# Terpenes as Potential Anti-Alzheimer's Disease Agents
## 2 Activities of Terpenes on the Mechanisms Associated with AD
### Inhibition of AB Production
#### 2.1.2 Triterpenes and Meroterpenes  
From _Panax ginseng_ [PERSON]. [PERSON] from China, as well as from other species of ginseng, ginseng were extracted. These compounds are steroidal triterpene saponins with the usual four rings (A, B, C, and D) of the steroid backbone [64]. Ginsenoside Rg1 (**7**) presented a BACE1 IC\({}_{50}\) value of 6.18 \(\pm\) 0.96 uM [64; 66]. Ginsenoside Re (**8**) also presented some activity as a BACE1 inhibitor; however, the IC\({}_{50}\) value was not determined [64; 67]. These ginseng Rg1 (**7**) and Re (**8**), as well as Rg3 (**9**), significantly reduce the amount of A@40/A@42 [64; 68]. Pseudoginsenoside-F11 (PF11) (**10**), an occtillol-type saponin contained in _Panax quinquefolium_ L. and isolated from leaves of _Panax pseudoginseng_ Wall. subsp. _Himalaicus HARA_ (Himalayan ginseng), suppresses the expression of BACE1 [69; 70]. Meroterpenes are hybrid SMs that derive partially from the terpene pathway [57]. Biosynthesistically, the complex structures of these compounds are mostly derived from simple precursors like a linear isoprene or a C-2 unit like acetyl-CoA, via several chemical transformations [71; 72]. The meroterpenes asperterpenes, extracted from the mold _Aspergillus terreus_ Thom., showed BACE1 inhibitory activities. The asperterpenes A (**11**), B (**12**), E (**13**), F (**14**), and J (**15**) presented IC\({}_{50}\) values of 0.08, 0.06, 3.32, 5.85, and 31.68 uM, respectively [73; 74]. However, other asperterpenes like D (**16**), G (**17**), H (**18**), I (**19**), K (**20**), L (**21**), or M (**22**) were inactive (IC\({}_{50}\)\(>\) 50 uM) [73; 74]. Other meroterpenes like terretonin (**23**) or terretonins A (**24**), D (**25**), G (**26**), and H (**27**) were also inactive (IC\({}_{50}\)\(>\) 50 uM) [74]. These results suggest that in asperterpenes A (**11**) and B (**12**), the unique \(\beta\)-oriented methyl group at C21 with the unprecedented 1,2,5-trimethyl-4,9-dioxobicyclo[3.3.1] non-2-ene-3-carboxylic acid moiety, and in asperterpenes E (**13**) F (**14**) and J (**15**) the cis-fused A/B rings, are important for BACE1 inhibition activity [64; 73]. Considering the terreusterpenes, another series of 3,5-dimethylorsellinic acid-based meroterpenes also obtained from _A. terreus_, some of them showed high BACE1 inhibition activity. Terreusterpenes A (**28**), B (**29**), C (**30**), and D (**31**) inhibited the activity of BACE1 with IC\({}_{50}\) values of 5.98, 11.42, \(\sim\)40, and 1.91 uM, respectively [75]. These results suggest that the 4-hydroxy-3 methyl \(\Upsilon\) lactone fragment of terreusterpene D (**31**), making a more planar molecule, is important for the inhibition of BACE1. From _Lycopodiella cernua_ L., with synonyms of _Lycopodium cernuum_ L., _Lepididis cernua_ (L.[PERSON] [PERSON], or _Pallinihaea cernua_ (L.[PERSON] [PERSON]. [PERSON], of Vietnam, twelve serrate-type pentacyclic triterpenes (compounds **32-43**) were isolated. While compounds 38,218,29-trihydroxyserrat-14-en-24-oic acid-3b-yl-(70-hydroxycinnamate) (**32**), 38,14,415,218-tetrahydroxyserratan-24-oic acid-38-yl-(40-methoxy-50-hydroxybenzoate) (**33**), 38,218,29-trihydroxyserrat-14-en-24-oic acid-38-yl-(40-hydroxybenzoate) (**35**), and 218-hydroxyserrat-14-en-3,16-dione (**36**) were active as BACE1 inhibitors with IC\({}_{50}\) values of 1.07, 1.0, 0.3, and 0.2 uM, respectively, all the other compounds were inactive (IC\({}_{50}\) > 10 uM). They were identified as 38,218,29-trihydroxyserrat-14-en-38-yl _p_-dihydrocumarate (**34**), 38,214-diacetoxyserrat-14-\(\beta\)-ol (**37**), serrat-14-en-34,21\(\alpha\)-diol (**38**), 38,218,29-trihydroxy-16-oxyserrat-14-en-24-oic acid (**39**), serrat-14-en-34,218-diol (**40**), 38,218,29-trihydroxy-16-oxyserrat-14-en-24-methyl ester (**41**), 38,21\(\alpha\)-dihydroxyserratan-148-ol (**42**), and 3\(\alpha\),218-dihydroxy-16-oxyserrat-14-en-24-oic acid (**43**) [76].