Alkaloids from Piper longum Exhibit Anti-inflammatory Activity and Synergistic Effects with Chemotherapeutic Agents against Cervical Cancer Cells.

Piper longum L. is widely cultivated for food, medicine, and other purposes in tropical and subtropical regions. Sixteen compounds including nine new amide alkaloids were isolated from the roots of P. longum. The structures of these compounds were determined by spectroscopic data. All compounds showed better anti-inflammatory activities (IC50 = 1.90 ± 0.68-40.22 ± 0.45 µM) compared to indomethacin (IC50 = 52.88 ± 3.56 µM). Among the isolated compounds, five dimeric amide alkaloids exhibited synergistic effects with three chemotherapeutic drugs (paclitaxel, adriamycin, or vincristine) against cervical cancer cells. Moreover, these dimeric amide alkaloids also enhanced the efficacy of paclitaxel in paclitaxel-resistant cervical cancer cells. The combination treatment of one of these dimeric amide alkaloids and paclitaxel promoted cancer cell apoptosis, which is related to the Src/ERK/STAT3 signaling pathway.

The role of Chinese herbal medicine in the treatment of diabetic nephropathy by regulating endoplasmic reticulum stress.

Diabetic nephropathy (DN), a prevalent microvascular complication of diabetes mellitus, is the primary contributor to end-stage renal disease in developed countries. Existing clinical interventions for DN encompass lifestyle modifications, blood glucose regulation, blood pressure reduction, lipid management, and avoidance of nephrotoxic medications. Despite these measures, a significant number of patients progress to end-stage renal disease, underscoring the need for additional therapeutic strategies. The endoplasmic reticulum (ER) stress response, a cellular defense mechanism in eukaryotic cells, has been implicated in DN pathogenesis. Moderate ER stress can enhance cell survival, whereas severe or prolonged ER stress may trigger apoptosis. As such, the role of ER stress in DN presents a potential avenue for therapeutic modulation. Chinese herbal medicine, a staple in Chinese healthcare, has emerged as a promising intervention for DN. Existing research suggests that some herbal remedies may confer renoprotective benefits through the modulation of ER stress. This review explores the involvement of ER stress in the pathogenesis of DN and the advancements in Chinese herbal medicine for ER stress regulation, aiming to inspire new clinical strategies for the prevention and management of DN.

Ferroptosis: a new strategy for Chinese herbal medicine treatment of diabetic nephropathy.

Diabetic nephropathy (DN) is a serious microvascular complication of diabetes. It has become a leading cause of death in patients with diabetes and end-stage renal disease. Ferroptosis is a newly discovered pattern of programmed cell death. Its main manifestation is the excessive accumulation of intracellular iron ion-dependent lipid peroxides. Recent studies have shown that ferroptosis is an important driving factor in the onset and development of DN. Ferroptosis is closely associated with renal intrinsic cell (including renal tubular epithelial cells, podocytes, and mesangial cells) damage in diabetes. Chinese herbal medicine is widely used in the treatment of DN, with a long history and definite curative effect. Accumulating evidence suggests that Chinese herbal medicine can modulate ferroptosis in renal intrinsic cells and show great potential for improving DN. In this review, we outline the key regulators and pathways of ferroptosis in DN and summarize the herbs, mainly monomers and extracts, that target the inhibition of ferroptosis.

iMSEA: A Novel Metabolite Set Enrichment Analysis Strategy to Decipher Drug Interactions.

