The world's scientific and social network for malaria professionals
Subscribe to free Newsletter | 10087 malaria professionals are enjoying the free benefits of MalariaWorld today

Malaria, diabetes and arginine

December 12, 2015 - 09:26 -- Pierre Lutgen

Diabetes burden is rising sharply in the African Region according to Dr Matshidiso Moeti, the WHO Regional Director for Africa. Reports of type 2 diabetes in children – previously rare – is a growing concern. In some countries, children and adolescents account for almost half of all newly diagnosed cases of type 2 diabetes. Diabetes is a leading cause of blindness, amputation, kidney failure and heart disease.

An effect which is less known and studied is the impact on malaria. Malaria parasites are dependent on glucose as a nutrient source. As Plasmodium has no capacity to store energy in the form of glycogen they rely entirely on an exogenous supply of glucose. The infected erythrocyte exhibits a substantial increase in its permeability to low molecular weight sugar. The metabolism of the parasite utilizes up to 75 times more glucose than uninfected erythrocytes. Glucose is vital for Plasmodium. An in vitro study (H Humeida et al., J of Diabetology, October 2011, 3:6) has shown that growth and proliferation is impaired below 5.5 mM in plasma.

A case–control study of 1,466 urban adults in Ghana (Ina Danquah et al., Emerg Infect Dis. 2010 Oct; 16(10): 1601–1604) found that patients with type 2 diabetes mellitus had a 46% increased risk for infection with Plasmodium falciparum. A decade ago, type 2 diabetes mellitus prevalence in urban Ghana was 6.3%. By 2030, ≈20 million affected persons may live in sub-Saharan Africa

Several medicinal herbs are known by the local population to alleviate diabetes. Our partners in Burundi (Ginette Karire, Ingo Vicens, personal communication) report that seeds of Moringa oleifera or their powder are extensively used to this effect. A literature survey easily finds a number of peer reviewed papers confirming the efficiency of Moringa oleifera against diabetes. But most of the research teams work with extracts with organic solvents or distilled water. We are not confident that this is the right approach for several reasons

- Any solvent only extracts a small part of the constituents, either lipophilic or hydrophilic

- Several of our partners (University of Al Quds, University of Louvain) have found that these lyophilized extracts are not stable, for any possible reason, oxidation or evaporation for example

- For a poor inhabitant of Africa it is virtually impossible to find these solvents, to properly prepare and conserve the extracts.

The only valid approach in our eyes is either hot water infusion or powdered plant material. Nevertheless, it is interesting to have a look at some of these papers, particularly if they are dealing with aqueous infusions. Most of them are very recent.

In Nigeria the antidiabetic activity of an aqueous Moringa oleifera seed infusion in alloxan-induced diabetic rats (AA Rafiu et al., J Biol Sc and Bioconservation, 2015, 7, doi: 10.1515/jbcpp-2014-0126) gave a glucose reduction from 8.70 to 3.64 mmol/L. A strong effect for Moringa seeds was also documented in Egypt (A Al-Malki et al., Biomed Res Internat. 2015 Article ID 381040). Moringa seeds can be added to soups, stews, casseroles, and sauces or popped like popcorn. Not only seeds of Moringa oleifera are effective, but also leaves. In the Philippines it was found that for hyperglycemic individuals, the blood sugar levels significantly dropped after 2 hours. A mean drop of 28.15 mg/dl in the blood sugar levels was observed. The results point to the benefit of using Moringa oleifera tea in the management of hyperglycemia. (Michael Ples1 et al., article available from: http://www.ehealthinternational.org) and in Nigeria (AO Adeeyo et al., Diabetologia Croatica, 2013, 42-3, 81-87).

Artemisia plants also have a solid reputation as antidiabetics. All species of this family seem to have a hypoglycemic effect. Treatment of rats with Artemisia annua aqueous extract reduced the serum glucose after 4 weeks from 110 to 70 mg/mL (TB Mojarad et al., Iranian Biomedical Journal, 9:2, 2005, 57-62). In South Africa Artemisia afra is extensively used for several diseases including diabetes (IA Issa et al., Evidence based Complement and Alternat Med. 2015 Article ID 752486) . Methanol extracts of A. absinthium have a strong hypoglycemic and hepatoprotective activity (BJ Goud, Int J Adv Pharmac Res., 2:7, 2011). For A. herba alba the ethanol-water extract produced stronger hypoglycemic effect than the hexane extract (NE Awad et al., J Appl Pharmac Sc. 02:03, 2012, 30-39). A. sieberi has been studied for a similar effect in Iran. Hypoglycemic properties of some preparations and compounds from Artemisia ludoviciana have been studied in Mexico. A. ludoviciana preparations showed hypoglycemic and antihyperglycemic effects, which could explain its effectiveness for treating diabetes (Anaya-Eugenio GD1Ethnopharmacol. 2014 Aug 8;416-25. pii:S0378-8741(14)00420-6. doi:10.1016/j.jep.2014). In Algeria phytotherapy with Artemisia herba alba aqueous infusions against diabetes is common and is documented in several papers (Allali H., et al., Asian Journal of Chemistry, 2008, 20, 2701-2710), (A Boudjelal et al., Planta Medica, 2015, 81, 696-704). Artemisia judaica extracts have even been patented as antidiabetics (US 6350478 B1, 2002) Other herbs which are used as antidiabetics are thyme, rosemary and salvia. Cod liver oil rich in arginine is a well known antidiabetic. Mature coconut water exhibits antidiabetic potential in alloxan induced diabetic rats. (Preetha PP, J Basic Clin Physiol Pharmacol. 2015 Nov).

