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  • Reply to: Artemisia afra, pancreas, diabetes   4 weeks 4 hours ago

     

    Kansango C, Gisenya P, Lutgen P.

     

    The exhaustive analysis of Artemisia annua plants by F.F. Ferreira in 2009 has shown a result which is often neglected : stems contain 20x more starch than leaves. Leaves and inflorescences had the highest percentage of protein, crude fat and in vitro digestible fractions, but the lowest levels of detergent fibres.

          E Brisibe, Umoren E. Umoren, F Brisibe, P Magalhäes, J. Ferreira, Nutritional characterisation and antioxidant capacity of different tissues of Artemisia annua. Food Chemistry. Volume 115, Issue 4, 2009, 1240-1246, doi.org/10.1016/j.foodchem.2009.01.033.

    A study from Korea also found that the polysaccharide content is higher in stems than in leaves for a local Artemisia plant.

           Byung Yong Ahn and Mun Yhung Jung. Antioxidative and Protective Activi ty of Polysaccharide Extract fromArtemisia iwayomogi Kitamura Stems on UVB-Damaged Mouse Epidermis J. Appl. Biol. Chem. 54(3), 184-189 (2011)

    It is difficult to find a good explanation on the difference between detergent, physically inaccessible, non-digestible  and resistant starch. But it is easy to find many papers which describe the high concentrations of starch in the stems of plants, for example weath (Triticum aestivum).

          Graham N. Scofield, Sari A. Ruuska, Naohiro Aoki, David C. Lewis, Linda M. Tabe, Colin L. D. Jenkins, Starch storage in the stems of wheat plants: localization and temporal changes, Annals of Botany, Volume 103, Issue 6, April 2009, Pages 859–868, https://doi.org/10.1093/aob/mcp010

    Grasses make up the vast majority of agricultural commodities. How these grasses capture, transport, and store carbohydrates underpins many aspects of crop productivity. Sink–source dynamics within the plant direct how much, where, and when carbohydrates are allocated, as well as determine the harvestable tissue. Grasses have the ability to buffer this sink–source interaction by transiently storing carbohydrates in stem tissue when production from the source is greater than whole-plant demand. Domesticated grasses such as sugarcane and sweet sorghum have undergone selection for high accumulation of stem carbohydrates.

          Thomas L. Slewinski, Non-structural carbohydrate partitioning in grass stems: a target to increase yield stability, stress tolerance, and biofuel production, Journal of Experimental Botany, Volume 63, 13, 2012, 4647–4670, https://doi.org/10.1093/jxb/ers124

    It is well established that part of starch is resistant to human amylases and escapes undigested to large bowel. This fraction of starch is resistant starch.  Dietary fibers, polysaccharides and resistant starch have a beneficial effect on digestion and contribute to bowel health. Inulin is a good example of a non-digestible polysaccharide. These are often called prebiotics.

          Šubarić, Drago, Ačkar, D urđica; Babić, Jurislav; Miličević, Borislav. Starch for health. Medicinski Glasnik . Feb2012, Vol. 9 Issue 1, p17-22. 6p.

    The worldwide increase in diabetes is probably related to lifestyle changes. In developed countries the intake of resistant starch is low (3 to 6 g/day in the EU, 3 to 8 g/day in the USA) compared to 30 to 40 gr/day in developing countries.

    Type 2 diabetes mellitus, a common metabolic and endocrine disorder worldwide, causes severe health and economic problems. At present, pharmacotherapy involving synthetic diabetic agents is clinically administered for diabetic therapy, which has certain side effects. Fortunately, various natural polysaccharides (commonly called fibers) have anti-diabetic activity and use of these polysaccharides as adjuncts to conventional therapies is increasing in developing countries. A literature search was conducted by a Chinese team to obtain relevant information of anti-diabetic polysaccharides from electronic databases. In total, 114 types of polysaccharides from 78 kinds of natural sources, namely plants, fungi, algae, animals, and bacteria, have shown anti-diabetic properties. In vivo and in vitro experiments have shown that administering these polysaccharides has hypoglycaemic effects and alleviates β-cell dysfunction in addition to eliciting other anti-diabetic activities which are equally efficient and even more efficient than those of synthetic diabetic agents.

