The world's scientific and social network for malaria professionals
Subscribe to free Newsletter | 11148 malaria professionals are enjoying the free benefits of MalariaWorld today

Artemisia afra, pancreas, diabetes

December 16, 2021 - 17:00 -- Pierre Lutgen

A few years ago, whilst running the clinical trials against malaria and bilharzia with Artemisia plants in Maniema, RDCongo, Dr. Jerome Munyangi noticed that these plants had cured or alleviated the diabetes of several patients.

     Munyangi J, Idumbo M, Mupenda B, Lutgen P. Five case reports on treatment of diabetes by Artemisia annua and Artemisia afra herbal tea. Pharm Pharmacol. Int J. 2020; 8(2):79‒85. DOI: 10.15406/ppij.2020.08.00283

This finding was recently confirmed by a case study in Burundi (see annex 1).

In the PPIJ paper of 2020 we had tried to explain the antidiabetic effect by several molecules present in Artemisia plants : arachidonic acid, proanthocyanidins, arginine, chlorogenic acid, polysaccharides, pentacyclic triterpenes and saponins. We had mostly based the efficiency on hepatic effects.

In this paper we also bluntly stated that flavonoids and essential oils only have a minor impact and that their role is controversial. It is difficult to find scientific papers on this subject. Our opinion might also be based on a prejudice. In 2010, we were astonished that an extensive analysis on flavonoids we had made did not detect quercetin or luteolin in Artemisia annua samples from Luxembourg, Cameroun, Brasil

       Dr Cécile Beauve, Mme Stéphanie Dessy, Dr Stéphane Kohnen , Celabor, B-4650 Herve. 29 avril 2010.

But recently a more thorough analysis of the scientific literature, shows that  luteolin and quercetin analogues were indeed not identified  in Artemisia annua , but are well present  in Artemisia afra.

       NQ Liu, R Verpoorte, F van der Kooy. H-NMR identification of metabolites in Artemisia annua and Artemisia afra, Journal of Ethnopharmacology 2010, 128, 230-235

The presence of luteolin in Artemisia afra and its absence in Artemisia annua was confirmed by a recent personal communication from M Fréderich, ULg, Belgium (project ARES «Emptying Plasmodium reservoirs to accelerate malaria elimination in high transmission settings: case study in Cameroon »).

 

FIg in attached pdf

 Analyse TLC. On the left Artemisia afra with the yellow luteolin spot.

Artemisia annua does not show a luteolin spot

In our paper we also neglected the essential role of the pancreas in diabetes. This organ is responsible for the secretion of insulin, the hormone that regulates blood glucose levels. Pancreatic β-cells are essential for the generation of insulin.

Again our opinion may have been based on an apprehension. It is often claimed that artemisinin present in Artemisia annua and eventually in other Artemisia plants is the key molecule responsible for many therapeutic properties, but has also some serious side effects. It is well documented that artemisinin inhibits and even causes the apoptosis of β-cells. The consumption of ACTs comcommittant with Artemisia herbal tea could thus enhance the diabetes of the patients.

Artemisia afra is widely used in South Africa to treat hyperglycemia, but the mechanism of action has yet to be elucidated. A study from South Africa explored the effect of oral administration of aqueous leaf extract of Artemisia afra on the pancreas of streptozotocin-induced diabetic rats. It was  found that the extract significantly reduced blood glucose levels, accompanied by an increase in the serum insulin concentration. Diabetes also leads to constriction of the pancreatic beta cells, an indication of damage to the pancreas. Treatment of diabetic rats with Artemisia afra extract  extract enhanced pancreatic weight, and this can be attributed to regeneration of β-cells.

 

Fig in attached pdf

Effects of Oral Administration of Aqueous Extract of A. afra treatment during 14 days

on Blood Glucose, Insulin Concentration, and Pancreas/Body Weight Ratio in Diabetic Rats.

 

      Afolayan AJ, Sunmonu TO. Artemisia afra Jacq. ameliorates oxidative stress in the pancreas of streptozotocin-induced diabetic Wistar rats. Biosci Biotechnol Biochem. 2011;75(11):2083-6. doi: 10.1271/bbb.100792.. PMID: 22056428.

Sangeetha R. Luteolin in the Management of Type 2 Diabetes Mellitus. Curr Res Nutr Food Sci 2019; 7(2). doi : http://dx.doi.org/10.12944/CRNFSJ.7.2.09

      Vinayagam R., Xu B. Antidiabetic properties of  dietary  flavonoids:  a  cellular  mechanism  review. Nutr Metab. 2015; 12:60

In Iraqi folk medicine Artemisia herba alba has been widely used for the treatment of diabetes mellitus. Oral administration of an aqueous extract (0.39 g/kg) of the aerial parts of this plant to normoglycemic and to alloxandiabetic rabbits produced significant hypoglycemic  activity. A subsequent study shows for 2-4 weeks treatment  a significant reduction in blood glucose level, prevents elevation of glycosylated haemoglobin level and possesses a hypoliposis effect, in addition to the protection against body weight loss of diabetic animals.

