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The present study was designed to evaluate the effects of flavonoids luteolin (L) and quercetin + luteolin (Q + L) in combination with commonly used antibacterial agents against methicillin-resistant Staphylococcus aureus (MRSA) clinical isolates and S. aureus (ATCC 43300). Minimum inhibitory concentrations (MICs) of L and Q + L, as well as the MICs of flavonoids in combination with antibiotics were determined and results showed an increased activity of flavonoids with antibiotics. The synergistic, additive, or antagonistic relationships between flavonoids (L and Q + L) and antibiotics were also evaluated, and additive and synergistic effects were observed for some antibiotic + flavonoid combinations. In addition, some combinations were also found to damage the bacterial cytoplasmic membrane, as assessed through potassium leakage assay. The effects of flavonoids and flavonoids + antibiotics on mecA gene mutations were also tested, and no functional variation was detected in the coding region. [ABSTRACT FROM AUTHOR]

• Pomegranate juice with artemether showed no alterations in the blood parameters and ECG pattern. • The AUC (0-∞) was increased from 742 to 859 ng/mL for artemether (P = 0.45). • The C max , t 1/2 , and t max for artemether revealed non-significant (P > 0.05) effect. • Administration of pomegranate juice had no significant effect on pharmacokinetic profile of artemether. • Pomegranate juice may be safely co-administered with artemether and with other drugs primarily metabolized by CYP3A4. This study was designed to evaluate the effect of fresh pomegranate (Punica granatum L.) juice on the pharmacokinetic profile of artemether in healthy volunteers. A randomized, open-label, crossover study was conducted on healthy subjects (n = 26). Each volunteer received 250 mL of fresh pomegranate juice twice daily for 2 weeks. On day 14, they were administered a single oral dose of artemether (80 mg) with either water or 250 mL of pomegranate juice. Thirteen blood samples were collected up to 12 h and 6 electrocardiograms were recorded. Plasma concentrations of artemether and its metabolite dihydroartemisinin were analyzed by a noncompartmental method using LC–MS/MS. The lower limit of detection (LLOD) and lower limit of quantification (LLOQ) for artemether were estimated as 0.3 and 0.8 ng/mL, respectively, while for dihydroartemisinin it was 0.2 and 0.6 ng/mL, respectively. The pharmacokinetic parameters of artemether and dihydroartemisinin were not significantly altered when co-administered with the fresh pomegranate juice. AUC (0-∞) was slightly increased from 742 to 859 ng/mL for artemether [geometric mean ratio: 1.14 (95 % CI, 1.08,1.18); P = 0.45] and from 699 to 818 ng/mL for dihydroartemisinin [geometric mean ratio: 1.15 (95 % CI, 1.09, 1.15); P = 0.4]. Difference in C max for artemether was also statistically non-significant [173 vs 195 ng/mL; geometric mean ratio: 1.09 (95 % CI, 0.91, 1.15); P = 0.61]. Likewise, elimination half-life (t 1/2) for both artemether and dihydroartemisinin remained unchanged (P = 0.43 and 0.31, respectively). In addition, there was no significant difference in t max for artemether (P = 0.66) and its metabolite (P = 0.65). In conclusion, findings of the present study demonstrated that the administration of pomegranate juice had no significant effect on the pharmacokinetic profile of artemether. [ABSTRACT FROM AUTHOR]

Wulfenia amherstiana belongs to the Scrophulariaceae family and various plants of this family are known for their biological activities. The present study was focused on the isolation of bioactive compounds including a novel flavone 6,7,4'-trimethyl flavone (TMF) along with three known flavonoids such as quercetin, rutin, and a steroid β -sitosterol which were isolated from the ethanolic extract of W. amherstiana (Himalayan Wulfenia) through column chromatography and purified by using HPLC. Their structures were identified and elucidated through electron ionization mass spectroscopy (EIMS), 1DNMR ( 1 H-NMR and 13 C-NMR), and 2DNMR (COSY, HMQC, and HMBC) spectroscopy. The antimicrobial activities of this novel compound were evaluated through agar well diffusion method, while antioxidant and cytotoxic activities were assessed through 2,2-diphenyl-1-picrylhydrazyl (DPPH) free-radical scavenging assay and brine shrimp lethality assay, respectively. The NMR data revealed that TMF is a novel compound. TMF showed potential antibacterial and antifungal activities against Staphylococcus aureus (MIC = 128  μ g/ml) and Candida albicans (MIC = 128  μ g/ml). The cytotoxic potential of TMF was determined from brine shrimp lethality assay with LD 50 of 127.01  μ g/ml. The free-radical scavenging potential of TMF at various concentrations implicated its strong antioxidant activity in vitro. The results revealed that TMF demonstrated substantial antimicrobial activity against S. aureus and C. albicans , strong antioxidant activity, and moderately cytotoxic activity., Competing Interests: All authors declare that they have no conflicts of interest regarding the publication of this paper., (Copyright © 2020 Maria Kakar et al.)