Evaluation of polyphenolic profile and antibacterial activity of pomegranate juice in combination with rifampin (R) against MDR-TB clinical isolates.
Curr Pharm Biotechnol. 2019 03 8. Epub 2019 Mar 8. PMID: 30854955
BACKGROUND: The global rise of multi-drug resistant M. tuberculosis demands unconventional treatment to enhance the efficiency of current drugs. Punica granatum, which is known as pomegranate, is considered as a member of the Punicaceae family. Pomegranate, which is broadly documented for its activity against a wide spectrum of bacterial pathogens, deserves further scrutiny in this respect.
METHODS: Within this scope, this study investigated the effect of fresh pomegranate juice (FPJ) on the antibacterial activity of anti-tuberculosis drugs (Rifampin (R) and Isoniazid (INH)) against MDR-TB clinical isolates. The drug resistance profiles in M. tuberculosis clinical isolates were determined by susceptibility test using BACTEC MGIT 960 system. Four concentrations of fresh pomegranate juice (FPJ) (5%, 10%, 15%, and 20%) were evaluated in combination with R and INH at a dose range of (1.0µg/ml), and (0.1µg/ml), respectively against the MDR-TB isolates by the BACTEC MGIT 960 system. Moreover, this study scrutinized individual phenolic compounds of FPJ by using high-performance liquid chromatography (HPLC). The total polyphenols (TP), total flavonoid (TF), total anthocyanins content(TAC), and the antioxidant capacity were also assessed in FPJ.
RESULTS: Synergistic effects were observed between R and INH with FPJ against all tested strains. However, combination therapy of rifampin was more effective than isoniazid one. Therefore, the combination of R and FPJ has been used against (27) MDR-TB clinical isolates. 5% of FPJ plus R (1.0µg/ml) were found to suppress the growth of one isolates for first group (INH and R resistant), while, for second (SM, R and INH resistant) and third group (INH, EMB, R and SM resistant), 5% of FPJ demonstrated no synergistic impact with R. Moreover, 10% of FPJ and R (1.0 µg/ml) inhibited the bacterial growth of three isolates of first group and two isolates and one isolate for second and third group, respectively. Remarkably, 15% of FPJ plus R (1.0 µg/ml) appeared to inhibit the growth of MDR-TB isolates for all tested groups indicating a strong synergistic effect. Regarding H37RV, the complete inhibition of the bacterial growth was found to occur at 15% and 20% concentrations of FPJ only. Minimum inhibitory concentration (MIC) of FPJ for first group ranged from (4%-13%), while for second group and third group were approximately between (10%-15%). Thus, FPJ at 15% inhibited 100% of bacteria for all tested isolates (MIC100% =15%). Phenolic compounds identified in FPJ were gallic acid, benzoic acid, syringic, folic acid, pelargonidin, naringin+ellagic acid, naringenin, chlorogenic acid, caffeic acid, catechin, myricetin, Kaempferol, Quercetin, cyanidin-3-glycoside, p-cummaric acid, ferulic acid, and rutin. Total phenolic (TP), total flavonoid (TF), and total anthocyanin (TA) content were 841.5 mg /L, 638.73 mg RE/L, and 47.43 mg/L, accordingly.
CONCLUSION: Overall, FPJ displayed synergistic effect with R against MDR-TB clinical isolates due to its high content of polyphenol and antioxidant capability