## 6 Pharmacological Properties of _Apium_ Plants
### Bioactivities of Phytochemicals Identified in Apium spp. The various activities observed for the extracts are strongly supported by the presence of peculiar phytochemical constituents in both volatile fraction and polar compounds (Figure 2). [PERSON] et al. designed an in vivo study to investigate the chemopre potential of flavonoid fractions of _Apium_ plants (FFAP) on Swiss mice. The co-administration of FFAP with DMBA-treated groups provided significant (\(p\leq 0.001\)) prevention against skin papilloma and lipid peroxidation statue was normalized as compared to a carcinogenic control. Thus, they suggested that FFAP had chemopre potential on DMBA-induced carcinogenesis in mice, which may be due to the modulation of cutaneous lipid peroxidation or enhancement of total antioxidant capacity [95]. [PERSON] et al. indicated that FFAP is effective on the enzyme activities of the liver as well as lipid peroxidation, thus, it can possess chemopre activity. FFAP was effective in suppressing skin tumor growth especially when a dose of 20 mg/kg was treated, which was probably attributed to anti-lipid peroxididative or antioxidant potential during DMBA tumor induction [100]. [PERSON] et al. investigated the antitumor effects of _A. gravelens_ extract (AGE) and related mechanisms of apoptosis in human gastric cancer BGC-823 cells [166]. In the study by [PERSON] et al. it was shown that, AGE had an antiproliferative effect on human gastric cancer BGC-823 cells in a dose- and time-dependent manner [166]. The apoptotic rate significantly increased after uptake of AGE with morphological changes typical of apoptosis. The findings indicated that AGE could significantly inhibit the growth and induce apoptosis via the bcl-2 family related mitochondria-mediated pathway of human gastric cancer cell line BGC-823 in vitro. Thus, it would seem to be worth to investigate AGE as a novel natural therapeutic alternative, and the induction of apoptosis by AGE in other cancer cell lines can be the current subject of on-going investigations. [166]. Several studies are available in the literature on the bioactivities of _Apium_ constituents. Among these, _p_-mentha-2,8-dien-1-ol (1-methyl-4-prop-1-en-2-ylcyclohexyl-2-en-1-ol) (1), 3-\(n\)-butyl-phthalide (3-butyl-2-benzofuran-1(3\(H\))-one) (2), and sedanolide (3-butyl-3a,4,5,6-tetrahydro-1(3\(H\))-isobenzofuranone) (3) in 20 mg/dose every two days for a total of three doses, resulted to be effective in the induction of synthesis of the detoxifying enzyme glutathione S-transferase (GST) in a female A/J mice model. The GST activity increased 4.5-5.9 and 3.2-5.2 times as compared to the controls. These oil components inhibited  
Figure 2: Chemical structure of the most common bioactive ingredients in _Apium_ plants. the benzo[a]pyrene-induced tumor formation. In particular, the administration of 3-\(n\)-butyl-phthalide (2) and sedanolide (3) reduced the tumor formation in the order of 68% to 30% and 11%, respectively. Conversely, \(p\)-mentha-2,8-dien-1-ol (1) produced only a small or no significant reduction of tumor formation [209]. Sedanolide (3) has been reported to be the most active of the phthalides in the reduction of tumors in laboratory animals, i.e., 83% reduction. From the phytochemical standpoint, it is interesting to note that these compounds belong to the monoterepenoid (\(p\)-mentha-2,8-dien-1-ol) (1) and phthalides (3-\(n\)-butyl-phthalide and sedanolide) (2 and 3), which are two classes of natural products that are well represented, and to some extent, peculiar, in botanical entities comprised in the Apiaceae family [210,211]. In addition, 3-\(n\)-butylphthalide (3), was investigated for its neuroprotective potentialities in rat hippocampal neurons and human neuroblastoma SH-SY5Y cells. The results indicated it was an anti-cerebral ischemia agent, and it proved to have therapeutic effects on learning and memory deficits induced by intracerebral infusion and chronic cerebral hypoperfusion.