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.

The species of the genus Trillium (Melanthiaceae alt. Trilliaceae) include perennial herbs with characteristic rhizomes mainly distributed in Asia and North America. Steroids and saponins are the main classes of phytochemicals present in these plants. This review summarizes and discusses the current knowledge on their chemistry, as well as the in vitro and in vivo studies carried out on the extracts, fractions and isolated pure compounds from the different species belonging to this genus, focusing on core biological properties, i.e., cytotoxic, antifungal and anti-inflammatory activities.

Cognitive decline in dementia is associated with deficiency of the cholinergic system. In this study, five mono-carbonyl curcumin analogs were synthesized, and on the basis of their promising in vitro anticholinesterase activities, they were further investigated for in vivo neuroprotective and memory enhancing effects in scopolamine-induced amnesia using elevated plus maze (EPM) and novel object recognition (NOR) behavioral mice models. The effects of the synthesized compounds on the cholinergic system involvement in the brain hippocampus and their binding mode in the active site of cholinesterases were also determined. Compound h2 (p < 0.001) and h3 (p < 0.001) significantly inhibited the cholinesterases and reversed the effects of scopolamine by significantly reducing TLT (p < 0.001) in EPM, while (p < 0.001) increased the time exploring the novel object. The % discrimination index (DI) was significantly increased (p < 0.001) in the novel object recognition test. The mechanism of cholinesterase inhibition was further validated through molecular docking study using MOE software. The results obtained from the in vitro, in vivo and ex vivo studies showed that the synthesized curcumin analogs exhibited significantly higher memory-enhancing potential, and h3 could be an effective neuroprotective agent. However, more study is suggested to explore its exact mechanism of action.

Trillium govanianum rhizome is used as an analgesic and anti-inflammatory remedy in traditional medicine in northern Pakistan. In an attempt to establish its medicinal value, the present research evaluated the analgesic and anti-inflammatory potential of T. govanianum. The in vivo anti-inflammatory activity of extract and fractions was investigated in the carrageenan induced paw edema assay. The in vitro suppression of oxidative burst of extract, fractions and isolated compounds was assessed through luminol-enhanced chemiluminescence assay. The in vivo analgesic activity was assayed in chemical and thermal induced nociceptive pain models. The crude methanol extract and its solvent fractions showed anti-inflammatory and analgesic responses, exhibited by significant amelioration of paw edema and relieve of the tonic visceral chemical and acute phasic thermal nociception. In the oxidative burst assay, based on IC₅₀, the crude methanol extract and n-butanol soluble fraction produced a significant inhibition, followed by chloroform and hexane soluble fractions as compared to ibuprofen. Similarly, the isolated compounds pennogenin and borassoside E exhibited significant level of oxidative burst suppressive activity. The in vivo anti-inflammatory and analgesic activities as well as the in vitro inhibition of oxidative burst validated the traditional use of T. govanianum rhizomes as a phytotherapeutic remedy for both inflammatory conditions and pain. The observed activities might be attributed to the presence of steroids and steroid-based compounds. Therefore, the rhizomes of this plant species could serve as potential novel source of compounds effective for alleviating pain and inflammation.

Alzheimer’s disease is the commonest form of dementia associated with short-term memory loss and impaired cognition and, worldwide, it is a growing health issue. A number of therapeutic strategies have been studied to design and develop an effective anti-Alzheimer drug. Curcumin has a wide spectrum of biological properties. In this regard, the antioxidant potentials of mono-carbonyl curcumin analogues (h1–h5) were investigated using in vitro antioxidant assays and hippocampal-based in vivo mouse models such as light–dark box, hole board, and Y-maze tests. In the in vitro assay, mono-carbonyl curcumin analogues h2 and h3 with methoxy and chloro-substituents, respectively, showed promising 2,2-diphenyl-1-picrylhydrazyl (DPPH) and 2, 2′-azinobis-3-ethylbenzothiazo-line-6-sulfonate (ABTS) free radical scavenging activities. In the in vivo studies, scopolamine administration significantly (p < 0.001) induced oxidative stress and memory impairment in mice, in comparison to the normal control group. The pretreatment with mono-carbonyl curcumin analogues, specifically h2 and h3, significantly decreased (123.71 ± 15.23 s (p < 0.001), n = 8; 156.53 ± 14.13 s (p < 0.001), n = 8) the duration of time spent in the light chamber and significantly enhanced (253.95 ± 19.05 s (p < 0.001), n = 8, and 239.57 ± 9.98 s (p < 0.001), n = 8) the time spent in the dark compartment in the light–dark box arena. The numbers of hole pokings were significantly (p < 0.001, n = 8) enhanced in the hole board test and substantially increased the percent spontaneous alternation performance (SAP %) in the Y-maze mouse models in comparison to the stress control group. In the biomarker analysis, the significant reduction in the lipid peroxidation (MDA) level and enhanced catalase (CAT), superoxide dismutase (SOD), and glutathione (GSH) activities in the brain hippocampus reveal their antioxidant and memory enhancing potentials. However, further research is needed to find out the appropriate mechanism of reducing oxidative stress in pathological models.

Plant extracts are complex matrices and, although crude extracts are widely in use, purified compounds are pivotal in drug discovery. This study describes the application of automated preparative-HPLC combined with a rapid off-line bacterial bioassay, using reduction of a tetrazolium salt as an indicator of bacterial metabolism. This approach enabled the identification of fractions from Dodonaea viscosa that were active against Staphylococcus aureus and Escherichia coli, which, ultimately, resulted in the identification of a clerodane type diterpenoid, 6β-hydroxy-15,16-epoxy-5β, 8β, 9β, 10α-cleroda-3, 13(16), 14-trien-18-oic acid, showing bacteriostatic activity (minimum inhibitory concentration (MIC) = 64–128 µg/mL) against test bacteria. To the best of our knowledge, this is the first report on antibacterial activity of this metabolite from D. viscosa.