Clinical correlation between serum cytokines and the susceptibility to Polygonum multiflorum-induced liver injury and an experimental study.

Polygonum multiflorum (PM), a popular functional food, and a herbal and dietary supplement, is widely used as a tonic in China and East Asia. In recent years, it has attracted great concern for its ability to cause idiosyncratic drug-induced liver injury (IDILI). However, identifying individuals susceptible to IDILI remains challenging. This is a prospective study. For 6 patients whose serum alanine aminotransferase (ALT) levels after consuming PM were abnormally elevated (susceptible group), 15 patients with normal levels of liver injury markers were matched (tolerant group) based on similar baseline characteristics. ProcartaPlex immunoassays were adopted to quantitatively detect 33 serum cytokines in the two groups of patients before consuming PM, to characterize the cytokine profile and screen differential cytokines. Subsequently, the susceptibility of a potential biomarker to regulate PM-induced liver injury was validated in animal models. There were significant differences in the cytokine profiles between the susceptible and tolerant groups, wherein the susceptible patients showed immune perturbation characterized by high expression of multiple inflammatory cytokines, especially the proinflammatory cytokine TNF-α (P = 0.006). Among them, the cytokine TNF-α had the strongest correlation with ALT, where the correlation coefficient was greater than 0.6, and the area under the receiver operating characteristic curve was more than 0.8. Animal experiments revealed that both PM water extract and its susceptibility component of liver injury, cis-stilbene glucoside, could cause liver injury in the mice pre-stimulated using TNF-α. Conversely, administration of the same dose of drugs on control mice did not show any hepatotoxicity. In conclusion, immune perturbation mainly mediated by TNF-α may regulate the susceptibility to PM-induced liver injury. This provides a new perspective for the study of susceptibility to IDILI.

Molecular Simulation Studies on the Interactions of Bilirubin at Different States with a Lipid Bilayer.

The unconjugated bilirubin (BR) may penetrate through the cell membrane and cause a severe cytotoxicity. However, the molecular mechanism underlying the penetration of BR into the cell membrane is still largely unknown. In this work, we systematically investigate the interaction of BR and a lipid bilayer under different conditions by using all-atom molecular dynamics simulations. It is found that BR at the Z,Z conformation can easily enter into the interior of the lipid bilayer due to its hydrophobicity. However, when BR transforms from the Z,Z conformation to the E,E conformation (after the blue-light emission), its penetration ability is greatly reduced (especially at its ionized state). This study may offer useful physical insights into the effect of phototherapy on the penetration behavior and the cytotoxicity of the unconjugated BR.

Detection of chlorophyll fluorescence parameters of potato leaves based on continuous wavelet transform and spectral analysis.

The tuber development and nutrient transportation of potato crops are closely related to canopy photosynthesis dynamics. Chlorophyll fluorescence parameters of photosystem II, especially the maximum quantum yield of primary photochemistry (Fv/Fm), are intrinsic indicators for plant photosynthesis. Rapid detection of Fv/Fm of leaves by spectroscopy method instead of time-consuming pulse amplitude modulation technique could help to indicate potato development dynamics and guide field management. Accordingly, this study aims to extract fluorescence signals from hyperspectral reflectance to detect Fv/Fm. Hyperspectral imaging system and closed chlorophyll fluorescence imaging system were applied to collect the spectral data and values of Fv/Fm of 176 samples. The spectral data were decomposed by continuous wavelet transform (CWT) to obtain wavelet coefficients (WFs). Three mother wavelet functions including second derivative of Gaussian (gaus2), biorthogonal 3.3 (bior3.3) and reverse biorthogonal 3.3 (rbio3.3) were compared and the bior3.3 showed the best correlation with Fv/Fm. Two variable selection algorithms were used to select sensitive WFs of Fv/Fm including Monte Carlo uninformative variables elimination (MC-UVE) algorithm and random frog (RF) algorithm. Then the partial least squares (PLS) regression was used to establish detection models, which were labeled as bior3.3-MC-UVE-PLS and bior3.3-RF-PLS, respectively. The determination coefficients of prediction set of bior3.3-MC-UVE-PLS and bior3.3-RF-PLS were 0.8071 and 0.8218, respectively, and the root mean square errors of prediction set were 0.0181 and 0.0174, respectively. The bior3.3-RF-PLS had the best detection performance and the corresponding WFs were mainly distributed in the bands affected by fluorescence emission (650-800 nm), chlorophyll absorption and reflection. Overall, this study demonstrated the potential of CWT in fluorescence signals extraction and can serve as a guide in the quick detection of chlorophyll fluorescence parameters.

