Antitubercular Activity Of Garlic Oil

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And garlic oil were investigated for antimycobacterial activity whereas allicin-rich extract and garlic oil were also evaluated for antibacterial activity. Garlic bulb samples were procured from the local market and identity of the sample was verified from Department of Botany, St. Xavier’s College, Mumbai. Garlic Oil Sulfides and Garlic Powder of Methodologies and Comparisons with against Human Enteric Bacteria: Evaluation. Antimicrobial Properties of Garlic Oil against Human Enteric Bacteria: Evaluation of Methodologies and Comparisons. Activity of garlic components in the gut. In summary, the methodology of early experiments might.

Antitubercular Activity Of Garlic Oil Change

Abstract

The in vitro antibacterial activities of garlic oil and four diallyl sulphides naturally occurring in this oil were studied against Pseudomonas aeruginosa and Klebsiella pneumoniae (total 237 clinical isolates). Garlic oil at 4 × MIC could reduce original inoculum to ≤2 log10 in both P. aeruginosa and K. pneumoniae within 8 h. The MIC values of four diallyl sulphides against these two pathogens followed the order diallyl monosulphide > diallyl disulphide > diallyl trisulphide (DAT) > diallyl tetrasulphide (DATS) (P < 0.05). Most interactions of ceftazidime, gentamicin, imipenem and meropenem with DAT or DATS, determined according to the fractional inhibitory concentration index, showed synergic or additive effects. These results suggest that garlic oil, DAT and DATS may have potential for the prevention or treatment of nosocomial, antibiotic-resistant bacterial infections.

Introduction

Pseudomonas aeruginosa and Klebsiella pneumoniae are common nosocomial pathogens in Taiwan.1–3 Because these bacterial pathogens are multiply resistant to many antibiotics such as ceftazidime and gentamicin, the infections caused by them not only require expensive antibiotic treatment but also increase the morbidity and mortality in hospitalized patients.3,4 In order to control these infections, there is a need for the development of agents with marked antibacterial activity, greater sensitivity and less toxicity.

The antimicrobial activity and other medical benefits of garlic oil have been widely recognized.5–8 The potential for clinical benefit from the use of garlic oil as an antimicrobial agent has been suggested by recent studies.5,6 Chemical analysis of garlic oil showed that 54.5% of the total sulphides was the sum of diallyl monosulphide (DAS), diallyl disulphide (DADS), diallyl trisulphide (DAT) and diallyl tetrasulphide (DATS).9 Because the commercial sources of DAS and DADS are less expensive and easily obtained, the antimicrobial activities of these two sulphide compounds have been focused upon in many studies.7,8,10 Although DAT and DATS represented 26.6% of the total sulphides found in garlic oil, little attention has been paid to them so far with respect to their antimicrobial activity.

The inhibitory effect of DAS, DADS, DAT and DATS against Helicobacter pylori has been observed in a previous report,5 the authors of which indicated that the bactericidal activity of these sulphides correlated with the number of sulphur atoms contained within them. On the other hand, it has also been indicated that the bactericidal effects of DAS and DADS against K. pneumoniae are due to them inhibiting the activity of arylamine N-acetyltransferase, an enzyme found in this pathogen.11 Thus, it is reasonable to examine the antibacterial activity of these sulphides against other medically important bacterial pathogens such as P. aeruginosa.

This study aimed to examine and compare the inhibitory activity of garlic oil and its four diallyl sulphides against two bacterial pathogens, P. aeruginosa and K. pneumoniae. The interaction of sulphide agents with antibiotics was also investigated. The results were expected to be beneficial for the development of new therapeutic agents.

Materials and methods

Garlic oil preparation

Garlic bulbs (Allium sativum L.) were purchased directly from farms. The method of Ravid & Putievsky12 was followed to prepare the garlic oil. Fresh plant materials were steam distilled for 3 h in a 100 L direct steam pilot plant apparatus. The recovered oil (2.2–4.3 g oil/kg garlic bulb) was stored at –80°C before use.

Diallyl sulphide preparation

DAS (purity 97%) and crude DADS (purity 80%) were purchased from Aldrich Chemical Co. (Milwaukee, WI, USA). DADS was purified further by fractional distillation to reach a final purity of >98%, which was examined by high performance liquid chromatography (HPLC). DAT and DATS were obtained by fractional distillation from crude DADS. The identification of DAT and DATS was confirmed by 1H-NMR spectroscopy (CDCl3, 300 MHz) and corresponded with the published data of Sparnins et al.13 The prepared standards were stored at –80°C before use. The concentrations of DAS, DADS, DAT and DATS in the prepared garlic oil were quantified by the HPLC method of Lawson et al.,9 and were found to be 1.8 ± 0.3, 26.7 ± 1.2, 17.2 ± 0.8 and 7.4 ± 0.5%, respectively; close to those of Lawson's original study.

