Severe acute respiratory syndrome coronavirus (SARS-CoV-2) disease is a global rapidly spreading virus showing very high rates of complications and mortality. Till now, there is no effective specific treatment for the disease. Aloe is a rich source of isolated phytoconstituents that have an enormous range of biological activities. Since there are no available experimental techniques to examine these compounds for antiviral activity against SARS-CoV-2, we employed an in silico approach involving molecular docking, dynamics simulation, and binding free energy calculation using SARS-CoV-2 essential proteins as main protease and spike protein to identify lead compounds from Aloe that may help in novel drug discovery. Results retrieved from docking and molecular dynamics simulation suggested a number of promising inhibitors from Aloe. Root mean square deviation (RMSD) and root mean square fluctuation (RMSF) calculations indicated that compounds 132, 134, and 159 were the best scoring compounds against main protease, while compounds 115, 120, and 131 were the best scoring ones against spike glycoprotein. Compounds 120 and 131 were able to achieve significant stability and binding free energies during molecular dynamics simulation. In addition, the highest scoring compounds were investigated for their pharmacokinetic properties and drug-likeness. The Aloe compounds are promising active phytoconstituents for drug development for SARS-CoV-2.
Methotrexate (MTX) is a chemotherapeutic agent and an immunosuppressant used to treat cancer and autoimmune diseases. However, its use is limited by its multi-organ toxicity, including nephrotoxicity, which is related to MTX-driven oxidative stress. Silencing oxidative stressors is therefore an important strategy in minimizing MTX adverse effects.
Medicinal plants rich in phenolic compounds are probable candidates to overcome these oxidants. Herein,
C
.
pentandra
ethyl acetate extract showed powerful
in vitro
radical-scavenging potential (IC
50
= 0.0716) comparable to those of the standard natural (ascorbic acid, IC
50
= 0.045) and synthetic (BHA, IC
50
= 0.056) antioxidants. The effect of
C
.
pentandra
ethyl acetate extract against MTX-induced nephrotoxicity in rats was evaluated by administering the extract (400 mg/kg/day) or the standard antioxidant silymarin (100 mg/kg/day) orally for 5 days before and 5 days after a single MTX injection (20 mg/kg, i.p.).
C. pentandra
showed slight superiorities over silymarin in restoring the MTX-impaired renal functions, with approximately twofold decreases in overall kidney function tests.
C. pentandra
also improved renal antioxidant capacity and reduced the MTX-induced oxidative stress. Moreover,
C. pentandra
inhibited MTX-initiated apoptotic and inflammatory cascades, and attenuated MTX-induced histopathological changes in renal tissue architecture.
Phytochemical investigation of the extract led to the purification of the phenolics quercitrin (
1
), cinchonains 1a (
2
) and 1b (
3
),
cis
-clovamide (
4
),
trans
-clovamide (
5
), and glochidioboside (
6
); a structurally similar with many of the reported antioxidant and nephroprotective agents. In conclusion, these data demonstrate that
C. pentandra
exhibits nephroprotective effect against MTX-induced kidney damage via its antioxidant, antiapoptotic and anti-inflammatory mechanisms.
Taxonomy
Functional Disorder, Traditional Medicine, Herbal Medicine.
The aim of the present study is the evaluation of the in-vitro cytotoxicity and antileishmanial activities of a methanolic extract and its different fractions of the soft coral Sarcophyton spongiosum collected from the Egyptian Red Sea against three cancer cell lines, A549, HepG2, and MCF-7, and a protozoan, Leishmania major, by the MTT assay protocol. The dichloromethane fraction exhibited significant anti-L. major (IC50 28.1 ± 1.2 µg/mL) and cytotoxic activities against MCF-7 cell line IC50 (31.5 ± 1.1 µg/mL). The ethyl acetate fraction showed promising cytotoxicity against A549 and HepG2 cell lines (IC50 13.4 ± 1.2 and 11.6 ± 1.9 µg/mL, respectively). A preliminary chemical screening of the total methanolic extract indicated of the presence of sterols and diterpenes.
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