Limits...
Anthelmintic activity of trans-cinnamaldehyde and A- and B-type proanthocyanidins derived from cinnamon (Cinnamomum verum).

Williams AR, Ramsay A, Hansen TV, Ropiak HM, Mejer H, Nejsum P, Mueller-Harvey I, Thamsborg SM - Sci Rep (2015)

Bottom Line: Cinnamon (Cinnamomum verum) has been shown to have anti-inflammatory and antimicrobial properties, but effects on parasitic worms of the intestine have not been investigated.It is proposed that the rapid absorption or metabolism of CA in vivo may prevent it from being present in sufficient concentrations in situ to exert efficacy.Therefore, further work should focus on whether formulation of CA can enhance its activity against internal parasites.

View Article: PubMed Central - PubMed

Affiliation: Department of Veterinary Disease Biology, Faculty of Health and Medical Sciences, University of Copenhagen, Frederiksberg, Denmark.

ABSTRACT
Cinnamon (Cinnamomum verum) has been shown to have anti-inflammatory and antimicrobial properties, but effects on parasitic worms of the intestine have not been investigated. Here, extracts of cinnamon bark were shown to have potent in vitro anthelmintic properties against the swine nematode Ascaris suum. Analysis of the extract revealed high concentrations of proanthocyanidins (PAC) and trans-cinnamaldehyde (CA). The PAC were subjected to thiolysis and HPLC-MS analysis which demonstrated that they were exclusively procyanidins, had a mean degree of polymerization of 5.2 and 21% of their inter-flavan-3-ol links were A-type linkages. Purification of the PAC revealed that whilst they had activity against A. suum, most of the potency of the extract derived from CA. Trichuris suis and Oesophagostomum dentatum larvae were similarly susceptible to CA. To test whether CA could reduce A. suum infection in pigs in vivo, CA was administered daily in the diet or as a targeted, encapsulated dose. However, infection was not significantly reduced. It is proposed that the rapid absorption or metabolism of CA in vivo may prevent it from being present in sufficient concentrations in situ to exert efficacy. Therefore, further work should focus on whether formulation of CA can enhance its activity against internal parasites.

No MeSH data available.


Related in: MedlinePlus

Anthelmintic effects of pure trans-cinnamaldehyde (CA).(a) Anthelmintic effects of CA against Ascaris suum third stage (L3) and fourth stage (L4) larvae. Mortality of A. suum was assessed after 12 hours incubation for L3 and 6 hours for L4. L3 results are the mean of three independent experiments, each performed in triplicate, and the L4 results are from a single experiment performed in triplicate. Error bars indicate the inter-replicate SEM. (b) Anthelmintic effects of CA against Oesophagostomum dentatum L3 and Trichuris suis first-stage larvae (L1). Mortality of O. dentatum was measured by agar-based migration inhibition assay after overnight incubation in CA, and T. suis mortality by observation of motility after 2 hours incubation. O. dentatum results are the mean of two independent experiments, each performed in triplicate, and T. suis results from a single experiment performed in triplicate. Error bars indicate the inter-replicate SEM.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC4588565&req=5

f5: Anthelmintic effects of pure trans-cinnamaldehyde (CA).(a) Anthelmintic effects of CA against Ascaris suum third stage (L3) and fourth stage (L4) larvae. Mortality of A. suum was assessed after 12 hours incubation for L3 and 6 hours for L4. L3 results are the mean of three independent experiments, each performed in triplicate, and the L4 results are from a single experiment performed in triplicate. Error bars indicate the inter-replicate SEM. (b) Anthelmintic effects of CA against Oesophagostomum dentatum L3 and Trichuris suis first-stage larvae (L1). Mortality of O. dentatum was measured by agar-based migration inhibition assay after overnight incubation in CA, and T. suis mortality by observation of motility after 2 hours incubation. O. dentatum results are the mean of two independent experiments, each performed in triplicate, and T. suis results from a single experiment performed in triplicate. Error bars indicate the inter-replicate SEM.

Mentions: As CA was present in relatively high concentrations in the extract, but was removed almost entirely from the PAC-fractions, we hypothesised that CA was the compound mainly responsible for the anthelmintic activity. To test this, we used pure CA (>99%) in an efficacy assay against A. suum. We found that pure CA had similar activity to the whole cinnamon extract against both A. suum L3 and L4 (Fig. 5A). Concentrations of around 200 μM (equivalent to 25.6 μg CA/mL) resulted in larval death within three hours, which corresponds very well to the amount of CA that would be present in the extract concentrations used (Fig. 2), given that 7.8% of the extract was determined to be CA. CA has been shown to be a potent antimicrobial with activity against, amongst others, Salmonella sp. and Campylobacter2728, as well as having activity against parasitic plant nematodes29. However, this is the first demonstration of anthelmintic activity of CA against a gastrointestinal nematode parasite. To confirm that the activity was not only restricted to A. suum, we tested the activity of pure CA against Oesophagostomum dentatum and Trichuris suis, two other porcine nematodes which fall in different clades to A. suum and are related to human hookworm and whipworm species, respectively30. CA also had potent activity against larvae from these other species (Fig. 5B), demonstrating that CA has in vitro activity against a range of gastrointestinal parasites.


