Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by peripheral pain involving joints (hands, feet, wrists, shoulders, elbows, hips, and knees). It is characterized by a tight interaction between cells and mediators of the innate and adaptive immune system ^[1][39]. While the cause of RA is unknown, it is influenced by genetic, epigenetic, and environmental factors. Pain, swelling secondary to inflammation of the synovial membrane, and stiffness occur, especially in the morning or after prolonged periods of rest. In addition to damaging the joints and surrounding tissues (tendons and muscles) that can lead to decreased mobility and joint function, chronic inflammation can affect other organs, such as the heart, lung, or kidney ^[2][40]. In addition, if the inflammation is high and sustained, it can cause fever, fatigue, asthenia, weight loss, and loss of appetite. Therefore, rheumatoid arthritis is considered a systemic disease ^[3][41]. The pathophysiological mechanisms for RA are not fully elucidated; however, it is clear that the immune system is compromised, causing chronic inflammation, and there is also oxidative stress ^[4][5][42,43]. Actual treatment for RA consists of immunomodulation or immunosuppression and symptomatic treatment (anti-inflammatories), but this treatment does not cure the disease. Since the development of RA depends on environmental factors, including diet, it is logical to think that certain foods or nutrients with an anti-inflammatory and antioxidant character may be useful in this pathology ^[6][44]. In this sense, ginger is a very good candidate, as it has antioxidant and anti-inflammatory properties. In fact, since ancient times, ginger has been used in medicine as an anti-inflammatory. It is currently known that this is due to the fact that the bioactive compounds in ginger are capable of inhibiting the COX-2 and LOX pathway ^[7][45]. Both in vitro and in vivo models have proved that ginger has antiarthritic effects ^[7][8][45,46]. One of the most abundant bioactive compounds of ginger is 6-shogaol. In vitro and in vivo, 6-shogaol has been shown to exhibit cancer protective effects, anti-inflammatory, antioxidant, and neuroprotective actions ^[9][47]. In vivo, 6-shogaol successfully reduced the formation of paw edema ^[10][48], leukocyte infiltration into the tissue, or symptoms of arthritis ^[11][12][13][49,50,51]. Bashir et al. verified how zingerone is capable of improving inflammation and oxidative stress in an animal model of arthritis ^[14][52]. 2.

Inflammatory Bowel Disease Inflammatory bowel disease (IBD) is an umbrella term for various chronic inflammatory digestive processes, the etiology of which is unknown. Crohn’s disease and ulcerative colitis are among these processes. Crohn’s disease can be located anywhere in the gastrointestinal tract, from the mouth to the anus, although it usually occurs in the distal ileum and ascending colon. Ulcerative colitis is mainly located in the rectum and distal colon, although it may extend to the entire colon. The inflammatory process is discontinuous and asymmetrical. Unlike Crohn’s disease, ulcerative colitis starts in the rectum, where it gives rise to the so-called ulcerative proctitis ^[15][55]. The most common clinical symptoms of ulcerative colitis include abdominal pain, diarrhea, and bloody mucoid stools. In relation to the pathogenesis of the disease, it is recognized that in addition to genetic factors, there are additional triggering factors, so-called environmental precipitants, and disease cofactors. In this sense, a precipitating factor would be an infection by a certain pathogen, coupled with a defective function of the intestinal barrier, which would trigger a chronic inflammatory response in genetically predisposed individuals with impaired regulation of the immune system. The immune response of the gastrointestinal tract can lead to inflammation when the immune system and commensal bacteria balance is altered. This alteration occurs more frequently in genetically predisposed individuals. The gut microbiome plays an important role in the treatment of IBD ^[16][56]. For the already reported dysbiosis in patients with ulcerative colitis and Crohn’s disease compared to controls, Guo et al. ^[17][57] showed that ginger can improve the functions of the gut microbiota, restoring its diversity. Patients with Crohn’s disease and ulcerative colitis have an increased proportion of Proteobacteria and a decreased proportion of Firmicutes ^[18][58]. In gut homeostasis, Toll-like receptors (TLRs) play a pivotal role as mediators between the gut microbiome and the immune response. Pathogen-associated molecular patterns (PAMPs) are recognized by TLRs and upon recognition are activated, regulating dendritic cell maturation, adaptive immunity, and innate immunity. Expression of TLRs increases when these regulations are altered, leading to an increase in inflammatory cytokines and an increased risk of inflammatory bowel diseases ^[19][59]. TLR4 signaling is involved in inflammatory bowel disease and drug treatment efficacy ^[20][60]. Pharmacological treatment of IBD is based