Frailty in hemodialysis patients: results of a screening program and multidisciplinary interventions.

Background: The number of frail patients of advanced age with end-stage kidney disease (ESKD) undergoing hemodialysis is increasing globally. Here we evaluated a frailty screening program of ESKD patients starting hemodialysis, and subsequent multidisciplinary interventions. Methods: This was a prospective observational study of ESKD patients in a hemodialysis program. Patients were evaluated for frailty (Fried frail phenotype) before and after a 12-month period. Patients followed standard clinical practice at our hospital, which included assessment and multidisciplinary interventions for nutritional (malnutrition-inflammation score, protein-energy wasting), physical [short physical performance battery (SPPB)] and psychological status. Results: A total of 167 patients (mean ± standard deviation age 67.8 ± 15.4 years) were screened for frailty, and 108 completed the program. At screening, 27.9% of the patients were frail, 40.0% pre-frail and 32.1% non-frail. Nutritional interventions (enrichment, oral nutritional supplements, intradialytic parenteral nutrition) resulted in stable nutritional status for most frail and pre-frail patients after 12 months. Patients following recommendations for intradialytic, home-based or combined physical exercise presented improved or stable in SPPB scores after 12 months, compared with those that did not follow recommendations, especially in the frail and pre-frail population (P = .025). A rate of 0.05 falls/patient/year was observed. More than 60% of frail patients presented high scores of sadness and anxiety. Conclusions: Frailty screening, together with coordinated interventions by nutritionists, physiotherapists, psychologists and nurses, preserved the health status of ESKD patients starting hemodialysis. Frailty assessment helped in advising patients on individual nutritional, physical or psychological needs.

TRPM8 indicates poor prognosis in colorectal cancer patients and its pharmacological targeting reduces tumour growth in mice by inhibiting Wnt/ß-catenin signalling.

BACKGROUND AND PURPOSE: Transient receptor potential melastatin type-8 (TRPM8) is a cold-sensitive cation channel protein belonging to the TRP superfamily of ion channels. Here, we reveal the molecular mechanism of TRPM8 and its clinical relevance in colorectal cancer (CRC). EXPERIMENTAL APPROACH: TRPM8 expression and its correlation with the survival rate of CRC patients was analysed. To identify the key pathways and genes related to TRPM8 high expression, Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses were conducted in CRC patients. TRPM8 functional role was assessed by using Trpm8-/- mice in models of sporadic and colitis-associated colon cancer. TRPM8 pharmacological targeting by WS12 was evaluated in murine models of CRC. KEY RESULTS: TRPM8 is overexpressed in colon primary tumours and in CD326+ tumour cell fraction. TRPM8 high expression was related to lower survival rate of CRC patients, Wnt-Frizzled signalling hyperactivation and adenomatous polyposis coli down-regulation. In sporadic and colitis-associated models of colon cancer, either absence or pharmacological desensitization of TRPM8 reduced tumour development via inhibition of the oncogenic Wnt/ß-catenin signalling. TRPM8 pharmacological blockade reduced tumour growth in CRC xenograft mice by reducing the transcription of Wnt signalling regulators and the activation of ß-catenin and its target oncogenes such as C-Myc and Cyclin D1. CONCLUSION AND IMPLICATIONS: Human data provide valuable insights to propose TRPM8 as a prognostic marker with a negative predictive value for CRC patient survival. Animal experiments demonstrate TRPM8 involvement in colon cancer pathophysiology and its potential as a drug target for CRC.

Prevalence of Protein-Energy Wasting in Dialysis Patients Using a Practical Online Tool to Compare with Other Nutritional Scores: Results of the Nutrendial Study.

