Volume 13,Issue 3,2021 Table of Contents

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  • 1  Back to beginning: Searching for Rosetta Stone of enhancing herbal medicine quality
    Da-Cheng Hao Chang-Xiao Liu
    2021, 13(3).
    [Abstract](276) [HTML](0) [PDF 0.00 Byte](0)
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    Chinese herbal medicines (CHMs) are an integral part of ecosystem service for humankind and represent one of most important bioresources in our planet, in which nature's ability is fully unlocked to prevent/treat human diseases. From the world-wide research and practice in recent years, we can feel that the process of globalization of traditional Chinese medicine (TCM) is accelerating; especially since the outbreak and spread of COVID-19 since December 2019, the world has gained more recognition of its important/unique values. Nowadays, considerable studies have focused on the quality evaluation of CHMs (Liu, 2021), which, however, cannot meet the growing demand for drug safety, if the problem of pesticide residues and heavy metals in CHMs cannot be effectively tackled. Hence, the eligible medicinal plant cultivation pattern should be actively explored, so as to solve the quality problems of CHMs from the source and provide quality CHMs sustainably. In the review “How to improve CHMs quality: Enlighten from CHMs ecological cultivation” (Cao et al., 2021), the situation and characteristics of medicinal plant resources, including wild-harvested and cultivated ones, in different historical periods are scrutinized. In Dream Creek Talk (梦溪笔谈) of Song Dynasty, the scholar Shen Kuo thought that “In ancient times, herbs are mostly collected in February or August, which is very inappropriate. It's just that the February grass has sprouted and the August seedling hasn't dried up, so it's easy for the picker to recognize it, but it's not a good time for medicine picking”. Shen sagaciously realized the influence of ecological/environmental factors on the quality of phytomedicine; he said that “the peach and plum trees in ZhuYue of southern China bear fruit in winter, while those in the northern desert only bloom in summer. This is the difference of telluric effluvium (i.e., soil/climate conditions). The crops in the same Mu germinate first with good water and fertilizer conditions…... How can the collection of herbs be limited to a fixed month”. The growth stage, season and phenological factors should be paid attention to when harvesting TCM plants. Based on ancient experiences, the ecological cultivation is recommended in developing medicinal plant cultivation to obtain quality CHMs. The rhizosphere, a slender region of soil, is unswervingly influenced by roots and associated soil microbes. Studies on rhizosphere microbes of TCM plants are critical for applied microbiology, microbial ecology, and industrial biotechnology with regard to ecological cultivation and CHM quality (Hao & Xiao, 2017). In contrast to the inability of culturing most rhizosphere microbes (around 99%) in the laboratory, currently there are enormous advances in applying culture-independent techniques based on molecular biology and omics to the study of rhizosphere microbial community structure/composition and plant-microbe interactions. The various omics tools, such as FISH, stable isotope probing (SIP), next/third generation sequencing, etc., evolve quickly to provide more comprehensive understanding of the rhizosphere microbiota and microbiome. The flexible applications of high-throughput sequencing technologies, e.g., amplicon sequencing, shotgun metagenomic sequencing, whole genome sequencing, and transcriptome sequencing, continuously address the biology and biotechnology potentials of the rhizosphere microbiome of medicinal plants. The review “How to improve CHMs quality: Enlighten from CHMs ecological cultivation” (Cao et al., 2021) discusses recent findings and future challenges in the study of rhizosphere microbes, highlighting multi-faceted roles of microbial inoculants. Moreover, the evolution of research methods and innovative combinations of different techniques should also be encouraged. The top-down approaches such as metagenomics and bottom-up approaches targeting individual species or strains should be integrated and combined with modeling approaches to afford a wide-ranging understanding of the microbial community as a whole. Searching for Rosetta Stone of enhancing herbal medicine quality is never an easy task. Green technologies, e.g., bioaugmentation and biostimulation, are cost effective and eco-friendly, and are becoming Rosetta Stone for the remediation of soil heavy metal and pesticides. The bacteria, fungi and their consortia can be combined with physical and chemical techniques for the targeted remediation of soil organic pollution, heavy metal contamination or both. The review of Cao et al. (2021) exemplifies the representative studies, summarizes the potentials of microbial strains in transforming/degrading pollutants, and highlights the roles of biochar and mineral elements in laboratory,greenhouse and field conditions. The complexity of microbial remediation is ascribed to not only the variations of physiological and metabolic traits, but also numerous environmental factors, including abiotic factors, e.g., pH, temperature, type of soil, pollutant concentration, content of water and organic matter, additional carbon and nitrogen sources, and biotic factors, e.g., inoculum size, interactions between the introduced strains