Drug combinations are commonly used to treat various diseases to achieve synergistic therapeutic effects or to alleviate drug resistance. Nevertheless, some drug combinations might lead to adverse effects, and thus, it is crucial to explore the mechanisms of drug interactions before clinical treatment. Generally, drug interactions have been studied using nonclinical pharmacokinetics, toxicology, and pharmacology. Here, we propose a complementary strategy based on metabolomics, which we call interaction metabolite set enrichment analysis, or iMSEA, to decipher drug interactions. First, a digraph-based heterogeneous network model was constructed to model the biological metabolic network based on the Kyoto Encyclopedia of Genes and Genomes (KEGG) database. Second, treatment-specific influences on all detected metabolites were calculated and propagated across the whole network model. Third, pathway activity was defined and enriched to quantify the influence of each treatment on the predefined functional metabolite sets, i.e., metabolic pathways. Finally, drug interactions were identified by comparing the pathway activity enriched by the drug combination treatments and the single drug treatments. A data set consisting of hepatocellular carcinoma (HCC) cells that were treated with oxaliplatin (OXA) and/or vitamin C (VC) was used to illustrate the effectiveness of the iMSEA strategy for evaluation of drug interactions. Performance evaluation using synthetic noise data was also performed to evaluate sensitivities and parameter settings for the iMSEA strategy. The iMSEA strategy highlighted synergistic effects of combined OXA and VC treatments including the alterations in the glycerophospholipid metabolism pathway and glycine, serine, and threonine metabolism pathway. This work provides an alternative method to reveal the mechanisms of drug combinations from the viewpoint of metabolomics.

The bioactive amide alkaloids from the stems of Piper nigrum.

Piper nigrum is an important aromatic plant, and its fruits (black and white pepper) are commonly used as food additives and spices. However, its stems were disposed as wastes. This research comprehensively investigated bioactive alkaloids of the stems, eight new dimeric amide alkaloids and eight known compounds were obtained. All obtained compounds showed excellent anti-inflammatory activity. Additionally, the dimeric amide alkaloids enhanced the anticancer effect of paclitaxel against cervical cancer cells. These results demonstrate that the stems of P. nigrum could be the sustainable source of bioactive alkaloids for development and utilization in the food and health fields.

The Role of AMPK Signaling in Ulcerative Colitis.

Ulcerative colitis (UC) is a chronic non-specific inflammatory bowel disease characterized by inflammation and ulcer formation of the intestinal mucosa. Due to its high recurrence rate, prolonged course, limited curative options, and significant impact on patients' quality of life, along with a notable potential for malignant transformation, UC is designated as a refractory global health challenge by the World Health Organization (WHO). The elucidation of the pathogenesis and therapeutic strategies for UC requires further in-depth investigation. AMP-activated protein kinase (AMPK) serves as a central regulator of cellular energy metabolic homeostasis. Emerging evidence indicates that interventions involving traditional Chinese medicine (TCM) components, as well as other pharmacological measures, exert beneficial effects on the intestinal mucosal inflammation and epithelial barrier dysfunction in UC by modulating AMPK signaling, thereby influencing biological processes such as cellular autophagy, apoptosis, inflammatory responses, macrophage polarization, and NLRP3 inflammasome-mediated pyroptosis. The role of AMPK in UC is of significant importance. This manuscript provides a comprehensive overview of the mechanisms through which AMPK is involved in UC, as well as a compilation of pharmacological agents capable of activating the AMPK signaling pathway within the context of UC. The primary objective is to facilitate a deeper comprehension of the pivotal role of AMPK in UC among researchers and clinical practitioners, thereby advancing the identification of novel therapeutic targets for interventions in UC.

Enhanced nitrogen use efficiency, growth and yield of wheat through soil urea hydrolysis inhibition by Vachellia nilotica extract.

