Integrative transcriptomic and metabolomic analysis in mice reveals the mechanism by which ginseng stem-leaf saponins enhance mucosal immunity induced by a porcine epidemic diarrhea virus vaccination.

Porcine epidemic diarrhea virus (PEDV) is a main cause of severe enteric disease in piglets, leading to millions of dollars lost annually in the global pig industry. Parenteral vaccination is limited in generating sufficient mucosal immunity, which is crucial for early defense against PEDV. Here, we orally administered ginseng stem-leaf saponins (GSLS) to mice before parenteral vaccination and found that GSLS significantly enhanced the phagocytosis of dendritic cells, promoted the activities of CD4+ T cells and increased PEDV-specific IgA antibodies in the intestinal mucosa. Transcriptomic results showed that the altered genes following GSLS treatment were mostly related to the immune response and metabolism. In addition, integrated analysis of the transcriptome and metabolome revealed that the mechanism by which GSLS enhances mucosal immunity may be associated with progesterone-related pathways. Further studies are needed to explore the detailed molecular mechanisms.

Inducing Intermediates in Biotransformation of Natural Polyacetylene and A Novel Spiro-γ-Lactone from Red Ginseng by Solid Co-Culture of Two Gut Chaetomium globosum and The Potential Bioactivity Modification by Oxidative Metabolism.

The ω-hydroxyl-panaxytriol (1) and ω-hydroxyl-dihydropanaxytriol (2)-are rare examples of polyacetylene metabolism by microbial transformation, and these new metabolites (1, 2) from fermented red ginseng (FRG) by solid co-culture induction of two Chaetomium globosum should be the intermediates of biotransformation of panaxylactone (metabolite A). The metabolic pathway of panaxylactone was also exhibited. The ingredients of red ginseng (RG) also induced the production of rare 6/5/5 tricyclic ring spiro-γ-lactone skeleton (3). The ω-hydroxylation of new intermediates (1, 2) decreases cytotoxicity and antifungal activity against C. globosum compared with that of its bioprecursor panaxytriol. Additionally, compounds 1 and 2 indicated obvious inhibition against nitric oxide (NO) production, with ratios of 44.80 ± 1.37 and 23.10 ± 1.00% at 50 µM. 1 has an equivalent inhibition of NO production compared with the positive drug. So, the microbial biotransformation that occurred in FRG fermented by gut C. globosum can change the original bioactivity of polyacetylene, which gave a basis about the metabolic modification of red ginseng by intestinal fungus fermentation.

Inducing secondary metabolite production from Daldinia eschscholzii JC-15 by red ginseng medium.

Red ginseng (RG) is one of the most popular herbal medicines and used as a dietary supplement in recent years. The bioactive ingredient in RG can induce the production of novel microbial metabolite from fermented RG. Using the one strain-many compounds strategy, the reinvestigation of the metabolites from Daldinia eschscholzii JC-15 cultured in red ginseng medium led to the isolation of an unprecedented benzopyran-naphthalene hybrid, daldinsin (1) and a new lactone (2). In this research, a new lactone, 8-hydroxylhelicascolide A (2) instead of helicascolide A was produced by the D. eschscholzii JC-15 induced by the red ginseng medium. Compound 1 showed anti-acetylcholinesterase activity with the inhibition ratio of 38.8% at 50 µM. Compound 2 indicated antimicrobial activities against Fusarium Solani, F. oxysporum, and Escherichia coli with MICs at 128 µg/mL. RG is therefore a promising activator in production of novel microbial metabolite.

Hesperetin derivative attenuates CCl4-induced hepatic fibrosis and inflammation by Gli-1-dependent mechanisms.

