Cloning, sequencing, and heterologous expression of the elmGHIJ genes involved in the biosynthesis of the polyketide antibiotic elloramycin from Streptomyces olivaceus Tü2353

Elloramycin A (1) belongs to a small family of naphthacenequinones characterized by a unique highly hydroxylated cyclohexenone moiety. A cosmid clone 16F4, harboring genes for the production of 1 from Streptomyces olivaceus Tü2353, has been previously isolated. DNA sequence analysis of a 3.2-kb fragment from 16F4 revealed four open reading frames--the elmGHIJ genes. Heterologous expressions of the elmGHI genes in either Escherichia coli or Streptomyces lividans, followed by biochemical characterizations of the ElmGHI proteins, established ElmG as tetracenomycin B2 oxygenase, ElmH as tetracenomycin F1 monooxygenase, and ElmI as tetracenomycin F2 cyclase. These results provide direct biochemical evidence for the hypothesis that the biosynthesis of 1 in S. olivaceus parallels that of tetracenomycin C (2) in Streptomyces glaucescens and support the notion that the biosynthesis of the highly hydroxylated cyclohexenone moiety in other polyketides most likely follows the same paradigm as the tetracenomycin B2 or A2 oxygenase.     

Tracheal relaxation of five Ivorian anti-asthmatic plants: role of epithelium and K⁺ channels in the effect of the aqueous-alcoholic extract of Dichrostachys cinerea root bark

Ethnopharmacological relevance

Leaves of Boerhavia diffusa (Nyctaginaceae), Baphia nitida, Cassia occidentalis, Desmodium adscendens (Fabaceae), and root bark of Dichrostachys cinerea (Fabaceae) are used in Ivory Coast for the treatment of asthma. The aim of this study was to evaluate the potential airway relaxant activity of different extracts of these plants.

Materials and methods

Extracts of different polarities (H₂O, EtOH/H₂O, MeOH and CH₂Cl₂) were obtained from these five plants. Their ex vivo relaxant activity was tested in mice isolated trachea precontracted with carbachol (1 μM).

Results

Cumulative concentrations of most extracts induced moderate to strong relaxation, the methanolic extracts being the most potent and the polar extracts the most active at the concentrations used, supporting the traditional use of these five plants as anti-asthmatic remedies. We further investigated the molecular and cellular mechanisms of the mouse trachea relaxant effect of the aqueous-alcoholic extract of Dichrostachys cinerea root bark, the most potent extract. Its effect was not modified in the presence of β-adrenoceptor antagonists (propranolol or ICI 118,551) or a PKA inhibitor (H89). By contrast, it was decreased after depolarization-induced precontraction (with 80 mM KCl), in the presence of some K⁺ channels blockers [4-aminopyridine as voltage-dependent K⁺ (K_v) channel blocker and tetraethylammonium chloride as large conductance Ca²⁺-activated K⁺ (BK_Ca) channel blocker, but not with glibenclamide, an ATP-sensitive K⁺ (K_ATP) channel blocker] or after epithelium removal.

Conclusions

The mouse tracheal relaxant effect of Dichrostachys cinerea EtOH/H₂O extract was independent of β₂-adrenoceptors activation and cAMP/PKA pathway, but dependent on epithelium and K⁺ channels, namely K_v and BK_Ca channels. Further investigation will be required to identify the component(s) responsible for this airways relaxant activity.     

The effect of the extract of Crocus sativus on tracheal responsiveness and plasma levels of IL-4, IFN-γ, total NO and nitrite in ovalbumin sensitized Guinea-pigs

Ethnomedical relevance

Anti-inflammatory, anti oxidant and effect of Crocus sativus (C. sativus) on Th₁/Th₂ balance were described previously.

Aim of the study

The preventive effects of the extract of Crocus sativus on tracheal responsiveness and plasma levels of IL-4, IFN-γ, total NO and nitrite were examined on sensitized guinea pigs.

