Synthesis, acute toxicity and anti-inflammatory effect of bornyl salicylate, a salicylic acid derivative

Abstract

Bornyl salicylate (BS) is a salicylic derivative, obtained by sterification of salicylic acid and monoterpene (-)-borneol, and its topical use in inflammatory diseases was described in the early 20th century. It is also known that borneol presents neuroprotective, genoprotective and analgesic properties. The purpose of this study was to evaluate BS in experimental models of acute inflammation. The toxicity of BS was analyzed by measuring water and food intake, weight, mortality and weight of main organs. To assess its anti-inflammatory effect, BS-treated mice were challenged with carrageenan, prostaglandin E2 (PGE2), bradikynin (BK) or histamine (HIS)-induced paw edema, zymosan-induced peritonitis and vascular permeability induced by acetic acid. Nitric oxide (NO) production was analyzed in peritoneal macrophage cultures. There was no sign of acute toxicity of BS in male and female mice. Furthermore, treatment with BS was significantly (p < 0.05) effective in reducing paw edema induced by carrageenan in early and late phases; this effect was related to PGE2 and BK, but HIS independent. Neutrophil migration and cytokine release (TNF-α, IL-1β and IL-6) induced by zymosan and fluid leakage induced by acetic acid were also reduced in BS-treated animals. In vitro, BS (10 µg/mL) reduced NO production in LPS-stimulated macrophages. These data suggest that BS has an anti-inflammatory effect, which is related, at least in part, with decrease of mediators as PGE2, NO and pro-inflammatory cytokines. However, further studies should be done to explore its potential as an anti-inflammatory drug.

Comparison of Chemical Profiles, Anti-Inflammatory Activity, and UPLC-Q-TOF/MS-Based Metabolomics in Endotoxic Fever Rats between Synthetic Borneol and Natural Borneol

“…AKE reduced the LPS-induced secretion of TNF-α, IL-1β, IL-6, NO and PGE 2 in RAW 264.7 cells, indicating that it has anti-inflammatory effects [ 27 ]. Moreover, bornyl salicylate, the esterification product of salicylic acid and monoterpene (−)-borneol, has been demonstrated to inhibit inflammation at least for 24 hours mainly by reducing pro-inflammatory cytokines [ 28 ]. Thyme extracts containing 1, 8 cineole, thymol, camphor, borneol, and carvacrol significantly reduced production and gene expression of the pro-inflammatory factors such as TNF-α, IL-1B, and IL-6 [ 29 ].…”

Monoterpenes and Their Derivatives—Recent Development in Biological and Medical Applications

“…In China’s and India’s traditional medicine, borneol has long since been used as a remedy against gastrointestinal diseases. (–)-Borneol and its derivatives are antimicrobial [ 103 ], anti-inflammatory [ 104 ], and antiviral [ 105 ]. Borneol has been shown to promote drugs crossing through the blood–brain barrier, thus improving the efficiency of these drugs [ 106 ].…”

“…The particular biological properties of (–)-borneol derivatives belonging to the ester compounds significantly affect their applicability in medical areas, especially for diverse therapeutic fields [ 104 , 107 , 108 , 109 ]. (–)-Borneol esters are also found in a few plant families: For instance, the hydroxycinnamic variety in Eupatorium deltoideum Poepp.…”

“…Bornyl salicylate—commonly known salicylic derivative, obtained by esterification of salicylic acid and (–)-borneol in the early 20th century—was used topically in inflammatory diseases. Interestingly, it was only in 2012 that the first detailed analysis of the anti-inflammatory effects of bornyl salicylate (BS) in experimental models of acute inflammation was done [ 104 ]. That research showed that signs of acute toxicity are not observed either in male or female mice.…”

Synthesis of natural phenylpropanoid esters via conventional chemical reactions

“…These naturally occurring compounds have displayed interesting biological activities. For example, (-)-bornyl salicylate (4, Figure 1) and (-)-bornyl trans-p-coumarate have been reported as having anti-inflammatory activity, [3][4][5][6][7] while (-)-bornyl cis-p-coumarate has shown antifungal and anthelmintic activity, 8 and, (-)-bornyl trans-p-coumarate has exhibited trypanosomicidal activity. 9 Despite having a simple structure, so far no reports have been found in the literature for the synthesis of (-)-bornyl cis/trans-ferulate (5-7, Figure 1).…”