Recently, AYUSH has advised utilizing Kadha (herbal tea/decoction) composing basil, cinnamon, black pepper, dry ginger, and raisin and golden milk to boost the immune system as a prophylactic measure against COVID-19. Due to the complex composition of multiple phytoconstituents from all these medicinal plants, the mixture of this combination could modulate multiple proteins and would help to boost the immune system which can be explained via network pharmacology and gene-set enrichment analysis. Network pharmacology and gene set enrichment analysis are well-accepted approaches to identify the disease target, lead hit molecules and modulated pathways via “multiple component-protein interactions” [9-11].
Boosting of the immune system involves the modulation of multiple proteins that are involved in the homeostatic regulation. In the present analysis, we identified the modulation of multiple pathways that are related to infectious/non-infectious diseases and the immune system. A subject suffering from infectious/non-infectious diseases possesses a lower immune system [12]; are at higher risk to be affected by COVID-19. Hence, the herbal tea which has been recommended by the AYUSH is not limited over the boosting of the immune system but also may modulate other pathways which are involved in the pathogenesis of multiple diseases provides beneficial effect to the patients with diabetes and hypertension who cannot undergo to the pharmacotherapy of 4-hydroxy quinoline.
Enrichment analysis of modulated proteins identified the regulation of HIF-1, p53, PI3K-Akt, MAPK, cAMP, Ras, Wnt, NF-kappa B, IL-17, TNF, and cGMP-PKG signaling pathway which are directly involved in boosting the immune system. The task of HIF-1α has been reported to be dysregulated in viral infection which is involved to boost the immune system by regulating the task of macrophages, neutrophils, dendritic cells, and lymphocytes during the hypoxic condition [13]; primarily occurs in COVID-19 infection due to improper exchange O2/CO2 in lungs [14]. In the present study, we identified five genes i.e. ALDOA, FLT1, HMOX1, NOS2, and TIMP1 to be modulated related to this pathway. Further, PI3K-Akt functions as a rheostat in orchestrating the differentiation of memory CD8 T cells [15] which further regulate the functioning of multiple chemokines and cytokines [16] from multiple pathways like NF-kappa B, IL-17, and TNF signaling pathway which were found to be modulated in the present study. Hence, the next approach to boost the immune system by suggested Kadha could occur via regulation of PI3K-Akt, NF-kβ, interleukin, and TNF mediated cytokine regulation. Further in infectious diseases including viral infection MAPK pathway gets targeted by pathogens. Since this pathway is involved in the synthesis of immunomodulatory cytokines like interleukins and TNF-α via the activation of p38 MAPK pathways, modulation of this pathway could play important coordination with an immune response via the promotion of Th1 and Th2 against extracellular infectious agents [17]; has been regulated in the present study via the modulation of six proteins i.e. CD14, FLT1, HSPA6, RAC1, RAP1A, TNFRSF1A. Further, in COVID-19 there is an increase in cell apoptosis and necrosis in lung tissue. As the phytoconstituents were also predicted to modulate the Ras signaling pathway, the suggested herbal tea could also function in multiple cellular tasks including the regulation of cell survival and proliferation [18]. Additionally, we also identified the multiple pathways (Table S2) which get modulated in the pathogenesis of multiple infectious (bacterial/viral) and non-infectious diseases (diabetes, obesity, hypertension, etc) in which the immune system is compromised. Hence, the intake of this tea would also add a beneficial effect to maintain their daily lifestyle and also may improve the immunity system.
Since the AYUSH suggested the intake of the composition as an herbal tea and is to be taken orally, we attempted to identify the probable lead hits to get absorbed from the human intestinal tract in which the majority of the compounds were predicted to be absorbed from the gastrointestinal tract. Based on the Rule of Five, we identified camphoratin D to possess the highest drug-likeness score. Similarly, camphoratin B was predicted to have the highest human oral bioavailability. However, the single-molecule may not be as effective compared to the advised herbal tea as the amount required to boost the immune system may not sufficient enough. Hence, intake of the multiple compounds in the form of herbal tea as suggested by AYUSH could be more beneficial rather than a single molecule for boosting the immune system as a prophylactic against COVID-19 and could be helpful in subjects who are suffering diabetes and hypertension in which 4-hydroxychloroquine treatment cannot be proceed.