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    2021,13(3), DOI:
    Abstract:
    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.
    2021,13(3), DOI: 10.1016/j.chmed.2021.04.014
    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.
    2021,13(3), DOI: 10.1016/j.chmed.2021.06.001
    Abstract:
    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.
    2021,13(3), DOI: 10.1016/j.chmed.2021.06.005
    Abstract:
    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.
    2021,13(3), DOI: 10.1016/j.chmed.2021.05.001
    Abstract:
    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.
    2021,13(3), DOI: 10.1016/j.chmed.2021.04.016
    Abstract:
    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.
    2021,13(3), DOI: 10.1016/j.chmed.2021.06.002
    Abstract:
    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.
    2021,13(3), DOI: 10.1016/j.chmed.2021.06.004
    Abstract:
    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.
    2021,13(3), DOI: 10.1016/j.chmed.2020.09.007
    Abstract:
    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.
    2021,13(3), DOI: 10.1016/j.chmed.2021.04.015
    Abstract:
    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.
    2021,13(3), DOI: 10.1016/j.chmed.2021.03.001
    Abstract:
    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.
    2021,13(3), DOI: 10.1016/j.chmed.2021.04.013
    Abstract:
    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.
    2021,13(3), DOI: 10.1016/j.chmed.2021.06.003
    Abstract:
    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.
    2021,13(3), DOI: 10.1016/j.chmed.2021.05.002
    Abstract:
    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.
    2021,13(3), DOI: 10.1016/j.chmed.2021.05.003
    Abstract:
    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.
    2021,13(3), DOI: 10.1016/j.chmed.2021.05.004
    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.
    2021,13(3):267-273, DOI: 10.1016/j.chmed.2020.10.002
    Abstract:
    Objective: The moisture content in the soil directly affects the yield and quality of Panax notoginseng, especially at the age of three years old. However, the suitable moisture for the growth of P. notoginseng is unknown. In this study, the effects of different soil moisture on the growth of P. notoginseng were studied. Methods: Four different water treatments (0.45 field capacity (FC), 0.60 FC, 0.70 FC, and 0.85 FC) were set up in Shilin County, Yunnan Province, China. The water consumption and daily dynamic of water consumption were determined daily (from April 21 to October 18, 2012), and the daily dynamic of water consumption under different weather conditions (sunny and rainy) was determined. The transpiration coefficient and water use efficiency were calculated through dry matter accumulation and total water consumption. Accumulation of saponins of roots of P. notoginseng were analyzed by HPLC after treated, and the soil moisture content suitable for the growth of P. notoginseng was estimated by regression fitting of the active ingredient accumulation and the soil moisture content. Results: The water consumption of 0.85 FC, 0.70 FC, 0.60 FC and 0.45 FC were 2.89, 3.68, 3.37 and 2.73 kg/plant per day, respectively. The water consumption of P. notoginseng from June to August was greater than other months. The daily dynamic of water consumption on sunny days and sunny days after rain showed a “double peak” feature, and it showed a “single peak” feature on rainy days. The water uses efficiency (WUE) of 0.85 FC, 0.70 FC, 0.60 FC and 0.45 FC were 2.51, 3.32, 4.59, 3.39 gDW/kg H2O, respectively. The increase of soil moisture content would reduce the WUE of P. notoginseng. With the increase of soil water content, the content of notoginsenoside R1 and ginsenoside Rg1 did not change significantly, while the content of ginsenoside Rb1 and Rd showed a decreasing trend. Conclusion: Soil moisture content significantly affected the water consumption of P. notoginseng, and when it was 56.4% of the maximum water holding capacity in the field, the sum of the four saponins of 100 strains of P. notoginseng was the highest.
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    2012,4(1):63-69, DOI: 10.3969/j.issn.1674-6384.2012.01.010
    [Abstract] (1677) [HTML] (0) [PDF 160.29 K] (10578)
    Abstract:
    Objective To identify and analyze the volatile constituents in the leaves and fruits of Ficus carica. Methods Gas chromatography (GC) and gas chromatography-mass spectrometry (GC-MS) were used. Results The major components detected in volatile oil of the leaves were psoralen (10.12%), β-damascenone (10.17%), benzyl alcohol (4.56%), behenic acid (4.79%), and bergapten (1.99%), etc. The major components detected in volatile oil of the fruits were furfural (10.55%), 5-methyl-2-furaldehyde (10.1%), and benzeneacetaldehyde (6.59%), etc. Conclusion A total of 121 volatile constituents are identified in the leaves and 108 in the fruits of F. carica, among which 103 constituents are identified for the first time in the leaves and 100 in the fruits. Eighteen volatile constituents are identified in both leaves and fruits.
