# Phytochemicals and Their Possible Mechanisms in Managing COVID-19 and Diabetes
## 4 Alternative Treatments with Phytochemicals (Curcumin, Silymarin, and Sulphorafane)
### Sulforaphane  
Sulforaphane is an isothicyanate deriving from the hydrolysis of glucosinolate glucoraphanin (GRA) in cruciferous vegetables such as Brussels sprouts, cabbages, and, mainly, in broccoli [74; 75]. Studies have shown that sulforaphane exerts effects on diseases including neurological diseases and chronic pulmonary diseases, and antidiabetic, anticancer, and anti-inflammatory effects [74; 75; 76; 77; 78; 79; 80].  
These benefits are due to sulforaphane having faster absorption and high bioavailability [81; 82], with appropriate plasma and urine (low excretion) concentrations present [83].  
Sulforaphane and Its Effect on COVID-19 and Diabetes  
It has been observed that, in patients with infection by COVID-19, their condition often becomes critical; therefore, the proinflammatory system (C-reactive protein, the cytokines IL-6 and IL-8, and TNF-\(\alpha\), etc.) is activated. There is an increase of ROS that gives rise to cellular and tissue damage. The acute respiratory distress syndrome (ARDS) develops and there is an alteration in vascular permeability (endothelial dysfunction and thrombosis). It has been suggested that the activation of Nrf could improve the state caused by SARS-CoV-2; to date it has suppressed the expression of cytokines and activation of the inflammasome; in addition, it protects the respiratory epithelium and the vascular endothelium and enhances the expression of antioxidant enzymes [84]. It has been reported that sulforaphane tends to be an activator of Nrf. On the other hand, sulforaphane has been proposed as a strategic treatment against COVID-19, because this compound possesses the function of activating Nrf, which provides cytoprotection due to the homeostasis of proteins and redox, in addition to it inhibiting inflammation [85]. According to [PERSON] et al. [86], natural products such as sulforaphane maintain a beneficial effect on confronting SARS-CoV-2 in terms of blocking the ACE2 receptor or the serine protease TMPRRS2, which are indispensable for human cellular infection (Figure 4).  
According to studies carried out by [PERSON] et al. [87], the authors reported that diabetes treated with sulforaphane inhibits the production of glucose by hepatic cells through the nuclear translocation factor 2, relating it to erythroid nuclear factor 2 (Nrf2), and that, in addition, it produces a diminution in the key enzymatic expression of glyoneogenesis and attenuates glucose intolerance. It was also observed that sulforaphane reduces fasting blood glucose and glycosylated hemoglobin (HbA1c) in obese populations with uncontrolled type 2 diabetes. [PERSON] et al. [88] suggested sulforaphane as a potent activator of Nrf, whose effect is to revert the diabetic, cardiometabolic, and cytoprotective complications related to proinflammatory factors such as Nf-kB PPAR. The findings reported by [PERSON] et al. [89] suggest that sulforaphane could delay diabetic retinopathy as a result of the degeneration of the photoreceptors in diabetes and sulforaphane may inhibit stress in the endoplasmatic reticule and the inflammation and expression of Txnip by activation of the AMPK pathway.  
In COVID-19, diabetes predisposes to the incidence of COVID-19, increases disease severity, and even causes COVID-related death [90]. This is because SARS-CoV-2 could be involved in chronic inflammation, in the increase of the activity of coagulation, and in the destruction of the immune response, as well as in possible pancreatic injury, thus associating itself with diabetes and COVID-19 [91]. Therefore, it is important to find therapeutic alternatives destined for the control of diabetes and COVID-19, as well as the use of sulforaphane, which has been described as maintaining an effective control over diabetes, but that additionally has been considered to manifest an antiviral effect.