            Wu J, Shi S, Wang H, Wang S. Mechanisms underlying the effect of polysaccharides in the treatment of type 2 diabetes: A review. Carbohydr Polym. 2016 Jun 25;144:474-94. doi: 10.1016/j.carbpol.2016.02.040. Epub 2016 Feb 18.                                        

             Liu FJ, Liu XY, Ma Y, Wang WL, Li JY. Research progress and analysis on mechanism of polysaccharides against type 2 diabetes mellitus]. Zhongguo Zhong, Yao Za Zhi. 2021 Feb;46(3):552-559. doi: 10.19540/j.cnki.cjcmm.20201125.601. PMID: 33645019.

              Xue Lin. Polysaccharides reducing the decomposition of starch and the absorption of blood sugar. International Conference on Frontiers of Biological Sciences and Engineering (FBSE 2018). AIP Conf. Proc. 2058, 020010-1–020010-8; https://doi.org/10.1063/1.5085523

             Ekaterina Antonceva and Mark Shamtsyan. Antidiabetical and hypoglycemic action of mushroom polysaccharides. E3S Web of Conf., 215 (2020) 05001, doi.org/10.1051/e3sconf/202021505001

            Teti Estiasih, Donny Umaro, Harijonp. Hypoglycemic effect of crude water soluble polysaccharide extracted from tubers of purple and yellow water yam (Dioscorea alata L.) on alloxan-induced hyperglycemia Wistar rats, Progress in Nutrition 2018; Vol. 20, Supplement 1: 59-67 DOI: 10.23751/pn.v20i1-S.5322

    One of the many functional benefits of dietary fiber when present in the human diet is its ability to reduce the rate of absorption of glucose after consumption of high glycaemic foods, leading to a blunted glucose response curve and less demand for insulin. A literature review suggests that those consuming the highest amounts of dietary fiber, especially cereal fiber, may benefit from a reduction in the incidence of developing type 2 diabetes.

              Marc P. McRae, MSc, Dietary Fiber Intake and Type 2 Diabetes Mellitus: An Umbrella Review of Meta-analyses. J Chiropr Med 2018;17:44-53

    Addition of soluble fiber to the diet can slow absorption of refined carbohydrates, i.e., lower the glycemic index of foods and overcome or at least ameliorate many of the adverse reactions resulting from increased refined carbohydrate ingestion.

           Preuss HG. Bean amylase inhibitor and other carbohydrate absorption blockers: effects on diabesity and general health. J Am Coll Nutr. 2009 Jun;28(3):266-76. doi: 10.1080/07315724.2009.10719781. PMID: 20150600.

    A Japanese study examined the inhibitory effect of a single ingestion of bread containing resistant starch on the postprandial increase in blood glucose. Bread not containing resistant starch (placebo) was used as the control. Postprandial increases in both blood glucose and blood insulin were significantly inhibited in subjects in the test group who took the test food in comparison with the placebo group.

            Yamada Y, Hosoya S, Nishimura S, Tanaka T, Kajimoto Y, Nishimura A, Kajimoto O. Effect of bread containing resistant starch on postprandial blood glucose levels in humans. Biosci Biotechnol Biochem. 2005 Mar;69(3):559-66. doi: 10.1271/bbb.69.559

             Al-Tamimi EK, Seib PA, Snyder BS, Haub MD. Consumption of Cross-Linked Resistant Starch (RS4(XL)) on Glucose and Insulin Responses in Humans. J Nutr Metab. 2010:651063. doi: 10.1155/2010/651063.