on non-specific anti-inflammatory and immunosuppressive drugs with suboptimal results. The goal of IBD therapy is to induce and maintain remission and ameliorate the disease’s secondary effects ^[21][61]. In addition to pharmacological treatment, diet plays a key role ^[22][62]. There are bioactive substances from different foods that can be used in the prevention and treatment of inflammatory bowel diseases. Among these substances is glycomacropeptide (GMP), a peptide derived from milk K-casein with immunomodulatory, bactericidal, and prebiotic effects. Curcumin is a yellow pigment from turmeric (Curcuma longa), a spice of Indian origin that has beneficial health effects. Curcumin ameliorates altered intestinal barrier function caused by inflammation by reducing myosin light chain kinase (MLCK) expression. It also decreases the production of TNF-α, IL-4, IL-6, and IL-13 by MCs in response to allergens ^[23][63]. There is a need to develop novel effective therapies and adjuvants for the treatment of IBD, as conventional treatment can have side effects (such as nausea, pancreatitis, allergic reactions) and is relatively often ineffective in some patients ^[24][64]. Ginger has antioxidant, antitumor, anti-inflammatory, and anti-ulcer effects, and has also been used for many years throughout the world to treat vomiting, diarrhea, and infections ^[25][65]. In IBD, ginger modulates the inflammatory response through suppression of nuclear factor kappa B (NF-κB), TNF-α, Nod-like receptor family proteins (NLRP), TLR, signal transducer of activators of transcription (STAT), mitogen-activated protein kinase (MAPK), and mTOR pathways, as well as inhibiting several proinflammatory cytokines (I L-6, IL-1β) and myeloperoxidase enzyme (MPO) ^[26][27][66,67]. Several authors have observed that gingerols and shogaols present in the rhizome decrease hepatic markers of inflammation by inhibiting NF-κB activity after consumption of a high-fat diet ^[28][68]. TNF-alpha inhibition leads to modulation of the inflammatory response, resulting in downregulation of the NF-κB signaling ^[29][69]. The oral consumption of gingerol, a bioactive substance in ginger, decreased the values of cytokines (IL-1beta, IL-6), TNF-alpha, NF-kB (p65), and increased IL-10 in an animal model of mice with ulcerative colitis induced by dextran sulfate sodium. Moreover, it decreased cyclooxygenase-2 (COX-2) enzyme activity and monocyte chemoattractant protein-1 (MCP-1) ^[26][66]. 6-shogaol is a bioactive substance from dried ginger with anti-inflammatory properties. Several authors have observed that it increases the expression of the nuclear factor (erythroid-derived 2)-like 2 (Nrf-2) and heme oxygenase (HO-1) in DDS-induced colitis in a mouse model. It has also been shown to reduce the expression of IL-6, IL-1beta, and TNF-alpha ^[29][30][69,70]. However, the results are still scarce and in some cases contradictory, since in a pilot study of 45 patients with IBD, Van Tilburg et al. ^[31][71] observed that ginger did not have any beneficial effect when compared to a placebo group.

Systemic lupus erythematosus (SLE) is a chronic autoimmune inflammatory connective tissue disease that affects the joints, kidneys, skin, mucous membranes, and blood vessel walls. SLE is characterized by overactivation of the autoimmune system with abnormal functions of innate and adaptive immune cells and the production of a large number of autoantibodies against nuclear components ^[32][72]. However, at the present time, there is no clear etiology for this inflammatory disease, although enough evidence is gathered about the implication of genetic and environmental factors. Additionally, a wide variety of clinical manifestations, comorbid conditions, and a complex pathogenesis coexist in SLE. According to the literature, for the disease to manifest, there must be (in addition to a genetic predisposition) different hormonal, nutritional, and environmental factors that contribute to its pathogenesis ^[33][73]. There are many immune cells and proinflammatory proteins that are part of the complex pathogenesis of lupus which could be therapeutic targets ^[34][74]. The pharmacological treatment of SLE is based on four main types of drugs: non-steroidal anti-inflammatory drugs, antimalarial drugs, anti-inflammatory corticosteroids, and biological therapies ^[35][75]. The right pharmacological treatment for SLE is still a matter of controversy, and multiple simultaneous approaches are currently being used. However, in recent years, diet, microbiota, stress, and physical activity are receiving more attention from researchers. Bearing in mind that in SLE there is a there is a dysfunction of the immune system and an exacerbated inflammatory response, those bioactive substances that improve immune function and reduce chronic inflammation could be useful in the treatment of this pathology. The bioactive compounds of ginger have been proved these actions. It is clear that ginger has a potent antioxidant and anti-inflammatory activity. Hence, the anti-inflammatory effects of ginger are yet to be further investigated in the context of SLE.