    2010,2(4):272-288, DOI: 10.3969/j.issn.1674-6384.2010.04.005
    [Abstract] (2964) [HTML] (0) [PDF 307.65 K] (9992)
    Abstract:
    Callicarpa Linn. (beautyberry) is one of the major genera in Verbenaceous, about 20 of which are medicinal plants. Beautyberry, called Zizhu in China, is a generic name of those species and largely used as hemostatic medicine. The Chinese Pharmacopoeia 2010 has admitted three new crude drugs from the genus of Callicarpa Linn. including Callicarpae Macrophyllae Folium, Callicarpae Caulis et Folium, and Callicarpae Formosanae Folium for the first time since the 1977 version of the Chinese Pharmacopoeia. In order to better understand these new crude drugs, we systematically described their bibliography, admission reasons, botanical identification, chemistry, and pharmacology. Several other species, out of national regulations but intensively studied and widely used, are also covered in this review.
    2012,4(3):245-251, DOI: 10.3969/j.issn.1674-6384.2012.03.012
    [Abstract] (2263) [HTML] (0) [PDF 221.06 K] (9957)
    Abstract:
    Objective Establishing a ?ngerprint method to identify the characteristic chemicals in the roots of Gentiana macrophylla and evaluate their quality. Methods RP-HPLC was developed for ?ngerprint analysis and determination of four ingredients in G. macrophylla roots from different sources. LC-ESI-TOF-MS was employed to identify the chromatographic peaks of the ?ngerprint. Results Five common peaks were identified by comparing their retention time with reference secoiridoid glucosides. Eight major peaks in chromatographic fingerprint were analyzed by on-line LC-ESI-TOF-MS. Four secoiridoid glucosides were identified based on their MS data. Conclusion The method is specific and could be served for the quality identi?cation and comprehensive evaluation of G. macrophylla.
    2015,7(), DOI:
    [Abstract] (2100) [HTML] (0) [PDF 503.58 K] (9378)
    Abstract:
    Traditional Chinese medicine (TCM) has developed over thousands of years and has accumulated abundant clinical experience, forming a comprehensive and unique medical system. Emerging evidence has begun to illustrate TCM as an area of important medical rediscoveries. This paper briefly introduced the concept, significance, and technology of network pharmacology based on network biology and systems biology. It focused on the theoretical system and potential prospect of TCM network applied in TCM research and development including predicting new drug targets, action mechanism, new drug discovery; evaluating pharmacodynamics, pharmacokinetics, safety, toxicology, quality control, and bioinformatics of drugs. We also discussed the opportunities and challenges in the development and application of network pharmacology in the modernization of TCM research.
    [Abstract] (2046) [HTML] (0) [PDF 583.26 K] (8943)
    Abstract:
    Rhubarb is a perennial herb belonging to the genus Rheum L. (Polygonaceae). Rhei Radix et Rhizoma (rhubarb roots and rhizomes) is one of the most popular Chinese materia medica and has been widely used for strong laxative function. About 200 compounds with six different types of skeletons (anthraquinone, anthrone, stilbene, flavonoids, acylglucoside, and pyrone) have so far been isolated from eighteen species of the genus Rheum L. These constituents showed extensive pharmacological activities including cathartic, diuretic, anticancer, hepatoprotective, anti-inflammatory, and analgesic effects, as well as toxicological effects. Chemical fingerprint, LC-MS, and other analytical techniques have been used for the quality control of rhubarb. This comprehensive review summarizes the researches into the isolation, pharmacological activities, and phytochemical analysis reported since investigations began in the late 1940s. In addition, pharmacokinetic studies and clinical application of rhubarb are also discussed in present paper.
    2016,8(3):196-208, DOI: 10.1016/S1674-6384(16)60043-6
    Abstract:
    Chinese Pharmacopoeia is updated every five years, of which traditional Chinese medicine (TCM) is the most important part. The 2015 version completed by the 10th Pharmacopoeia Commission has come into operation since December 1, 2015. Here we introduced the revision and improvement of quality evaluation and control standards of TCMs in Chinese Pharmacopoeia 2015.
