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Σάββατο, 29 Ιουνίου 2019

Natural Medicines

Six new monacolin analogs from red yeast rice
Publication date: 20 May 2019
Source: Chinese Journal of Natural Medicines, Volume 17, Issue 5
Author(s): Bing-Yu LIU, Fei XU, Jian BAI, Dao-Jiang YAN, Le ZHANG, Dan ZHANG, You-Cai HU
Abstract
Six novel monacolin analogs, monacolins V1–V6 (16), together with seven known ones (713), were isolated from the ethyl acetate extract of red yeast rice. Their structures and absolute configurations were determined by spectroscopic methods, especially 2D NMR (1H-1HCOSY, HSQC, HMBC, and NOESY/ROESY) and CD spectroscopic analyses as well as chemical derivation. Monacolins V2 (2) and V3 (3) represent the first examples of monacolins with 3-hydroxybutyrate substitute. The anti-inflammatory inhibitory activities against the lipopolysaccharide (LPS) induced NO production in BV-2 cells as well as antioxidant activities against rat liver microsomal lipid peroxidation were evaluated.

Dalestones A and B, two anti-inflammatory cyclopentenones from Daldinia eschscholzii with an edited strong promoter for the global regulator LaeA-like gene
Publication date: 20 May 2019
Source: Chinese Journal of Natural Medicines, Volume 17, Issue 5
Author(s): Zhen-Zhen ZHOU, Hong-Jie ZHU, Cheng-Long YANG, Yan-Jun LIU, Nan JIANG, Yong-Sheng XIAO, Li-Yun SHI, Rui-Hua JIAO, Hui-Ming GE, Ren-Xiang TAN
Abstract
Replacement of the native promoter of theglobal regulator LaeA-like gene of Daldinia eschscholzii by a strong gpdA promoter led to the generation of two novel cyclopentenone metabolites, named dalestones A and B, whose structures were assigned by a combination of spectroscopic analysis, modified Mosher’s reaction, and electronic circular dichroism (ECD). Dalestones A and B inhibit the gene expression of TNF-α and IL-6 in LPS-induced RAW264.7 macrophages.

Prenylated stilbenes and flavonoids from the leaves of Cajanus cajan
Publication date: 20 May 2019
Source: Chinese Journal of Natural Medicines, Volume 17, Issue 5
Author(s): Gui-Yun WU, Xiao ZHANG, Xue-Ying GUO, Lu-Qiong HUO, Hong-Xin LIU, Xiao-Ling SHEN, Sheng-Xiang QIU, Ying-Jie HU, Hai-Bo TAN
Abstract
Three new prenylated stilbenes, named as cajanusins A-C (1-3), and one new natural product cajanusin D (4), along with six known derivatives (5-10) were isolated from the leaves of Cajanus cajan. Their structures were fully elucidated by means of extensive spectroscopic methods and comparison with data in the reported literatures. The new compounds of 1 and 2 were evaluated for in vitro cytotoxic activities against a panel of human cancer cell lines.

Broussonin E suppresses LPS-induced inflammatory response in macrophages via inhibiting MAPK pathway and enhancing JAK2-STAT3 pathway
Publication date: 20 May 2019
Source: Chinese Journal of Natural Medicines, Volume 17, Issue 5
Author(s): Shao-Peng HUANG, Xin GUAN, Guo-Yin KAI, Ya-Zhou XU, Yuan XU, Hao-Jie WANG, Tao PANG, Lu-Yong ZHANG, Ying LIU
Abstract
Macrophages play an important role in inflammation, and excessive and chronic activation of macrophages leads to systemic inflammatory diseases, such as atherosclerosis and rheumatoid arthritis. In this paper, we explored the anti-inflammatory effect of broussonin E, a novel phenolic compound isolated from the barks ofBroussonetia kanzinoki, and its underlying molecular mechanisms. We discovered that Broussonin E could suppress the LPS-induced pro-inflammatory production in RAW264.7 cells, involving TNF-α, IL-1β, IL-6, COX-2 and iNOS. And broussonin E enhanced the expressions of anti-inflammatory mediators such as IL-10, CD206 and arginase-1 (Arg-1) in LPS-stimulated RAW264.7 cells. Further, we demonstrated that broussonin E inhibited the LPS-stimulated phosphorylation of ERK and p38 MAPK. Moreover, we found that broussonin E could activate janus kinase (JAK) 2, signal transducer and activator of transcription (STAT) 3. Downregulated pro-inflammatory cytokines and upregulated anti-inflammatory factors by broussonin E were abolished by using the inhibitor of JAK2-STAT3 pathway, WP1066. Taken together, our results showed that broussonin E could suppress inflammation by modulating macrophages activation statevia inhibiting the ERK and p38 MAPK and enhancing JAK2-STAT3 signaling pathway, and can be further developed as a promising drug for the treatment of inflammation-related diseases such as atherosclerosis.

