Quality evaluation of Hawk tea from different months and regions based on quantitative analysis of multiple components with a single marker (QAMS) combined with HPLC fingerprint.

BACKGROUND: Hawk tea, a medicinal and edible plant, has been consumed for thousands of years in Southwest China. To date, no unified food safety standard for Hawk tea has been established, and systematic research on the quality of Hawk tea is lacking. OBJECTIVE: The aim of this study was to develop a comprehensive evaluation method for the quality of Hawk tea based on inclusions content, high-performance liquid chromatography (HPLC) fingerprinting combined with the quantitative analysis of multiple components with a single marker (QAMS) method. METHODS: The contents of total flavonoids, total phenols, total polysaccharides, and total protein were determined using the colorimetric method. An effective comprehensive evaluation method was established to classify the 16 batches of samples based on HPLC fingerprint analysis combined with similarity analysis (SA), hierarchical cluster analysis (HCA), principal component analysis (PCA), partial least-squares discrimination analysis (PLS-DA), and the QAMS method. RESULTS: Flavonoids were the main chemical components of Hawk tea. The accuracy of the QAMS method was verified by comparing the calculated results with those of the external standard method (ESM). No significant differences were found between the two methods. Additionally, the fingerprint of Hawk tea was also established. CONCLUSION: The method established in this study can be used for the comprehensive quality evaluation of Hawk tea and can also provide a reference for the quality evaluation of other herbal medicines.

Effect of Huatan Tongluo Prescription on Vulnerability of Carotid Atherosclerotic Plaque in Hypertension / 中国实验方剂学杂志

ObjectiveTo evaluate the effect of Huatan Tongluo prescription on the vulnerability of atherosclerotic plaques in the carotid arteries of patients with hypertension of phlegm-stasis combination syndrome. MethodA total of 132 eligible patients were randomly divided into an observation group （66 cases） and a control group （66 cases）. The control group received oral atorvastatin calcium tablets and enteric-coated aspirin tablets， while the observation group received Huatan Tongluo prescription in addition to the treatment received by the control group. The treatment duration was 6 months. A carotid artery ultrasound examination was performed to record the number of plaques， the maximum plaque area， the maximum plaque cross-sectional thickness， and the intima-media thickness （IMT） of the carotid artery. Crouse score， plaque vulnerability score， and phlegm-stasis combination syndrome score were assessed. Blood lipid levels ［total cholesterol （TC）， triglyceride （TG）， high-density lipoprotein cholesterol （HDL-C）， and low-density lipoprotein cholesterol （LDL-C）］， inflammatory markers ［neutrophil-to-lymphocyte ratio （NLR）， monocyte-to-lymphocyte ratio （MLR）， interleukin-6 （IL-6）， and high-sensitivity C-reactive protein （hs-CRP）］， vascular endothelial function ［endothelin-1 （ET-1）， von Willebrand factor （vWF）， and nitric oxide （NO）］， and relevant proteins ［pentraxin 3 （PTX3） and galectin-3 （Gal-3）］ levels were measured. Safety evaluation was conducted， and comparisons were made in terms of carotid artery stenosis rate， plaque regression efficacy， and traditional Chinese medicine （TCM） syndrome efficacy. ResultCompared with the results before treatment， both groups showed significant reductions in IMT， plaque number， maximum plaque area， and maximum plaque cross-sectional thickness （P<0.05）. After treatment， the observation group exhibited more significant reductions in the above indicators compared with the control group （P<0.05）. After treatment， Crouse scores， plaque vulnerability scores， and phlegm-stasis combination syndrome scores in both groups were lower than those before treatment （P<0.05）. After treatment， the observation group had lower scores in these indicators than the control group （P<0.05）. In terms of blood lipid levels， both groups showed decreases in TC， TG， and LDL-C levels， and an increase in HDL-C levels after treatment compared to those before treatment （P<0.05）. The observation group exhibited greater improvements in these lipid parameters than the control group （P<0.05）. Inflammatory markers NLR， MLR， IL-6， and hs-CRP significantly decreased in both groups after treatment compared with those before treatment （P<0.05）. The observation group showed more significant reductions in these markers than the control group after treatment （P<0.05）. After treatment， both groups demonstrated decreases in levels of ET-1， vWF， PTX3， and Gal-3， along with an increase in NO levels compared with those before treatment （P<0.05）. The observation group showed more significant improvements in these markers than the control group after treatment （P<0.05）. After treatment， the observation group had a lower carotid artery stenosis rate than the control group （P<0.05）. The plaque regression efficacy rate was 51.72% （30/58） in the observation group， and the total effective rate of TCM syndrome was 84.48% （49/58）， both of which were higher than 18.64% （11/59） and 52.54% （31/59） in the control group （χ²=10.061， 13.799， P<0.05）. No adverse reactions related to the Huatan Tongluo prescription were observed during the treatment period. ConclusionIn addition to statin therapy， Huatan Tongluo prescription can effectively reverse carotid artery atherosclerotic plaques in patients with hypertension and carotid artery stenosis， reduce plaque vulnerability， exhibit lipid-lowering and anti-inflammatory effects， and improve vascular endothelial function. The treatment demonstrates favorable clinical efficacy and safety. Therefore， it is very worthy of clinical promotion and application.