This cross-sectional study aims to explore the prevalence of protein-energy wasting (PEW) in dialysis patients in Catalonia, Spain, using a new and practical online tool which enables rapid calculation and comparison with other nutritional scores. METHODS: A web tool (Nutrendial) was created to introduce different variables and automatically calculate PEW, Malnutrition inflammation Score (MIS) and Subjective Global Assessment (SGA) in 1389 patients (88% in haemodialysis (HD)), 12% in peritoneal dialysis (PD) from different regions of Catalonia. RESULTS: A prevalence of 23.3% (26% HD, 10.2% PD) of PEW was found, with a mean MIS score of 6 and SGA score of C in 7% of the patients. ROC analysis showed MIS as the best nutritional score to diagnose PEW (AUC 0.85). Albumin delivered lower diagnostic precision (AUC 0.77) and sensitivity (66%). A cut off point of 7 (86% sensitivity and 75% specificity) for MIS and 3.7 mg/dL for albumin were found to predict the appearance of PEW in this population. SGA B or C showed an 87% sensitivity and 55% specificity to diagnose PEW. Very low nutritional intervention (14%) was recorded with this tool in patients with PEW. CONCLUSIONS: This new online tool facilitated the calculation of PEW, enabling different professionals-including nephrologists, dieticians and nurses-to efficiently obtain insights into the nutritional status of the Catalonian dialysis population and implement the required nutritional interventions. MIS is the score with more sensitivity to diagnose PEW.

Patient Experience in Pancreas-Kidney Transplantation-A Methodological Approach Towards Innovation in an Established Program.

Simultaneous pancreas-kidney transplantation (SPKT) leads to increased survival and quality of life, and is an alternative treatment for insulin-dependent diabetes mellitus and end-stage kidney disease. Due to the particularities of this population (often with multiple comorbidities) and of the surgery (only performed in a few centers), a comprehensive analysis of patients' experience along the SPKT process is crucial to improve patient care and add value to this procedure. Therefore, we applied a systematic and iterative methodology with the participation of both patients and professional teams working together to explore and identify unmet needs and value-adding steps along the transplant patient journey at an established pancreas transplant program. Four main steps (to comprehend, to explore, to experiment and to assess) led to several interventions around three major areas: Administration and logistics, information and communication, and perceived quality of assistance. As a result, both displacements to the hospital for diagnostic purposes and the time delay involved in joining the patient waiting list for transplantation were reduced in parallel to the administrative procedures. In conclusion, the methodological implementation of key organizational changes has great impact on overall patient experience. Further quantitative analysis from the patient's perspective will consolidate our program and may add new prototype service design components.

Sphingosine-1-phosphate/TGF-ß axis drives epithelial mesenchymal transition in asthma-like disease.

BACKGROUND AND PURPOSE: Airway remodelling is a critical feature of chronic lung diseases. Epithelial-mesenchymal transition (EMT) represents an important source of myofibroblasts, contributing to airway remodelling. Here, we investigated the sphingosine-1-phosphate (S1P) role in EMT and its involvement in asthma-related airway dysfunction. EXPERIMENTAL APPROACH: A549 cells were used to assess the S1P effect on EMT and its interaction with TGF-ß signalling. To assess the S1P role in vivo and its impact on lung function, two experimental models of asthma were used by exposing BALB/c mice to subcutaneous administration of either S1P or ovalbumin (OVA). KEY RESULTS: Following incubation with TGF-ß or S1P, A549 acquire a fibroblast-like morphology associated with an increase of mesenchymal markers and down-regulation of the epithelial. These effects are reversed by treatment with the TGF-ß receptor antagonist LY2109761. Systemic administration of S1P to BALB/c mice induces asthma-like disease characterized by mucous cell metaplasia and increased levels of TGF-ß, IL-33 and FGF-2 within the lung. The bronchi harvested from S1P-treated mice display bronchial hyperresponsiveness associated with overexpression of the mesenchymal and fibrosis markers and reduction of the epithelial.The S1P-induced switch from the epithelial toward the mesenchymal pattern correlates to a significant increase of lung resistance and fibroblast activation. TGF-ß blockade, in S1P-treated mice, abrogates these effects. Finally, inhibition of sphingosine kinases by SK1-II in OVA-sensitized mice, abrogates EMT, pulmonary TGF-ß up-regulation, fibroblasts recruitment and airway hyperresponsiveness. CONCLUSION AND IMPLICATIONS: Targeting S1P/TGF-ß axis may hold promise as a feasible therapeutic target to control airway dysfunction in asthma.

