2015 Vol. 13, No. 5

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Ethnopharmacology, phytochemistry, and biological activities of Cymbopogon citratus (DC.) Stapf extracts
Christopher E Ekpenyong, Ernest Akpan, Azah Nyoh
2015, 13(5): 321-337.
Cymbopogon citratus is a widely distributed perennial herb belonging to the Poaceae family and has been extensively consumed for its medicinal, cosmetic, and nutritional effects for centuries. A large number of reports have been published describing the pharmacological, biological, and therapeutic actions of this herb. In this review, we summarized the literatures on related studies (up to January, 2014) that highlighted the pharmacologic and biological effects of the major phytochemicals isolated from C. citratus extracts and its essential oil. The components of the essential oils found in C. citratus have a similar pharmacokinetic properties, including absorption, distribution, metabolism, and excretion. They are quickly absorbed following oral, pulmonary, and dermal administration. Based on the published reports, it can also be inferred that, after absorption from the small intestine, some phytochemicals in C. citratus can undergo oxidation, glucuronidation, sulfation, and/or O-methylation. Excretion is through urine, feces and/or expired volatiles. The biotransformation reactions of C. citratus bioactive constituents are essential for its relatively safe consumption and therapeutic applications. The data available so far warrant further studies evaluating C. citratus pharmacokinetics. Reliable pharmacokinetic data in humans would be critical for a better understanding of the the systemic handling of C. citratus.
Enhancing ergosterol production in Pichia pastoris GS115 by overexpressing squalene synthase gene from Glycyrrhiza uralensis
LIU Ying, ZHU Xiao-Qing, LI Wen-Dong, WEN Hao, LIU Chun-Sheng
2015, 13(5): 338-345.
The present study was designed to determine the effects of copy number variations (CNVs) of squalene synthase 1(SQS1) gene on the mevalonate (MVA) pathway. SQS1 gene from G. uralensis (GuSQS1) was cloned and over-expressed in Pichia pastoris GS115. Six recombinant P. pastoris strains containing different copy number of GuSQS1 were constructed. HPLC was used to assay the level of ergosterol in all transgenic P. pastoris strains containing GuSQS1. HPLC analysis showed that the contents of ergosterol in all of the transgenic P. pastoris containing GuSQS1 were higher than that in the negative control. And with the increase of copy number of GuSQS1, the content of ergosterol showed an increasing-decreasing-increasing pattern. The contents of ergosterol in 10-copy-GuSQS1 P. pastoris and 47-copy-GuSQS1 P. pastoris were significantly higher than that in the rest recombinant P. pastoris strains. In conclusion, the CNVs of GuSQS1 influence the content of secondary metabolites in the MVA pathway. The present study provides a basis for over-expressing GuSQS1 and increasing the content of glycyrrhizin in G. uralensis cultivars.
Inhibition of HMG-CoA reductase by MFS, a purified extract from the fermentation of marine fungus Fusarium solani FG319, and optimization of MFS production using response surface methodology
ZHOU Yu, WU Wen-Hui, ZHAO Qing-Bo, WANG Xiao-Yu, BAO Bin
2015, 13(5): 346-354.
The present study was designed to isolate and characterize a purified extract from Fusarium solani FG319, termed MFS (Metabolite of Fusarium solani FG319) that showed anti-atherosclerosis activity by inhibiting 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase. Response surface methodology (RSM) was employed to achieve an improved yield from the fermentation medium. The inhibiting effect of the isolate, MFS, on HMG-CoA reductase was greater than that of the positive control, lovastatin. The average recovery of MFS and the relative standard deviation (RSD) ranged between 99.75% to 101.18%, and 0.31% to 0.74%, respectively. The RSDs intra- and inter-assay of the three samples ranged from 0.288% to 2.438%, and from 0.934% to 2.383%, respectively. From the RSM, the concentration of inducer, cultivation time, and culture temperatures had significant effects on the MFS production, with the effect of inducer concentration being more pronounced that other factors. In conclusion, the optimal conditions for the MFS production were achieved using RSM and that MFS could be explored as an anti-atherosclerosis agent based on its ability to inhibit HMG-CoA reductase.
