Artemdubosides A-G, seven unusual polyacetylenes from Artemisia dubia var. subdigitata and their antihepatoma activity.

Artemdubosides A-E (1-5), the first examples of natural polyacetylenes substituted by 6'-O-crotonyl ß-glucopyranoside, and artemdubosides F-G (6-7) that were two unusual polyacetylenes featuring a 6'-O-acetyl ß-glucopyranoside moiety, were isolated from Artemisia dubia var. subdigitata. Their structures were elucidated based on the spectral data including HRESIMS, UV, IR, 1D and 2D NMR, and ECD calculations. Antihepatoma assay suggested that compound 1 exhibited activity against HepG2, Huh7, and SK-Hep-1 cells with inhibitory ratios of 77.1%, 90.8%, and 73.1% at 200.0 µM, respectively.

Patents research and development prospects of spleen-invigorating health food with the homology of medicine and food from 2000 to 2022: a bibliometric analysis / 数字中医药（英文）

@#,Objective To analyze the current status and development trends of the patents of spleen-invigorating health food with the homology of medicine and food in China, and to provide ideas and references for the research and development of traditional Chinese medicine (TCM) spleen-invigorating health food with the homology of medicine and food. @*Methods@#The State Administration for Market Regulation website’s “Special Food Information Query Platform” and the incoPat global patent database were searched in this study. Based on the methods of bibliometrics, the registered health food and patents related to spleen-invigorating health food with the homology of medicine and food in China were sorted out. Furthermore, the research and development numbers, provinces, institutions, technology and efficacy classification, major drugs, active ingredients and others of invigorating spleen health food in China were analyzed, and filtered patent data were visualized and analyzed by R programming language and CytoScape software. @*Results@# A total of 285 patents of health food with the homology of medicine and food for invigorating spleen were included and analyzed. From 2012, the patent registration numbers of these spleen-invigorating health food with the homology of medicine and food increased significantly in China. Over the past 20 years, the top five provinces in terms of patent disclosures were Guangdong, Anhui, Jiangsu, Shandong, and Guangxi. It was found that the technical efficacy of over 20 patents was described as “immune enhancement” “digestion” “disease prevention”, etc. Patent applications were mainly aimed at the research and development of the preservation of food or ingredients, the specific therapeutic activity of compounds, and pharmaceutical preparations, which were led by corporation research and development registrations, and supplemented by applications from research institutions and individuals. Among the 285 patents, the top 10 raw materials of spleen-invigorating health food with the homology of medicine and food were Shanyao (Dioscoreae Rhizoma), Fuling (Poria), Shanzha (Crataegi Fructus), Baizhu (Atractylodis Macrocephalae Rhizoma), Chenpi (Citri Reticulatae Pericarpium), Dazao (Jujubae Fructus), Gancao (Glycyrrhizae Radix et Rhizoma), Fengmi (Mel), Maiya (Hordei Fructus Germinatus), and Dangshen (Salviae Miltiorrhizae Radix et Rhizoma). The main functions were to nourish spleen and replenish Qi, invigorate spleen and benefit lungs, nourish blood and promote fluid production, and nourish spleen and stomach. @*Conclusion@#The main drug composition and functional components of spleen-invigorating health food with the homology of medicine and food are relatively clear, and the technical effects of invigorating the spleen and stomach, eliminating accumulation of food, and enhancing immunity are highly targeted. This paper provides evidence for the research and development, mechanism research, and process improvement of spleen-invigorating health food with the homology of medicine and food in the future.

