## 4 _Cucurbita_ Plants Phytochemical Composition
### Terpenoids, Saponins and Sterols in Cucurbita
On the other hand, cotyledons of this species were found to include cucurbitacin D and E in moderate and low concentrations, respectively [103]. Freeze-dried samples of Blackjack cultivar of _C. pepo_ were analyzed by two research teams in different years. [PERSON] et al. [101] found 1.12 mg cucurbitacin E-glycoside/g fresh weight, whereas [PERSON] and [PERSON] [100] detected 0.6 mg cucurbitacin E-glycoside/g fresh weight. [PERSON] et al. [104] investigated _C. pepo_ cv dayangua for its phytochemical content, and cucurbitacin L and cucurbitacin K were isolated at concentrations of 2.13 mg/kg dry matter and 2.67 mg/kg dry matter, respectively. In a very recent study, cucurbitacin C and E glycosides in _C. pepo_ fruit were reported for the first time. The corresponding concentrations of compounds were 105 ug/g fresh fruit for cucurbitacin C and 438 ug/g fresh fruit cucurbitacin E. The authors also demonstrated that gamma irradiation did not affect the cucurbitacins concentration, when compared to non-irradiated control group [105]. From a biological point of view, it has been demonstrated that cucurbitacins exert several bioactivities, such as antitumor, anti-inflammatory, anti-atheosclerotic, antidiabetic effects [106]. There is a large body of evidence suggesting that cucurbitacins hold very high orders of cytotoxicity towards a vast quantity of malignancies. Seed and fruit portions of few cucurbits are found to exhibit purgative, emetic and anthelmintic activities due to presence of cucurbitacin triterpenoids [107; 108]. [PERSON] et al. [109] isolated cucurbitacins B, D, E, and I from _C. andreana_ fruits and evaluated their effects at a level of growth suppression of human breast (MCF-7), colon (HCT-116), lung (NCI-H460), and central nervous system (CNS) (SF-268) tumor cell lines; cyclooxygenasease-1 (COX-1) and cyclooxygenase-2 (COX-2) enzymes; and even on lipid peroxidation. All isolated cucurbitacins were able to abate the proliferation of investigated cancer cell lines in varying percentages. Among them, cucurbitacin B exhibited more than 80% proliferation inhibitory activity. Additionally, cucurbitacins B, D, E, and I inhibited COX-2 enzyme, an enzyme responsible for inflammation, by 32%, 29%, 35%, and 27%, respectively, at a concentration of 100 mg/mL. A cucurbitacin derivative, with a cucurbitacin D-like structure, was separated from the methanolic extract of _C. pepo_ seeds and revealed to have antiulcer activity in a dose-dependent manner [110]. In contrast to their biological activities, cucurbitacins have toxic effects in mammalians. According to [PERSON] et al. [111], 353 poisoning cases linked to _C. pepo_ cucurbitacins were reported to French Poison Control Centers between 1 January 2012 and 12 December 2016. In 1980s, various human poisoning cases were stated due to the consumption of commercially produced zucchini (_C. pepo_) in Australia. The most common developed characteristic symptoms evidenced by exposed individualsinclude a bitter taste in the mouth, abdominal pain, diarrhea and rarely, collapse [101]. [PERSON] et al. [112] reported that, 81 symptomatic cases were registered to Poison Information Centre (PIC) Munich between 2002 to 2015. The primary symptom was colitis with bloody diarrhea after zucchini (_C. pepo_) consumption. As the authors stated, cucurbitacins, the responsible toxins of poisonings, are not often identified in cultivated fruits, but some fruits spontaneously produced them. In an in vivo experiment, mice were fed with _C. pepo_ fruit of two cultivars, 'Blackjack' and 'Straightneck', and an accession of the bitter species, _C. texana_. As a result, mice having the diet with 1% _C. texana_, containing cucurbitacins E glycoside and I, exhibited poor growth, severe diarrhea, anemia and 40% mortality. When the _C. texana_ percentage increased to 10 or 20%, mortality rate reached 100% within a few days. However, no detectable cucurbitacins in _C. pepo_ cultivars were identified and, animals fed up to 20% freeze-dried squash in their diets displayed no toxicity-related symptoms [113].