Bacterial strains and medium

P. aeruginosa and K. pneumoniae were isolated from infected patients in Chungshan Hospital (Taichung, Taiwan). The total numbers of clinical isolates of P. aeruginosa and K. pneumoniae in this study were 123 and 114, respectively. All isolates were identified by Vitek (Vitek AMS; bioMérieux Vitek, Inc., Hazelwood, MO, USA) and API 20E (API-bioMérieux, La Balme Les Grottes, France). Antibiotic resistance profiles were determined by using discs with antibiotics placed on the surface of nutrient agar plates seeded with the test organism. Inhibition zones were measured after 24 h incubation at 37°C. Interpretation of resistance was based on the National Committee for Clinical Laboratory Standards (NCCLS) criteria. The antibiotics used were meropenem, ceftazidime, imipenem and gentamicin. The discs with antibiotics were purchased from Sigma Chemical Co. (St Louis, MO, USA). All cultures were routinely maintained on nutrient agar (Difco, Detroit, MI, USA) at 25°C until used.

MIC determination

Garlic oil and prepared standards of DAS, DADS, DAT and DATS were used for antibacterial tests, and their MICs determined using both antibiotic-susceptible and -resistant P. aeruginosa and K. pneumoniae. Microdilution MICs were determined with strains grown in cation-adjusted Mueller–Hinton broth according to NCCLS guidelines.14 The agent concentrations ranged from 128 to 0.125 mg/L. All incubations were at 37°C. Garlic oil, DAT and DATS had lower MICs (Table I), and were therefore used for the following two experiments.

Time–kill study of garlic oil

Twelve P. aeruginosa and 14 K. pneumoniae clinical isolates, which were multiply resistant to ceftazidime, gentamicin, imipenem and meropenem, were used in this study. In vitro kill of garlic oil against 12 multiply antibiotic-resistant P. aeruginosa or 12 K. pneumoniae was monitored in 10 mL volumes over 24 h at 37°C, after inoculation with actively growing cultures in cation-adjusted Mueller– Hinton broth without agitation. Aliquots (100 μL) were cultured on solid medium at intervals for determination of cfu/mL, and viable counts were read after 24 h incubation. The limit of detection was 20 cfu/mL.

Interaction of DAT or DATS with antibiotics

The interactive relationships between DAT or DATS and the four antibiotics against both antibiotic-susceptible and -resistant P. aeruginosa and K. pneumoniae were evaluated by the chequerboard method recommended by the NCCLS.15 Aliquots (100 μL) of each agent at 10 times the targeted final concentration were used. Agent–agent interactions were classified as synergic, additive or less-than-additive based on the fractional inhibitory concentration (FIC) index, which is the sum of FICs for each agent. The FIC of each agent is calculated as the MIC of the agent in combination, divided by the MIC of the agent alone. Agent–agent interactions are considered synergic if the FIC index is <1.0, additive if the FIC is equal to 1.0 and less-than-additive if the FIC index is >1.0.

Results

The proportions of P. aeruginosa and K. pneumoniae clinical isolates from Chungshan Hospital resistant to the four commonly used antibiotics were examined, and the resistance rates of the two pathogens to these antibiotics were in the range 12.2–36.8%. Gentamicin was the antibiotic with the highest resistance rate in this study. The MIC values of garlic oil and four diallyl sulphides for P. aeruginosa and K. pneumoniae are presented in Table I and followed the order DAS > DADS > DAT > garlic oil = DATS (P < 0.05). For each test organism, there was no significant difference in the MIC value of test agent between antibiotic-susceptible and antibiotic-resistant strains (P > 0.05).

The bactericidal effects of garlic oil determined by in vitro time–kill curves are shown in the Figure. After 6 h incubation, the bactericidal effects of garlic oil against both organisms increased significantly with increasing garlic oil concentrations from 0.5 × MIC to 4 × MIC. Garlic oil at 4 × MIC could effectively reduce the original inoculum to <2 log10 in P. aeruginosa and K. pneumoniae within 6 and 8 h, respectively.

The interactions of DAT or DATS with the four antibiotics against both antibiotic-susceptible and -resistant P. aeruginosa and K. pneumoniae, determined according to the FIC index, are shown in Tables II and III. Two combinations of DAT with antibiotics were less-than-additive because their FIC indices were >1 (Table II). They were DAT plus ceftazidime against ceftazidime-resistant K. pneumoniae, and DAT plus gentamicin against gentamicin-resistant K. pneumoniae. The other interactions of DAT or DATS with the four antibiotics against both P. aeruginosa and K. pneumoniae were classed as synergic or additive because the FIC indices were <1 (Tables II and III).

Discussion

The antimicrobial activity of garlic oil against H. pylori and Aspergillus species has been reported.5,6 The results of our present study show the antimicrobial activity of garlic oil against two other medically important pathogens. Since about 50% of garlic oil consisted of these four diallyl sulphides9 and these sulphides also possessed antibacterial activities (Table I), the observed antibacterial activity of garlic oil is partly explained by them. It is known that the multiply antibiotic-resistant bacteria tested can cause severe nosocomial infections, which increase morbidity and mortality in hospitalized patients.3,4 Garlic oil with the lower MICs (Table I) and effective bactericidal activity (Figure) may be considered as a functional food in human nutrition for prevention or treatment of nosocomial infections.