    2010,2(2):148-152, DOI: 10.3969/j.issn.1674-6384.2010.02.010
    [Abstract] (3209) [HTML] (0) [PDF 215.71 K] (8085)
    Abstract:
    Objective To develop an efficient method to isolate and purify the main components isoaloeresin D and aloin from Aloe vera for its industrial production. Methods High-speed counter-current chromatography was used to isolate isoaloeresin D and aloin in a one-step separation from dried crude extract of A. vera. The biphasic solvent system composed of hexane-ethyl acetate-acetone-water (0.2︰5︰1.5︰5) was used at a flow rate of 1.0 mL/min, while the lipophilic phase was selected as the mobile phase and the apparatus was rotated at 840 r/min. The effluent was detected at 254 nm. Results Isoaloeresin D (53.1 mg) and aloin (106.9 mg) were separated from the crude extract (384.7 mg) with the purities of 98.6% and 99.5%, respectively. Conclusion HSCCC is a powerful technique for isolation and separation of chemical composition from aloe.
    2010,2(4):250-261, DOI: 10.3969/j.issn.1674-6384.2010.04.003
    [Abstract] (2844) [HTML] (0) [PDF 401.07 K] (7831)
    Abstract:
    For the protection of consumers and developments of relevant industry, authentication of medicinal plants is a critical issue. This review covers various aspects of authentication methods and techniques based on molecular biology and genomics with special emphasis on molecular biology techniques including genome-based authentication, microchip-based authentication, DNA barcoding, and their applications.
    2015,7(), DOI:
    [Abstract] (1724) [HTML] (0) [PDF 273.72 K] (7378)
    Abstract:
    Cistanches Herba, a famous traditional Chinese materia medica, has a laudatory title “desert ginseng”. According to Chinese Pharmacopoeia 2000, Cistanches Herba is the dry fleshy stem with scale-like leaves of Cistanche deserticola. In order to expand the drug source, Chinese Pharmacopoeia 2005 increased the plants in Cistanche Hoffmg. et Link (Orobanchaceae), C. tubulosa, and dry scaly leaf succulent stems were as genuine Cistanches Herba and still in use. In order to have more comprehensive understanding on Cistanches Herba, this paper focuses the reviews on the biological characteristics, chemical constituents, and pharmacological activities of Cistanches Herba, and its development prospects are looked forward. It provides the relative theoretical basis for the subsequent research work of Cistanches Herba and can be conducive to the development and utilization of Cistanches Herba.
    2011,3(2):150-155, DOI: 10.3969/j.issn.1674-6384.2011.02.011
    [Abstract] (2396) [HTML] (0) [PDF 157.86 K] (7133)
    Abstract:
    Objective Ginger (Zingiber officinale) is widely used as a spice in cooking and as a medicinal herb in traditional herbal medicine. The present study was to investigate the analgesic and anti-inflammatory activities of ginger oil in experimental animal models. Methods The analgesic effect of the oils was evaluated by the “acetic acid” and “hot-plate” test models of pain in mice. The anti-inflammatory effect of the oil was investigated in rats, using rat paw edema induced by carrageenan, adjuvant arthritis, and vascular permeability induced by bradykinin, arachidonic acid, and histamine. Indomethacin (1 mg/kg), Aspirin (0.5 g/kg) and Dexamethasone (2.5 mg/kg) were used respectively as reference drugs for comparison. Results The ginger oil (0.25-1.0 g/kg) produced significant analgesic effect against chemically- and thermally-induced nociceptive pain stimuli in mice (P < 0.05, 0.01). And the ginger oil (0.25-1.0 g/kg) also significantly inhibited carrageenan-induced paw edema, adjuvant arthritis, and inflammatory mediators-induced vascular permeability in rats (P < 0.05, 0.001). Conclusion These findings confirm that the ginger oil can be used to treat pain and chronic inflammation such as rheumatic arthritis.
    2015,7(), DOI:
    [Abstract] (1738) [HTML] (0) [PDF 324.52 K] (7095)
    Abstract:
    Objective To predict the total flavonoids concentration of Aurantii Fructus fried with bran in its extraction process. Methods Ultraviolet spectrophotometry was used to determine the concentration of total flavonoids in different extraction time (t ) and solvent load (M ). Then the predicted procedure was carried out using the following data: 1) based on Ficks second law, the parameters of the kinetic model could be deduced and the equation was established; 2) Locally weighted regression (LWR) code was developed in the WEKA software environment to predict the concentration. And then we used both methods to predict the concentration of total flavonoids in new experiments. Results After comparing the predicted results with the experimental data, the LWR model had better accuracy and performance in the prediction. Conclusion LWR is applied to analyze the extraction process of Chinese herb for the first time, and it is totally fit for the extraction. LWR-based system is a more simple and accurate way to predict than the established equation. It is a good choice especially for a process which exists no clearly rules, and can be used in the real-time control during the process.
