27 January 2020

Sanguinarine

NATURAL TOXIN: Eutrophication

has accelerated during the last years, thanks of the increase of phosphorus and nitrogen into water bodies, soil and in general, in the environment.

Due of that, harmful cyanobacteria are increasing, forming cyanobacterial bloom in water bodies even in unusual time for their bloom [1]. Not only, but the environment can also be affected by the presence of other toxins coming from the vegetation and the botanical diversity of the area. Plants can contain a wide range of phytochemicals that can explain different pharmacological activities. However, not all the toxins produced have to be connected to negative connotations. In fact, thanks to their extremely wide diversity, plants can also produce toxins that may explain an important role in the control of plague in the environment. Medicinal plants are also extensively used for healthcare in developing countries [2]. Besides, many of these plants contain harmful natural toxins that have been engineered for plague control and anti-parasitic effects.


Figure 1: Bloodroot (Sanguinaria Canadiensis), figure adapted from https://maiahausler.com/2016/05/16/bloodroot/

Sanguinarine is an alkaloid. Alkaloids are nitrogen-containing compounds, which may be found as “secondary metabolites” or “natural products” in plants. Sanguinarine is a benzophenanthridine alkaloid, isolated from Bloodroot (Sanguinaria Canadiensis), Corydalis edulis, Chelidonium majus, Macleaya cordata, Poppy fumaria and Bocconia frutescens,[3, 4]. It has several biological activities [5, 6], this is why it has been investigated to be used as a control for plagues[7] and cyanobacteria bloom (HAB) [8].

Plague control; Many efforts have been spent to study the biological effects that can explain sanguinarine against tissues, plagues and organisms.

Huang et al recently reported its anthelmintic activity. The lethal effect of sanguinarine on larvae at different stages was dose-dependent, the 100% effective concentration in vitro was 30ug/L against T. Spiralis. Adults of T. Spiralis had a fatal dose with half of the concentration used for larvae (15 ug/L). The LC50 and LC90 at 24 h were 6.69  μg/L and 12.89  μg/L, respectively [7].

Thanks to that sanguinarine showed a lethal effect on new-born larvae, muscle larvae and adults and focused on the elimination of the adults in vitro. In in vivo experiments, showed effects on mice with different stages of Trichinella infection (pre-adult, migrating, encysted) after sanguinarine inoculation[7].


Figura 2: Typical flower of Bloodroot (Sanguinaria Canadiensis). Figure adapted from http://www.thimblefarms.com/htm/perennial_h_sanguinaria%20canadensis%20multiplex.htm


Algal bloom control;
Sanguinarine is also known to induce apoptosis, perturb microtubules, and to have antimicrobial effects. Shao et al. showed a strong inhibitory effect of sanguinarine against Microcystis aeruginosa a typical water bloom-forming able to produce dangerous microcystins toxins[9]. As reported, it is strongly time and dose-dependent since the reduction of M. aeruginosa cells were significantly reduced after 5 days of exposition and with increasing chemical concentration 10 μg/L [9]. In other studies, alternatives to reduce blooms in water were tested.

The toxicity of sanguinarine is higher against M. aeruginosa than the one against other algae[10]. Thanks to this property, sanguinarine can become a strong alternative to the use of chemicals for bloom control. Lin et al reported the efficacy of the sanguinarine as elimination protocol for cyano-HAB. Microcystis cells treated with sanguinarine decreased from 1.34 × 109 cells/L to 1.26 × 107 cells/L on day 3, to 7.85 × 105 cells/L on day 5, after which Microcystis cells stabilised [8]. This is to say that sanguinarine decreased the cells suspended in the medium.

Conclusions
These findings might affect the scientific world since a new compound for the control of plagues and cyano HAB has been discovered. At the time it is important to focus on this new natural chemical that can be used as an alternative to artificial compounds.

CAS Registry Number: 2447-54-3
IUPAC Name: 24-methyl-5,7,18,20-tetraoxa-24-azoniahexacyclotetracosa-1(24),2,4(8),9,11,13,15,17(21),22-nonaene
Molecular Formula: C20H14NO4+
Molecular Weight: 332.0922
Figure 3: chemical structure of sanguinarine (https://www.ijunoon.com/dictionary/Sanguinarine

Literature
[1] S.N. Scholz, M. Esterhuizen-Londt, S. Pflugmacher, Rise of toxic cyanobacterial blooms in temperate freshwater lakes: causes, correlations and possible countermeasures, Toxicological & Environmental Chemistry, 99 (2017) 543-577.

[2] M.B. Adinortey, I.K. Galyuon, N.O. Asamoah, Trema orientalis Linn. Blume: A potential for prospecting for drugs for various uses, Pharmacogn Rev, 7 (2013) 67-72.

[3] M. Bavarsadi, A.H. Mahdavi, S. Ansari-Mahyari, E. Jahanian, Effects of different levels of sanguinarine on antioxidant indices, immunological responses, ileal microbial counts and jejunal morphology of laying hens fed diets with different levels of crude protein, Journal of Animal Physiology and Animal Nutrition, 101 (2017) 936-948.

[4] C. Caballero-George, P.M. Vanderheyden, S. Apers, H. Van den Heuvel, P.N. Solis, M.P. Gupta, M. Claeys, L. Pieters, G. Vauquelin, A.J. Vlietinck, Inhibitory activity on binding of specific ligands to the human angiotensin II AT(1) and endothelin 1 ET(A) receptors: bioactive benzo[c]phenanthridine alkaloids from the root of Bocconia frutescens, Planta medica, 68 (2002) 770-775.

[5] M. Artini, R. Papa, G. Barbato, G.L. Scoarughi, A. Cellini, P. Morazzoni, E. Bombardelli, L. Selan, Bacterial biofilm formation inhibitory activity revealed for plant derived natural compounds, Bioorganic & Medicinal Chemistry, 20 (2012) 920-926.

[6] Z.-J. Zhang, Z.-Y. Jiang, Q. Zhu, G.-H. Zhong, Discovery of β-Carboline Oxadiazole Derivatives as Fungicidal Agents against Rice Sheath Blight, Journal of Agricultural and Food Chemistry, 66 (2018) 9598-9607.

[7] H. Huang, J. Yao, K. Liu, W. Yang, G. Wang, C. Shi, Y. Jiang, J. Wang, Y. Kang, D. Wang, C. Wang, G. Yang, Sanguinarine has anthelmintic activity against the enteral and parenteral phases of trichinella infection in experimentally infected mice, Acta Tropica, 201 (2020) 105226.

[8] Y. Lin, A. Chen, S. Luo, X. Kuang, R. Li, J.E. Lepo, J.-D. Gu, Q. Zeng, J. Shao, Cyanobacterial bloom mitigation by sanguinarine and its effects on aquatic microbial community structure, Environmental Pollution, 253 (2019) 497-506.

[9] J. Shao, D. Liu, D. Gong, Q. Zeng, Z. Yan, J.-D. Gu, Inhibitory effects of sanguinarine against the cyanobacterium Microcystis aeruginosa NIES-843 and possible mechanisms of action, Aquatic Toxicology, 142-143 (2013) 257-263.

[10] Y.L. Yi, Y.J. Kang, L. Xia, G.X. Wang, Growth inhibition and oxidative stress of cyanobacteria induced by sanguinarine and 6-methoxydihydrochelerythrine isolated from Macleaya microcarpa, Allelopathy Journal, 31 (2013) 211-224.