Materials and methods

Five groups of sensitized guinea pigs to ovalbumin (OVA), were given drinking water containing three concentrations of the extract of Crocus sativus, dexamethasone (S+D) or alone (group S). Tracheal responses (TR) of control animals (group C) and sensitized guinea pigs (n=6, for each group) to methacholine, OVA and the levels of IL-4, IFN-γ, total NO and nitrite in serum were examined.

Results

The TR to both methacholine and OVA, the levels of serum IL-4, total NO and nitrite in S guinea pigs were significantly increased but that of IFN-γ and IFN-γ/IL-4 ratio (Th₁/Th₂ balance) were decreased compared to the controls (p<0.05 to p<0.001). In the treated animals with dexamethasone and all concentrations of the extract, TR to both methacholine and OVA, IL-4, total NO and nitrite were significantly decreased but IFN-γ and IFN-γ/IL-4 ratio increased compared to S group (p<0.05 to p<0.001). The effects of the highest concentration of the extract was greater than those of other concentrations and the effect of dexamethasone (p<0.05 to p<0.01).

Conclusions

These results not only showed a preventive effect of C. sativus extract on tracheal responses and serum levels of inflammatory mediators in sensitized guinea pigs but also showed increased Th₁/Th₂ balance.     

Fruit extracts of Momordica charantia potentiate glucose uptake and up-regulate Glut-4, PPARγ and PI3K

Ethnopharmacological relevance

Momordica charantia fruit is a widely used traditional medicinal herb as, anti-diabetic, anti-HIV, anti-ulcer, anti-inflammatory, anti-leukemic, anti-microbial, and anti-tumor.

Aims of study

The present study is undertaken to investigate the possible mode of action of fruit extracts derived from Momordica charantia (MC) and study its pharmacological effects for controlling diabetic mellitus. Effects of aqueous and chloroform extracts of Momordica charantia fruit on glucose uptake and up-regulation of glucose transporter (Glut-4), peroxisome proliferator activator receptor gamma (PPARγ) and phosphatidylinositol-3 kinase (PI3K), were investigated to show its efficacy as a hypoglycaemic agent.

Materials and methods

Dose dependent glucose uptake assay was performed on L6 myotubes using 2-deoxy-d-[1-³H] glucose. Up-regulatory effects of the extracts on the mRNA expression level of Glut-4, PPARγ and PI3K have been studied.

Results

The association of Momordica charantia with the aqueous and chloroform extracts of Momordica charantia fruit at 6 μg/ml has shown significant up-regulatory effect, respectively, by 3.6-, 2.8- and 3.8-fold on the battery of targets Glut-4, PPARγ and PI3K involved in glucose transport. The up-regulation of glucose uptake was comparable with insulin and rosiglitazone which was approximately 2-fold over the control. Moreover, the inhibitory effect of the cyclohexamide on Momordica charantia fruit extract mediated glucose uptake suggested the requirement of new protein synthesis for the enhanced glucose uptake.

Conclusion

This study demonstrated the significance of Glut-4, PPARγ and PI3K up-regulation by Momordica charantia in augmenting the glucose uptake and homeostasis.     

Chinese Herbal Medicine for the Treatment of Human Immunodeficiency Virus/Acquired Immune Deficiency Syndrome‑Associated Diarrhea: A Protocol for the Systematic Review and Meta‑Analysis of Randomized Clinical Trials

