Hui, QI Jin, HAN Dong-Qi, XU Tian, LIU Ji-Hua, QIN Min-Jian, ZHU Dan-Ni, YU Bo-Yang
2015, 13(1): 73-80.
In the storage of Radix Ophiopogonis, browning often happens to cause potential risk with regard to safety. Previously few reports investigate the browning of Radix Ophiopogonis. In this research, the causes and mechanisms of the browning of Radix Ophiopogonis were preliminarily elucidated. Content determination by high-performance liquid chromatography (HPLC) and spectrophotometry, enzyme activity determination by colorimetry, and morphological observation by electron microscopy were performed in the present study. Uniform design and three-dimensional response surfaces were applied to investigate the relationship between browning and storage factors. The cortex cell wall of browned Radix Ophiopogonis was ruptured. Compared with the normal Radix Ophiopogonis, cellulase and polyphenol oxidase enzymes were activated, the levels of 5-hydroxymethylfurfural (5-HMF), total sugars, and reducing sugars were increased, while the levels of polysaccharides and methylophiopogonanone A were decreased in browned Radix Ophiopogonis. The relationship between the storage factors and degree of browning (Y) could be described by following correlation equation:Y=-0.6254+0.02084X3+0.001514X1X2-0.0009644X2X3. Accompanied with browning under storage conditions, the chemical composition of Radix Ophiopogonis was altered. Following the activation of cellulase, the rupture of the cortex cell wall and the outflow of cell substances flowed out, which caused the Radix Ophiopogonis tissue to become soft and sticky. The main causes of the browning were the production of 5-HMF, the activation of polyphenol oxidase, Maillard reactions and enzymatic browning. Browning could be effectively prevented when the air relative humidity (HR), temperature, and moisture content were under 25% RH, 12℃ and 18%, respectively.