According to NCCLS standards, a breakpoint for antibiotic susceptibility is 8 mg/L. The MIC values of the four antibiotics tested for these antibiotic-resistant strains were >256 mg/L (data not shown). In practice, the MIC values for DAS and DADS may be too high to allow their clinical use. Although the MIC values of DAT and DATS still exceed 8 mg/L, these two agents were more effective in inhibiting antibiotic-resistant P. aeruginosa and K. pneumoniae when compared with the antibiotics tested. Furthermore, it should be pointed out that loss of garlic oil and sulphides by volatilization might occur during experimental procedure, although these materials have been treated with caution. Consequently, the MIC values obtained might be overestimated. On the other hand, these sulphide agents are naturally occurring components of garlic oil9 and certain vegetables, such as garlic and onion.13 The dietary nature of these vegetables may suggest the possible safety of these agents at these concentrations; however, further in vivo studies are needed to evaluate the metabolism, cytotoxicity, bactericidal efficiency and side effects of both.

In the studies by Chen et al.11 and Naganawa et al.,16 the anti-K. pneumoniae and anti-Candida albicans activities of DADS were significantly greater than DAS. O'Gara et al.5 indicated a relationship between lower MICs and number of sulphur atoms/molecule for diallyl sulphides against H. pylori. Our present study found a similar relationship in inhibition of P. aeruginosa. These results agreed with previous studies,5,11,16 and suggested that the number of sulphur atoms/molecule and/or disulphide bonds in these diallyl sulphides was an important factor in determining their antimicrobial activities.

In our present study, the inhibitory effects of DAS and DADS upon K. pneumoniae were close to those previously reported in a study11 that also suggested that inhibition of arylamine N-acetyltransferase activity might be responsible. As the latter enzyme is also present in P. aeruginosa,17,18 the same explanation may apply to the inhibition of growth reported here for this species. It is known that all four antibiotics could interfere with bacterial cell wall synthesis, increase bacterial membrane permeability and/ or inhibit bacterial protein synthesis at the 30S subunit of ribosomes.19–21 Therefore, the different modes of action of sulphide agents from antibiotics may be an important factor in the enhanced bactericidal efficacy observed when used in combination (Tables II and III). Since the combinations of diallyl polysulphides with antibiotics could inhibit both antibiotic-susceptible and antibiotic-resistant pathogenic bacteria, and most combinations were synergic or additive, the application of DAT or DATS combined with these antibiotics may be practical and beneficial in inhibiting both pathogens. Also, the required dosage of these antibiotics used in combination may be less than when used alone, which may further reduce the occurrence of side effects caused by these antimicrobials. Several studies have proved that DAS and DADS could be recovered in circulation via oral supply, and showed medical benefits.22,23 The iv administration of the sulphides would be more suitable because antibiotics could be administered simultaneously.

In conclusion, garlic oil and its two components, DAT and DATS, possessed in vitro antibacterial activity against multiply antibiotic-resistant P. aeruginosa and K. pneumoniae. Both additive and synergic effects were observed in the combinations of ceftazidime, gentamicin, imipenem and meropenem with these two sulphide agents; therefore, garlic oil and both sulphides may have the potential to prevent or treat nosocomial infections caused by P. aeruginosa and K. pneumoniae.

MICs (mg/L) of garlic oil and four diallyl sulphides (DAS, DADS, DAT and DATS) against antibiotic-susceptible and -resistant P. aeruginosa and K. pneumoniae (data are expressed as mean ± s.d.)