Screening of hepatotoxic compounds in Psoralea corylifolia L., a traditional Chinese herbal and dietary supplement, using high-resolution mass spectrometry and high-content imaging.

Owing to the complexity of the composition of herbal and dietary supplements, it is a challenging problem to efficiently screen and identify active or toxic compounds. Psoralea corylifolia L. (PCL) was selected as the subbject to establish a methodology for rapid screening and identification of hepatotoxic compounds. High-content imaging, ultra-performance liquid chromatography and high-resolution mass spectrometry were used in this study to detect the hepatotoxicity and identify unknown compounds in PCL samples. Then, putative toxic compounds which are highly related to hepatotoxicity were screened by spectrum-toxicity correlation analysis, and the toxicity intensity verified by high-content imaging. The maximum nontoxic dose of processed samples with good detoxification effect reduced more than 9 times compared with unprocessed raw medicinal materials. Spectrum-toxicity correlation analysis showed that bavachinin A, bavachin, isobavachalcone and neobavaisoflavone had high correlation with the hepatotoxicity of PCL, and psoralen and isopsoralen had low correlation with hepatotoxicity. This study verified the hepatotoxicity of these six putative compound monomers, proving the results of spectrum-toxicity correlation analysis. Based on the correlation analysis of high-resolution mass spectrometry of detection compounds and high-content imaging of hepatocyte toxicity data, the potential toxic compound of herbal and dietary supplement products can be quickly and accurately screened.

Early Post-Stroke Electroacupuncture Promotes Motor Function Recovery in Post-Ischemic Rats by Increasing the Blood and Brain Irisin.

OBJECTIVE: Recent studies have shown that irisin, a novel peptide hormone derived from muscles, could be used as a potential therapeutic drug against ischemic stroke. Moreover, electroacupuncture (EA) is widely used in the treatment of ischemic stroke. Yet, whether irisin is involved in the EA neuroprotection remains unclear. The following study investigated the association between serum and peri-lesional cortex irisin and EA-induced post-stroke motor recovery in rats. METHODS: The middle cerebral artery occlusion (MCAO) method was used to induce ischemic stroke in rats. Rats were randomly divided into two groups: a middle cerebral artery occlusion (MCAO) group (MCAO rats without treatment) and an electroacupuncture (EA) group (MCAO rats treated with EA). On the 3rd day post-stroke, infarct volume, behavioral deficits, surviving neurons, irisin protein expression in peri-infarction cortex, muscle tissue, and serum were evaluated to identify the neuroprotective of EA in acute ischemic stroke. RESULTS: Compared with the MCAO group, the EA group showed better behavioral performance, a smaller cerebral infarct volume, more surviving neurons, and a significant increase in irisin expression in the peri-infarction cortex and serum (p<0.05). However, no difference in irisin expression in the muscle tissue was found between the MCAO group and the EA group (p>0.05). CONCLUSION: EA promotes motor function recovery, reduces the volume of cerebral infarction, and alleviates neuronal death following ischemic stroke by enhancing the expression of irisin in both the blood and peri-lesional cortex.

Components synergy between stilbenes and emodin derivatives contributes to hepatotoxicity induced by Polygonum multiflorum.

Polygonum multiflorum Thunb. (PM) is a famous traditional Chinese medicine with liver tonic effect, but arousing great concerns for hepatotoxicity issue. In this study, we elucidated the contribution of the two major compounds, emodin-8-O-ß-D-glucoside (EG) and 2,3,5,4´-tetrahydroxyl diphenylethylene-2-O-glucoside (TSG), in PM-induced liver injury.Based on LC-MS, the two concerned compounds were detected simultaneously in the sera of patients with PM-induced liver injury. In the lipopolysaccharide (LPS)-mediated inflammatory stress rat model, by the analysis of plasma biochemistry and liver histopathology, we observed that the solo treatment of EG, not TSG, could induce significant liver injury; and the combined administration of EG and TSG caused more severe liver injury than that of EG.Metabolomics analysis revealed that the EG-triggered liver injury was associated with significant disturbances of sphingolipids and primary bile acids metabolism pathways. In the combined administration group, much more disturbances in EG-triggered metabolic pathways, as well as alterations of several additional pathways such as retinol metabolism and vitamin B6 metabolism, were observed.Taken together, we considered EG was involved in the idiosyncratic liver injury of PM, and TSG played a synergetic role with EG, which contributed to the understanding of the hepatotoxic basis of PM.

Heterocyclic pyrrolizinone and indolizinones derived from natural lactam as potential antifungal agents.

