BMC Complementary and Alternative Medicine

Germany is a country with a high use of herbal medicinal products. Population-based data on the use of herbal medicinal products among children are lacking. The aim of this study is to investigate the prevalence, patterns and determinants of herbal medicine use among children and adolescents in Germany. As data base served the German Health Interview and Examination Survey for Children and Adolescents (KiGGS), a representative population based survey conducted 2003–2006 by the Robert Koch Institute. 17,450 boys and girls aged 0–17 years provided information on drug use in the preceding seven days. Herbal medicinal products were defined according to the European and German drug laws. SPSS Complex Sample method was used to estimate prevalence rates and factors associated with herbal medicine use. The prevalence rate of herbal medicinal product use amounts to 5.8% (95% confidence interval 5.3-6.3%). Use of herbal medicine declines along with increasing age and shows no difference between boys and girls in younger age groups. Teenage girls are more likely to use herbal medicines than teenage boys. Two thirds of herbal medicines are used for the treatment of coughs and colds; nearly half of herbal medicines are prescribed by medical doctors. Determinants of herbal medicinal product use are younger age, residing in South Germany, having a poor health status, having no immigration background and coming from a higher social class family. Children’s and parents-related health behavior is not found to be associated with herbal medicine use after adjusting for social class. Use of herbal medicinal products among children and adolescents between the ages of 0 and 17 years in Germany is widely spread and shows relatively higher rates compared to international data. This study provides a reference on the use of herbal medicinal products for policy-makers, health professionals and parents. Further studies are needed to investigate the effectiveness and safety of specific herbal medicinal products, potential effects of long term use as well as possible interactions of herbal medicinal products with concomitantly used conventional medicines.

Ayurved Siriraj Brand Wattana formula (AVS073), a Thai herbal formula, has traditionally been used for health promotion and prevention of age-related problems. Ultraviolet A (UVA) is recognized to play a vital role in stimulation of melanin synthesis responsible for abnormal skin pigmentation possibly mediated by photooxidative stress. We thus aimed to study the inhibitory effect of AVS073 extracts on UVA-induced melanogenesis via a redox mechanism involving glutathione (GSH) synthesis and glutathione S-transferase (GST) using human melanoma (G361) cell culture. The standardization of AVS073 extracts was carried out by TLC and UHPLC to obtain fingerprinting profiles of the formula, which identified several phenolic compounds including gallic acid (GA) in the formula. Antimelanogenic actions of AVS073 (up to 60 μ g/ml) and GA (up to 10 μ g/ml) were investigated by measuring tyrosinase activity and mRNA as well as melanin level in G361 cells irradiated with UVA. Moreover, antioxidant actions of the herbal formula and GA were determined by evaluating oxidant formation and modulation of GSH-related antioxidant defenses including GSH content, GST activity and mRNA level of γ-glutamate cysteine ligase catalytic (γ-GCLC) and modifier (γ-GCLM) subunit and GST. AVS073 extracts and GA, used as a reference compound, suppressed UVA-augmented tyrosinase activity and mRNA and melanin formation. In addition, pretreatment with AVS073 and GA was able to inhibit cellular oxidative stress, GSH depletion, GST inactivation and downregulation of γ-GCLC, γ-GCLM and GST mRNA in G361 cells exposed to UVA radiation. AVS073 formula exerted antimelanogenic effects possibly through improving the redox state by upregulation of GSH and GST. Moreover, pharmacological activity of the polyherbal formula would be attributed to combined action of different phenolic compounds present in the formula.

Xingnaojing (XNJ), a well known prescription in traditional Chinese medicine, has been used for treatment of stroke in China. However, the effects and mechanisms of XNJ on autophagy are not clear. Here, we used the cell models of autophagy induced by serum-free condition and ischemia stroke in rats to further investigate whether the p53-DRAM pathway is involved in the effects of XNJ on autophagy. We used the cell model of autophagy induced by serum-free condition and the rat model of ischemia caused by a middle cerebral artery occlusion (MCAO). The effects of XNJ on p53 transcriptional activity of PC12 cells were evaluated by the luciferase activity assay. The mRNA levels and the expression of p53 and its target autophagy gene DRAM (damage-regulated autophagy modulator) were analyzed respectively by Quantitative-RTPCR and Western blot assay. The activation of autophagy was detected by the levels of autophagy markers, microtubule associated protein light chain 3 (LC3) and p62 by Immunofluorescence and Western blot. p53 inhibitor was used to determine whether p53 is responsible for the effects of XNJ on preventing autophagy. The assay for luciferase activity of p53 promoter indicated that XNJ inhibited p53 transcriptional activity. XNJ reduced the expression of p53 and its target autophagy gene DRAM (damage-regulated autophagy modulator) in serum-free condition PC12 cells and the cortex in MCAO rats. XNJ reduced autophagy of PC12 cells induced by serum-free condition and the cortex in MCAO rats. Furthermore, suppression of p53 by p53 inhibitor significantly reduced the effects of XNJ on the autophagy of PC12 cells in serum-free condition. XNJ prevents autophagy in experimental stroke by repressing p53/DRAM pathway. Our findings are therefore of considerable therapeutic significance and provide the novel and potential application of XNJ for the treatment of brain diseases.

