“All things are poison and not without poison; only the dose makes a thing not a poison” Philippus Aureolus Theophrastus Bombastus von Hohenheim, also known as Paracelsus (1493–1541).
Hormesis is the term that describes any process in a cell or organism that exhibits a biphasic response to exposure to increasing amounts of a substance. Within the hormetic zone there is generally a favorable biological response at moderate exposures and a negative impact at very low or at high doses. In the case of natural compounds an example of hormesis is vitamin A which in relatively low amounts is essential for normal development and eye function, but in high amounts can cause anorexia, headaches, drowsiness, altered mental states and other symptoms. Another well known example, the hormetic effects of wine drinking
The hormetic effect for the antimalarial methylene blue on locomotor activity and memory has been described in rats. The optimal dose for intraperoneal injection is 1-10 mg/kg. The effect at lower or higher doses did not differ from the baseline.
Penny D Riha, Aleksandra K Bruchey Memory facilitation by methylene blue: Dose-dependent effect on behavior and brain oxygen consumption. European Journal of Pharmacology 511(2-3):151-8· April 2005 DOI: 10.1016/j.ejphar.2005.02.001 ·
The strong antimalarial hypoestoxide, extracted from Hypoestes rosea in Nigeria, also shows a clear hermetic effect with an optimal dose at 200 µg/kg in mice.
E Ojo_Amaize, E Nchekwube, J Okogun. Plasmodium berghei: Antiparasitic effects of orally administered Hypoestoxide in mice. Experimental Parasitology 2007 117, 218-221.
Artemisia annua is able to sterilize water. In 2008 a research team at Luxembourg found that adding fresh Artemisia annua tea, even to heavily contaminated water, had a stronger bactericidal effect than boiling the contaminated water for 5 minutes or irradiating it for 10 minutes under a 365 nm UV lamp.
P. Lutgen. B Michels, Proceedings International Conference, Luxembourg June 3-4 2008
This effect was confirmed by several other laboratories, at the University of Bangui, at the University of Gent, at the University of Antioquia, at the University of Dakar. The bactericidal effect was supposedly related to artemisinin. Until the Universities in Medellin and Bangui found that after 24 hours this bactericidal property had vanished. The bacterial concentration was even increasing in the infusion. A possible explanation is that artemisinin only plays a minor role but that the initial high concentration of hydrogen peroxide in the infusion vanishes in a few hours and that the remaining organic matter of the plant acts as food for the bacteria.
Mobili OB Mabingui J, Nola M, Synergistic effect of light, pH and Artemisia annua extract on Enteroccus faecalis. Int J Applied Microobiol Biotech Res. 2015, 362 72.
Marıa Cecilia Escobar, Yamilet Arcos. Efecto microbicida de laradiacion solar(SODIS) combinado con Artemisia annua, Universidad de Antioquia, submitted
The Université des Montagnes in Cameroon has shown that tea Artemisia annua is hepatoprotective. On the other hand, some studies have shown that the high doses of artesunate prescribed by the ACT treatment are hepatotoxic. The same recent research work from the Université des Montagnes shows that in infusions the concentration of artemisinin reaches a plateau in function of increasing quantities of dry herb.
In clinical trials which were run in Kenya and in Katanga no dose effect was notices in the range administred. In other words, low doses were as efficient as high doses.
Whole-Leaf Artemisia annua based Antimalarial Drug, ICIPE, KEMRI and NUSAG project. April 2005 Nairobi Kenya.
C Kansango Tchandema P Lutgen. , In vivo Trials on the Therapeutic effect of encapsulated Artemisia annua and Artemisia afra, Global J Res Analysis, 2016, 5(6) ISSN 2277-8160
Artemisia annua also displayed hormesis in the treatment of osteoarthritis. Statistically significant reductions for stiffness and pain were seen from baseline in the Artemisia annua low-dose group. No statistically significant changes occurred in the placebo or in the high-dose groups for any parameter.
Stebbings, S., Beattie, E., McNamara, D. A pilot randomized, placebo-controlled clinical trial to investigate the efficacy and safety of an extract of Artemisia annua administered over 12 weeks, for managing pain, stiffness, and functional limitation associated with osteoarthritis of the hip and knee. Clin Rheumatol (2016) 35: 1829. doi:10.1007/s10067-015-3110-z
At the University of Al Quds it was noticed that the addition of calcium carbonate enhanced the inhibitory effect of Artemisia annua on beta-hematin formation.
Suhair Jaber, Saleh Abu-Lafi, Pierre Lutgen, Mutaz Qutob, Qassem Abu-Remeleh and Mutaz Akkawi. Bicarbonate effect on Beta-Hematin Inhibition by Artemisia Sieberi Aqueous Infusion Journal of Pharmacy and Pharmacology 3 (2015) 63-72 doi: 10.17265/2328-2150/2015.02.003
Université de Liège-Gembloux noticed a concentration effect of the insecticidal properties of Artemisia annua infusions.