    2010,2(2):81-105, DOI: 10.3969/j.issn.1674-6384.2010.02.001
    [Abstract] (2802) [HTML] (0) [PDF 822.05 K] (7001)
    Abstract:
    Objective The 1-aminocyclopropanecarboxylic acid (ACPC) is a natural micromolecule non-protein amino acid that exists only in plants. Despite the determination of its regulating effects on plants, several bioactivities and effects on animals or humans are still unclear. This review focuses the pharmaceutical effects,above all, the neuroprotective effects of ACPC on the cerebro- and cardiovascular system. Methods Two hundred and seventy nine studies were selected and identified from a total of 2457 references in Medline and Chemical Abstracts from 1957 to 2008. Only 38 articles on neuroprotective effects of ACPC from seven different countries qualified to be included in the analysis. Results ACPC has altogether following six general neuroprotective effects on the brain and nervous system: anti-neurotoxicity induced by NMDA, dynorphin-A, glutamate, and morphine; protection from cerebral neurological injury induced by ischemia; antidepressant and anxiolytic effects; anti-convulsion and -seizures and control of epilepsy; facilitation of spatial learning and memory; and the effect of reducing alcohol consumption. Conclusion ACPC has shown a variety of effects on plants and animals. The bioactivities and pharmaceutical effects on animals are of great significance to medical research and public health. Further clinical trials or epidemiological studies are needed to determine its effect in humans. Food intervention with ACPC-rich vegetables and fruits may be a suitable therapy for cerebro- and cardiovascular system diseases. Administration of trace exogenous ACPC could produce vegetables and fruits of rich endogenous ACPC.
    2015,7(), DOI:
    [Abstract] (1917) [HTML] (0) [PDF 488.37 K] (6704)
    Abstract:
    Bentysrepinine (Y101), a derivative of repensine, is a novel di-peptide structure isolated from Dichondra repens. In vitro and in vivo tests exhibited that bentysrepinine markedly inhibited DNA-HBV and cccDNA activities. The binding mode of Y101 and repensine with DNA polymerase was driven by hydrophobic interactions. This might provide novel recognition of inhibitory effect of Y101 against HBV, though its inhibition mechanism needs to be validated by bio-assay at cellular level and of polymerase activity. Preliminary docking study suggested that Y101 might be able to inhibit HIV inverse transcriptase, also have the potential to interact with DNA polymerase and HCV NS5B polymerase.
    2011,3(2):117-126, DOI: 10.3969/j.issn.1674-6384.2011.02.006
    [Abstract] (2802) [HTML] (0) [PDF 211.05 K] (6627)
    Abstract:
    The reports on chemical constituents of Hyoscyamus niger were summarized. The compounds include alkaloids, saponins, lignans, coumarinolignans, flavonoids, and some other nonalkaloidal compounds. TLC, HPLC, and GC were used for the qualitative and quantitative analyses of some chemical constituents in H. niger. Modern pharmacological experiments showed that H. niger had the analgesic, anti-inflammatory, antipyretic, anticonvulsant, spasmolytic, antidiarrhoeal, antisecretory, bronchodilatory, urinary bladder relaxant, hypotensive, cardiosuppressant, vasodilator, antitumor, and feeding deterrent properties. In addition, the toxicities of this medicinal plant were also described.
    2015,7(), DOI:
    [Abstract] (1808) [HTML] (0) [PDF 299.63 K] (6469)
    Abstract:
    The inception of network pharmacology comes from the advance in “multi-target, multi-drug” paradigm and opens up a new field for pharmaceutical science. Traditional Chinese medicine (TCM) is well-known for its use of medicinal herb combinations to treat the functional disorders induced by diseases through a holistic view, which naturally followed the principal of network pharmacology. In this review, the methodologies of network pharmacology in TCM studies were summarized. Specifically, the methodologies for network construction and network analysis were detailed by following several TCM study cases followed. The perspectives for TCM network pharmacology were also provided.
    2015,7(), DOI:
    [Abstract] (1716) [HTML] (0) [PDF 360.32 K] (6393)
    Abstract:
    Objective A reversed-phase HPLC method was established for the simultaneous determination of five hydrophilic and lipophilic components in the roots of Salvia miltiorrhiza. Methods Hydrophilic components including danshensu, protocatechuic aldehyde, and salvianolic acid B, and lipophilic components such as cryptotanshinone and tanshinone IIA, were successfully separated on a Waters Symmetry C18 reverse- phase column (250 mm × 4.6 mm, 5 μm), with acetonitrile-0.5% phosphoric acid (gradient elution) as mobile phase, the detection wavelength was set at 281 nm with flow rate of 1.0 mL/min, and the column temperature was maintained at 30 °C. Results The recovery of the method was in the range of 95.1%–102.5% and the precision was less than 3% for all five analytes. All the compounds showed good linearity (R2 > 0.9990) in a relatively wide concentration range. Therefore, this HPLC method demonstrated good reproducibility, stability, and accuracy in validation studies. Conclusion Simultaneous quanti?cation of the multiple components by HPLC would be a better strategy for the quality evaluation on the roots of S. miltiorrhiza.
