Total phenolic content, antioxidant and cytotoxic activity of cocoa (Theobroma cacao L.) polyphenols extracts on cancer cell lines

Introduction: Cancer chemopreventive agents from natural sources have been actively investigated over the years to seek prevention against cancer. In this study, cocoa polyphenols extract (CPE) was examined to explore its antioxidant and cytotoxicity activities. Methods: CPE was analysed for total phenolic content (TPC) and antioxidant activity (DPPH radical scavenging activity and FRAP ferric-reducing antioxidant power assays). In vitro cytotoxicity effect of CPE against HepG2, HT-29, HeLa, MCF-7, MDA-MB-231 and WRL-68 cell lines after 48 h exposure was measured by MTT assay. Results: The study showed that CPE had higher total phenolic content (13560.0±420.1 mg GAE/100g dry weight of sample) than vitamin E (p<0.05). CPE exhibited strong antioxidant activity comparable with ascorbic acid in both DPPH (IC50 = 14.73±1.47 μg/ml) and FRAP (2130.33±2.33 μM of FE/1 mg of dry weight of sample). The cytotoxicity study showed that CPE exhibited the highest cytotoxicity effect against MCF-7 with lowest IC50 value (3.00±0.29 mg/ml) compared to other cancer cell lines after 48 h treatment (p<0.05). Conclusion: Our results indicate that CPE demonstrated high total phenolic content, free radical scavenging activity, ferric reducing ability and cytotoxicity activity towards HepG2, HT-29, HeLa, A549, MDA-MB- 231 and MCF-7 cancer cell lines. Further isolation of bioactive constituents from CPE should be done to characterise its potential chemopreventive activity as well as to elucidate the mechanism of cancer cell death induced by CPE

Effect of Dietary Fiber Supplementation on Metabolic Endotoxemia: A Protocol for Systematic Review and Meta-Analysis of Randomized Clinical Trials

Introduction: Metabolic endotoxemia (ME) is the main cause of sub-clinical chronic inflammation, which subsequently triggers the onset of several chronic diseases. However, recent reports have indicated that dietary fiber (DF) contributes significantly to ameliorating ME and inflammation. This protocol aims to provide an outline of all procedures in synthesizing the available data on the effect of DF against ME. Methods: Following the PRISMA 2020 guidelines for preparing protocols, this protocol was registered in the International Prospective Registry of Systematic Reviews (PROSPERO) with registration number (CRD42023417833). In this review, we specifically focused on the inclusion of clinical trials that met the following criteria: they were published or available as preprints, employed random, quasi-random, or cross-over designs, and were exclusively documented in the English language. Clinical medical subject headings (MeSH) as search terms were used on prominent databases such as MEDLINE, COCHRANE library, PubMed, World Health Organization International Clinical Trials Registry Platforms, and US National Institutes of Health Ongoing Trials Register Clinicaltrials.gov. Results and discussion: This protocol will guide the exploration of articles that report changes in ME biomarkers in subjects supplemented with DF. The findings of this protocol will ensure a comprehensive evaluation of available evidence, provide a quantitative summary, identify patterns and trends, enhance statistical power, and address heterogeneity, which collectively will clarify the optimal types, doses, and duration of DF interventions for managing ME and low-grade inflammation. Ethics and dissemination: The quantitative data of clinical trials will be collected, and a meta-analysis will be performed using RevMan V.5.3 software. Therefore, no ethical approval is required

Melastoma malabathricum (L.) Smith Ethnomedicinal Uses, Chemical Constituents, and Pharmacological Properties: A Review

Melastoma malabathricum L. (Melastomataceae) is one of the 22 species found in the Southeast Asian region, including Malaysia. Considered as native to tropical and temperate Asia and the Pacific Islands, this commonly found small shrub has gained herbal status in the Malay folklore belief as well as the Indian, Chinese, and Indonesian folk medicines. Ethnopharmacologically, the leaves, shoots, barks, seeds, and roots of M. malabathricum have been used to treat diarrhoea, dysentery, hemorrhoids, cuts and wounds, toothache, and stomachache. Scientific findings also revealed the wide pharmacological actions of various parts of M. malabthricum, such as antinociceptive, anti-inflammatory, wound healing, antidiarrheal, cytotoxic, and antioxidant activities. Various types of phytochemical constituents have also been isolated and identifed from different parts of M. malabathricum. Thus, the aim of the present review is to present comprehensive information on ethnomedicinal uses, phytochemical constituents, and pharmacological activities of M. malabathricum

Safety and immunogenicity of rVSVΔG-ZEBOV-GP Ebola vaccine in adults and children in Lambaréné, Gabon: A phase I randomised trial.