Psoriasis is a chronic inflammatory skin condition marked by keratinocyte overgrowth and inflammation, which leads to epidermal hyperplasia, a characteristic of lesioned psoriatic skin. The elbows, knees, and scalp are the most common sites for psoriatic plaques. There is still no therapy for psoriasis, despite recent research revealing aspects of the pathogenesis and the extensive interplay involving nerves, immune system, endocrine system, and skin cells ^[36][77]. Oxidative stress is a key factor in the development and progression of psoriasis, which is known to be caused by a number of factors, including alcohol consumption, smoking, infection, drugs, obesity, cell metabolism, immune response, and pathological state ^[37][78]. The production of reactive oxygen species is a critical step in the creation of oxidative stress in psoriasis. They generally act as second messengers during this process and lead to an increase in the levels of oxidative products which result in the activation of Th1 and Th17 cells and keratinocytes through the MAPK, NF-kβ, and JAK-STAT pathways. This results in a cascade of inflammatory cytokines and growth factors. NF-kβ is an essential inflammatory mediator in the pathogenesis of psoriasis; increased expression of NF- β has been demonstrated in psoriatic lesions ^[38][79]. The phosphorylation of the inhibitor of kappa B kinase (IKK) complex by ROS can activate NF-kβ ^[39][80]. H₂O₂, which is transported by AQP3, has been linked to the activation of the NF-kβ signaling pathway in keratinocytes and the pathogenesis of psoriasis ^[40][81]. Altered NF-kβ signaling disrupts the balance of apoptotic signals, leading to the upregulation of cyclins and survivins, thereby inhibiting apoptosis. Furthermore, NF-kβ stimulates the synthesis of IL-17 and TNF-, boosting the inflammatory response downstream ^[37][78]. Eukaryotic cells use the NF-kβ pathway as a regulator of genes that affect cell proliferation and survival. NF-kβ regulates the inflammatory response by increasing the expression of inflammatory target genes such as cytokines, chemokines, and COX2. This enzyme increases the production of proinflammatory cytokines by triggering the creation of certain prostaglandins in response to inflammation. Ginger inhibits inflammatory responses by decreasing NF-kβ, which results in a decrease in cytokine gene expression ^[41][82]. Several authors ^[42][27] have observed that administration for 21 days of ginger and metformin in liposomes decreases TNF-α and IL-22 levels. These results show that ginger’s bioactive compounds could be an alternative treatment for psoriasis treatment.

There is growing evidence linking diet to cancer prevention and treatment. Cancer is the second leading cause of death in the world after cardiovascular disease, with important socio-economic consequences. Certain dietary components, such as ginger and its compound 6-gingerol, may be associated with a reduced risk of cancer development ^[43][83]. Inflammatory processes are associated with tumor progression ^[44][84]. Several authors ^[45][85] described the anti-inflammatory action of ginger extract in vivo cancer models in animals significantly reduced the elevated expression of TNF-alpha and NF-kβ in rats with liver cancer. De Lima et al. ^[46][86] showed that ginger derivatives, as an extract or isolated compounds, exhibit relevant antiproliferative effects on tumoral cells, as well as anti-inflammatory activities. 6-gingerol is the most pharmacologically active compound possessing potential cancer protection properties via its effect on a variety of biological pathways involved in apoptosis, inhibition of angiogenesis, cell cycle regulation, and cytotoxic activity. Ginger extract and 6-gingerol exert their action through important mediators and pathways of cell signaling, including p38/MAPK, Bax/Bcl2, Nrf2, TNF-α, p65/NF-κB, p53, ERK1/2, SAPK/JNK, caspases-3/-9, and ROS/NF-κB/COX-2 ^[47][87]. Some cancer types such as breast neoplasms ^[48][88] have been associated with inflammation ^[49][33]. Thus, females that may experience two inflammatory processes (e.g., obesity and breast cancer) have been followed in clinical trials to assess ginger’s anti-inflammatory effects compared to placebo ^[50][89]. Ginger was associated with a decrease in IL-10 compared to the placebo group, and other advantages, such as reductions in insulin, glucose, insulin resistance, LDL-C, and triglycerides. Some benefits were also measured, such as increases in HDL-C and HDL-C/LDL-C compared to the initial moment in the study. Therefore, ginger supplementation successfully modulated both inflammatory and metabolic indicators, suggesting mitigation of inflammation symptoms. Since these biomarkers are connected to the inception of breast neoplasms, ginger supplementation may, therefore, exert some protection against cancer. Furthermore, patients in the early stages of cancer may also benefit from ginger supplementation, especially those patients receiving a chemotherapy treatment that causes a highly inflammatory internal process ^[51][52][23,90].