and autochthonous microbes, and survival of inoculants, etc. The ingeniously combined remediation and rational applications of molecular methods will maximize the soil remediation without much cost. Microbes in arable soil participate in the biogeochemical cycling of nitrogen, which profoundly impact on the fertility and greenhouse gas emission. As the effects of environmental factors on the structure and functions of microbial communities have not been thoroughly elucidated, it is necessary to perform the microcosm/mesocosm study to collect the soil samples under different moisture (e.g., constant and wetting)/pH/gas (air, 10% acetylene, oxygen and argon) regimes and investigate the alterations of microbial community structure, gene abundance and nitrogen metabolic functions under different conditions by high-throughput sequencing, quantitative PCR and RT-PCR, SIP, physicochemical analyses and bioinformatics. The impact of moisture/gas regimes, processing time and interaction item on NH4+-N and NO3--N would be conspicuous. The water/gas regime could significantly affect the microbial community diversity. The key responsive microbial classes under different moisture/pH/gas conditions would be disclosed in such a study. Novel microbial species that are positively correlated with moisture and N2O emission will be found; the dominant processes of nitrogen cycle, e.g., denitrification, nitrate reduction to ammonium, nitrification, nitrogen mineralization/fixation, in different types of soil will be determined, which, along with the co-occurring network and gene-species correlation heatmap, are invaluable information in improving medicinal plant growth and production of medicinal compounds. Medicinal plant scholars should communicate and cooperate with soil researchers more. The findings therefrom shed light on the prevention and control of soil fertility decline and global warming, as well as heavy metals and pesticide residues exceeding the standard in CHM products.
    2  How to improve CHMs quality: enlighten from CHMs ecological cultivation
    Pei Caoa Gang Wanga Xue-Min Weia Shi-Lin Chenb Jian-Ping Hana
    2021, 13(3). DOI: 10.1016/j.chmed.2021.04.014
    [Abstract](537) [HTML](0) [PDF 0.00 Byte](0)
    Abstract:
    Chinese herbal medicines (CHMs) are one of the important bioresources of medicine, which works by unlocking nature's ability to prevent diseases and recover from illnesses. Recently, it has ascended to the world stage and become a global icon. Nowadays, a considerable of researches have focused on the quality evaluation of CHMs. However, it is difficult to meet the reasonable needs of human beings for safe drug use to evaluate the quality of a huge number of inferior goods for the CHMs contaminated by pesticides and heavy metals. Hence to explore an eligible medicinal plant cultivation pattern, which can provide high quality CHMs sustainably, is most promising. This review analyzed the situation and characteristics of medicinal plant resources in different periods, including wild-harvested resources and domestic cultivation during different stages, putting forward that ecological cultivation must be the way to develop medicinal plant cultivation and to obtain high quality CHMs.
    3  Systems pharmacology dissection of action mechanisms for herbs in osteoporosis treatment
    Ying Huaia b c Wen-juan Zhang a b c Wei Wang a b c Kai Dang a b c Shan-feng Jiang a b c Dan-ming Lid Meng Lie Qiang Haoe Zhi-ping Miao a b c Yu Li a b c Ai-rong Qian a b c
    2021, 13(3). DOI: 10.1016/j.chmed.2021.06.001
    [Abstract](797) [HTML](0) [PDF 0.00 Byte](0)
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    Objective: Osteoporosis has become the biggest cause of non-fatal health issue. Currently, the limitations of traditional anti-osteoporosis drugs such as long-term ill-effects and drug resistance, have raised concerns toward complementary and alternative therapies, particularly herbal medicines and their natural active compounds. Thus, this study aimed to provide an integrative analysis of active chemicals, drug targets and interacting pathways of the herbs for osteoporosis treatment. Methods: Here, we introduced a systematic pharmacology model, combining the absorption, distribution, metabolism, and excretion (ADME) screening model, drug targeting and network pharmacology, to probe into the therapeutic mechanisms of herbs in osteoporosis. Results: We obtained 86 natural compounds with favorable pharmacokinetic profiles and their 58 targets from seven osteoporosis-related herbs. Network analysis revealed that they probably synergistically work through multiple mechanisms, such as suppressing inflammatory response, maintaining bone metabolism or improving organism immunity, to benefit patients with osteoporosis. Furthermore, experimental results showed that all the five compounds (calycosin, asperosaponin VI, hederagenin, betulinic acid and luteolin) enhanced osteoblast proliferation and differentiation in vitro, which corroborated the validity of this system pharmacology approach. Notably, gentisin and aureusidin among the identified compounds were first predicted to be associated with osteoporosis. Conclusion: Herbs and their natural compounds, being characterized as the classical combination therapies, might be engaged in multiple mechanisms to coordinately improve the osteoporosis symptoms. This work may contribute to offer novel strategies and clues for the therapy and drug discovery of osteoporosis and other complex diseases.
