*3.7. Antioxidant E*ff*ects*

*C. vulgaris* hot-water extract [151] and acetone extract [152] are reported to have antitumor activity. A *Chlorella* aqueous extract containing substantial amounts of antioxidants also exhibit antiproliferative activity in human hepatoma cells [153]. Lipophilic pigments, including carotenoids antheraxanthin, zeaxanthin, and lutein, extracted from *Chlorella* cells were observed to significantly inhibit the growth of human colon cancer cells [154]. These results sugges<sup>t</sup> that the antitumor activity of *Chlorella* might be the synergistic e ffect of multiple bioactive compounds. Romos et al. [155] reported that *Chlorella* supplementation can modulate immunomyelopoietic activity and disengage tumor-induced suppression of various cytokines and related cell activities in tumor-bearing mice. Interestingly, a 63.1-kD antitumor glycoprotein was isolated from the culture supernatant of *C. vulgaris* strain CK22 [156,157], and its chemical and antitumor properties were characterized [158], suggesting possible contribution of this glycoprotein toward the observed antitumor activity.

Alzheimer's disease is a severe neurodegenerative condition a ffecting humans [159]. The erythrocytes of Alzheimer's disease patients are known to be in an excessively oxidized

state [160]. α-Tocopherol and carotenoids such as lutein are important lipophilic antioxidants in human erythrocytes [161]. Erythrocyte lutein levels were found to be significantly lower in Alzheimer's disease patients than in normal subjects [162]. Oral intake of lutein capsules increases lutein levels and prevents phospholipid hydroperoxide accumulation in human erythrocytes [163], suggesting that dietary lutein has the potential to act as an important antioxidant in erythrocytes and thus may have beneficial e ffects in Alzheimer's disease patients. According to the labels on *Chlorella* products D and M, the products contain substantial amounts of lutein (approximately 200 mg/100 g dry weigh). A randomized, double-blind, placebo-controlled human study was conducted to evaluate the e ffects of *Chlorella* supplementation (8 g *Chlorella*/day/person; equivalent to 22.9 mg lutein/day/person) on phospholipid hydroperoxide and lutein levels in erythrocytes [164]. After two months of *Chlorella* supplementation, erythrocyte lutein levels increased 4.6-fold, but tocopherol levels did not change [164], suggesting that daily *Chlorella* intake may be e ffective for improving and maintaining erythrocyte antioxidant status and lutein levels in humans. These results sugges<sup>t</sup> that *Chlorella* supplementation contributes to maintaining the normal function of erythrocytes and has beneficial e ffects on Alzheimer's disease-related dementia in humans.

Major depressive disorder is a widespread mental disorder that greatly impairs the quality of life of humans. Approximately 12% of people experience at least one episode of depression during their lifetime [165]. Although various antidepressant drugs are available for treating depression, a considerable proportion of patients are not responsive to these drugs and some experience side effects [166,167]. Therefore, alternative antidepressant drugs with adequate e fficacy and safety are needed. The therapeutic e ffect of dried *C. vulgaris* extract administration (1.8 g/day) for six weeks was evaluated in patients with major depressive disorder [168]. After treatment, the participants exhibited improvements in physical and cognitive symptoms of depression [168]. As oxidative stress is an important pathophysiological mechanism underlying major depressive disorder, major depressive disorder has been e ffectively reversed via antioxidant therapy [169,170]. These observations sugges<sup>t</sup> that the therapeutic e ffectiveness of *Chlorella* supplementation may result from the action of its antioxidant nutrients and compounds [171].