The polysaccharide isolated from Pleurotus nebrodensis (PN-S) shows immune-stimulating activity in RAW264.7 macrophages
CUI Hai-Yan, WANG Chang-Lu, WANG Yu-Rong, LI Zhen-Jing, ZHANG Ya-Nan
2015, 13(5): 355-360.
A novel Pleurotus nebrodensis polysaccharide (PN-S) was purified andcharacterized, and its immune-stimulating activity was evaluated in RAW264.7 macrophages. PN-S induced the proliferation of RAW264.7 cells in a dose-dependent manner, as determined by the MTT assay. After exposure to PN-S, the phagocytosis of the macrophages was significantly improved, with remarkable changes in morphology being observed. Flow cytometric analysis demonstrated that PN-S promoted RAW264.7 cells to progress through S and G2/M phases. PN-S treatment enhanced the productions of interleukin-6 (IL-6), nitric oxide (NO), interferon gamma (INF-), and tumor necrosis factor- (TNF-) in the macrophages, with up-regulation of mRNA expressions of interleukin-6 (IL-6), inducible nitric oxide synthase (iNOS), interferon gamma(INF-) and tumor necrosis factor- (TNF-) being observed in a dose-dependent manner, as measured by qRT-PCR. In conclusion, these results suggest that the purified PN-S can improve immunity by activating macrophages.
Antiarrhythmic ionic mechanism of Guanfu base A-Selective inhibition of late sodium current in isolated ventricular myocytes from guinea pigs
JIN Si-Si, GUO Qiao, XU Jing, YU Peng, LIU Jing-Han, TANG Yi-Qun
2015, 13(5): 361-367.
The present study was designed to determine the effects of Guanfu base A (GFA) on the late sodium current (INa.L), transient sodium current (INa.T), HERG current (IHERG), and Kv1.5 current (IKv1.5).The values of INa.L, INa.T, IHERG and IKv1.5 were recorded using the whole-cell patch clamp technique. Compared with other channels, GFA showed selective blocking activity in late sodium channel. It inhibited INa.L in a concentration-dependent manner with an IC50 of (1.570.14) molL-1, which was significantly lower than its IC50 values of (21.174.51) molL-1 for the INa.T. The inhibitory effect of GFA on INa,L was not affected by 200 molL-1 H2O2. It inhibited IHERG with an IC50 of (27334) molL-1 and has slight blocking effect on IKv1.5, decreasing IKv1.5 by only 20.6% at 200 molL-1. In summary,GFA inhibited INa.L selectively and remained similar inhibition in presence of reactive oxygen species.. These findings may suggest a novel molecular mechanism for the potential clinical application of GFA in the treatment of cardiovascular disorders.
Anti-asthmatic effects of oxymatrine in a mouse model of allergic asthma through regulating CD40 signaling
ZHANG Tian-Zhu, FU Qiang, CHEN Tong, MA Shi-Ping
2015, 13(5): 368-374.
The aim of the study was to investigate the anti-asthmatic effects of oxymatrine (OXY) and the possible underlying mechanisms. The mouse asthma model was established by ovalbumin (OVA) intraperitoneal injection. A total of fifty mice were randomly assigned to five groups:control, OVA, OVA+dexamethasone (Dex, 2 mgkg-1), and OVA+OXY (40 mgkg-1), and OVA+OXY (80 mgkg-1), respectively. Histological studies were conducted by the hematoxylin and eosin (HE) staining, the levels of interleukin-4 (IL-4), interleukin-5 (IL-5), interleukin-13, and IgE were evaluated by enzyme-linked immunosorbent assay (ELISA), and the protein level of CD40 was analyzed by Western blotting. OXY inhibited OVA-induced increases in eosinophil count; the levels of IL-4, IL-5, IgE, and IL-13 were recovered. It also substantially inhibited OVA-induced eosinophilia in lung tissues and the expression of CD40 protein. These findings suggest that OXY may effectively ameliorate the progression of asthma and could be explored as a possible therapy for patients with allergic asthma.