With the aim to develop highly potential active heterocyclic compounds, two series of multi-substituted pyrrolizinone and indolizinones derived from lactam were designed, synthesized and evaluated for their potential antifungal activities against six species of the plant pathogen fungi (Fusarium graminearum, Sclerotinia sclerotiorum, Phomopsis adianticola, Gloeosporium theae-sinensis, Alternaria tenuis Nees, Magnaporthe oryzae). The structure of all the newly molecules were confirmed by analytical spectroscopic data, including 1H NMR, 13C NMR and ESI-MS. According to the preliminary studies on bio-evaluation assay, some of the obtained compounds exhibited moderate and broad-spectrum activities against six fungi compared to the intermediates 6a, 6f and the hymexazol. Particularly, the inhibition rate of compounds 7l, 7m and 7t reached 69.25%, 74.76%, 65.38% against Phomopsis adianticola and Magnaporthe oryzae in vitro activity. Furthermore, compounds 7l and 7t displayed obviously inhibition activities against Phomopsis adianticola compared to the hymexazol. Consequently, compounds 7l and 7t with six-membered alkane ring could be used as new motifs for further investigation.

Ginsenoside-Rd Promotes Neurite Outgrowth of PC12 Cells through MAPK/ERK- and PI3K/AKT-Dependent Pathways.

Panax ginseng is a famous herbal medicine widely used in Asia. Ginsenosides have been identified as the principle active ingredients for Panax ginseng's biological activity, among which ginsenoside Rd (Rd) attracts extensive attention for its obvious neuroprotective activities. Here we investigated the effect of Rd on neurite outgrowth, a crucial process associated with neuronal repair. PC12 cells, which respond to nerve growth factor (NGF) and serve as a model for neuronal cells, were treated with different concentrations of Rd, and then their neurite outgrowth was evaluated. Our results showed that 10 µM Rd significantly increased the percentages of long neurite- and branching neurite-bearing cells, compared with respective controls. The length of the longest neurites and the total length of neurites in Rd-treated PC12 cells were much longer than that of respective controls. We also showed that Rd activated ERK1/2 and AKT but not PKC signalings, and inhibition of ERK1/2 by PD98059 or/and AKT by LY294002 effectively attenuated Rd-induced neurite outgrowth. Moreover, Rd upregulated the expression of GAP-43, a neuron-specific protein involved in neurite outgrowth, while PD98059 or/and LY294002 decreased Rd-induced increased GAP-43 expression. Taken together, our results provided the first evidence that Rd may promote the neurite outgrowth of PC12 cells by upregulating GAP-43 expression via ERK- and ARK-dependent signaling pathways.

Proliferative effects on neural stem/progenitor cells of a sulfated polysaccharide purified from the sea cucumber Stichopus japonicus.

To test the effects of a sulfated polysaccharide, Haishen (HS) on the viability and proliferation of neural stem/progenitor cells (NSPCs), we isolated the polysaccharide from the body wall of the sea cucumber Stichopus japonicus by enzymolysis extraction, anion-exchange and gel-permeation chromatography. HS is a highly sulfated fucoidan with a molecular weight of 4.23x10(5) Da. Due to its safety being of invertebrate origin they are less likely to contain infectious agents, the effects of HS on the viability and proliferation of NSPCs in vitro were examined by MTT assay, BrdU labeling and neurosphere formation assay, respectively. Our results showed that HS alone increased NSPC viability in a dose-dependent manner. Moreover, HS acted synergistically with fibroblast growth factor-2 (FGF-2) but not epidermal growth factor (EGF) to enhance the proliferation of NSPCs. Finally, HS did not induce apoptosis of NSPCs. Our findings suggest that HS can serve as an adjuvant for promoting the proliferation of NSPCs.

[Study on needling depth of Fengfu (GV 16) with CT].

OBJECTIVE: To study on needling safe depth of Fengfu (GV 16) with CT, so as to provide reference for safe needling depth of Fengfu (GV 16) in clinical acupuncture treatment. METHODS: Forty-one adult volunteers were divided into 3 groups, a thin person group, a moderate person group and a fat person group according to Luo's indexes, and computer-aided tomography (CT) was used to measure the needling depth of Fengfu (GV 16). RESULTS: The safe depths of perpendicular needling of Fengfu (GV 16) were different for persons of different somatotypes. The safe needling depth was (27.73 +/- 3.45) mm for the thin person group, (30.78 +/- 2.90) mm for the moderate person group, and (33.39 +/- 4.27) mm for the fat person group. CONCLUSION: The safe needling depth < or = the dangerous depth x 75% can be used for reference for the safe needling depth of Fengfu (GV 16) for different somatotypes persons.