Network Meta-analysis of efficacy and safety of Chinese patent medicines in treatment of ankylosing spondylitis / 中国中药杂志

To evaluate the efficacy and safety of Chinese patent medicines in the treatment of ankylosing spondylitis(AS) by frequency network Meta-analysis. Randomized controlled trials(RCTs)of Chinese patent medicines for AS were retrieved from CNKI, Wanfang, VIP, CBM, PubMed, EMbase and Cochrane Library databases from the time of database establishment to January 2021. The quality of the included RCTs was evaluated according to the Cochrane bias risk standard, and the data was analyzed by RevMan 5.3 and Stata/MP 15.1. A total of 12 kinds of Chinese patent medicines in 55 RCTs were included. According to Meta-analysis, in term of the effectiveness, the top three optimal medication regimens were Biqi Capsules, Yishen Juanbi Pills and Yaobitong Capsules combined with western medicine. The top three interventions to reduce the erythrocyte sedimentation rate(ESR)were Yishen Juanbi Pills, Xianling Gubao Capsules and Fufang Xuanju Capsules combined with western medicine. The top three interventions to reduce the C-reactive protein(CRP)were Biqi Capsules, Xianling Gubao Capsules and Fufang Xuanju Capsules combined with western medicine. In terms of the safety, top three optimal medication regimens were Total Glucosides of Paeony Capsules, Yishen Juanbi Pills, and Wangbi Tablets combined with western medicine. This network Meta-analysis suggests that Chinese patent medicines combined with conventional western medicine can effectively improve the joint pain symptoms of AS patients and reduce the acute inflammatory indicators, with high safety. However, the literature included in this study is generally of low methodological quality, and the conclusion needs to be verified by high-quality research.

Effect of electroacupuncture of "Hegu" (LI4) and "Zusanli" (ST36) on intestinal sensitivity and motility in irritable bowel syndrome rats / 针刺研究

OBJECTIVE: To observe the effect of electroacupuncture (EA) of "Hegu"(LI4) and "Zusanli"(ST36)on changes of intestinal sensitivity and colonic motility and expression of colonic 5-hydroxytryptamine 3A receptor (5-HT3AR) in irritable bowel syndrome (IBS) rats, so as to reveal its mechanism underlying improvement of IBS. METHODS: A total of 40 neonatal Wistar rats were randomly and equally divided into normal control, model, LI4 and ST36 groups (n＝10). The IBS model was induced by mother-infant separation, acetic acid enema and colorectal distension (CRD). EA (2 Hz/100 Hz, a tolerable strength) was applied to bilateral LI4 and ST36 for 20 min, once every other day for 5 times. The Bristol stool form scale was used to assess the gastrointestinal function, and the latency and number of abdominal muscular contraction waves of abdominal withdrawal reflex (AWR) were used to evaluate the intestinal sensitivity and motility respectively. The immunoactivity of 5-HT3AR of the colon tissue was detected by immunohistochemistry. RESULTS: After modeling, the score of Bristol fecal form scale, number of muscular contraction waves and expression levels of colonic 5-HT3AR in the myometrium and mucosal layers were significantly increased (P<0.01), and the latency of muscular initial contraction wave was obviously shortened in the model group relevant to the normal control group (P<0.01). After the intervention, the increased Bristol fecal form score, number of muscular contraction waves and expression levels of 5-HT3AR in the myometrium and mucosal layers as well as the decreased latency of muscular contraction were reversed in both LI4 and ST36 groups (P<0.01, P<0.05). The effect of EA of ST36 was significantly superior to those of EA-LI4 in lowering Bristol fecal scale score and 5-HT3AR expression in the muscular layer (P<0.01), but obviously inferior to those of EA-LI4 in increasing the latency of of muscular initial contraction wave and down-regulating muscular contraction waves and 5-HT3AR expression in the mucosal layer (P<0.05, P<0.01). CONCLUSION: Both EA-LI4 and EA-ST36 can significantly improve the symptoms of abdominal pain and diarrhea, but EA-LI4 is better in suppressing intestinal high sensitivity, and EA-ST36 is better in promoting intestinal motility, suggesting a specificity of effect of acupoints of different meridians.