Garlic oil DAS DADS DAT DATS
CZ, ceftazidime; GE, gentamicin; IM, imipenem; ME, meropenem.
P. aeruginosa
susceptible 16 ± 2 80 ± 12 64 ± 8 32 ± 4 12 ± 2
CZ resistant 16 ± 4 84 ± 16 64 ± 4 32 ± 8 12 ± 2
GE resistant 16 ± 8 88 ± 12 64 ± 8 36 ± 4 12 ± 4
IM resistant 20 ± 2 80 ± 16 72 ± 8 36 ± 8 16 ± 2
ME resistant 16 ± 4 84 ± 12 64 ± 8 32 ± 8 16 ± 4
K. pneumoniae
susceptible 24 ± 8 96 ± 12 72 ± 8 40 ± 8 20 ± 4
CZ resistant 28 ± 4 96 ± 16 72 ± 4 48 ± 4 24 ± 2
GE resistant 24 ± 4 104 ± 8 80 ± 8 48 ± 8 20 ± 8
IM resistant 24 ± 8 96 ± 8 80 ± 12 40 ± 4 24 ± 4
ME resistant 28 ± 8 104 ± 16 72 ± 8 40 ± 4 24 ± 8
Garlic oil DAS DADS DAT DATS
CZ, ceftazidime; GE, gentamicin; IM, imipenem; ME, meropenem.
P. aeruginosa
susceptible 16 ± 2 80 ± 12 64 ± 8 32 ± 4 12 ± 2
CZ resistant 16 ± 4 84 ± 16 64 ± 4 32 ± 8 12 ± 2
GE resistant 16 ± 8 88 ± 12 64 ± 8 36 ± 4 12 ± 4
IM resistant 20 ± 2 80 ± 16 72 ± 8 36 ± 8 16 ± 2
ME resistant 16 ± 4 84 ± 12 64 ± 8 32 ± 8 16 ± 4
K. pneumoniae
susceptible 24 ± 8 96 ± 12 72 ± 8 40 ± 8 20 ± 4
CZ resistant 28 ± 4 96 ± 16 72 ± 4 48 ± 4 24 ± 2
GE resistant 24 ± 4 104 ± 8 80 ± 8 48 ± 8 20 ± 8
IM resistant 24 ± 8 96 ± 8 80 ± 12 40 ± 4 24 ± 4
ME resistant 28 ± 8 104 ± 16 72 ± 8 40 ± 4 24 ± 8

MICs (mg/L) of garlic oil and four diallyl sulphides (DAS, DADS, DAT and DATS) against antibiotic-susceptible and -resistant P. aeruginosa and K. pneumoniae (data are expressed as mean ± s.d.)

Garlic oil DAS DADS DAT DATS
CZ, ceftazidime; GE, gentamicin; IM, imipenem; ME, meropenem.
P. aeruginosa
susceptible 16 ± 2 80 ± 12 64 ± 8 32 ± 4 12 ± 2
CZ resistant 16 ± 4 84 ± 16 64 ± 4 32 ± 8 12 ± 2
GE resistant 16 ± 8 88 ± 12 64 ± 8 36 ± 4 12 ± 4
IM resistant 20 ± 2 80 ± 16 72 ± 8 36 ± 8 16 ± 2
ME resistant 16 ± 4 84 ± 12 64 ± 8 32 ± 8 16 ± 4
K. pneumoniae
susceptible 24 ± 8 96 ± 12 72 ± 8 40 ± 8 20 ± 4
CZ resistant 28 ± 4 96 ± 16 72 ± 4 48 ± 4 24 ± 2
GE resistant 24 ± 4 104 ± 8 80 ± 8 48 ± 8 20 ± 8
IM resistant 24 ± 8 96 ± 8 80 ± 12 40 ± 4 24 ± 4
ME resistant 28 ± 8 104 ± 16 72 ± 8 40 ± 4 24 ± 8
Garlic oil DAS DADS DAT DATS
CZ, ceftazidime; GE, gentamicin; IM, imipenem; ME, meropenem.
P. aeruginosa
susceptible 16 ± 2 80 ± 12 64 ± 8 32 ± 4 12 ± 2
CZ resistant 16 ± 4 84 ± 16 64 ± 4 32 ± 8 12 ± 2
GE resistant 16 ± 8 88 ± 12 64 ± 8 36 ± 4 12 ± 4
IM resistant 20 ± 2 80 ± 16 72 ± 8 36 ± 8 16 ± 2
ME resistant 16 ± 4 84 ± 12 64 ± 8 32 ± 8 16 ± 4
K. pneumoniae
susceptible 24 ± 8 96 ± 12 72 ± 8 40 ± 8 20 ± 4
CZ resistant 28 ± 4 96 ± 16 72 ± 4 48 ± 4 24 ± 2
GE resistant 24 ± 4 104 ± 8 80 ± 8 48 ± 8 20 ± 8
IM resistant 24 ± 8 96 ± 8 80 ± 12 40 ± 4 24 ± 4
ME resistant 28 ± 8 104 ± 16 72 ± 8 40 ± 4 24 ± 8

Interaction of DAT with antibiotics, determined according to the FIC index, against antibiotic-susceptible and -resistant P. aeruginosa and K. pneumoniae

