The WNT/β-catenin pathway mediates the anti-adipogenic mechanism of SH21B, a traditional herbal medicine for the treatment of obesity

Aim of the study

This study was conducted to elucidate the molecular mechanisms of SH21B, a traditional Korean herbal medicine commonly used for the treatment of obesity.

Materials and methods

3T3-L1 preadipocytes were differentiated into adipocytes in the presence or absence of SH21B. Changes in mRNA or protein levels were analyzed using microarray, real-time polymerase chain reaction and western blotting analyses. Small interference (si)RNA transfection experiments were conducted to elucidate the essential role of β-catenin.

Results

Microarray analyses showed that components of the WNT/β-catenin pathway including β-catenin, cyclin D1 and dishevelled 2 were up-regulated more than two-fold as a result of SH21B treatment during adipogenesis, which were confirmed by real-time PCR and western blotting. Modulation of the WNT/β-catenin pathway by SH21B resulted in the nuclear accumulation of β-catenin. Both intracellular lipid droplet formation and expressions of adipogenic genes including PPARγ, C/EBPα, FABP4 and LPL, which were inhibited by SH21B, were significantly recovered by β-catenin siRNA transfection.

Conclusions

SH21B modulates components of the WNT/β-catenin pathway during adipogenesis, and β-catenin plays a crucial role in the anti-adipogenic mechanism of SH21B.     

the recent Olympic Games,the pa

mes;Beijing Olympic Games itself have huge economic energy objectively,but negative effect should be avoid when Olympic economic positive effect are bring out.Olympic economy;investment model;effect;thought0北京体育大学学报Journal of Beijing Sport University15-16G812.13H13422H;H134_22王园园;1306-1307北京奥运会与我     

Evaluation of a granulated formula for the nerve root type and vertebral artery type of cervical spondylosis:a multicenter,single-blind,randomized,controlled,phase Ⅲ clinical trial

OBJECTIVE:To evaluate the effectiveness and safety of cervical spondylosis formula granules in reducing the symptoms of patients with the nerve root type and the vertebral artery type of cervical spondylosis.METHODS:This was a multicenter, single-blind,randomized, controlled trial.From April 2002 to November 2003, 499 patients were randomly assigned to either the treatment or the control group.The treatment group was orally administered granules prepared with a formula for cervical spondylosis, while the control group was given Jingfukang granules.The treatment course was 1 month for both groups.RESULTS:In patients with the nerve root type of cervical spondylosis, the total effect rate in the treatment group(87.21%) was significantly higher than that in the control group(80.70%, P 0.01).After the treatment period in both groups, the treatment group had a significantly greater rate of resolution of pain, numbness of the upper limbs, muscle strength of the upper limbs, and fatigue than the control group(all P 0.05).In patients with the vertebral artery type of cervical spondylosis, the total effect rate in the treatment group(82.07%) was similar to that in the control group(71.21%, P 0.05).After the treatment period in both groups,the treatment group had a significantly greater rate of resolution of weakness of the waist and knees than the control group(P 0.05).CONCLUSION:The cervical spondylosis formula granules significantly improve numbness, muscle strength, and fatigue, and reduce pain in patients with the nerve root type of cervical spondylosis,and improve the weakness of the waist and knees in patients with the vertebral artery type of cervical spondylosis.     

Phyllanthus piscatorum, ethnopharmacological studies on a women's medicinal plant of the Yanomamï Amerindians

The shrub Phyllanthus piscatorum Kunth (Euphorbiaceae) is cultivated by various ethnic groups of the Amazon because of its piscicidal properties. During ethnobotanical fieldwork among the Yanomam? Amerindians in Venezuela we observed that Phyllanthus piscatorum was exclusively cultivated and used by the women. Aerial parts of this herbaceous shrub are employed as fish poison and medicine to treat wounds and fungal infections. In addition, the leaves are used as tobacco substitute. Ethnobotanical data regarding the context of the use of this plant are presented. To validate ethnobotanical information related to its medicinal indications, antimicrobial, and antiprotozoal properties of water, methanol (MeOH) and dichloromethane (DCM) extracts were studied. No activity against Gram-positive bacterial strains but significant activity against the fungi Aspergillus fumigatus, Aspergillus flavus and the yeast Candida albicans were found. All extracts showed weak in vitro activity against Plasmodium falciparum and Trypanosoma brucei rhodesiense. The extracts were further investigated for cytotoxic effects in an in vitro test system with leukemia Jurkat T, HeLa, and human peripheral mononuclear blood cells (PBMCs). During the first 48 h the extracts did not exhibit any cytotoxicity. After 72 h the DCM extract potently inhibited viability of HeLa cells. Although in several communities along the upper Orinoco the cultivation and use of Phyllanthus piscatorum is being lost because of the ongoing acculturation, the traditional medicinal use of Phyllanthus piscatorum might provide an effective and cheap remedy against dermatological diseases linked with Candida albicans infections.     