    4  Comparison of anti-inflammatory effects of Lonicerae Japonicae Flos and Lonicerae Flos based on network pharmacology
    Yu Gao Feng-xue Wang Qing Liu Yao-dong Qi Qiu-ling Wang Hai-bo Liu
    2021, 13(3). DOI: 10.1016/j.chmed.2021.06.005
    [Abstract](603) [HTML](0) [PDF 0.00 Byte](0)
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    Objective In TCM history, Lonicerae Japonicae Flos and Lonicerae Flos were used clinically as one drug, but now they are admitted as two herbal medicines in Chinese Pharmacopoeia (2010 edition). This study used network pharmacology to investigate whether the two can be used interchangeably for the treatment of inflammatory diseases in TCM clinical practice. Methods Lonicerae Japonicae Flos and Lonicerae Flos were compared in the inflammation mechanism including core targets, Gene Ontology (GO), pathway and principle chemical components by the method of network pharmacology. Results Both herbs shared in six targets accounting for 66.7% of the entire core targets and more than half of the GO terms and pathways are similar. Organic acids are dominent compounds responsible for anti-inflammatory effects. Three of the compounds that bind to core targets including luteolin, quercetin and kaempferol, are shared in both herbs. Conclusion Due to high similarity between Lonicerae Japonicae Flos and Lonicerae Flos, we believe that they can be used interchangeably for the inflammation in clinical treatment.
    5  Investigating pharmacological mechanisms of andrographolide on non-alcoholic steatohepatitis (NASH): A bioinformatics approach of network pharmacology
    Lei Li a b Sheng-he Li a Jin-peng Jiang a Chang Liu a Li-li Ji b
    2021, 13(3). DOI: 10.1016/j.chmed.2021.05.001
    [Abstract](345) [HTML](0) [PDF 0.00 Byte](0)
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    Objective: To investigate the mechanisms of andrographolide against non-alcoholic steatohepatitis (NASH) based on network pharmacology, so as to provide a reference for further study of andrographolide in the treatment of NASH and other metabolic diseases. Methods: The methionine- and choline-deficient (MCD) diet-induced NASH mice were treated by administration of andrographolide, and serum transaminase and pathological changes were analyzed. The network pharmacology-based bioinformatic strategy was then used to search the potential targets, construct protein-protein interaction (PPI) network, analyze gene ontology (GO) and Kyoto encyclopedia of genes and genomes (KEGG) pathway enrichment, and conduct molecular docking to explore the molecular mechanisms. Results: The predicted core targets TNF, MAPK8, IL6, IL1B and AKT1 were enriched in non-alcoholic fatty liver disease (NAFLD) signaling pathway and against NASH by regulation of de novo fatty acids synthesis, anti-inflammation and anti-oxidation. Conclusion: This work provides a scientific basis for further demonstration of the anti-NASH mechanisms of andrographolide.
