Anti-Inflammatory Activity of Choisya ternata Kunth Essential Oil, Ternanthranin, and Its Two Synthetic Analogs (Methyl and Propyl N-Methylanthranilates)

Abstract

Choisya ternata Kunth (Rutaceae) is native to North America where it is popularly known as “Mexican orange”. In this study, the anti-inflammatory effects of the essential oil (EO) obtained from the leaves of C. ternata, one of its minor components (ternanthranin—ISOAN) and its two synthetic analogues (methyl and propyl N-methylanthranilate – MAN and PAN) were evaluated. Mice pretreated with the EO (EO) obtained from C. ternata leaves (3–100 mg/kg, p.o.), ISOAN, MAN or PAN (1–30 mg/kg, p.o.) and the reference drugs, morphine (1 mg/kg, p.o.) and acetylsalicylic acid (ASA, 100 mg/kg, p.o.), were evaluated in inflammation models such as formalin and subcutaneous air pouch models, with measurement of cell migration, exudate volume, protein extravasation, nitric oxide and pro-inflammatory cytokines. The EO from C. ternata significantly inhibited the time that the animals spent licking the formalin-injected paw in the second phase of the model at their higher doses (30 and 100 mg/kg, respectively). An inhibition of the inflammatory reaction induced after subcutaneous carrageenan injection into air pouch was also observed. In this model, the EO significantly reduced cell migration, exudate volume, protein extravased, and the increase in levels of inflammatory mediators (nitric oxide, TNF-α and IL-1β). ISOAN, MAN and PAN behaved in the same fashion at much smaller doses. Also, these molecules were able to show significant effects in the reduction of paw edema (at all tested doses) when the phlogistic agent was carrageenan, bradykinin, 5-HT, PGE2, C48/80 or 12-O-tetradecanoylphorbol-acetate (TPA). None of the tested doses had any effect in reducing histamine-induced edema. Our results indicate that the EO from C. ternata and anthranilate derivatives demonstrates an anti-inflammatory effect.

In vitro and In vivo Models for Anti-inflammation: An Evaluative Review

“…This model evaluates the activity of substances against the proliferative stage of inflammation. [42,43].…”

“…According to reports [42,43], air cavities were produced in the animals under anesthesia by subcutaneous injection of 20 mL of sterile air into the interscapular area of the back. An extra 10 ml of air was injected into the cavity every 3 days to keep the space open.…”

“…After 48 h of injection of carrageenan or zymosan, the animals were anesthetized, the pouch opened, and the volume of exudates collected and determined. The leukocyte concentration was quantified appropriately [42,43]. This technique also offers a good method of monitoring the immune system response.…”

Structural elucidation of thermolysis products of methyl N-methyl-N-nitrosoanthranilate

“…7 Generally, they have favorable partition coefficients into most organic solvents versus water, and there are attempts to link their "liposolubility" to their carcinogenic activity in certain organs. [13][14][15][16][17][18] Methyl N-methylanthranilate is a part of our everyday diet as it naturally occurs in various fruits and plants and is used as a food flavor. N-nitroso compounds are well-known alkylating agents; they can undergo cleavage to produce the parent amines and NO, reduction to give di-substituted hydrazines, and oxidation to yield nitramines.…”

Chemical Composition and Antibacterial Activity of Essential Oils From Azorella Spinosa (Apiaceae) Against Wild Phytopathogenic Bacteria

“…Essential oils are known to be important antimicrobial agents present in plants, and they may also have antioxidant and anti-inflammatory activities 2,3 . In nature, the essential oils play important roles in protection of plants to microorganisms.…”