14-Deoxy-11,12-didehydroandrographolide inhibits apoptosis in influenza A(H5N1) virus-infected human lung epithelial cells via the caspase-9-dependent intrinsic apoptotic pathway which contributes to its antiviral activity.

Influenza A virus (IAV) infection represents a global health challenge. Excavating antiviral active components from traditional Chinese medicine (TCM) is a promising anti-IAV strategy. Our previous studies have demonstrated that 14-deoxy-11,12-didehydroandrographolide (DAP), a major ingredient of a TCM herb called Andrographis paniculata, shows anti-IAV activity that is mainly effective against A/chicken/Hubei/327/2004 (H5N1), A/duck/Hubei/XN/2007 (H5N1), and A/PR/8/34 (H1N1) in vitro and in vivo. However, the underlying anti-IAV molecular mechanism of DAP needs further investigation. In the present work, we found that DAP can significantly inhibit the apoptosis of human lung epithelial (A549) cells infected with A/chicken/Hubei/327/2004 (H5N1). After DAP treatment, the protein expression levels of cleaved PARP, cleaved caspase-3, and cleaved caspase-9, and the activities of caspase-3 and caspase-9 in H5N1-infected A549 cells were all obviously downregulated. However, DAP had no inhibitory effect on caspase-8 activity and cleaved caspase-8 production. Meanwhile, the efficacy of DAP in reducing the apoptotic cells was lost after using the inhibitor of caspase-3 or caspase-9 but remained intact after the caspase-8 inhibitor treatment. Moreover, DAP efficiently attenuated the dissipation of mitochondrial membrane potential, suppressed cytochrome c release from the mitochondria to the cytosol, and decreased the protein expression ratio of Bax/Bcl-2 in the mitochondrial fraction. Furthermore, the silencing of caspase-9 reduced the yield of nucleoprotein (NP) and disabled the inhibitory ability of DAP in NP production in A549 cells. Overall results suggest that DAP exerts its antiviral effects by inhibiting H5N1-induced apoptosis on the caspase-9-dependent intrinsic/mitochondrial pathway, which may be one of the anti-H5N1 mechanisms of DAP.

Effect of non-surgical periodontal therapy on glycemic control of type 2 diabetes mellitus: a systematic review and Bayesian network meta-analysis.

BACKGROUND: Glycemic control is vital in the care of type 2 diabetes mellitus (T2DM) and is significantly associated with the incidence of clinical complications. This Bayesian network analysis was conducted with an aim of evaluating the efficacy of scaling and root planning (SRP) and SRP + adjuvant treatments in improving glycemic control in chronic periodontitis (CP) and T2DM patients, and to guide clinical practice. METHODS: We searched the Pubmed, Embase, Cochrane Library and Web of Science databases up to 4 May 2018 for randomized controlled trials (RCTs). This was at least three months of the duration of study that involved patients with periodontitis and T2DM without other systemic diseases given SRP. Patients in the control group did not receive treatment or SRP combination with adjuvant therapy. Outcomes were given as HbA1c% and levels fasting plasma glucose (FPG). Random-effects meta-analysis and Bayesian network meta-analysis were conducted to pool RCT data. Cochrane's risk of bias tool was used to assess the risk of bias. RESULTS: Fourteen RCTs were included. Most were unclear or with high risk of bias. Compared to patients who did not receive treatment, patients who received periodontal treatments showed improved HbA1c% level, including SRP (the mean difference (MD) -0.399 95% CrI 0.088 to 0.79), SRP + antibiotic (MD 0.62, 95% CrI 0.18 to 1.11), SRP + photodynamic therapy (aPDT) + doxycycline (Doxy) (MD 1.082 95% CrI 0.13 to 2.077) and SRP + laser (MD 0.66 95% CrI 0.1037, 1.33). Among the different treatments, SRP + aPDT + Doxy ranked best. Regarding fasting plasma glucose (FPG), SRP did not show advantage over no treatment (MD 4.91 95% CI - 1.95 to 11.78) and SRP with adjuvant treatments were not better than SRP alone (MD -0.28 95% CI -8.66, 8.11). CONCLUSION: The results of this meta-analysis seem to support that periodontal treatment with aPDT + Doxy possesses the best efficacy in lowering HbA1c% of non-smoking CP without severe T2DM complications. However, longer-term well-executed, multi-center trails are required to corroborate the results.