    6  Mechanism of Huoxue Tongluo Decoction in treatment of erectile dysfunction caused by ischemic stroke based on network pharmacology
    Ji-sheng Wanga b Heng-heng Daia b Kai-ge Zhanga b Ke-gang Caob c Sheng Denga b Bing-hao Baoa b Jun-long Fenga b Fan-chao Menga b Hai-song Lib Bin Wangb
    2021, 13(3). DOI: 10.1016/j.chmed.2021.04.016
    [Abstract](352) [HTML](0) [PDF 0.00 Byte](0)
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    Objective: To study the therapeutic effect of Huoxue Tongluo Decoction (HXTLD) on erectile dysfunction caused by ischemic stroke and identify the mechanisms involved. Methods: Network pharmacology was used to predict the key active ingredients and targets of HXTLD. Surgical methods were used to create a rat model of ischemic stroke. The rats were then given a suspension of HXTLD by ig administration. Erectile function was evaluated by Apomorphine (APO) induction. Real-time fluorescence quantitative reverse transcription-polymerase chain reaction (Real-time PCR) and Western blotting were used to detect the expression of related mRNAs and proteins in rat penile corpus cavernous tissue and brain tissue. Hematoxylin & Eosin (HE) staining was used to investigate structural changes in the penile cavernous tissue. Results: Network pharmacology showed that tumor necrosis factor (TNF), nitric oxide synthase 3 (eNOS), and vascular endothelial growth factor (VEGF) were the key targets of HXTLD in the treatment of erectile dysfunction caused by ischemic stroke. Experimental studies showed that HXTLD improved erectile dysfunction caused by ischemic stroke. HE results showed that HXTLD improved the structure of the corpus cavernosa. HXTLD also inhibited the expression of TNF and VEGF proteins in penile tissue (P < 0.05) and enhanced the expression of eNOS protein in penile tissue (P < 0.05). Conclusion: HXTLD improved the erectile function of rats with erectile dysfunction caused by ischemic stroke by regulating the mRNA and protein levels of TNF, eNOS and VEGF.
    7  Dual inhibition of COVID-19 spike glycoprotein and main protease 3CLpro by Withanone from Withania somnifera
    Vishal Shivalingappa Patila Vrushabh B. Hupparagea Ajay P. Malgia Sanjay ?. Deshpandeb Sathgowda A. Patila Shamanad P. Mallapura
    2021, 13(3). DOI: 10.1016/j.chmed.2021.06.002
    [Abstract](508) [HTML](0) [PDF 0.00 Byte](0)
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    Objective To identify the safe and effective natural inhibitors of spike glycoprotein and main protease 3CLpro using potential natural antiviral compounds which are studied under various animal models and viral cell lines. Methods First, compounds were retrieved from the PubChem database and predicted for their druggability using the MolSoft web server, and compounds having drug-like property were predicted for major adverse drug reactions like cardiotoxicity, hepatotoxicity, arrhythmia, myocardial infarction, and nephrotoxicity using ADVERpred. Docking of nontoxic antiviral compounds with spike glycoprotein and main protease 3CLpro was performed using AutoDock vina by PyRx 0.8 version. The stability of compound-protein interactions was checked by molecular dynamic (MD) simulation using Schrodinger Desmond software. Results Based on the druggable and nontoxic profile, nine compounds were selected. Among them, Withanone from Withania somnifera showed the highest binding affinity and best fit at active sites 1 of spike glycoprotein (glycosylation site) and main protease 3CLpro via interacting with active site amino acid residues before and after MD simulation at 50 ns. Withanone, which may reduce the glycosylation of SARS-CoV-2 via interacting with Asn343 and inhibit viral replication. Conclusion The current study reports Withanone as a non-toxic antiviral against SARS-CoV-2 and serve as a potential lead hit for further experimental validation.