N-Acylethanolamine acid amidase (NAAA) is dysregulated in colorectal cancer patients and its inhibition reduces experimental cancer growth.

BACKGROUND AND PURPOSE: N-Acylethanolamine acid amidase (NAAA) is a lysosomal enzyme accountable for the breakdown of N-acylethanolamines (NAEs) and its pharmacological inhibition has beneficial effects in inflammatory conditions. The knowledge of NAAA in cancer is fragmentary with an unclarified mechanism, whereas its contribution to colorectal cancer (CRC) is unknown to date. EXPERIMENTAL APPROACH: CRC xenograft and azoxymethane models were used to assess the in vivo effect of NAAA inhibition. Further, the tumour secretome was evaluated by an oncogenic array, CRC cell lines were used for in vitro studies, cell cycle was analysed by cytofluorimetry, NAAA was knocked down with siRNA, human biopsies were obtained from surgically resected CRC patients, gene expression was measured by RT-PCR and NAEs were measured by LC-MS. KEY RESULTS: The NAAA inhibitor AM9053 reduced CRC xenograft tumour growth and counteracted tumour development in the azoxymethane model. NAAA inhibition affected the composition of the tumour secretome inhibiting the expression of EGF family members. In CRC cells, AM9053 reduced proliferation with a mechanism mediated by PPAR-α and TRPV1. AM9053 induced cell cycle arrest in the S phase associated with cyclin A2/CDK2 down-regulation. NAAA knock-down mirrored the effects of NAAA inhibition with AM9053. NAAA expression was down-regulated in human CRC tissues, with a consequential augmentation of NAE levels and dysregulation of some of their targets. CONCLUSION AND IMPLICATIONS: Our results show novel data on the functional importance of NAAA in CRC progression and the mechanism involved. We propose that this enzyme is a valid drug target for the treatment of CRC growth and development.

Triterpenoids from Vitellaria paradoxa Stem Barks Reduce Nitrite Levels in LPS-Stimulated Macrophages.

Vitellaria paradoxa C. F. Gaertn is widely used in African traditional medicine as an anti-inflammatory remedy to treat rheumatism, gastric problems, diarrhea, and dysentery. The phytochemical investigation of the ethyl acetate extract of V. paradoxa stem bark collected in Burkina Faso led to the isolation of eight known and two triterpenes undescribed to date (7 and 10), in the free alcohol form or as acetyl and cinnamyl ester derivatives. The stereostructures of the new compounds were elucidated using HR-ESIMS and 1D and 2D NMR data. The isolated compounds were evaluated in vitro for their inhibitory effect on nitrite levels on murine macrophages J774 stimulated with the lipopolysaccharide (LPS). Among all the compounds tested, lupeol cinnamate (3) and betulinic acid (5) showed a beneficial effect in reducing nitrite levels produced after LPS stimulation.

Halting the Spread of Herpes Simplex Virus-1: The Discovery of an Effective Dual αvß6/αvß8 Integrin Ligand.

Over recent years, αvß6 and αvß8 Arg-Gly-Asp (RGD) integrins have risen to prominence as interchangeable co-receptors for the cellular entry of herpes simplex virus-1 (HSV-1). In fact, the employment of subtype-specific integrin-neutralizing antibodies or gene-silencing siRNAs has emerged as a valuable strategy for impairing HSV infectivity. Here, we shift the focus to a more affordable pharmaceutical approach based on small RGD-containing cyclic pentapeptides. Starting from our recently developed αvß6-preferential peptide [RGD-Chg-E]-CONH2 (1), a small library of N-methylated derivatives (2-6) was indeed synthesized in the attempt to increase its affinity toward αvß8. Among the novel compounds, [RGD-Chg-(NMe)E]-CONH2 (6) turned out to be a potent αvß6/αvß8 binder and a promising inhibitor of HSV entry through an integrin-dependent mechanism. Furthermore, the renewed selectivity profile of 6 was fully rationalized by a NMR/molecular modeling combined approach, providing novel valuable hints for the design of RGD integrin ligands with the desired specificity profile.