Soil urease inhibition slows down the urea hydrolysis and prolongs nitrogen (N) stay in soil, resulting in an increased N uptake by plants. Apart from several chemical urease inhibitors, the urease inhibition potential of plant extracts is rarely reported. In our previous study, the soil urease inhibition by Vachellia nilotica leaf extract was reported; however, its role in relation to growth and yield of wheat (Triticum aestivum) under pot and field conditions remains unknown. The acetonic extracts of 10, 20, and 50 g Vachellia nilotica leaves were given code names viz. Vn.Fl-10, Vn.Fl-20 and Vn.Fl-50, respectively, and coated on 100 g of urea individually. The enhancements of growth (total number of tillers, number of productive tillers, number of spikelets per spike, number of grains per spike, and 1000-grains weight) and yield (biological yield, straw yield, and grain yield) parameters of wheat by Vn.Fl-20 and Vn.Fl-50 coated urea treatments were compared with uncoated urea in a pot experiment. The experiment indicated that the Vachellia nilotica extract coatings were effective at improving N persistence in soil, as reflected by increased grain and straw N concentrations as well as uptakes. The reproduction of the aforementioned results, at the half and full recommended dose of urea under field conditions, reconfirmed the effectiveness of Vachellia nillotica coatings. Moreover, the Vn.Fl-20 and Vn.Fl-50 coated urea, at the half as well as full recommended dose under field conditions, proved equally effective in terms of higher biological, straw, and grain yield, and grain N uptake. The increments in the total number of tillers, number of productive tillers, 1000-grain weight, biological yield, straw yield, grain yield, grain N concentration, grain N-, and straw N uptake along with nitrogen use efficiency (NUE) components, i.e. nitrogen partial factor productivity (NPFP), nitrogen agronomic efficiency (NAE), partial nitrogen balance (PNB), and nitrogen recovery efficiency (NRE) of wheat highlighted the superiority of Vn.Fl-20 coating over the hydroquinone (Hq) coating on urea at the full recommended dose under field conditions. Given the findings of this study, Vachellia nilotica leaf extract coating (Vn.Fl-20) can be used as a natural urease inhibitor to reduce urea hydrolysis and enhance wheat productivity.

Assessing the post-treatment therapeutic effect of tongxie in irritable bowel syndrome: A randomized controlled trial.

Diarrhea predominant irritable bowel syndrome (IBS) is a highly relapsing gastrointestinal disorder decreasing the quality of life. Existing studies indicated that the therapeutic effects maintained for a period of time after the treatments were discontinued (post-treatment therapeutic effects or PTTE). In this study, we aim to assess the PTTE of tongxie. We performed a multiple center, controlled, double blind study of patients with IBS randomized to tongxie (n = 120) or placebo (n = 120) for 4 weeks and followed up for 57 weeks. The primary outcomes were abdominal pains and stool consistency. The secondary outcomes were pain frequency and stool frequency. Tertiary outcomes were adverse effects and global overall symptom. The outcome data were collected at days 1, 2, 3, weeks 1 and 4 during the treatment and at days 1, 2, 3, until week 57 during the post-treatment. Significantly more patients receiving tongxie were clinical responders to the primary and secondary endpoints from day 1 until the end of the treatment. The positive effects of tongxie were maintained until 17-25 weeks after tongxie was discontinued. The relapse-free probabilities in the tongxie group were significantly higher than those in the placebo group (P < .001). Twenty-five weeks after the therapies were discontinued could be considered as IBS natural history. During this period, an average of 53.8-56.3% of patients (pool tongxie and placebo data together) had IBS symptoms (pain scale ≥ 3, stool consistency ≥ 5). In particular, at the end of this study (week 61), 145 (54.2%) patients had IBS symptoms. Our results provide clinical insights into efficient and cost-effective management of refractory IBS, and lend support to the IBS management that the selection of a therapy should consider both its effectiveness during treatment and its PTTE after the treatment.

Inhibition of BRUTUS Enhances Plant Tolerance to Zn Toxicity by Upregulating Pathways Related to Iron Nutrition.

The identification of the key genes regulating plant tolerance to Zn stress is important for enhancing the Zn phytoremediation of targeted plants. Here, we showed that the T-DNA insertion-induced inhibition of the BRUTUS (BTS) gene in the bts-1 mutant greatly improved Zn tolerance, as indicated by increased biomass production and reduced leaf chlorosis. The ProBTS::BTS-GFP complementation in the bts-1 mutant abolished the improvement of Zn tolerance. Unexpectedly, the bts-1 mutant had higher and comparable Zn concentrations in the roots and citrate effluxer shoots, respectively, compared to wild-type plants. As a result, the shoots and roots of bts-1 mutants had 53% and 193% more Zn accumulation than the wild-type plants, respectively. RNA-seq analyses revealed that the Fe nutrition-related genes were upregulated in bts-1 mutants, especially under Zn stress conditions. Therefore, the bts-1 mutants had a greater Fe concentration and a higher Fe/Zn ratio than the wild-type plants exposed to Zn toxicity. Further study showed that the differences in Zn tolerance between bts-1 and wild-type plants were minimized by eliminating Fe or supplementing excessive Fe in the growth medium. Taken together, the T-DNA insertion-induced inhibition of BTS improves plant Zn tolerance by optimizing Fe nutrition; thus, the knockdown of BTS may be a promising approach for improving Zn phytoremediation efficiency.