Diarrhea can occur at an early or advanced stage of acquired immunodeficiency syndrome (AIDS) as a usual symptom in people with humanimmunodeficiency virus (HIV) infection. While it is usually not fatal, it can influence patients’ quality of life seriously. It has shown to beefficacious and improves people’simmune statusto a certain extent to treat HIV/AIDS?related diarrhea on the basis ofsyndrome differentiationand treatment or Chinese herbs plus conventional treatment. Therefore, it may have a good application potential. Here, we outline a protocolfor the systematic review of this health?care intervention, with the aim to evaluate the beneficial effects and safety of Traditional ChineseMedicine (TCM) for patients who suffer from HIV/AIDS?associated diarrhea. Randomized controlled trials that compare Chinese herbs withplacebo or other effective treatments will be searched and included, in spite of publication status or language. The primary outcomes includediarrhea frequency and fecal character. The databases we will search as follows: China Science and Technology Journal Database (VIP),Chinese Biomedical Literature Database (SinoMed), Wanfang Data, China National Knowledge Infrastructure, PubMed and the CENTRALin Cochrane Library. Two authors will respectively conduct the screening of trials, data extraction, and use the Cochrane risk of bias tool toassess the methodological quality. We will analyze the data and perform a meta-analysis if possible. We intend to identify potential therapeuticmodalities that may be of benefit to inform clinical practice by supplying existing evidence of the helpful effects and safety of TCM to treatpatients suffering from HIV/AIDS?associated diarrhea.     

The effects of lignan-riched extract of Shisandra chinensis on amyloid-β-induced cognitive impairment and neurotoxicity in the cortex and hippocampus of mouse

Ethnopharmacological relevance

The fruits of Schisandra chinensis (Trucz.) Baill. (Schisandraceae) which have been used as a tonic especially for kidney yin deficiency in Chinese traditional medicine are recently receiving attention for its preventive activity on age-related neurodegenerative diseases. A variety of studies demonstrated the cognitive-enhancing effects of Schisandra chinensis through animal tests and also in clinical trials.

Aim of study

In this study, we attempted to investigate the effects of the lignan-riched extract of Schisandra chinensis fruits (ESP-806) on neurotoxicity and memory impairment induced by Aβ_1–42 injection in mice.

Materials and methods

The fruits of Schisandra chinensis were extracted with the mixture of n-hexane:ethanol (9:1), which is riched with bioactive dibenzocyclooctadiene lignans, schizandrin, gomisin N, wuweigisu C. After oral treatment of ESP-806 (100 mg/kg body weight) followed by injection of Aβ_1–42 (2 μg/mouse, i.c.v.), novel object recognition and passive avoidance tests were evaluated. To verify the cognition enhancing effects of ESP-806, we examined the effects of ESP-806 on the activities of β-secretase and acetylcholinesterase, and the contents of Aβ and the reduced glutathione within the cortex and hippocampus of Aβ-injected mice.

Results

Oral treatment of ESP-806 (100 mg/kg body weight) significantly attenuated Aβ_1–42-induced memory impairment evaluated by behavioral tests. Furthermore, the treatment of ESP-806 attenuated the elevation of β-secretase activity accompanying the reduced level of Aβ_1–42 in the cortex and hippocampus of the brain. ESP-806 also significantly inhibited the acetylcholinesterase activity in the hippocampus and increased the content of the reduced glutathione in the cortex and hippocampus of mouse brain.

Conclusions

These data suggested that the extract of Schisandra chinensis fruits riched with dibenzocyclooctadiene lignans may be useful in the prevention and treatment of Alzheimer's disease.     

Inhibition of pancreatic lipase, α-glucosidase, α-amylase,and hypolipidemic effects of the total flavonoids from Nelumbo nucifera leaves

Ethnopharmacological relevance

Nelumbo nucifera Gaertn. leaves have been used as medicinal herbs in the past 1300 years, specifically utilized to cure hyperlipidemia, hyperglycemia, and obesity. It has been recorded in the most famous medicinal book in China for more than 400 years. The present study aims to identify the potential therapeutic activities of the flavonoids isolated from Nelumbo nucifera leaves.

Materials and methods

Nelumbo nucifera leaf flavonoids (NLF) were tested for the inhibition of lipase, α-glucosidase, and α-amylase activities in vitro. A single dose of NLF was administered by oral gavage in mice for acute toxicity. Wistar rats with high-fat diet-induced hyperlipidemia and two other animal models were used to evaluate the hypolipidemic effects of NLF.

