Coronavirus disease 2019 (COVID-19) is a disease that has occurred since late 2019 in Wuhan, Hubei Province, China, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) (WHO, 2021). Indonesia ranks 16th globally and 4th in Asia in the number of COVID-19 cases (WHO, 2021). The most common symptoms found in COVID-19 patients are dry cough, fever, and shortness of breath; however, they may vary in patients. Dentists play an important role in examining and managing oral manifestations of COVID-19 found on intraoral examination.
A poorly understood immune malfunction has resulted in an uncontrolled inflammatory response, which has been the hallmark of severe COVID-19 illness. Previous research using cytometric and transcriptome profiling indicated a unique regulatory T cells (Treg) profile in severe COVID-19 patients, with a rise in Treg proportions and intracellular levels of the lineage-defining transcription factor forkhead box P3 (FoxP3), which was linked to poor outcomes. . Treg may play a sinister role in COVID-19, inhibiting antiviral T cell responses during the disease’s severe phase and acting as a direct pro-inflammatory factor. Interleukin (IL) IL-6 levels are considerably higher in COVID-19 patients and are related to poor clinical outcomes. Inhibiting IL-6 may be a unique therapeutic target for controlling dysregulated host responses in COVID-19 patients.
The development of COVID-19 has been linked to dysregulation of IL-1β and IL-6 responses but not cytokine transcripts themselves, especially in the nasopharynx and blood. However, it is not linked with COVID-19 disease severity, length of stay, or death. The transcriptional response modules for IL-1β and IL-6 give a dynamic readout of functional cytokine activity in vivo, which aids in quantifying the biological effects of immunomodulatory therapy in COVID-19. Besides, there were an increase in tumor necrosis factor-α (TNF-α) levels in COVID-19 patients. Thus, this condition leads to neutrophil chemotaxis in the oral mucosa and develops into aphthous lesions. The inflammatory response in COVID-19 patients is improved with immunoregulation when the inflammation takes place and is considered a potential therapy for the oral manifestations of COVID-19. Levels of vascular endothelial growth factor (VEGF) and fibroblast growth factor-2 (FGF-2) in COVID-19 patients dramatically rises with disease severity. VEGF, a key factor in angiogenesis, can stimulate endothelial cell migration and proliferation, resulting in tissue regeneration. On the other hand, VEGF has been linked to inflammation and the pathophysiology of vasculitis diseases.
Increased VEGF expression in oral aphthous lesions in connection with a cluster of differentiation (CD) CD34 positivity may indicate a role for VEGF in the development of these vasculitis lesions. VEGF may be involved in the progression of oral aphthous lesions. FGF-2 is a crucial angiogenesis mediator that is required for proper reproduction and wound repair. FGF-2 promotes angiogenesis by attaching to heparin sulfate proteoglycan as well as a tyrosine kinase receptor. FGF-2 promotes cell attachment via interactions with two FGF receptor-1 isoforms as well as an extracellular matrix or cell-associated heparin sulfate proteoglycans. Previous research found that FGF-2 paste is effective in relieving ulcer pain and encouraging healing without causing severe adverse effects in the treatment of mild recurring aphthous stomatitis.
Cytokine storm has an important role in the pathophysiology of COVID-19. The relation between inflammation and oxidative stress has been extensively established. Malondialdehyde (MDA), an oxidative stress measure, is considerably higher in COVID-19 patients. This might have a crucial role in disease development mechanisms. Patients with COVID-19 may benefit from methods for lowering or avoiding peroxidation, such as the use of an antioxidant substance. Oxidative stress is causing an increase in heat shock proteins (HSPs) expression.
Natural ingredients are proven to have the ability to control infectious diseases. In several countries, including Indonesia, the roselle flower (Hibiscus sabdariffa L., family Malvaceae) is one of the medicinal plants that can be easily found and consumed. The chemical components present in H. sabdariffa have potential health benefits, including antiseptic, diuretic, antihypertensive, anti-cholesterol, antibacterial, and antioxidant. The content of ascorbic acid and flavonoids make this plant have natural antioxidant activity, which can act as an immunoregulatory agent. Therefore, this study is aimed to identify the potential of H. sabdariffa chemical compounds such as anthocyanins, (+)-tartaric acid, and ascorbic acid as antiviral, anti-inflammatory, antioxidant, and increase tissue regeneration in oral manifestation due to COVID-19 infection through an immunoinformatic approach, an in silico study.
Virtual screenings through molecular docking, an in silico study targeting ACE2-spike, IL-10, Foxp3, IL6, IL1B, VEGF, FGF-2, HSP70, TNFR, and MDA-ovalbumin showed that anthocyanins in H. sabdariffa act as an antioxidant natural biomaterial has active compounds that potential as adjuvant immunoregulators therapy, which may play an important role in increasing wound regeneration of oral manifestation of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) as documented with bioinformatics exploration (in silico). Thus, further study is still needed to explore and elucidate the mechanism of H. sabdariffa active compound as a natural biomaterial for COVID-19 oral manifestations.
Authors: Nastiti Faradilla Ramadhani, Alexander Patera Nugraha
Link: https://jppres.com/jppres/pdf/vol10/jppres21.1316_10.3.418.pdf
