# Terpenes as Potential Anti-Alzheimer's Disease Agents
## 2 Activities of Terpenes on the Mechanisms Associated with AD
### Inhibition of NFTs Formation
#### 2.3.4. Triterpenes  
The triterpene ginseng Reg3 (**9**) from _P. ginseng_, significantly reduces the production of TNF-\(\alpha\), IL-1\(\beta\), and COX-2 [102; 103; 104]. Ginsenoside Re (**8**) and ginseng Rg1 (**7**) are other ginsensoides exhibiting strong neuroprotective activity by inhibiting ROS and activating Nrf antioxidant pathways [105; 106; 107; 78]. Other ginensoides like ginseng Rd (**63**) and protopanaxatriol (PPT) (**64**) also exhibit neuroprotective effect by activating Nrf2 [108; 109; 78]. These molecules with 30 carbon atoms can easily penetrate the BBB into the brain tissue [110]. Other triterpene glycosides, with different scaffolds, such as gypenoside XVII (**65**), isolated from _Gynostemma pentaphyllum_ ([PERSON].) [PERSON], from China, exhibits neuroprotective activity by activating Nrf2 antioxidant pathways [111; 78].  
From the bark of _Melia azedarach_ L., indigenous to Southeast Asia, the triterpene methyl kulonate (methyl 3-oxo-16B-hydroxyeupha-7,24-dien-21-oate) (**66**) was isolated. This triterpene exhibits potent inhibitory activity against NO production from LPS-activated macrophages with an IC\({}_{50}\) value of 4.6 uM [112].  
The triterpene 3\(\beta\)-hydroxy-24-nor-urs-4(23),12-dien-28-oic acid (**67**), extracted from _Patrinia scabiosaefolia_ [PERSON] from China, exhibits inhibitory activity against NO with IC\({}_{50}\) value of 10.1 uM [113].  
Limonoids are highly oxygenated triterpenes existing mostly in the _citrus_ genus, as well as in other plant families, such as Meliaceae. Three limonoids were extracted from the seeds of _Trichilia welwitschia_ C.DC. existing in Nigeria, Gabon, Angola, and Cameroon, Africa. They were identified as trichilia lactone D5 (**68**), rohituka 3 (**69**), and dregeanin DM4 (**70**). At the lowest concentration of 0.5 \(\upmu\)g/mL, compounds **69** and **70** release the lowest amount of NO with IC\({}_{50}\) values of 2.97 and 2.93 \(\upmu\)M, respectively, while trichilia lactone D5 (**68**) with the same concentration releases an amount of NO above 4.0 \(\upmu\)M [114,115]. Ten other limonoids were extracted from the seeds of _Xylocarpus rumphii_ ([PERSON].) [PERSON] from Thailand. They were identified as 2-hydroxyxylorumphii F (**71**), E (**72**), F (**73**), G (**74**), H (**75**), I (**76**), and J (**77**), and the xyloccensus X (**78**), E (**79**), and K (**80**). While xylorumphii I (**76**) and 2-hydroxyxylorumphii F (**71**) exhibit a moderate inhibitory activity against NO production from LPS-activated macrophages with IC\({}_{50}\) values of 31.3 and 24.5 \(\upmu\)M, respectively, all the other compounds do not show any significant effects at a concentration of 50 \(\upmu\)M [116]. Nine other limonoids were isolated from the leaves of _M. azadarach_ indigenous to Japan, Taiwan, China, India, and Southeast Asia, namely, trichilinin B (**81**), 3-deacetyl-28-oxosalannin (**82**), 3-deacetyl-4\({}^{\prime}\)-demethyl-28-oxosalannin (**83**), 3-deacetyl-28-oxosalannolactone (**84**), 3-deacetyl-28-oxoisosalanninolide (**85**), 3-deacetyl-17-defurano-17,28-dioxosalannin (**86**), ohchinin (**87**), 23-hydroxyohchininolide (**88**), and 21-hydroxyisoohchinolide (**89**). Trichilinin B (**81**) and ohchinin (**87**) exhibit potent inhibitory activities toward NO production, induced by lipopolysaccharidesaccharides (LPSs), by murine macrophage-derived RAW264.7 cells, with IC\({}_{50}\) values of 29.2 and 28.7 \(\upmu\)M, respectively. 3-Deacetyl-28-oxosalannolactone (**84**), 23-hydroxyohchininolide (**88**), and 21-hydroxyisoohchinolide (**89**) also exhibit inhibitory activities with IC\({}_{50}\) values of 86.0, 58.6, and 87.3 \(\upmu\)M, respectively. All the others were inactive toward NO production (IC\({}_{50}>\) 100 \(\upmu\)M) [112]. Another triterpene, gedunin (**90**), found in the seeds of _Azadirachta indica_ A. Juss. (neem), from Southeast Asia, exhibits neuroprotective activity by activating Nrf2 antioxidant pathways [78,117].