Key Genes of Peripheral Blood Mononuclear Cells in Hepatocellular Carcinoma and Effective Chinese Herbs： A Bioinformatics Analysis and Systematic Review / 中国实验方剂学杂志

Objective:To explore the key gens of peripheral blood mononuclear cells in hepatocellular carcinoma（HCC-PBMC） and potentially effective Chinese herbs based on bioinformatics， and to verify the clinical efficacy of these Chinese herbs via a systematic review. Method:The chips GSE58208 and GSE36076 of HCC-PBMC were downloaded from the Gene Expression Omnibus （GEO）， followed by the identification of differentially expressed genes （DEGs） using RStudio. After protein-protein interaction （PPI） analysis by STRING， the DAVID was employed for gene ontology （GO） and Kyoto Encyclopedia of Genes and Genomes （KEGG） enrichment analysis. The DEGs of HCC-PBMC were visualized by Cytoscape. The key genes of HCC-PBMC were calculated by CytoHubba plug-in and mapped with those in Coremine Medical for screening out the potential Chinese herbs for the treatment of HCC， which were then included for subsequent systematic review. Result:A total of 203 DEGs were obtained （194 up-regulated and nine down-regulated）. As revealed by DAVID analysis， the DEGs were mainly enriched in such biological processes and signaling pathways as transcriptional regulation of DNA template， hydrolysis of ribonucleic acid phosphodiester bond， positive regulation of intranuclear mitosis and division， skeletal muscle fiber development， activation of mitogen-activated protein kinase（MAPK）activity， Fanconi anemia pathway， and metabolic pathway. The key genes of HCC-PBMC were calculated by Cytoscape to be<italic> </italic>GTPase IMAP family member 1 （GIMAP1）， GTPase IMAP family member 4 （GIMAP4）， GTPase IMAP family member 6 （GIMAP6）， GTPase IMAP family member 7 （GIMAP7）， GTPase IMAP family member 8 （GIMAP8）， interleukin-1<italic>β </italic>（IL-1<italic>β）</italic>， CX3C chemokine receptor 1 （CX3CR1）， C-C chemokine receptor type 2 （CCR2）， Toll-like receptor 7（TLR7）， and epidermal growth factor（EGF）. Through Coremine Medical analysis， it was concluded that Ginseng Radix et Rhizoma， Curcumae Longae Rhizoma， Centellae Herba， and Hedyotidis Herba were closely related to the key genes. Ginseng Radix et Rhizoma has the effects of tonifying and benefiting lung and spleen and enhancing strength， suitable for the liver depression and spleen deficiency syndrome or Qi-Yin deficiency syndrome of HCC. Hence， Si Junzitang with Ginseng Radix et Rhizoma as the sovereign medicinal was included for systematic review. It has been confirmed that Ginseng Radix Et Rhizoma was superior to western medicine alone in improving the overall clinical efficacy， alleviating TCM syndrome， elevating serum CD4⁺and CD4⁺/CD8⁺levels， and reducing the serum CD8⁺and TBIL levels （<italic>P</italic><0.01）， with high safety. Conclusion:This study conducted at the gene level has provided new ideas for clinical diagnosis and treatment of HCC. The systematic review of Ginseng Radix Et Rhizoma against HCC provides a basis for the clinical prevention and treatment of HCC with TCM.

Study on mechanism of enhancing antioxidant activity in fermented Ziziphi Spinosae Semen with Poria cocos / 中国中药杂志

In this study, the antioxidant property changes in fermented Ziziphi Spinosae Semen(FZSS) with Poria cocos were analyzed by DPPH, ABTS and FRAP methods. Then the content determination of active ingredients and ~1H nuclear magnetic resonance(~1H-NMR) spectroscopy were also used to investigate the mechanism of FZSS with P. cocos in enhancing the antioxidant activity. The results showed that the content of active ingredients such as total phenols, total saponins and total polysaccharides were significantly increased during the fermentation time. The results of ~1H-NMR metabonomics showed that the contents of amino acids such as leucine, lysine, valine and alanine, nitrogen compounds such as creatine, creatinine, and betaine, and secondary metabolites, for instance, jujuboside A and spinosin were higher after fermentation, and above components showed positive correlation with antioxidant capacity in Pearson correlation analysis. Therefore, it was inferred that the enhancement of antioxidant activity of FZSS may be the result of the joint action of various chemical components. This study preliminarily clarified the mechanism of FZSS in enhancing the antioxidant activity, and provided new research ideas for the product development and utilization of FZSS.