        Husni A.A.Twaij, A.Al-Badr. Hypoglycemic activity of Artemisia herba alba Journal of Ethnopharmacolog. Volume 24, Issues 2–3, December 1988, Pages 123-126https://doi.org/10.1016/0378-8741(88)90143-2

L al-Shamaony, S M al-Khazraji, H A Twaij. Hypoglycaemic effect of Artemisia herba alba. II. Effect of a valuable extract on some blood parameters in diabetic animals.  J Ethnopharmac. 1994 Jul 22;43(3):167-71.  doi: 10.1016/0378-8741(94)90038-8.

In Egypt it was found that aqueous and alcoholic extracts of Artemisia judaica from the Sinai desert significantly reduced the blood glucose level in experimentally diabetic rats. The authors relate this effect to the flavonoids present in the plant.

Salwa M. Nofal, Sawsan S. Anti-Diabetic Effect of Artemisia judaica Extracts. Research Journal of Medicine and Medical Sciences, 4(1): 42-48, 2009

As a natural flavonoid, low-dose diet supplement of Luteolin ameliorates diet-induced obesity and insulin resistance in mice, suggesting a new therapeutic and interventional approach for these diseases.

         Xu N, Zhang L, Dong J, Zhang X, Chen YG, Bao B, Liu J. Low-dose diet supplement of a natural flavonoid, luteolin, ameliorates diet-induced obesity and insulin resistance in mice. Mol Nutr Food Res. 2014 Jun;58(6):1258-68. doi: 10.1002/mnfr.201300830. 2014 Feb 24. PMID: 24668788.

Findings from a Chinese study demonstrate that luteolin protects mice from pancreatitis by inducing HO-1-mediated anti-inflammatory and antioxidant activities, in association with the suppression of the activation of the NF-κB pathway.

       Xiong J, Wang K, Yuan C, Xing R, Ni J, Hu G, Chen F, Wang X. Luteolin protects mice from severe acute pancreatitis by exerting HO-1-mediated anti-inflammatory and antioxidant effects. Int J Mol Med. 2017 Jan;39(1):113-125. doi: 10.3892/ijmm.2016.2809. Epub 2016 Nov 22. PMID: 27878246; PMCID: PMC5179180.

Although several drugs are targeting pancreatic β-cell to improve their function, there still lack agents to alleviate pancreatic stress conditions. Screening the Traditional Chinese drug library it was discovered that luteolin improves β-cell function. Moreover, luteolin improved insulin secretion ability. Luteolin is thus a promising agent against pancreatic dysfunction.

       Wu W, He S, Shen Y, Zhang J, Wan Y, Tang X, Liu S, Yao X. Natural Product Luteolin Rescues THAP-Induced Pancreatic β-Cell Dysfunction through HNF4α Pathway. Am J Chin Med. 2020;48(6):1435-1454. doi: 10.1142/S0192415X20500706. Epub 2020 Sep 9. PMID: 32907363.

       Deqiu Z, Kang L, Jiali Y, Baolin L, Gaolin L. Luteolin inhibits inflammatory response and improves insulin sensitivity in the endothelium. Biochimie. 2011 Mar;93(3):506-12. doi: 10.1016/j.biochi.2010.11.002. Epub 2010 Nov 21. PMID: 21081149. Ding Y, Shi X, Shuai X, Xu Y, Liu Y, Liang X, Wei D, Su D.

Luteolin also strongly inhibits the enzymes α-glucosidase and the pancreatic α-amylase. Twenty-one naturally occurring flavonoids were tested against α-glucosidase and α-amylase for inhibitory activities. Luteolin was the strongest inhibitor among these flavonoids and stronger against α-glucosidase than α-acarbose, a prescribed antidiabetic drug. Alpha-glucosidase and alpha-amylase are enzymes that catalyze the final step in the digestive process of carbohydrates. The inhibition by luteolin offers the possibility to effectively reduce postprandial hyperglycemia. The effect of postprandial hyperglycemia on diabetes complications is well documented, from cardiovascular diseases to the overproduction of thrombin.

        Jong-Sang KIM, Chong-Suk KWON & Kun Ho SON (2000) Inhibition of Alphaglucosidase and Amylase by Luteolin, a Flavonoid, Bioscience, Biotechnology, and Biochemistry,64:11, 2458-2461, DOI: 10.1271/bbb.64.2458

In another assay luteolin, quercetin and diosmetin were evaluated as inhibitors against the pancreatic α-amylase.

        Yuan E, Liu B, Wei Q, Yang J, Chen L, Li Q. Structure activity relationships of flavonoids as potent alpha-amylase inhibitors. Nat Prod Commun. 2014 Aug;9(8):1173-6. PMID: 25233601.