    8  Self-assembled aggregations in Coptis chinensis decoction dynamically regulate intestinal tissue permeability through Peyer's patch-associated immunity
    Qing-qing Zhang Ye Yang Rong-rong Ren Qing-qing Chen Jing-jing Wu Yu-yu Zheng Xiao-hui Hou Yu-feng Zhang Ming-song Xue Deng-ke Yin
    2021, 13(3). DOI: 10.1016/j.chmed.2021.06.004
    [Abstract](721) [HTML](0) [PDF 0.00 Byte](0)
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    Objective To investigate the dynamic regulation of self-assembled aggregations (SAA) in Coptis chinensis (C. chinensis) decoction on the permeability of intestinal tissue and the mechanism underlying. Methods The effects of SAA on berberine (Ber) absorption were respectively analyzed in an in situ intestinal perfusion model and in an Ussing Chamber jejunum model with or without Peyer's patches (PPs). The expression levels of ZO-1, Occludin and Claudin-1 were detected by immunofluorescence to evaluate the tight junction (TJ) between intestinal epithelium cells. The expression levels of T-box-containing protein expressed in T cells, signal transducers and activators of tranion-6, retinoic acid receptor-related orphan receptor γt and forkhead box P3 in PPs were detected by the reverse transcription-polymerase chain reaction and the secretions of interferon-γ (IFN-γ), interleukin-4 (IL-4), interleukin-17 (IL-17) and transforming growth factor-β (TGF-β) in PPs were evaluated by immunohistochemistry, to reflect the differentiation of T lymphocyte in PPs to helper T (Th) cell 1, Th2, Th17 and regulatory T (Treg) cell. To confirm the correlation between SAA in C. chinensis decoction, PPs-associated immunity and intestinal epithelium permeability, SAA were administrated on an Ussing Chamber jejunum model with immunosuppressed PPs and evaluated its influences on intestinal tissue permeability and TJ proteins expression. Results SAA in C. chinensis decoction could dose-dependently promote Ber absorption in jejunum segment, with the participation of PPs. The dose-dependent and dynamical regulations of SAA on permeability of intestinal tissue and TJ proteins expression level between intestinal epithelium cells occurred along with the dynamically changed T lymphocyte differentiation and immune effectors secretion in PPs. The administration of SAA on immunosuppressed PPs exhibited dose-dependent PPs activation, inducing dynamic promotion on intestinal tissue permeability and inhibition on TJ proteins expression. Conclusion SAA can improve the Ber absorption in small intestine, through the PPs-associated immunity induced dynamic regulation on intestinal tissue permeability and TJ proteins expression. These findings might enlighten the research of traditional Chinese medicine decoction.
    9  Polyphenols from Securidaca inappendiculata alleviated acute lung injury in rats by inhibiting oxidative stress sensitive pathways
    Cong-lan Jia Sheng Daia Hong Liua Ji-yang Dongb Chun-sheng Liuc Jian Zuoc d e
    2021, 13(3). DOI: 10.1016/j.chmed.2020.09.007
    [Abstract](197) [HTML](0) [PDF 0.00 Byte](0)
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    Objective: Securidaca inappendiculata is a medicinal plant frequently used in the treatment of inflammatory diseases in south China. In this study, we aimed to explore its bioactive constituent which contributes to the anti-inflammatory activity. Methods: Polyphenol-enriched and polyphenol-deprived fractions (PRF and PDF, respectively) were separated from the ethanolic extract by HPD300 macroporous resin-based method, and their anti-inflammatory activities were investigated on a lipopolysaccharide (LPS)-induced acute lung injury (ALI) model in rats. The possible mechanism of action in alleviating acute inflammation was studied using RAW264.7 cells. Results: Both Folin-Ciocalteu and 1H nuclear magnetic resonance (NMR) analyses showed that polyphenolic content in PRF was approximately 10 times higher than that of PDF, and this observation reflected in their antioxidative capacities. PRF but not PDF significantly decreased the level of malondialdehyde, suppressed the expression of nicotinamide phosphoribosyltransferase (NAMPT) protein, and improved the severity of ALI in rats. PRF at 10 μg/mL effectively downregulated the expression of proteins NAMPT, HMGB1, TLR4, and p-p65, and scavenged the intracellular reactive oxygen species (ROS) in LPS- primed RAW264.7 cells. N-acetyl-L-cysteine exhibited similar inhibitory effects on ROS production and NAMPT-mediated TLR4/NF-κB activation in vitro, whereas nicotinamide mononucleotide antagonized all the changes induced by PRF during cotreatments. Conclusion: As an antioxidant, PRF exhibited potent anti-inflammatory activity under both in vivo and in vitro conditions by downregulating NAMPT and TLR4/NF-κB. Accordingly, polyphenols were identified as important bioactive constituents in S. inappendiculata targeting oxidative stress-sensitive pro-inflammatory pathways.
