**4. Effects of ginger in the prevention of cardiovascular disease**

#### **4.1 Antioxidant activity**

Oxidative stress is increased under the condition in which there is a decrease in the body's antioxidant defenses; therefore, there is an imbalance between the production and elimination of reactive oxygen species (ROS). As a consequence of this imbalance, ROS accumulate, generating cellular damage in the different systems of the organism, since they produce lipid peroxidation [51, 52].

Ginger has great antioxidant activity; in fact, many of its therapeutic applications are due to this activity. That ginger has antioxidant activity is a fact that has been shown both in vitro and in vivo. Although studies on the effects to human are not as numerous, it is beginning to be verified that its intake is capable of increasing the concentration of antioxidant enzymes and decreasing oxidative stress markers in cancer patients [53]. Morvaridzadeh et al. carried out a systematic review and meta-analysis where they concluded that there is sufficient evidence to show that ginger intake

*Ginger in the Prevention of Cardiovascular Diseases DOI: http://dx.doi.org/10.5772/intechopen.103970*

increases the levels of oxidative stress parameters [54]. There are many bioactive compounds in ginger that exhibit antioxidant activity, such as 6-gingerol, 8-gingerol, 10-gingerol, and 6-shogaol. Of all of them, the one with the highest antioxidant activity in vitro is 6-gingerol, followed by 6-shogaol [55].

The mechanism involved in its antioxidant activity has to do both with preventing the appearance of free radicals [56] and with being able to eliminate them [57]. 6-Gingerol has been shown to be capable of inhibiting xanthine oxidase, an enzyme that catalyzes the oxidation of hypoxanthine to xanthine and of xanthine to uric acid in the last stage of purine metabolic degradation, with the production of reactive oxygen species [58]. In addition, it has been proven that this compound is capable of increasing superoxide dismutase and catalase activity, two antioxidant enzymes [53].

It has been seen how the antioxidant activity depends on the time of harvest of ginger, if it is early, the antioxidant activity is higher, decreasing if the harvest is done later [59].

#### **4.2 Anti-inflammatory activity**

Another of the great biological activities attributed to ginger is its anti-inflammatory activity. Inflammation is one of the body's first responses to a risk situation [60]. When that inflammation is maintained over time, is then problematic. Today it is known that there are many diseases in which inflammation plays a determining role, in fact it is being studied how low-grade systemic inflammation is related to the development of different pathologies (autoimmune diseases, metabolic diseases, CVDs, cancer) [61, 62]. In chronic or low-grade inflammation, different proinflammatory factors are released, such as cytokines and prostaglandins [61].

Many researchers have shown that ginger reduces different proinflammatory markers such as: NF-κB, signal transducer activators of transcription (STAT), proteins of the Nod-like receptor family (NLRP), receptors toll-like (TLR), mitogenactivated protein kinase (MAPK), and mTOR (mTOR) pathways, in addition to inhibiting several proinflammatory cytokines [19, 58].

In the systematic review and meta-analysis carried out by Jalali et al, it is shown how ginger is capable of significantly reducing the levels of different proinflammatory parameters such as IL-6, TAC, CRP, TNF-α, MDA, and the serum prostaglandin E2 (PGE2) [63]. Song et al. have examined how ginger extract is capable of reducing proinflammatory markers produced by *Helicobacter pylori*. The expressions of interleukin (IL)-8, TNF-α, IL-6, inducible NOS (iNOS), and IFN-γ were reduced [64].

The most active compounds from the anti-inflammatory point of view of ginger are 6-shogaol, 6-gingerol, and 6-dehydroshogaol [45, 65, 66]. It has been described how 6-shogaol has an anti-inflammatory effect because it inhibits the production of PGE2 and proinflammatory cytokines (IL-1β and TNF-α) and decreases the expression of cyclooxygenase-2 (COX-2), p38 mitogen-activated protein kinase (MAPK), and nuclear NF-κB [45]. In other studies, 6-shogaol has been shown to inhibit LPSinduced iNOS and COX-2 expression in macrophages [67]. Furthermore, studies showed that 6-shogaol could protect against lipopolysaccharide (LPS)-induced toxicity in murine astrocytes [68].

#### **4.3 Antiobesity activity**

Worldwide, obesity has become the main pandemic of the twenty-first century [69, 70], as the rates of this pathology have increased considerably during the last

decades [71, 72]. According to the World Health Organization (WHO), obesity is characterized by an excessive accumulation of fatty tissue in the body, causing harmful effects on health [73]. Concerning problems associated with obesity are mainly its deleterious effect on other non-detectable diseases: CVDs, hypertension, nonalcoholic fatty liver disease, various types of cancer, and hyperlipidemia [74, 75]. In addition, it should be noted that patients with obesity show worse prognosis against COVID-19 infection and higher mortality rates [76, 77]. Additionally, it induces low-grade inflammation, oxidative stress, and contributes in the etiology of type 2 diabetes mellitus [78]. In recent years, natural compounds have aroused great interest in the prevention/treatment of obesity, and several studies have shown that ginger seems to be effective for this pathology [45].

It seems that gingerenone-A has a more potent inhibitory effect on adipogenesis and lipid accumulation than gingerols and 6-shogaol in 3T3-L1 preadipocyte cells, while it appears to activate the adenine monophosphate (AMP)-activated protein kinase (AMPK) pathway modulating fatty acid metabolism, thus attenuating obesity [79]. For its part, the daily dose of 2 g of ginger powder in obese women resulted in a decrease in body mass index (BMI) [80]. Daily dose of ginger powder also appears to increase fat oxidation in humans [81]. Several studies have shown that ginger can reduce body weight by increasing thermogenesis through catecholamines as well as lipolysis of white adipose tissue [78]. Therefore, it seems evident that both ginger and certain bioactive components are effective against obesity by enhancing lipolysis and inhibiting adipogenesis.
