Therapeutic prospects of naturally occurring p38 MAPK inhibitors tanshinone IIA and pinocembrin for the treatment of SARS‐CoV‐2‐induced CNS complications

Abstract

P38 mitogen‐activated protein kinase (p38 MAPK) signaling pathway is closely related to severe acute respiratory syndrome coronavirus‐2 (SARS‐CoV‐2) replication and hyperinflammatory responses in coronavirus disease 2019 (COVID‐19). Therefore, blood–brain barrier‐penetrating p38 MAPK inhibitors have good potential for the treatment of central nervous system (CNS) complications of COVID‐19. The aim of the present study is the characterization of the therapeutic potential of tanshinone IIA and pinocembrin for the treatment of CNS complications of COVID‐19. Studies published in high‐quality journals indexed in databases Scopus, Web of Science, PubMed, and so forth were used to review the therapeutic capabilities of selected compounds. In continuation of our previous efforts to identify agents with favorable activity/toxicity profiles for the treatment of COVID‐19, tanshinone IIA and pinocembrin were identified with a high ability to penetrate the CNS. Considering the nature of the study, no specific time frame was determined for the selection of studies, but the focus was strongly on studies published after the emergence of COVID‐19. By describing the association of COVID‐19‐induced CNS disorders with p38 MAPK pathway disruption, this study concludes that tanshinone IIA and pinocembrin have great potential for better treatment of these complications. The inclusion of these compounds in the drug regimen of COVID‐19 patients requires confirmation of their effectiveness through the conduction of high‐quality clinical trials.

Long COVID‐19 gastrointestinal related disorders and traditional Chinese medicine: A network target‐based approach

“…Recent studies have shown that Tanshinone IIA (Figure 8) inhibits P38 mitogen-activated protein kinase (p38 MAPK) linked to both the replication and inflammatory effects of COVID-19. Interestingly, these inhibitors can penetrate the blood-brain barrier, making their potential application possible in the treatment of central nervous system complications induced by COVID-19 (Valipour, 2023). The demonstrated biological properties of Tanshinone IIA also make it potentially useful in the treatment of various pathologies (Shang et al, 2012).…”

Plant-Derived Epi-Nutraceuticals as Potential Broad-Spectrum Anti-Viral Agents

“…Tanshinone IIA was reported to be an inhibitor of MAPK p38 [450]. MAPK p38 is explored by many viruses for their efficient replications [47].…”

“…MAPK p38 is explored by many viruses for their efficient replications [47]. Natural products that inhibit MAPK p38 activity might be a good candidate to exhibit broad-spectrum anti-viral activity [450], including DENV [43], coronavirus [44], VEEV [45], EV71 [46], SFTSV, HSV-1, and SARS-CoV-2 [47,450].…”

“…Inhibits replications of HCV and DENV [444] Tanshinone IIA Decreases the expression and activity of HDACs [449]. Inhibits MAPK p38 which resulted in , lowering the replications of a number of viruses including DENV [43], coronavirus [44], VEEV [45], EV71 [46], SFTSV, HSV-1, and SARS-CoV-2 [47,450].…”

Evaluating NSAIDs in SARS-CoV-2: Immunomodulatory mechanisms and future therapeutic strategies

“…However, it underscores the imperative for further preclinical trials to delineate p38 activation's role in SARS-CoV-2 animal models, emphasizing the necessity for comprehensive clinical trials to assess the efficacy and safety of p38 MAPK inhibitors in severe COVID-19 cases [ 40 ]. In the same context, Valipour [ 43 ] emphasized the potential of blood-brain barrier-penetrating p38 MAPK naturally occurring inhibitors in addressing CNS complications of COVID-19. This was highlighted through the characterization of tanshinone IIA and pinocembrin's therapeutic potential in treating these complications.…”