    10  Discovery and identification of quality markers of Sparganii Rhizoma based on zebrafish thrombosis model
    Nan Xu Rong Sun Yin-ping Shi Li-wen Han Hai-yan Shi
    2021, 13(3). DOI: 10.1016/j.chmed.2021.04.015
    [Abstract](225) [HTML](0) [PDF 0.00 Byte](0)
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    Objective: The aim of the present study was to determine the Q-markers of Sparganii Rhizoma against thrombus through an integration of investigations on its antithrombotic effect, content determination and spectrum-effect correlation analysis. Methods: Based on the concept of Q-Marker, Sparganii Rhizoma was investigated for the identification of chemical component. The pharmacological effects on arachidonic acid-induced thrombosis in zebrafish were also investigated. The material basis in ethanol extract was determined by HPLC-UV. Furthermore, the potential Q-markers were analyzed and predicted according to the effect-chemical correlation analysis. Finally, the anti-thrombotic Q-markers were verified through the anti-thrombotic test of monomer components. Results: The model of thrombosis zebrafish was established with larvae exposed to 100 μmol/L arachidonic acid for 1 h. Nine ingredients in Sparganii Rhizoma were identified as 5-hydroxymethylfurfural, vanillic acid, ferulic acid, p-hydroxybenzaldehyde, p-hydroxybenzoic acid, vanillin, protocatechuic acid, p-coumaric acid and isoferulic acid. According to the determination effect of zebrafish thrombosis model and HPLC content analysis results, all the other contents present positive correlation except 5-hydroxymethylfurfural, and the P values of three representative potential Q-markers (ferulic acid, protocatechuic acid and p-coumaric acid) were 0.002, 0.001 and 0.026, respectively. Conclusion: Sparganii Rhizoma showed a dose-dependent effect on the recovery of reducing cardiac red blood cell on zebrafish model. Three phenolic acids (ferulic acid, protocatechuic acid and p-coumaric acid) were proved to possess the anti-thrombotic effects which could be regarded as the potential Q-markers for quality assessment of Sparganii Rhizoma.
    11  Molecular mechanism of Chuanxiong Rhizoma in treating coronary artery diseases
    Bang-qiao Yin Yu-hong Guo Yuan Liu Yang-yang Zhao Shan-mei Huang Xia-wei Wei Heng-sheng Wang Ruo-ya Liu Ying Liu Yao-ping Tang
    2021, 13(3). DOI: 10.1016/j.chmed.2021.03.001
    [Abstract](419) [HTML](0) [PDF 0.00 Byte](0)
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    Objective: Most of the studies on the herb Chuanxiong Rhizoma (CR) have focused on the l-arginine-nitric oxide (NO) pathway, but the nitrate-nitrite-NO (NO3?-NO2?-NO) pathway was rarely investigated. Therefore, the aim of this study was to evaluate the effects and mechanisms of action of CR in coronary artery disease (CAD). Methods: The NO3?, NO2? and NO levels were examined in the NO3?-NO2?-NO pathway. High-performance ion chromatography was used to quantify NO3? and NO2? levels. Then, NO was quantified using a multifunctional enzyme marker with a fluorescent probe. The tension of aortic rings was measured using a multi myograph system. Results: High content of NO3? and low content of NO2? was found in CR, and which could potently convert NO3? to NO2? in the presence of endogenous reductase enzyme. Incubating human coronary artery endothelial cells (HCAECs) with CR-containing serum showed that CR significantly decreased the NO3? content and increased the levels of NO2? and NO in the cells under hypoxic conditions. In addition, CR significantly relaxed isolated aortic rings when the l-arginine -NO pathway was blocked. The optimal concentration of CR for relaxation was 200 mg/mL. Conclusion: CR supplements large amounts of NO in cells and vessels to achieve relaxation via the NO3?-NO2?-NO pathway, thereby making up for the deficiency caused by the lack of NO after the l-arginine-NO pathway is suppressed. This study also supports the potential use of a traditional Chinese herb for future drug development.
