Anti-inflammatory Potential of Macamides Isolated from Yellow Tubers of Mashua (Tropaeolum Tuberosum)

Abstract

Although Tropaeolum tuberosum tubers have been consumed cooked as a folk remedy for the treatment of skin, lungs, liver and kidneys diseases, these uses have very limited scientific basis. Therefore, this article develops a phytochemical analysis of the yellow tubers of T. tuberosum with the objective to assess whether the isolated compounds have anti-inflammatory potential in the CCD-1109Sk, MRC-5 and RWPE-1 cell lines. We performed an extraction of T. tuberosum tubers using different organic solvents, followed by a bioguided chromatographic separation. Four macamides were identified by LC/MS techniques, but only N-benzyllinoleamide (1) and N-benzyloleamide (2) were isolated and elucidated by NMR/MS techniques, given that they were present in a larger proportion in the tubers. The anti-inflammatory potential of macamides was evaluated by the inhibition of NF-κB and STAT3 activation. Both compounds displayed inhibition of NF-κB activation with IC50 values of 2.28±0.54 µM; 3.66±0.34 µM and 4.48±0.29 µM for compound (1) and 6.50±0.75 µM; 7.74±0.19 µM and 8.37 ±0.09 µM for compound (2) in CCD-1109Sk, MRC-5 and RWPE-1 cell lines, respectively. Moreover, both compounds inhibited the STAT3 activation with IC50 of 0.61±0.76 µM; 1.24±0.05 µM and 2.10±0.12 µM for compound (1) and 5.49±0.31 µM; 7.73 ±0.94 µM and 7.79±0.30 µM for compound (2). Therefore, isolated macamides of T. tuberosum tubers showed promising anti-inflammatory effects, suggesting a possible beneficial use to combat inflammatory processes of skin, lung and prostate.

Synthesis and biological screening of a library of macamides as TNF-α inhibitors

“…subunit of the κB kinase inhibitor complex. 7,25 In this sense, we can indicate that the derivatives synthesised in this work lead to direct inhibition of IκB, preventing its degradation and the subsequent inhibition of NF-κB activation. 7,31 These results open the way to the development of new antiinflammatory drugs with a better safety profile compared to the drugs available on the market.…”

“…24 The difference between derivatives 1e and 1f was not statistically significant ( ns p > 0.999) ( Table 1). Consequently, it was decided to use derivative 1f for subsequent modifications, since this macamide is found in a greater proportion in nature 25 and because it showed considerable biological activity (14.2 ± 1.47 μM).…”

Design, Synthesis and Pharmacological Evaluation ofN‐Benzyl Linoleamide Analogues fromTropaeolum tuberosumas NF‐κB Inhibitors and Nrf2 Activators

“…Regarding the isolated macamides from Tropaeolum tuberosum, previous studies have concluded that N-benzyl oleamide and N-benzyl linoleamide (Figure 1) [14] The difference in pharmacological activity between N-benzyl oleamide and Nbenzyl linoleamide is due to the different number of double bonds of the fatty acid chain, [14,[17][18] being the N-benzyl linoleamide more active because of the additional double bond. This is because, as shown by mechanistic studies, the increase of double bonds in polyunsaturated fatty acids (PUFAs) leads to an increased activity in specific inflammatory disorders, through the interaction with the signalling pathway of JAK-STAT3 (Janus kinases/signal transducer and activator of transcription 3).…”

“…N-benzyl linoleamide is the most important, showing a higher anti-inflammatory activity when compared to other macamides. [14] Likewise, it has been indicated that this macamide is found in a higher proportion in relation to the other macamides which were isolated from the T. tuberosum tubers. [14] The objective of the present work is to synthesise different N-benzyl linoleamide analogues for the treatment of migraine (anti-inflammatory activity), making modifications to the characteristic fragments of the N-benzyl linoleamide.…”

“…[11][12] While its traditional use relates this plant species to treating headaches, recent pharmacological studies have reported that T. tuberosum tubers have antioxidant [13] and anti-inflammatory activities. [14] The compounds related to the anti-inflammatory activity of T. tuberosum have been reported as having a macamide structure (Figure 1). N-benzyl linoleamide is the most important, showing a higher anti-inflammatory activity when compared to other macamides.…”