Τρίτη, 7 Μαΐου 2019

Natural Medicines

Quantification of Panax notoginseng saponins metabolites in rat plasma with in vivo gut microbiota-mediated biotransformation by HPLC-MS/MS

Publication date: March 2019

Source: Chinese Journal of Natural Medicines, Volume 17, Issue 3

Author(s): Yin-Ping GUO, Man-Yun CHEN, Li SHAO, Wei ZHANG, Tai RAO, Hong-Hao ZHOU, Wei-Hua HUANG

Abstract

Panax notoginseng saponins (PNS) are the major components of Panax notoginseng, with multiple pharmacological activities but poor oral bioavailability. PNS could be metabolized by gut microbiota in vitro, while the exact role of gut microbiota of PNS metabolism in vivo remains poorly understood. In this study, pseudo germ-free rat models were constructed by using broad-spectrum antibiotics to validate the gut microbiota-mediated transformation of PNS in vivo. Moreover, a high performance liquid chromatography-electrospray ionization tandem mass spectrometry (HPLC-ESI-MS/MS) was developed for quantitative analysis of four metabolites of PNS, including ginsenoside F1 (GF1), ginsenoside Rh2 (GRh2), ginsenoside compound K (GCK) and protopanaxatriol (PPT). The results showed that the four metabolites could be detected in the control rat plasma, while they could not be determined in pseudo germ-free rat plasma. The results implied that PNS could not be biotransformed effectively when gut microbiota was disrupted. In conclusion, gut microbiota plays an important role in biotransformation of PNS into metabolites in vivo.



Two new nimbolinin- and trichilin-class limonoids isolated from the fruits of Melia azedarach

Publication date: March 2019

Source: Chinese Journal of Natural Medicines, Volume 17, Issue 3

Author(s): Lu QIU, Li HENG, Rong XU, Jun LUO, Yi LI

Abstract

Two new furan fragment isomerized limonoids, meliazedalides A and B (compounds 1 and 2), were isolated from the fruits of Melia azedarach Linn.. Their chemical structures were elucidated on the basis of HR-ESI-MS and 1D and 2D NMR data, which belonged to nimbolinin- and trichilin-class, respectively. Compound 2 exhibited weak inhibitory effect on NO production in lipopolysaccharide (LPS)-activated RAW 264.7 macrophages with IC50 being 37.41 μmol·L−1.



Lower clearance of sodium tanshinone IIA sulfonate in coronary heart disease patients and the effect of total bilirubin: a population pharmacokinetics analysis

Publication date: March 2019

Source: Chinese Journal of Natural Medicines, Volume 17, Issue 3

Author(s): Wei-Wei QIN, Li WANG, Zheng JIAO, Bin WANG, Cheng-Yu WANG, Li-Xuan QIAN, Wei-Lin QI, Ming-Kang ZHONG

Abstract

This study developed a population pharmacokinetic model for sodium tanshinone IIA sulfonate (STS) in healthy volunteers and coronary heart disease (CHD) patients in order to identify significant covariates for the pharmacokinetics of STS. Blood samples were obtained by intense sampling approach from 10 healthy volunteers and sparse sampling from 25 CHD patients, and a population pharmacokinetic analysis was performed by nonlinear mixed-effect modeling. The final model was evaluated by bootstrap and visual predictive check. A total of 230 plasma concentrations were included, 137 from healthy volunteers and 93 from CHD patients. It was a two-compartment model with first-order elimination. The typical value of the apparent clearance (CL) of STS in CHD patients with total bilirubin (TBIL) level of 10 μmol(L−1 was 48.7 L(h−1 with inter individual variability of 27.4%, whereas that in healthy volunteers with the same TBIL level was 63.1 L(h−1. Residual variability was described by a proportional error model and estimated at 5.2%. The CL of STS in CHD patients was lower than that in healthy volunteers and decreased when TBIL levels increased. The bootstrap and visual predictive check confirmed the stability and validity of the final model. These results suggested that STS dosage adjustment might be considered based on TBIL levels in CHD patients.