    12  Anaphylaxis effect and substance basis of honeysuckle extract
    Yu-fei Fenga Guo-zhao Qina Zhong-xu Jingb Yan-hong Wanga Yan-yan Zhoua
    2021, 13(3). DOI: 10.1016/j.chmed.2021.04.013
    [Abstract](370) [HTML](0) [PDF 0.00 Byte](0)
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    Objective: To explore the anaphylaxis effect and anaphylaxis substances of honeysuckle. Methods: Rat peritoneal mast cells (PMC) were separated and purified, the cells were incubated with compound 48/80 (0.02 g/L), physiological saline and honeysuckle extract (120 g/L) at 37 °C for 0, 15, 30, 45 and 60 min. Degranulation were observed by optical microscope and transmission electron microscope. Annexin?V?positive?cell?rate was detected by?flow cytometry to reflect the degranulation rate of PMC. SD rats were supplied with honeysuckle extract by?intravenous?injection at a dose of 2.25 g/L. After administration, different parameters were analyzed, including the symptoms, histamine (HIS) and tryptase (MCT) levels, which were determined to explore the effect of anaphylaxis. Regression analysis was used to calculate the relationships between the peaks and the pharmacological effects to explore potentially anaphylactoid components. Results: The percentage of Annxin V positive cells and the degranulation ratio were markedly elevated in PMC treated with honeysuckle extract for more than 15 min (P < 0.05). HIS and MCT level were significantly elevated after injection of honeysuckle extract for more than 15 min. Morphology of PMC and systemic symptoms were also changed compared with the controlled group (P < 0.05). Regression analysis was used to calculate the relationship between peaks and pharmacological effects, and to determine peaks 7, 10 and 13 as possible anaphylactoid ingredients. Conclusion: This study established a prospective method to clarify the anaphylactoid components of honeysuckle extract, which would provide guidance for screening anaphylactoid components in traditional Chinese medicine injections containing honeysuckle in the prescription.
    13  Ethanol extract of Ardisiae Japonicae Herba inhibits hepatoma carcinoma cell proliferation in vitro through regulating lipid metabolism
    Xue Gong Huan-tian Cui Yu-hong Bian Yu-ting Li Yang-xue Wang Yan-fei Peng Wei-bo Wen Kuan Li Hong-wu Wang Zhai-yi Zhang Fang Zheng
    2021, 13(3). DOI: 10.1016/j.chmed.2021.06.003
    [Abstract](251) [HTML](0) [PDF 0.00 Byte](0)
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    Objective: The aim of this study is to discover the possible working mechanisms of Ardisiae Japonicae Herba (AJH) on hepatoma carcinoma (HCC). Methods: In this study, ethanol extract of AJH was prepared and used to treat HCC cell in vitro. Furthermore, a genomic wide RNA sequencing (RNA-seq) was performed to screen deregulated genes in HCC cells after the treatment of AJH extract. The gene and protein expression related to lipid metabolism in HCC cells were also investigated to validate the results obtained from RNA-seq. Results: AJH extract could inhibit HCC cell proliferation in vitro. RNA-seq analysis has identified 1,601 differentially expressed genes (DEGs, fold change ≥ 2.0 or fold change ≤ 0.5, P < 0.05) in HCC after AJH extract treatment, which included 225 up-regulated genes and 1,376 down-regulated genes. KEGG pathway analysis of DEGs demonstrated that lipid metabolism was a potential pathway related to AJH treatment. In agreement with the RNA-seq data, qPCR and Western-blot analysis indicated that expression of genes and proteins related to lipid metabolism (SREBP1, ACC, ACLY and FASN) were significantly down-regulated in AJH treatment group as compared with the control group. Furthermore, AJH extract could also decrease lipid contents and cellular free fatty acid levels in HCC cells. Conclusion: Ethanol extract of AJH could inhibit HCC cell proliferation in vitro, the possible mechanism may be related to the inhibition of lipid metabolism.
    14  Genome sizes of four important medicinal species in Kadsura by flow cytometry
    Jing Xua Xue-ping Weia b Jiu-shi Liua b Yao-dong Qia b Ben-gang Zhanga b Hai-tao Liua b Pei-gen Xiaoa b
    2021, 13(3). DOI: 10.1016/j.chmed.2021.05.002
    [Abstract](447) [HTML](0) [PDF 0.00 Byte](0)
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    Objective: Dianjixueteng is a geoherb in Yunnan Province, the source plant of which is Kadsura interior. However, the formation of this geoherb is not clear in genetic mechanism, in which genome size is the first step that should be known on the genomic level. In this study we aimed to estimate the genome sizes of source plants of K. interior compared with three related herbs K. heteroclita, K. longipedunculata, and K. coccinea by flow cytometry (FCM). Methods: The genome sizes of K. interior, K. heteroclita, K. longipedunculata and K. coccinea, i.e., the source plants of K. interior and its relative medicinal materials, were estimated by FCM. The nuclei of K. interior were isolated using modified LB01 buffer, for the rest species, by the Galbraith’s buffer. Results: The genome sizes of K. interior, K. heteroclita, K. longipedunculata, and K. coccinea were 7.36, 7.12, 7.01, and 5.15 pg/1C, respectively. Genome size of K. interior had no significant variation with those of K. heteroclita and K. longipedunculata (P = 0.296), which were larger than that of K. coccinea. Conclusion: Genome size did not distinguish K. interior, K. heteroclita and K. longipedunculata, but did distinguish from K. coccinea, which lays the foundation for future studies on genetic mechanism of the geoherb formation.
