Amide alkaloids and neolignans from Piper hongkongense and their inhibitory activities of PCSK9 expression.

Four undescribed amide alkaloids hongkongensines A-C and 1-(1-oxo-6-hydroxy-2E,4E-dodecadienyl)-piperidine, five known amide alkaloids, and three known neolignans were isolated from the aerial part of Piper hongkongense. The planar structures of these compounds were determined by detailed analyses of HR-ESI-MS and NMR data. The absolute configurations of hongkongensines A-C were elucidated by single-crystal X-ray diffraction analysis and ECD calculations. Moreover, the inhibitory activities of PCSK9 expression in vitro for all compounds were assessed by PCSK9 AlphaLISA screening. Kadsurenone (10) displayed a significant inhibitory activity at 5 µM with an inhibition rate of 51.98%, compared with 55.55% of berberine (BBR 5 µM).

Synthesis and in†vitro Anti-Inflammatory Activity of Novel Dendrobine Amide/Sulfonamide Derivatives.

A traditional Chinese medicine ingredient, dendrobine, has been demonstrated to have anti-inflammatory properties. However, due to its poor anti-inflammatory properties, its clinical use is limited. Consequently, we have designed and synthesized 32 new amide/sulfonamide dendrobine derivatives and screened their anti-inflammatory activities in vitro. Experiments showed that nitric oxide (NO) generation in lipopolysaccharide (LPS)-induced RAW264.7 cells was strongly reduced by derivative 14, with an IC50 of 2.96 µM. Western blot research revealed that 14 decreased the concentration-dependent expression of cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (INOS). Molecular docking was used to predict the binding of the inflammation-associated proteins COX-2 and INOS to compound 14.

Expanded Application of Piper nigrum: Guided Isolation of Alkaloids with Inhibitory Activities of AChE/BuChE and Aß Aggregation.

Piper nigrum is a popular crop that can be used as seasoning or as an additive but its active ingredients also have an effect on the nervous system. Nineteen new amide alkaloids (1a/1b, 2-5, 6a/6b, 7, 8a/8b, 9, 10a/10b, 11a-11b, 12-14) were isolated from P. nigrum, guided by inhibitory activity of AChE and LC-MS/MS based on GNPS. The configurations were determined by extensive spectral analysis, Bulkiness rule, and NMR calculations. The inhibitory activities of AChE/BuChE and Aß aggregation were tested, and the results showed compounds 2, 7, and 12 had significant inhibitory activities. These components were identified in the crude fraction and their relative quantities were tested, which suggested that compound 2 was the index component in the active site from P. nigrum.

Amide herbicides: Analysis of their environmental fate, combined plant-microorganism soil remediation scheme, and risk prevention and control strategies for sensitive populations.

In this study, we predicted the environmental fate of amide herbicides (AHs) using the EQC (EQuilibrium Criterion) model. We found that the soil phase is the main reservoir of AHs in the environment. Second, a toxicokinetic prediction indicated that butachlor have a low human health risk, while the alachlor, acetochlor, metolachlor, napropamide, and propanil are all uncertain. To address the environmental and human-health-related threats posed by AHs, 27 new proteins/enzymes that easily absorb, degrade, and mineralize AHs were designed. Compared with the target protein/enzyme, the comprehensive evaluation value of the new proteins/enzymes increased significantly: the absorption protein increased by 20.29-113.49%; the degradation enzyme increased by 151.26-425.22%; and the mineralization enzyme increased by 23.70-52.16%. Further experiments revealed that the remediating effect of 13 new proteins/enzymes could be significantly enhanced to facilitate their applicability under real environmental conditions. The hydrophobic interactions, van der Waals forces, and polar solvation are the key factors influencing plant-microorganism remediation. Finally, the simulations revealed that appropriate consumption of kiwifruit or simultaneous consumption of ginseng, carrot, and spinach, and avoiding the simultaneous consumption of maize and carrot/spinach are the most effective means reduce the risk of exhibiting AH-linked toxicity.