Intervention effect of Modified Dahuang Zhechong Granule on epididymal morphological changes in experimental varicocele rats / 中华男科学杂志

<p><b>Objective</b>To explore the effect of Modified Dahuang Zhechong Granule (MDZG) on the development and maturation of epididymal sperm in experimental varicocele (VC) rats.</p><p><b>METHODS</b>Sixty SD male rats were randomly divided into six groups of equal number, sham operation, VC model, Aescuven forte, and low-, medium- and high-dose MDZG. The model of left VC was made by the Turner method in all the rats except those of the sham operation group, followed by treatment with 0.9% normal saline for the animals in the sham operation and VC model groups, Aescuven forte tablets at 54 mg per kg of the body weight for those in the Aescuven forte group, and MDZG at 0.6, 1.2 and 2.4 g/ml for those in the low-, medium- and high-dose MDZG groups, all administered intragastrically qd for 8 successive weeks. Then, all the rats were sacrificed and their left epididymides harvested for examination of the quality of the epididymal sperm and the local microscopic and ultrastructural changes of the epididymal tissue.</p><p><b>RESULTS</b>The VC model rats showed significant apoptosis of the epididymal sperm cells, interstitial edema, microvascular dilatation, degeneration and degeneration of the epithelial cells, degeneration of some principal cells and basal cell vacuoles, and immature spermatids in the lumen. Sperm motility was significantly increased in the Aescuven forte and low-, medium- and high-dose MDZG groups as compared with the VC models (P <0.01). Both sperm concentration and motility were markedly higher in the high-dose MDZG than in the Aescuven forte group (P <0.05). Remarkable apoptosis of epididymal sperm cells was observed in the microenvironment of sperm development in the VC models, which exhibited no statistically significant difference from that in the rats of the medium- and high-dose MDZG groups.</p><p><b>CONCLUSIONS</b>Experimental varicocele induced local apoptosis of epididymal sperm cells, interstitial edema and microvascular dilatation in the rat epididymis, while Modified Dahuang Zhechong Granule could improve the stability of epididymal sperm maturation and contribute to their development.</p>

Fraction n-Butanol of Radix Notoginseng Protects PC12 Cells from Aß25-35-Induced Cytotoxicity and Alleviates Cognitive Deficits in SAMP8 Mice by Attenuating Oxidative Stress and Aß Accumulation.

Chinese medicine has been used for Alzheimer's disease (AD) treatment for thousands of years with more effective and fewer side effects. Therefore, developing effective potential candidates from Chinese medicine against AD would be considered as critical and efficient therapy for AD treatment. This study was designed to evaluate the neuronal protective effect of fraction n-butanol (NB) of Radix Notoginseng on Aß25-35-induced PC12 cells, explore the effect of the tested fraction on spatial learning and memory, and characterize the impacts of fraction NB on antioxidant enzymes, Aß production, and APP and BACE1 expressions. The results revealed that fraction NB could promote proliferation of PC12 cells and protect and rescue PC12 cells from Aß25-35-induced cell death. Moreover, fraction NB could improve spatial learning and memory impairments of senescence-accelerated prone8 (SAMP8) mice and attenuate oxidative stress and reduce the production of Aß by inhibiting the expressions of APP and BACE1 in the brains of SAMP8 mice. The result of single dose acute toxicity assay showed that fraction NB had a mild toxicity in vivo. The pronounced actions against AD and in vivo low toxicity of fraction NB suggest that fraction NB may be a useful alternative to the current AD treatment.

Effects of ethanol extract of Bombax ceiba leaves and its main constituent mangiferin on diabetic nephropathy in mice / 中国天然药物