BACKGROUND: The rVSVΔG-ZEBOV-GP vaccine prevented Ebola virus disease when used at 2 × 107 plaque-forming units (PFU) in a trial in Guinea. This study provides further safety and immunogenicity data. METHODS AND FINDINGS: A randomised, open-label phase I trial in Lambaréné, Gabon, studied 5 single intramuscular vaccine doses of 3 × 103, 3 × 104, 3 × 105, 3 × 106, or 2 × 107 PFU in 115 adults and a dose of 2 × 107 PFU in 20 adolescents and 20 children. The primary objective was safety and tolerability 28 days post-injection. Immunogenicity, viraemia, and shedding post-vaccination were evaluated as secondary objectives. In adults, mild-to-moderate adverse events were frequent, but there were no serious or severe adverse events related to vaccination. Before vaccination, Zaire Ebola virus (ZEBOV)-glycoprotein (GP)-specific and ZEBOV antibodies were detected in 11% and 27% of adults, respectively. In adults, 74%-100% of individuals who received a dose 3 × 104, 3 × 105, 3 × 106, or 2 × 107 PFU had a ≥4.0-fold increase in geometric mean titres (GMTs) of ZEBOV-GP-specific antibodies at day 28, reaching GMTs of 489 (95% CI: 264-908), 556 (95% CI: 280-1,101), 1,245 (95% CI: 899-1,724), and 1,503 (95% CI: 931-2,426), respectively. Twenty-two percent of adults had a ≥4-fold increase of ZEBOV antibodies, with GMTs at day 28 of 1,015 (647-1,591), 1,887 (1,154-3,085), 1,445 (1,013-2,062), and 3,958 (2,249-6,967) for the same doses, respectively. These antibodies persisted up to day 180 for doses ≥3 × 105 PFU. Adults with antibodies before vaccination had higher GMTs throughout. Neutralising antibodies were detected in more than 50% of participants at doses ≥3 × 105 PFU. As in adults, no serious or severe adverse events related to vaccine occurred in adolescents or children. At day 2, vaccine RNA titres were higher for adolescents and children than adults. At day 7, 78% of adolescents and 35% of children had recombinant vesicular stomatitis virus RNA detectable in saliva. The vaccine induced high GMTs of ZEBOV-GP-specific antibodies at day 28 in adolescents, 1,428 (95% CI: 1,025-1,989), and children, 1,620 (95% CI: 806-3,259), and in both groups antibody titres increased up to day 180. The absence of a control group, lack of stratification for baseline antibody status, and imbalances in male/female ratio are the main limitations of this study. CONCLUSIONS: Our data confirm the acceptable safety and immunogenicity profile of the 2 × 107 PFU dose in adults and support consideration of lower doses for paediatric populations and those who request boosting. TRIAL REGISTRATION: Pan African Clinical Trials Registry PACTR201411000919191

Stingless bee honey protects against lipopolysaccharide induced-chronic subclinical systemic inflammation and oxidative stress by modulating Nrf2, NF-κB and p38 MAPK

Background: Epidemiological and experimental studies have extensively indicated that chronic subclinical systemic inflammation (CSSI) and oxidative stress are risk factors for several chronic diseases, including cancer, arthritis, type 2 diabetes, and cardiovascular and neurodegenerative diseases. This study examined the protective effect of stingless bee honey (SBH) supplementation against lipopolysaccharide (LPS)-induced CSSI, pointing to the possible involvement of NF-κB, p38 MAPK and Nrf2 signaling. Methods: CSSI was induced in male Sprague Dawley rats by intraperitoneal injection of LPS three times per week for 28 days, and SBH (4.6 and 9.3 g/kg/day) was supplemented for 30 days. Results: LPS-induced rats showed significant leukocytosis, and elevated serum levels of CRP, TNF-α, IL-1β, IL-6, IL-8, MCP-1, malondialdehyde (MDA) and 8-hydroxy-2′-deoxyguanosine (8-OHdG), accompanied with diminished antioxidants. Treatment with SBH significantly ameliorated inflammatory markers, MDA and 8-OHdG, and enhanced antioxidants in LPS-induced rats. In addition, SBH decreased NF-κB p65 and p38 MAPK, and increased Nrf2 expression in the liver, kidney, heart and lung of LPS-induced rats. Furthermore, SBH prevented LPS-induced histological and functional alterations in the liver, kidney, heart and lung of rats. Conclusion: SBH has a substantial protective role against LPS-induced CSSI in rats mediated via amelioration of inflammation, oxidative stress and NF-κB, p38 MAPK and Nrf2 signaling