Five novel and highly efficient endophytic fungi isolated from Huperzia serrata expressing huperzine A for the treatment of Alzheimer's disease.

Huperzine A (Hup A) is an important drug for treating Alzheimer's disease (AD) and mainly extracted from the Huperzia serrata (Thunb.) Trevis. (Lycopodiaceae) (HS). Nevertheless, the content of Hup A in HS is very low of 0.007% with growing circle of 8 to 10 years, and the chemical synthesis of Hup A still has some insurmountable limitations in the industrialized production. So, the available resources of Hup A for clinical treatment of AD are scarce. The purpose of this work was to construct a biosynthesis platform based on the endophytic fungi from HS. In this work, five endophytic fungi Mucor racemosus NSH-D, Mucor fragilis NSY-1, Fusarium verticillioides NSH-5, Fusarium oxysporum NSG-1, and Trichoderma harzianum NSW-V were firstly found and isolated from the Chinese folk medicine HS, which were identified according to their morphological characteristics and nuclear ribosomal DNA ITS sequences. The highest efficient fungus could effectively biosynthesize Hup A in a liquid culture of 319.8 ± 0.17 mg/L which were 112 times higher than that of other reported conventional endophytic fungi. Moreover, these fungi with higher hereditary stability could possess the initial expressing ability of Hup A after 40 generations, and the expressed Hup A from these biosynthesis systems has prior physicochemical properties, a better inhibition activity of acetylcholinesterase and a lower cytotoxicity compared with the listed active pharmaceutical ingredients (APIs) of Hup A. These results provide promising alternative resources for producing Hup A at an industrial scale by biosynthesis, and it may also shed light on millions of AD patients. KEY POINTS: • Five novel endophytic fungi with high stability could highly express prior Hup A Graphical abstract.

Lipoic acid protects spermatogenesis in male rats with ornidazole-induced oligoasthenozoospermia / 中华男科学杂志