14-Deoxy-11,12-didehydroandrographolide attenuates excessive inflammatory responses and protects mice lethally challenged with highly pathogenic A(H5N1) influenza viruses.

Traditional Chinese medicine (TCM) has been an excellent treasury for centuries' accumulation of clinical experiences, which deserves to be tapped for potential drugs and improved using modern scientific methods. 14-Deoxy-11,12-didehydroandrographolide (DAP), a major component of an important TCM named Andrographis paniculata, with non-toxic concentration of 1000 mg/kg/day, effectively reduced the mortality and weight loss of mice lethally challenged with A/chicken/Hubei/327/2004 (H5N1) or A/PR/8/34 (H1N1) influenza A viruses (IAV) when initiated at 4 h before infection, or A/duck/Hubei/XN/2007 (H5N1) when initiated at 4 h or 48 h before infection, or 4 h post-infection (pi). DAP (1000 or 500 mg/kg/day) also significantly diminished lung virus titres of infected mice when initiated at 4 h or 48 h before infection, or 4 h pi. In the infection of A/duck/Hubei/XN/2007 (H5N1), DAP (1000 mg/kg/day) treatment initiated at 48 h before infection gained the best efficacy that virus titres in lungs of mice in log10TCID50/mL reduced from 2.61 ± 0.14 on 3 days post-infection (dpi), 2.98 ± 0.17 on 5 dpi, 3.54 ± 0.19 on 7 dpi to 1.46 ± 0.14 on 3 dpi, 1.86 ± 0.18 on 5 dpi, 2.03 ± 0.21 on 7 dpi. Moreover, DAP obviously alleviated lung histopathology and also strongly inhibited proinflammatory cytokines/chemokines expression. The mRNA levels of TNF-α, IL-1ß, IL-6, CCL-2/MCP-1, IFN-α, IFN-ß, IFN-γ, MIP-1α, MIP-1ß in lungs of A/duck/Hubei/XN/2007 (H5N1)-infected mice and serum protein expression of TNF-α, IL-1ß, IL-6, CCL-2/MCP-1 and CXCL-10/IP-10 in mice infected with all the three strains of IAV were all significantly reduced by DAP. Results demonstrated that DAP could restrain both the host intense inflammatory responses and high viral load, which were considered to contribute to the pathogenesis of H5N1 virus and should be controlled together in a clinical setting. Considering the anti-inflammatory and anti-IAV activities of DAP, DAP may be a promising active component obtained from A. paniculata, which can be further investigated as a useful constitute of curative strategies in the future against IAV, the H5N1 strains in particular.

Chinese herbal medicine Yougui Pill reduces exogenous glucocorticoid-induced apoptosis in anterior pituitary cells.

Long-term glucocorticoid use may result in sustained suppression of one or more secreted components from the hypothalamo-pituitary-adrenal axis, and often results in apoptosis. Yougui Pill (YGP), a 10-component traditional Chinese herbal medicine, has been shown to be clinically effective for glucocorticoid-induced suppression of the hypothalamo-pituitary-adrenal axis. However, the pharmacological and molecular mechanisms remain unclear. We hypothesized that YGP would exert an anti-apoptosis effect on dexamethasone-treated anterior pituitary cells. In vivo experiments showed that YGP significantly reduced the number of apoptotic cells, down-regulated mRNA expression of cytochrome c, caspase-3, and caspase-9, and up-regulated mRNA expression of Bcl-2. These findings suggest that YGP reduced glucocorticoid-induced apoptosis in rat anterior pituitary cells by regulating the mitochondria-mediated apoptosis pathway.

The Use of Traditional Chinese Medicine in Some Dermatologic Diseases: Part II--Autoimmune Bullous Disorders and Lichen Planus.

Over the centuries, traditional Chinese medicine (TCM) and Western medicine have traveled along parallel lines with no opportunity for collaboration. In recent decades, while an interest in TCM has been growing among Western clinicians, progress has been made in the comprehension of pathogenic mechanisms of skin disorders, and the communication between Western and Eastern medicines has become more and more intensive. In this paper, the authors discuss TCM remedies used in the treatment of autoimmune bullous disorders (pemphigus and bullous pemphigoid) and lichen planus. Future studies on the active components of the TCM will certainly shed new light on the still obscure aspects of some dermatologic diseases.