          Flammang AM, Kendall DM, Baumgartner CJ, Slagle TD, Choe YS. Effect of a viscous fiber bar on postprandial glycemia in subjects with type 2 diabetes. J Am Coll Nutr. 2006 Oct;25(5):409-14. doi: 10.1080/07315724.2006.10719553. PMID: 17031010.

    The polysaccharide inulin is also used in the fight against diabetes

          Dehghan P, Pourghassem Gargari B, Asgharijafarabadi M. Effects of High Performance Inulin in Women with Type 2 Diabetes: A Randomized, Placebo-Controlled Clinical Trial. Health Promot Perspect 2013; 3(1): 55-63

    Inulin is the polysaccharide with the strongest stimulation of NO synthesis.

        Koo HN, Hong SH, Seo HG, Yoo TS, Lee KN, Kim NS, Kim CH, Kim HM. Inulin stimulates NO synthesis via activation of PKC-alpha and protein tyrosine kinase, resulting in the activation of NF-kappaB by IFN-gamma-primed RAW 264.7 cells. J Nutr Biochem. 2003 Oct;14(10):598-605.

    The content of inulin is higher in stems than in leaves: 0.84 g/100gr vs 0.46 (personal communication Pamela Weathers 2014).

    The Artemisia afra plant is rich in luteolin. This flavone delays the digestion of starch and is an inhibitor of α-amylase. Thus, luteolin has the potential to prevent and control diabetes by being added into starch-based food to delay starch digestion.

       Yiling Zhao, Ming Wang, Jinsheng Zhang,  The mechanism of delaying starch digestion by luteolin.  Food & Function. 2021,12, 11862-11871

    Compared with the drug acarbose which is used to treat type 2 diabetes starch extract obtained from tubers also has a significant α-amylase inhibitory effect.       

          Chinedum Ogbonnaya Eleazu, Abagha Sampson Saidu Sani, Starch digestibility, polyphenol contents and in vitro alpha amylase inhibitory properties of two varieties of cocoyam (Colocassia esculenta and Xanthosoma mafafa) as affected by cooking. Journal of Food Measurement and Characterization 2018 12(2):1047-1053. DOI:10.1007/s11694-018-9720-9

    Artemisia afra also contains thujone, which is absent in Artemisia annua. In a murine trial, rats were divided into four groups (non-diabetic control, diabetic streptotocin induced control, non-diabetic with thujone, and diabetic with thujone) and were orally given either thujone (60mg/kg) or vehicle for 4 weeks. After thujone administration, plasma glucose level and glucose tolerance, as estimated were improved.

        Hakam Hasan Alkhateeb, Mohammed Al-Duais. Plasma glucose-lowering effect of thujone and its molecular mechanisms of action in streptozotocin-induced diabetic rats.  April 2018 Pharmacologyonline 1:196-208

    The use of thujone, a monoterpene ketone often present in sage Salvia officinalis or wormwood Artemisia absinthium, for the treatment of diabetes mellitus was recently suggested in a German study. Evidence was based on the findings obtained in a diabetic rat model.

           Dirk W. Lachenmeier, Stephan G. Walch. The choice of thujone as drug for diabetes Natural Product Research, Volume 25, 2011,  1890-1892. doi.org/10.1080/14786419.2011.622279

    Artemisia sp., especially A. annua and A. afra, have been used for centuries to treat many ailments. While in studies against malaria artemisinin is the main therapeutically active component, emerging evidence demonstrates that the other phytochemicals in this genus are also therapeutically active. Synergy between these ingredients probably plays a major role. This is what the French call the « totum » effect of a plant.