Hepatic fibrosis, a common pathological feature and leading cause of various chronic liver diseases, still lacks effective therapy. Hesperetin derivative (HD) is a derivative of Traditional Chinese Medicine monomer isolated from the fruit peel of Citrusaurantium L. (Rutaceae). In the present study, we revealed the anti-fibrotic effects of HD in CCl4-induced mouse hepatic fibrosis model and in TGF-ß1-activated LX-2 cells, in vivo and in vitro. Results showed that HD prevented CCl4-induced liver injury and histological damage. Consistently, HD inhibited the up-regulation of liver fibrogenesis markers α-SMA, Col1α1, Col3α1 and TIMP-1 in primary hepatic stellate cells (HSCs) and suppressed inflammatory responses in primary liver macrophages from hepatic fibrosis mice. Furthermore, HD promoted the apoptosis of activated HSCs, a key step in the onset of fibrosis regression. Mechanistically, the Hedgehog pathway was involved in HD-treated hepatic fibrosis, and HD specifically contributed to attenuate the aberrant expression of Glioma associated oncogene-1 (Gli-1). Interestingly, blockade of Gli-1 removed the inhibitory effect of HD on activated HSCs, indicating that Gli-1 may play a pivotal role in mediating the anti-fibrotic effect of HD in hepatic fibrosis. Collectively, our results suggest that HD may be a potential anti-fibrotic Traditional Chinese Medicine monomer for the treatment of hepatic fibrosis.

Da-cheng-qi decoction, a traditional Chinese herbal formula, for intestinal obstruction: systematic review and meta-analysis.

BACKGROUND: This study was aimed at determining the effects and safety of Da-Cheng-Qi decoction (DCQD) or DCQD combined with conservative therapy in patients with intestinal obstruction. MATERIALS AND METHODS: PubMed, EMBASE, Cochrane Controlled Trials Register, and several other databases were searched. Randomised controlled trials (RCTs) of DCQD or DCQD plus conservative therapy in patients with intestinal obstruction were eligible. Therapeutic effect was estimated by the improvement of clinical manifestations and diagnostic imaging; dichotomous/ordinal data assessment of overall response to therapy, adverse effects; or continuous variable were identified, including time to first bowel movement, time to first flatus, length of hospital stay. RESULTS: Sixty eligible RCTs including 6,095 patients were identified. Response rate: (1) DCQD versus conservative therapy (6 RCTs, 361 patients, RR of respond =1.13; 95% CI 0.97 to 1.31). (2) DCQD plus conservative therapy versus conservative therapy (48 RCTs, 4,916 patients, RR of respond =1.25 which favoured DCQD plus conservative therapy; 95% CI 1.20 to 1.30). Treatment effect remained similar when RCTs at high risk of bias were excluded. Time to first flatus postoperatively: (1) DCQD versus conservative therapy (2 RCTs, 240 patients, SMD=-3.65; 95% CI -8.17 to 0.87). (2) DCQD plus conservative therapy versus conservative therapy (11 RCTs, 1,040 patients, SMD=-2.09 which favoured DCQD plus conservative therapy; 95% CI -3.04 to -1.15). CONCLUSION: DCQD combined with conservative therapy may increase the success rate of conservative therapy for intestinal obstruction significantly and can shorten the duration of postoperative ileus in patients undergoing abdominal surgery compared with conservative therapy alone.

Effect of dietary lysine on growth, intestinal enzymes activities and antioxidant status of sub-adult grass carp (Ctenopharyngodon idella).

The dietary lysine requirement of sub-adult grass carp (460 ± 1.5 g) was assessed by feeding diets supplemented with grade levels of lysine (6.6, 8.5, 10.8, 12.9, 15.0 and 16.7 g kg(-1) diet) for 56 days. The test diets (28% CP) contained fish meal, casein and gelatin as sources of intact protein, supplemented with crystalline amino acids. Weight gain (WG), feed intake and feed efficiency were significantly improved with increasing levels of lysine up to 12.9 g kg(-1) diet and thereafter declined (P < 0.05). Quadratic regression analysis of WG at 95% maximum response indicated lysine requirement was 10.9 g kg(-1) diet. Activities of trypsin, chymotrypsin, lipase, Na(+), K(+)-ATPase and alkaline phosphatase in intestine, creatine kinase activity in proximal and mid-intestine responded similar to WG (P < 0.05). In addition, lipid and protein oxidation decreased with increasing levels of lysine up to certain values and increased thereafter (P < 0.05); the anti-hydroxyl radical capacity, dismutase, catalase, glutathione peroxidase, glutathione reductase, glutathione-S-transferase (GST) activities and glutathione content were increased with increasing dietary lysine levels up to certain values in the detected tissues, except for hepatopancreatic GST. Requirement estimated on the basis of malondialdehyde content in intestine and hepatopancreas was 10.6 and 9.53 g lysine kg(-1) diet, respectively.

