Sanguinarine, a major alkaloid from Zanthoxylum nitidum (Roxb.) DC., inhibits urease of Helicobacter pylori and jack bean: Susceptibility and mechanism.

ETHNOPHARMACOLOGICAL RELEVANCE: Zanthoxylum nitidum (Roxb.) DC. (Z. nitidum) is a traditional Chinese medicine and mainly adopted to treat gastric ulcer, gastritis and stomach cancer. Sanguinarine (SNG), a natural alkaloid isolated from Z. nitidum, possesses significant anti-Helicobacter pylori and gastric protection effects. However, the underlying mechanism is sparsely elucidated. AIM OF THIS STUDY: The present study aims to explore the inhibition effect, kinetics and potential mechanism of SNG against H. pylori urease (HPU) and jack bean urease (JBU). MATERIALS AND METHODS: The improved spectrophotometric berthelot method was applied to estimate the inhibitory effect of SNG against HPU and JBU. The Lineweaver-Burk plots were adopted for investigating the inhibitory pattern in enzymatic kinetics. Sulfydryl-containing compounds and competitive active-site Ni2+ binding depressors were used for mechanism research. RESULTS: SNG remarkably suppressed the activities of HPU and JBU in concentration-and time-dependent mode with IC50 of 0.48 ± 0.14 mM and 0.11 ± 0.02 mM, respectively, in comparison with urease retardant acetohydroxamic acid (0.06 ± 0.01 mM for HPU and 0.03 ± 0.00 mM for JBU, respectively). Kinetic analysis demonstrated that the inhibition of SNG against HPU and JBU were separately characterized by slow-binding, mixed-type and slow-binding, non-competitive type. Addition of sulfydryl-containing reagents (dithiothreitol, glutathione and L-cysteine) and competitive Ni2+ binding restrainers (boric acid and sodium fluoride) significantly abrogated the urease inhibitory effect of SNG, suggesting the significant role of the thiols and Ni2+ for the urease inhibition by SNG. By contrast, interaction with thiol groups possibly contributed to the repression of SNG on JBU. Furthermore, the urease suppression was proved to be partially reversible since the SNG-blocked enzyme could be partly reactivated by glutathione. CONCLUSION: SNG could observably inhibit H. pylori urease targeting the thiols and Ni2+, which indicated that SNG was a new urease suppressant with great promise. The present research also provided scientific evidence for the application of SNG and Z. nitidum treating H. pylori-associated gastrointestinal diseases.

Natural-Derived Polysaccharides From Plants, Mushrooms, and Seaweeds for the Treatment of Inflammatory Bowel Disease.

Inflammatory bowel disease (IBD) is a chronic inflammatory disease impairing the gastrointestinal tract, and its incidence and prevalence have been increasing over time worldwide. IBD greatly reduces peoples' quality of life and results in several life-threatening complications, including polyp, toxic colonic dilatation, intestinal perforation, gastrointestinal bleeding, and cancerization. The current therapies for IBD mainly include drugs for noncritical patients and operation for critical patients. However, continuous use of these drugs causes serious side effects and increased drug resistance, and the demand of effective and affordable drugs with minimal side effects for IBD sufferers is urgent. Natural-derived polysaccharides are becoming a research hotspot for their therapeutic effects on IBD. This study focuses on the research progress of various natural polysaccharides from plants, seaweeds, and mushrooms for the treatment of IBD during recent 20 years. Regulation of oxidative stress, inflammatory status, gut microbiota, and immune system and protection of the intestinal epithelial barrier function are the underlying mechanisms for the natural-derived polysaccharides to treat IBD. The excellent efficacy and safety of polysaccharides make them promising candidates for IBD therapy.

[Joint effects of nano-selenium and nano-cerium on the male reproductive function of mice exposed to microwave radiation].