          Gruessner BM, Cornet-Vernet L, Desrosiers MR, Lutgen P, Towler MJ, Weathers PJ. It is not just artemisinin: Artemisia sp. for treating diseases including malaria and schistosomiasis. Phytochem Rev. 2019;18(6):1509-1527. doi:10.1007/s11101-019-09645-9

    CYP3A4 inhibition by Artemisia plants may play a major role. In a pioneering study in 2010, the University of Louvain had studied the anti-inflammatory effect and modulation of cytochrome P450 activities by Artemisia annua tea infusions in human intestinal Caco-2 cells

           Melillo de Magalhães, Yves-Jacques Schneider. Anti-inflammatory effect and modulation of cytochrome P450 activities by Artemisia annua tea infusions in human intestinal Caco-2 cellFood Chemistry 134(2):864-71 · September 2012

    This was confirmed at the VUB in Brussels. CYP3A4 inhibition was surprisingly high for all Artemisia samples, up to 6 times higher than for ketoconazole (0.11 µg/mL), the well known CYP3A4 inhibitor, or for diluted grapefruit juice.

         Lazaridi Kristina. Invloed van de chemische samenstelling van Artemisia annua op CYP3A4-activiteit en antioxidant vermogen. Masterproef VUB, 2014

    New developments in polysaccharide chemistry are taking place in clinical drug delivery systems. The clinical efficacy of drugs is often limited by a number of obstacles, including unfavorable solubility, loss of bioactive structure prior to reaching the disease lesion site, inadequate cellular uptake.

         Tianxin Miao, Junqing Wang, Yun Zeng, Gang Liu, Xiaoyuan Chen Polysaccharide-Based Controlled Release Systems for Therapeutics Delivery and Tissue. Advanced Science 08 January 2018. https://doi.org/10.1002/advs.201700513

    Conclusion

    All this highlights the vital importance to include in aqueous Artemisia infusions, not only the leaves, but also the stems. Decoction might also be recommended to obtain higher extraction yields from the ligneous stems.

  • Reply to: Artemisia afra, pancreas, diabetes   1 month 6 days ago

    Constant Kansango, Pascal Gisenya and Pierre Lutgen

     

    There is abundant evidence for impairment of the vascular nitric oxide (NO) system in diabetes mellitus. Already in 2003 a scientific paper quoted 28 studies. The contribution of hyperglycemia may be one of the best studied and most reversible causes of vascular NO system dysfunction in diabetes.

        Tuck, Michael L Nitric oxide in diabetes mellitus, Journal of Hypertension: June 2003 - Volume 21 - Issue 6 - p 1081-1083

    NO, nitricoxide, is a significant component of the insulin-signaling cascade executing microvascular vasodilation stimulated by local NO production from the vascular endothelium. Vasodilation has the potential to decrease systemic blood pressur. This may serve to prevent cardiovascular disease, and insulin resistance and vice versa: that insulin resistance, such as that observed in diabetes, the metabolic syndrome, and hypertension, impairs NO-dependent vasodilation. This is a vicious cycle : hypertension, diabetes, and cardiovascular disease cosegregate.

                Hans Erik Bøtker and Niels Møller. The Continuing Story of Nitric Oxide, Diabetes, and Cardiovascular Disease. Diabetes 2013 Aug; 62(8): 2645-2647. https://doi.org/10.2337/db13-0542

    High blood pressure is reported in over two-thirds of patients with type 2 diabetes, and its development coincides with the development of hyperglycaemia. Many pathophysiological mechanisms underlie this association. Of these mechanisms, insulin resistance in the nitric-oxide pathway;

               Ferrannini E, Cushman WC. Diabetes and hypertension: the bad companions. Lancet. 2012 Aug 11;380(9841):601-10. doi: 10.1016/S0140-6736(12)60987-8. PMID: 22883509.

    Reduced NO availability may not only be of relevance to the development of atherosclerotic complications in diabetes but may also interfere with insulin-mediated postprandial glucose disposal and possibly contribute to the development of insulin resistance. Understanding of the complex metabolic disturbances interacting with the NO system may provide us with further therapeutic options to decrease cardiovascular morbidity and mortality in diabetes mellitus..

             Honing ML, Morrison PJ, Banga JD, Stroes ES, Rabelink TJ. Nitric oxide availability in diabetes mellitus. Diabetes Metab Rev. 1998 Sep;14(3):241-9. doi: 10.1002/(sici)1099-0895(1998090)14:3<241::aid-dmr216>3.0.co;2-r. PMID: 9816472.