[Study on Chemical Constituents of Petroleum Ether Fraction from Rubus alceaefolius].

OBJECTIVE: To investigate the chemical constituents of Rubus alceaefolius. METHODS: Nine compounds were isolated and purified from the petroleum ether extract of 95% alcohol extract of Rubus alceaefolius by repeated column chromatography on silica, Sephadex LH-20 and structurally identified by spectral analysis. RESULTS: The compounds were identified as chrysophanol(1), physcion (2), ß-sitosterol(3), 3-oxotirucalla-7, 24-dien-21-oic acid(4), myricadiol(5), 19-α-hydroxy-3-acetyl-ursolic acid(6), N-benzoylphenylalaninyl-N-benzoylphenylalaninate(7), aurantiamide acetate(8) and euscaphic acid(9). CONCLUSION: Compounds land 4~8 are isolated from this plant for the first time, and compounds 4 - 8 are found in plants of Rubus genus for the first time.

The use of traditional Chinese medicine in some dermatologic diseases: Part I--Acne, psoriasis, and atopic dermatitis.

Traditional Chinese medicine (TCM) is increasingly being used in the Western world particularly in specialty areas such as gynecology, pediatrics, nutrition, and dermatology. TCM is an alternative method of therapy that proposes to treat symptoms that Western medicine is unable to manage by treating the underlying causes of disease. The authors provide a general overview of TCM remedies used in the treatment of various dermatologic disorders (acne, psoriasis, atopic dermatitis) for dermatologists interested in this unconventional therapeutic approach.

14-Deoxy-11,12-dehydroandrographolide exerts anti-influenza A virus activity and inhibits replication of H5N1 virus by restraining nuclear export of viral ribonucleoprotein complexes.

The highly pathogenic avian influenza H5N1 virus has become a worldwide public health threat, and current antiviral therapies have limited activity against the emerging, resistant influenza viruses. Therefore, effective drugs with novel targets against influenza A viruses, H5N1 strains in particular, should be developed. In the present study, 14-deoxy-11,12-dehydroandrographolide (DAP), a major component of the traditional Chinese medicine Andrographis paniculata, exerted potent anti-influenza A virus activity against A/chicken/Hubei/327/2004 (H5N1), A/duck/Hubei/XN/2007 (H5N1), A/PR/8/34 (H1N1), A/NanChang/08/2010 (H1N1) and A/HuNan/01/2014 (H3N2) in vitro. To elucidate the underlying mechanisms, a series of experiments was conducted using A/chicken/Hubei/327/2004 (H5N1) as an example. Our results demonstrated that DAP strongly inhibited H5N1 replication by reducing the production of viral nucleoprotein (NP) mRNA, NP and NS1proteins, whereas DAP had no effect on the absorption and release of H5N1 towards/from A549 cells. DAP also effectively restrained the nuclear export of viral ribonucleoprotein (vRNP) complexes. This inhibitory effect ought to be an important anti-H5N1 mechanism of DAP. Meanwhile, DAP significantly reduced the upregulated expression of all the tested proinflammatory cytokines (TNF-α, IL-6, IL-8, IFN-α, IL-1ß and IFN-ß) and chemokines (CXCL-10 and CCL-2) stimulated by H5N1. Overall results suggest that DAP impairs H5N1 replication at least in part by restraining nuclear export of vRNP complexes, and the inhibition of viral replication leads to a subsequent decrease of the intense proinflammatory cytokine/chemokine expression. In turn, the effect of modification of the host excessive immune response may contribute to overcoming H5N1. To our knowledge, this study is the first to reveal the antiviral and anti-inflammatory activities of DAP in vitro against H5N1 influenza A virus infection.

[Comparative study on the content of chlorogenic acid in Solanum torvum from different origin, different harvest time and different part].

OBJECTIVE: To develop a HPLC method for determination of chlorogenic acid in Solanum torvum and provide a scientific basis for evaluating the quality and reasonable utilization of the herb. METHODS: HPLC was used to quantitatively determine the chlorogenic acid content in Solanum torvum from different origin, different harvest time and different part. The assay was performed on a Agela Promosil C18 (4.6 mm x 250 mm, 5 microm) column and eluted with a mobile phase consisted of acetonitrile -0.1% phosphoric acid solution at a flow rate of 1.0 ml/min. The column temperature was set at 35 degrees C. The detection wavelength was 327 nm. RESULTS: The calibration curve was linear within the range of 0.1000 - 200.0 microg/mL (r = 0.9999). The average recoveries were 99.8% (RSD = 0.71%). The contents of chlorogenic acid in Solanum torvum were different from different origin, different harvest time and different part. CONCLUSION: The method is reliable, accurate and specific. It can be used for quality control of Solanum torvum and reasonable utilization of the herb.