Molecular markers of anti-malarial drug resistance in Central, West and East African children with severe malaria.

BACKGROUND: The Plasmodium falciparum multidrug resistance 1 (PfMDR1), P. falciparum Ca(2+)-ATPase (PfATP6) and Kelch-13 propeller domain (PfK13) loci are molecular markers of parasite susceptibility to anti-malarial drugs. Their frequency distributions were determined in the isolates collected from children with severe malaria originating from three African countries. METHODS: Samples from 287 children with severe malaria [(Gabon: n = 114); (Ghana: n = 89); (Kenya: n = 84)] were genotyped for pfmdr1, pfatp6 and pfk13 loci by DNA sequencing and assessing pfmdr1 copy number variation (CNV) by real-time PCR. RESULTS: Pfmdr1-N86Y mutation was detected in 48, 10 and 10% in Lambaréné, Kumasi and Kisumu, respectively. At codon 184, the prevalence of the mutation was 73% in Lambaréné, 63% in Kumasi and 49% Kisumu. The S1034C and N1042D variants were absent at all three sites, while the frequency of the D1246Y mutation was 1, 3 and 13% in Lambaréné, Kumasi and Kisumu, respectively. Isolates with two pfmdr1 gene copy number predominantly harboured the N86Y wild-type allele and were mostly found in Kumasi (10%) (P < 0.0001). Among the main pfmdr1 haplotypes (NFD, NYD and YFD), NYD was associated with highest parasitaemia (P = 0.04). At the pfatp6 locus, H243Y and A623E mutations were observed at very low frequency at all three sites. The prevalence of the pfatp6 E431K variant was 6, 18 and 17% in Lambaréné, Kumasi and Kisumu, respectively. The L263E and S769N mutations were absent in all isolates. The pfk13 variants associated with artemisinin resistance in Southeast Asia were not observed. Eleven novel substitutions in the pfk13 locus occurring at low frequency were observed. CONCLUSIONS: Artemisinins are still highly efficacious in large malaria-endemic regions though declining efficacy has occurred in Southeast Asia. The return of chloroquine-sensitive strains following the removal of drug pressure is observed. However, selection of wild-type alleles in the multidrug-resistance gene and the increased gene copy number is associated with reduced lumefantrine sensitivity. This study indicates a need to constantly monitor drug resistance to artemisinin in field isolates from malaria-endemic countries

<it>In vitro </it>cytotoxicity of <it>Strobilanthes crispus </it>ethanol extract on hormone dependent human breast adenocarcinoma MCF-7 cell

<p>Abstract</p> <p>Background</p> <p><it>Strobilanthes crispus </it>has been traditionally used as antidiabetic, anticancer, diuretic, antilytic and laxative agent. However, cytotoxicity and antiproliferative effect of <it>S. crispus </it>is still unclear.</p> <p>Results</p> <p><it>Strobilanthes cripus </it>was able to reduce cell viability and proliferation in MTT and BrdU assays. Both cell cycle progression and Tunel assay suggested that IC₅₀of <it>S. crispus </it>ethanol extract induced sub-G1 cell cycle phase, and DNA fragmentation. On the other hand, translocation of mitochondria cytochrome c release, induction of caspase 3/7 and p53 while suppress XIAP on treated MCF-7 cell were also observed in this study.</p> <p>Conclusion</p> <p>Our findings suggest that <it>S. crispus </it>ethanol extract induced apoptosis and DNA fragmentation on hormone dependent breast cancer cell line MCF-7 via mitochondria dependent p53 apoptosis pathway.</p