A Chinese Herb Prescription "Fang-gan Decoction" Protects Against Damage to Lung and Colon Epithelial Cells Caused by the SARS-CoV-2 Spike Protein by Regulating the TGF-ß/Smad2/3 and NF-κB Pathways.

Objective To explore the effects and mechanisms of a traditional Chinese medicine (TCM) prescription, "Fang-gan Decoction" (FGD), in protecting against SARS-CoV-2 spike protein-induced lung and intestinal injuries in vitro and in vivo.Methods Female BALB/c mice and three cell lines pretreated with FGD were stimulated with recombinant SARS-CoV-2 spike protein (spike protein). Hematoxylin-eosin (HE) staining and pathologic scoring of tissues, cell permeability and viability, and angiotensin-converting enzyme 2 (ACE2) expression in the lung and colon were detected. Enzyme-linked immunosorbent assay (ELISA) was performed to detect the levels of inflammatory factors in serum and cell supernatant. The expression of NF-κB p65, p-NF-κB p65, p-IκBα, p-Smad2/3, TGF-ß1, Caspase3, and Bcl-2 was evaluated by Western blotting.Results FGD protected against the damage to the lung and colon caused by the spike protein in vivo and in vitro according to the pathologic score and cell permeability and viability (P<0.05). FGD up-regulated ACE2 expression, which was reduced by the spike protein in the lung and colon, significantly improved the deregulation of inflammatory markers caused by the spike protein, and regulated the activity of TGF-ß/Smads and NF-κB signaling.Conclusion Traditional Chinese medicine has a protective effect on lung and intestinal tissue injury stimulated by the spike protein through possible regulatory functions of the NF-κB and TGF-ß1/Smad pathways with tissue type specificity.

Four new steroids from the marine soft coral-derived fungus Penicillium sp. SCSIO41201.

Penicildiones A-D (1-4), four new steroids derivatives together with three known compounds including 16α-methylpregna-17α,19-dihydroxy-(9,11)-epoxy-4-ene-3,18-dione-20-acetoxy (5), stachybotrylactone B (6) and stachybotrin (7) were isolated from the soft coral-derived fungus Penicillium sp. SCSIO41201, cultured in the 1% NaCl PDB substrate. Their structures were determined through spectroscopic methods and X-ray crystallography. Biological evaluation results revealed that 6 exhibited significant cytotoxic activity against HL-60, K562, MOLT-4, ACHN, 786-O, and OS-RC-2 cell lines with IC50 values of 5.23, 4.12, 4.31, 23.55, 7.65 and 10.81 µmol·L-1, respectively, while other compounds showed weak or no cytotoxicity at 50 µmol·L-1.

New chlorinated diphenyl ethers and xanthones from a deep-sea-derived fungus Penicillium chrysogenum SCSIO 41001.

Seven new compounds, including four new chlorinated diphenyl ethers, namely chrysines A-D (1-4), one new dichlorinated xanthone, chrysoxanthone (5), dichloroorcinol (6), and one new benzeneacetic acid derivative, 3-isopentyl-4-hydroxy phenylacetic acid methyl ester (7), along with fourteen known compounds (8-21), were isolated from a deep-sea-derived fungus Penicillium chrysogenum SCSIO 41001. Their structures were determined by extensive spectroscopic methods and X-ray single-crystal diffraction analysis. All of the isolated compounds (1-21) were evaluated for their α-glucosidase inhibitory activity using PNPG method. Among them, nine compounds (2, 3, 5, 6, 8, 9, 13, 17, and 18) exhibited inhibitory activity against α-glucosidase with IC50 values of 0.35, 0.20, 0.04, 0.16, 0.15, 0.09, 0.14, 0.14, and 0.12mM, respectively (IC50 0.28mM for the positive control acarbose).

Vaccinols J-S, ten new salicyloid derivatives from the marine mangrove-derived endophytic fungus Pestalotiopsis vaccinii.

Ten new salicyloid derivatives, namely vaccinols J-S (1-10), along with five known compounds (11-15) were isolated from Pestalotiopsis vaccinii (cgmcc3.9199) endogenous with the mangrove plant Kandelia candel (L.) Druce (Rhizophoraceae). Their structures including absolute configurations were established on the basis of spectroscopic analysis, optical rotation, CD spectra, quantum ECD calculations. To the best of our knowledge, vaccinol J (1) is the first example of salicyloid derivatives containing 2-methylfuran moiety. All of the new compounds were tested for their anti-enterovirus 7l (EV71) and cytotoxic activities. Among them, vaccinol J (1) exhibited in vitro anti-EV71 with IC50 value of 30.7µM (IC50 177.0µM for the positive control ribavirin).