<p><b>Objective</b>To study the protective effect of lipoic acid (LA) on the spermatogenic function of the male rats with oligoasthenozoospermia induced by ornidazole (ORN).</p><p><b>METHODS</b>Seventy male SD rats were equally randomized into groups A (solvent control: 1 ml 0.5% CMC-Na + 1 ml olive oil), B (low-dose ORN model: 400 mg/kg ORN suspension + 1 ml olive oil), C (low-dose ORN + low-dose LA treatment: 400 mg/kg ORN + 50 mg/kg LA), D (low-dose ORN + high-dose LA treatment: 400 mg/kg ORN + 100 mg/kg LA), E (high-dose ORN model: 800 mg/kg ORN suspension + 1 ml olive oil), F (high-dose ORN + low-dose LA treatment: 800 mg/kg ORN + 50 mg/kg LA), and G (high-dose ORN + high-dose LA treatment: 800 mg/kg ORN + 100 mg/kg LA), and treated respectively for 20 successive days. Then all the rats were sacrificed and the weights of the body, testis, epididymis and seminal vesicle obtained, followed by calculation of the organ index, determination of epididymal sperm concentration and motility, and observation of the histomorphological changes in the testis and epididymis by HE staining.</p><p><b>RESULTS</b>Compared with group A, group E showed significantly decreased body weight (［117.67 ± 11.53］ vs ［88.11 ± 12.65］ g, P < 0.01) and indexes of the testis (［1.06 ± 0.12］ vs ［0.65 ± 0.13］ %, P < 0.01) and epididymis (［0.21 ± 0.03］ vs ［0.17 ± 0.01］ %, P < 0.01). In comparison with group E, group F exhibited remarkable increases in the epididymal index (［0.17 ± 0.01］ vs ［0.20 ± 0.02］ %, P < 0.01), and so did group G in the body weight (［88.11 ± 12.65］ vs ［102.70 ± 16.10］ g, P < 0.05) and the indexes of the testis (［0.65 ± 0.13］ vs ［0.95 ± 0.06］ %, P < 0.01) and epididymis (［0.17 ± 0.01］ vs ［0.19 ± 0.02］ %, P < 0.05), but no obvious difference was observed in the index of seminal vesicle among different groups. Compared with group A, group B manifested significant decreases in sperm motility (［74.12 ± 8.73］ vs ［40.25 ± 6.08］ %, P < 0.01), and so did group E in sperm count (［38.59 ± 6.40］ vs ［18.67 ± 4.59］ ×105/100 mg, P < 0.01) and sperm motility (［74.12 ± 8.73］ vs ［27.58 ± 8.43］ %, P < 0.01). Sperm motility was significantly lower in group B than in C and D (［40.25 ± 6.08］ vs ［58.13 ± 7.62］ and ［76.04 ± 8.44］%, P < 0.01), and so were sperm count and motility in group E than in F and G (［18.67 ± 4.59］ vs ［25.63 ± 9.66］ and ［29.92 ± 4.15］ ×105/100 mg, P < 0.05 and P < 0.01; ［27.58 ± 8.43］ vs ［36.56 ± 11.08］ and ［45.05 ± 9.59］ %, P < 0.05 and P < 0.01). There were no obvious changes in the histomorphology of the testis and epididymis in groups A, B, C and D. Compared with group A, group E showed necrotic and exfoliated spermatogenic cells with unclear layers and disorderly arrangement in the seminiferous tubules and remarkably reduced sperm count with lots of noncellular components in the epididymal cavity, while groups F and G exhibited increased sperm count in the seminiferous tubules and epididymis lumen, also with exfoliation, unclear layers and disorderly arrangement of spermatogenic cells, but significantly better than in group E.</p><p><b>CONCLUSIONS</b>LA can reduce ORN-induced damage to the spermatogenetic function of rats, improve sperm quality, and protect the reproductive system.</p>

The effects of essential oils of traditional Chinese medicine on the pharmaceutical properties of flexible nano-liposomes loaded with palmatine chloride / 药学学报

Flexible liposomes are an excellent drug delivery nanocarrier, however, the leakage of drugs from liposomes has become common technical obstacle in the industry and also hindered its further application seriously. It is very urgent and necessary to avoid or reduce the leakage of drugs from liposomes. In this work, five kinds of essential oils such as Folium Artemisiae Argyi oil (FA), Folium Eucalypti oil (FE), Arabian Jasmine oil (AJ), Syzygium Aromaticum oil (SA) and Fructus Forsythiae oil (FF) were encapsulated in the lipid bilayer of palmatine chloride (PC) loaded flexible nano-liposomes (PFL), then the optimal essential oil and its dosage level were determined by the external leakage curve of PC. The female Japanese white rabbits were used to evaluate the vaginal irritancy potential of liposomes samples. The pharmaceutical properties such as encapsulation efficiency, particle size, zeta potential, deformability and structure of liposomes samples were evaluated. In order to investigate the permeability of liposomes samples to deliver PC across skin and mucous membrane in vitro, the side-by-side diffusion cells were used. The results showed that the leakage of hydrosoluble PC from PFL was reduced at different degrees by the essential oils in the lipid bilayer of PFL, however, the reduction in leakage degree was obviously higher for FA than thoses of FE, AJ, SA and FF (P < 0.05), and the highest reduction in leakage degree was obtained when the FA and lipid mass ratio was 1:6. The encapsulation efficiency, particle size, zeta potential and deformability of PFL were not significantly changed after FA was encapsulated in the lipid bilayer of the PFL (P > 0.05), so did the lamellar structure of PFL. In addition, the transdermal and transmucosal permeability of PC were also enhanced obviously by encapsulating FA in the lipid bilayer of PFL, and there was no vaginal/vulvar irritation observed in the rabbits. In summary, the drug leakage was reduced by encapsulating suitable essential oil (such as FA) in the lipid bilayer of flexible liposomes, and the vaginal mucosa permeability were improved for the drug. These results provide a novel technique in the improvement of flexible nano-liposomes for drug delivery.