P. aeruginosaK. pneumoniae
susceptible resistant susceptible resistant
CZ, ceftazidime; GE, gentamicin; IM, imipenem; ME, meropenem.
aThe interaction of DAT with antibiotics was evaluated by the chequerboard method recommended by the NCCLS for each agent.
bThe interaction was additive.
cThe interaction was less than additive.
DAT 0.5 0.75 0.5 0.75
CZ 0.25 0.25 0.5 0.375
FIC indexa0.75 1.0b1.0b1.125c
DAT 0.25 0.625 0.25 0.75
GE 0.5 0.25 0.75 0.5
FIC index 0.75 0.875 1.0§1.25c
DAT 0.25 0.5 0.25 0.5
IM 0.5 0.375 0.5 0.5
FIC index 0.75 0.875 0.75 1.0b
DAT 0.25 0.75 0.625 0.625
ME 0.125 0.125 0.125 0.25
FIC index 0.625 0.875 0.75 0.875
P. aeruginosaK. pneumoniae
susceptible resistant susceptible resistant
CZ, ceftazidime; GE, gentamicin; IM, imipenem; ME, meropenem.
aThe interaction of DAT with antibiotics was evaluated by the chequerboard method recommended by the NCCLS for each agent.
bThe interaction was additive.
cThe interaction was less than additive.
DAT 0.5 0.75 0.5 0.75
CZ 0.25 0.25 0.5 0.375
FIC indexa0.75 1.0b1.0b1.125c
DAT 0.25 0.625 0.25 0.75
GE 0.5 0.25 0.75 0.5
FIC index 0.75 0.875 1.0§1.25c
DAT 0.25 0.5 0.25 0.5
IM 0.5 0.375 0.5 0.5
FIC index 0.75 0.875 0.75 1.0b
DAT 0.25 0.75 0.625 0.625
ME 0.125 0.125 0.125 0.25
FIC index 0.625 0.875 0.75 0.875

Interaction of DAT with antibiotics, determined according to the FIC index, against antibiotic-susceptible and -resistant P. aeruginosa and K. pneumoniae

P. aeruginosaK. pneumoniae
susceptible resistant susceptible resistant
CZ, ceftazidime; GE, gentamicin; IM, imipenem; ME, meropenem.
aThe interaction of DAT with antibiotics was evaluated by the chequerboard method recommended by the NCCLS for each agent.
bThe interaction was additive.
cThe interaction was less than additive.
DAT 0.5 0.75 0.5 0.75
CZ 0.25 0.25 0.5 0.375
FIC indexa0.75 1.0b1.0b1.125c
DAT 0.25 0.625 0.25 0.75
GE 0.5 0.25 0.75 0.5
FIC index 0.75 0.875 1.0§1.25c
DAT 0.25 0.5 0.25 0.5
IM 0.5 0.375 0.5 0.5
FIC index 0.75 0.875 0.75 1.0b
DAT 0.25 0.75 0.625 0.625
ME 0.125 0.125 0.125 0.25
FIC index 0.625 0.875 0.75 0.875
P. aeruginosaK. pneumoniae
susceptible resistant susceptible resistant
CZ, ceftazidime; GE, gentamicin; IM, imipenem; ME, meropenem.
aThe interaction of DAT with antibiotics was evaluated by the chequerboard method recommended by the NCCLS for each agent.
bThe interaction was additive.
cThe interaction was less than additive.
DAT 0.5 0.75 0.5 0.75
CZ 0.25 0.25 0.5 0.375
FIC indexa0.75 1.0b1.0b1.125c
DAT 0.25 0.625 0.25 0.75
GE 0.5 0.25 0.75 0.5
FIC index 0.75 0.875 1.0§1.25c
DAT 0.25 0.5 0.25 0.5
IM 0.5 0.375 0.5 0.5
FIC index 0.75 0.875 0.75 1.0b
DAT 0.25 0.75 0.625 0.625
ME 0.125 0.125 0.125 0.25
FIC index 0.625 0.875 0.75 0.875

Interaction of DATS with antibiotics, determined according to the FIC index, against antibiotic-susceptible and -resistant P. aeruginosa and K. pneumoniae

P. aeruginosaK. pneumoniae
susceptible resistant susceptible resistant
CZ, ceftazidime; GE, gentamicin; IM, imipenem; ME, meropenem.
aThe interaction of DATS with antibiotics was evaluated by the chequerboard method recommended by the NCCLS for each agent.
bThis interaction was additive.
DATS 0.25 0.5 0.375 0.5
CZ 0.5 0.375 0.5 0.5
FIC indexa0.75 0.875 0.875 1.0b
DATS 0.5 0.5 0.75 0.75
GE 0.25 0.375 0.125 0.25
FIC index 0.75 0.875 0.875 1.0b
DATS 0.5 0.5 0.25 0.625
IM 0.125 0.25 0.5 0.25
FIC index 0.625 0.75 0.75 0.875
DATS 0.125 0.25 0.5 0.75
ME 0.5 0.5 0.25 0.125
FIC index 0.625 0.75 0.75 0.875
P. aeruginosaK. pneumoniae
susceptible resistant susceptible resistant
CZ, ceftazidime; GE, gentamicin; IM, imipenem; ME, meropenem.
aThe interaction of DATS with antibiotics was evaluated by the chequerboard method recommended by the NCCLS for each agent.
bThis interaction was additive.
DATS 0.25 0.5 0.375 0.5
CZ 0.5 0.375 0.5 0.5
FIC indexa0.75 0.875 0.875 1.0b
DATS 0.5 0.5 0.75 0.75
GE 0.25 0.375 0.125 0.25
FIC index 0.75 0.875 0.875 1.0b
DATS 0.5 0.5 0.25 0.625
IM 0.125 0.25 0.5 0.25
FIC index 0.625 0.75 0.75 0.875
DATS 0.125 0.25 0.5 0.75
ME 0.5 0.5 0.25 0.125
FIC index 0.625 0.75 0.75 0.875