Palmitoylethanolamide Reduces Colon Cancer Cell Proliferation and Migration, Influences Tumor Cell Cycle and Exerts In Vivo Chemopreventive Effects.

Palmitoylethanolamide (PEA) is an endogenous fatty acid amide related to the endocannabinoid anandamide. PEA exerts intestinal anti-inflammatory effects, but knowledge of its role in colon carcinogenesis is still largely fragmentary. We deepened this aspect by studying the effects of PEA (ultramicronized PEA, um-PEA) on colon cancer cell proliferation, migration and cell cycle as well as its effects in a murine model of colon cancer. Results showed that um-PEA inhibited tumor cell proliferation via peroxisome proliferator-activated receptor α and G protein-coupled receptor 55, induced cell cycle arrest in the G2/M phase, possibly through cyclin B1/CDK1 upregulation, and induced DNA fragmentation. Furthermore, um-PEA reduced tumor cell migration by reducing MMP2 and TIMP1 expression. In vivo administration of um-PEA exerted beneficial effects in the azoxymethane model of colonic tumors, by reducing the number of preneoplastic lesions and tumors. Collectively, our findings provide novel proofs on the effects of um-PEA in colon carcinogenesis.

Ethnomedicinal uses, phytochemistry, and biological activities of plants of the genus Gynura.

ETHNOPHARMACOLOGICAL RELEVANCE: The genus Gynura (Compositae) includes around 46 species and is native to the tropical regions of Southeast Asia, Africa and Australia. Many species within this genus are used in ethnomedicine to treat various disorders including skin diseases, injuries, ulcers, wounds, burns, sores, scalds, as well as for the management of diabetes, hypertension, hyperlipidemia, constipation, rheumatism, bronchitis and inflammation. AIM OF THE REVIEW: This review is an attempt to provide scientific information regarding the ethnopharmacology, phytochemistry, pharmacological and toxicological profiles of Gynura species along with the nomenclature, distribution, taxonomy and botanical features of the genus. A critical analysis has been undertaken to understand the current and future pharmaceutical prospects of the genus. MATERIALS & METHODS: Several electronic databases, including Google scholar, PubMed, Web of Science, Scopus, ScienceDirect, SpringerLink, Semantic Scholar, MEDLINE and CNKI Scholar, were explored as information sources. The Plant List Index was used for taxonomical authentications. SciFinder and PubChem assisted in the verification of chemical structures. RESULTS: A large number of phytochemical analyses on Gynura have revealed the presence of around 342 phytoconstituents including pyrrolizidine alkaloids, phenolic compounds, chromanones, phenylpropanoid glycosides, flavonoids, flavonoid glycosides, steroids, steroidal glycosides, cerebrosides, carotenoids, triterpenes, mono- and sesquiterpenes, norisoprenoids, oligosaccharides, polysaccharides and proteins. Several in vitro and in vivo studies have demonstrated the pharmacological potential of Gynura species, including antidiabetic, anti-oxidant, anti-inflammatory, antimicrobial, antihypertensive and anticancer activities. Although the presence of pyrrolizidine alkaloids within a few species has been associated with possible hepatotoxicity, most of the common species have a good safety profile. CONCLUSIONS: The importance of the genus Gynura both as a prominent contributor in ethnomedicinal systems as well as a source of promising bioactive molecules is evident. Only about one fourth of Gynura species have been studied so far. This review aims to provide some scientific basis for future endeavors, including in-depth biological and chemical investigations into already studied species as well as other lesser known species of Gynura.

Topical Collection "Pharmacology of Medicinal Plants".