5, 7, 2’, 4’, 5’-Pentamethoxyflavanone regulates M1/M2 macrophage phenotype and protects the septic mice
Publication date: 20 May 2019
Source: Chinese Journal of Natural Medicines, Volume 17, Issue 5
Author(s): Li-Li FENG, Li-Sha XU, Meng-Meng GUO, Wei HUANG, Jia-Zhen ZHU, Ling-Dong KONG, Xu-Dong WU, Qiang XU
Abstract
Flavonoids have been reported to exert protective effect against many inflammatory diseases, while the underlying cellular mechanisms are still not completely known. In the present study, we explored the anti-inflammation activity of 5, 7, 2’, 4’, 5’-pentamethoxyflavanone (abbreviated as Pen.), a kind of polymethoxylated flavonoid, both in vitro and in vivo experiments. Pen. was showed no obvious toxicity in macrophages even at high dosage treatment. Our results indicated that Pen. significantly inhibited both mRNA and protein level of proinflammatory cytokines, IL-1β, IL-6, TNF-α and iNOS, which was characteristic expressed on M1 polarized macrophages. These effects of Pen. were further confirmed by diminished expression of CD11c, the M1 macrophage surface marker. Further researches showed that the mechanism was due to that Pen. downregulated the activity of p65, key transcription factor for M1 polarization. On the other hand, Pen. also enhanced M2 polarization with upregulation of anti-inflammatory factors and increase of M2 macrophage surface markers, which lead to the balance of M1 and M2 macrophages. Moreover, in vivo research verified that Pen. treatment alleviated LPS-induced sepsis in mice by increasing survival rate, decreasing inflammatory cytokines and improving lung tissue damage. In summary, our results suggested that Pen. modulated macrophage phenotype via suppressing p65 signal pathway to exert the anti-inflammation activity.

Modified Da-chai-hu Decoction regulates the expression of occludin and NF-κB to alleviate organ injury in severe acute pancreatitis rats
Publication date: 20 May 2019
Source: Chinese Journal of Natural Medicines, Volume 17, Issue 5
Author(s): Guang ZHAO, Yu-Zhen ZHUO, Li-Hua CUI, Cai-Xia LI, Sha-Yan CHEN, Dan LI, Jun-Hong LIU, Di-Hua LI, Nai-Qiang CUI, Shu-Kun ZHANG
Abstract
Modified Da-chai-hu Decoction (MDD), a traditional Chinese medicinal formulation, which was empirically generated from Da-chai-hu decoction, has been utilized to treat severe acute pancreatitis (SAP) for decades. The aim of the present study was to explore its potential organprotective mechanism in SAP. In the present study, rat SAP model was induced by retrograde injection of 3.5% sodium taurocholate into the biliopancreatic duct, MDD (23.35 g/kg body weight, twelve times the clinical dose) were orally given at 2 h before and 10 h after injection. At 12 h after model induction, blood was taken from vena cava for analysis of amylase, diamine oxidase (DAO), pulmonary surfactant protein-A (SP-A), and C-reactive protein (CRP). Histopathological change of pancreas, ileum and lung was assayed by H&E staining, myeloperoxidase (MPO) activity were determinated using colorimetric assay, and the expressions of occludin and nuclear factor-κB (NF-κB) were detected by real-time RT-PCR and western blot, respectively. In addition, the tissue concentrations of tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), and monocyte chemoattractant protein-1 (MCP-1) were measured by enzyme-linked immunosorbent assay (ELISA). The results showed that in SAP rats, MDD significantly alleviated histopathological damage, depressed the MPO activity and the concentrations of TNF-α, IL-1β, and MCP-1 of pancreas, ileum and lung, and reduced the serum levels of amylase [(3283.4 ± 585.5) U·L–1vs (5626.4 ± 795.1)U·L–1], DAO [(1100.1 ± 334.3) U·L–1 vs (1666.4 ± 525.3) U·L–1] and CRP [(7.6 ± 1.2) μg·mL–1 vs (17.8 ± 3.8) μg·mL–1]. However, the serum SP-A concentration [(106.1 ± 16.6) pg·mL–1 vs (90.1 ± 14.9) pg·mL–1] was elevated when treated SAP rats with MDD. Furthermore, MDD increased the occludin expression and reduced the NF-κB expression in pancreas, ileum and lung of SAP rats. Our findings suggested that MDD administration was an effective therapeutic approach for SAP treatment. It could up-regulate occludin expression to protect intercellular tight junction and down-regulate NF-κB expression to inhibit inflammatory reaction of pancreas, ileum and lung.

