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Previous research has shown that resveratrol can increase cerebral blood flow (CBF) in the absence of improved cognitive performance in healthy, young human subjects during the performance of cognitively demanding tasks. This lack of cognitive effects may be due to low bioavailability and, in turn, reduced bioefficacy of resveratrol in vivo. Piperine can alter polyphenol pharmacokinetics, but previous studies have not investigated whether this affects the efficacy of the target compound. Therefore, the objective of the present study was to ascertain whether co-supplementation of piperine with resveratrol affects the bioavailability and efficacy of resveratrol with regard to cognition and CBF. The present study utilised a randomised, double-blind, placebo-controlled, within-subjects design, where twenty-three adults were given placebo, trans-resveratrol (250 mg) and trans-resveratrol with 20 mg piperine on separate days at least a week apart. After a 40 min rest/absorption period, the participants performed a selection of cognitive tasks and CBF was assessed throughout the period, in the frontal cortex, using near-IR spectroscopy. The presence of resveratrol and its conjugates in the plasma was confirmed by liquid chromatography–MS analysis carried out following the administration of the same doses in a separate cohort (n 6). The results indicated that when co-supplemented, piperine and resveratrol significantly augmented CBF during task performance in comparison with placebo and resveratrol alone. Cognitive function, mood and blood pressure were not affected. The plasma concentrations of resveratrol and its metabolites were not significantly different between the treatments, which indicates that co-supplementation of piperine with resveratrol enhances the bioefficacy of resveratrol with regard to CBF effects, but not cognitive performance, and does this without altering bioavailability.

In this trial involving smokers who called the New Zealand national quitline, cytisine (a partial agonist of the nicotinic acetylcholine receptor) was superior to nicotine-replacement therapy in helping smokers quit. Nausea and sleep disorders were more frequent with cytisine. Cytisine is a plant-based alkaloid found in members of the Leguminosae family. 1 , 2 Like varenicline, cytisine is a partial agonist of nicotinic acetylcholine receptors (nAChRs), with an affinity for the α4β2 receptor subtype, 3 and a half-life of 4.8 hours. 4 Cytisine is a generic agent currently manufactured by Sopharma as Tabex and by Aflofarm Pharma as Desmoxan. It has been available both with and without prescription for smoking cessation since the 1960s, largely in Eastern Europe. 5 Four systematic reviews report cytisine to be superior to placebo for short-term and long-term abstinence. 6 – 9 When taken at the recommended dosage (1.5 to 9 . . .

•Dyslipidemia is a leading component of metabolic syndrome (MS).•Curcuminoids have been shown to regulate lipid metabolism and serum lipid concentrations.•Patients with MS were supplemented with a bioavailable curcuminoid formula (1000mg/day) for eight weeks.•Adjunctive therapy with curcuminoids reduced serum levels of LDL-C, non-HDL-C and Lp(a).•Curcuminoids can be used as a safe supplement in patients with MS. Dyslipidemia is an established feature of metabolic syndrome (MS) that is associated with an increased risk of atherosclerotic cardiovascular disease. Curcuminoids are natural products with anti-atherosclerotic and lipid-modifying effects but their efficacy in patients with MS has not yet been tested. To investigate the effects of bioavailability-enhanced curcuminoids, as adjunctive to standard of care, on serum lipid concentrations in patients with MS. Patients diagnosed with MS according to the NCEP-ATPIII criteria who were receiving standard of care were assigned to either curcuminoids (C3 complex®; 1000mg/day; n=50) or placebo (n=50; matched with drug capsules in shape and color) for 8 weeks. In order to improve the oral bioavailability, curcuminoids were co-administered with piperine (bioperine®) in a ratio of 100:1. Serum concentrations of total cholesterol, low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), triglycerides, small dense LDL (sdLDL), lipoprotein(a) [Lp(a)], and non-HDL-C were determined at baseline and at the end of 8-week treatment period. Curcuminoids were more effective than placebo in reducing serum LDL-C, non-HDL-C, total cholesterol, triglycerides and Lp(a), and elevating HDL-C concentrations. However, changes in serum sdLDL levels were found to be comparable between the study groups. The effects of curcuminoids on triglycerides, non-HDL-C, total cholesterol and Lp(a) remained significant after adjustment for baseline values of lipids and body mass index. Curcuminoids–piperine combination is an efficacious adjunctive therapy in patients with MS and can modify serum lipid concentrations beyond what is achieved with standard of care.