IS ARGININE THE COMMON ANTIDIABETIC MOLECULE IN ALL THESE PLANTS?

Experiments conducted by researchers from the University of Copenhagen show that the amino acid arginine – found in a wide variety of foods such as salmon, eggs and nuts – greatly improves the body’s ability to metabolize glucose. Arginine stimulates a hormone linked to the treatment of type 2 diabetes, and works just as well as several established drugs on the market. The research findings were recently published in the American scientific journal Endocrinology under the heading Oral l-arginine Stimulates GLP-1 Secretion to Improve Glucose Tolerance in Male Mice. In fact, already in 1966 the University of Michigan had found that the intravenous administration of amino-acids to healthy subjects, either as mixtures or individually, stimulated the release of insulin (JC Floyd et al., J Clic Investig. 1966, 45 1487-1501). The most effective stimulus was by arginine given alone. In 1998 a study from India (IK Mohan et al, Free Radical Biology & medicine, 1998, 7, 757-765) showed that the action of arginine is related to the production of nitric oxide. The finding that coconut water was antidiabetic (Preetha op.cit.) also clearly indicated that L-arginine is a major factor responsible for the antidiabetic efficiency potential and is mediated through the L-arginine-nitric oxide pathway ARGININE

CONTENT IN VARIOUS PLANTS

If arginine is an important factor in hyperglycemic control, it is obvious that Moringa seeds should have such a strong effect. They contain an astronomic amount of arginine: 8.06 g/100g (8.06%). It is thus understandable that Moringa leaves also have an effect. They contain 1.88 g/100 g (CJ Okereke et al., 2013, 4, 34-38) Most nuts are very rich in arginine: 3 g/100 g on the average and are known for their antidiabetic effect. Amino-acids in Artemisia annua have barely been studied. The analytical data published by EA Brisibe and J Ferreira date back to 2009 (Food Chemistry, 2009, 115, 1240-1246). All Artemisia plants are rich in arginin. A recent study from Ukraine (O Ochkur et al., Pharm Innovat J. 2013, 2, 64-67) has analyzed the amino acid content in some 8 plants of this subgenus and found that they are all 5 to 10 times richer in arginine than other herbs or vegetables, with A annua top-ranking (2 g/100g). Very interesting is a document from Libya concerning 3 medicinal herbs with antidiabetic properties: Rosemary, Salvia and Thyme. For these plants the authors find high concentrations of arginine in stems but none in leaves (H Idres Hasan et al., World J of Chemistry, 2014 9, 15-19).

Based on many anecdotic health effects concerning twigs and stems of Artemisia annua, it is likely that they contain more arginine than leaves. This needs to be investigated.

Comments

Submitted by Marc Vanacker (not verified) on

Lifestyle strategies including diets rich in nitrite and nitrate along with moderate physical exercise, which promotes NO production, may be the best approach for management of diabetes through restoration of NO homeostasis and glucose transporter 4 (GLUT4) function (M Gilchrist et al., BMJ 2010 PubMed ID 20880918). The plasma concentration of NO is significantly lower in both hypertensive patients and diabetic patients (SG Ayub et al., JCDR, 2011, 2 172-176)

Other authors (H.Jiang, AC Torregrossa et al., Free Radic Biol Med 2014, Feb;67:51-57) confirm these findings: NO-mediated nitrosation of GLUT4 by nitrite or other nitrosating agents is necessary and sufficient for GLUT4 translocation in target tissue. Recent evidence suggests that the supposedly inert anions nitrate and nitrite are metabolized in blood and tissues to form nitric oxide NO and other bioactive nitrogen oxides. These stimulate pancreatic Langerhans islet function and subsequent insulin formation in vivo (T Nystöm et al., Free Radic Biol Med 2012, 53-5 1017-23). It seems that dietary nitrate/nitrite could be a compensatory fuel for a disrupted nitrate/nitrite/NO pathway and related disorders in diabetes (Z Bahadoran et al., Nutrition & Metabolism, 2015, 12:16).

A British systematic review and meta-analysis (P Carter et al., BMJ 2010;341:c4229 doi:10.1136/bmj.c4229) demonstrated that a diet rich in green, leafy vegetables, but not fruit and other vegetables may confer protection against the risk of developing type 2 diabetes mellitus. The green leafy vegetables described (eg spinach, lettuce) differ from fruits and other vegetables in one important way: all have a high nitrate and/or arginine content.
This is definitely the case for some medicinal herbs like Artemisia annua or Artemisia maritima which are very rich in nitrates and arginine.

(This comment is largely based on information received from Philippe Pavard “La France Agricole”)