    Compared with normal subjects, NO synthesis is lower in the elderly and in people with type 2 diabetes. It is generally increased after insulin stimulation

    Our interest rests for the moment on the surprising effect of Artemisia afra infusions on diabetes.

              Pierre Lutgen. Artemisa afra, pancreas, diabetes. www.malariaworld Dec 16 2021.

    Artemisia afra is rich in luteolin. A paper from Virginia- USA shows that luteolin can directly act on vascular endothelial cells, leading to nitric oxide production and subsequent vascular relaxation and hypotensive effects

             Hongwei Si.The flavonoid luteolin induces nitric oxide production and arterial relaxation. Eur J Nutr. 2014 February ; 53(1): 269–275. doi:10.1007/s00394-013-0525-

    A molecule which has been studied extensively for its antidiabetic properties is arginine. 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. 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. The most effective stimulus was by arginine given alone. In 1998 a study from India showed that the action of arginine is related to the production of nitric oxide.

    A recent study from Ukraine has analyzed the amino acid content in some 8 Artemisia plants of this subgenus and found that they are all 5 to 10 times richer in arginine than other herbs or vegetables, with Artemisia annua top-ranking (2g/100g).

              Ochkur O, Kovaleva AM, Amino acids composition  of subgenus Artemisia herbs. Chemistry of Natural Compounds, 2013: 49(3):589-591

    In a clinical study in Italy 144 middle-aged subjects with impaired glucose tolerance and metabolic syndrome were randomized in 2006 to an L-arginine supplementation (6.4 g orally/day) or placebo therapy lasting 18 months. This period was followed by a 90-month follow-up. At the end of the study, the cumulative incidence of diabetes was 40.6% in the argine group and 57.4 in the placebo group. The intervention period was followed by 90-month follow-up. The positive effects were maintained during the 9-year period. Previously, a similar result was achieved only in intensive lifestyle modification after 3 years. This is the first study to demonstrate a « metabolic memory in the prevention of TDM2.

             Monti LD, Galluccio E, Villa V, Fontana B, Spadoni S, Piatti PM. Decreased diabetes risk over 9 year after 18-month oral L-arginine treatment in middle-aged subjects with impaired glucose tolerance and metabolic syndrome (extension evaluation of L-arginine study). Eur J Nutr. 2018 Dec; 57(8):2805-2817. doi: 10.1007/s00394-017-1548-2.

    In a pilot study with 82 volunteers in Lubumbashi, we found that the administration of Artemisia annua and Artemisia afra capsules during 10 days increased the CD4 count by 20%.

             Constant Kansango Tchandema, Pierre Lutgen PhD, In vivo trials on the therapeutic effects of encapsulated Artemisia annua and Artemisia afraGlobal Journal for Research AnalysisVolume-5, Issue-6, June – 2016 pp 228-234 • ISSN No 2277 - 8160        

    The small increase in CD4 cell count in this pilot study might be related to the arginine content in the Artemisia plants. Metabolic activity is intimately linked to T cell fate and function. Naive CD4+T cells activated in L-arginine-supplemented medium showed a slightly delayed onset of proliferation, but once proliferation started, doubling rates were comparable to controls. Metabolomic and proteomic profiling unveil intracellular L-arginine as a crucial regulator of central memory T cells.

    Improved T cell survival is another striking effect induced by elevated intracellular L-arginine levels. L-arginine supplementation significantly increased the survival of activated CD4+and CD8+T cells. This was confirmed by mouse T Cell survival in vivo.

               Geiger R, JC Riekmann, T Wolf., L-Arginine Modulates T Cell Metabolism and Enhances Survival, 167, 829–842, 2016. doi.org/10.1016/j.cell.2016.09.031

    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.