Synthesis and cytotoxic activities of E-resveratrol derivatives
HONG Ting, JIANG Wei, DONG Huai-Ming, QIU Sheng-Xiang, LU Yu
2015, 13(5): 375-382.
The present study was designed to synthesize derivatives of E-resveratrol and evaluate their cytotoxic activity in vitro. Different functional groups were conjugated with the phenolic hydroxyl group of E-resveratrol, and the double bond of E-resveratrol was reduced. The in vitro cytotoxicity of the synthetic derivatives was evaluated against three tumor cell lines (A549, LAC, and HeLa) using the MTT assay. Twenty-six E-resveratrol derivatives were synthesized and their structures were confirmed by 1H NMR, MS, IR, and elemental analyses. Compounds 1-6, 12, 15-21, and 23-26 were reported for the first time. Among them, Compounds 1, 2, 4, 5, and 9-11, showed significant cytotoxicity against tumor cells; especially, Compound 1 showed an IC50 value of 4.38 molL-1 in the A549 cells which was 15-fold more active than E-resveratrol; Compound 9 showed an IC50 value of 1.41 molL-1 in the HeLa cell line which was 90-fold more active than E-resveratrol, and close to adriamycin. The structure-activity relationships were also investigated. Compounds 1, 2 and 9-11 may serve as potential lead compounds for the discovery of new anticancer drugs.
Six new cytotoxic and anti-inflammatory 11, 20-epoxy-ent-kaurane diterpenoids from Isodon wikstroemioides
WU Hai-Yan, WANG Wei-Guang, DU Xue, YANG Jin, PU Jian-Xin, SUN Han-Dong
2015, 13(5): 383-389.
The present study was designed to determine the chemical constituents of EtOAc extracts of the aerial parts of Isodon wikstroemioides. Compounds 1-8 were isolated and purified by normal-phase silica gel and reversed-phase C18 silica gel column chromatography and HPLC. Their structures were elucidated by extensive spectroscopic methods. Most of them were evaluated for their in vitro cytotoxicity against human cancer HL-60, SMMC-7721, A-549, MCF-7, and SW-480 cells and their inhibitory activity against nitric oxide (NO) production in LPS-activated RAW264.7 macrophages. Among the eight 11, 20-epoxy-ent-kauranoids isolated, compounds 1-6 (isowikstroemins H-M) were new diterpenoids. Compounds 1, 3, and 7 exhibited significant cytotoxicity with IC50 values ranging from (0.840.02) to (4.090.34) molL-1, while compounds 4 and 5 showed selective cytotoxicity. In addition, compounds 1, 3, 4, and 7 exhibited inhibitory activity against nitric oxide (NO) production in LPS-activated RAW264.7 macrophages. These results provide a basis for future development of these compounds as anti-cancer and anti-inflammatory agents.
Diagnostic ion filtering strategy for chemical characterization of Guge Fengtong Tablet with high-performance liquid chromatography coupled with electrospray ionization quadrupole time-offlight tandem mass spectrometry
ZENG Su-Ling, LIU Xin-Guang, LAI Chang-Jiang-Sheng, LIU E-Hu, LI Ping
2015, 13(5): 390-400.
The present study was designed to characterize the chemical constituents of Guge Fengtong Tablet (GGFTT). Based on the chromatographic retention behavior, fragmentation pathways of chemical components and the published literatures, a diagnostic ion filtering strategy with electrospray ionization quadrupole time-of-flight tandem mass spectrometry (HPLC-ESI-Q-TOF/MS) was established to identify the multiple bioactive constituents of GGFTT. The rapid identification of forty-seven components, including 18 phenolic acids, 8 saponins, 14 gingerol-related compounds, and 7 diarylhepatonoids, was accomplished using this newly developed method.The coupling of HPLC-ESI-Q-TOF/MS with the diagnostic ion filtering strategy was useful and efficient for the in-depth structural elucidation of chemical compounds of GGFTT.