Antifeedant, cytotoxic, and anti-inflammatory neo-clerodane diterpenoids in the peltate glandular trichomes and fresh leaves of Ajuga forrestii Wang, Ying Liu, Yan-Chun Li, Wen-Yuan Guo, Kai Liu, Yan Li, Sheng-Hong Phytochemistry 2021 112731 2021-06-30 186 1 9 BDNL 2684401 Diels Diels [545,640,1203,1223] Magnoliopsida Lamiaceae Ajuga Plantae Lamiales 5 6 Tracheophyta species forrestii  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, 3–8and 11–12against cotton bollworms (  Helicoverpa armigera) were tested ( Table 3). Consequently, compounds 3and 8were found to exhibit obvious antifeedant effects, with EC 50values 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  3inthe peltate GTs and diastereomers 8a/ 8bmight 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 14showed significant inhibitory activity on the secretion of interleukin-2 (IL-2), with an IC 50value 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 14showed obvious cytotoxicity against three cancer cell lines, NCI-H1975, HepG2 and MCF-7, with IC 50values 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 15,16double bond of the furan functionality would increase its anti-inflammatory and cytotoxic activity.