Identification of a novel anti-inflammatory compound, α-cubebenoate from Schisandra chinensis

Aims of the study

Extracts of Schisandra chinensis have been used as an anti-fatigue and tonic agent. Because chronic fatigue syndrome is related to inflammatory and oxidative stress, we assessed whether Schisandra chinensis has anti-inflammatory constituents and studied the effect of a novel α-cubebenoate isolated from Schisandra chinensis.

Materials and methods

α-Cubebenoate was isolated from an extract of Schisandra chinensis fruits. The inductions of inducible nitric oxide synthase (iNOS) and cyclooxygenase 2 (COX-2) by lipopolysaccharide (LPS) were quantified by RT-PCR and Western blotting in mouse peritoneal macrophages. Nitric oxide (NO) and prostaglandin E₂ (PGE₂) were also measured in the media by Griess reagent and EIA method. A mouse model of LPS-induced peritonitis was used to test the in vivo efficacy of α-cubebenoate.

Results

α-Cubebenoate (5–10 μg/ml) inhibited the inductions of iNOS and COX-2 in mouse peritoneal macrophages at the mRNA and protein levels. LPS-induced productions of NO and PGE₂ were inhibited by α-cubebenoate (5–10 μg/ml). In addition, α-cubebenoate inhibited the LPS-induced activation of JNK, but not those of ERK and p38 MAPK in mouse peritoneal macrophages. Furthermore, in the LPS-induced in vivo peritonitis model, α-cubebenoate (1 mg/kg) strongly inhibited the accumulation of polymorph nuclear lymphocytes in the peritoneal cavity.

Conclusion

α-Cubebenoate inhibited LPS-induced expression of iNOS and COX-2 in a concentration-dependent manner, thereby suppressing productions of NO and PGE₂ in vitro in peritoneal macrophages. α-Cubebenoate also inhibited LPS-induced accumulation of polymorph nuclear lymphocytes in LPS-induced peritonitis model in vivo. α-Cubebenoate may act as an anti-fatigue constituent of Schisandra chinensis through anti-inflammation and could be of therapeutic use as a treatment for inflammatory diseases.     

Ginseng,a traditional Herbal Medicine

Ginseng is a root vegetable whose shape resembles the human body, and its name （pronounced “insam” in Korean） contains the Chinese characters for “man”. Korean ginseng is also known by the names of Korea＇ s last two royal dynasties：Goryeo and Joseon. Its scientific name is “Panax Ginseng C.A.Meyer” ,panax being a composite term formed from the Greek words pan（all） and axos（medicine）,which also give us the English word “panacea”.     

Nitropyrrolins A-E, cytotoxic farnesyl-α-nitropyrroles from a marine-derived bacterium within the actinomycete family Streptomycetaceae

Five new farnesyl-α-nitropyrroles, nitropyrrolins A-E (1-5), were isolated from the saline culture of the marine actinomycete strain CNQ-509. This strain belongs to the "MAR4" group of marine actinomycetes, which have been demonstrated to be a rich source of hybrid isoprenoid secondary metabolites. The structures of the nitropyrrolins are composed of α-nitropyrroles with functionalized farnesyl groups at the C-4 position. These compounds are the first examples of naturally occurring terpenyl-α-nitropyrroles. Chemical modifications, including one-step acetonide formation from an epoxide, and application of the modified Mosher method provided the full stereostructures and absolute configurations of these compounds. Several of the nitropyrrolins, nitropyrrolin D in particular, are cytotoxic toward HCT-116 human colon carcinoma cells, but show weak to little antibacterial activity against methicillin-resistant Staphylococcus aureus (MRSA).     

Anticancer Activities and the Drug Targets of Botanical Saponins from a Medicinal Herb, Gynostemma Pentaphyllum

Triterpenoid saponins are metabolites produced in most plant species through complex biosynthetic pathways. They play important roles to humans owing to their diverse medicinal effects, including antiinflammatory, antimicrobial, and anticancer activities. In our laboratory, the author have been investigating the anticancer activities of a mixture of triterpenoid saponins （designated GpMix） extracted from a medicinal plant, known as Jiao Gu Lan （Gynostemma pentaphyllum, 胶股蓝 ） or southern ginseng in China. The key findings are summed up as following.     