[Variation Characteristics and Sources of Polycyclic Aromatic Hydrocarbons in Karst Subterranean River During Rainfall Events].

The water samples were continuously collected at the outlet of Nanshan Laolongdong subterranean river basin, which is located in Chongqing, during the rainfall event in June 2014. Sixteen priority polycyclic aromatic hydrocarbons (PAHs) in water were quantitatively analyzed by gas chromatography-mass spectrometry (GC-MS). The objectives of this study were to reveal the variation characteristics and sources of PAH16 in karst subterranean river during the rainfall event. The results showed that the subterranean river responded promptly to the rainfall, and there were four peaks of the total concentrations of PAH16, two peaks occurred during the flow rise stage, the others were in the maximum flow and flow decline stages. The total concentrations of PAH16 ranged 101-3 624 ng x L(-1), with a mean of 578 ng x L(-1), the total concentrations of 7 carcinogenic PAHs ranged ND-336 ng x L(-1), with a mean of 31.1 ng x L(-1). The PAH compositional profiles were dominated by 2,3-ring compounds, which accounted for 86.17% of the total concentrations of PAH16. The total concentrations of PAH16 were most influenced by the rainfall, through the cleaning of atmospheric pollutants by the rain and the scouring of the surface contaminants by the rainfall runoff. The PAHs in water mainly originated from the incomplete combustion of petroleum products and fossil fuels such as coal, as well as natural digenetic process. Compared to other areas in the world, the concentrations of PAH16 were generally at moderately polluted and heavily polluted levels.

Application of micellar solubilization technology in pilot production of Chinese materia medica cataplasma containing volatile oil / 中草药

Objective: Through the studies on pilot production of the cataplasma of Chinese materia medica (CMM) containing volatile oil, to provide a rational and feasible preparation technology for the pilot production of CMM cataplasma, so as to promote the development of CMM cataplasma. Methods: The CMM containing volatile oil was extracted by steam distillation method (SDM), ethanol reflux extraction (ERE), and CO2 supercritical fluid extraction (SFE), respectively. The extracts were prepared to cataplasma in order to investigate the effects of extracting methods on the preparation process and quality of CMM cataplasma. The effects of micellar solubilization in the distilled liquid of STM on the quality of cataplasma such as adhesiveness, flexibleness, and stability were also investigated. Results: There was the significant difference among the groups of STM, ERE, and SFE on the quality of cataplasma. The extract by STM was beneficial to the preparation process and enhancement of the quality of cataplasma obviously, while the distilled liquid by STM would cause some limitations such as oil-water separation and volatile oil volatilization losses, which could contribute to obvious difference among batches. These disadvantages by STM would be overcome by the adoption of micellar solubilization technology and the stability would be increased (P < 0.01); segregation happened for the extract by ERE at room temperature, thereby, the water bath heating was needed in the preparation; this characteristics would cause the homogeneous appearance of cataplasma due to some black spots, lower flexibleness of matrix, and the preparation was not easy to control; the extract by SFE contained a lot of impurity of grease and performed half solid. As a result, it was very difficult to blend the extract by SFE with other materials uniformly, the adhesive force of cataplasma was also reduced. In addition, the cost of higher energy consumption and production was another disadvantage for SFE. Conclusion: The STM followed by micellar solubilization would be a feasible preparation technology for the pilot production of CMM cataplasma containing volatile oil, so it is worth popularizing and applying widely.

[Normal alkanes characteristic parameters of Jinzhou Bay surface sediments].