Results

Our in vitro biochemistry tests revealed that the NLF showed high inhibitory activity against porcine pancreatic lipase, α-amylase, and α-glucosidase with IC₅₀ values of 0.38±0.022, 2.20±0.18, and 1.86±0.018 mg/mL, respectively. Furthermore, the NLF significantly lowered the lipid components, such as the total cholesterol, triglycerides, low-density lipoprotein cholesterol, and malondialdehyde, in various established in vivo systems and raised the high-density lipoprotein cholesterol. Moreover, the NLF alleviated high-fat diet-induced lipid accumulation in the liver.

Conclusions

The results demonstrate that NLFs can effectively ameliorate hyperlipidemia and inhibit the key enzymes related to type 2 diabetes mellitus. Our findings may provide new pharmacological basis for the treatment of hyperlipidemia, hyperglycemia, and obesity using NLFs.     

Mechanisms of anti-inflammatory property of Anacardium occidentale stem bark: Inhibition of NF-κB and MAPK signalling in the microglia

Ethnopharmacological relevance

Anacardium occidentale is used in traditional African medicine for the treatment of arthritis, fever, aches, pains, and inflammation of the extremities.

Aim of the study

In this study, we investigated the molecular mechanisms responsible for anti-inflammatory effects of a stem bark extract of A. occidentale (ANE) in LPS-stimulated microglia.

Materials and methods

Nitric oxide (NO), prostaglandin E₂ and cytokine (TNFα and IL-6) production were evaluated in supernatants from LPS-stimulated BV-2 cells. Cyclooxygenase-2 (COX-2), inducible nitric oxide synthase (iNOS) and microsomal prostaglandin E2 synthase (mPGES-1) protein expressions in rat primary microglia were measured using western blot. The effects of ANE on NF-κB activation and nuclear translocation were evaluated in the luciferase reporter gene assay and ELISA, while ability of ANE to influence IκB phosphorylation was determined using ELISA specific for phospho-IκB. The involvement of MAPK phosphorylation in the anti-inflammatory actions of ANE was evaluated using specific ELISA for phospho-p38, phospho-p42/44 and phospho-JNK. The MTT assay was used to determine the effect of ANE on BV-2 microglia viability.

Results

ANE (25–100 μg/ml) produced significant (p<0.05) reduction in the production of NO, PGE₂, TNFα and IL-6 in BV-2 microglia stimulated with LPS for 24 h. Pre-treatment with ANE caused a significant (p<0.05) inhibition of COX-2, iNOS and mPGES-1 protein expressions in the rat primary microglia. Further experiments showed that ANE inhibited COX-2 and iNOS protein expression via IκB-mediated nuclear translocation and transactivation of NF-κB. Our studies also revealed that ANE produced significant (p<0.05) and dose-dependent inhibition of p38, p42/44 and JNK MAPK phosphorylation in LPS-activated BV-2 microglia.

Conclusions

We conclude that ANE has an anti-inflammatory property related to inhibition of inflammation-associated cytokine production as well as iNOS and COX-2 gene expression by blocking NF-κB and MAPK pathways in the microglia. It is also suggested that mPGES-1 inhibition contributes to the effect of ANE on PGE₂ production in the microglia.     

Regulatory effects of herbal cake-partitioned moxibustion on the expressions of IL-17, IL-23 and their mRNAs in the colon of rats with Crohn’s disease

Objective

To observe the regulatory effects of herbal cake-partitioned moxibustion on Crohn's disease (CD) rat’s colon inflammatory cytokine interleukin-17 (IL-17), IL-23 and their mRNAs, and to investigate the action mechanism of moxibustion in treating CD.

