C-Geranylated flavonoids fromPaulownia tomentosafruits with antimicrobial potential and synergistic activity with antibiotics

Abstract

Context C-6-Geranylated flavonoids possess promising biological activities. These substances could be a source of lead compounds for the development of therapeutics. Objective The study was designed to evaluate their antibacterial and antileishmanial activity. Materials and methods C-6-Geranylated flavanones were tested in micromolar concentrations against promastigote forms of Leishmania brazilensis, L. donovani, L. infantum, and L. panamensis against methicillin-resistant Staphylococcus aureus (MRSA); and synergistic potential with antibiotics was analyzed. IC50 values (after 72 h) were calculated and compared with that of miltefosine. Flow cytometry and DNA fragmentation analysis were used the mechanism of the effect. Geranylated flavanones or epigallocatechin gallate were combined with oxacillin, tetracycline, and ciprofloxacin, and the effects of these two-component combinations were evaluated. Minimal inhibitory concentrations (MICs) and minimal bactericidal concentrations (MBCs) were established (after 24 h), the synergy was measured by the checkerboard titration technique, and the sums of the fractional inhibitory concentrations (∑FICs) were computed. Results 3'-O-Methyl-5'-O-methyldiplacone and 3'-O-methyldiplacone showed good antileishmanial activities (IC50 8-42 μM). 3'-O-Methyl-5'-hydroxydiplacone activates the apoptotic death at leishmanias, the effect of 3'-O-methyl-5'-O-methyldiplacone has another mechanism. The test of the antibacterial activity showed good effects of 3'-O-methyldiplacol and mimulone against MRSA (MIC 2-16 μg/mL), and in six cases, the results showed synergistic effects when combined with oxacillin. Synergistic effects were also found for the combination of epigallocatechin gallate with tetracycline or oxacillin. Conclusion This work demonstrates anti-MRSA and antileishmanial potential of geranylated flavanones and uncovers their promising synergistic activities with antibiotics. In addition, the mechanism of antileishmanial effect is proposed.

Antibacterial activity of flavonoids and their structure–activity relationship: An update review

“…aureus . Out of them, mimulone ( 81 ), (geranylated flavonoids) was more effective than the oxacillin (antibiotic standard) with MIC values of 2/4.9 μg/ml (Navrátilová et al, ). The relationship between lipophilicity and the structure of flavonoid analogues in growth inhibition of Gram‐positive and Gram‐negative bacteria were evaluated by flavones from Heliotropium filifolium .…”

“…aureus with FIC: 0.3–0.5. Navrátilová et al () evaluated the antibacterial activity of 3′‐O‐methyldiplacol ( 100 ) alone and in combination with oxacillin against MRSA strain. Based on MIC/Minimum Bactericidal Concentration (MBC) result (4/4 and 2/4 μg/ml, alone, and combined, respectively), this combination had a synergistic effect against MRSA and this compound was more potent than the standard drug.…”

Paulownia C-geranylated flavonoids: their structural variety, biological activity and application prospects

“…The antiparasitic activities of Paulownia C-geranylated flavonoids mainly involved the effects of seven unmodified C-geranylflavanones on Leishmania species, including mimulone (1), diplacone (2), 3′-Omethyldiplacone (4), 3′-O-methyl-5′-hydroxydiplacone (5), 3′-O-methyl-5′-O-methyldiplacone (6), 4′-O-methyldiplacone (7), and 3′-O-methyldiplacol (15). Compounds 4 and 6 achieved significant antileishmanial activity with IC 50 values of 10.4 and 12.7 μM against L. donovani, and 11.3 and 8.0 μM against L. braziliensis, respectively, compared with 9.5 and 6.7 μM of miltefosine as the positive control (Navrátilová et al 2016). Furthermore, diplacone (2) was also active (IC 50 1.4 µg mL −1 ) against the related kinetoplastid parasite Trypanosoma brucei brucei (Salem et al 2011).…”

Flavonoid-Rich Extract of Paulownia fortunei Flowers Attenuates Diet-Induced Hyperlipidemia, Hepatic Steatosis and Insulin Resistance in Obesity Mice by AMPK Pathway

“…Epidemiological studies revealed that an increased daily intake of phenolic compounds in dietary supplements act as anti-oxidant and anti-inflammatory agents to increase thermogenesis and energy expenditure while decreasing inflammation and oxidative stress, further supporting progress towards decreased metabolic disorders [ 1 , 5 ]. Previous studies confirmed that the species of the genus Paulownia (belonging to the family scrophulariaceae) exhibited a broad spectrum of biological effects, including antioxidant, anticarcinogenic [ 6 , 7 ], antiphlogistic [ 8 ], antiviral [ 9 ], antimicrobial [ 10 ] and anti-cholinesterase activities [ 11 ]. Paulownia fortunei (Seem.)…”

“…Hemsl. is a fast growing ornamental tree, native to Mainland China and distributed almost all over the world [ 10 ]. This species is renowned as a polyphenol rich plant, which has been used in traditional Chinese medicine for the treatment of hypertension, enteritis, tonsillitis, bronchitis and dysentery [ 7 , 12 , 13 ].…”