The use of remedies based on medicinal plants continues to expand rapidly around the world, with many people now resorting to this type of product for the treatment and prevention of several pathologies [...].

Efficacy of combined therapy with fish oil and phytocannabinoids in murine intestinal inflammation.

Fish oil (FO) and phytocannabinoids have received considerable attention for their intestinal anti-inflammatory effects. We investigated whether the combination of FO with cannabigerol (CBG) and cannabidiol (CBD) or a combination of all three treatments results in a more pronounced intestinal antiinflammatory action compared to the effects achieved separately. Colitis was induced in mice by 2,4-dinitrobenzenesulfonic acid (DNBS). CBD and CBG levels were detected and quantified by liquid chromatography coupled with time of flight mass spectrometry and ion trap mass spectrometry (LC-MS-IT-TOF). Endocannabinoids and related mediators were assessed by LC-MS. DNBS increased colon weight/colon length ratio, myeloperoxidase activity, interleukin-1ß, and intestinal permeability. CBG, but not CBD, given by oral gavage, ameliorated DNBS-induced colonic inflammation. FO pretreatment (at the inactive dose) increased the antiinflammatory action of CBG and rendered oral CBD effective while reducing endocannabinoid levels. Furthermore, the combination of FO, CBD, and a per se inactive dose of CBG resulted in intestinal anti-inflammatory effects. Finally, FO did not alter phytocannabinoid levels in the serum and in the colon. By highlighting the apparent additivity between phytocannabinoids and FO, our preclinical data support a novel strategy of combining these substances for the potential development of a treatment of inflammatory bowel disease.

Pharmacological insights on the antidepressant, anxiolytic and aphrodisiac potentials of Aglaonema hookerianum Schott.

ETHNOPHARMACOLOGICAL RELEVANCE: Aglaonema hookerianum Schott is an ethnomedicinally important plant used to treat a variety of diseases, including sexual and depression-like disorders. However, the scientific basis underlying the aforesaid properties have not been well justified. AIM OF THE STUDY: The present investigation aimed to investigate the anxiolytic, antidepressant and aphrodisiac potentials of methanol leaves extract of A. hookerianum (MEAH) in Swiss albino mice. MATERIALS & METHODS: Swiss albino mice (20-30 g) were orally administrated with MEAH at the doses ranging from 100 to 400 mg/kg, b.w. The elevated plus maze (EPM) and hole board test (HBT) were performed to determine the anxiolytic activity and the forced swimming test (FST) and tail suspension test (TST) were performed to determine the antidepressant activity of MEAH. Besides, the aphrodisiac activity of MEAH was conducted through the mounting behaviour and orientation behaviour analysis. Diazepam (1 mg/kg, b.w., i.p.) for EPM and HBT; fluoxetine HCl (20 mg/kg, b.w., p.o.) for FST and TST, and sildenafil (5 mg/kg, b.w., p.o.) for the mounting behaviour analysis and orientation behaviour analysis were used as reference drugs. RESULTS: The administration of the MEAH produced a strong (p < 0.001) dose-dependent anxiolytic effects in both HBT and EPM tests. Likewise, the extract revealed a significant (p < 0.001) reduction in the immobility time in both FST and TST as compared to the control group. Besides, the MEAH also found to possess marked aphrodisiac activity complying several facets such as an increase in the sexual performance at the highest dose (400 mg/kg, p.o.) as well as the orientation toward female mice (p < 0.001) at all tested doses. CONCLUSION: Taken together, MEAH can be recommended as a potent source of neuroprotective and a libido-boosting drug candidate for the management of neurological and sexual disorders.

Multimodal prehabilitation as strategy for reduction of postoperative complications after cardiac surgery: a randomised controlled trial protocol.