N-Acetyl cysteine amide and cerium oxide nanoparticles as a drug delivery for ischemic stroke treatment: Inflammation and oxidative stress crosstalk.

BACKGROUND: Inflammation and oxidative stress crosstalk is involved in the ischemic stroke(IS) pathogenesis and the new therapeutic options should be offered based on the targets that are critical in the golden hour of IS. YKL-40 and total antioxidant capacity(TAC), the inflammation and oxidative stress biomarkers, provide us with clues for proper intervention targets. N-acetyl cysteine amide (NACA), a lipophilic antioxidant, with a nanoparticle-based drug delivery system is permeable enough to penetrate blood-brain barrier (BBB) and was proposed as a new treatment option for IS. In this study, we evaluated the YKL-40 and TAC levels in the sera of IS patients to elucidate the best intervention target. A rat tissue model is used to assess the NACA efficiency. The microbiology tests performed to figure out the potential NACA and antibiotics interactions. MATERIAL AND METHODS: The YKL-40 and TAC were measured in the serum of IS patients by ELISA and FRAP methods, respectively. The serum samples were obtained 12 h after the patient's admission and meantime other laboratory findings and NIHSS-based prognosis were recorded. In the animal study, the brain cortex, liver, kidney, adipose, and the heart of healthy rats were dissected and then incubated in DMEM cell culture media containing 50 micrograms/milliliter of nanoparticles; the nanoparticles were titanium dioxide nanoparticles (TiO2 NPs), copper oxide nanoparticles (CuO NPs) and cerium dioxide nanoparticles (CeO2 NPs). Olive oil and human serum albumin solution were exposed to the nanoparticles with and without NACA. TAC was measured in the supernatant culture media. With similar concentrations and settings, we evaluated the NACA, nanoparticle, and antibiotics interactions on pseudomonas aeruginosa. RESULTS: There was a nonparametric correlation between YKL-40 levels and post stroke serum TAC levels. Nonsmokers had higher YKL-40 and TAC levels than smokers. A new calculated variable, urea*lymphocyte/age, predicts a poor prognosis with an acceptable AUC (0.708). Exposing to the nanoparticles, the liver, kidney, and brain had a significantly higher TAC than adipose and cardiac tissue. The NACA had an ameliorative effect against TiO2 NPs in the brain. This effectiveness of NACA was also observed against CuO NPs treatment. However, the CeO2 NPs exert a strong antioxidant property by reducing the TAC in the brain tissue but not the others. Albumin showed antioxidant properties by itself, but olive oil had an inert behavior. NACA had no interaction with the action of routine antibiotics. CONCLUSION: Oxidative stress but not inflammation is the best point for intervention in IS patients because YKL-40 has not a relationship with NIHSS score. The CeO2 NPs and NACA combination are eligible option to develop antioxidant-based drug for the treatment of IS. As a complementary finding, the urea*lymphocyte/age is proposed as a NIHSS-based prognosis biomarker.

Fluorinated and N-Acryloyl-Modified 3,5-Di[(E)-benzylidene]piperidin-4-one Curcuminoids for the Treatment of Pancreatic Carcinoma.

Pancreatic carcinoma is a cancer disease with high mortality. Thus, new and efficient treatments for this disease are badly needed. Curcumin has previously shown promising effects in pancreatic cancer patients; however, this natural compound suffers from inadequate efficacy and bioavailability, preventing its clinical approval. The synthetic curcuminoid EF24 was developed with activities superior to curcumin against various cancer types. In this study, a series of analogs of EF24 were investigated for anticancer effects on pancreatic carcinoma models. A distinct activity boost was achieved by straightforward N-acrylation of EF24 analogs, in particular, of compounds bearing 3-fluoro-4-methoxybenzylidene, 3,4-difluorobenzylidene, and 4-trifluoromethylbenzylidene moieties, while no improvement was seen for N-acryloyl-modified EF24. Apoptosis induction and suppression of phospho-STAT3 levels were determined, the latter corroborated by docking of active curcuminoids into STAT3. Hence, promising new clues for the development of efficient and superior curcuminoids as valuable treatment options for one of the most lethal cancer diseases were discovered in this study.

