Abstract
Objective: Plant based drugs have been a solution in the search for more cost-effective and less harmful drugs for the treatment of neoplasia. Citrus aurantium L. (Rutaceae) is abundant in Brazil and D-limonene, a monoterpene used in the prevention and treatment of neoplasia, was identified as a major compound in the oil of this specie. Objective of current study includes estimation of anti-tumor activity of Citrus aurantium L. (Rutaceae) (crude extract, essential oil and D-limonene) against Ehrlich carcinoma, as well as their phytochemical evaluation (D-limonene and essential oil).
 Methods: There was a randomized non-clinical trial in which were used adult male mice (Balb-C). Four groups of animals were used having 6 numbers of animal in each group. All groups were inoculated with the Ehrlich tumor and then received the treatment (control, crude extract, essential oil and D-limonene) by oral route daily (28 day treatment). Essential oil was obtained by hydro-distillation and analyzed by the means of GC (Gas Chromatography) that was attached to mass spectrometry. In last of the observations hemogram was obtained.
 Results: Animals treated with the essential oil has shown no significant difference compared to the group treated with D-limonene. The group treated with crude extract had a growth inhibition close to the essential oil and D-limonene groups.
 Conclusion: It´s concluded that the essential oil and the crude extract of Citrus aurantium, L. (Rutaceae) can become therapeutic agents because of their anti-tumor activity with no toxicity to the blood cells and have low cost of production. Further studies are necessary, so they can be used in the treatment of neoplasia in humans. The chromatographic and spectrometric analyzes indicated the presence of other components in smaller amounts in the essential oil, which suggests that they could have a synergic activity to the D-limonene.
 Peer Review History: 
 Received 2 June 2020; Revised 25 June; Accepted 4 July, Available online 15 July 2020
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 Received file 
 
 Average Peer review marks at initial stage: 6.0/10
 Average Peer review marks at publication stage: 8.0/10
 Reviewer(s) detail:
 Name: Ahmad Najib
 Affiliation: Universitas Muslim Indonesia, Makassar, Indonesia
 E-mail: ahmad.najib@umi.ac.id
 
 Name: Dr. Mohamed Said Fathy Al-Refaey
 Affiliation: University of Sadat City, Menofia, Egypt
 E-mail: mido_ph212@yahoo.com
 
 Comments of reviewer(s): 
 
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Highlights
MATERIALS AND METHODS Essential oil GC-MS Shimadzu gas chromatograph (GC-2012) was used for the GC analysis, it was equipped with flame ionization detector and DB-5 column having film thickness 0.25 μm, 30m×0.25mm, and 1:25 split ration
Total 54 components were detected in essential oil and 44 components were detected in the extracts
The levels of p-GSK-3β, and p-Akt gets reduced. These results indicate induction of apoptosis by the D-limonene due to the suppression of PI3K/Akt pathway and mitochondrial death[22]
Summary
Plant based drugs have been a solution in the search for more cost-effective and less harmful drugs for the treatment of neoplasia. The anticancer of orange essential oil and other compounds present, were investigated in cancer cell lines A549 (human lung) and 22RV-1 (prostate). As far as structure of Limonene is concerned it has two isoprene units that have >90% essential oil It induce apoptosis on the tumor cells and has shown potential for the treatment of skin, fore stomach, lung and liver cancer[5,6]. Perillyl alcohol and limonene metabolites have cytotoxic potential because of several properties like their hyperthermia inducing effects, RAS pathways, antiangiogenic activities and negative apoptosis regulations[10]. The study of orange oil, limonene and extracts has shown an interesting effect of these compounds upon cancer and several illnesses associated to antioxidant activity. The objective of current study was to estimate the anti-tumor potential of essential oil, crude extract and D-limonene against Ehrlich carcinoma as well as the phytochemical analyses of the essential oil and D-limonene of C. aurantium and the comparison among these products
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