        Yiling Zhao,  Jinsheng Zhang The mechanism of delaying starch digestion by luteolin Food & Function 2021. https://doi.org/10.1039/D1FO02173G

Luteolin  can  maintain  fasting  blood  glucose  in  normal levels. This helps preventing  the  onset  of  diabetic  cardiomyopathy.

         Zhang Y.,  Xiao-Qin Tian.,  Xiang-Xin  Song.,  Jia-Pu  Ge., Yan-Cheng  Xu.  Luteolin  protect  against  diabetic  cardiomyopathy  in  rat  model  via  regulating  the  AKT/GSK-3β signalling pathway. Biomed Res. 2017; 28 (3): 1359-1363

         Luo Y., Shang P., Li D. Luteolin: A Flavonoid that Has Multiple Cardio-Protective Effects and Its Molecular Mechanisms. Front Pharmacol. 2017; 8: Article 692

Luteolin attenuates diabetes associated cognitive decline.

          Liu Y, Tian X, Gou L, Sun L, Ling X, Yin X. Luteolin attenuates diabetes-associated cognitive decline in rats. Brain Res Bull. 2013 May;94:23-9. doi: 10.1016/j.brainresbull.2013.02.001.

The association between diabetes and tuberculosis is known since 1934. Most of us ignore that on Nov 3, 2015 a Convention was signed in Bali declaring the fight against the looming TB-Diabetes co-epidemic, one of the greatest global health challenges.

          H F Root, The Association of Diabetes and Tuberculosis, New England Journal of Medicine, 1934, 210 1-13.

The association between elevated serum uric acid level and type 2 diabetes mellitus (T2D) has been established for years. Elevated uric acid not only induces insulin resistance in peripheral tissues but also exerts a strongly negative effect on pancreatic β-cell survival and insulin secretion. A study from China found that luteolin prevents uric acid-induced pancreatic β-cell dysfunction.

         Ying Ding, Xuhui Shia, Xuanyu Shuaia, Luteolin prevents uric acid-induced pancreatic β-cell dysfunction. The Journal of Biomedical Research, 2014, 28(4):292-298

Luteolin prevents uric acid-induced pancreatic β-cell dysfunction. J Biomed Res. 2014 Jul;28(4):292-8. doi: 10.7555/JBR.28.20130170. Epub 2014 Mar 28. PMID: 25050113; PMCID: PMC4102843.

Luteolin among the flavonoids shows the strongest inhibition of xanthine oxidase, the enzyme which generates uric acid.

         A Nagao, M Seki, H Kobayashi, Inhibition of xanthine oxidase by flavonoids. Biosci Biotechnol Biochem, 1999, 63, 1787-90.

Luteolin was found to be stable in assay procedures, which is not the case for other constituants of Artemisia plants, like artemisinin or saponin.  Luteolin  is  heat  stable  and  hence  losses due to boiling water decoctions do not incur.

         Waithaka J. The evaluation of markers for quality control studies of flavonoid-
containing medicinal preparations. Master’s Thesis, Discipline of Pharmacology,
School of Pharmacy, University of Western Cape, Bellville

Annex 1.

 
   

REPUBLIQUE DU BURUNDI

MINISTERE DE LA SANTE PUBLIQUE ET DE LUTTE CONTRE LE SIDA                                                                                                                                                 IJENDA,  HOPITAL                                                                                                                                           

EFFET DE L'ARTEMISIA SUR LE DIABÈTE : CAS D'UN DIABÈTE DÉCOMPENSÉ

  • Il s'agit d'un patient diabétique connu, qui nous a consulté pour polyurie, soif intense, altération de l'état général.
  • Le diagnostic du diabète était confirmé par une glycémie élevée à 20,13 mmol/l
  • Le patient était mis sous insuline ordinaire pendant 4 jours mais la glycémie variant de 20,13-19,1 mmol/l.
  • A partir du 4ème jour d'hospitalisation, nous avons débuté l'Artemisia afra ; et 24 heures plus tard la courbe glycémique commençait à descendre progressivement jusqu'à la valeur normale au 5ème jour du début d'Artemisia afra (voir tableau ci-dessous)
  • L’état général s'est amélioré au 4ème jour du traitement par Artemisia et la sortie du patient était accordé au 10ème jour d'hospitalisation (c'est-à-dire 5ème jour du traitement par Artemisia).

Tableau du traitement

Traitement Insuline ordinaire

Traitement Artemisia afra

Date (Jour/mois)

10/11

12/11

16/11

17/11

 

18/11

19/11

20/11

21/11

22/11

23/11

Glycémie en mmol/l

20,13

19,6

19,3

19,1

 

19,4

17,3

14

9,9

6,9

5,3

Glucosurie

 

 

 

 

 

++

++

++

 

 

 

 

Dr Elkan KATOTOLA, Médecin consultant à l'hôpital Ijenda

AttachmentSize
PDF icon Artemisia afra, pancreas, diabetes.pdf371.34 KB

Comments

Submitted by Pierre Lutgen on

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  

Submitted by Pierre Lutgen on

 

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.