Umbelliferone ameliorates renal function in diabetic nephropathy rats through regulating inflammation and TLR/NF-κB pathway
Publication date: 20 May 2019
Source: Chinese Journal of Natural Medicines, Volume 17, Issue 5
Author(s): Han-Qing WANG, Sha-Sha WANG, Kuok Chiufai, Qi WANG, Xiao-Lan CHENG
Abstract
Diabetic nephropathy (DN) is a leading cause of renal failure, contributing to severe morbidity and mortality in diabetic patients. Umbelliferae (Umb) has been well characterized to exert protective effects in diabetes. However, the action and mechanism of Umb in DN remains unclear. In this work, we studied the effect of Umb in a streptozotocin (STZ)-induced DN rat model and explore its underlying mechanism. DN rats were treated withUmb (20, 40 mg·kg–1) orirbesartan (15 mg·kg–1) for 4 weeks. Levels of serum glucose, insulin, blood uric acid, creatinine, triglycerides (TG) and total cholesterol (TC) were measured bycommercial assay kits, respectively. Histopathological changes andinflammatory cytokine levels including IL-6, IL-1β and TNF-α in the kidney were also evaluated. Alterations in the expression of podocin, CD2AP and TLR/NF-κB were assessed by western blotting. Our results showed that Umb reduced renal injury in DN rat model, as evidenced by the decrease in blood glucose, 24 h urinary protein, serum creatinine, and blood uric acid. Umb also significantly ameliorated the renal histopathological alteration, and down-regulated the expression of epithelial-to-mesenchymal transition-related molecular markers podocin and CD2AP. Moreover, Umb inhibited TLR2, TLR4, MyD88 expressions, NF-κB activation and considerably reduced levels of other downstream inflammatory molecules (TNF-α, IL-6, IL-1β). These findings indicated that Umb improved renal function through regulating inflammation and TLR/NF-κB pathway, suggesting the potential efficacy of Umb in DN treatment.

Rapid identification of Dendrobium officinale using Loop-Mediated Isothermal Amplification (LAMP) method
Publication date: 20 May 2019
Source: Chinese Journal of Natural Medicines, Volume 17, Issue 5
Author(s): Lu YANG, Wen-Ru WU, Hua ZHOU, Hui-Li LAI, Fei FU
Abstract
Dendrobium officinale is not only an ornamental plant, but also a valuable medicinal herb that is widely used in traditional Chinese medicine. However, distinguishing D. officinale from other Dendrobium species is usually a difficult task. In this study, we developed a rapid identification protocol for D. officinale using the loop-mediated isothermal amplification (LAMP) method. A set of primers were specifically designed to detect a modified internal transcribed spacer region of D. officinale at 65 °C within 40 min after adding SYBR® Green I, which was used for the detection of D. officinale. Unlike commonly used adulterants, reaction mixtures containing D. officinale DNA changed from orange to green, and this color change was easily observed with the naked eye. Thus, this methodology can be used to accurately differentiate D. officinale from other Dendrobium species, is quick as all D. officinale samples were amplified within 40 min, and specific as samples of the adulterants were not amplified. The specificity of this LAMP-based method was confirmed by testing 17 samples of D. officinaleand 32 adulterant samples from other Dendrobium species. This LAMP-based rapid identification method does not require expensive equipment or specialized techniques and can be used in field surveys for accurate and fast on-site identification.

A brief history of artemisinin: Modes of action and mechanisms of resistance
Publication date: 20 May 2019
Source: Chinese Journal of Natural Medicines, Volume 17, Issue 5
Author(s): Feng LU, Xin-Long HE, Culleton Richard, Jun CAO
Abstract
The cornerstone of antimalarial treatment, artemisinin, has reduced malaria associated morbidity and mortality worldwide. However, Plasmodium falciparum parasites with reduced sensitivity to artemisinin have emerged, and this threatens malaria control and elimination efforts. In this minireview, we describe the initial development of artemisinin as an antimalarial drug, its use both historically and currently, and our current understanding of its mode of action and the mechanisms by which malaria parasites achieve resistance.

Metabolomics and its application in the treatment of coronary heart disease with traditional Chinese medicine
Publication date: 20 May 2019
Source: Chinese Journal of Natural Medicines, Volume 17, Issue 5
Author(s): Gao-Song WU, Hou-Kai LI, Wei-Dong ZHANG
Abstract
Traditional Chinese Medicine (TCM) is the treasure of Chinese Nation and gained the gradual acceptance of the international community. However, the methods and theories of TCM understanding of diseases are lack of appropriate modern scientific characterization systems. Moreover, traditional risk factors cannot promote to detection and prevent those patients with coronary artery disease (CAD) who have not developed acute myocardial infarction (MI) in time. To sum up, there is still no objective systematic evaluation system for the therapeutic mechanism of TCM in the prevention and cure of cardiovascular disease. Thus, new ideas and technologies are needed. The development of omics technology, especially metabolomics, can be used to predict the level of metabolites in vivo and diagnose the physiological state of the body in time to guide the corresponding intervention. In particular, metabolomics is also a very powerful tool to promote the modernization of TCM and the development of TCM in personalized medicine. This article summarized the application of metabolomics in the early diagnosis, the discovery of biomarkers and the treatment of TCM in CAD.

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