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Dandelion polysaccharide (DP) can potentially reduce iron overload in hepatocellular carcinoma (HCC) by downregulating hepcidin levels and inhibiting the IL-6-activated JAK-STAT signaling pathway.
In the study, researchers focused on clarifying the effects of dandelion polysaccharide (DP) on iron metabolism and the mechanisms underlying these effects. The basis of their study was earlier findings that indicated a correlation between iron overload and the risk of hepatocellular carcinoma (HCC), conditions that their previous studies showed could be managed with DP through causing cell cycle arrest and inhibiting the PI3K/AKT/mTOR pathway. To get their results, researchers used RNA sequencing and western blot testing on hepatoma cells and grafted tumors subjected to DP treatment.
The results of the mentioned testing methods showed that DP could lower the iron burden in hepatoma cells. It was further discovered that DP had the ability influence hepcidin, a significant regulator in iron metabolism, expression levels. Hepcidin was found in higher levels in HCC tumor tissues compared to adjacent non-tumor tissues. But, with DP treatment, expression of hepcidin was downregulated in both hepatoma cells and the liver of the mouse model used. These findings led to the conclusion that the DP was effective in inhibiting the IL-6-activated JAK-STAT signaling pathway.
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The body begins to upregulate iron absorption at a ferritin concentration of less than 50 µg/L, indicating an incipient iron deficiency in young women.
2021 EClinicalMedicine Threshold ferritin and hepcidin concentrations indicating early iron deficiency in young women based on upregulation of iron absorption Galetti V, Stoffel NU, Sieber C, Zeder C, Moretti D, Zimmermann MB
Cohort Study Ferritin Hepcidin Iron Absorption
In the methodology, this study utilizes a pooled analysis of stable iron isotope studies conducted between 2006 and 2019 on healthy women aged 18 to 50. These studies quantified iron absorption from meals providing physiological quantities of iron. A mathematical model known as generalized additive modeling was employed to ascertain the relationships between iron absorption, ferritin, and a molecule called hepcidin. By estimating the first derivatives of the trend created by the model, inflection points (or thresholds) in these relationships were established.
The results revealed that hepcidin increased in a linear fashion parallel to ferritin. Iron absorption increased when hepcidin reached a threshold value and when a threshold ferritin value was detected, beyond which iron absorption remained stable. An auxiliary validation within the results found that a hepcidin of approximately 3 nmol/l corresponded to a ferritin level of approximately 51 µg/l. These findings collectively suggest that if the body's ferritin concentration falls below 50 µg/L—corresponding to a hepcidin level of less than 3 nmol/l—the body will respond by absorbing more iron from the diet, signaling an emerging iron deficiency.
Black pepper and its major component, piperine, can effectively regulate anemia of inflammation by reducing the overexpression of hepcidin, a hormone that controls iron levels.
2021 Free Radical Biology and Medicine Black pepper prevents anemia of inflammation by inhibiting hepcidin over-expression through BMP6-SMAD1/ IL6-STAT3 signaling pathway Banerjee S, Katiyar P, Kumar L, Kumar V, Saini SS, Krishnan V, et al.
Experimental Study Anaemia Black Pepper Hepcidin
The study involves a two-tier investigation, first in vitro, and then in vivo. In the laboratory, different black pepper extracts were interacted with a human liver cell line known as HepG2, and the one derived from methanol (BPME) showed the most promising result because it reduced the transcription of the hepcidin gene significantly. In addition to BPME, piperine was proven to almost entirely suppress hepcidin protein expression at specific concentrations.
In the subsequent in vivo experimentation, live mice were artificially induced with an elevated level of hepcidin through oil of turpentine injections. Then they were administered with BPME and piperine, the effects of which significantly reduced the enhanced hepcidin expression. The molecular interaction studies further suggest that piperine directly binds with SMAD1 and STAT3 proteins, the critical factors behind the overexpression of hepcidin.
The study found a demonstrable downregulation in hepcidin expression with the use of both the methanol extract of black pepper and the bioactive alkaloid piperine. These substances also interacted with some proteins to lower the overexpression of hepcidin initiated by inflammation. Additionally, there was a noticeable increase in iron bioavailability in the liver of treated test animals, pointing to the potential of these compounds to rectify anemia of inflammation. The findings posited black pepper as a possible therapeutic option for managing this anemic condition.
