Ajuga forrestii, Diels, Diels

Wang, Ying, Liu, Yan-Chun, Li, Wen-Yuan, Guo, Kai, Liu, Yan & Li, Sheng-Hong, 2021, Antifeedant, cytotoxic, and anti-inflammatory neo-clerodane diterpenoids in the peltate glandular trichomes and fresh leaves of Ajuga forrestii, Phytochemistry (112731) 186, pp. 1-9 : 6

2.4. Biological activity of the diterpenoids in the A. forrestii GTs and leaves

Considering that plant GT-specific metabolites and clerodane diterpenoids have been frequently shown to serve as defensive chemicals against herbivores, the antifeedant effects of neo -clerodane compounds 1, 3–8 and 11–12 against cotton bollworms ( Helicoverpa armigera ) were tested ( Table 3 ). Consequently, compounds 3 and 8 were found to exhibit obvious antifeedant effects, with EC 50 values of 15.2 ±1.65 and 16.8 ±1.87 μg/cm 2, respectively (neem oil: EC 50 =6.9 ±0.29 μg/cm 2). Thus, it was suggested that compound 3 in the peltate GTs and diastereomers 8a / 8b might help the plant defend against insect herbivores. A preliminary structure-activity relationship analysis indicated a free hydroxy group at C-6 might be important to maintain the antifeedant activity of this class of compounds.

In addition, selected diterpenoids (1, 3–7, 11, 13–14) were evaluated for their anti-inflammatory and cytotoxic activities. As shown in Table 4 , abietane diterpenoid 14 showed significant inhibitory activity on the secretion of interleukin-2 (IL-2), with an IC 50 value of 8.9 μM, and interestingly displayed no obvious cytotoxicity on the proliferation of phytohemagglutinin (PHA)/phorbol 12-myristate-13-acetate (PMA)- induced Jurkat cells. However, all tested compounds were inactive on the TNF-α and MCP-1 production in lipopolysaccharide (LPS)-induced RAW264.7 cells at 40 μM. In addition, compound 14 showed obvious cytotoxicity against three cancer cell lines, NCI-H1975, HepG2 and MCF-7, with IC 50 values of 15.1, 12.4, and 12.9 μM, respectively (cis - platinum: IC 50 = 18.5, 7.5 and 11.5 μM, respectively). It appeared that reduction of the Δ 15,16 double bond of the furan functionality would increase its anti-inflammatory and cytotoxic activity.