Three Undescribed Flavonoids and Amide from Abrus mollis Hance with Hepatoprotective Effects.

Through a phytochemical investigation of Abrus mollis Hance, a folk medicinal plant in China, we isolated and identified three undescribed compounds, including two flavonoids and one amides alkaloid, along with nine known from this plant. Their structures were elucidated by analyses of 1D, 2D NMR, HR-ESI-MS, ECD, and DP4+ analysis. Furthermore, we evaluated the hepatoprotective effects of all twelve compounds on D-GalN-induced Brl-3 A cells. According to the results, at a concentration of 25 µM, the cell survival rates were observed to be 71.92±0.34 %, 70.03±1.29 %, and 69.11±1.90 % for compound 2, 4, and 11, respectively. Further experimental studies showed that compound 2 (EC50 5.76±0.37 µM) showed more significant protective activity than the bicyclol.

Identification and characterization of phenolamides in tea (Camellia sinensis) flowers using ultra-high-performance liquid chromatography/Q-Exactive orbitrap mass spectrometry.

Phenolamides (PAs) are important secondary metabolites present in plants with multiple bioactivities. This study aims to comprehensively identify and characterize PAs in tea (Camellia sinensis) flowers using ultra-high-performance liquid chromatography/Q-Exactive orbitrap mass spectrometry based on a lab-developed in-silico accurate-mass database. The PAs found in tea flowers were conjugates of Z/E-hydroxycinnamic acids (p-coumaric, caffeic and ferulic acids) with polyamines (putrescine, spermidine and agmatine). The positional and Z/E isomers were distinguished through characteristic MS2 fragmentation rules and chromatographic retention behavior summarized from some synthetic PAs. 21 types of PAs consisting of over 80 isomers were identified, and the majority of them were found in tea flowers for the first time. Among 12 tea flower varieties studied, they all possessed tris-(p-coumaroyl)-spermidine with the highest relative content, and C. sinensis 'Huangjinya' had the highest total relative contents of PAs. This study shows the richness and structural diversity of PAs in tea flowers.

Gut microbiota-based metabolites of Xiaoyao Pills (a typical Traditional Chinese medicine) ameliorate depression by inhibiting fatty acid amide hydrolase levels in brain.

ETHNOPHARMACOLOGICAL RELEVANCE: Traditional Chinese medicines (TCMs) are often prepared in oral dosage forms, making TCMs interact with gut microbiota after oral administration, which could affect the therapeutic effect of TCM. Xiaoyao Pills (XYPs) are a commonly used TCM in China to treat depression. The biological underpinnings, however, are still in its infancy due to its complex chemical composition. AIM OF THE STUDY: The study aims to explore XYPs' underlying antidepressant mechanism from both in vivo and in vitro. MATERIALS AND METHODS: XYPs were composed of 8 herbs, including the root of Bupleurum chinense DC., the root of Angelica sinensis (Oliv.) Diels, the root of Paeonia lactiflora Pall., the sclerotia of Poria cocos (Schw.) Wolf, the rhizome of Glycyrrhiza uralensis Fisch., the leaves of Mentha haplocalyx Briq., the rhizome of Atractylis lancea var. chinensis (Bunge) Kitam., and the rhizome of Zingiber officinale Roscoe, in a ratio of 5:5:5:5:4:1:5:5. The chronic unpredictable mild stress (CUMS) rat models were established. After that, the sucrose preference test (SPT) was carried out to evaluate if the rats were depressed. After 28 days of treatment, the forced swimming test and SPT were carried out to evaluate the antidepressant efficacy of XYPs. The feces, brain and plasma were taken out for 16SrRNA gene sequencing analysis, untargeted metabolomics and gut microbiota transformation analysis. RESULTS: The results revealed multiple pathways affected by XYPs. Among them, the hydrolysis of fatty acids amide in brain decreased most significant via XYPs treatment. Moreover, the XYPs' metabolites which mainly derived from gut microbiota (benzoic acid, liquiritigenin, glycyrrhetinic acid and saikogenin D) were found in plasma and brain of CUMS rats and could inhibit the levels of FAAH in brain, which contributed to XYPs' antidepressant effect. CONCLUSIONS: The potential antidepressant mechanism of XYPs by untargeted metabolomics combined with gut microbiota-transformation analysis was revealed, which further support the theory of gut-brain axis and provide valuable evidence of the drug discovery.