Investigation and analysis of plasma trace elements of oldest elderly in longevity areas in China / 中华预防医学杂志

<p><b>OBJECTIVE</b>To investigate the levels and differences of plasma selenium, manganese, iron, copper, zinc among oldest elderly in longevity areas in China.</p><p><b>METHODS</b>446 oldest elderly including 208 centenarians, 238 aged 90 and over, who lived in Xiayi county of Henan province (110 persons), Zhongxiang city of Hubei province (111 persons), Mayang county of Hunan province (60 persons), Sanshui district of Guangdong province (113 persons), Yongfu county of Guangxi Zhuang autonomous region (52 persons) in China, were selected. The contents of plasma selenium, manganese, iron, copper, zinc were detected and compared among these elderly who were classified into different genders, different regions and different age groups.</p><p><b>RESULTS</b>In oldest elderly, the median (inter-quartile range) of content of plasma selenium was 1.44 (0.91) micromol/L, content of manganese was 0.54 (0.94) micromol/L, content of iron was 69.17 (102.85) micromol/L, content of copper was 20.19 (8.73) micromol/L, content of zinc was 31.66 (32.51) micromol/L. Contents of plasma selenium of oldest elderly in Xiayi, Zhongxiang, Mayang, Sanshui, Yongfu region were 1.46 (0.66), 1.30 (0.80), 1.06 (0.51), 2.39 (1.53) and 1.35(0.55) micromol/L; contents of plasma manganese were 0.56 (0.51), 1.40 (1.11), 0.35 (0.71), 0.44 (0.55) and 0.15 (0.21) micromol/L; contents of plasma iron were 86.77 (86.87), 141.42 (101.83), 38.88 (36.28), 31.38 (46.19) and 79.64 (75.34) micromol/L; contents of plasma copper were 22.16 (8.11), 19.46 (9.26), 21.36 (12.38), 18.12 (6.74) and 21.47 (7.85) micromol/L; contents of plasma zinc were 36.85 (26.18), 36.59 (35.94), 39.98 (56.91), 25.05 (24.92) and 16.74 (16.81) micromol/L. Contents of plasma trace elements among oldest elderly in different longevity areas were significantly different (F values were 29.76, 38.75, 47.18, 11.51 and 13.47, P values were all less than 0.05). Contents of plasma trace elements in different gender groups (contents of plasma selenium were 1.38 (0.83) micromol/L in male and 1.45 (0.91) micromol/L in female; contents of plasma manganese were 0.52 (0.95) and 0.54 (0.91) micromol/L; contents of plasma iron were 69.23 (104.06) and 69.11 (101.05) micromol/L; contents of plasma copper were 20.28 (8.72) and 20.06 (8.76) micromol/L; contents of plasma zinc were 28.39 (32.58) and 31.85 (34.26) micromol/L) were not significantly different (t(Se) = -1.82, P = 0.07; t(Mn) = 0.64, P = 0.52; t(Fe) = 0.65, P = 0.52; t(Cu) = -1.90, P = 0.06; t(Zn) = -0.96, P = 0.34). The contents of plasma selenium, iron, copper in centenarians were higher than those aged 90 and over (contents of plasma selenium were 1.63 (0.94) micromol/L and 1.30 (0.82) micromol/L, contents of plasma iron were 112.63 (119.78) and 60.13 (58.43) micromol/L, contents of plasma copper were 21.07 (9.03) and 18.81 (8.86) micromol/L, F value were 41.99, 27.32, 24.45, P values were less than 0.01). Content of plasma manganese in centenarians was lower than those aged 90 and over (0.44 (0.76) and 0.64 (0.93) micromol/L, F = 10.76, P < 0.01). No significant differences were detected in plasma zinc between concentration and those aged 90 and over (31.78 (34.06) and 31.11 (33.85) micromol/L; F = 1.32, P = 0.25).</p><p><b>CONCLUSION</b>The concentrations of plasma selenium, manganese, iron, copper and zinc were high in oldest elderly in the longevity areas. The contents of plasma selenium, iron, copper increased with age.</p>