INTRODUCTION: Prehabilitation programmes that combine exercise training, nutritional support and emotional reinforcement (multimodal prehabilitation) have demonstrated efficacy reducing postoperative complications in the context of abdominal surgery. However, such programmes have seldom been studied in cardiac surgery, one of the surgeries associated with higher postoperative morbidity and mortality. This trial will assess the feasibility and efficacy in terms of reduction of postoperative complications and cost-effectiveness of a multimodal prehabilitation programme comparing to the standard of care in cardiac surgical patients. METHODS AND ANALYSIS: This is a single-centre, randomised, open-label, controlled trial with a 1:1 ratio. Consecutive 160 elective valve replacement and/or coronary revascularisation surgical patients will be randomised to either standard of care or 4-6 weeks of multimodal prehabilitation that will consist in (1) two times/week supervised endurance and strength exercise training sessions, (2) promotion of physical activity and healthy lifestyle, (3) respiratory physiotherapy, (4) nutrition counselling and supplementation if needed, and (5) weekly mindfulness sessions. Baseline, preoperative and 3-month postoperative data will be collected by an independent blinded evaluator. The primary outcome of this study will be the incidence of postoperative complications. ETHICS AND DISSEMINATION: This study has been approved by the Ethics Committee of Clinical investigation of Hospital Clinic de Barcelona (HCB/2017/0708). The results will be disseminated in a peer-reviewed journal. TRIAL REGISTRATION NUMBER: NCT03466606.

Pharmacological insights and prediction of lead bioactive isolates of Dita bark through experimental and computer-aided mechanism.

Dita bark (Alstonia scholaris (L.) R. Br.) is an ethnomedicine used for the management of various ailments. This study aimed to investigate the biological properties of methanol extract of A. scholaris bark (MEAS), through in vivo, in vitro and in silico approaches alongside its phytochemical profiling. Identification and nature of the bioactive secondary metabolites were studied by the established qualitative tests and GC-MS analysis. The antidepressant activity was determined by forced swimming test (FST) and tail suspension test (TST) in mice. The anti-inflammatory and thrombolytic effect was evaluated using inhibition of protein denaturation technique and clot lysis technique, respectively. Besides, computational studies of the isolated compounds and ADME/T analysis were performed by Schrödinger-Maestro (v11.1) software, and PASS prediction was conducted through PASS online tools. The GC-MS analysis revealed the presence of several secondary metabolites in MEAS. Treatment with MEAS revealed a significant reduction of immobility time in a dose-dependent manner in FST and TST. Besides, MEAS showed substantial anti-inflammatory effects at the higher dose (400 µg/mL) as well as revealed notable clot lysis effect as compared to control. In the case of computer-aided investigation, all compounds meet the condition of Lipinski's rule of five. PASS study also predicted for all compounds, and among these safe compound furazan-3-amine showed the most spontaneous binding energy for both antidepressant and thrombolytic activities, as well as 5-dimethylamino-6 azauracil, found promising for anti-inflammatory activity. Taken together, the investigation concludes that MEAS can be a potent source of antidepressant, anti-inflammatory, and thrombolytic agents.

Unveiling role of sphingosine-1-phosphate receptor 2 as a brake of epithelial stem cell proliferation and a tumor suppressor in colorectal cancer.

