Cooperation of Doxycycline with Phytochemicals and Micronutrients Against Active and Persistent Forms of Borrelia sp

Abstract

Phytochemicals and micronutrients represent a growing theme in antimicrobial defense; however, little is known about their anti-borreliae effects of reciprocal cooperation with antibiotics. A better understanding of this aspect could advance our knowledge and help improve the efficacy of current approaches towards Borrelia sp. In this study, phytochemicals and micronutrients such as baicalein, luteolin, 10-HAD, iodine, rosmarinic acid, and monolaurin, as well as, vitamins D3 and C were tested in a combinations with doxycycline for their in vitro effectiveness against vegetative (spirochetes) and latent (rounded bodies, biofilm) forms of Borrelia burgdorferi and Borrelia garinii. Anti-borreliae effects were evaluated according to checkerboard assays and supported by statistical analysis. The results showed that combination of doxycycline with flavones such as baicalein and luteolin exhibited additive effects against all morphological forms of studied Borrelia sp. Doxycycline combined with iodine demonstrated additive effects against spirochetes and biofilm, whereas with fatty acids such as monolaurin and 10-HAD it produced FICIs of indifference. Additive anti-spirochetal effects were also observed when doxycycline was used with rosmarinic acid and both vitamins D3 and C. Antagonism was not observed in any of the cases. This data revealed the intrinsic anti-borreliae activity of doxycycline with tested phytochemicals and micronutrients indicating that their addition may enhance efficacy of this antibiotic in combating Borrelia sp. Especially the addition of flavones balcalein and luteolin to a doxycycline regimen could be explored further in defining more effective treatments against these bacteria.

Vitamin C and Doxycycline: A synthetic lethal combination therapy targeting metabolic flexibility in cancer stem cells (CSCs)

“…Similarly, Goc et al, 2016, showed that Doxycycline is synergistic in vitro with certain phytochemicals and micronutrients, including Vitamin C, in the in vitro killing of the vegetative spirochete form of Borrelia spp., the causative agent underlying Lyme disease [ 38 ]. Vitamin C has also been shown to be synergistic with Tetracycline and Chloramphenicol, against the pathogenic bacteria, Pseudomonas aeruginosa [ 39 ].…”

Reciprocal cooperation of phytochemicals and micronutrients against typical and atypical forms ofBorreliasp.

“…Their anti-inflammatory and cell protective properties were also intensively researched worldwide (Woo et al 2006;Cheng et al 2007;Hsieh et al 2007;Nabavi et al 2015). It is worth noting that their cooperation with antibiotics is remarkable as shown by ours and many other research groups Su et al 2014;Qian et al 2015;Siriwong et al 2015;Cai et al 2016;Goc et al 2016). According to the aforementioned data, baicalein and luteolin have a broad spectrum of antimicrobial activity, but their efficacy is shown to be in relatively high effective concentrations.…”

“…; Goc et al . ). According to the aforementioned data, baicalein and luteolin have a broad spectrum of antimicrobial activity, but their efficacy is shown to be in relatively high effective concentrations.…”

Extraction and Fractionation of Bioactives from Dipsacus fullonum L. Leaves and Evaluation of Their Anti-Borrelia Activity

“…For example, grape (Vitis vinifera) seed extract [8], sugar leaf (Stevia rebaudiana) [9] and cat's claw (Uncaria tomentosa) [6] have shown potential activity against acute Borrelia spirochetes and the nongrowing stationary phase. This is further supported by the use of treatments where phytochemicals are used in combination with antibiotics [10] or micronutrients such as vitamin D [11], enabling lower LD 50 (median lethal dose) and MIC (minimum inhibitory concentration) concentrations against latent rounded forms of B. burgdorferi. This demonstrates a wide future potential of novel bioactives as both individual and synergic compounds for possible anti-Borrelia treatments [10,11].…”

“…This is further supported by the use of treatments where phytochemicals are used in combination with antibiotics [10] or micronutrients such as vitamin D [11], enabling lower LD 50 (median lethal dose) and MIC (minimum inhibitory concentration) concentrations against latent rounded forms of B. burgdorferi. This demonstrates a wide future potential of novel bioactives as both individual and synergic compounds for possible anti-Borrelia treatments [10,11].…”