    15  A novel technology to reduce astringency of tea polyphenols extract and its mechanism
    Jin-yan Wan Yu-lu Zhang Yan Xiang Nan Li Ding-kun Zhang
    2021, 13(3). DOI: 10.1016/j.chmed.2021.05.003
    [Abstract](614) [HTML](0) [PDF 0.00 Byte](0)
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    Objective: Tea polyphenols are natural extracts used widely throughout the world. However, the severe astringency of tea polyphenols has reduced patient compliance. Based on the analysis of the formation mechanism of astringency, this paper hopes to propose a new method to control the astringency of tea polyphenols and improve patient compliance without changing its effect. Methods: Artificial saliva was used to prepare the tea polyphenols solution with different pH, using β-casein to imitate salivary protein, and preparing 1.2 mg/mL β-casein solution. A fluorescence quenching test was used to study the interaction between tea polyphenols and β-casein, combined with the stability test results of the compound, we can choose the pH with weak binding but good stability as the best pH for masking astringency. The taste-masking tablets were prepared under the best pH conditions, and the Xinnaojian Original Tablets were prepared according to the conventional preparation method. The disintegration time limit and solubility were tested respectively. The astringency of Xinnaojian original tablets and taste-masking tablets was evaluated by visual analogue scale (VAS). Results: The result of the fluorescence quenching test prompted that the combination force was the weakest when the pH was 4.9. Further synchronous fluorescence analysis showed that an increase in pH resulted in a decrease of the binding sites between tea polyphenols and β-casein, and this decrease was closely related to changes in tryptophan residues in β-casein. Both original and taste-masking Xinnaojian Tablets were prepared. Volunteers’ VAS scores illustrated that the astringency improved significantly with the masking tablets (P < 0.05). Conclusion: This pH-adjusting masking treatment had little effect on the recovery of polyphenols from the tablets or the dissolution of the tablets. This study provides a novel and feasible astringency masking technology for tea polyphenols and its preparation.
    16  A strategy for rapid discovery of traceable chemical markers in herbal prod-ucts using MZmine 2 data processing toolbox: A case of Jing Liqueur
    Jing Zhou Feng-jie Liu Xin-xin Li Ping Li Hua Yang Yuan-cai Liu Yan-he Chen Chao-dan Wei Hui-jun Li
    2021, 13(3). DOI: 10.1016/j.chmed.2021.05.004
    [Abstract](299) [HTML](0) [PDF 0.00 Byte](0)
    Abstract:
    Objective: The quality evaluation of herbal products remains a big challenge. Traceable markers are the core concept of the authentication of herbal products. However, the discovery of traceable markers is labor-intensive and time-consuming. The aim of this study is to develop a convenient approach to rapidly screen the traceable markers for herbal product authentication. Methods: Commercial Jing Liqueur and its 22 species of herbal ingredients were analyzed using HPLC-QTOF-MS and GC-MS to characterize nonvolatile and volatile chemicals. The acquired data were imported into MZmine 2 software for mass detection, chromatogram building, deconvolution and alignment. The aligned data were exported into a csv file and then traceable markers were selected using the built-in filter function in Excel. Finally, the traceable markers were identified by searching against online databases or publications, some of which were confirmed by reference standards. Results: A total of 288 chemical features transferred from herbal materials to Jing Liqueur product were rapidly screened out. Among them, 52 markers detected by HPLC-QTOF-MS were annotated, while nine volatile markers detected by GC-MS were annotated. Moreover, 30 of these markers were confirmed by comparing with reference standards. A chemical fingerprint consisting of traceable markers was finally generated to ensure the authentication and quality consistency of Jing Liqueur. Conclusion: A strategy for rapid discovery of traceable markers in herbal products using MZmine 2 software was developed.

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