There are strong synergistic and antagonistic effects between the different constituents of Artemisia annua,
X Zhu, Lan Yang,Yujie J. Li,Petra Kostecká, Eva Kmoníčková, Zdeněk Zídek. Effects of sesquiterpene, flavonoid and coumarin types of compounds from Artemisia annua L. on production of mediators of angiogenesis. Pharmacol Rep, Volume 2013; 65(2): 410–420
The allelopathic properties of Artemisia annua seem to depend on artemisinin concentration and the presence of other substances.
R Belz, K Hurle, A Challenge in Allelopathy, Nonlinearity in Biology, Toxicology, and Medicine, 3: 173–211, 2005
J Lydon, JR Teasdale, PK Chen, Allelopathic activity of annual wormwood (Artemisia annua) and the role of artemisinin, Weed Science, 1997, 45. 807-811.
US patent 5578637 (Lai H. Singh N, University of Washington, 1996) states that artesunate stimulates the immune system at low doses and inhibits it at high doses.
This is in line with a recent paper from Iran. Extracts of different parts of 7 Artemisia species increased PBMC number in a dose dependent manner up to 250 µg/mL. After that the effect sharply decreased. Flower extract of Artemisia sieberi increased the PBCM number up to 5 folds
Hassan Mohabatkar, Mandana Behbahani Effects of root, shoot, leaf and seed extracts of seven Artemisia species on HIV-1 replication and CD4 expression J of Coastal Life Medicine, 2015 3(12) 996-999 DOI: 10.12980/jclm.3.2015j5-126
There is one study on artemisinin which clearly shows a hormetic effect. The toxic effects of artesunate and dihydroartemisinin on the growth metabolism of Tetrahymena thermophila were studied by microcalorimetry. The results showed that: low concentrations of artesunate (<or=1 mg L(-1)) and dihydroartemisinin (<or= 2 mg L(-1)) promoted the growth metabolism of T. thermophila BF5, whereas high concentrations of artesunate (1-60 mg L(-1)) and dihydroartemisinin (2-60 mg L(-1)) inhibited its growth.
Shen XS, Su Q, Qiu ZP, Xu JY, Xie YX, Liu HF, Liu Y. Effects of artemisinin derivative on the growth metabolism of Tetrahymena thermophila BF5 based on expression of thermokinetics. Biol Trace Elem Res. 2010 Jul;136(1):117-25. doi: 10.1007/s12011-009-8527-2
AJ Vargas. Hormesis and Synergy: Pathways and Mechanisms of Quercetin in Cancer Prevention and Management. Nutr Rev 68 (7), 418-428. 7 2010
Scopoletin well present in Artemisia plants demonstrates hormetic effects.
YONG Xiao-Ju ZHANG Yong-Qiang DING Wei. Repellent and oviposition deterrent properties of scopoletin to Tetranychus cinnabarinus Chinese Journal of Applied Entomology 2012-02
Condensed tannins also exert a hormetic effect and they are well present in Artemisia plants
De Nicola E, Gallo M, Iaccarino M, Meriç S, Oral R, Russo T, Sorrentino T, Tünay O, Vuttariello E, Warnau M, Pagano G. Hormetic versus toxic effects of vegetable tannin in a multitest study. Arch Environ Contam Toxicol. 2004 Apr;46(3):336-44.
Antioxidants: friends or foes?
Digestion and gut permeability
Most medicinal plants have a bitter taste, which is quite variable depending on geological and climatological conditions. This influences the postprandial haemodynamics and influences digestion
MK McMullen, JM Whitehouse, A Towell. Bitter tastants alter gastric-phase postprandial haemodynamics, J Ethnopharmacology 2014 submitted.
Biological variations among patients -- due to variations in stomach acidity and other factors -- can reduce the effectiveness of oral drugs. The team of an American pharmaceutical company showed that Sprite seemed to control stomach acidity in a way likely to allow greater absorption of the drug into the body. Based on the results, the scientists suggest that patients in future clinical trials take the drug with Sprite.
Christopher S. Polster, Faraj Atassi, Sy-Juen Wu, David C. Sperry. Use of Artificial Stomach-Duodenum Model for Investigation of Dosing Fluid Effect on Clinical Trial Variability. Molecular Pharmaceutics, 2010; 7 (5): 1533 DOI: 10.1021/mp100116g.
Lime juice also has an influence on the efficacy of antimalarial drugs. One hundred and twenty children with acute uncomplicated malaria children were randomized into treatment with ACTs either alone or with lime juice. The average time to achieve >75% reduction in parasite load was significantly lower in patients on ACT and lime; Also, while a significantly higher proportion of children on antimalarial drugs and lime juice achieved complete parasite clearance by 72 h of therapy ten (18.2%) patients without lime had early treatment failure.
Adegoke SA1, Oyelami OA, Olatunya OS, Adeyemi LA. Effects of lime juice on malaria parasite clearance. Phytother Res. 2011 Oct;25(10):1547-50. doi: 10.1002/ptr.3418
Possible synergistic effects of the constituents in Artemisia annua have been studied extensively, but antagonistic and hormetic effects have been neglected