Alternative pain management via endocannabinoids in the time of the opioid epidemic: Peripheral neuromodulation and pharmacological interventions.

The use of opioids in pain management is hampered by the emergence of analgesic tolerance, which leads to increased dosing and side effects, both of which have contributed to the opioid epidemic. One promising potential approach to limit opioid analgesic tolerance is activating the endocannabinoid system in the CNS, via activation of CB1 receptors in the descending pain inhibitory pathway. In this review, we first discuss preclinical and clinical evidence revealing the potential of pharmacological activation of CB1 receptors in modulating opioid tolerance, including activation by phytocannabinoids, synthetic CB1 receptor agonists, endocannabinoid degradation enzyme inhibitors, and recently discovered positive allosteric modulators of CB1 receptors. On the other hand, as non-pharmacological pain relief is advocated by the US-NIH to combat the opioid epidemic, we also discuss contributions of peripheral neuromodulation, involving the electrostimulation of peripheral nerves, in addressing chronic pain and opioid tolerance. The involvement of supraspinal endocannabinoid systems in peripheral neuromodulation-induced analgesia is also discussed. LINKED ARTICLES: This article is part of a themed issue on Advances in Opioid Pharmacology at the Time of the Opioid Epidemic. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v180.7/issuetoc.

Electroacupuncture relieves visceral hypersensitivity through modulation of the endogenous cannabinoid system.

BACKGROUND: Electroacupuncture (EA) can effectively relieve visceral hypersensitivity (VH). However, its mechanisms are still unclear. OBJECTIVE: To investigate the impact of EA on VH caused by ileitis, and whether EA relieves VH by modulating the endogenous cannabinoid system (ECS). METHODS: Thirty male native goats were randomly divided into a saline-treated control group (Saline, n = 9) and three 2,4,6-trinitro-benzenesulfonic acid (TNBS)-treated VH model groups that underwent injection of TNBS into the ileal wall to induce VH and remained untreated (TNBS, n = 9) or received six sessions of EA (for 30 min every 3 days) (TNBS + EA, n = 6) or sham acupuncture (TNBS + Sham, n = 6). The visceromotor response (VMR) to colorectal distention (CRD) was measured after each EA treatment. Three goats in the Saline/TNBS groups were euthanized after 7 days for histopathological examination; the remaining 24 (n = 6/group) underwent sampling of the ileal wall, T11 spinal cord and brain nuclei/areas related to visceral regulation and ascending pain modulation system on day 22. Expression of cannabinoid receptor 1 (CB1R), fatty acid amide hydrolase (FAAH) and monoacylglycerol lipase (MAGL) was detected by immunohistochemistry. RESULTS: VMR to CRD was greater in TNBS-treated goats than in saline-treated goats (p < 0.01) from day 7 to 22. After day 7, EA-treated goats showed a decreased (p < 0.05) VMR compared with untreated TNBS-exposed goats. TNBS treatment decreased CB1R and increased FAAH and MAGL expression in the ileum and related nuclei/areas; this was reversed by EA. CONCLUSION: EA ameliorates VH, probably by regulating the ECS in the intestine and nuclei/areas related to visceral regulation and descending pain modulation systems.

Selected plant triterpenoids and their amide derivatives in cancer treatment: A review.