Pain remains a key therapeutic area with intensive efforts directed toward finding effective and safer analgesics in light of the ongoing opioid crisis. Amongst the neurotransmitter systems involved in pain perception and modulation, the mu-opioid receptor (MOR), a G protein-coupled receptor, represents one of the most important targets for achieving effective pain relief. Most clinically used opioid analgesics are agonists to the MOR, but they can also cause severe side effects. Medicinal plants represent important sources of new drug candidates, with morphine and its semisynthetic analogues as well-known examples as analgesic drugs. In this study, combining in silico (pharmacophore-based virtual screening and docking) and pharmacological (in vitro binding and functional assays, and behavioral tests) approaches, we report on the discovery of two naturally occurring plant alkaloids, corydine and corydaline, as new MOR agonists that produce antinociceptive effects in mice after subcutaneous administration via a MOR-dependent mechanism. Furthermore, corydine and corydaline were identified as G protein-biased agonists to the MOR without inducing β-arrestin2 recruitment upon receptor activation. Thus, these new scaffolds represent valuable starting points for future chemical optimization towards the development of novel opioid analgesics, which may exhibit improved therapeutic profiles.

Background Sepsis, an organ dysfunction caused by deregulated host response to infection, is a major health problem worldwide. Sepsis is associated with high rates of mortality, especially in critically ill patients. Curcumin may improve sepsis through its anti-inflammatory and antioxidant effects. This study aimed to investigate the effects of curcumin-piperine administration in critically ill septic patients. Method This double-blind randomized controlled trial (RCT) conducted on 66 patients with sepsis hospitalized in the intensive care unit (ICU). Patients were randomized to either the intervention group receiving two tablets of curcumin-piperine (each containing 500 mg curcuminoids and 5 mg piperine) ( n  = 33), or the placebo group receiving two matched tablets of placebo ( n  = 33) daily for 7 consecutive days along with enteral feeding. Clinical, laboratory, and biochemical indices were evaluated before and after the intervention. Statistical analyses were performed based on an intention-to-treat method. Result Mortality was observed in 10 patients in the curcumin-piperine group, and 12 patients in the control group. Curcumin-piperine significantly reduced bilirubin-total ( P  = 0.02), bilirubin-direct ( P  = 0.02), pH ( P  < 0.001), C-reactive protein ( P  = 0.04), erythrocyte sedimentation rate ( P  < 0.001), and platelet count ( P  = 0.01) compared with the placebo. A significantly lower reduction was found in red blood cell ( P  = 0.003), hemoglobin ( P  = 0.001), and hematocrit ( P  = 0.002) levels in the intervention vs. placebo group. In addition, mean corpuscular hemoglobin ( P  < 0.001) and mean corpuscular hemoglobin concentration ( P  = 0.001) were significantly higher in the intervention vs. placebo group. Conclusion Curcumin–piperine supplementation over a short period had beneficial effects on some inflammatory and laboratory indices in critically ill patients with sepsis. Trial registration IRCT20150613022681N4; available on: https://en.irct.ir/trial/52661 . Registration date: 2021-01-02, 1399/10/13.

Cryptolepine (1,5-methyl-10 H -indolo[3,2- b ]quinoline), an indoloquinoline alkaloid, found in the roots of Cryptolepis sanguinolenta (Lindl.) Schltr (family: Periplocaceae), is associated with the suppression of cancer and protozoal infections. Cryptolepine also exhibits anti-bacterial, anti-fungal, anti-hyperglycemic, antidiabetic, anti-inflammatory, anti-hypotensive, antipyretic, and antimuscarinic properties. This review of the latest research data can be exploited to create a basis for the discovery of new cryptolepine-based drugs and their analogues in the near future. PubMed, Scopus, and Google Scholar databases were searched to select and collect data from the existing literature on cryptolepine and their pharmacological properties. Several in vitro studies have demonstrated the potential of cryptolepine A as an anticancer and antimalarial molecule, which is achieved through inhibiting DNA synthesis and topoisomerase II. This review summarizes the recent developments of cryptolepine pharmacological properties and functional mechanisms, providing information for future research on this natural product.

This study aimed to evaluate the clinical application of different myopia correction methods in the prevention and control of myopia in adolescents. A total of 145 myopic adolescents aged 8 to 15 years were included, and their eyes were divided into four groups based on the treatment modality: wearing Defocus Incorporated Multiple Segments (DIMS) spectacle lenses alone (Group A), orthokeratology (OK) lenses alone (Group B), DIMS spectacle lenses combined with racemic anisodamine eye drops (Group C), and OK lenses combined with racemic anisodamine eye drops (Group D). The primary outcomes, including axial length and refractive error (expressed as spherical equivalent refraction, SER), were measured at baseline and at the 12-month follow-up. The clinical effects of each group were compared. The results showed significant differences in myopia progression across the groups, with Group D showing the least axial elongation. OK lenses were more effective than DIMS spectacle lenses in controlling myopia progression, and the combination of racemic anisodamine eye drops further enhanced the correction effect. This study provides important clinical evidence for myopia control interventions in adolescents.