Study on needling depth of Fengfu (GV 16) with CT / 中国针灸

<p><b>OBJECTIVE</b>To study on needling safe depth of Fengfu (GV 16) with CT, so as to provide reference for safe needling depth of Fengfu (GV 16) in clinical acupuncture treatment.</p><p><b>METHODS</b>Forty-one adult volunteers were divided into 3 groups, a thin person group, a moderate person group and a fat person group according to Luo's indexes, and computer-aided tomography (CT) was used to measure the needling depth of Fengfu (GV 16).</p><p><b>RESULTS</b>The safe depths of perpendicular needling of Fengfu (GV 16) were different for persons of different somatotypes. The safe needling depth was (27.73 +/- 3.45) mm for the thin person group, (30.78 +/- 2.90) mm for the moderate person group, and (33.39 +/- 4.27) mm for the fat person group.</p><p><b>CONCLUSION</b>The safe needling depth < or = the dangerous depth x 75% can be used for reference for the safe needling depth of Fengfu (GV 16) for different somatotypes persons.</p>

[Study on needling depth of Dazhui (GV 14), Jianzhongshu (SI 15), Xuanshu (GV 5) and Mingmen (GV 4) with CT].

OBJECTIVE: To provide reference for the safe needling depth of Dazhui (GV 14), Jianzhongshu (SI 15), Xuanshu (GV 5) and Mingmen (GV 4) in clinical acupuncture and moxibustion treatment. METHODS: Thirty-two adult volunteers were divided into 3 groups, thin person group, moderate person group and fat person group according to Luo's indexes, and computer-aided tomography was used to measure the needling depth of Dazhui (GV 14), Jianzhongshu (SI 15), Xuanshu (GV 5) and Mingmen (GV 4). RESULTS: The safe depths of perpendicular needling were different for persons of different somatotypes, for example the needling depth for Dazhui (GV 14) was (32.86 +/- 3.96) mm for the thin person group, (37.76 +/- 4.91) mm for the moderate person group, and (47.93 +/- 5.30) mm for the fat person group.

Study on needling depth of Dazhui (GV 14), Jianzhongshu (SI 15), Xuanshu (GV 5) and Mingmen (GV 4) with CT / 中国针灸

<p><b>OBJECTIVE</b>To provide reference for the safe needling depth of Dazhui (GV 14), Jianzhongshu (SI 15), Xuanshu (GV 5) and Mingmen (GV 4) in clinical acupuncture and moxibustion treatment.</p><p><b>METHODS</b>Thirty-two adult volunteers were divided into 3 groups, thin person group, moderate person group and fat person group according to Luo's indexes, and computer-aided tomography was used to measure the needling depth of Dazhui (GV 14), Jianzhongshu (SI 15), Xuanshu (GV 5) and Mingmen (GV 4).</p><p><b>RESULTS</b>The safe depths of perpendicular needling were different for persons of different somatotypes, for example the needling depth for Dazhui (GV 14) was (32.86 +/- 3.96) mm for the thin person group, (37.76 +/- 4.91) mm for the moderate person group, and (47.93 +/- 5.30) mm for the fat person group.</p>

Effect of selective 5alpha-reductase inhibitor or/and testosterone undecanoate on the reproductive function of male rats / 中华男科学杂志

<p><b>OBJECTIVE</b>To investigate whether 5alpha-reductase inhibitor and dihydrotestosterone (DHT) play a role in spermatogenesis in male rats.</p><p><b>METHODS</b>Thirty-two male rats were divided into 4 groups (Groups C, T, F and FT). Group C received plant oil injection and oral starch perfusion, Group T testosterone undecanoate (TU, 20 mg/kg) injection and oral starch perfusion, Group F plant oil injection and oral Finasteride perfusion, and Group FT TU (20 mg/kg) injection and oral Finasteride perfusion. Data on serum T and DHT, sperm count, sperm mobility and reproductive function were collected and analysed.</p><p><b>RESULTS</b>(1) 5alpha-reductase inhibitor, Finasteride and TU reduced the weight of the testis and epididymis in the experiment groups compared with the negative control (Group C), but TU increased the weight of the prostate while Finasteride decreased it compared with the positive control (Group T). TU combined with Finasteride could counteract the effect of the weight increase of the prostate, but not that of the testis. (2) Finasteride, or Finasteride combined with TU, reduced the DHT but increased the testosterone level in comparison with the control group. (3) Both Finasteride and TU could inhibit epididymal sperm count and reproductive function compared with the control, but the effect was less significant in Group FT than in Group F.</p><p><b>CONCLUSION</b>High dosages of 5alpha-reductase inhibitor, Finasteride, can suppress male reproductive function, but the inhibiting effect could be counteracted by administration of 5alpha-reductase inhibitor along with TU.</p>