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In-depth hepatoprotective mechanistic study of Phyllanthus niruri: In vitro and in vivo studies and its chemical characterization

Ezzat MI, Okba MM, Ahmed SH, El-Banna HA, Prince A, Mohamed SO, et al.

PLoS One, 2020;15(1):e0226185.
PMID: 31940365 DOI: 10.1371/journal.pone.0226185

Phyllanthus niruri L. is a widespread tropical plant which is used in Ayurvedic system for liver and kidney ailments. The present study aims at specifying the most active hepatoprotective extract of P. niruri and applying a bio-guided protocol to identify the active compounds responsible for this effect. P. niruri aerial parts were extracted separately with water, 50%, 70% and 80% ethanol. The cytoprotective activity of the extracts was evaluated against CCl4-induced hepatotoxicity in clone-9 and Hepg2 cells. Bioassay-guided fractionation of the aqueous extract (AE) was accomplished for the isolation of the active compounds. Antioxidant activity was assessed using DPPH (1, 1-diphenyl-2-picrylhydrazyl) radical scavenging method and ferric reducing antioxidant power (FRAP). The in vivo hepatoprotective activity of AE was evaluated in CCl4-induced hepatotoxicity in rats at different doses after determination of its LD50. Pretreatment of clone-9 and Hepg2 with different concentrations of AE (1, 0.1, 0.01 mg/ml) had significantly reduced the levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) against CCl4 injures, and restored the activity of the natural antioxidants; glutathione (GSH) and superoxide dismutase (SOD) towards normalization. Fractionation of AE gave four fractions (I-IV). Fractions I, II, and IV showed a significant in vitro hepatoprotective activity. Purification of I, II and IV yielded seven compounds; corilagin C1, isocorilagin C2, brevifolin C3, quercetin C4, kaempferol rhamnoside C5, gallic acid C6, and brevifolin carboxylic acid C7. Compounds C1, C2, C5, and C7 showed the highest (p< 0.001) hepatoprotective potency, while C3, C4, and C6 exhibited a moderate (p< 0.001) activity. The AE exhibited strong antioxidant DPPH (IC50 11.6 ± 2 μg/ml) and FRAP (79.352 ± 2.88 mM Ferrous equivalents) activity. In vivo administration of AE in rats (25, 50, 100 and 200 mg/kg) caused normalization of AST, ALT, alkaline phosphatase (ALP), lactate dehydrogenase (LDH), total cholesterol (TC), triglycyrides (TG), total bilirubin (TB), glucose, total proteins (TP), urea and creatinine levels which were elevated by CCl4. AE also decreased TNF-α, NF-KB, IL-6, IL-8, IL10 and COX-2 expression, and significantly antagonizes the effect of CCl4 on the antioxidant enzymes SOD, catalase (CAT), glutathione reductase (GR), and glutathione peroxidase (GSP). The histopathological study also supported the hepatoprotective effect of AE. P. niruri isolates exhibited a potent hepatoprotective activity against CCl4-induced hepatotoxicity in clone-9 and Hepg2 cell lines through reduction of lipid peroxidation and maintaining glutathione in its reduced form. This is attributable to their phenolic nature and hence antioxidative potential.
Fulltext Brain Cortical and Hippocampal Dopamine: A New Mechanistic Approach for Eurycoma longifolia Well-Known Aphrodisiac Activity and Its Chemical Characterization

Ezzat SM, Ezzat MI, Okba MM, Hassan SM, Alkorashy AI, Karar MM, et al.

Evid Based Complement Alternat Med, 2019;2019:7543460.
PMID: 31275418 DOI: 10.1155/2019/7543460

Eurycoma longifolia Jack (Fam.: Simaroubaceae), known as Tongkat Ali (TA), has been known as a symbol of virility and sexual power for men. Metabolic profiling of the aqueous extract of E. longifolia (AEEL) using UPLC-MS/MS in both positive and negative modes allowed the identification of seventeen metabolites. The identified compounds were classified into four groups: quassinoids, alkaloids, triterpenes, and biphenylneolignans. AEEL is considered safe with oral LD50 cut-off >5000 mg/kg. Oral administration of 50, 100, 200, 400, or 800 mg/kg of AEEL for 10 consecutive days to Sprague-Dawley male rats caused significant reductions in mounting, intromission, and ejaculation latencies and increased penile erection index. AEEL increased total body weight and relative weights of seminal vesicles and prostate. Total and free serum testosterone and brain cortical and hippocampal dopamine content was significantly elevated in treated groups with no significant effects on serotonin or noradrenaline content.
Prognostic value of grip strength: findings from the Prospective Urban Rural Epidemiology (PURE) study

Leong DP, Teo KK, Rangarajan S, Lopez-Jaramillo P, Avezum A, Orlandini A, et al.

Lancet, 2015 Jul 18;386(9990):266-73.
PMID: 25982160 DOI: 10.1016/S0140-6736(14)62000-6

Reduced muscular strength, as measured by grip strength, has been associated with an increased risk of all-cause and cardiovascular mortality. Grip strength is appealing as a simple, quick, and inexpensive means of stratifying an individual's risk of cardiovascular death. However, the prognostic value of grip strength with respect to the number and range of populations and confounders is unknown. The aim of this study was to assess the independent prognostic importance of grip strength measurement in socioculturally and economically diverse countries.
Airborne transmission of SARS-CoV-2 is the dominant route of transmission: droplets and aerosols

Rabaan AA, Al-Ahmed SH, Al-Malkey M, Alsubki R, Ezzikouri S, Al-Hababi FH, et al.