Abstract Background Fatty acid synthase (FAS) is a promising antifungal target due to its marked structural differences between fungal and mammalian cells. The aim of this study was to evaluate the antifungal activity of flavonoids described in the scientific literature as FAS inhibitors (quercetin, trans-chalcone, ellagic acid, luteolin, galangin, and genistein) against the dermatophyte Trichophyton rubrum and their effects on fatty acid and ergosterol synthesis. Methods The antifungal activity of the natural products was tested by the microdilution assay for determination of the minimum inhibitory concentration (MIC). The effect of the compounds on the cell membrane was evaluated using a protoplast regeneration assay. Ergosterol content was quantified by spectrophotometry. Inhibition of FAS by flavonoids was evaluated by an enzymatic assay to determine IC50 values. Quantitative RT-PCR was used to measure transcription levels of the FAS1 and ERG6 genes involved in fatty acid and ergosterol biosynthesis, respectively, during exposure of T. rubrum to the flavonoids tested. Results The flavonoids quercetin and trans-chalcone were effective against T. rubrum, with MICs of 125 and 7.5 μg/mL for the wild-type strain (MYA3108) and of 63 and 1.9 μg/mL for the ABC transporter mutant strain (ΔTruMDR2), respectively. The MICs of the fluconazole and cerulenin controls were 63 and 125 μg/mL for the wild-type strain and 30 and 15 μg/mL for the mutant strain, respectively. Quercetin and trans-chalcone also reduced ergosterol content in the two strains, indicating that interference with fatty acid and ergosterol synthesis caused cell membrane disruption. The MIC of quercetin reduced the number of regenerated protoplasts by 30.26% (wild-type strain) and by 91.66% (mutant strain). Half the MIC (0.5 MIC) of quercetin did not reduce the number of regenerated wild-type fungal colonies, but caused a 36.19% reduction in the number of mutant strain protoplasts. In contrast, the MIC and 0.5 MIC of trans-chalcone and cerulenin drastically reduced protoplast regeneration in the two strains. The FAS1 gene was repressed in the presence of MICs of quercetin, trans-chalcone, fluconazole and cerulenin. The ERG6 gene was induced in the presence of MICs of fluconazole and cerulenin and was repressed in the presence of MICs of trans-chalcone and quercetin. Trans-chalcone and quercetin inhibited the enzymatic activity of FAS, with IC50 values of 68.23 and 17.1 μg/mL, respectively. Conclusion Trans-chalcone and quercetin showed antifungal activity against T. rubrum, reducing ergosterol levels and modulating the expression of FAS1 and ERG6.

Crocin (CRO), chlorogenic acid (CGA), geniposide (GEN), and quercetin (QUE) are all natural compounds with anti-obesity properties, in particular, hypolipidemic effects, which have been widely used for the treatment of obesity-related metabolic diseases. However, it is not yet known whether these compounds interact synergistically. Here, we investigated the effects and molecular mechanisms of CRO, CGA, GEN, QUE, and a combination of all four compounds (CCGQ), on lipid accumulation in human hepatoma (HepG2 cells). The optimal concentration of CRO, CGA, GEN, QUE to stimulate HepG2 cells proliferation was determined using MTT assay. HepG2 cells were pretreated with 10 μmol/L simvastatin, 1 μmol/L CRO, 30 μmol/L CGA, 10 μmol/L GEN, 10 μmol/L QUE, and CCGQ (a combination of 1 μmol/L CRO, 30 μmol/L CGA, 10 μmol/L GEN, and 10 μmol/L QUE) for 24 or 48 h. Oil red O staining and extracellular TC and TG levels were detected. The RT-PCR was used to observe on cholesterol metabolism-related gene expression. Immunocytochemistry and western-blot assayed the 3-hydroxy-3-methylglutaryl-coenzyme (HMGCR) protein expression in HepG2 cells. Compared to those of control, we demonstrated that treating HepG2 cells for 48 h with CCGQ resulted in a strong synergistic effect, causing a marked decrease in lipid deposition in comparison to individual treatments, in both triglyceride and total cholesterol (CRO, 5.74- and 1.49-folds; CGA, 3.38- and 1.12-folds; GEN, 4.04- and 1.44-folds; QUE, 3.36- and 1.24-folds; simvastatin, 5.49- and 1.83-folds; and CCGQ, 7.75- and 2.20-folds), and Oil red O staining assays. In addition, CCGQ treatment increased ATP-binding cassette transporter (ABCA1), cholesterol 7α-hydroxylase (CYP7A1), and AMP-activated protein kinase 2α (AMPKα2) mRNA expression, while decreasing sterol regulatory element binding protein 2 (SREBP2), and liver X receptor alpha (LXRα) mRNA expression. Notably, CCGQ was more effective in decreasing HMGCR expression than the individual treatments. The CCGQ combination has potential, both as a complementary therapy for hyperlipemia, and in preventing further obesity-related complications.