    2010,2(3):180-188, DOI: 10.3969/j.issn.1674-6384.2010.03.004
    [Abstract] (1936) [HTML] (0) [PDF 265.22 K] (6127)
    Abstract:
    The publications on the journal of Chinese Traditional and Herbal Drugs in Vol.40, 2009 are briefly reviewed in the categories of chemical constituents, preparations and technologies, analysis and quality control, pharmacological and clinical studies, reviews, and finally healthy principles. Some comments, especially for hot topics have been personally provided.
    2011,3(1):27-35, DOI: 10.3969/j.issn.1674-6384.2011.01.007
    [Abstract] (2989) [HTML] (0) [PDF 234.17 K] (6125)
    Abstract:
    Objective To study the antibacterial mechanisms of berberine and try to understand the reasons why bacteria cells difficultly resisted to it. Methods Detecting the minimal inhibitory concentration (MIC) of bacterial cultures incubated under sub-MIC concentration of berberine, Huanglian, and Neomycin for more than 200 generations, in order to analyze the bacteria resistance. Detecting the binding kinetics of berberine to DNA, RNA, and proteins. Observing the changes in bacterial cell surface structure with scanning electron microscopy. Detecting the Ca2+ and K+ released from berberine-treated bacterial cells with atomic absorption spectrum. Detection the absorption of methyl-3H-thymine (3H-dT), 3H-uridine (3H-U), and 3H-tyrosine (3H-Tyr) into berberine-treated bacterial cells. Results MICs of bacterial cultures, growing more than 200 generations in MH medium with 1/2 MIC of berberine (BA200) or Huanglian (HA200), did not increase compared to the control, while remarkably increased in MH medium with 1/2 MIC of Neomycin (NA200). In addition, from the culture NA200 it was easy to isolate resistant mutant strains which could grow in MH medium with more than four times MIC Neomycin, but from the culture BA200 and HA200 it was difficult to isolate berberine or Huanglian mutant strains could grow in MH medium with more than four times MIC berberine or Huanglian. The binding kinetics of berberine to DNA, RNA, and proteins illustrated that berberine could easily and tightly bind to DNA and RNA, and hardly dis-bind from DNA- and RNA-berberine complexes. Berberine could easily bind to protein too, but also easily dis-bind from berberine-protein complex. The bacterial cells treated with berberine sharply decreased the absorption of 3H-dT, 3H-U, and 3H-Tyr, as the radioactive precursors of DNA, RNA, and protein biosynthesis. Berberine could damage bacterial cell surface structure, especially for Gram-negative bacteria. Ca2+ and K+ released from berberine-treated cells increased significantly compared to the control. Conclusion All of above results indicate that bacterial cells could not easily become resistant mutants to berberine. The mechanisms for the bactericidal effect of berberine include: inhibiting DNA duplication, RNA transcription, and protein biosynthesis; influencing or inhibiting enzyme activities; destructing the bacterial cell surface structure and resulting in Ca2+ and K+ released from cells. All of the berberine bactericidal mechanisms are the most essential physiological functions for a live cell, if influenced any one such function, the mutation would be lethal mutation, so that it is difficult to get berberine resistant cells. The results in this paper also prefigure that berberine and its related Chinese medicines would provide a feasible way to control antibiotic resistance problem.
    [Abstract] (3143) [HTML] (0) [PDF 469.82 K] (6100)
    Abstract:
    This review is briefly to recall the history of research and development (R&D) of Chinese materia medica (CMM) and to discuss the challenges of Chinese traditional and herbal medicines (CTHM) facing the modern science and technology. The R&D of CTHM is thought to be an important pathway for new drug discovery. Since1949, about 140 approved new drugs have been developed, among which about 80 originated directly or indirectly from medicinal plants. CTHM has gained interest from the international medical, biomedical, and pharmaceutical institutions as a valuable source of potential medicines. For the modernization of CMM and innovative research of CTHM, there are following challenges to be faced: (1) to evaluate the efficacy, pharmacological properties, action mechanism, and active chemical constituents; (2) to develop new methodologies for the quality and safety of CTHM; (3) to apply new “-omics” techniques to accelerate drug discoveries developed from CTHM; and (4) to apply international practices including good agricultural practice, good manufacturing practice, good laboratory practice, and good clinical practice in the R&D of CTHM.

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