Berberine plays a cardioprotective role by inhibiting macrophage Wnt5a/β-catenin pathway in the myocardium of mice after myocardial infarction

Myocardial infarction (MI) is one of the diseases with high fatality rate. Berberine (BBR) is a monomer compound with various biological functions. And some studies have confirmed that BBR plays an important role in alleviating cardiomyocyte injury after MI. However, the specific mechanism is unclear. In this study, we induced a model of MI by ligation of the left anterior descending coronary artery and we surprisingly found that BBR significantly improved ventricular remodeling, with a minor inflammatory and oxidative stress injury, and stronger angiogenesis. Moreover, BBR inhibited the secretion of Wnt5a/β-catenin pathway in macrophages after MI, thus promoting the differentiation of macrophages into M2 type. In summary, BBR effectively improved cardiac function of mice after MI, and the potential protective mechanism was associated with the regulation of inflammatory responses and the inhibition of macrophage Wnt5a/β-catenin pathway in the infarcted heart tissues. Importantly, these findings supported BBR as an effective cardioprotective drug after MI.     

Intervention effects of QRZSLXF,a Chinese medicinal herb recipe,on the DOR-β-arrestin1-Bcl2 signal transduction pathway in a rat model of ulcerative colitis

Ethnopharmacological relevance

Qingre Zaoshi Liangxue Fang (QRZSLXF) is a Chinese medicinal herb recipe that is commonly prescribed for the treatment of ulcerative colitis. It includes 5 quality assured herbs: Sophora flavescens Aiton., Baphicacanthus cusia (Nees) Bremek., Bletilla striata Rchb.f., Glycyrrhiza uralensis Fisch. and Coptis chinensis Franch. The main phytochemical ingredient of QRZSLXF includes ammothamnine, sophocarpidine, liquiritin, berberine and indirubin. QRZSLXF has been clinically proven for use in the treatment of ulcerative colitis for over twenty years. In the past ten years, research has confirmed the therapeutic effect of QRZSLXF in ulcerative colitis and partially revealed its mechanism of action. Here, we further reveal the therapeutic mechanism of QRZSLXF in ulcerative colitis. To investigate the role of the DOR-β-arrestin1-Bcl-2 signal transduction pathway in ulcerative colitis and to determine the effects of QRZSLXF on this signal transduction pathway.

Materials and methods

Eighty-four Sprague-Dawley rats were randomly divided into six groups: normal control group, model group, mesalazine group, and QRZSLXF high-dose, medium-dose group and low-dose groups (n=14). Experimental colitis was induced by trinitrobenzenesulfonic acid (TNBS) in each group, except the normal control group. After modeling, bloody stool, mental state and diarrhea were observed and recorded. Two rats were randomly selected from the model groups adfnd sacrificed on day 3 to observe pathological changes in the colon tissue by microscopy. The rats in the QRZSLXF-treated groups received intramuscular injections of different concentrations of QRZSLXF for 15 days. The rats in the mesalazine group were treated with mesalazine solution (0.5 g/kg/day) by gastric lavage for 15 days. The rats in the normal control group and the model group were treated with 3 mL water by gastric lavage for 15 days. On the 16th day, after fasting for 24 h, the remaining rats were sacrificed and their colon tissues were used to detect the mRNA and protein expressions of DOR, β-arrestin1 and Bcl-2 by Real-time PCR and immunohistochemistry, respectively. Histological changes in the colon tissues were also examined.

Results and conclusions

The expressions of DOR, β-arrestin1 and Bcl-2 were significantly different among the four groups. The expressions of DOR, β-arrestin1 and Bcl-2 protein and mRNA were significantly increased in the model group compared with the other groups (P<0.05). In contrast to the model group, the expressions of DOR, β-arrestin1 and Bcl-2 were significantly decreased in the mesalazine group and the groups that received different doses of QRZSLXF (P<0.05), and there were no statistically significant differences among the mesalazine and QRZSLXF-treated groups (P>0.05). This study indicates that the DOR-beta-arrestin1-Bcl-2 signal transduction pathway may participate in the pathologic course of ulcerative colitis. Moreover, QRZSLXF could attenuate ulcerative colitis by regulating the DOR-β-arrestin1-Bcl-2 signal transduction pathway.     

