An exploratory effect of Phaleria macrocarpa fruit extract on interleukin-6 mRNA expression in human PBMCs induced by glucose-enhanced SARS-CoV-2 spike protein and lipopolysaccharide in vitro

Nurhasanah, A.H. and Louisa M., Louisa M. and Angelina M., Angelina M. and Estuningtyas A, Estuningtyas A (2026) An exploratory effect of Phaleria macrocarpa fruit extract on interleukin-6 mRNA expression in human PBMCs induced by glucose-enhanced SARS-CoV-2 spike protein and lipopolysaccharide in vitro. Медичні перспективи = Medicni perspektivi (Medical perspectives), Т.31 (2). pp. 108-119. ISSN 2307-0404 (print), 2786-4804 (online)

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Abstract

Type 2 diabetes mellitus is a significant risk factor for dysregulated inflammatory responses during Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) infection. Corticosteroids, commonly used as anti-inflammatory agents in diabetic patients, often cause hyperglycemia, making infections and inflammation more difficult to control. These conditions highlight the need for laboratory models that can support preliminary screening of antiinflammatory drug candidates under elevated-glucose conditions. This exploratory study aimed to establish a human peripheral blood mononuclear cell (PBMC) inflammatory model induced by SARS-CoV-2 and lipopolysaccharide in the presence of high glucose and to assess the modulatory activity of Phaleria macrocarpa fruit ethanol extract on interleukin-6 (IL-6) mRNA expression under combined stimulation. This in vitro study used a human PBMC model induced by the SARS-CoV-2 spike protein and lipopolysaccharide under elevated glucose conditions. PBMCs were isolated from venous blood of a limited number of healthy adult volunteers. The concentrations of glucose, SARS-CoV-2 spike protein, and lipopolysaccharides used in PBMC cultures were selected for their ability to increase IL-6 mRNA expression under the tested conditions. Non-cytotoxic concentrations of Phaleria macrocarpa fruit ethanol extract were identified by maintaining cell viability of at least 80 percent. Combined stimulation with the SARS-CoV-2 spike protein, lipopolysaccharide, and high glucose increased IL-6 mRNA expression. Treatment with Phaleria macrocarpa fruit ethanol extract was comparable with dexamethasone in reducing IL-6 mRNA expression under the combined stimulation condition. These preliminary findings suggest that Phaleria macrocarpa suppresses IL-6 mRNA expression in response to combined stimulation in this in vitro PBMC model. However, our findings should be interpreted as exploratory due to the small number of the PBMC donor pool. Further studies using a larger, sexbalanced donor population, broader cytokine panels, and chemical standardization are required

Item Type:	Article
Additional Information:	doi: 10.26641/2307-0404.2026.2.365902
Uncontrolled Keywords:	Key words: hyperglycemia, inflammation, interleukin-6, peripheral blood mononuclear cells, type-2 diabetes mellitus; гіперглікемія, запалення, інтерлейкін-6, мононуклеарні клітини периферичної крові, цукровий діабет 2 типу
Subjects:	Clinical Pharmacology Diabetes
Divisions:	University periodicals > Medical perspectives
Depositing User:	Ирина Медведева
Date Deposited:	09 Sep 2026 08:20
Last Modified:	09 Sep 2026 08:20
URI:	http://repo.dma.dp.ua/id/eprint/10273

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