OBJECTIVE: To study effect of nano-selenium and nano-cerium(nano cerium oxide) on the spermatogenic ability of mice irradiated by 1800 MHz microwave radiation(MR). METHODS: Forty-two ICR mice were randomly divided into groups: blank control group, solvent control group, microwave radiation model group, low, medium and high dose groups of nano-selenium+nano-cerium. In joint effects groups of nano-selenium and nano-cerium, the nano-selenium solution(60, 120 and 240 µg/kg) and the nano-cerium oxide solution(15, 30, 60 µg/kg) were administered to the stomach at 7:30 in the morning and 18:30 in the evening, respectively. The blank control group was orally administered with an equal volume of distilled water, and the solvent control group and the MR group were orally administered with an equal volume of carboxymethylcellulose sodium solution. During the second week of gastric administration, the mice were exposed to microwave radiation(1800 MHz) for 2 h every day(specific absorption ratio: 0. 2986 W/kg). After MR treatment, the daily sperm production of testis, sperm motility and sperm deformity rate in epididymis were measured, and the testicular marker enzymes [G6 PDH(6-phosphatedehydrogenase), ACP(acid phosphatase), LDH(lactate dehydrogenase)], antioxidant indexes [CAT(catalase), MDA(malondialdehyde) and T-AOC(total antioxidant capacity)] in testicular tissue were analyzed. RESULTS: Compared with the solvent control group, MR led to the decrease of sperm motility and the increase of sperm deformity rate, decreased the enzymes activities of G6 PDH, ACP and CAT, increased LDH activity and MDA content, and decreased the T-AOC level in testicular tissue, and the differences were statistically significant(P<0. 05). Compared with the MR group, the joint action of nano-selenium and nano-cerium with medium dose increased the daily sperm production of testis((18. 98±1. 27) ×10~6/g) vs. (15. 53±1. 24) ×10~6/g), decreased the sperm deformity rate(11. 74%±0. 91% vs. 16. 84%±2. 05%), and the joint action of nano-selenium and nano-cerium with medium and high dose increased the sperm motility in epididymis(61. 98%±6. 33%, 54. 17±4. 38 vs. 45. 16%±5. 01%), and the differences were statistically significant(P<0. 05). Compared with the MR group, the joint action of nano-selenium and nano-cerium with low and medium dose increased the activity of ACP(11. 07±0. 98, 14. 85±1. 39 vs. 8. 72±0. 91 nmol/(min·mg prot), P<0. 05). The joint action of nano-selenium and nano-cerium with medium and high dose increased the activity of G6 PDH(24. 12±2. 06, 21. 36±3. 65 vs. 15. 11±1. 73 nmol/(min·mg prot), P<0. 05) and decreased the activity of LDH(15. 52±1. 17, 13. 51±1. 68 vs. 22. 46±2. 01 nmol/(min·mg prot), P<0. 05). The joint action of nano-selenium and nano-cerium with medium dose increased the activity of CAT(17. 92±2. 03 vs. 11. 69±0. 87 nmol/(min·mg prot), P<0. 05) and decreased the content of MDA(5. 17 ±0. 62 vs. 9. 03 ±0. 63 nmol/mg prot, P<0. 05). The joint action of nano-selenium and nano-cerium with low, medium and high dose increased the level of T-AOC(22. 06±1. 54, 29. 36±2. 39, 21. 01±2. 47 vs. 12. 88±1. 82 U/mg prot, P<0. 05). CONCLUSION: The joint addition of nano-selenium and nano-cerium can improve the reproductive function of male mice exposed to MR, and can effectively alleviate the changes of mouse testicular marker enzyme activity and the decline of antioxidant capacity caused by MR.

From Ancient Medicine to Targeted Nanocarrier: A Sparganii Rhizoma-Derived Nanoparticle for Diagnostic Imaging and Endocrine Therapy in Cancer.

The traditional Chinese medicine Sparganii Rhizoma has a long history in the treatment of gynecological diseases. In our previous work, we found that an extract of Sparganii Rhizoma had antitumor activity, attributed to the aluminum-rich polysaccharide, "SpaTA", which we isolated. SpaTA can selectively regulate the estrogen receptor, but its mechanism of antitumor activity is poorly understood. In the present study, we found that SpaTA naturally exists as a nanoparticle with a regular physical morphology. SpaTA induced apoptosis in human breast cancer cells mainly through interaction with estrogen receptors, ERα and GPR30, followed by activation of the PI3K/Akt and MEK/ERK pathways. Notably, cells also adjusted their cytoskeletal plasticity in response to SpaTA, which inhibited cell motility by suppressing focal adhesion and cytoskeleton reorganization via FAK. On the basis of these antitumor effects, we further modified SpaTA by conjugating it with the near-infrared dye, ICG, and loading the particles with the TGFß inhibitor, LY2157299, to form the tumor-targeting nanomedicine, "SpaTAX". The application of SpaTAX to breast cancer models enables a dual use regimen: a single dose for fluorescence imaging of the tumor site, where SpaTAX accumulates due to the enhanced permeability and retention effect, and a multidose for antitumor treatment through estrogen receptor- and TGFß-related signaling pathways. The synergetic roles of estrogen receptors and TGFß pathways are responsible for SpaTAX-induced reinforced suppression on tumor growth. Finally, we assessed the biosafety of the formulation and found that SpaTAX is highly tolerable and may therefore be considered safe for future clinical theranostic application. Altogether, our results demonstrated a superior tumor targeting ability of SpaTA both in diagnostic imaging and endocrine therapy and also proved SpaTA as a promising nanocarrier with a high therapeutic capacity and a favorable modification potential.