Infez Med, 2021 03 01;29(1):10-19.
PMID: 33664169

Coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has become a pandemic worldwide. On a daily basis the number of deaths associated with COVID-19 is rapidly increasing. The main transmission route of SARS-CoV-2 is through the air (airborne transmission). This review details the airborne transmission of SARS-CoV-2, the aerodynamics, and different modes of transmission (e.g. droplets, droplet nuclei, and aerosol particles). SARS-CoV-2 can be transmitted by an infected person during activities such as expiration, coughing, sneezing, and talking. During such activities and some medical procedures, aerosols and droplets contaminated with SARS-CoV-2 particles are formed. Depending on their sizes and the environmental conditions, such particles stay viable in the air for varying time periods and can cause infection in a susceptible host. Very few studies have been conducted to establish the mechanism or the aerodynamics of virus-loaded particles and droplets in causing infection. In this review we discuss the various forms in which SARS-CoV-2 virus particles can be transmitted in air and cause infections.
Fulltext Long-term exposure to outdoor and household air pollution and blood pressure in the Prospective Urban and Rural Epidemiological (PURE) study

Arku RE, Brauer M, Ahmed SH, AlHabib KF, Avezum Á, Bo J, et al.

Environ Pollut, 2020 Jul;262:114197.
PMID: 32146361 DOI: 10.1016/j.envpol.2020.114197

Exposure to air pollution has been linked to elevated blood pressure (BP) and hypertension, but most research has focused on short-term (hours, days, or months) exposures at relatively low concentrations. We examined the associations between long-term (3-year average) concentrations of outdoor PM2.5 and household air pollution (HAP) from cooking with solid fuels with BP and hypertension in the Prospective Urban and Rural Epidemiology (PURE) study. Outdoor PM2.5 exposures were estimated at year of enrollment for 137,809 adults aged 35-70 years from 640 urban and rural communities in 21 countries using satellite and ground-based methods. Primary use of solid fuel for cooking was used as an indicator of HAP exposure, with analyses restricted to rural participants (n = 43,313) in 27 study centers in 10 countries. BP was measured following a standardized procedure and associations with air pollution examined with mixed-effect regression models, after adjustment for a comprehensive set of potential confounding factors. Baseline outdoor PM2.5 exposure ranged from 3 to 97 μg/m3 across study communities and was associated with an increased odds ratio (OR) of 1.04 (95% CI: 1.01, 1.07) for hypertension, per 10 μg/m3 increase in concentration. This association demonstrated non-linearity and was strongest for the fourth (PM2.5 > 62 μg/m3) compared to the first (PM2.5
Association of nut intake with risk factors, cardiovascular disease, and mortality in 16 countries from 5 continents: analysis from the Prospective Urban and Rural Epidemiology (PURE) study

de Souza RJ, Dehghan M, Mente A, Bangdiwala SI, Ahmed SH, Alhabib KF, et al.

Am J Clin Nutr, 2020 07 01;112(1):208-219.
PMID: 32433740 DOI: 10.1093/ajcn/nqaa108

BACKGROUND: The association of nuts with cardiovascular disease and deaths has been investigated mostly in Europe, the USA, and East Asia, with few data available from other regions of the world or from low- and middle-income countries.
OBJECTIVE: To assess the association of nuts with mortality and cardiovascular disease (CVD).
METHODS: The Prospective Urban Rural Epidemiology study is a large multinational prospective cohort study of adults aged 35-70 y from 16 low-, middle-, and high-income countries on 5 continents. Nut intake (tree nuts and ground nuts) was measured at the baseline visit, using country-specific validated FFQs. The primary outcome was a composite of mortality or major cardiovascular event [nonfatal myocardial infarction (MI), stroke, or heart failure].
RESULTS: We followed 124,329 participants (age = 50.7 y, SD = 10.2; 41.5% male) for a median of 9.5 y. We recorded 10,928 composite events [deaths (n = 8,662) or major cardiovascular events (n = 5,979)]. Higher nut intake (>120 g per wk compared with <30 g per mo) was associated with a lower risk of the primary composite outcome of mortality or major cardiovascular event [multivariate HR (mvHR): 0.88; 95% CI: 0.80, 0.96; P-trend = 0.0048]. Significant reductions in total (mvHR: 0.77; 95% CI: 0.69, 0.87; P-trend <0.0001), cardiovascular (mvHR: 0.72; 95% CI: 0.56, 0.92; P-trend = 0.048), and noncardiovascular mortality (mvHR: 0.82; 95% CI: 0.70, 0.96; P-trend = 0.0046) with a trend to reduced cancer mortality (mvHR: 0.81; 95% CI: 0.65, 1.00; P-trend = 0.081) were observed. No significant associations of nuts were seen with major CVD (mvHR: 0.91; 95% CI: 0.81, 1.02; P-trend = 0.14), stroke (mvHR: 0.98; 95% CI: 0.84, 1.14; P-trend = 0.76), or MI (mvHR: 0.86; 95% CI: 0.72, 1.04; P-trend = 0.29).
CONCLUSIONS: Higher nut intake was associated with lower mortality risk from both cardiovascular and noncardiovascular causes in low-, middle-, and high-income countries.