Methods

Forty SPF grade Sprague-Dauley (SD) male rats were randomly divided into a normal group, a model group, an herbal cake-partitioned moxibustion group and a Western medicine group, with 10 rats in each group. Except the normal group, rats in the other three groups were used to make CD model by giving an enema in colon with Trinitro-benzene-sulfonic acid (TNBS). When the models were successful made, rats in the model group had no therapeutic intervention; rats in the herbal cake-partitioned moxibustion group were subjected to herbal cake-partitioned moxibustion treatment at bilateral Tianshu (ST 25) plus Qihai (CV 6); and rats in the Western medicine group were given oral Mesalazine. After treatment, the histopathological changes and inflammatory cytokines IL-17, IL-23 and their mRNAs expressions were observed in descending colon by hematoxylin-eosin (HE) staining, immunohistochemistry (IHC) and real-time polymerase chain reaction (RT-PCR) methods.

Results

Colon tissues of TNBS enema rat models showed cracks-like ulcers accompanied by mucous layer inflammation, granulomas, and inflammatory cytokines IL-17, IL-23 and their mRNAs expressions were all higher than those in the normal group (P<0.01); after intervention, colon tissue cracks-like ulcers and inflammation degree reduced, inflammatory cytokines IL-17, IL-23 and their mRNAs expressions were all significantly decreased (P<0.01) in the herbal cake-partitioned moxibustion group and the Western medicine group.

Conclusion

Herbal cake-partitioned moxibustion may improve colon tissue ulcers and relieve intestinal inflammation by down-regulation of IL-17, IL-23 and their mRNAs expressions in CD model rats’ colonic mucosa.

     

Treatment of leishmaniasis in the Oyapock basin (French Guiana): A K.A.P. survey and analysis of the evolution of phytotherapy knowledge amongst Wayãpi Indians

Ethnopharmacological relevance

Cutaneous leishmaniasis is a neglected disease with a high incidence in French Guiana, mainly in the middle and upper Oyapock basin, where Amerindian and some Brazilian people live. The main goals of this work were (i) to assess the knowledge about leishmaniasis in the different populations of the middle and upper Oyapock basin, (ii) to study the therapeutic strategies adopted by people affected by leishmaniasis and (iii) to document the use of phytotherapeutic remedies for leishmaniasis. Knowledge, attitudes and practices (K.A.P.) related to this disease and its treatments have been studied according to cultural group and geographical settlement. Within the Wayãpi group, the evolution of the knowledge of phytoremedies over the last 20 years has been characterised by literature-based comparisons.

Materials and methods

A total of 144 questionnaires were administered in all the villages of the upper Oyapock and Camopi basins. Correspondence analyses were used for multivariate analysis. Plant species were identified at the Cayenne Herbarium (CAY).

Results

The biomedical concept of leishmaniasis correlates well with the Teko and Wayãpi concepts of kalasapa and kalasapau. Although the vector of this disease was not correctly identified, the most commonly cited aetiology (74.5%) was vector-borne, and related epidemiological schemes correlate well with the one encountered in French Guiana.Theoretically and practically, health centres were the most commonly used resource for diagnostic in instances of leishmaniasis infection (65.9%), independently of the patient's cultural group, along with the use of pharmaceutical drugs (85.3%). Pharmaceuticals were commonly utilised despite the frequent (51.5%) use of phytotherapeutic remedies, alone or in combination with drugs. The most cited medicinal plant species for the treatment of leishmaniasis included Eleutherine bulbosa (Mill.) Urb. (Iridaceae, cited 14 times), Euterpe oleracea Mart. (Arecaceae, 9), Cecropia obtusa Trecul (Cecropiaceae, 8), Jatropha curcas L. (Euphorbiaceae, 7), Ceiba pentandra (L.) Gaertn. (Bombacaceae, 6) and Carica papaya L. (Caricaceae, 6).Multiple correspondence analyses demonstrated that the species used in leishmaniasis remedies are more prone to vary by the user's place of residence than by their cultural origin, which indicates that exchange of knowledge about leishmaniasis remedies has occurred across different cultural groups.Literature-based comparisons between the remedies for leishmaniasis used by the Wayãpi during the 1980s showed a striking evolution, both in terms of diversity of species and number of plants used. The large number of species shared with other Guianese groups argues for intercultural exchange and may explain the majority (57.1%) of the newly used species highlighted in our study.