BACKGROUND: Sphingosine-1-phosphate receptor 2 (S1PR2) mediates pleiotropic functions encompassing cell proliferation, survival, and migration, which become collectively de-regulated in cancer. Information on whether S1PR2 participates in colorectal carcinogenesis/cancer is scanty, and we set out to fill the gap. METHODS: We screened expression changes of S1PR2 in human CRC and matched normal mucosa specimens [N = 76]. We compared CRC arising in inflammation-driven and genetically engineered models in wild-type (S1PR2+/+) and S1PR2 deficient (S1PR2-/-) mice. We reconstituted S1PR2 expression in RKO cells and assessed their growth in xenografts. Functionally, we mimicked the ablation of S1PR2 in normal mucosa by treating S1PR2+/+ organoids with JTE013 and characterized intestinal epithelial stem cells isolated from S1PR2-/-Lgr5-EGFP- mice. RESULTS: S1PR2 expression was lost in 33% of CRC; in 55%, it was significantly decreased, only 12% retaining expression comparable to normal mucosa. Both colitis-induced and genetic Apc+/min mouse models of CRC showed a higher incidence in size and number of carcinomas and/or high-grade adenomas, with increased cell proliferation in S1PR2-/- mice compared to S1PR2+/+ controls. Loss of S1PR2 impaired mucosal regeneration, ultimately promoting the expansion of intestinal stem cells. Whereas its overexpression attenuated cell cycle progression, it reduced the phosphorylation of AKT and augmented the levels of PTEN. CONCLUSIONS: In normal colonic crypts, S1PR2 gains expression along with intestinal epithelial cells differentiation, but not in intestinal stem cells, and contrasts intestinal tumorigenesis by promoting epithelial differentiation, preventing the expansion of stem cells and braking their malignant transformation. Targeting of S1PR2 may be of therapeutic benefit for CRC expressing high Lgr5.

Caesalpinia ferrea C. Mart. (Fabaceae) Phytochemistry, Ethnobotany, and Bioactivities: A Review.

Caesalpinia ferrea C. Mart., popularly known as "Jucá" or "Pau-ferro", belongs to the Fabaceae family, and is classified as a native and endemic species in Brazil. Numerous studies that portray its ethnobotany, chemical composition, and biological activities exist in the literature. The present study aimed to systematically review publications addressing the botanical aspects, uses in popular medicine, phytochemical composition, and bioactivities of C. ferrea. The searches focused on publications from 2015 to March 2020 using the Scopus, Periódicos Capes, PubMed, Google Scholar, and ScienceDirect databases. The leaves, fruits, seeds, and bark from C. ferrea are used in popular medicine to treat disorders affecting several systems, including the circulatory, immune, cardiovascular, digestive, respiratory, genitourinary, musculoskeletal, and conjunctive systems. The most commonly found chemical classes in phytochemical studies are flavonoids, polyphenols, terpenoids, tannins, saponins, steroids, and other phenolic compounds. The biological properties of the extracts and isolated compounds of C. ferrea most cited in the literature were antibacterial, antifungal, antioxidant, antiproliferative, anti-inflammatory, and healing potential. However, further studies are still needed to clarify a link between its traditional uses, the active compounds, and the reported pharmacological activities, as well as detailed research to determine the toxicological profile of C. ferrea.

Deciphering the Pharmacological Properties of Methanol Extract of Psychotria calocarpa Leaves by In Vivo, In Vitro and In Silico Approaches.

The present study explores the neuropharmacological, antinociceptive, antidiarrheal, antioxidant, thrombolytic and cytotoxic activity of methanol extract of Psychotria calocarpa leaves (MEPC). In anxiolytic activity testing of MEPC by elevated plus maze test, hole-board test and light-dark test, the extract exhibited a dose-dependent reduction of anxiety while the open field test observed a decreased locomotion. The administration of MEPC revealed a significant dose-dependent reduction of depressant behavior in forced swimming and tail suspension test. Additionally, the antinociceptive and antidiarrheal activity exposed a significant reduction of nociception and diarrheal behavior at the highest dose. In addition, a strong antioxidant activity was observed in DPPH-free radical-scavenging assay (IC50 = 461.05 µg/mL), total phenol content (118.31 ± 1.12 mg) and total flavonoid content (100.85 ± 0.97 mg). The significant clot-lysis activity was also observed with moderate toxicity (LC50 = 247.92 µg/mL) level in the lethality assay of brine shrimp. Moreover, in silico molecular docking study showed that the compound Psychotriasine could offer promising active site interactions for binding proteins. Furthermore, ADME/T and toxicological properties of the compound satisfied the Lipinski's rule of five and Veber rules for drug-like potential and toxicity level. Overall, MEPC had a potential neuropharmacological, antinociceptive, antidiarrheal and antioxidant activity that warranted further investigation.