Two natural molecules preferentially inhibit azole-resistant Candida albicans with MDR1 hyperactivation

Publication date: March 2019

Source: Chinese Journal of Natural Medicines, Volume 17, Issue 3

Author(s): Hong-Zhuo SHI, Wen-Qiang CHANG, Ming ZHANG, Hong-Xiang LOU

Abstract

Antifungal drug resistance is a significant clinical problem, and antifungal agents that can evade resistance are urgently needed. In infective niches, resistant organisms often co-existed with sensitive ones, or a subpopulation of antibiotic-susceptible organisms may evolve into resistant ones during antibiotic treatment and eventually dominate the whole population. In this study, we established a co-culture assay in which an azole-resistant Candida albicans strain was mixed with a susceptible strain labeled with green fluorescent protein to mimic in vivo conditions and screen for antifungal drugs. Fluconazole was used as a positive control to verify the validity of this co-culture assay. Five natural molecules exhibited antifungal activity against both susceptible and resistant C. albicans. Two of these compounds, retigeric acid B (RAB) and riccardin D (RD), preferentially inhibited C. albicans strains in which the efflux pump MDR1 was activated. This selectivity was attributed to greater intracellular accumulation of the drugs in the resistant strains. Changes in sterol and lipid compositions were observed in the resistant strains compared to the susceptible strain, and might increase cell permeability to RAB and RD. In addition, RAB and RD interfered with the sterol pathway, further aggregating the decrease in ergosterol in the sterol synthesis pathway in the MDR1-activated strains. Our findings here provide an alternative for combating resistant pathogenic fungi.



The Zuo Jin Wan Formula increases chemosensitivity of human primary gastric cancer cells by AKT mediated mitochondrial translocation of cofilin-1

Publication date: March 2019

Source: Chinese Journal of Natural Medicines, Volume 17, Issue 3

Author(s): Meng-Yao SUN, Dan-Dan WANG, Jian SUN, Xiao-Hua ZHAO, Si CAI, Qiu-Xue WU, Tao JIE, Zhen-Hua NI, Jian-Yue SUN, Qing-Feng TANG

Abstract

Resistance to cisplatin (DDP)-based chemotherapy is a major cause of treatment failure in human gastric cancer (GC). It is necessary to identify the drugs to re-sensitize GC cells to DDP. In our previous research, Zuo Jin Wan Formula (ZJW) has been proved could increase the mitochondrial apoptosis via cofilin-1 in a immortalized cell line, SGC-7901/DDP. Due to the immortalized cells may still difficult highly recapitulate the important molecular events in vivo, primary GC cells model derived from clinical patient was constructed in the present study to further evaluate the effect of ZJW and the underlying molecular mechanism. Immunofluorescent staining was used to indentify primary cultured human GC cells. Western blotting was carried out to detect the protein expression. Cell Counting Kit-8 (CCK-8) was used to evaluate cell proliferation. Flow cytometry analysis was performed to assess cell apoptosis. ZJW inhibited proliferation and induced apoptosis in primary DDP-resistant GC cells. Notably, the apoptosis in GC cells was mediated by inducing cofilin-1 mitochondrial translocation, down-regulating Bcl-2 and up-regulating Bax expression. Surprisingly, the level of p-AKT protein was higher in DDP-resistant GC cells than that of the DDP-sensitive GC cells, and the activation of AKT could attenuate ZJW-induced sensitivity to DDP. These data revealed that ZJW can increase the chemosensitivity in DDP-resistant primary GC cells by inducing mitochondrial apoptosis and AKT inactivation. The combining chemotherapy with ZJW may be an effective therapeutic strategy for GC chemoresistance patients.



Houttuynia cordata polysaccharide alleviated intestinal injury and modulated intestinal microbiota in H1N1 virus infected mice

Publication date: March 2019

Source: Chinese Journal of Natural Medicines, Volume 17, Issue 3

Author(s): Mei-Yu CHEN, Hong LI, Xiao-Xiao LU, Li-Jun LING, Hong-Bo WENG, Wei SUN, Dao-Feng CHEN, Yun-Yi ZHANG

Abstract

Houttuynia cordata polysaccharide (HCP) is extracted from Houttuynia cordata, a key traditional Chinese medicine. The study was to investigate the effects of HCP on intestinal barrier and microbiota in H1N1 virus infected mice. Mice were infected with H1N1 virus and orally administrated HCP at a dosage of 40 mg(kg−1(d−1. H1N1 infection caused pulmonary and intestinal injury and gut microbiota imbalance. HCP significantly suppressed the expression of hypoxia inducible factor-1α and decreased mucosubstances in goblet cells, but restored the level of zonula occludens-1 in intestine. HCP also reversed the composition change of intestinal microbiota caused by H1N1 infection, with significantly reduced relative abundances of Vibrio and Bacillus, the pathogenic bacterial genera. Furthermore, HCP rebalanced the gut microbiota and restored the intestinal homeostasis to some degree. The inhibition of inflammation was associated with the reduced level of Toll-like receptors and interleukin-1β in intestine, as well as the increased production of interleukin-10. Oral administration of HCP alleviated lung injury and intestinal dysfunction caused by H1N1 infection. HCP may gain systemic treatment by local acting on intestine and microbiota. This study proved the high-value application of HCP.



