Medicinal Plants Classification Biosynthesis and ... - Index of

328
Philippe N. Okusa, Caroline Stevigny and Pierre Duez
bacteria to antibiotics; (ii) reverse acquired resistance; and (iii) reduce the frequency of
resistant mutant strains emergence.
Medicinal plants extracts and natural compounds have been reported to inhibit efflux
systems, thus enhancing or restoring the activity of diverse antibiotics. Among them:
4.1.2.1. Alkaloids
Reserpine, an antihypertensive alkaloid isolated from Rauwolfia sp, is known to inhibit
the P-gp and potentiate the activity of fluoroquinolones on MDR Gram-positive bacteria; it
enhances also the activity of tetracycline against MRSA strains and it has been shown to
inhibit the LmrA of L. lactis, the ABC efflux system that confers MDR to this strain
(Marquez, 2005). These effects of reserpine however appear at concentrations too high to be
clinically relevant and moreover bacterial resistance to reserpine has been selected in some
strains.
4.1.2.2. Flavonoids
Several Berberis medicinal plants producing berberine, an antimicrobial alkaloid, were
found to also synthesize 5-methoxyhydnocarpin (5-MHC), an inhibitor of the NorA MDR
pump of S. aureus (Stermitz et al., 2000a). 5-MHC, an amphipathic weak acid, distinctly
different from the cationic substrates of the NorA, has no antimicrobial activity per itself but
increases the intracellular accumulation of berberine and strongly potentiates its activity
(Stermitz et al., 2000b).
4.1.2.3. Alkyl Gallates
Numerous biological properties have been reported for the green tea phenols, epigallocatechin
gallates and epicatechin gallates, including antimicrobial activities, reversal of
methicillin resistance or inhibition of P-gp. These compounds were also found to reverse
tetracycline resistance in Staphylococci strains and to potentiate the activity of norfloxacin
against a NorA over-expressing S. aureus (Hatano et al., 2005).
4.1.2.4. Terpenoids
Diterpens compounds, carnosic acid from Rosmarinus officinalis and isopimarane
derivatives from Lycopus europaeus, potentiate the activity of erythromycin and tetracycline
against a macrolide- highly resistant S. aureus harboring the ABC transporter MsrA (Brehm-
Stecher and Johnson, 2003).
4.2. Β-Lactamases Inhibitors
The production of β-lactamases, enzymes that hydrolyse the β-lactam ring of
cephalosporins and penicillins, is the most determinant cause of resistance to β-lactams
(Livermore, 1995).
To overcome β-lactamases related resistance, antibiotics association including non βlactams
can be used; an other approach, more interesting, is the use of β-lactams in
association with inhibitors of β-lactamases. Clavulanic acid combination with amoxicillin
demonstrates how successful this approach can be; this beta-lactamase inhibitor is combined