Conclusions

Leishmaniasis is a well-known disease in the studied area. Phytotherapeutic treatments are still in use, although they are not the main source of remedies, and should undergo pharmacological studies to evaluate their potential therapeutic value.     

Acupuncture on Health Preservation and Care—Second Stop of the WFAS Acupuncture Around the Globe—Held in Moscow,Russia

To strengthen international academic exchanges,spread acupuncture knowledge and enhance clinical value of acupuncture in the world,the second stop of the WFAS Acupuncture around the Globe—Acupuncture on Health Preservation and Care was held in Moscow from August 14 to     

Isoimperatorin, cimiside E and 23-O-acetylshengmanol-3-xyloside from Cimicifugae rhizome inhibit TNF-α-induced VCAM-1 expression in human endothelial cells: involvement of PPAR-γ upregulation and PI3K, ERK1/2, and PKC signal pathways

Ethnopharmacological relevance

The methanol extract of Cimicifugae Rhizome has been traditionally used in various disorders including inflammation.

Aim of the study

The aim of the study is to explore whether anti-inflammatory action of 3 active compounds, two triterpenoid glycosides (cimiside E, 23-O-actylshengmanol-3-xyloside) and one furanocoumarin (isoimperatorin), isolated from Cimicifugae Rhizome is related with peroxisome proliferator-activated receptor-γ (PPAR-γ) expression in human umbilical endothelial cell line, EA.hy926 cells.

Materials and methods

Cell viability and production of reactive oxygen species were performed. In addition, adhesion of monocyte into endothelial cells and western blot for expression of adhesion molecules and signal proteins were investigated in tumor necrosis factor-α (TNF-α)-activated cells.

Results

Pretreatment of test compounds significantly reduced reactive oxygen species (ROS) production and expression of vascular cell adhesion molecule-1 (VCAM-1), but not intercellular cell adhesion molecule-1 (ICAM-1). Three compounds all dose-dependently increased not only PPAR-γ expression in EA.hy926 cells but inhibited TNF-α-induced phosphorylation of Akt, extracelullar-signal-regulated kinase (ERK) and protein kinase C (PKC) with different specificity. Finally, they prevented TNF-α-induced adhesion of U937 monocytic cells to EA.hy926 cells.

Conclusions

The present results show that cimiside E, 23-O-actylshengmanol-3-xyloside, isoimperatorin isolated from Cimicifugae Rhizome selectively inhibits TNF-α-induced expression of VCAM-1 at least by upregulation of PPAR-γ, and signals for ERK1/2, PI3K, and PKC are involved in this effect.     

Effects of acupotomy on the activity of osteoclasts and osteoblasts in the subchondral bone of rabbits with early and mid-stage knee osteoarthritis modelsOA

Objective: To investigate whether acupotomy could inhibit subchondral bone remodeling in knee osteoarthritis(KOA) rabbits by regulating the activity of osteoblasts and osteoclasts.Methods: KOA rabbits were prepared by immobilization for 6 and 9 weeks by Videman method. Nine groups of rabbits(control, 6 weeks and 9 weeks model, 6 weeks and 9 weeks acupotomy, 6 weeks and 9 weeks electroacupuncture, and 6 weeks and 9 weeks drug groups) received acupotomy, electroacupuncture and risedronate sodium i...     