Flexible Tongue Electrode Array System for In Vivo Mapping of Electrical Signals of Taste Sensation.

Tongue is a unique organ that senses tastes, and the scientific puzzle about whether electricity can evoke taste sensations and how the sensations have been distributed on the tongue has not been solved. Investigations on tongue stimulation by electricity might benefit the developments of techniques for clinical neuromodulation, tissue activation, and a brain-tongue-machine interface. To solve the scientific puzzle of whether electrical stimulation induces taste-related sensations, a portable flexible tongue electrode array system (FTEAS) was developed, which can synchronously provide electrical stimulation and signal mapping at each zone of the tongue. Utilizing the FTEAS to perform tests on the rat tongue in vivo, specific electrical signals were observed to be evoked by chemical and electrical stimulations. The features and distributions of the electric signals evoked during the rat tongue tests were systematically studied and comprehensively analyzed. The results show that an appropriate electrical stimulation can induce multiple sensations simultaneously, while the distribution of each sensation was not significantly distinguished among different zones of the tongue, and at the same time, this taste-related electrical signal can be recorded by the FTEAS. This work establishes a promising platform to solve the scientific puzzle of how sensations are activated chemically and electrically on the tongue and may provide advanced noninvasive oral-electrotherapy and a brain-tongue-machine interface.

8-hydroxypinoresinol-4-O-ß-D-glucoside from Valeriana officinalis L. Is a Novel Kv1.5 Channel Blocker.

ETHNOPHARMACOLOGY RELEVANCE: In folkloric medicine of many cultures, one of the medical uses of Valeriana officinalis Linn is to treat heart-related disease. Recently, it was shown that the ethanol extracts from V. officinalis could effectively prevent auricular fibrillation, and 8-hydroxypinoresinol-4-O-ß-D-glucoside (HPG) from the extracts is one of the two active compounds showing antiarrhythmia activities. AIM OF THE STUDY: The human Kv1.5 channel (hKv1.5) has potential antiarrhythmia activities, and this study arms at investigating the current blocking effects of HPG on hKv1.5 channel. MATERIAL AND METHODS: HPG was obtained from V. officinalis extracts, and hKv1.5 channels were expressed in HEK 293 cells. HPG was perfused while recording the current through hKv1.5 channels. Patch-clamp recording techniques were used to study the effects of HPG at various concentrations (10 µM, 30 µM, and 50 µM) on hKv1.5 channels. RESULTS: The present study demonstrated that HPG inhibited hKv1.5 channel current in a concentration-dependent manner; the higher the concentration, the greater is the inhibition at each depolarization potential. During washout, the channels did not full recover indicating that the un-coupling between HPG and hKv1.5 channels is a slow process. CONCLUSION: HPG may be an effective and safe active ingredient for AF having translational potential.

Six new anthraquinone glycosides from Lasianthus acuminatissimus Merr.

Six new anthraquinones named lasianthuoside F (1), G (2), H (3), I (4), J (5), K (6) were isolated from an acetone extract of the root of Lasianthus acuminatissimus. Their structures were elucidated by physical and chemical evidence and spectral analysis.

Compound sophorae decoction enhances intestinal barrier function of dextran sodium sulfate induced colitis via regulating notch signaling pathway in mice.

