*4.6. Iron Overload Prevention*

Ginger's ability in modulating iron absorption in the case of overload was an unexpected finding in a study that used ginger nanoparticle-derived lipid vectors (GDLV) to deliver DMT-1 short-interference RNAs (siRNA) that suppressed DMT-1 mRNA expression to reduce iron absorption in an iron-loading mice model [152]. The study found that GDLV containing negative control appeared to repress some iron-related parameters similar to the DMT-1 siRNA treatment. The observed effects were reductions of 20% in 59Fe absorption, approximately 65% of pancreatic non-haem iron, and 40 to 50% lower SF compared to controls. Hence, the authors suggested that the bioactive lipids in ginger could influence iron absorption and homeostasis.

In another animal model, Gholampour et al. [153] showcased the protective properties of ginger against the deleterious effects of iron overloading. To induce iron overload, male Wistar rats were given ferrous sulphate at 30 mg/kg/day, dissolved in 1 mL distilled water, intraperitoneally for 14 days. These rats showed significantly higher serum hepatic markers and bilirubin levels, elevated MDA levels, lower serum albumin levels, total protein, triglyceride, cholesterol, and glucose, decreased creatinine clearance and higher fractional excretion of sodium compared to controls (*p* < 0.001). The histopathological examination further confirmed their liver and kidney damage. A separate group of iron overloaded rats was fed with a hydroalcoholic ginger extract at 400 mg/kg/day dissolved in 1 mL distilled water and given by gavage for 11 days from the fourth day of ferrous sulphate injection. The feeding of ginger markedly reversed the adverse impacts of iron overload, as evidenced

in the significantly higher levels of hepatic serum markers, renal functional markers and lipid peroxidation markers in this group compared to the iron only group (*p* < 0.01). Moreover, depleted serum total protein, albumin, glucose, triglycerides, and cholesterol were restored with bilirubin concentration decreased in the blood. Hence, ginger extract demonstrated strong protective effects against iron toxicity potentially through its free radical scavenging activities. The preservation of the liver and kidney was also corroborated through histological examinations.

The potential of ginger, especially its 6-shogaol derivative, in preventing iron overload is further demonstrated in a case series reported by Golombick et al. [154]. In this study, 6 early-stage, transfusion-independent patients with myelodysplastic syndrome (MDS) were given a daily supplement of 20 mg of a ginger extract standardised for 20% 6-shogaol. Blood and urine samples were collected monthly. At three months, the study found that 6-shogaol was able to reduce the SF levels (>40% reductions) of three of the patients who had elevated SF (>300 g/μL) at baseline. Two of the patients who had SF reduction repeated the study for another 3 months after a washout period. Again, a greater than 40% reduction in SF was observed in the repeat tests for both patients. The two patients were tested for their serum hepcidin levels at the repeat tests. Both patients demonstrated elevation of serum hepcidin that accompanied the SF reduction. Furthermore, one patient who had high liver function enzymes due to alcohol consumption also saw normalisation of liver function with a greater than 40% reduction in these enzymes at the end of the study. The restoration of liver function was achieved without changing alcohol consumption habits. The research concluded that ginger extract rich in 6-shogaol prevented iron overload in MDS patients through upregulation of hepcidin, potentially with liver function restoration.