The present study was designed to explore the mechanism by which ethanol extract of Bombax ceiba leaves (BCE) and its main constituent mangiferin (MGF) affect diabetic nephropathy by combating oxidative stress. Oral administration of BCE and MGF to normal and streptozotocin (STZ)-induced diabetic mice were carried out. Fasting blood glucose, 24-h urinary albumin, serum creatinine, and blood urea nitrogen were tested, histopathology, and immunohistochemical analysis of kidney tissues were performed. Moreover, mesangial cells were treated with BCE and MGF for 48 h with or without 25 mmol·L of glucose. Immunofluorescence, Western blot and apoptosis analyses were used to investigate their regulation of oxidative stress and mitochondrial function. BCE and MGF ameliorated biochemical parameters and restored STZ-induced renal injury in the model mice. In vitro study showed that high glucose stimulation increased oxidative stress and cell apoptosis in mesangial cells. BCE and MGF limited mitochondrial membrane potential (Δψm) collapse by inhibiting Nox4, mitochondrially bound hexokinase II dissociation, and subsequent ROS production, which effectively reduced oxidative stress, cleaved caspase-3 expression and cell apoptosis. Our work indicated that BCE and MGF had protective effects on diabetic caused kidney injury and prevented oxidative stress in mesangial cells by regulation of hexokinase II binding and Nox4 oxidase signaling.

Antihyperglycemic, antihyperlipidemic and antioxidant effects of standard ethanol extract of Bombax ceiba leaves in high-fat-diet- and streptozotocin-induced Type 2 diabetic rats / 中国天然药物

The present study aimed at exploring the therapeutic potential of standard extract of Bombax ceiba L. leaves (BCE) in type 2 diabetic mellitus (T2DM). Oral administration of BCE at doses of 70, 140, and 280 mg·kg, to the normal rats and the high-fat-diet- and streptozotocin-induced T2DM rats were carried out. Effects of BCE on blood glucose, body weight, and a range of serum biochemical parameters were tested, and histopathological observation of pancreatic tissues was also performed. HPLC-ESI-Q/TOF-MS/MS analysis indicated that the chemical composition of BCE mainly contained mangiferin, isoorientin, vitexin, isomangiferin, isovitexin, quercetin hexoside, 2'-trans-O-cumaroyl mangiferin, and nigricanside. BCE caused a significant decrease in the concentrations of fasting blood glucose, glycosylated hemoglobin, total cholesterol, triglyceride, low density lipoprotein-cholesterol, serum insulin, and malondialdehyde, and increases in oral glucose tolerance, high density lipoprotein-cholesterol, and superoxide dismutase in the T2DM model rats. Moreover, considerable pancreatic β-cells protection effect and stimulation of insulin secretion from the remaining pancreatic β-cells could be observed after BCE treatment. The results indicated that BCE exhibited an excellent hypoglycemic activity, and alleviated dyslipidemia which is associated with T2DM. Antioxidant activity and protecting pancreatic β-cells are the possible mechanisms involved in anti-diabetic activity of BCE.

Curcumin inhibits the replication of enterovirus 71 in vitro

Human enterovirus 71 (EV71) is the main causative pathogen of hand, foot, and mouth disease (HFMD) in children. The epidemic of HFMD has been a public health problem in Asia-Pacific region for decades, and no vaccine and effective antiviral medicine are available. Curcumin has been used as a traditional medicine for centuries to treat a diversity of disorders including viral infections. In this study, we demonstrated that curcumin showed potent antiviral effect again EV71. In Vero cells infected with EV71, the addition of curcumin significantly suppressed the synthesis of viral RNA, the expression of viral protein, and the overall production of viral progeny. Similar with the previous reports, curcumin reduced the production of ROS induced by viral infection. However, the antioxidant property of curcumin did not contribute to its antiviral activity, since N-acetyl-l-cysteine, the potent antioxidant failed to suppress viral replication. This study also showed that extracellular signal-regulated kinase (ERK) was activated by either viral infection or curcumin treatment, but the activated ERK did not interfere with the antiviral effect of curcumin, indicating ERK is not involved in the antiviral mechanism of curcumin. Unlike the previous reports that curcumin inhibited protein degradation through ubiquitin-proteasome system (UPS), we found that curcumin had no impact on UPS in control cells. However, curcumin did reduce the activity of proteasomes which was increased by viral infection. In addition, the accumulation of the short-lived proteins, p53 and p21, was increased by the treatment of curcumin in EV71-infected cells. We further probed the antiviral mechanism of curcumin by examining the expression of GBF1 and PI4KB, both of which are required for the formation of viral replication complex. We found that curcumin significantly reduced the level of both proteins. Moreover, the decreased expression of either GBF1 or PI4KB by the application of siRNAs was sufficient to suppress viral replication. We also demonstrated that curcumin showed anti-apoptotic activity at the early stage of viral infection. The results of this study provide solid evidence that curcumin has potent anti-EV71 activity. Whether or not the down-regulated GBF1 and PI4KB by curcumin contribute to its antiviral effect needs further studies.