Non-volatile constituents and pharmacology of Chimonanthus: A review

Publication date: March 2019

Source: Chinese Journal of Natural Medicines, Volume 17, Issue 3

Author(s): Ren-Geng SHU, Yi-Li WAN, Xiao-Min WANG

Abstract

Chimonanthus plants widely distributed in southern area of China, which have a long history of edibles and medicine. Phytochemical investigations have shown that Chimonanthus produced 143 non-volatile constituents, including alkaloids, flavonoids, terpenoids, coumarins and others, which exhibit significant anti-oxidant, anti-bacterial, anti-cancer, anti-inflammatory, antihyperglycemic, antihyperlipidemic and other biological activities. On the basis of systematic reviewing of literatures, this article overviews the non-volatile constituents and pharmacology of Chimonanthus from domestic and foreign over the last 30 years (until June 2018), and may provide a useful reference for the further development of Chimonanthus.



Romipeptides A and B, two new romidepsin derivatives isolated from Chromobacterium violaceum No.968 and their antitumor activities in vitro

Publication date: February 2019

Source: Chinese Journal of Natural Medicines, Volume 17, Issue 2

Author(s): Lei XIONG, Chang-Fa CHEN, Tao-Ling MIN, Hai-Feng HU

Abstract

Romipeptides A and B (1 and 2), two new romidepsin derivatives, and three known compounds, chromopeptide A (3), romidepsin (4) and valine-leucine dipeptide (5) were isolated from the fermentation broth of Chromobacterium violaceum No. 968. Their structures were elucidated by interpretation of their UV, HR-ESI-MS and NMR spectra. The absolute configuration of compound 1 and 2 were established by single crystal X-ray diffraction analysis. Compounds 1–5 were evaluated for their anti-proliferative activities against three human cancer cell lines, SW620, HL60, and A549. The results showed most of these compounds exhibited antitumor activities in vitro, in which compound 2 displayed potent cytotoxicity to SW620, HL60 and A549 cell lines, with IC50 of 12.5, 6.7 and 5.7 nmol·L−1, respectively.



Peptides and polyketides isolated from the marine sponge-derived fungus Aspergillus terreus SCSIO 41008

Publication date: February 2019

Source: Chinese Journal of Natural Medicines, Volume 17, Issue 2

Author(s): Xiao-Wei LUO, Yun LIN, Yong-Jun LU, Xue-Feng ZHOU, Yong-Hong LIU

Abstract

Two new isomeric modified tripeptides, aspergillamides C and D (compounds 1 and 2), together with fifteen known compounds (compounds 3–17), were obtained from the marine sponge-derived fungus Aspergillus terreusSCSIO 41008. The structures of the new compounds, including absolute configurations, were determined by extensive analyses of spectroscopic data (NMR, MS, UV, and IR) and comparisons between the calculated and experimental electronic circular dichroism (ECD) spectra. Butyrolactone I (compound 11) exhibited strong inhibitory effects against Mycobacterium tuberculosis protein tyrosine phosphatase B (MptpB) with the IC50 being 5.11 ± 0.53 μmol·L−1, and acted as a noncompetitive inhibitor based on kinetic analysis.



Two symmetrical unsaturated acids isolated from Viscum album

Publication date: February 2019

Source: Chinese Journal of Natural Medicines, Volume 17, Issue 2

Author(s): Duo CAO, Li-Qing WANG, Xiao-Min HAN, Hui-Rui GUAN, Meng LEI, Ya-Hui WEI, Liang CHENG, Pei-Ming YANG, Zheng-Liang SUN, Wen GAO, Jia-Kun DAI

Abstract

In the present study, two new acetylene conjugate compounds, dibutyl (2Z, 6Z)-octa-2, 6-dien-4-yne dioate (1), and dibutyl (2E, 6E)- octa-2, 6-dien-4-yne dioate (2), were isolated from the dry stem leaves of Viscum album, along with nine known compounds (3 – 11). Their structures were confirmed on the basis of spectroscopic data. Compounds 1 and 8 showed antioxidant activity against xanthine oxidase (XOD) and 1,1-diphenyl-2-picrylhydrazyl radical 2,2-diphenyl-1-(2,4,6-trinitrophenyl) hydroxyl (DPPH), with the IC50 of 1.22 and 1.33 μmol·L−1, and the SC50 of 4.34 and 8.22 μmol·L−1, respectively.



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