Effect of Tongxinluo on nestin and vascular endothehal growth factor mRNA expression in rat brain tissue after cerebral ischemia-reperfusion injury / 南方医科大学学报

<p><b>OBJECTIVE</b>To investigate the expressions of nestin and vascular endothehal growth factor (VEGF) mRNAs in rat brain tissue after cerebral ischemia-reperfusion injury and their changes in response to Tongxinluo (a traditional Chinese herbal preparation) treatment.</p><p><b>METHODS</b>Cerebral ischemia was induced in rats by temporary middle cerebral artery occlusion (MCAO) followed by treatment with Tongxinluo at high and low doses. On days 3, 7, 14 and 21 after MCAO, nestin and VEGF mRNA expressions in the ependyma, subventricular zone (SVZ), and hippocampal subdentate gyrus zone (HDG) in the ischemic hemisphere were quantitatively analyzed using immunohistochemistry and RT-PCR.</p><p><b>RESULTS</b>Compared with the sham-operated group, the rats with cerebral ischemia-reperfusion injury showed significantly increased nestin-positive neurons and VEGF mRNA expression in the SVZ and HDG 7, 14 and 21 days after MCAO (P<0.05). Treatment with Tongxinluo, especially at high doses, significantly increased the number of nestin-positive neurons and VEGF mRNA expression in the rats 7, 14 and 21 days after MCAO (P<0.05).</p><p><b>CONCLUSION</b>Focal cerebral ischemia in rats results in rapid response and proliferation of neural stem cells in the SVZ and HDG in the ischemic hemisphere possibly by increasing VEGF mRNA expression in the adjacent tissues around the ischemic focus. Tongxinluo may enhance the differentiation and proliferation capacity of the neural stem cells after MCAO by inducing the expression of VEGF mRNA.</p>

Effect of Tongxinluo on the proliferation and differentiation of rat embryonic neural stem cells / 南方医科大学学报

<p><b>OBJECTIVE</b>To investigate the effect of Tongxinluo in on the proliferation and differentiation of rat embryonic neural stem cells (NSCs).</p><p><b>METHODS</b>NSCs were isolated from 12- to 14-day SD rat embryo and treated with Tongxinluo at different doses, and the proliferation and differentiation of the cells were observed by immunofluorescence staining at different time points.</p><p><b>RESULTS</b>The ratio of embryonic NSCs labeled with nestin decreased soon after Tongxinluo treatment, but increased afterwards. Significant difference was noted in the number of cells labeled with beta-tubulin between Tongxinluo group and the control group 3 and 7 days after the treatment, and also between high-dose and low-dose Tongxinluo groups at 7 days.</p><p><b>CONCLUSION</b>Tongxinluo can induce the proliferation and neuronal differentiation of rat embryonic NSCs, and the effect is related to the dose of Tongxinluo administered.</p>

Icariine stimulates proliferation and differentiation of human osteoblasts by increasing production of bone morphogenetic protein 2 / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Icariine is a flavonoid isolated from a traditional Chinese medicine Epimedium pubescens and is the main active compound of it. Recently, Epimedium pubescens was found to have a therapeutic effect on osteoporosis. But the mechanism is unclear. The aim of the study was to research the effect of Icariine on the proliferation and differentiation of human osteoblasts.</p><p><b>METHODS</b>Human osteoblasts were obtained by inducing human marrow mesenchymal stem cells (hMSCs) directionally and were cultured in the presence of various concentrations of Icariine. 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT) test was used to observe the effect of Icariine on cell proliferation. The activity of alkaline phosphatase (ALP) and the amount of calcified nodules were assayed to observe the effect on cell differentiation. The expression of bone morphogenetic protein 2 (BMP-2) mRNA was detected by reverse transcriptase-polymerase chain reaction (RT-PCR).</p><p><b>RESULTS</b>Icariine (20 microg/ml) increased significantly the proliferation of human osteoblasts. And, Icariine (10 microg/ml and 20 microg/ml) increased the activity of ALP and the amount of calcified nodules of human osteoblasts significantly (P < 0.05). BMP-2 mRNA synthesis was elevated significantly in response to Icariine (20 microg/ml).</p><p><b>CONCLUSIONS</b>Icariine has a direct stimulatory effect on the proliferation and differentiation of cultured human osteoblast cells in vitro, which may be mediated by increasing production of BMP-2 in osteoblasts.</p>

