*4.3. Anti-Inflammatory Action*

The anti-inflammatory action of ginger and its potential application in AI were aptly reviewed by Kumar et al. [145]. Inflammation stimulates hepcidin production in response to pro-inflammatory cytokines such as IL-1, tumour necrotic factor (TNF)-*α* and, in particular, IL-6. As an acute phase protein, hepcidin's role is to inhibit iron absorption and thus minimise the free iron supply to invading pathogens. Hence, sustained elevation of hepcidin will cause hypoferremia leading to anaemia. Additionally, an increase in IL-6 activates the nuclear factor kappa B (NF-*κβ*) pathway, resulting in the synthesis of CRP from the hepatocytes. The rising CRP levels indicate systemic inflammation and can blunt the erythropoiesis stimulation response in AI, especially in chronic kidney disease [145]. The bioactive compounds in ginger, such as 6-gingerol, 6-shogaol and 6-paradol, are known to possess broad anti-inflammatory properties that can block the activation of NF-*κβ* by suppressing pro-inflammatory cytokines [145,158].

The human intervention study on ginger and iron absorption reported by Kulkarni et al. [139,140] mentioned earlier also measured malondialdehyde (MDA) as the serum biomarker for oxidative stress and TNF-*α* as the inflammatory marker of the 62 participants receiving either ginger and iron treatment or oral iron therapy only. Both groups had an insignificant difference in mean MDA and TNF-*α* levels at baseline. After 30 days, both oxidative stress (MDA: −18.62%, *p* < 0.001) and inflammatory markers (TNF-*α*: −20.11%, *p* < 0.05) were significantly reduced in the oral iron plus ginger group. Conversely, in the control group taking only oral iron therapy, there was a significant decrease in post-trial MDA levels (−9.67%, *p* < 0.05) and a non-significant increase in TNF-*α* (+3.86%, *p* > 0.05) [140]. The estimated mean difference between groups was not significant in changes in MDA but was significant in TNF-*α* (*p* < 0.05). It can be inferred from these results that, compared to oral iron therapy alone, combining ginger with oral iron therapy can better alleviate oxidative stress and reduce inflammation in patients with IDA while correcting their anaemic condition.