Anthelmintic activity of trans-cinnamaldehyde and A- and B-type proanthocyanidins derived from cinnamon (Cinnamomum verum).

Williams AR, Ramsay A, Hansen TV, Ropiak HM, Mejer H, Nejsum P, Mueller-Harvey I, Thamsborg SM - Sci Rep (2015)

Anthelmintic effects of pure trans-cinnamaldehyde (CA).(a) Anthelmintic effects of CA against Ascaris suum third stage (L3) and fourth stage (L4) larvae. Mortality of A. suum was assessed after 12 hours incubation for L3 and 6 hours for L4. L3 results are the mean of three independent experiments, each performed in triplicate, and the L4 results are from a single experiment performed in triplicate. Error bars indicate the inter-replicate SEM. (b) Anthelmintic effects of CA against Oesophagostomum dentatum L3 and Trichuris suis first-stage larvae (L1). Mortality of O. dentatum was measured by agar-based migration inhibition assay after overnight incubation in CA, and T. suis mortality by observation of motility after 2 hours incubation. O. dentatum results are the mean of two independent experiments, each performed in triplicate, and T. suis results from a single experiment performed in triplicate. Error bars indicate the inter-replicate SEM.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4588565&req=5

f5: Anthelmintic effects of pure trans-cinnamaldehyde (CA).(a) Anthelmintic effects of CA against Ascaris suum third stage (L3) and fourth stage (L4) larvae. Mortality of A. suum was assessed after 12 hours incubation for L3 and 6 hours for L4. L3 results are the mean of three independent experiments, each performed in triplicate, and the L4 results are from a single experiment performed in triplicate. Error bars indicate the inter-replicate SEM. (b) Anthelmintic effects of CA against Oesophagostomum dentatum L3 and Trichuris suis first-stage larvae (L1). Mortality of O. dentatum was measured by agar-based migration inhibition assay after overnight incubation in CA, and T. suis mortality by observation of motility after 2 hours incubation. O. dentatum results are the mean of two independent experiments, each performed in triplicate, and T. suis results from a single experiment performed in triplicate. Error bars indicate the inter-replicate SEM.
Mentions: As CA was present in relatively high concentrations in the extract, but was removed almost entirely from the PAC-fractions, we hypothesised that CA was the compound mainly responsible for the anthelmintic activity. To test this, we used pure CA (>99%) in an efficacy assay against A. suum. We found that pure CA had similar activity to the whole cinnamon extract against both A. suum L3 and L4 (Fig. 5A). Concentrations of around 200 μM (equivalent to 25.6 μg CA/mL) resulted in larval death within three hours, which corresponds very well to the amount of CA that would be present in the extract concentrations used (Fig. 2), given that 7.8% of the extract was determined to be CA. CA has been shown to be a potent antimicrobial with activity against, amongst others, Salmonella sp. and Campylobacter2728, as well as having activity against parasitic plant nematodes29. However, this is the first demonstration of anthelmintic activity of CA against a gastrointestinal nematode parasite. To confirm that the activity was not only restricted to A. suum, we tested the activity of pure CA against Oesophagostomum dentatum and Trichuris suis, two other porcine nematodes which fall in different clades to A. suum and are related to human hookworm and whipworm species, respectively30. CA also had potent activity against larvae from these other species (Fig. 5B), demonstrating that CA has in vitro activity against a range of gastrointestinal parasites.

Bottom Line: Cinnamon (Cinnamomum verum) has been shown to have anti-inflammatory and antimicrobial properties, but effects on parasitic worms of the intestine have not been investigated.It is proposed that the rapid absorption or metabolism of CA in vivo may prevent it from being present in sufficient concentrations in situ to exert efficacy.Therefore, further work should focus on whether formulation of CA can enhance its activity against internal parasites.

View Article: PubMed Central - PubMed

Affiliation: Department of Veterinary Disease Biology, Faculty of Health and Medical Sciences, University of Copenhagen, Frederiksberg, Denmark.

ABSTRACT
Cinnamon (Cinnamomum verum) has been shown to have anti-inflammatory and antimicrobial properties, but effects on parasitic worms of the intestine have not been investigated. Here, extracts of cinnamon bark were shown to have potent in vitro anthelmintic properties against the swine nematode Ascaris suum. Analysis of the extract revealed high concentrations of proanthocyanidins (PAC) and trans-cinnamaldehyde (CA). The PAC were subjected to thiolysis and HPLC-MS analysis which demonstrated that they were exclusively procyanidins, had a mean degree of polymerization of 5.2 and 21% of their inter-flavan-3-ol links were A-type linkages. Purification of the PAC revealed that whilst they had activity against A. suum, most of the potency of the extract derived from CA. Trichuris suis and Oesophagostomum dentatum larvae were similarly susceptible to CA. To test whether CA could reduce A. suum infection in pigs in vivo, CA was administered daily in the diet or as a targeted, encapsulated dose. However, infection was not significantly reduced. It is proposed that the rapid absorption or metabolism of CA in vivo may prevent it from being present in sufficient concentrations in situ to exert efficacy. Therefore, further work should focus on whether formulation of CA can enhance its activity against internal parasites.

No MeSH data available.


Related in: MedlinePlus