Medicinal plants have been used to treat different diseases throughout the human history namely in traditional medicine. Most of the plants mentioned in this review article belong among them, including those that are widely spread in the nature, counted frequently to be food and nutrition plants and producing pharmacologically important secondary metabolites. Triterpenoids represent an important group of plant secondary metabolites displaying emerging pharmacological importance. This review article sheds light on four selected triterpenoids, oleanolic, ursolic, betulinic and platanic acid, and on their amide derivatives as important natural or semisynthetic agents in cancer treatment, and, in part, in pathogenic microbe treatment. A literature search was made in the Web of Science for the given key words covering the required area of secondary plant metabolites and their amide derivatives. The most recently published findings on the biological activity of the selected triterpenoids, and on the structures and biological activity of their relevant amide derivatives have been summarized therein. Mainly anti-cancer effects, and, in part, antimicrobial and other effects of the four selected triterpenoids and their amide derivatives have also been reviewed. A comparison of the effects of the parent plant products and those of their amide derivatives has been made.

Synthesis, biological evaluation and mechanism studies of C-3 substituted nitrogenous heterocyclic 23-Hydroxybetulinic acid derivatives as anticancer agents.

A series of novel nitrogenous heterocycle substituted 23-Hydroxybetulinic acid (23-HBA) derivatives with amide linkages at the C-3 position were designed, synthesized and evaluated for their antitumor activities. The biological screening results showed that most of the derivatives exhibited more potent antiproliferative activities than 23-HBA. In particular compound II-9 exhibited the most potent activities with IC50 values ranging from 1.96 µM to 6.20 µM against five cancer cell lines (B16, HepG2, A2780, MCF-7 and A549). The preliminary mechanism study showed that compound II-9 caused cell cycle arrest at G1 phase, induced cell apoptosis and depolarized mitochondria of B16 cells in a dose dependent manner. Moreover, western blot analysis indicated that compound II-9 down-regulated the expression of anti-apoptotic protein Bcl-2, up-regulated the expression of pro-apoptotic protein Bad, and activated cytochrome C and caspase 3 to cause cell apoptosis. In summary, II-9 may serve as a promising lead for the development of new natural product-based antitumor agents and deserve further investigation.

Metabolomics reveals that phenolamides are the main chemical components contributing to the anti-tyrosinase activity of bee pollen.

Bee pollen, which is known as a "full-nutrient food", has outstanding anti-tyrosinase activity. However, the chemical components contributing to this activity remain unknown. To comprehensively elucidate the chemical components of bee pollen inhibiting tyrosinase, we performed the anti-tyrosinase activity evaluation of bee pollen extract (BPE) of eight species, metabolomic analysis of chemical composition, multivariate statistical analysis and correlation analysis. The results revealed that the anti-tyrosinase activity of eight BPEs was significantly different (p < 0.05), with IC50 value ranging from 10.08 to 408.81 µg/mL. A total of 725 metabolites were detected from these BPEs, and 40 differential metabolites were identified, all of which were phenolamides. All these phenolamides were positively correlated with the anti-tyrosinase activity, among which 26 phenolamides (21 spermidine derivatives and five spermine derivatives) showed particularly high correlations (r > 0.7). This is the first report to reveal the main contributor to the anti-tyrosinase activity of bee pollen.

Novel Thymoquinone Nanoparticles Using Poly(ester amide) Based on L-Arginine-Targeting Pulmonary Drug Delivery.

Thymoquinone (TQ), the main active constituent of Nigella sativa, has demonstrated broad-spectrum antimicrobial, antioxidant, and anti-inflammatory effects, which suggest its potential use in secondary infections caused by COVID-19. However, clinical deployment has been hindered due to its limited aqueous solubility and poor bioavailability. Therefore, a targeted delivery system to the lungs using nanotechnology is needed to overcome limitations encountered with TQ. In this project, a novel TQ-loaded poly(ester amide) based on L-arginine nanoparticles was prepared using the interfacial polycondensation method for a dry powder inhaler targeting delivery of TQ to the lungs. The nanoparticles were characterized by FTIR and NMR to confirm the structure. Transmission electron microscopy and Zetasizer results confirmed the particle diameter of 52 nm. The high-dose formulation showed the entrapment efficiency and loading capacity values of TQ to be 99.77% and 35.56%, respectively. An XRD study proved that TQ did not change its crystallinity, which was further confirmed by the DSC study. Optimized nanoparticles were evaluated for their in vitro aerodynamic performance, which demonstrated an effective delivery of 22.7-23.7% of the nominal dose into the lower parts of the lungs. The high drug-targeting potential and efficiency demonstrates the significant role of the TQ nanoparticles for potential application in COVID-19 and other respiratory conditions.

