Neuroprotection by Alstonia boonei De Wild., Anacardium occidentale L., Azadirachta indica A.Juss. and Mangifera indica L.

ETHNOPHARMACOLOGY RELEVANCE: Alstonia boonei De Wild. (stem bark), Anacardium occidentale L. (stem bark), Azadirachta indica A.Juss (leaves), Enantia chlorantha Oliv. (stem bark), Khaya senegalensis A.Juss (stem bark) Mangifera indica L. (stem bark), and Nauclea latifolia Sm. (stem bark) are used for treating malaria in southwest Nigeria. Surveys revealed that these plants are also employed for treating symptoms of malaria and cerebral malaria in the region. AIM OF THE STUDY: In this study, the effects of freeze-dried extracts of these plants were investigated on synthetic hemozoin (HZ)-induced neuroinflammation, neuronal damage, and increased permeability of brain microvascular endothelial cells. MATERIALS AND METHODS: Effects of freeze-dried plant extracts were investigated on neuroinflammation by measuring levels of pro-inflammatory mediators in culture supernatants, while in-cell western assays were used to measure protein levels of iNOS and NLRP3. Effects on HZ-induced neurotoxicity and ROS generation was measured using MTT and DCFDA assays, respectively. HZ-induced permeability of hCMEC/D3 endothelial cells was determined using the in vitro vascular permeability assay kit. RESULTS: The extracts produced significant (p < 0.05) reduction in TNFα, IL-6, IL-1ß, MCP-1, RANTES and iNOS/NO production in HZ-stimulated BV-2 microglia. Pre-treatment with 50 µg/mL of A. boonei, A. indica, A. occidentale, E. chlorantha and M. indica also resulted in the inhibition of NF-κB activation. Pre-treatment with A. indica produced, A. occidentale, M. indica and A. boonei reduced HZ-induced increased NLRP3 protein expression. HZ-induced increased caspase-1 activity was also reduced by A. boonei, A. occidentale, A. indica, E. chlorantha, and M. indica. Freeze-dried extracts of A. boonei, A. occidentale, A. indica and M. indica produced neuroprotective effect in HT-22 neuronal cells incubated with HZ by preventing HZ-induced neurotoxicity, ROS generation, DNA fragmentation and caspase 3/7 activity. Inhibition of HZ-induced increase in permeability of human hCMEC/D3 brain endothelial cells was also observed with A. boonei, A. occidentale, A. indica and M. indica, while reducing the release of TNFα and MMP-9. CONCLUSIONS: These results suggest that A. boonei, A. occidentale, A. indica and M. indica are neuroprotective through inhibition of neuroinflammation, neuronal damage and increased permeability of blood brain barrier. The outcome of the study provides pharmacological evidence for the potential benefits of plants as herbal treatments for cerebral malaria symptoms.

Garcinia kola and garcinoic acid suppress SARS-CoV-2 spike glycoprotein S1-induced hyper-inflammation in human PBMCs through inhibition of NF-κB activation.

Symptoms and complications associated with severe SARS-CoV-2 infection such as acute respiratory distress syndrome (ARDS) and organ damage have been linked to SARS-CoV-2 spike protein S1-induced increased production of pro-inflammatory cytokines by immune cells. In this study, the effects of an extract of Garcinia kola seeds and garcinoic acid were investigated in SARS-CoV-2 spike protein S1-stimulated human PBMCs. Results of ELISA experiments revealed that Garcinia kola extract (6.25, 12.5, and 25 µg/ml) and garcinoic acid (1.25, 2.5, and 5 µM) significantly reduced SARS-CoV-2 spike protein S1-induced secretion of TNFα, IL-6, IL-1ß, and IL-8 in PBMCs. In-cell western assays showed that pre-treatment with Garcinia kola extract and garcinoic acid reduced expressions of both phospho-p65 and phospho-IκBα proteins, as well as NF-κB DNA binding capacity and NF-κB-driven luciferase expression following stimulation of PBMCs with spike protein S1. Furthermore, pre-treatment of PBMCs with Garcinia kola extract prior to stimulation with SARS-CoV-2 spike protein S1 resulted in reduced damage to adjacent A549 lung epithelial cells. These results suggest that the seed of Garcinia kola and garcinoic acid are natural products which may possess pharmacological/therapeutic benefits in reducing cytokine storm in severe SARS-CoV-2 and other coronavirus infections.