Anti-atherogenic role of green tea (Camellia sinensis) in South Indian smokers.

ETHNOPHARMACOLOGICAL RELEVANCE: Green tea (Camellia sinensis) is a popular beverage consumed all over the world due to its health benefits. Many of these beneficial effects of green tea are attributed to polyphenols, particularly catechins. AIM OF THE STUDY: The present study focuses on underlying anti-platelet aggregation, anti-thrombotic, and anti-lipidemic molecular mechanisms of green tea in South Indian smokers. MATERIALS AND METHODS: We selected 120 South Indian male volunteers for this study to collect the blood and categorised them into four groups; control group individuals (Controls), smokers, healthy control individuals consuming green tea, and smokers consuming green tea. Smokers group subjects have been smoking an average 16-18 cigarettes per day for the last 7 years or more. The subjects (green tea consumed groups) consumed 100 mL of green tea each time, thrice a day for a one-year period. RESULTS: LC-MS analysis revealed the presence of multiple phytocompounds along with catechins in green tea extract. Increased plasma lipid peroxidation (LPO), protein carbonyls, cholesterol, triglycerides, and LDL-cholesterol with decreased HDL-cholesterol levels were observed in smokers compared to the control group and the consumption of green tea showed beneficial effect. Furthermore, docking studies revealed that natural compounds of green tea had high binding capacity with 3-hydroxy-3-methyl-glutaryl-CoA reductase (HMG-CoA) when compared to their positive controls, whereas (-) epigallocatechin-3-gallate (EGCG) and (-) epicatechin-gallate (ECG) had high binding capacity with sterol regulatory element-binding transcription factor 1 (SREBP1c). Further, our ex vivo studies showed that green tea extract (GTE) significantly inhibited platelet aggregation and increased thrombolytic activity in a dose dependent manner. CONCLUSION: In conclusion, in smokers, catechins synergistically lowered oxidative stress, platelet aggregation and modified the aberrant lipid profile. Furthermore, molecular docking studies supported green tea catechins' antihyperlipidemic efficacy through strong inhibitory activity on HMG-CoA reductase and SREBP1c. The mitigating effects of green tea on cardiovascular disease risk factors in smokers that have been reported can be attributed majorly to catechins or to their synergistic effects.

Mutational analysis in international isolates and drug repurposing against SARS-CoV-2 spike protein: molecular docking and simulation approach.

The novel SARS-CoV-2 (severe acute respiratory syndrome coronavirus-2) is spreading, as the causative pathogen of coronavirus disease-19 (COVID-19). It has infected more than 1.65 billion people all over the world since it was discovered and reported 3.43 million deaths by mid of May 2021. SARS-CoV-2 enters the host cell by binding to viral surface glycoprotein (S protein) with human ACE2 (angiotensin-converting enzyme2). Spike protein (contains S1 and S2 sub-domains) molecular interaction with the host cells is considered as a major step in the viral entry and disease initiation and progression and this identifies spike protein as a promising therapeutic target against antiviral drugs. Currently, there are no efficient antiviral drugs for the prevention of COVID-19 infection. In this study, we have analyzed global 8719 spike protein sequences from patients infected with SAR-CoV-2. These SAR-CoV-2 genome sequences were downloaded from the GISAID database. By using an open reading frame (ORF) tool we have identified the spike protein sequence. With these, all spike protein amino acid sequences are subjected to multiple sequence alignment (MSA) with Wuhan strain spike protein sequence as a query sequence, and it shows all SAR-CoV strain spike proteins are 99.8% identical. In the mutational analysis, we found 639 mutations in the spike protein sequence of SARS-CoV-2 and identified/highlighted 20 common mutations L5F, T22I, T29I, H49Y, L54F, V90F, S98F, S221L, S254F, V367F, A520S, T572I, D614G, H655Y, P809S, A879S, D936Y, A1020S, A1078S, and H1101Y. Further, we have analyzed the crystal structure of the 2019-nCoV chimeric receptor-binding complex with ACE2 (PDB ID: 6VW1) as a major target protein. The spike receptor binding protein (RBD) used as target region for our studies with FDA-approved drugs for repurposing, and identified few anti-SARS-CoV2 potential drugs (Silmitasertib, AC-55541, Merimepodib, XL413, AZ3451) based on their docking score and binding mode calculations expected to strongly bind to motifs of ACE2 receptor and may show impart relief in COVID-19 patients.

Blood pressure homeostasis is maintained by a P311-TGF-ß axis.

P311 is an 8-kDa intracellular protein that is highly conserved across species and is expressed in the nervous system as well as in vascular and visceral smooth muscle cells. P311-null (P311-/-) mice display learning and memory defects, but alterations in their vasculature have not been previously described. Here we report that P311-/- mice are markedly hypotensive with accompanying defects in vascular tone and VSMC contractility. Functional abnormalities in P311-/- mice resulted from decreased total and active levels of TGF-ß1, TGF-ß2, and TGF-ß3 that arise as a specific consequence of decreased translation. Vascular hypofunctionality was fully rescued in vitro and in vivo by exogenous TGF-ß1-TGF-ß3. Conversely, P311-transgenic (P311(TG)) mice had elevated levels of TGF-ß1-TGF-ß3 and subsequent hypertension. Consistent with findings attained in mouse models, arteries recovered from hypertensive human patients displayed increased P311 expression. Thus, we identified P311 as the first protein known to modulate TGF-ß translation and the first pan-regulator of TGF-ß expression under steady-state conditions. Together, our findings point to P311 as a critical blood pressure regulator and establish a potential link between P311 expression and the development of hypertensive disease.