The impact of Helicobacter pylori infection, eradication therapy and probiotic supplementation on gut microenvironment homeostasis: An open-label, randomized clinical trial.

BACKGROUND: Helicobacter pylori (H. pylori) infection is associated with remodeling of gastric microbiota. However, comprehensive analyses of the impact of H. pylori infection, eradication therapy and probiotic supplementation on gut microbiota are still lacking. We aimed to provide evidence for clinical decision making. METHODS: Seventy H. pylori-positive and 35 H. pylori-negative patients (group C) were enrolled. H. pylori-positive patients were randomly assigned to group A (14-day bismuth-containing quadruple therapy) and group B (quadruple therapy supplemented with Clostridium butyricum). Stool samples of group A and B were collected on day 0, 14 and 56 while stool samples of group C were collected on day 0. Gut microbiota was investigated by 16S rRNA sequencing. FINDINGS: The Sobs index (richness estimator) was significantly higher in H. pylori-positive samples than H. pylori-negative samples (p < .05). Several metabolic pathways were more abundant in H. pylori-positive communities while some disease-associated pathways had higher potential in H. pylori-negative community through KEGG pathway analysis. Abundances of most butyrate-producing bacteria significantly decreased, while several detrimental bacteria increased after eradication therapy. Probiotic supplementation was associated with improved gastrointestinal symptoms as well as increased Bacteroidetes:Firmicutes ratio. INTERPRETATION: While H. pylori infection may not be necessarily detrimental in all patients, eradication of H. pylori was associated with widespread changes in gut microbial ecology and structure. Probiotic supplementation could relieve more gastrointestinal symptoms by inducing alterations in gut microbiota and host immune responses. As such, the decision to eradicate H. pylori should be based on comprehensive analysis of individual patients.

Advances and prospects in biogenic substances against plant virus: A review.

Plant virus diseases, known as 'plant cancer', are the second largest plant diseases after plant fungal diseases, which have caused great damage to agricultural industry. Since now, the most direct and effective method for controlling viruses is chemotherapeutics, except for screening of anti-disease species. As the occurrence and harm of plant diseases intensify, production and consumption of pesticides have increased year by year, and greatly contributed to the fertility of agriculture, but also brought a series of problems, such as the increase of drug resistance of plant pathogens and the excessive pesticide residues. In recent years, biopesticide, as characterized by environmentally safe due to low residual, safe to non-target organism due to better specificity and not as susceptible to produce drug resistance due to diverse work ways, has gained more attention than ever before and exhibited great development potential. Now much progress has been made about researches on new biogenic anti-plant-virus substances. The types of active components include proteins, polysaccharides and small molecules (alkaloids, flavonoids, phenols, essential oils) from plants, proteins and polysaccharides from microorganisms, polysaccharides from algae and oligochitosan from animals. This study summarized the research advance of biogenic anti-plant-virus substances in recent years and put forward their further development in the future.

[Study of introperitoneal hyperthermic perfusion chemotherapy combined with systemic neoadjuvent chemotherapy in treatment of gastric cancer patients with peritoneal carcinomatosis].