Interaction of DATS with antibiotics, determined according to the FIC index, against antibiotic-susceptible and -resistant P. aeruginosa and K. pneumoniae

P. aeruginosaK. pneumoniae
susceptible resistant susceptible resistant
CZ, ceftazidime; GE, gentamicin; IM, imipenem; ME, meropenem.
aThe interaction of DATS with antibiotics was evaluated by the chequerboard method recommended by the NCCLS for each agent.
bThis interaction was additive.
DATS 0.25 0.5 0.375 0.5
CZ 0.5 0.375 0.5 0.5
FIC indexa0.75 0.875 0.875 1.0b
DATS 0.5 0.5 0.75 0.75
GE 0.25 0.375 0.125 0.25
FIC index 0.75 0.875 0.875 1.0b
DATS 0.5 0.5 0.25 0.625
IM 0.125 0.25 0.5 0.25
FIC index 0.625 0.75 0.75 0.875
DATS 0.125 0.25 0.5 0.75
ME 0.5 0.5 0.25 0.125
FIC index 0.625 0.75 0.75 0.875
P. aeruginosaK. pneumoniae
susceptible resistant susceptible resistant
CZ, ceftazidime; GE, gentamicin; IM, imipenem; ME, meropenem.
aThe interaction of DATS with antibiotics was evaluated by the chequerboard method recommended by the NCCLS for each agent.
bThis interaction was additive.
DATS 0.25 0.5 0.375 0.5
CZ 0.5 0.375 0.5 0.5
FIC indexa0.75 0.875 0.875 1.0b
DATS 0.5 0.5 0.75 0.75
GE 0.25 0.375 0.125 0.25
FIC index 0.75 0.875 0.875 1.0b
DATS 0.5 0.5 0.25 0.625
IM 0.125 0.25 0.5 0.25
FIC index 0.625 0.75 0.75 0.875
DATS 0.125 0.25 0.5 0.75
ME 0.5 0.5 0.25 0.125
FIC index 0.625 0.75 0.75 0.875

In vitro time–kill of garlic oil at various concentrations against P. aeruginosa (a) and K. pneumoniae (b) within 24 h. –♦–, control; ▪, 0.5 × MIC; ▴, 1 × MIC; •, 2 × MIC; - -♦- -, 4 × MIC. Data are expressed as mean ± s.d. (n = 12).

In vitro time–kill of garlic oil at various concentrations against P. aeruginosa (a) and K. pneumoniae (b) within 24 h. –♦–, control; ▪, 0.5 × MIC; ▴, 1 × MIC; •, 2 × MIC; - -♦- -, 4 × MIC. Data are expressed as mean ± s.d. (n = 12).

Corresponding author. Tel: +886-4-2473-0022 ext. 1753; Fax: +886-4-2473-9030; E-mail: mcyin@mercury.csmc.edu.tw

This study was supported by grants from the National Science Council, Republic of China (NSC 89-2320-B-040-060 and NSC 90-2320-B-040-007).

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Scientific Name(s): Tussilago farfara L.
Common Name(s): Folia farfarae, Coltsfoot, Filius ante patrem, Kuan Don Hua, Kuandong Hua

Medically reviewed by Drugs.com. Last updated on Dec 3, 2018.

Clinical Overview

Use

Information to support traditional uses (eg, antioxidant, antitussive, antimicrobial, pressor effects) is limited to in vitro and animal studies.

Dosing

Clinical trials are lacking to provide dosage recommendations.

Contraindications

Antitubercular Activity Of Garlic Oil

Information is lacking. Avoid in pregnancy and in patients with hepatic disease.

Pregnancy/Lactation

Avoid use. Preparations may contain hepatotoxic pyrrolizidine alkaloids with carcinogenic and mutagenic potential.

Interactions

None well documented. Caution is warranted if used concurrently with anticoagulants (eg, warfarin) or antiplatelet agents (eg, aspirin, clopidogrel, prasugrel).

Adverse Reactions

Clinical trials are lacking. Allergic and hypertensive effects are possible.

Toxicology

Carcinogenicity, mutagenicity, and phototoxicity have been described for various chemical constituents.

Scientific Family

  • Asteraceae (daisies)

Botany

Coltsfoot is an invasive, perennial plant growing up to 30 cm tall. Golden flowers that look similar to dandelions appear and die before leaves are produced, hence the name Filius ante patrem (the son before the father). The seeds of the plant are soft, hair-like tufts often used by birds to build nests, and the leaves are broad and hoof-shaped, with hairs on upper and lower surfaces. The leaves and flowering buds are of primary medicinal interest. Although related to Petasites (butterbur), activities of coltsfoot should be regarded separately.USDA.2014, Duke.2002, Shikov 2014 Although sometimes considered synonymous with Petasites Mill., butterbur and coltsfoot are monographed separately (see Butterbur monograph).