This study aimed to develop and validate scales to assess attitudes towards patient’ s use of TCM (APUTCM) and to measure a communicative competence in TCM (CCTCM) among nurses. The instrument development process was conducted from Sep 2013 to Jul 2014, using the following steps: 1) item development; 2) internal review and refinement; 3) face and content validation; 4) instrument administration to a development sample; and 5) evaluation of validity and reliability. A convenience sample was used to recruit registered and advanced practice nurses who worked in different regions throughout Taiwan. A total of 755 respondents completed the online questionnaire. Statistical analyses were performed using the software of SPSS Version 21.0 and Analysis of Moment Structures (AMOS) version 24.0. The scale-level indexes (S-CVI) of content validity for both scales were over 80%. The reliabilities for the 13-item APUTCM scale and for the five-item CCTCM scale were 0.88 and 0.84, respectively. The model suitability for both scales was assessed, and the findings revealed suitable parameters for all indicators: GFI = 0.954, AGFI = 0.932, CFI = 0.959, RMSEA = 0.62, and chi-square/df = 3.891 for APUTCM; and GFI = 0.992, AGFI = 0.969, CFI = 0.992, RMSEA = 0.63, and chi-square/df = 4.04 for CCTCM. The convergent and divergent validity of scores on both scales provided evidence in the expected direction. This scale development study provides preliminary evidence that suggests that the 13-item APUTCM and the five-item CCTCM are reliable and valid scales for assessing attitudes toward patient’s TCM use and communicative competence in TCM.

Previous study showed that extracts from Croton macrostachyus (Euphorbiaceae) exhibit analgesic effects in acute pain models. The present study evaluates the antinociceptive properties of the methanol/methylene chloride extract (MECM) of the stem bark of this plant using mice models of persistent inflammatory and neuropathic pain, and assesses its mechanism of action. MECM was tested on Complete Freund adjuvant (CFA)-induced persistent thermal and mechanical pain, neuropathic pain induced by partial sciatic nerve ligation (PSNL), prostaglandin E2 (PGE2)-induced acute mechanical hyperalgesia, as well as on nociception induced by capsaicin in mice. Mechanical hyperalgesia was assessed using von Frey hair in awake mice. The mechanism of action of MECM was evaluated by using glibenclamide on PGE2-induced hyperalgesia or rimonabant on capsaicin-induced pain. MECM administered orally at the doses of 250 and 500 mg/kg, induced long lasting and significant antihyperalgesic effects on CFA-inflammatory and PSNL-induced neuropathic pain. MECM significantly reduced the mechanical hyperalgesia induced by PGE2 either when administered preventively or therapeutically. MECM also significantly and time dependently inhibited the capsaicin-induced nociception. These effects were not affected by glibenclamide or by rimonabant. The present results demonstrate that the oral administration of MECM to mice resulted in long lasting antihyperalgesic activity in inflammatory and neuropathic pain as well as in acute and persistent pain. The mechanism underlying the long lasting MECM antihyperalgesic effect is currently unknown, but might be mediated, at least partially, through the modulation of TRPV1 receptors.

Guibi-Tang is a traditional herbal prescription made from 12 different herbs that is used in the treatment of amnesia and poor memory. In the present study, we evaluated the acute oral toxicity and genotoxic potential of Guibi-Tang water extract (GBT) at doses up to 2000 μg/plate an using a bacterial reverse mutation test (Ames test) with Salmonella typhimurium strains TA100, TA1535, TA98, and TA1537, and Escherichia coli strain WP2uvrA. Acute toxicity and genotoxic potential were measured in the presence and absence of an exogenous source of metabolic activation, in an in vitro chromosome aberration assay with Chinese hamster lung (CHL) cells, and in an in vivo micronucleus test using ICR mice bone marrow as recommended by the Korean Food and Drug Administration. An acute oral toxicity test of GBT was performed in Sprague Dawley rats. The Ames test showed that GBT did not induce gene mutations in S. typhimurium or in E. coli in the presence or absence of S9 activation. GBT did not significantly increase the number of structural aberrations in CHL cells with or without S9 activation. The oral administration of GBT at a dose of up to 2000 mg/kg caused no significant increase in the number of micronucleated polychromatic erythrocytes or in the mean ratio of polychromatic to total erythrocytes. However, as we did not identify the components of GBT responsible for these effects, other assays are needed to confirm its genotoxicity.