BACKGROUND: Compound sophorae decoction (CSD), a Chinese Herbal decoction, is frequently clinically prescribed for patients suffered from ulcerative colitis (UC) characterized by bloody diarrhea. Yet, the underlying mechanism about how this formulae works is remain elusive. METHODS: In the present study, the experimental colitis in C57BL/6 J mice was induced by oral administration of standard diets containing 3% dextran sodium sulfate (DSS), and CSD was given orally for treatment at the same time. The clinical symptoms including stool and body weight were recorded each day, and colon length and its histopathological changes were observed. Apoptosis of colonic epithelium was studied by detecting protein expression of cleaved caspase-3, and cell proliferation by Ki-67 immunohistochemistry. Tight junction complex like ZO-1 and occludin were also determined by transmission electron microscope and immunofluorescence. The concentration of FITC-dextran 4000 was measured to evaluate intestinal barrier permeability and possible signaling pathway was investigated. Mucin2 (MUC2) and notch pathway were tested through western blot. The M1/M2 ratio in spleen and mesenteric lymph nodes were detected by flow cytometry. And the mRNA levels of iNOS and Arg1 were examined by qRT-PCR. RESULTS: CSD could significantly alleviate the clinical manifestations and pathological damage. Body weight loss and DAI score of mice with colitis were improved and shortening of colon was inhibited. The administration of CSD was able to reduce apoptotic epithelial cells and facilitate epithelial cell regeneration. Increased intestinal permeability was reduced in DSS-induced colitis mice. In addition, CSD treatment obviously up-regulated the expression of ZO-1 and occludin and the secretion of MUC2, regulated notch signaling, and decreased the ratio of M1/M2. CONCLUSIONS: These data together suggest that CSD can effectively mitigate intestinal inflammation, promote phenotypic change in macrophage phenotype and enhance colonic mucosal barrier function by, at least in part, regulating notch signaling in mice affected by DSS-induced colitis.

Rhizoma Bletillae polysaccharide elicits hemostatic effects in platelet-rich plasma by activating adenosine diphosphate receptor signaling pathway.

Rhizoma Bletillae, the tubes of Bletilla striata, has been traditionally used in China as a hemostatic agent. In preliminary studies, the major active fraction responsible for its hemostatic effect have been confirmed to be Rhizoma Bletillae polysaccharide (RBp), but the hemostatic mechanism of action of RBp is still unknown.The main aim of this study was to clarify its mechanism of hemostatic effect. RBp was prepared by 80 % ethanol precipitation of the water extract of Rhizoma Bletillae followed by the Sevag method to remove proteins. The average molecular weight (Mw) of the crude RBp maintained at a range of 30.06-200 KDa. The hemostatic effects of RBp were evaluated by testing its effect on the platelet aggregation of rat platelet-rich plasma (PRP). PRP was dealt with different concentrations of RBp and platelet aggregation was measured by the turbidimetric method. The hemostatic mechanism of RBp was investigated by examining its effect on platelet shape, platelet secretion, and activation of related receptors (P2Y1, P2Y12 and TXA2) by electron microscopy and the turbidimetric method. RBp significantly enhanced the platelet aggregations at concentrations of 50-200 mg/L in a concentration-dependent manner. The inhibitory rate of platelet aggregation was significantly increased by apyrase and Ro31-8220 in a concentration-dependent manner, while RBp-induced platelet aggregation was completely inhibited by P2Y1, P2Y12 and the PKC receptor antagonists. However, the aggregation was not sensitive to TXA2. RBp, the active ingredients of Rhizoma Bletillae responsible for its hemostatic effect, could significantly accelerate the platelet aggregation and shape change. The hemostatic mechanism may involve activation of the P2Y1, P2Y12, and PKC receptors in the adenosine diphosphate (ADP) receptor signaling pathway.

The Chinese medicinal herb decoction QRZSLXF enhances anti-inflammatory effect in TNBS-induced colitis via balancing Th17/Tregs differentiation.