History

Coltsfoot has been widely used for multiple indications, including the treatment of bronchitis, lung cancer, emphysema, inflammation, rheumatism, swelling and water retention, and tuberculosis. It is listed in the Chinese and Russian pharmacopoeias as having been used for centuries for coughs.Duke 2002, Kim 2013, Shikov 2014

Chemistry

Pyrrolizidine alkaloids, especially senkirkine, are present; however, the total alkaloid content is lower than in butterbur.Duke 2002, Shikov 2014

Sequiterpenes, including tussilagone, bisabolene, triterpenes, flavonoids, and pyrrolizidine alkaloids, are well described.Li 2012, Liu 2011, Liu 2008, Park 2008 An overview of the chemical constituents in the flowers, leaves, and whole plant is available.Duke 2014

Uses and Pharmacology

Cardiovascular effects

Animal data

In dogs, cats, and rats, an alcoholic extract produced a pressor effect similar to that of dopamine, but without tachyphylaxis. Increased heart rate was observed.Shikov 2014, Li 1988

Clinical data

Research reveals no clinical data regarding the use of coltsfoot in cardiovascular conditions.

Respiratory effects

Animal data

Antitussive and expectorant effects of coltsfoot flowers have been investigated in mice.Li 2012, Li 2013

Clinical data

Despite traditional use for coughs, research reveals no clinical data regarding the use of coltsfoot in respiratory conditions.

Other uses

Antimicrobial effects have been shown against Bacillus cereus, Mycobacterium tuberculosis, and Staphylococcus aureus.Kokoska 2002, Zhao 2014

Several studies have demonstrated antioxidant effects for coltsfoot; clinical applications are lacking, but may relate to anti-inflammatory and chemo- and neuroprotective effects.Cho 2005, Kim 2006, Li 2012, Lim 2008

Further in vitro studies suggest extracts of coltsfoot may have applications in diabetes and cancer.Li 2014, Park 2008

Dosing

Clinical trials are lacking to provide dosage recommendations.

Traditional dosage: 2 to 4 mL liquid leaf extract or 0.6 to 2 mL liquid flower extract.Duke 2002

No more than 4.5 to 6 g/day for no longer than 4 to 6 weeks per year in total, due to pyrrolizidine alkaloid content.Duke 2002, Blumenthal 2000

Pregnancy / Lactation

Avoid use. Preparations may contain hepatotoxic pyrrolizidine alkaloids with carcinogenic and mutagenic potential.Blumenthal 2000, Duke 2002, Ernst 2002

Interactions

None well documented.Chen 2012, Ulbricht 2008 High doses of coltsfoot may interact with cardiovascular medicines.Duke 2002 The constituent tussilagone demonstrates weak antiplatelet and calcium channel blocking activity.Hwang 1987, Liu 2008 Caution is warranted if coltsfoot is used concurrently with anticoagulants (eg, warfarin) or antiplatelet agents (eg, aspirin, clopidogrel, prasugrel).

Adverse Reactions

Animal studies reported allergenic potential.Duke 2002 A warning label regarding the presence of potentially hepatotoxic pyrrolizidine alkaloids has been recommended for all coltsfoot preparations.Kim 2013, Dangerous supplements 2010

Toxicology

Pyrrolizidine alkaloids are liver toxins with carcinogenic and mutagenic potential.Blumenthal 2000, Shikov 2014 Phototoxicity has been reported in guinea pig skin.Duke 2002 Development of hepatic tumors in rats has been reported.Duke 2002, Hirono 1976 Case reports exist of both fatal (in a newborn) and reversible (in an 18-month-old) hepatic vaso-occlusive disease; causality was suspected but not established.Shikov 2014, Sperl 1995 Coltsfoot was implicated in another case report of deep vein thrombosis and pulmonary embolism in an adult consuming a combination of herbal preparations.Freshour 2012