The concentration, composition and characteristic parameters of 18 surface sediment samples collected from Jinzhou Bay were studied. The samples were soxhlet-extracted with a mixture of 1: 1 (V/V) dichloromethane-hexane and analyzed by GC-MS after purification and concentration. Concentrations of n-alkanes vary from 1.9 to 4.2 microg x g(-1) with an average value of 2.6 microg x g(-1) dry weight. n-Alkanes distribution patterns of all positions were characterized by double peak-cluster, which means double sources from terrestrial and marine origin. The sum of nC25 to nC31 accounts for 20%-32% of the total n-alkanes, while the average value of L/H, C31/C19, TAR ratio are 0.67, 3.06, 2.02, respectively. All of these three indices suggest that the terrestrial contributions are higher than marine sources, especially for No. 2, 3 and 7 stations, which were influenced by riverinput nearby. Carbon Preference Index (CPI) ranges from 1.19 to 2.63 with an average value of 1.73, which is close to 1; the ratio of Pristane/Phytane (Pr/Ph) and unresolved/resolved compounds (U/R) range from 0.91 to 1.28, 2.2 to 4.3, respectively. All of these three parameters indicate that No. 13 and 15 stations are influenced by petroleum pollution. Comprehensive analysis of various parameters shows that Jinzhou Bay is threatened by both terrestrial inputs and petroleum hydrocarbons contaminations, which may relate to river discharging and port shipping in Jinzhou Bay.

Combination of acupuncture, cupping and medicine for treatment of fibromyalgia syndrome: a multi-central randomized controlled trial / 中国针灸

<p><b>OBJECTIVE</b>To evaluate the clinical effect of combination of acupuncture, cupping and medicine for treatment of fibromyalgia syndrome.</p><p><b>METHODS</b>By using multi-central randomized controlled method, 186 cases were randomly divided into an acupuncture combined with cupping and western medicine group (group A), an acupuncture combined with cupping group (group B) and a western medicine group (group C) and treated continuously for 4 weeks. The treatment of acupuncture combined with cupping was produced by acupuncture at five mental points and moving cupping on the Hechelu of the back, once evrey other day, thrice each week, and the western medicine therapy by oral administration of Amitriptyline, once each day. The scores of McGill Pain Questionnaire (MPQ), the amount of tenderness point and the time of producing effect were compared and the therapeutic effects were assessed with the Hamilton Depression Scale (HAMD).</p><p><b>RESULTS</b>The cured and markedly effective rate was 65.0% (39/60) in the group A, which was superior to 15.9% (10/63) in the group B and 16.1% (9/56) in the group C (both P < 0.001). After treatment, the scores of MPQ and HAMD and the amount of tenderness point all decreased in the three groups, group A being significantly better than group B and group C, and the time of producing effect in the group A was more earlier than those in the group B and the group C.</p><p><b>CONCLUSION</b>The therapeutic effect of combination of acupuncture, cupping and medicine on fibromyalgia syndrome is superior to that of the simple acupuncture combined with cupping or the simple medicine.</p>

Effect of sea buckthorn on liver fibrosis: a clinical study.

AIM: To appraise the effect of sea buckthorn (Hippophae rhamnoides) on cirrhotic patients. METHODS: Fifty cirrhotic patients of Child-Pugh grade A and B were randomly divided into two groups: Group A as the treated group (n=30), taking orally the sea buckthorn extract, 15 g 3 times a day for 6 months. Group B as the control group (n=18), taking vitamin B complex one tablet, 3 times a day for 6 months. The following tests were performed before and after the treatment in both groups to determine LN, HA, collagens types III and IV, cytokines IL-6 and TNFalpha, liver serum albumin, total bile acid, ALT, AST and prothrombin time. RESULTS: The serum levels of TNFalpha, IL-6, laminin and type IV collagen in group A were significantly higher than those in the control group. After a course of sea buckthorn treatment, the serum levels of LN, HA, collagen types III and IV, total bile acid (TBA) decreased significantly as compared with those before and after treatment in the control group. The sea buckthorn notably shortened the duration for normalization of aminotransferases. CONCLUSION: Sea buckthorn may be a hopeful drug for prevention and treatment of liver fibrosis.