The Biomedical Acupuncture Model – The best explanation of a given phenomenon is generally the simplest,the one with the fewest assumptions. – Principle of Parsimony

The Biomedical Acupuncture Model for Pain Management is a novel clinical model characterized by reproducibility, predictability and standardization while still maintaining all the benefits of the Classical Acupuncture Model. The Biomedical Acupuncture Model is based on biomedical research and clinical evidence collected over the past 40 years.The Biomedical Acupuncture Model, which is based on the non-specific nature of acupuncture mechanisms, introduces the Clinical Integrative Neuromuscular Acupoint System (INMAS™). INMAS™ offers:

• (A)a neuroanatomically and physiologically defined acupoint system;
• (B)a quantitative evaluation method predicting the prognosis of acupuncture treatments; and
• (C)a standard yet individualized (adjustable to each patient) treatment protocol for the majority of pain patients.

The Biomedical Acupuncture Model permits medical practitioners^** to implement acupuncture in their daily practice, in the context of their biomedical knowledge, without the difficulty of having to learn the antiquated procedures of traditional acupuncture models.For a wider understanding of our approach please refer to our textbook [1].     

Viridaphin A₁ glucoside, a green pigment possessing cytotoxic and antibacterial activity from the aphid Megoura crassicauda

A green pigment, viridaphin A? glucoside (1), was isolated from the green aphid Megoura crassicauda. One- and two-dimensional NMR spectrometric analyses of 1 and its aglycone established the structure as an octacyclic compound. Viridaphin A? glucoside exhibited cytotoxicity against HL-60 human tumor cells with an IC?? of 23 μM and antibacterial activity against Bacillus subtilis NBRC 3134 with a minimum inhibitory concentration of 10.0 μg/mL. These results suggested that aphid pigments may protect aphids from invasive species, including viruses and bacteria.     

Chebulagic acid,a COX–LOX dual inhibitor isolated from the fruits of Terminalia chebula Retz., induces apoptosis in COLO-205 cell line

Ethnopharmacological relevance

Terminalia chebula has an esteemed origin in Indian mythology; its fruits are used to treat many diseases such as digestive, diabetes, colic pain, chronic cough, sore throat, asthma, etc.

Aim of the study

The water or ethanolic extracts of the fruits were reported to have anti-oxidant, anti-inflammatory, anti-cancer and radio-protector properties. The present study is to isolate and identify the compounds that inhibit COX and 5-LOX, the key enzymes involved in inflammation and carcinogenesis.

Materials and methods

The ethanolic extract of the fruits was fractionated by RP-HPLC and fractions were tested for enzyme inhibition activity against COX and 5-LOX. One of the fractionated compounds showed potent dual inhibition against COX and 5-LOX. It was identified as chebulagic acid by LC–MS, NMR and IR analyses. The chebulagic acid was also tested for anti-proliferative activity.

Results

Chebulagic acid showed potent COX–LOX dual inhibition activity with IC₅₀ values of 15 ± 0.288, 0.92 ± 0.011 and 2.1 ± 0.057 μM for COX-1, COX-2 and 5-LOX respectively. It also showed anti-proliferative activity against HCT-15, COLO-205, MDA-MB-231, DU-145 and K562 cell lines. Further mechanistic studies on COLO-205 cells revealed induction of apoptosis by chebulagic acid.

Conclusions

Chebulagic acid, a COX-2 and 5-LOX dual inhibitor isolated from the fruits of Terminalia chebula, induces apoptosis in COLO-205 cells.     

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.     

Deqi sensation between the acupuncture-experienced and the naïve: a Korean study II

Previous experience of acupuncture is believed to affect people's expectation of future treatments. Therefore, subjects who have had acupuncture are generally excluded from sham-controlled acupuncture clinical trials. However, this assumption has not been proven, but just accepted because of the lack of evidence to the contrary. To investigate the difference in frequency and intensity of acupuncture sensation between subjects who have had acupuncture and those who have not, 36 acupuncture-experienced subjects were invited to take part in the study. After informed consent was obtained, participants were asked to complete the acupuncture sensation scale (ASS) according to what they expected needling to feel like. The needling was done at the left Hegu (LI 4) point and consisted of insertion, stimulation for 30 seconds and removal. After needling, the subjects were asked to complete the same ASS according to what they actually experienced. Adverse events were monitored. The frequency of each sensation expected and experienced, as well as acupuncture sensation scores were compared. More than 60% of the subjects expected to feel sensations of penetrating (87.6% to 100%), aching (71.2% to 95.5%), tingling (87.6% to 100%), pricking (79.7% to 99.2%) and throbbing (64.2% to 91.4%). In fact, the subjects experienced sharp (60.9% to 89.1%), intense (60.9% to 89.1%), radiating (71.2% to 95.5%) and heavy (74.8% to 97.4%) sensations just as much. The subjects expected more hurting (p = 0.001), tingling (p < 0.001), pricking (p = 0.010), stinging (p = 0.012), burning (p = 0.001) and pulsing (p = 0.009) than they experienced, while more heaviness (p = 0.011) was experienced than expected. The same outcome measures were also compared between experienced and naive groups. Apart from the fact that the acupuncture-experienced participants expected to feel pricking (p = 0.030) and stinging (p = 0.002), and experienced hurting (p = 0.022) and stinging (p = 0.028) significantly less than those who had not had acupuncture before, there was no significant difference between first time and experienced subjects. The results indicate that previous experience does not affect the people's expectation and does not hinder people from experiencing Deqi. In addition, a constellation of Deqi-related acupuncture-specific sensations is more than just a general pain intensity dimension, which requires a biochemical and physiological exploration.     

