# Phytochemicals and Their Possible Mechanisms in Managing COVID-19 and Diabetes
## 4 Alternative Treatments with Phytochemicals (Curcumin, Silymarin, and Sulphorafane)
### Curcumin
In addition to blocking transduction pathways, it blocks activation of the in-flammasome and inhibits the expression of ACE2 through the activation of Nrf2 caused by curcumin. Therefore, cur-cumin inhibits inflammation and avoids the development of the acute respiratory distress syndrome (ARDS), Acute Lung Injury (ALI), and the Multiple Organ Dysfunction Syndromes (MOD) of lungs, liver, kidneys, and brain. Created with BioRender.com (accessed on 1 September 2021). According to the activity that curcumin presents, it has been suggested that it could inhibit the production of inflammatory cytokines, TGF-\(\beta\) collagen, TN-C, \(\alpha\)-SMA and E-cadherin, and NF-kB signaling COX-2, as well as Nrf2, PPARy, JNK, and P38 in severe viral pneumonia, besides inhibiting fibrosis, in addition to activating the nuclear factor erythropoietin-2-related factor-2 (Nrf2)/heme oxygenase 1 (HO-1) signaling axis, which reduces the oxidative stress caused by a viral environment [42]. Investigations in silico have suggested that curcumin is a promising bioactive compound against COVID-19, due to the fact that it has been proposed that curcumin can bind the spike S (glycoprotein that forms homotrimers prominent on the viral surface) of the SARS-CoV-2 virus [43; 44; 45]. Exhaustive investigations conducted on the effect of curcumin on SARS-CoV-2 have suggested that this molecule and one of its derivatives could bind with Mpro (Mpro protease), indispensable for the maturation of SARS-CoV-2 [45]. Additionally, curcumin could bind to the glycoprotein receptor-binding domain (RBD) and to the peptidase (PD)-ACE2 domain, which are necessary for the entry of the virus and for the latter to produce a viral infection [46]. Lastly, it has been suggested, in some investigations on curcumin, that, in addition to its being effective against COVID-19, it is also effective against diabetes in terms of controlling the blood glucose, improving the function of the cells, preventing the necrosis or apoptosis of the islets of Langerhans, diminishing insulin resistance, and helping in the prevention of the damage wrought by diabetes-associated complications such as diabetic nephropathy and cardiopathy, due to curcumin's anti-inflammatory and antioxidant properties [47; 48]. Other studies have found that the effect of curcumin on diabetes is related to the increase of the peroxisome proliferator-activated receptor (PPAR) and its effect on the increase of the gene expression of GLUT4, GLUT2, and GLUT3, and due to the expression of the adiponectin genes [49]. Moreover, it has been observed that curcumin, in combination with metformin, diminishes glyco-oxidative stress in diabetic rats [50]. [PERSON] et al. [51] reported that the intervention of curcumin in the functional improvement of \(\beta\)-cells was associated with the increase in HOMA-b and the reduction of the C-peptide. The information collected on the potential effects of curcumin justifies it being catalogued as a promising coadjuvant for its utilization.