               Nyström T, Ortsäter H, Huang Z, et al. Inorganic nitrite stimulates pancreatic islet blood flow and insulin secretion. Free Radic Biol Med. 2012;53(5):1017–1023.

    Dietary nitrate/nitrite could be a compensatory fuel for a disrupted nitrate/nitrite/NO pathway and related disorders in diabetes.

                 Zahra Bahadoran, Asghar Ghasemi, Parvin Mirmiran, Fereidoun Azizi and Farzad Hadaegh.Beneficial effects of inorganic nitrate/nitrite in type 2 diabetes and its complications Nutrition & Metabolism 2015 12:16 DOI: 10.1186/s12986-015-0013-6

    Medicinal herbs contain on the avarage higher amounts of nitrate than fruits or vegetables: a mean nitrate concentration of 1.240 mg/kg fresh weight versus 336 mg/kg in fruits and vegetables. Nitrate content is much higher in stems and petioles than in leaves.

              Nitrate in vegetables. Scientific Opinion of the Panel on Contaminants in the Food chain. The EFSA Journal (2008) 689, 1-79

    Artemisia plants are rich in polysaccharides and these strongly enhance the production of NO and ROS by macrophages, up to 10fold for some fractions.

               G Xie, I Schepetkin, D Siemsen, MT Quinn. Fractionation and characterization of biologically active polysaccharides from Artemisia tripartita. Phytochemistry, 2008, 69, 1359-1371.

    The polysaccharide with the strongest stimulation of NO synthesis is inulin

              Koo HN, Hong SH, Seo HG, Yoo TS, Lee KN, Kim NS, Kim CH, Kim HM. Inulin stimulates NO synthesis via activation of PKC-alpha and protein tyrosine kinase, resulting in the activation of NF-kappaB by IFN-gamma-primed RAW 264.7 cells. J Nutr Biochem. 2003 Oct;14(10):598-605.

    The plant Artemisia is an accumulator for many minerals: potassium, selenium, nitrate, iron.

             Traore Alassane, Diallo Mouhamadou, Gueye Papa El Hadji Omar, Wague Ahmadou, Lutgen Pierre, Sarr Ousmane and Mboup Souleymane. Characterization of element and mineral content in Artemisia annua and Camellia sinensis leaves by handheld X-ray fluorescence.  African Journal of Biotechnology Vol. 12(26), pp. 4179-4186, 26 June, 2013  

  • Reply to: Homologous P. vivax malarial recurrences are not necessarily relapses   2 months 6 hours ago

    Genetically, this is a clonal parasite (as opposed to meiotic siblings) explanation for the origin of some or many non-reinfection homologous recurrences of P. vivax malaria.

    The explanation does not apply only to short-term recurrences. This is elucidated in reference 2 in the above blog.

  • Reply to: P. vivax Malaria Recurrence and Human Nature   2 months 1 week ago

    Some students are compiling a list of these literature background-deficient (thus non-authoritative) papers. It might be published.

  • Reply to: Do vaccines increase Malaria and Covid ?   2 months 3 weeks ago

    A study published last week in the Lancet describes alarming shortcomings on vaccines and transmission. The SARS-CoV-2 delta variant is highly transmissible and spreading globally, including in populations with high vaccination rates. Fully vaccinated individuals with breakthrough infections have peak viral load similar to unvaccinated cases and can efficiently transmit infection in household settings, including to fully vaccinated contacts.

    Anika Singanayagam, Seran Hakki, Jake Dunning. Community transmission and viral load kinetics of the SARS-CoV-2 delta (B.1.617.2) variant in vaccinated and unvaccinated individuals in the UK: a prospective, longitudinal, cohort study. Lancet Infect Dis 2021, Oct 29 doi.org/10.1016/

    The US CDC had already raised this alarm in August 2021, but nobody was eager to listen. The CDC report said Delta is highly contagious, likely more severe than other variants and breakthrough infections after vaccination may be as transmissible as for unvaccinated cases.