Dataset Information

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

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.

SUBMITTER: Williams AR

PROVIDER: S-EPMC4588565 | biostudies-literature | 2015 Sep

REPOSITORIES: biostudies-literature

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

Williams Andrew R AR Ramsay Aina A Hansen Tina V A TV Ropiak Honorata M HM Mejer Helena H Nejsum Peter P Mueller-Harvey Irene I Thamsborg Stig M SM

Scientific reports 20150930

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 t ...[more]

PMID: 26420588

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Project description:Parasitic nematodes pose a significant global socio-economic threat and contribute to neglected diseases. Current infection control relies on drug therapy, but increasing anthelmintic resistance highlights the urgent need for novel treatments. In this study, we investigate the molecular targets and mechanisms of action of trans-cinnamaldehyde (TCA), a principal component of Cinnamon Essential Oil (Cinnamomum verum EO), using Caenorhabditis elegans as a model organism. Our research offers new insights into the anthelmintic effects of TCA by identifying its specific interactions with key Cys-loop receptors and detailing its inhibitory mechanisms. The anthelmintic activity of C. verum EO and TCA manifests as rapid alterations in locomotor activity and inhibition of egg hatching. TCA screening of mutant worms lacking Cys-loop receptors reveal multiple receptor targets, including the levamisole-sensitive nicotinic ACh receptor (L-AChR), GABA-activated chloride channel (UNC-49) and glutamate-activated chloride channel. The mechanism behind the egg hatching inhibition by TCA remains unclear, as none of the mutants studied were found to be resistant to TCA. Furthermore, TCA increases the paralyzing effects of the anthelmintics levamisole and monepantel in a synergistic manner, offering a route for more effective polytherapy strategies. Electrophysiological studies on C. elegans Cys-loop receptors, in both native and heterologous systems, were used to elucidate the molecular mechanisms of TCA-induced paralysis. TCA reduces ACh- and GABA-elicited macroscopic currents and decreases single-channel activity and open durations of native muscle L-AChR channels, indicating an inhibitory action. Thus, by acting through a different mechanism to that of classical anthelmintics, TCA may be beneficial to counteract resistance in combined anthelmintic therapies. Our findings underscore the potential of the multitarget compound TCA as a valuable tool in integrated pharmacological strategies.

Project description:Klebsiella pneumoniae (KP) remains the most prevalent nosocomial pathogen and carries the carbapenemase (KPC) gene which confers resistance towards carbapenem. Thus, it is necessary to discover novel antimicrobials to address the issue of antimicrobial resistance in such pathogens. Natural products such as essential oils are a promising source due to their complex composition. Essential oils have been shown to be effective against pathogens, but the overall mechanisms have yet to be fully explained. Understanding the molecular mechanisms of essential oil towards KPC-KP cells would provide a deeper understanding of their potential use in clinical settings. Therefore, we aimed to investigate the mode of action of essential oil against KPC-KP cells from a proteomic perspective by comparing the overall proteome profile of KPC-KP cells treated with cinnamon bark (Cinnamomum verum J. Presl) essential oil (CBO) at their sub-inhibitory concentration of 0.08% (v/v). A total of 384 proteins were successfully identified from the non-treated cells, whereas only 242 proteins were identified from the CBO-treated cells. Proteins were then categorized based on their biological processes, cellular components and molecular function prior to pathway analysis. Pathway analysis showed that CBO induced oxidative stress in the KPC-KP cells as indicated by the abundance of oxidative stress regulator proteins such as glycyl radical cofactor, catalase peroxidase and DNA mismatch repair protein. Oxidative stress is likely to oxidize and disrupt the bacterial membrane as shown by the loss of major membrane proteins. Several genes selected for qRT-PCR analysis validated the proteomic profile and were congruent with the proteomic abundance profiles. In conclusion, KPC-KP cells exposed to CBO undergo oxidative stress that eventually disrupts the bacterial membrane possibly via interaction with the phospholipid bilayer. Interestingly, several pathways involved in the bacterial membrane repair system were also affected by oxidative stress, contributing to the loss of cells viability.

Project description:Cinnamon (Cinnamomum cassia) is a well-known traditional Chinese medicine used to treat nocturia by tonifying and warming the kidney. Our recent clinical study found that overactive bladder (OAB) patients treated with cinnamon powder (CNP) patches exhibited significantly ameliorated OAB symptoms without significant side effects, but the mechanism of action is unclear. To explore the beneficial effects and action mechanisms of CNP and its major active component cinnamaldehyde (CNA) in an OAB-related murine model, cyclophosphamide- (CYP-) induced OAB injury was performed on male ICR mice in the presence or absence of CNP and CNA, as well as solifenacin, a clinical drug for OAB as a reference. Twenty-four-hour micturition patterns (frequency of urination and volume of urine per time), as well as histopathological examination, immunohistochemistry (IHC), and Western blotting of the bladder, were analyzed for mechanism elucidation. Administration of CYP (300 mg/kg, i.p.) induced typical OAB pathophysiological changes, including increased frequency of urination and reduced volume of urine. CYP-induced mice displayed strong edema of the bladder and hemorrhagic cystitis, accompanied by loss of normal corrugated folds and decreased muscarinic receptors (M2/M3) in the urothelium, and disordered/broken structures of the lamina propria and detrusor. These changes were correlated with increased leukocyte (CD11b) infiltration colocalized with inflammatory (pp65 NFκB, macrophage migration inhibitory factor (MIF)/Toll-like receptor 4 (TLR4)) and fibrotic (stem cell factor (SCF)/c-Kit, α-smooth muscle actin (α-SMA)/β-catenin) signals. Treatment with CNP (600 mg/kg, p.o.) and CNA (10-50 mg/kg, p.o.), but not solifenacin (50 mg/kg), 30 min after CYP induction significantly ameliorated CYP-induced dysfunction in micturition patterns and pathophysiological changes. CNP and CNA further suppressed MIF/TLR4-associated inflammatory and SCF/c-Kit-related fibrotic signaling pathways. Our findings indicate that suppression of inflammatory and fibrotic signals contributes to the crucial mechanism in the improvement of CYP-induced OAB by CNP and CNA.

Dataset Information

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

Publications

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

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