Pyrolysisi Characteristics of Radix Rhizoma Rhei,Cortex Moudan Radicis,and Radix San-guisorbac and correlations with the carbonizing process of Chinese herbs简

AIM： The aim of the work is to study the pyrolysis characteristics of Radix Rhizoma Rhei, Cortex Moudan Radicis, and Radix Sanguisorbae in an inert atmosphere of argon （Ar）, and to investigate the mechanism of the carbonizing process of the three traditional Chinese herbs. METHODS： The pyrolysis characteristics of the crude materials and their extracts were studied by thermogravimetry-mass spectrometry （TG-MS） in a carrier gas of argon, coupled with Fourier transform infrared spectrometry （FTIR） and scanning electron microscopy （SEM） methods. Correlation of the pyrolysis behaviors with the carbonizing process by stir-frying of traditional Chinese medicines was made. RESULTS： Within the temperature range of 200-300 ℃, which is the testing range for the study of the carbonizing process of Chinese herbs, the temperatures indicated by the maximum weight loss rate peak of the above three extracts were taken as the upper-limit temperatures of the carbonizing process of the herbs, and which were 200, 240 and 247 ℃ for Radix Rhizoma Rhei, Cortex Moudan Radicis, and Radix Sanguisorbae, respectively. The ion monitoring signal peaks detected by the TG-MS method corresponded with reports that the level of chemical components of traditional Chinese medicinal materials would decrease after the carbonizing process. It was confirmed by Fourier transform infrared spectrometry （FTIR） and scanning electron microscopy （SEM） methods that better results of ＂medicinal property preservation＂ could be obtained by heating at 200 ℃ for Radix Rhizoma Rhei, at about 250 ℃ for Cortex Moudan Radicis, and Radix Sanguisorbae, as the relative intensity values of the common peaks were among the middle of their three carbonized samples by programmed heating. CONCLUSION： The upper-limit temperatures of the carbonizing process for Radix Rhizoma Rhei, Cortex Moudan Radicis and Radix Sanguisorbae were 200, 240 and 247 ℃ respectively. It is feasible to research the mechanism and technology of the carbonizing process of traditional Chinese medicinal materials using thermogravimetry, Fourier transform infrared spectrometry, and scanning electron microscopy methods.     

Liquiritigenin inhibits serum-induced HIF-1α and VEGF expression via the AKT/mTOR-p70S6K signalling pathway in HeLa cells

Liquiritigenin (LQ) is a non-toxic dietary flavonoid with chemopreventive and anticancer properties. However, the mechanism of its antiangiogenesis remains unclear. Hypoxia-inducible factor-1α (HIF-1α) and its downstream target, vascular endothelial growth factor (VEGF), play a critical role in tumour angiogenesis and represent an attractive chemotherapeutic target. In this study, we investigated the effect of LQ on the molecular mechanism of angiogenesis. We found that LQ inhibited VEGF expression at both mRNA and protein levels. Liquiritigenin did not affect HIF-1α expression at the mRNA level, but it dramatically inhibited both serum- and mimicked hypoxic-induced HIF-1α protein accumulation in HeLa cells. Furthermore, we showed that LQ inhibited serum-induced expression of HIF-1α by reducing its stability and decreased the synthesis in a dose-dependent manner. Mechanistically, we demonstrated that LQ inhibited HIF-1α and VEGF expression involved in blocking the protein kinase B (PKB/Akt) signalling pathway, and the mechanisms correlated with dephosphorylation of the mammalian target of rapamycin (mTOR) and its effector ribosomal protein S6 kinase (p70S6K). In addition, LQ inhibited VEGF-induced formation of capillary-like structures in human umbilical vein endothelial cells (HUVEC). Taken together, our study provided valuable insights into the mechanism of antiangiogenic effect of LQ.     

Studies on pharmaceutical ethnobotany in the regions of L'Alt Empordà and Les Guilleries (Catalonia, Iberian Peninsula)

An ethnobotanical survey was carried out in two regions (L'Alt Emporda and Les Guilleries), situated in North East Catalonia (Iberian Peninsula), with an approximate area of 800 km2 and a population of 68000. Through interviews with 73 people, data was obtained on the medicinal uses of 220 species. The most important findings are presented here concerning the ethnopharmacology of those areas. One hundred and ninty four unreported or uncommon uses corresponding to 101 plant species were detected.