Structurally diverse isoquinoline and amide alkaloids with dopamine D2 receptor antagonism from Corydalis bungeana.

Four new isoquinoline alkaloids including a benzophenanthridine alkaloid (1), a morphine derivative (2), a narceine-type alkaloid (3) and a simple isoquinoline alkaloid (4), a new amide alkaloid (5) and a new phthalic acid derivative (6), together with eleven known alkaloids (7-17) were obtained from the whole herbs extract of Corydalis bungeana Turcz. Their structures and absolute configurations were elucidated by extensive spectroscopic data analysis including HRESIMS, NMR and electronic circular dichroism (ECD) and ECD calculation. Compounds 1-17 were evaluated for dopamine D2 receptor activity in CHO-D2 cells. Among them, 16 showed the highest antagonistic activity on the D2 receptor with an IC50 value of 2.04 ± 0.01 µM. Compounds 14 and 15 exhibited moderate antagonism with IC50 values of 13.66 ± 2.28 and 31.72 ± 2.52 µM, respectively.

Chemical Profiles of Korean Bee Pollens and Their Catechol-O-methyltransferase Inhibitory Activities.

Bee pollen is an apicultural product collected by honeybees from flower stamens and is consumed to help maintain a healthy diet. In this study, the chemical profiles of 11 Korean bee pollens were investigated using molecular networking analysis. This analysis elucidated the presence of two major clusters, hydroxycinnamoyl acid amides (HCAAs, molecular network 1 (MN1)) and flavonoid glycosides (MN2), in the bee pollen samples. The inhibitory properties of the bee pollens and the isolated HCAAs toward human catechol-O-methyltransferase (COMT), a key neurotransmitter involved in Parkinson's disease and depression, were determined. N1,N5,N10-(E)-tricaffeoylspermidine ((E,E,E)-1) exhibited the highest activity of the four compounds isolated, with an IC50 value 16 µM, and inhibited COMT competitively. Quantitative analysis of HCAAs showed that the amounts of N1,N10-dicaffeoyl-N5-p-coumaroylspermidine (2) and N10-caffeoyl-N1,N5-di-p-coumaroylspermidine (3) contributed to the observed differences in the COMT inhibitory activities of Korean bee pollens. This study may lead to the prevention and treatment of Parkinson's disease and depression using bee pollens.

Bioactive fluorescent hybrid microparticles as a stand-alone osteogenic differentiation inducer.

Osteogenic differentiation of stem cells is one of the essential steps in bone regeneration. While supplementing exogenous factors using differentiation media is the established method to differentiate stem cells into osteoblasts on biomaterials, designing biomaterials that can act as a stand-alone differentiation inducer and promote bone regeneration is preferred for clinical translation. In this work, we report dexamethasone-loaded organic-inorganic hybrid microparticles synthesized from an intrinsically fluorescent poly (ester amide) and tertiary bioactive glass (PEA-BG) as a stand-alone osteogenic differentiation inducer. The mechanical properties data indicated that the compressive modulus of fluorescent hybrid microparticles could be modulated by its composition. The hybrid fluorescent microparticles supported the adhesion and proliferation of 10T1/2 â€‹cells in culture for up to seven days. Both pristine and dexamethasone-loaded PEA-BG microparticles were able to induce osteogenic differentiation of 10T1/2 â€‹cells in the absence of any media supplement, to a level even higher than standard osteogenic media, as evidenced by the expression of osteogenic markers on gene and protein levels and matrix mineralization. Taken together, the fluorescent PEA-BG hybrid microparticles have the potential to be used as a stand-alone biomaterial for osteogenic differentiation and bone regeneration.