Can the aggregation be a new approach for understanding the mechanism of Traditional Chinese Medicine?

"Frequent hitter" phenomenon emerged in the high-throughput screening; one of the most common mechanisms behind artifactual inhibition is that some organic molecules formed large colloid-like aggregates which are able to sequester and thereby inhibit enzymes. To investigate the situation in Traditional Chinese Medicine (TCM), 60 medicinal herbs and 24 Chinese herbal formulae were detected by dynamic light scattering (DLS), and aggregates were observed in all the 84 solution mixtures. The aggregates of two Chinese herbal formulae, 'Xue-Fu-Zhu-Yu Tang' (XF) and 'Jing-Guan Tang' (JG), were not only able to survive in the gastro-intestinal environment, but also had the ability to pass through the monolayer of the Caco-2 cell. The activities of XF and JG against three cardiovascular targets were also aggregates-related. Based on these findings, a new possible mechanism of the action of Chinese medicine was proposed.     

离子色谱法测定栀子中Cl-, Br-, NO3-, SO42-, PO43-5种阴离子的含量

目的: 建立一种同时测定中药栀子药材中Cl^-,Br^-,NO₃^-,SO₄^2-,PO₄^3-阴离子的含量测定方法。 方法: 采用离子色谱法,IonPac AS11-HC阴离子色谱柱,氢氧化钾梯度淋洗,电导检测栀子中5种无机阴离子。 结果: Cl^-,Br^-,NO₃^-,SO₄^2-,PO₄^3-的线性范围良好,加样回收率介于97%~102%,栀子中Cl^-,Br^-,NO₃^-,SO₄^2-,PO₄^3-重复性良好,含量分别为0.084%,0.063%,0.070%,0.30%,0.12%。 结论: 离子色谱法可以同时检测栀子中5种阴离子,灵敏度高,结果准确可行,为栀子的质量控制提供了一种简便快速的方法。     

Antimicrobial and cytotoxic activities of medicinal plants of the Brazilian cerrado, using Brazilian cachaça as extractor liquid

Ethnopharmacological importance

Many species of plants in the Brazilian cerrado (savanna) are widely used in ethnomedicine. However, the safety and effectiveness of medicinal plants used in communities with little or no access to manufactured drugs should be evaluated.

Aim of the study

Evaluate the antimicrobial and cytotoxic activities of extracts from eight plant species, obtained using Brazilian cachaça as the extractor liquid.

Materials and methods

The extracts were tested against Bacillus subtilis, Staphylococcus aureus, Escherichia coli, Pseudomonas aeruginosa, Candida albicans, Candida parapsilosis, promastigote forms of Leishmania amazonensis, and poliovirus. In addition, cytotoxic activity was assayed in Vero cells and in human erythrocytes.

Results

The plant species Curatella americana, Sclerolobium aureum, and Plathymenia reticulata showed the best activity against yeasts, especially the crude extract of C. americana and its ethyl-acetate fraction. Kielmeyera lathrophyton showed a minimum inhibitory concentration of 250 μg/ml against S. aureus, and was inactive against Gram-negative bacteria. The extract obtained from Annona coriacea showed the best activity against the promastigote forms of Leishmania amazonensis (IC₅₀ = 175 μg/ml). Only C. americana showed potential for antipoliovirus activity. The concentrations of the crude extracts that showed toxicity to VERO cells had CC₅₀ between 31 and 470 μg/ml, and the lyophilized Brazilian cachaça showed a CC₅₀ of 307 μg/ml. None of the extracts showed toxicity against human erythrocytes.

Conclusions

Among the plant species studied, C. americana proved to be effective against microorganisms, especially as an antifungal. The results will help in the search for alternative drugs to be used in pharmacotherapy, and will contribute to establish safe and effective use of phytomedicines in the treatment of infectious diseases.