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Increased adiposity has been associated with adipose tissue low‐grade inflammation leading to insulin resistance. Adipocyte differentiation inhibitors are expected to be effective in preventing obesity and related diseases. Anthocyanins (ACNs) are associated to enhanced adipocyte function and protection from metabolic stress. Herein, we evaluated the in vitro protective effects of an ACN rich extract against palmitic acid (PA)‐induced hypertrophy, inflammation, and insulin resistance in 3T3‐L1 adipocytes. ACN extract pretreatment reduces lipid accumulation and peroxisome proliferators‐activated receptor‐γ protein levels induced by PA. In addition, PA induces inflammation with activation of NF‐κB pathway, whereas ACN extract pretreatment dose‐dependently inhibited this pathway. Furthermore, adipocyte dysfunction associated with hypertrophy induces insulin resistance by affecting phosphatidylinositol 3‐kinase‐protein kinase B/Akt axis, GLUT‐1, and adiponectin mRNA levels. ACN extract pretreatment reverts these effects induced by PA and moreover was able to induce insulin pathway with levels higher than insulin control cells, supporting an insulin sensitizer role for ACNs. This study demonstrates a prevention potential of ACNs against obesity comorbidities, due to their protective effects against inflammation/insulin resistance in adipocytes. In addition, these results contribute to the knowledge and strategies on the evaluation of the mechanism of action of ACNs from a food source under basal and insulin resistance conditions related to obesity.

The outbreak of COVID-19 disease caused by SARS-CoV-2, along with the lack of targeted medicaments, forced the scientific world to search for new antiviral formulations. In the current emergent situation, drug repurposing of well-known traditional and/or approved drugs could be the most effective strategy. Herein, through computational approaches, we aimed to screen 14 natural compounds from limonoids and terpenoids class for their ability to inhibit the key therapeutic target proteins of SARS-CoV-2. Among these, some limonoids, namely deacetylnomilin, ichangin and nomilin, and the terpenoid β-amyrin provided good interaction energies with SARS-CoV-2 3CL hydrolase (Mpro) in molecular dynamic simulation. Interestingly, deacetylnomilin and ichangin showed direct interaction with the catalytic dyad of the enzyme so supporting their potential role in preventing SARS-CoV-2 replication and growth. On the contrary, despite the good affinity with the spike protein RBD site, all the selected phytochemicals lose contact with the amino acid residues over the course of 120ns-long molecular dynamics simulations therefore suggesting they scarcely can interfere in SARS-CoV-2 binding to the ACE2 receptor. The in silico analyses of docking score and binding energies, along with predicted pharmacokinetic profiles, indicate that these triterpenoids might have potential as inhibitors of SARS-CoV-2 Mpro, recommending further in vitro and in vivo investigations for a complete understanding and confirmation of their inhibitory potential.

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The spread of SARS‐CoV‐2, along with the lack of targeted medicaments, encouraged research of existing drugs for repurposing. The rapid response to SARS‐CoV‐2 infection comprises a complex interaction of cytokine storm, endothelial dysfunction, inflammation, and pathologic coagulation. Thus, active molecules targeting multiple steps in SARS‐CoV‐2 lifecycle are highly wanted. Herein we explored the in silico capability of silibinin from Silybum marianum to interact with the SARS‐CoV‐2 main target proteins, and the in vitro effects against cytokine‐induced‐inflammation and dysfunction in human umbilical vein endothelial cells (HUVECs). Computational analysis revealed that silibinin forms a stable complex with SARS‐CoV‐2 spike protein RBD, has good negative binding affinity with Mpro, and interacts with many residues on the active site of Mpro, thus supporting its potentiality in inhibiting viral entry and replication. Moreover, HUVECs pretreatment with silibinin reduced TNF‐α‐induced gene expression of the proinflammatory genes IL‐6 and MCP‐1, as well as of PAI‐1, a critical factor in coagulopathy and thrombosis, and of ET‐1, a peptide involved in hemostatic vasoconstriction. Then, due to endothelium antiinflammatory and anticoagulant properties of silibinin and its capability to interact with SARS‐CoV‐2 main target proteins demonstrated herein, silibinin could be a strong candidate for COVID‐19 management from a multitarget perspective.