[Study on the effect of extracts from the leaves of Phyllanthus emblica on immune function of mice].

OBJECTIVE: To explore the effect of extracts from the leaves of Phyllanthus emblica (PLFs) on the immune function of mice. METHODS: 70 Kunming mice were choosed to conduct the acute toxicity test of PLFs. The mice were randomly divided into four groups: PLFs high-dosage group, mid-dosage group, low-dosage group and control group. The high,mid,low-dosage groups were treated with PLFs 1.982, 0.991 and 0.496 g/kg respectively per day. The same volume of double distilled water was given to the control group. All by intragastric administration for 7 d. The animals were killed and indexes of thymus and spleen were calculated. The expurgation index K and phagocyte index a were detected after the mice being injected with a dilute India ink through caudal vein. In addition, prepared spleen cells conventionally,the activity of Natural Killer cells was measured and the proliferation of T and B cells were detected. The effect of the extracts on serum hemolysin was detected after the SRBC was injected into the enterocoelia. RESULTS: The LD50 of PLFs was 9. 911 g/kg. Compared with the control group, the indexes of thymus and spleen in the treatment groups had no markedly difference (P > 0.05). The high- and mid-dosage groups could obviously improve the expurgation index K (P < 0.05), phagocyte index alpha (P < 0.05) and NK cell activity (P < 0.05). CONCLUSION: The extracts from Phyllanthus emblica leaves can promote nonspecific immunity immune function in mice.

Add-on effect of chinese herbal medicine on mortality in myocardial infarction: systematic review and meta-analysis of randomized controlled trials.

In China, Chinese herbal medicine (CHM) is widely used as an adjunct to biomedicine (BM) in treating myocardial infarction (MI). This meta-analysis of RCTs evaluated the efficacy of combined CHM-BM in the treatment of MI, compared to BM alone. Sixty-five RCTs (12,022 patients) of moderate quality were identified. 6,036 patients were given CHM plus BM, and 5,986 patients used BM only. Combined results showed clear additional effect of CHM-BM treatment in reducing all-cause mortality (relative risk reduction (RRR) = 37%, 95% CI = 28%-45%, I(2) = 0.0%) and mortality of cardiac origin (RRR = 39%, 95% CI = 22%-52%, I(2) = 22.8). Benefits remained after random-effect trim and fill adjustment for publication bias (adjusted RRR for all-cause mortality = 29%, 95% CI = 16%-40%; adjusted RRR for cardiac death = 32%, 95% CI = 15%-46%). CHM is also found to be efficacious in lowering the risk of fatal and nonfatal cardiogenic shock, cardiac arrhythmia, myocardial reinfarction, heart failure, angina, and occurrence of total heart events. In conclusion, addition of CHM is very likely to be able to improve survival of MI patients who are already receiving BM. Further confirmatory evaluation via large blinded randomized trials is warranted.

Influence of moxibustion apparatus as adjuvant treatment for pulmonary tuberculosis and patient's immune function / 中国针灸

<p><b>OBJECTIVE</b>To verify efficacy of moxibustion apparatus on pulmonary tuberculosis (PT) and explore adjuvant treatment method for PT.</p><p><b>METHODS</b>One hundred cases of PT were randomly divided into a moxibustion group and a routine treatment group, 50 cases in each one. The regular antituberculous therapy (2HRZE/4HRE) was applied in both groups. In addition, the moxibustion apparatus was used at Bailao (EX-HN 15), Feishu (BL 13), Gaohuang (BL 43), Qihai (CV 6), Zhongfu (LU 1), Danzhong (CV 17), Guanyuan (CV 4), Zusanli (ST 36) and so on in the moxibustion group. The change of lesion area in chest radiography, degradation rate of bacte rium in the sputum, T-lymphocyte subsets and natural kill (NK) cells were observed before and after treatment in two groups.</p><p><b>RESULTS</b>After the treatment for 3 months, there were 45 cases (90.0%) in the moxibustion group with more than 45% of focal absorption in chest radiography, which was obviously higher than 72.0% (36/50) in the routine treatment group (P < 0.01). The degradation rate of bacterium in the sputum in the moxibustion group was higher than that in the routine treatment group [82.0% (41/50) vs 60.0% (30/50), P < 0.01]. The CD3+, CD4+/CD8+ ratio of T-lymphocyte subsets and NK cells in the moxibustion group were significantly higher than those in the routine treatment group (P < 0.05, P < 0.01).</p><p><b>CONCLUSION</b>On the basis of regular antituberculous therapy, moxibustion apparatus could significantly improve clinical effect, promote focal absorption and boost immunity, which is considered as an adjuvant treatment for PT.</p>