[Study on triterpenes from Solanum torvum].

OBJECTIVE: To study on the chemical constituents of Solanum torvum. METHOD: The aerial parts of S. torvum swartz were extracted with 95% alcohol and the constituents were isolated and purified by chromatographic silica gel and Sephadex LH-20. Their structures were determined by NMR and MS spectral analysis. RESULT: Six triterpenes were isolated and identified as 3beta-acetyloleanolic acid (1), 3-O-acetyl-11alpha, 12alpha-epoxy-oleanan-28, 13beta-olide (2), oleanolic acid (3), ursolic acid (4), 2alpha-hydroxy-oleanolic acid (5), 2alpha, 3beta-dihydroxyursolic acid (6). CONCLUSION: All compounds were obtained from this plant for the first time.

Applications of ultra-performance liquid chromatography to traditional Chinese medicines.

Ultra-performance liquid chromatography (UPLC), as a development of the chromatographic technique, was used in the quality control of Panax ginseng C.A. Mey. In the study, the UPLC methods were transferred from conventional high-performance liquid chromatography (HPLC) methods according to chromatographic equations. The results demonstrated that UPLC analysis methods could be transferred from HPLC without loss of efficiency. Compared with conventional HPLC, UPLC made a surprising 10-fold increase in speed and 20-fold decrease in solvent consumption. The study indicated UPLC as a suitable alternative to HPLC and can be reliably applied to quality control of traditional Chinese medicines.

[Bacterial diversity analysis of moderately thermophilic microflora enriched by different energy sources].

Bacterial biodiversities of three moderately thermophilic bioleaching microfloras grown at 50 degrees C on media with pyrite, chalcopyrite, and pure ferrous iron supplemented with sulfur as energy sources were investigated respectively. The 16S rRNA genes of the microorganisms in the cultures flasks were PCR amplified and cloned to identify the bacterial species by comparative sequence analysis, the structural differences of microfloras enriched by different energy sources were compared. A total of 303 clones were recovered and evaluated by restriction fragment length polymorphism (RFLP) analysis. Cluster analysis identified 29 unique RFLP patterns, and the inserted 16S rRNA genes sequences were determined and for phylogenetic analysis. Most of sequences obtained were similar (89.1%-99.7%) to the 16S rRNA gene sequences of the reported bioleaching microorganisms. The species identified from the flasks during bioleaching of pyrite, pure ferrous iron supplemented with sulfur, and chalcopyrite were closely related to Acidithiobacillus caldus, Sulfobacillus thermotolerans, Sulfobacillus thermosulfidooxidans, Leptospirillum ferriphilum, two uncultured forest soil bacterium clones and one uncultured proteobacterium clone. Among these bacteria, Acidithiobacillus caldus, Sulfobacillus thermotolerans and Leptospirillum ferriphilum were the dominant bacterial species. L. ferriphilum was the most dominant species in microfloras enriched in media with pyrite and ferrous iron supplemented with sulfur as energy sources, the abundance were 53.8% and 45.9% respectively. In the culture with chalcopyrite as energy sources, S. thermotolerans had the highest abundance of 70.1%.

[Determination of organochlorine pesticides redidues in traditional Chinese medicine including ginseng or American ginseng].

OBJECTIVE: To determine the residues of 19 organochlorine pesticides in traditional chinese medicine (TCM) including Radix ginseng or Radix panacis quinquefolii by capillary gas chromatograrhy. METHODS: The samples were extracted with ethyl acetate by ultrasonic, then cleaned up by a column packed with Florisil. The capillary column was DB-1701 (30 m x 0.32 m, 0.25 microm). The electron capture detector (ECD) was used. The pesticide residues were calculated by external standard method. RESULTS: The average recoveries and RSD ranged from 70.4% to 125.0% and 3.16% to 9.86%. CONCLUSION: The method is rapid, simple and accurate. It can be used to determine organochlorine pesticide residues in TCM.