Danggui Buxue Tang (DBT) supplement helps reduce running times and control exercise-induced hepcidin levels, boosting iron levels and speeding up iron balance during recovery.
2018 Nutrients Repressed Exercise-Induced Hepcidin Levels after Danggui Buxue Tang Supplementation in Male Recreational Runners Chang CW, Chen CY, Yen CC, Wu YT, Hsu MC
Experimental Study Dang Gui Bu Xue Tang Exercise Hepcidin
The study consisted of 36 recreationally active males who were arbitrarily assigned to receive either DBT or a placebo for 11 days, in groups following their aerobic capacities. On the eighth day, they were subjected to a 13-km run at maximum effort. Blood and urine samples were collected and analysed both before the treatment (Pre-Tre), immediately after the run (Post-Ex), and 24 hours as well as 72 hours after the run.
The findings showed that those supplemented with DBT significantly reduced their running times by 14.0% (12.3 minutes) in comparison to the placebo group. A notable difference was observed in serum hepcidin and iron levels. The DBT supplement suppressed the hepcidin levels after the run and 24 hours into recovery, leading to a significant increase in iron levels both immediately after the run and 72 hours post run. Despite this, DBT showed no significant anti-inflammatory or preventative effects against haemolysis.
Higher iron levels after menopause appear to be risk factors for osteoporosis, and hormone hepcidin, which regulates iron, might be a potential therapeutic target for this condition.
2018 Journal of Molecular Endocrinology Hepcidin is an endogenous protective factor for osteoporosis by reducing iron levels Zhang P, Wang S, Wang L, Shan BC, Zhang H, Yang F, et al.
Experimental Study Hepcidin Osteoporosis
In the study, researchers applied genetic modification techniques to alter the production of endogenous hormone hepcidin in a mouse model, aiming to affect the iron levels in the body. Making use of both knockout and overexpression murine models, researchers focused specifically on the correlational aspects of hepcidin levels and bone loss. Further to that, the impact of iron overload on reactive oxygen species (ROS) activity was tested, as well as its effect on the slowed down work of primary osteoblasts.
On the other hand, the effect of iron depletion was observed, presented as the reversed phenomenon through inhibiting the functions of the primary osteoclasts. Through this work, researchers investigated how iron accumulation interferes with general bone health in postmenopausal conditions. They further verified the 'Huang's hypothesis' - proposed in previous studies - about the potential therapeutic value of hepcidin for postmenopausal osteoporosis.
Angelica Sinensis polysaccharide treatment has been found to effectively alleviate anaemia of chronic disease in rats by inhibiting inflammatory pathways and mobilizing iron.
2017 Oxidative Medicine and Cellular Longevity Acidic Polysaccharide from Angelica sinensis Reverses Anemia of Chronic Disease Involving the Suppression of Inflammatory Hepcidin and NF-κB Activation Wang K, Wu J, Cheng F, Huang X, Zeng F, Zhang Y
Experimental Study Anaemia Dang Gui Hepcidin
The study utilized both HepG2 cells and rats suffering from Anemia of Chronic Disease (ACD) to assess the therapeutic efficacy of Polysaccharide. The cells and rats were administered the Polysaccharide, and the researchers observed its impact on two inflammatory pathways: the IL-6/STAT3 and BMP/SMAD.
The Polysaccharide administration showed significant effects, inhibiting inflammatory hepcidin in both the cell sample and the rat population. Furthermore, in the rats, the introduction of the polysaccharide triggered an increase in ferroportin expression, which enabled iron to be transported from the liver and spleen, leading to increased serum iron levels. This also led to an elevation of serum EPO and a general relief from the anemia symptoms. Additionally, the treatment inhibited the NF-B p65 activation via the IB kinases-IB pathway, leading to a reduction in interleukin-6 and TNF- secretion - both of which are known to inhibit erythropoiesis. Hence, the study provides evidence for the potential use of polysaccharide as a treatment option for anemia of chronic disease.
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