Frankincense essential oil nanoemulsion specifically induces lung cancer apoptosis and inhibits survival pathways

Abstract

Background The volatile fraction of frankincense (Boswellia sacra) oleogum was extracted, formulated in nanoemulsion and tested against lung cancer A549 cell line. First, the gum was hydro-distilled to isolate the volatile fraction (essential oil), which was analyzed via gas chromatography to identify its major volatile constituents. Then, the oil was formulated in two water-based nanoemulsions which differ from one another in the presence of propylene glycol (PG), which is used in the formulation step as a co-surfactant. The pure essential oil as well as its major volatile compound (α-pinene), its two nanoemulsions and a reference drug (Doxorubicin) were evaluated against lung cancer A549 cell lines and WI-38 normal lung cells. The evaluation included cytotoxicity (MTT and IC50), apoptosis (flow cytometric analysis) in addition to genetic assessments for some intrinsic and extrinsic genes relevant to apoptosis and survival pathways. Results Chromatographic analysis of frankincense essential oil revealed that α-pinene is the major volatile compound which constituent about 60% of that oil. Emulsification of the oil using the low energy technique gave nanoemulsions having major intense particles population (85–90%) with z-average diameter below 20.0 nm. Frankincense oil nanoemulsion fabricated with (PG) showed the best cytotoxic activity toward lung cancer A549 cell compared to PG-free nanoemulsion, α-pinene and the reference drug doxorubicin, along different incubation periods. Flow cytometric analysis also indicated that PG-containing nanoemulsion can induce cancer cells toward apoptosis better than the other formula and the pure oils. The same nanoemulsion was found to upregulate the pro-apoptotic genes [DR5, FAAD, Caspase 8 (Cas8), p53, and Bax] and downregulate the anti-apoptotic and reoccurrence genes (Bcl-2, NF-kB, and STAT-3). Most importantly, the PG-containing nanoemulsion had the least cytotoxic effect on the normal WI-38 lung cells. Conclusions These results point out to the potentials of frankincense essential oil (rich in α-pinene) and its PG-nanoemulsion as a promising adjuvant from plant-source to potentiate the activity of the systematic anti-lung cancer drugs.

Molluscicidal and Cercaricidal Effects of Myrciaria floribunda Essential Oil Nanoemulsion

“…The F10 and F11 formulations (HLB 5.54-4.3) presented visual phase separation and were discarded from the analysis. dall effect in nanodispersions (Figure 2) [34]. In addition, the formulation show smaller average droplet size of 99.71 ± 0.5220 nm, and the PDI was 0.262 ± 0.013 (F 3A).…”

“…To rationalize the experiments, only the F3 formulation (4:1 polysorbate 20 and sorbitan monooleate) was selected to continue the work, owing to its pronounced macroscopic characteristics and smaller droplet size. Also, it showed a typical bluish-white reflection characteristic of light scattering due to the Tyndall effect in nanodispersions ( Figure 2 ) [ 34 ]. In addition, the formulation showed a smaller average droplet size of 99.71 ± 0.5220 nm, and the PDI was 0.262 ± 0.013 ( Figure 3 A).…”

Progress of nanopreparation technology applied to volatile oil drug delivery systems

“…In addition, Ahmed et al prepared frankincense oil NE and investigated the cytotoxic activity of frankincense oil NE on lung cancer A549 cells at different latency stages. Frankincense oil NE were found to be effective in inducing apoptosis in cancer cells with minimal cytotoxic effects on normal lung cells, demonstrating the potential of frankincense oil NE to enhance the activity of systemic anti-lung cancer drugs [ 22 ]. In addition, many other volatile oils and their important constituents, including buckwheat flavonoids [ 23 ], limonene [ 24 ], cinnamon oil, coconut oil, sunflower oil, olive oil, palm oil, jojoba [ 25 ], red raspberry seed [ 26 ], peppermint [ 27 ], tea tree [ 28 ], clove [ 29 , 30 ], oregano [ 31 ], chilli pepper [ 32 ], and citrus [ 33 ], linseed [ 34 ], cinnamon [ 23 ], bitter fennel [ 24 ], thyme [ 35 , 36 ], Carlina acaulis L. [ 37 ], fritillary [ 38 ], lemongrass [ 39 , 40 ], cumin [ 41 ], lemon [ 42 ], peppermint [ 43 ], black pepper [ 44 ], cloves [ [45] , [46] , [47] ], lemon [ 48 ], fennel [ 49 , 50 ], Cinnamon [ [51] , [52] , [53] ], Lavender [ 54 , 55 ], Laurel [ 56 ], Peppermint [ 49 ], Thyme [ 57 ], Astragalus [ 58 ], Celandine [ 59 ], Cumin [ 60 ], Nettle [ 46 ] and other volatile oils of TCM, were loaded in NE to improve solubility, solubility and bioavailability.…”

Assessment of Lavender, Frankincense and Peppermint Oils Trans-dermal Nano Spray Formulation Effect on Wound Healing Activity in Rat Model

“…This test was conducted using kits of Bio Diagnostic Company for the enzymatic colorimetric measurement of MDA at wave length 534 nm according to the method of Abd-Rabou and Edris [27].…”