Index Terms

  • Petasites

References

Blumenthal M, Goldberg A, Brinckmann J. Herbal medicine: Expanded Commission E Monographs. Newton, MA: Integrative Medicine Communications; 2000.Chen X, Sneed K, Pan S, et al. Herb-drug interactions and mechanistic and clinical considerations. Curr Drug Metab. 2012;13(5):640-651.22292789Cho J, Kim HM, Ryu JH, Jeong YS, Lee YS, Jin C. Neuroprotective and antioxidant effects of the ethyl acetate fraction prepared from Tussilago farfara L. Biol Pharm Bull. 2005;28(3):455-460.15744068Dangerous supplements: what you don't know about these 12 ingredients could hurt you. Consum Rep. 2010;75(9):16-20.Duke J, Bogenschutz-Godwin M, duCellier J, Duke P. Handbook of Medicinal Herbs. 2nd ed. Boca Raton, FL: CRC Press; 2002.Ernst E. Herbal medicinal products during pregnancy: Are they safe? BJOG. 2002;109(3):227-235.11950176Freshour JE, Odle B, Rikhye S, Stewart DW. Coltsfoot as a potential cause of deep vein thrombosis and pulmonary embolism in a patient also consuming kava and blue vervain. J Diet Suppl. 2012;9(3):149-154.22876743Hirono I, Mori H, Culvenor CC. Carcinogenic activity of coltsfoot, Tussilago farfara L. Gann. 1976;67(1):125-129.1269853Hwang SB, Chang MN, Garcia ML, et al. L-652,469 — a dual receptor antagonist of platelet activating factor and dihydropyridines from Tussilago farfara L. Eur J Pharmacol. 1987;141(2):269-281.2824219Kim EJ, Chen Y, Huang JQ, et al. Evidence-based toxicity evaluation and scheduling of Chinese herbal medicines. J Ethnopharmacol. 2013;146(1):40-61.23286904Kim MR, Lee JY, Lee HH, et al. Antioxidative effects of quercetin-glycosides isolated from the flower buds of Tussilago farfara L. Food Chem Toxicol. 2006;44(8):1299-1307.16574296Kokoska L, Polesny Z, Rada V, Nepovim A, Vanek T. Screening of some Siberian medicinal plants for antimicrobial activity. J Ethnopharmacol. 2002;82(1):51-53.12169406Li H, Lee HJ, Ahn YH, et al. Tussilagone suppresses colon cancer cell proliferation by promoting the degradation of beta-catenin. Biochem Biophys Res Commun. 2014;443(1):132-137.24269588Li W, Huang X, Yang XW. New sesquiterpenoids from the dried flower buds of Tussilago farfara and their inhibition on NO production in LPS-induced RAW264.7 cells. Fitoterapia. 2012;83(3):318-322.22120501Li YP, Wang YM. Evaluation of tussilagone: a cardiovascular-respiratory stimulant isolated from Chinese herbal medicine. Gen Pharmacol. 1988;19(2):261-263.3350333Li ZY, Zhi HJ, Xue SY, et al. Metabolomic profiling of the flower bud and rachis of Tussilago farfara with antitussive and expectorant effects on mice. J Ethnopharmacol. 2012;140(1):83-90.22210102Li ZY, Zhi HJ, Zhang FS, et al. Metabolomic profiling of the antitussive and expectorant plant Tussilago farfara L. by nuclear magnetic resonance spectroscopy and multivariate data analysis. J Pharm Biomed Anal. 2013;75:158-164.23261808Lim HJ, Lee HS, Ryu JH. Suppression of inducible nitric oxide synthase and cyclooxygenase-2 expression by tussilagone from Farfarae flos in BV-2 microglial cells. Arch Pharm Res. 2008;31(5):645-652.18481023Liu LL, Yang JL, Shi YP. Sesquiterpenoids and other constituents from the flower buds of Tussilago farfara. J Asian Nat Prod Res. 2011;13(10):920-929.21972807Liu YF, Yang XW, Lu W, Xin XL. Determination and pharmacokinetic study of tussilagone in rat plasma by RP-HPLC method. Biomed Chromatogr. 2008;22(11):1194-1200.18651585Park HR, Yoo MY, Seo JH, et al. Sesquiterpenoids isolated from the flower buds of Tussilago farfara L. inhibit diacylglycerol acyltransferase. J Agric Food Chem. 2008;56(22):10493-10497.18937486Shikov AN, Pozharitskaya ON, Makarov VG, Wagner H, Verpoorte R, Heinrich M. Medicinal plants of the Russian Pharmacopoeia; their history and applications. J Ethnopharmacol. 2014;154(3):481-536.24742754Sperl W, Stuppner H, Gassner I, Judmaier W, Dietze O, Vogel W. Reversible hepatic veno-occlusive disease in an infant after consumption of pyrrolizidine-containing herbal tea. Eur J Pediatr. 1995;154(2):112-116.7720737Tussilago farfara. Dr. Duke's Phytochemical and Ethnobotanical Databases. http://www.ars-grin.gov/duke. Accessed November 6, 2014.Tussilago farfara L. USDA, NRCS. 2014. The PLANTS Database. (http://plants.usda.gov, 4 August 2014). National Plant Data Team, Greensboro, NC 27401-4901 USA. Accessed November 6, 2014.Ulbricht C, Chao W, Costa D, Rusie-Seamon E, Weissner W, Woods J. Clinical evidence of herb-drug interactions: A systematic review by the natural standard research collaboration. Curr Drug Metab. 2008;9(10):1063-1120.19075623Zhao J, Evangelopoulos D, Bhakta S, Gray AI, Seidel V. Antitubercular activity of Arctium lappa and Tussilago farfara extracts and constituents. J Ethnopharmacol. 2014;155(1):796-800.24955560

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