OBJECTIVE: The aim of this study is to discuss the curative effect of introperitoneal hyperthermic perfusion chemotherapy(IHPC) combined with systemic neoadjuvant chemotherapy on the gastric cancer patients with peritoneal carcinomatosis. METHODS: Sixty-four patients with gastric cancer and peritoneal carcinomatosis who were hospitalized in the Department of Gastrointestinal Surgery of First Hospital of Jilin University from December 2006 to December 2013. After peritoneal carcinomatosis was confirmed during laparoscopic exploration, FOLFOX6 (oxaliplatin and calcium folinate and 5-Fu) was performed for systemic chemotherapy. One course was 14 days and a complete treatment includes four courses. At the same time, patients underwent peritoneal catheter insertion and received IHPC(5-Fu 1 500 mg/m(2) and Cisplatin 35 mg/m(2) were added into 0.9% NaCl solution 2 000 ml, the infusion velocity was 35-45 ml/min, infusion time was 45-60 minutes, the temperature was controlled to 41°C). A comprehensive evaluation was taken after the fourth course of treatment before operation. Further surgical therapy was performed according to the assessment result. RESULTS: Sixty-four patients received IHPC combined with systemic chemotherapy. Thirty-two patients(50.0%) had partial response, 18(28.1%) stable disease, and 14(21.9%) progressive disease after chemotherapy. No severe complications or death occurred during the neoadjuvant chemotherapy. Thirty-two patients(50.0%) received radical resection, 10(15.6%) palliative operation, and another 22 patients(37.4%) didn't comply with inclusion criteria of operation. Patients receiving operation had a median survival time of 678 days, which was significantly longer than patients without operation, with a median survival time of 251(χ(2)=23.34, P=0.02). CONCLUSIONS: IHPC combined with systemic chemotherapy is an effective therapeutic method for gastric cancer patients with peritoneal carcinomatosis in terms of reducing preoperative tumor load and achieving radical resection.

Integrating clinical indexes into four-diagnostic information contributes to the Traditional Chinese Medicine (TCM) syndrome diagnosis of chronic hepatitis B.

Traditional Chinese Medicine (TCM) treatment has been commonly used to treat Chronic Hepatitis B (CHB) in Asian countries based on TCM syndrome diagnosis, also called "ZHENG". The syndrome is identified through the four-diagnostic methods, with certain degree of subjectivity and ambiguity from individual doctors. Normally those CHB patients also receive series of parameters from modern clinical examination, while they are routinely believed to be unrelated with the TCM syndrome diagnosis. In this study, we investigated whether these biomedical indexes in modern medicine could be beneficial to TCM syndrome diagnostics in an integrative way. Based on 634 patient samples from health controls and three subtypes of CHB syndromes, a two-view based hierarchical classification model was tested for TCM syndromes prediction based on totally 222 parameters integrated from both TCM practice and modern clinical tests. The results indicated that the performance of syndrome classification based on a proper integration of TCM and modern clinical indexes was significantly higher than those based on one view of parameters only. Furthermore, those indexes correlated with CHB syndrome diagnosis were successfully identified for CM indexes and biochemical indexes respectively, where potential associations between them were hinted to the MAPK signaling pathway.

Towards a bioinformatics analysis of anti-Alzheimer's herbal medicines from a target network perspective.

With the growth of aging population all over the world, a rising incidence of Alzheimer's disease (AD) has been recently observed. In contrast to FDA-approved western drugs, herbal medicines, featured as abundant ingredients and multi-targeting, have been acknowledged with notable anti-AD effects although the mechanism of action (MOA) is unknown. Investigating the possible MOA for these herbs can not only refresh but also extend the current knowledge of AD pathogenesis. In this study, clinically tested anti-AD herbs, their ingredients as well as their corresponding target proteins were systematically reviewed together with applicable bioinformatics resources and methodologies. Based on above information and resources, we present a systematically target network analysis framework to explore the mechanism of anti-AD herb ingredients. Our results indicated that, in addition to the binding of those symptom-relieving targets as the FDA-approved drugs usually do, ingredients of anti-AD herbs also interact closely with a variety of successful therapeutic targets related to other diseases, such as inflammation, cancer and diabetes, suggesting the possible cross-talks between these complicated diseases. Furthermore, pathways of Ca(2+) equilibrium maintaining upstream of cell proliferation and inflammation were densely targeted by the anti-AD herbal ingredients with rigorous statistic evaluation. In addition to the holistic understanding of the pathogenesis of AD, the integrated network analysis on the MOA of herbal ingredients may also suggest new clues for the future disease modifying strategies.