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Polyphenols as solution to the problem of sickle cell anemia

POLYPHENOLS AS SOLUTION TO THE PROBLEM OF SICKLE CELL ANEMIA

In a journal publication, “The effect of Antioxidants on the Properties of Red Blood Cells[1] “, https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6700761/ Sickle Cell Anaemia is stated to affect millions of people worldwide, especially in sub-Saharan Africa and India (Piel et al., 2013), where it results in considerable morbidity and mortality, as well as economic impact Blood transfusion, antibiotic therapy, and pneumococcal vaccination all ameliorate complications; however, these apart, treatment remains largely supportive. While hydroxyurea has emerged as a specific licensed therapy (Platt et al., 1984; Charache et al., 1987), it is not without problems, and new effective therapies are keenly sought (Rees, 2011; Gibson et al., 2015).

An important feature of SCA is oxidative stress (Hebbel et al., 1982; Rice-Evans et al., 1986). Increased levels of reactive oxygen species are released from activated endothelial and white cells, from ischemia-reperfusion injury and from within RBCs, as HbS is more unstable than HbA breaking down into hemichromes and free iron (Hebbel et al., 1982, 1988; Rice-Evans et al., 1986; Aslan et al., 2000; Banerjee and Kuypers, 2004). It is also likely that antioxidant provision is reduced, both within RBCs and without circulating in plasma (Silva et al., 2013). For example, sickle red cells have a lower redox ratio with reduced levels of reduced nicotinamide adenine dinucleotide (Zerez et al., 1988; Al-Ali, 2002). Oxidant stress can result in lipid and protein damage with important pathogenic sequelae. It may also increase the solute permeability of RBCs, which is in itself problematical. It is not surprising, therefore, that the possible beneficial roles of antioxidant provision have received considerable attention.

Polyphenols are abundant micronutrients in our diet, and evidence for their role in the prevention of degenerative diseases such as cancer and cardiovascular diseases is emerging. The health effects of polyphenols depend on the amount consumed and on their bioavailability.

Sorghum bicolor leaf sheath (Jobelyn) contains 106.86 mg/g. ( 10,686 mg/100g) of phenolics. With the exception of clove and dried peppermint (which are seasonings), it the richest polyphenols and phenolic plant in the whole world[2]. Pérez-Jiménez, J., Neveu, V., Vos, F. et al. Identification of the 100 richest dietary sources of polyphenols: an application of the Phenol-Explorer database. Eur J Clin Nutr 64, S112–S120 (2010).

In folk medicine, it was being used by the ancient people to solve all health problems including sickle cell anaemia, cardiovascular problems, anaemia, arthritis and even cancer. The claims by ancient people has now been scientifically validated that polyphenols and phenolic acids are responsible for antioxidant, anti-inflammatory, immune modulating and chemopreventive activities.

Sorghum bicolor leaf sheaths (Jobelyn) is described in the National Cancer Institute dictionary [3] as: An herbal-based nutritional supplement containing the leaf sheaths of the plant Sorghum bicolor, with potential antioxidant, anti-inflammatory, chemopreventive and immunomodulating activities. In addition, due to the strong antioxidant nature of the phytochemicals, these compounds are able to scavenge free radicals and prevent tissue damage.

It was reported that after 4 weeks of taking the Jobelyn, there were reduction in white blood cells (p= 0.10) and platelet counts (p= 0.03).There were significant reductions in the mean red cell haemoglobin (p=0.0004), mean cell haemoglobin concentration (p=0.0001) while the reduction in mean cell volume and haematocrit changes were minimal (p=0.3and 0.5 respectively). The reduction in leukocytes and platelets counts suggests an anti-inflammatory effect of the extract which may have a clinically positive effect. The significantly reduced cellular haemoglobin concentration and minimal changes in haematocrit demonstrate that the extract will not unduly increase the red cell haemoglobin concentration which may promote sickling.

The article concluded that the reduction in leukocytes and platelets counts suggests an inflammatory effect of Jobelyn which may have a clinically positive effect. The significantly reduced cellular hemoglobin concentration and minimal changes in hematocrit suggests that Jobelyn would not unduly increase the red cell haemoglobin concentration which a factor that may precipitate sickling. The antioxidant effect may also be beneficial in the reduction of the sickling phenomenon because increased oxidative stress has been shown to contribute damage to red cell membrane and hence permanent sickling.

The authors also remarked that there was reduction in the blood cellular counts in the two groups in the trial at the end of the study and that the values were within the normal range and this suggests that Jobelyn is not toxic to the bone marrow and would not increase the red cell mass which my make the blood viscous as increase in blood viscosity will promote blood sequestration in tissues. An increase in red cell mass beyond an optimal level would therefore be a disadvantage in sickle cell anemia.

The phytochemical in sorghum bicolor leaf sheaths have very potent anti-inflammatory and antioxidant effects in tissues. They are therefore expected to moderate organ damage, pain, and sequestration crisis in sickle cell anaemia. There were reduction in white cell though not significant but may be clinically important and a significant reduction in platelet counts. The effect is probably a demonstration of the antioxidant and anti-inflammatory effects. Jobelyn may therefore contribute to reduction of organ sequestration, painful crisis and progressive organ damage in sickle cell disease.

Currently, another clinical study is ongoing at the LASUTH . According to the researchers, Nigeria has a high burden of sickle cell disease and in this condition, antioxidant stress due to excessive production of reactive oxygen species (ROS), is cause of complex pathophysiology of sickle cell anaemia and that if Jobelyn is found to reduce oxidative stress levels, it can be a useful adjunct to Sickle Cell Anaemia management to control tissue damage and eventual life-threatening and disabling chronic complications so that school aged children may better survive and maximize their development potential through their learning years. Recruitment of children between 6 years and 14 years is currently taking place.

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