[Observation on therapeutic effect of chronic prostatitis treated mainly by warming needle moxibustion].

OBJECTIVE: To explore an effective method for increasing therapeutic effect on chronic prostatitis. METHODS: Eighty-two cases of chronic prostatitis were randomly divided into two groups. The western medicine group of 42 cases were treated with routine western medicine combined with retention enteroclysis of 30 g Danshen (Red Sage Root) decoction; the warming needle moxibustion plus western medicine group of 40 cases were treated with the western medicine of the western medicine group plus warming needle moxibustion at Guanyuan (CV 4), Qihai (CV 6) and Zhongji (CV 3), etc. RESULTS: In the warming needle moxibustion plus western medicine grbup, 20 cases were cured, 12 cases were markedly effective, 5 cases were effective and 3 cases were ineffective, the total effective rate being 92. 5%; and in the western medicine group, the corresponding figures were 13, 10, 7, 12 cases and 71.4%, with a significant difference between the two groups in the total effective rate (P < 0.05). CONCLUSION: Warming needle moxibustion can increase the therapeutic effect on chronic prostatitis.

Nestin activation after rat cerebral ischemia-reperfusion injury and its changes in response to Tongxinluo treatment / 南方医科大学学报

<p><b>OBJECTIVE</b>To investigate nestin activation in rat brain subjected to ischemia-reperfusion injury and its changes in response to Tongxinluo treatment.</p><p><b>METHODS</b>Cerebral ischemia was induced by temporary middle cerebral artery occlusion (MCAO) in rats. At 3, 7, 14 and 21 days after MCAO, nestin expression in the ependyma, subventricular zone (SVZ), hippocampal subdentate gyrus zone (HDG) of the rats treated with Tongxinluo were guantified by immunohistochemistry.</p><p><b>RESULTS</b>Compared with the sham operation group, nestin was significantly increased 7, 14 and 21 days after MCAO (P<0.05), and immunofluorescence of BrdU+nestin-positive neurons significantly increased in the SVZ. After treatment with Tongxinluo, the number of BrdU-positive neurons and BrdU+nestin-positive neurons significantly increased as compared with MCAO group (P<0.05).</p><p><b>CONCLUSION</b>Focal cerebral ischemia in the rat results in rapid response and proliferation of neural stem cells in the SVZ and HDG in the ischemic hemisphere, and Tongxinluo may enhance the differentiation and proliferation capacity of the neural stem cells after MCAO.</p>

Effects of Epimedium pubescens icariine on proliferation and differentiation of human osteoblasts / 中国中药杂志

<p><b>OBJECTIVE</b>To study the effects of epimedium pubescens icariine on the proliferation and differentiation of human osteoblasts.</p><p><b>METHOD</b>Human osteoblasts were obtained by inducting human marrow mesenchymal stem cells (hMSCs) directionally. MTT was used to observe the proliferation and activity of ALP was assayed to observe the differentiation of the third passage human osteoblasts cultured in vitro. The expression of BMP-2 mRNA was checked by RT-PCR.</p><p><b>RESULT</b>Epimedium pubescens icariine at the dose of 20 microg x mL(-1) increased greatly the proliferation and differentiation of human osteoblasts and promoted the expression of BMP-2 mRNA.</p><p><b>CONCLUSION</b>Epimedium pubescens icariine enhances significantly the proliferation and differentiation of human osteoblasts, which may be mediated by increasing the expression of BMP-2 mRNA.</p>