The efficacy of adjuvant N acetyl cysteine for the eradication of H pylori infections: A systematic review and meta-analysis of randomized clinical trials.

BACKGROUND: Biofilm-producing bacteria are relatively resistant to antibiotics, as the penetration of antibiotics into the endopolysaccharide envelope is incomplete. N Acetyl cysteine (NAC) is known to destabilize the biofilms, as it cleaves the disulfide bonds of mucus glycoproteins, reducing the viscosity and thickness of mucus. This allows NAC to act synergistically with antibiotics for the eradication of H Pylori. The meta-analysis evaluates the evidence of the efficacy of adjuvant N acetyl cysteine (NAC) compared to standard therapies in the eradication of H. Pylori infections. METHODS: We searched randomized clinical trials in MEDLINE, Cochrane Central Register of Clinical Trials (CENTRAL), EBSCO, Database of Abstracts of Reviews of Effects (DARE), and Google Scholar. We included trials comparing standard treatment protocols plus adjuvant NAC and the same regimen without NAC. These studies included adults with a diagnosis of Helicobacter pylori infection. Our primary outcome was the successful eradication of H. Pylori. The results were pooled using a random-effects model, and data were analyzed using RevMan 5.0 software. Cochrane collaboration's tool was used to assess the risk of bias. Publication bias and other inconsistencies were assessed. Sensitivity analyses and grading of evidence were performed. FINDINGS: Eight studies, comprising 1167 patients, were included in the meta-analysis, the pooled outcomes of patients on adjuvant NAC+ standard eradication therapy noted an eradication rate of 76.1% (n=581) compared to the patients in standard eradication therapy with a rate of 72.18% (n=586), RR 1.17 [95% CI (0.99, 1.39); I2= 64%; p value=0.07]. Moderate to severe heterogeneity was noted. These pooled results show that adjuvant NAC plus standard treatment protocols are not superior to standard treatment protocols for H pylori eradication. Similar results were seen in the use of adjuvant NAC with 'currently used standard treatment protocols' (78.3% versus 76.3%, RR 1.08, [95% CI 0.94 to 1.25]; I2=55%; p=0.28; n= 829 patients], as well as in the treatment of naïve patients (79.8% versus 80.9%, RR 1.00[95% CI 0.87 to 1.15]; i2=27%; P=-0.98; n= 775 patients]. CONCLUSION: Adjuvant NAC plus standard treatment protocols are not superior to standard treatment protocols for H. pylori eradication. These findings are consistent with the use of adjuvant NAC with 'currently used standard treatment protocols' (clarithromycin-based triple therapies) and also with adjuvant NAC used in the treatment of naïve patients. We are moderately certain of these findings. Future studies could explore the use of NAC as a pretreatment before using the current standard therapies in the eradication of H. Pylori rather than NAC as adjuvant therapy. FUNDING: None.

Amide alkaloids characterization and neuroprotective properties of Piper nigrum L.: A comparative study with fruits, pericarp, stalks and leaves.

Piper nigrum L. is commonly used worldwide and its pericarp, stalks, leaves will be major wastes materials. 42 amide alkaloids were identified in black, white pepper and pericarp by UHPLC-LTQ-Orbitrap HRMS method, followed by 40 constituents in stalks and 36 constituents in leaves. 8 amide alkaloids were reported for the first time in P. nigrum. An ultra-high-performance supercritical fluid chromatography (UHPSFC)-MS method was firstly applied to simultaneously determine 9 characteristic constituents (piperine, piperlonguminine, piperanine, pipercallosine, dehydropipernonaline, pipernonatine, retrofractamide B, pellitorine and guineensine). The most abundant compound in each extract was piperine with a concentration from 0.10 to 12.37 mg/g of dry weight. The fruits, pericarp and leaves extracts could improve cell viability in 6-OHDA-induced SK-N-SH and SH-SY5Y cells. The results showed the characteristics of amide alkaloids of different parts of P. nigrum and evaluated their neuroprotective activities.