Effects of electroacupuncture on the proprioception of athletes with functional ankle instability / 中国针灸

<p><b>OBJECTIVE</b>To observe the efficacy differences between electroacupuncture and physiotherapy on the proprioception of athletes with functional ankle instability (FAD.</p><p><b>METHODS</b>Fifty athletes with FAI were randomly divided into an electroacupuncture group and a physiotherapy group. The electroacupuncture group was treated with electroacupuncture at Jiexi (ST 41), Kunlun (BL 60), Qiuxu (GB 40) and Ashi acupoints, and the physiotherapy group was treated with low frequency electrical stimulation and infrared radiation at medial malleolus and lateral malleolus, thrice each week for consecutive 8 weeks. The Joint Position Sense: Active (JPSA), Joint Position Sense: Passive (JPSP) and Kinaesthesia (KT) were assessed at the ankle by use of Biodex System-III isokinetic dynamometer.</p><p><b>RESULTS</b>The JPSA of 11.090 +/- 3.1 degrees and the JPSP of 9.67 degrees +/- 2.8 degrees before the treatment reduced to 9.14 degrees +/- 4.0 degrees and 6.89 degrees +/- 3.3 degrees, respectively, after the treatment in the electroacupuncture group, with significant differences in JPSA and JPSP (both P < 0.05), compared with those in the physiotherary group, there were significant differences (both P < 0.05) and with no significant difference in KT (P > 0.05). There was no significant differences in the indices of JPSA, JPSP and KT in the physiotherapy group after 8 weeks than those before treatment (all P > 0.05).</p><p><b>CONCLUSION</b>Electroacupuncture can effectively improve the proprioception of athletes with FAI and achieves a superior efficacy as compared with the conventional physiotherapy.</p>

Rhein ameliorates fatty liver disease through negative energy balance, hepatic lipogenic regulation, and immunomodulation in diet-induced obese mice.

Nonalcoholic fatty liver disease (NAFLD) is associated with obesity, insulin resistance, and inflammatory disorders. In this study, we tested the effect of rhein, a lipophilic anthraquinone derived from a traditional Chinese herbal medicine Rheum palmatum L., on NAFLD-associated hepatic steatosis, insulin resistance, and the T helper (Th)1/Th2 cytokine imbalance in high-fat diet-induced obese (DIO) mice. We found that oral administration of rhein for 40 days significantly increased energy expenditure, reduced body weight, particularly body fat content, improved insulin resistance, and lowered circulating cholesterol levels in DIO mice without affecting food intake. Rhein treatment also reduced liver triglyceride levels, reversed hepatic steatosis, and normalized alanine aminotransferase (ALT) levels in these mice. Gene analysis and Western blot showed that rhein markedly suppressed the expression of the lipogenic enzyme sterol regulatory element-binding protein-1c (SREBP-1c) and its target genes in the liver. Luciferase reporter assay revealed that rhein suppressed the transcriptional activity of SREBP-1c through its upstream regulator, liver X receptor (LXR). This suggests that rhein exerts its effects by targeting LXR, which is also supported by its inability to reduce body weight in LXR knockout mice. Moreover, multiplex ELISA displayed a downregulated Th1 response after rhein treatment. Rhein shifted the Th1/Th2 responses by inhibiting T-box expressed in T-cells (T-bet) expression and enhancing GATA-binding protein-3 (GATA-3) expression through increased signal transducer and activator of transcription 6 (STAT6) phosphorylation. These data indicate that rhein ameliorated NAFLD and associated disorders through LXR-mediated negative energy balance, metabolic regulatory pathways, and immunomodulatory activities involved in hepatic steatosis. The combined effects of rhein to target hepatic metabolic and immune pathways may be beneficial for complex metabolic diseases such as NAFLD.

Regulation of fasting fuel metabolism by toll-like receptor 4.