ETHNOPHARMACOLOGICAL RELEVANCE: Inflammatory bowel disease (IBD) is one of the most common chronic inflammatory illnesses of the gastrointestinal tract due to the imbalance of immune homeostasis of T helper cells and/or regulatory T cells (Tregs). The Traditional Chinese medicine herb has been clinically proven for use in the treatment of IBD but its possible mechanism remains unknown. The study aims to assess the effect of Chinese medicinal herb decoction QRZSLXF (Qing Re Zao Shi Liang Xue receipt) for the treatment of TNBS-induced experimental colitis in mice and explore its relevant mechanism involved in Th17 and Tregs. MATERIALS AND METHODS: Mice colitis was induced by 50% 2,4,6-Trinitrobenzenesulfonic Acid (TNBS) ethanol solution weekly manner. These established model mice were divided into model control (0.8% NaCl treatment), FICZ, naphthoflavone (NaFTV), dexamethasone (DXM), and QRZSLXF (QrLx) groups. The colonoscopy, H&E staining, and immune staining were used to analyze the disease severity, inflammatory condition and Th17 or Treg related factors expression. High-performance liquid chromatography-mass spectrometry (HPLC/MS) was used to assess the content of FICZ in the colon tissues. Western blot and ELISA were used to examine the expression of Th17 or Treg related factors protein levels. Flow cytometry analysis was performed to assess the number and ratio of Th17/Tregs in splenocytes, and mesenteric lymph node lymphocytes (MLNCs), and lamina propria mononuclear cells (LPMCs). RESULTS: NaFTV, DXM and QrLx groups intestinal inflammation scores were significantly lower than that in colitis model control and FICZ groups, while the IL-6, STAT3, and RORγt expression levels were significantly lower than those in the model control and FICZ groups. Mass spectrometry results showed FICZ that in both DXM and QrLx groups was lower than control model and FICZ groups. Flow cytometry results showed that DXM, NaFTV and QrLx could significantly reduce Th17 proportion and increase Treg proportion in splenocytes, MLNCs, and LPMCs. CONCLUSIONS: NaFTV and QrLx treatment could decrease symptoms and inflammatory colitis, by decreasing of FICZ concentration and AhR signaling in colon, resulting in reducing the expression of IL-6, STAT3, and RORγt, whereas increasing the expression of FOXP3, consequently reducing the proportion of Th17 cells and increasing the proportion of Treg cells, respectively.

Nutrient distribution and structure affect the behavior and speciation of arsenic in coastal waters: A case study in southwestern coast of the Laizhou Bay, China.

The effects of nutrient distribution and structure on the behavior and speciation of dissolved inorganic arsenic (DIAs) in coastal waters were analyzed based on the data of 48 surface water samples collected in the southwestern coast of Laizhou Bay and its adjacent rivers (SWLZB). The concentration of DIAs in the SWLZB ranged from 0.016 to 0.099 µmol l-1 and generally decreased from west to south. The inshore waters exhibited higher DIAs level than the open ocean. The As5+/As3+ ratio was significantly positively correlated with the concentration of TDN, NO3-N, PO4-P, DSi, Chl-a and DO. The concentration of DIAs was strongly correlated with the concentration of PO4-P and DSi, suggesting that adsorption/desorption was an important process for regulating the total DIAs concentration. The results indicated that the distribution of nutrients might well be an important environmental factor affecting the speciation and behavior of DIAs in surface water of the SWLZB.

Are personalized tongxie formula based on diagnostic analyses more effective in reducing IBS symptoms?-A randomized controlled trial.

OBJECTIVES: To examine the efficacy and safety ofpersonalized tongxie formulas; to decrease type II errors to minimum. METHODS: Patients were randomized (1:1:1) into three groups given tongxie, placebo, or pinaverium 3 times daily for 4 weeks. Patients in the tongxie group were treated with personalized formulas based on TCM differential diagnosis, i.e., basic type of IBS, IBS due to liver depression and qi stagnation, excess heat in the liver, deficient spleen function, deficient kidney function, and others (groups 1-6). Primary endpoints were significantly greater reductions in abdominal pain and Bristol stool score. Secondary endpoints were reductions in pain and stool frequencies and abdominal discomfort and its frequency. RESULTS: There were significantly more patients whose stool consistencies were improved than pains were relieved in the entire population (p < 0.001), but there was no significantly difference in subpopulation group 3 (p > 0.05). There were significantly more patients whose stool frequencies were reduced than pain frequencies were reduced in the entire population (p < 0.001), but there were no significantly difference in the subpopulation Groups 1, 3, 4, and 6 (p > 0.05). Multiple active ingredients and their mechanisms of actions to relieve IBS symptoms were identified. CONCLUSION: The outcomes in subpopulations may be different from those of the entire population, indicating that personalized formulas are important to achieve optimal outcomes; the active ingredients and innovative mechanisms identified in this study can be the candidates for developing new IBS drugs, and used to manage IBS, respectively. TRIAL REGISTRATION: NCT01641224 (www.ClinicalTrials.gov).

