Comparison study of Beninese and Chinese herbal medicines in treating COVID-19

Abstract

Ethnopharmacological relevance: The worldwide use of natural remedies is an alternative therapeutic solution to strengthen immunity, fight, and prevent this disease. The rapid spread of the coronavirus disease worldwide has promoted the search for therapeutic solutions following different approaches. China and Benin have seen the use of natural remedies such as Chinese herbal medicine and local endemic plants as alternative solutions in treating COVID-19.

Aim of the study: The present study was designed to identify the prevalence of medicinal plant use in four municipalities of Benin most affected by COVID-19 and compare them with traditional Chinese medicine and finally verify the efficacy of the main components of the six plants most frequently used, via in vitro experiments.

Materials and methods: This study targeting market herbalists and traditional healers was conducted in the form of an ethnomedicinal survey in four representative communities (Cotonou, Abomey-Calavi, Zè, and Ouidah) of southern Benin. The chemical compositions of the six most commonly used herbs were investigated using network pharmacology. Network-based global prediction of disease genes and drug, target, function, and pathway enrichment analysis of the top six herbs was conducted using databases including IPA and visualised using Cytoscape software. The natural botanical drugs involved three medicines and three formulas used in the treatment of COVID-19 in China from the published literature were compared with the top six botanical drugs used in Benin to identify similarities between them and guide the clinical medication in both countries. Finally, the efficacy of the common ingredients in six plants was verified by measuring the viability of BEAS-2B cells and the release of inflammatory factors after administration of different ingredients. Binding abilities of six components to COVID-19 related targets were verified by molecular docking.

Results: According to the medication survey investigation, the six most used herbs were Citrus aurantiifolia (13.18%), Momordica charantia (7.75%), Ocimum gratissimum (7.36%), Crateva adansonii (6.59%), Azadirachta indica (5.81%), and Zanthoxylum zanthoxyloides (5.42%). The most represented botanical families were Rutaceae, Lamiaceae, Cucurbitaceae, Meliaceae, and Capparaceae. The network pharmacology of these six herbal plants showed that the flavonoids quercetin, kaempferol, and β-sitosterol were the main active ingredients of the Benin herbal medicine. Chinese and Beninese herbal medicine are similar in that they have the same targets and pathways in inflammation and oxidative stress relief. Mild COVID-19-related targets come from C. aurantiifolia and M. charantia, and severe COVID-19-related targets come from A. indica A. Juss. Cell viability and enzyme-linked immunosorbent assay results confirmed that six major compounds could protect BEAS-2B cells against injury by inhibiting the expression of inflammatory factors, among which quercetin and isoimperatorin were more effective. Docking verified that the six compounds have good binding potential with COVID-19 related targets.

Conclusions: These results suggest that Benin herbal medicine and Chinese herbal medicine overlap in compounds, targets, and pathways to a certain extent. Among the commonly used plants in Benin, C. aurantiifolia and M. charantia may have a good curative effect on the treatment of mild COVID-19, while for severe COVID-19, A. indica can be added on this basis.

Keywords: Active ingredient; COVID-19; Chinese medicine; Medicinal plant; Southern Benin; Traditional treatment.

Graphical abstract

Fig. 1

Use of herbs and their components. (A) Botanical families of the herbs. (B) Components of the medicinal herbs used. (C) Method of medicinal recipe preparation.

Fig. 2

Potential targets of the top six herbs in the treatment of COVID-19. (A) The number of active compounds from the top six herbs; (B) Venn diagram of the intersection relationship of target genes between top six herbs and COVID-19; (C) Intersection network of herbs, components, targets, and function in COVID-19.

Fig. 3

Signalling pathway analysis of common targets between the top six herbs and COVID-19. (A) KEGG enrichment analysis of the intersection targets of the top six herbs; (B) PPI network of the top six herbs with pathway-target analysis; (C) Heat map of the top six herbs in the treatment of disease and functions of potential targets of COVID-19; (D) Network ranking first by scoring of the top six herbs in the treatment of potential targets of COVID-19.

Fig. 4

Comparison of target pathways. (A) The pathogenesis of COVID-19 in distinct disease stages. (B) Targets of the ‘three medicines and three formulas’. (C) Targets of the top six herbs used in Benin. Vertical axis: disease type; Horizontal axis: target coincident with prescription.

Fig. 5

The protective effect of traditional Chinese medicine compounds on BEAS-2B cell injury and molecular docking models of them binding to the 3 COVID-19 related targets. The pattern of cellular lesions was established by LPS (10 mg/mL), and dexamethasone was used as a positive control (5 μmol/L). The inhibitory effects of the components on IL-6 (A) and TNF-α (B) were detected, and the state of cellular lesions was assessed by CCK-8 (C) and LDH (D). Data are expressed as mean ± SEM, n = 5 in each group; *p < 0.05, **p < 0.01, ***p < 0.001 versus model; ^##p < 0.01, ^###p < 0.001 versus control groups. Molecular docking models and the binding affinity of the 6 compounds binding to the 3 COVID-19 related targets (E).