OBJECTIVE: Toll-like receptor 4 (TLR4) has been reported to induce insulin resistance through inflammation in high-fat-fed mice. However, the physiological role of TLR4 in metabolism is unknown. Here, we investigated the involvement of TLR4 in fasting metabolism. RESEARCH DESIGN AND METHODS: Wild-type and TLR4 deficient (TLR4(-/-)) mice were either fed or fasted for 24 h. Glucose and lipid levels in circulation and tissues were measured. Glucose and lipid metabolism in tissues, as well as the expression of related enzymes, was examined. RESULTS: Mice lacking TLR4 displayed aggravated fasting hypoglycemia, along with normal hepatic gluconeogenesis, but reversed activity of pyruvate dehydrogenase complex (PDC) in skeletal muscle, which might account for the fasting hypoglycemia. TLR4(-/-) mice also exhibited higher lipid levels in circulation and skeletal muscle after fasting and reversed expression of lipogenic enzymes in skeletal muscle but not liver and adipose tissue. Adipose tissue lipolysis is normal and muscle fatty acid oxidation is increased in TLR4(-/-) mice after fasting. Inhibition of fatty acid synthesis in TLR4(-/-) mice abolished hyperlipidemia, hypoglycemia, and PDC activity increase, suggesting that TLR4-dependent inhibition of muscle lipogenesis may contribute to glucose and lipid homeostasis during fasting. Further studies showed that TLR4 deficiency had no effect on insulin signaling and muscle proinflammatory cytokine production in response to fasting. CONCLUSIONS: These data suggest that TLR4 plays a critical role in glucose and lipid metabolism independent of insulin during fasting and identify a novel physiological role for TLR4 in fuel homeostasis.

Regulation of Th1 and Th17 cell differentiation and amelioration of experimental autoimmune encephalomyelitis by natural product compound berberine.

Berberine (BBR), an isoquinoline alkaloid derived from plants, is widely used as an anti-inflammatory remedy in traditional Chinese medicine. In this study, we showed that BBR was efficacious in the amelioration of experimental autoimmune encephalomyelitis (EAE) through novel regulatory mechanisms involving pathogenic Th1 and Th17 cells. BBR inhibited differentiation of Th17 cells and, to a lesser degree, Th1 cells through direct actions on the JAK/STAT pathway, whereas it had no effect on the relative number of CD4(+)Foxp3(+) regulatory T cells. In addition, BBR indirectly influenced Th17 and Th1 cell functions through its effect on the expression and function of costimulatory molecules and the production of IL-6, which was attributable to the inhibition of NF-kappaB activity in CD11b(+) APCs. BBR treatment completely abolished the encephalitogenicity of MOG(35-55)-reactive Th17 cells in an adoptive transfer EAE model, and the same treatment significantly inhibited the ability of MOG(35-55)-reactive Th1 cells to induce EAE. This study provides new evidence that natural compounds, such as BBR, are of great value in the search for novel anti-inflammatory agents and therapeutic targets for autoimmune diseases.

Effect of combined therapy with Chinese drug and narrow broad ultraviolet B on Bcl-2, caspase-3 and survivin in skin lesion with psoriasis vulgaris / 中国中西医结合杂志

<p><b>OBJECTIVE</b>To reveal the possible role of combined therapy with Chinese drug and narrow broad ultraviolet B (NB-UVB) on keratinocytes apoptosis in skin lesion of psoriasis vulgaris (PV).</p><p><b>METHODS</b>Skin samples were taken from 20 healthy subjects and 30 PV patients before and after they received the combined therapy for 8 weeks. SP immunohistochemical method was used to detect the expressions of Bcl-2, Caspase-3 and survivin in the samples.</p><p><b>RESULTS</b>As compared with those in the normal skin, expression of Bcl-2 in PV skin was significantly lower (7.50 +/- 2.01 vs. 12.65 +/- 2.83), while expression of Caspase-3 (21.73 +/- 3.70 vs. 8.55 +/- 2.16), and survivin (23.90 +/- 2.82 vs. 7.06 +/- 1.96) were higher (all P < 0.01). After treatment, in skin of PV, Bcl-2 expression increased to 13.63 +/- 2.14, Caspase-3 and survivin decreased to 11.70 +/- 2.44 and 12.46 +/- 1.80, respectively (all P < 0.01), showing a normalizing trend. Moreover, patients' psoriasis area and severity index (PASI) score decreased from 14.24 +/- 3.42 before treatment to 3.52 +/- 1.07 after treatment (P < 0.01).</p><p><b>CONCLUSION</b>The curing effect of the combined therapy with Chinese drug and NB-UVB in treating PV is possibly realized by way of regulating Bcl-2, Caspase-3 and survivin expressions to adjust keratinocyte apoptosis.</p>

Berberine differentially modulates the activities of ERK, p38 MAPK, and JNK to suppress Th17 and Th1 T cell differentiation in type 1 diabetic mice.