Background Septic shock is characterized by an uncontrolled inflammatory response and microcirculatory dysfunction. There is currently no specific agent for treating septic shock. Anisodamine is an agent extracted from traditional Chinese medicine with potent anti-inflammatory effects. However, its clinical effectiveness remains largely unknown. Methods In a multicentre, open-label trial, we randomly assigned adults with septic shock to receive either usual care or anisodamine (0.1–0.5 mg per kilogram of body weight per hour), with the anisodamine doses adjusted by clinicians in accordance with the patients’ shock status. The primary end point was death on hospital discharge. The secondary end points were ventilator-free days at 28 days, vasopressor-free days at 28 days, serum lactate and sequential organ failure assessment (SOFA) score from days 0 to 6. The differences in the primary and secondary outcomes were compared between the treatment and usual care groups with the χ 2 test, Student’s t test or rank-sum test, as appropriate. The false discovery rate was controlled for multiple testing. Results Of the 469 patients screened, 355 were assigned to receive the trial drug and were included in the analyses—181 patients received anisodamine, and 174 were in the usual care group. We found no difference between the usual care and anisodamine groups in hospital mortality (36% vs. 30%; p  = 0.348), or ventilator-free days (median [Q1, Q3], 24.4 [5.9, 28] vs. 26.0 [8.5, 28]; p  = 0.411). The serum lactate levels were significantly lower in the treated group than in the usual care group after day 3. Patients in the treated group were less likely to receive vasopressors than those in the usual care group (OR [95% CI] 0.84 [0.50, 0.93] for day 5 and 0.66 [0.37, 0.95] for day 6). Conclusions There is no evidence that anisodamine can reduce hospital mortality among critically ill adults with septic shock treated in the intensive care unit. Trial registration ClinicalTrials.gov ( NCT02442440 ; Registered on 13 April 2015).

Postoperative nausea and vomiting (PONV) frequently occur in patients undergoing endoscopic retrograde cholangiopancreatography (ERCP) under general anesthesia. Glycopyrronium bromide, an anticholinergic medication, is believed to not only relieve gastrointestinal spasms but also effectively prevent PONV. To compare the incidence of nausea and vomiting and the effect of relieving spasm between patients administered glycopyrronium bromide and those given anisodamine hydrobromide following endoscopic retrograde cholangiopancreatography (ERCP). This is a monocentric prospective study. Patients eligible for ERCP were randomly assigned to two groups. One group received 0.2 mg glycopyrronium bromide (Group G) intravenously, while the other group received 10 mg anisodamine hydrobromide (Group A) intramuscularly for anesthesia induction. The study assessed duodenal motility during ERCP and the incidence of PONV within 24 hours. The study included 130 patients. Nausea and vomiting within 24 hours post-surgery occurred in nine patients (13.8%) in Group G and 19 patients (29.2%) in Group A, with statistical significance (relative risk (RR), 0.47; 95% confidence interval (CI) [0.02-0.29];  = 0.033). Vomiting specifically was observed in three patients (4.6%) in Group G and 12 patients (18.5%) in Group A, showing statistical significance (RR 0.25; 95% CI [0.03-0.25];  = 0.028). There was no significant difference in duodenal peristalsis between the groups (Group G: 10.9 ± 3.1 times/min; Group A: 11.6 ± 3.1 times/min;  = 0.174). For patients undergoing ERCP under general anesthesia, a subcutaneous injection of 0.2 mg glycopyrronium bromide significantly reduces PONV and provides similar anti-spasmodic effects to 10 mg intramuscular anisodamine hydrobromide.

Background Oropharyngeal dysphagia (OD) is a major gastrointestinal motility disorder that causes severe nutritional and respiratory complications in elderly and neurological patients. In an earlier study, we found that stimulation of pharyngeal sensory neurons by capsaicinoids acting on transient receptor potential vanilloid 1 (TRPV1) improved the swallow response of dysphagic patients. The aim of this study was to explore the effect of piperine, a dual TRPV1/TRPA1 agonist, on the swallow response of dysphagic patients. Methods A videofluoroscopic study was performed to assess the signs of impaired safety and efficacy of swallow and the swallow response of 40 dysphagic patients while swallowing one series of nectar control boluses and two series of nectar boluses supplemented with piperine. Patients were randomized into two groups: one group received 150 μM piperine and the other group received 1 mM. Results Piperine improved the safety of swallow by: (a) reducing the prevalence of unsafe swallows by −34.48 % ( P  = 0.004) at 150 μM and −57.19 % ( P  < 0.001) at 1 mM, and the severity score of the penetration-aspiration scale from 3.25 ± 0.51 to 1.85 ± 0.27 ( P  = 0.003, 1 mM); and (b) shortening the time to laryngeal vestibule closure from 0.366 ± 0.024 to 0.270 ± 0.022 s with 150 μM piperine ( P  < 0.001) and from 0.380 ± 0.032 to 0.306 ± 0.028 s with 1 mM piperine ( P  < 0.05). Conclusions Supplementing the alimentary bolus with piperine speeds swallow response and strongly improves safety of swallow in patients with OD, with a maximal therapeutic effect at 1 mM. Our results suggest that activation of TRPV1/A1 in oropharyngeal sensory neurons is a very promising neurostimulation strategy for dysphagic patients.