Tongxie Formula Reduces Symptoms of Irritable Bowel Syndrome.

BACKGROUND & AIMS: Irritable bowel syndrome (IBS) is the most common chronic gastrointestinal disorder, yet few drugs are effective in reducing symptoms. Approximately 50% of patients with IBS attempt herbal therapy at least once. We performed a randomized controlled trial to compare the efficacy of the herb formulation tongxie vs placebo or pinaverium (an antispasmodic agent) in reducing symptoms of IBS. METHODS: We performed a trial of 1044 adult patients with IBS (based on Rome III criteria) at 5 hospitals in China, from August 2012 through January 2015. Subjects were randomly assigned (1:1:1) to groups given tongxie (a combination of A macrocephalae, P lactiflora, C reticulata, S divaricata, C pilosula, C wenyujin, C medica, and P cocos, along with other herbs, based on patient features), placebo, or pinaverium (50 mg tablets) 3 times daily for 4 weeks. Primary end points were significantly greater reductions in abdominal pain and Bristol stool score (before vs after the 4-week study period) in patients given tongxie compared with patients given placebo or pinaverium. Secondary end points were reductions in pain and stool frequencies and abdominal discomfort and its frequency. RESULTS: Subjects given tongxie had significant reductions, before vs after the study period, in all 6 symptoms assessed, compared to patients given placebo (P < .001). A significantly higher proportion of patients given tongxie had increased stool consistency (75.6%) than patients given pinaverium (50.6%), and a significantly higher proportion of patients given tongxie had fewer daily stools (72.7%) than subjects given pinaverium (58.3%) (P < .001 for both). However, significantly higher proportions of patients given pinaverium had reduced pain (63.5%) and pain frequency (69.5%) than patients given tongxie (51.4% and 58.6%, respectively; P < .005 for both). CONCLUSIONS: In a randomized controlled trial of patients with IBS in China, we found 4 weeks of tongxie to produce significantly greater reduction in symptoms than placebo, and greater increases in stool consistency and reductions in stool frequency, than patients given pinaverium. Tongxie can therefore be considered an effective alternative therapy for patients with IBS who do not respond well to conventional therapies. Clinicaltrials.gov no: NCT01641224.

N-3 polyunsaturated fatty acids attenuates triglyceride and inflammatory factors level in hfat-1 transgenic pigs.

BACKGROUND: The consumption of n-3 polyunsaturated fatty acids (PUFAs) is important to human health, especially in cases of cardiovascular disease. Although beneficial effects of n-3 PUFAs have been observed in a number of studies, the mechanisms involved in these effects have yet to be discovered. METHODS: We generated hfat-1 transgenic pigs with traditional somatic cell nuclear transfer (SCNT) technology. The fatty acid composition in ear tissue of pigs were detected with gas chromatography. The cholesterol, triglycerides (TAG) and inflammation mediators in circulation were investigated. RESULTS: The hfat-1 transgenic pigs were developed which accumulate high levels of n-3 PUFAs than wild-types pigs. Gas chromatography results demonstrated that the total n-3 PUFAs in the ear tissues of the transgenic founders were 2-fold higher than the wild-type pigs. A lipid analysis demonstrated that the levels of TAG in the transgenic pigs were decreased significantly. The basal levels of the inflammation mediators tumor necrosis factor-α (TNF-α), monocyte chemoattractant protein-1 (MCP-1) and interleukin-6 (IL-6) in transgenic pigs were inhibited markedly compared with the wild-type pigs. CONCLUSIONS: These results suggest that n-3 PUFAs accumulation in vivo may have beneficial effects on vascular and hfat-1 transgenic pigs may be a useful tool for investigating the involved mechanisms.