Berberine, an alkaloid derivative from Berberis vulgaris L., has been used extensively in traditional Chinese medicine to treat diarrhea and diabetes, but the underlying mechanisms for treating diabetes are not fully understood. Recent studies suggested that berberine has many beneficial biological effects, including anti-inflammation. Because type 1 diabetes is caused by T cell-mediated destruction of beta cells and severe islet inflammation, we hypothesized that berberine could ameliorate type 1 diabetes through its immune regulation properties. Here we reported that 2 weeks of oral administration of berberine prevented the progression of type 1 diabetes in half of the NOD mice and decreased Th17 and Th1 cytokine secretion. Berberine suppressed Th17 and Th1 differentiation by reducing the expression of lineage markers. We found that berberine inhibited Th17 differentiation by activating ERK1/2 and inhibited Th1 differentiation by inhibiting p38 MAPK and JNK activation. Berberine down-regulated the activity of STAT1 and STAT4 through the suppression of p38 MAPK and JNK activation, and it controlled the stability of STAT4 through the ubiquitin-proteasome pathway. Our findings indicate that berberine targets MAPK to suppress Th17 and Th1 differentiation in type 1 diabetic NOD mice. This study revealed a novel role of ERK in Th17 differentiation through down-regulation of STAT3 phosphorylation and RORgamma t expression.

Neuroprotective effect of transcorneal electrical stimulation on light-induced photoreceptor degeneration.

Direct electrical stimulation of neural tissues is a strategic approach to treat injured axons by accelerating their outgrowth [Al-Majed, A.A., Neumann, C.M., Brushart, T.M., Gordon, T., 2000. Brief electrical stimulation promotes the speed and accuracy of motor axonal regeneration. J. Neurosci. 20, 2602-2608] and promoting their regeneration [Geremia, N.M., Gordon, T., Brushart, T.M., Al-Majed, A.A., Verge, V.M.K., 2007. Electrical stimulation promotes sensory neuron regeneration and growth-associated gene expression. Exp. Neurol. 205, 347-359]. Recently, transcorneal electrical stimulation (TCES), a novel less invasive method, has been shown to rescue axotomized and damaged retinal ganglion cells [Morimoto, T., Miyoshi, T., Matsuda, S., Tano, Y., Fujikado, T., Fukuda, Y., 2005. Transcorneal electrical stimulation rescues axotomized retinal ganglion cells by activating endogenous retinal IGF-1 system. Invest. Ophthalmol. Vis. Sci. 46(6), 2147-2155]. Here, we investigated the neuroprotection of TCES on light-induced photoreceptor degeneration and the underlying mechanism. Adult male Sprague-Dawley (SD) rats received TCES before (pre-TCES) or after (post-TCES) intense light exposure. After fourteen days of light exposure, retinal histology and electroretinography were performed to evaluate the neuroprotective effect of TCES. The mRNA and protein levels of apoptotic-associated genes including Bcl-2, Bax, Caspase-3 as well as ciliary neurotrophic factor (CNTF) and brain-derived neurotrophic factor (BDNF) in the retinas were determined by real-time PCR and Western blot analysis. The localization of these gene products in the retinas was examined by immunohistochemistry. Both pre- and post-TCES ameliorated the progressive photoreceptor degeneration. The degree of rescue depended on the strength of the electric charge. Post-TCES showed a relatively better and longer-term protective effect than pre-TCES. Real-time PCR and Western blot analysis revealed an upregulation of Bcl-2, CNTF, and BDNF and a downregulation of Bax in the retinas after TCES. Immunohistochemical studies showed that Bcl-2 and CNTF were selectively upregulated in Müller cells. These findings provide a new therapeutic method to prevent or delay photoreceptor degeneration through activating the intrinsic survival system.

Lecithin promotes adipocyte differentiation and hepatic lipid accumulation.

Lecithin is an essential biological component and widely used as a nutritional supplement for protecting cells from oxidation, increase fat burning and preventing cardiovascular disease. Lecithin contains fatty acids identified as the peroxisome proliferator-activated receptor (PPAR) agonists. However, the role of lecithin in adipogenesis and lipogenesis remains elusive. 3T3-L1 cells and mouse primary preadipocytes were used to characterize the properties of lecithin related to adipogenesis and lipogenesis. We found that lecithin promoted adipocyte differentiation and differentiation-specific gene expression, and increased triglycerides and free fatty acid levels in the adipocytes. These effects are independent of the clonal expansion of 3T3-L1 cells and the upstream PPARgamma regulator, CCAAT-enhancer-binding protein beta. Furthermore, lecithin induced lipid accumulation in human hepatoma HepG2 cells. Our data suggest that lecithin is involved in adipogenesis, lipogenesis and hepatic lipid accumulation and it is implicated in obesity and hepatic steatosis.