Diterpenes of Pinus pinaster aiton with anti-inflammatory, analgesic, and antibacterial activities

Abstract

Ethno-pharmacological relevance: The P. pinaster species, known as ‘Pino nigral or rodeno’, is used in the treatment of colds, asthma, flu, and tuberculosis. Aim of the study: This study determined the anti-inflammatory, analgesic, and antibacterial activities of the P. pinaster resin, identifying the compounds with higher biological activity. Materials and methods: A bio-guided isolation of the compounds of P. pinaster was carried out by selecting the most active extracts with anti-inflammatory and analgesic effects in the HBEC3-KT, MRC-5, and THP-1 cell lines. The antibacterial activity was determined against the S. aureus, S. pneumoniae, K. pneumoniae and P. aeruginosa strains. Results: The following compounds were identified by NMR: dehydroabietic acid (1), ( + )-cis-abienol (2), pimaric acid (3), isopimaric acid (4), 7α-hydroxy-dehydroabietic acid (5), 7-oxo-dehydroabietic acid (6), 15-hydroxy-abietic acid (7), 7-oxo-15-hydroxy-dehydroabietic acid (8), 13-oxo-8 (14)-podocarpen-18-oic acid (9), and pinyunin A (10). Regarding their anti-inflammatory activity, all compounds inhibited NF-κB. Compound 9 was the most active (IC50 = 3.90–12.06 μM). Concerning the analgesic activity, all the compounds inhibited NK-1, yet compound 9 was the most active (IC50 = 0.28–0.33 μM). Finally, compounds 6 (MIC = 12.80–25.55 μM) and 9 (MIC = 9.80–24.31 μM) were the most promising antibacterial compounds in all strains. Conclusion: This study managed to identify, for the first time, six diterpenes from the resin of P. pinaster, with anti-inflammatory, analgesic, and antibacterial activity. Among the identified compounds, compound 9 was the most active, being considered a promising candidate as an antagonist of the tachykinin NK-1 receptor and as an analgesic agent against inflammation and neuropathic pain. It also had an antibacterial effect against Gram negative bacteria.