# Phytochemicals and Their Possible Mechanisms in Managing COVID-19 and Diabetes
## 4 Alternative Treatments with Phytochemicals (Curcumin, Silymarin, and Sulphorafane)
### Curcumin  
Curcumin is a polyphenolic compound, obtained from the rhizome of the plant _Curcuma longa_ and _curcuma_ spp. of the Zingiberaceae family of Asian origin [28; 29], with its use extending from India to China [30; 31]. Curcumin is employed in gastronomy and in food and pharmaceutical industries; however, it has been utilized in traditional medicine due to its widely described therapeutic benefits (antiseptic, analgesic, anti-inflammatory, antimalarial, as an insect repellent, etc.). On the other hand, there are reports on curcumin with respect to it maintaining beneficial biological and pharmacological effects, such as antioxidant, anti-inflammatory, cardioprotector, antimicrobial, nephoprotector, humanomodulatory, hypoglycemic, hyperlipidemic, and antirheumatic effects [32]. For these reasons, curcumin improves inflammatory alterations occasioned by chronic obstructive pulmonary disease (COPD), acute respiratory distress syndrome (ARDS), pulmonary fibrosis, acute pulmonary lesion, and in lung cancer [33]. Several studies have marked curcumin as an effective therapeutic compound in many diseases. However, it has been shown to have lower bioavailability due to the low aqueous solubility oral [34; 35]. To improve the bioavailability of curcumin, numerous approaches have been undertaken. These approaches have involved, firstly, the use of an adjuvant, like piperine, which interferes with glucuronidation; secondly, the use of liposomal curcumin; thirdly, curcumin nanoparticles; fourthly, the use of curcumin phospholipid complex; and fifthly, the use of structural analogues of curcumin [35; 36; 37]. Curcumin and Its Effect on COVID-19 and Diabetes  
Currently, in the face of the demand for effective treatments for patients with diabetes and infected by SARS-CoV-2, the use of phytochemical compounds has been suggested,which could involve a coadjuvant option in the therapy of these patients. As reported by [PERSON] [38], curcumin could act as an effective antiviral, possessing functions such as inhibition of the virus, blocking 3-chymotrypsin-like cysteine protease (the 3 CLpro enzyme controls coronavirus replication and is necessary in the life cycle of the virus), the signaling of nuclear factor-kappa beta (NF-kB), and the inhibition of the production of proinflammatory markers. It has been suggested that curcumin could possess the ability to impair the entry of the virus into the cell, restraining encapsulation and inhibiting viral protease, in addition to regulating different signaling pathways [39]. On the other hand, curcumin is proposed as an anti-inflammatory and immunomodulatory agent, with an antifibrotic and pulmonary effect. This is in addition to it inhibiting NF-kB and several inflammatory cytokines, as well as inflammatory enzymes such as COX2 and iNOS (which tend to increase in serious cases of SARS-CoV-2) [39]. In addition, it inhibits the expression of the proinflammatory enzyme 5-LOX, as well as chemokines, and it reduces the expression of the C-reactive protein (CRP). Alternatively, curcumin expresses Nrf2 (transcription nuclear factor erythropoae-2-related factor-2), which inhibits the inflammasome, and, consequently, the development of inflammation, as well as cellular damage in injured organs [40]. Also, the activation of Nrf2 by curcumin promotes the biological effects through interaction with Cys151 in Keap1, inhibiting the pathologies in which oxidative stress, such as type 2 diabetes and cardiovascular diseases and various infections, are involved. Thus, it has been proposed that curcumin can be a therapeutic agent against SARS-CoV-2 [41] (Figure 2). Figure 2: The mechanism of action of curcumin. Curcumin can act through the possible interaction that it entertains with the S protein of the virus, blocking the entry of the virus into the cell. Curcumin inhibits exposure to proinflammatory cyto-kines, such as inflammatory enzymes.