*6.2. Antioxidant Activity*

Zeashan and colleagues documented the antioxidant activity of amaranth extract (obtained from the whole plant). In the study conducted by Zeashan et al., (2009), this extract showed significant antioxidant activity in the DPPH assay. In the next study by Lucero-Lopez et al., antioxidant properties of *Amaranthus hypochondriacus* seed extract were also examined. The study was conducted on the liver of rats sub-chronically exposed to ethanol. The results obtained in the experiments confirm the beneficial effect of the tested extract, which as a rich source of polyphenols, had a protective effect on the livers of rats [23]. Sarker and Oba's work characterized the phytochemical composition of *Amaranthus gangeticus* L. species. They particularly focused on the identification of phenolic compounds responsible for the antioxidant activity of these plants. Twenty-five different phenolic compounds were identified in the plant. Antioxidant components of *A. gangeticus* genotypes exhibited good radical scavenging activities [24]. In another study, the same authors presented chemical compounds found in amaranth *A. tricolor* (betaxanthins, betalains) that exhibit antioxidant activity [25]. In the study by Al-Mamun et al., the antioxidant activity of the methanol extract derived from the seed and stem of *A. hybridus* and *A. lividus* was tested. The DPPH radical scavenging assay showed that both extracts examined possessed significant dose-dependent antioxidant potential, exhibiting IC50 values of 28 ± 1.5 and 93 ± 3.23 μg/mL, respectively [26]. In a subsequent scientific paper, two polysaccharides from *A. hybridus* named AHP-H-1 and AHP-H-2 were characterized and examined as potential antioxidant factors. The results obtained in the study confirmed that the two polysaccharides purified from *A. hybridus* have strong antioxidant activity (DPPH radical scavenging activity and superoxide anion free radical scavenging activity) [27]. Kumari and colleagues confirmed the antioxidant properties of another amaranth species, *A. viridis.* Aqueous, chloroform, methanol, and hexane extracts were examined in several in vitro model systems. *A. viridis* exhibited dose-dependent effective antioxidant properties. Major components responsible for his antioxidant activity are gulonic and chlorogenic acids and also kaempferol [28]. In another paper describing the antioxidant activity of amaranth, the phenolic composition of the aerial part of *Amaranthus caudatus* was tested using ABTS+,

DPPH, and O2 scavenging activity, ferric-reducing antioxidant power (FRAP), and Fe2+ chelating ability methods. Different levels of antioxidant activity were observed depending on the stage of plant development and the content of biologically active substances (mainly a wide range of phenolic composition) responsible for generating such activity [3]. Studies focusing on the antioxidant capacity of amaranth over the period 2015–2020 were collected and summarized in Park et al.'s work. In this review, current knowledge on the antioxidant properties of different amaranth species was systematized and consolidated. These properties resulted not only from the presence of phenolic compounds but were also derived from hydrolysates and active peptides with superior antioxidant activity [8].

## *6.3. Anticancer Potential*

Water extracts of two amaranth species (*A. lividus* and *A. hybridus*) were examined as anticancer factors. Female Swiss albino mice divided into a few groups were injected with EAC cells and received 25, 50, or 100 μg/mL/day/mouse of test extracts after 24 h of EAC cells injection. The measurement of cancer cells growth inhibition was conducted. Administration of *A. hybridus* and *A. lividus* extracts led to 45 and 43% growth inhibition of EAC cells [26]. The seed extract of *A. hybridus* possessed higher growth inhibitory activity than the stem extract of *A. lividus* and exhibited 14, 26, and 45% growth inhibition at 25, 50, and 100 μg/mL, respectively. In animals treated with amaranth extracts, morphological changes suggestive of apoptosis were also observed in EAC cells. Amaranth preparations can be considered as a potential target for cancer cure studies [26].

#### *6.4. Antihyperglicemic and Hypolipidemic Activity*

There are scientific papers in the databases on the sugar-lowering and cholesterollowering effects of amaranth-containing products. Methanolic extract of *Amarantus viridis* leaves (at the dose of 200 mg/kg and 400 mg/kg per day, 21 days) reduced blood sugar levels in streptozotocin-induced diabetic rats. The administration of the extract also reduced serum cholesterol and triglyceride levels [29]. Girija et al. investigated the anti-diabetic and anti-cholesterolemic activity of the methanol extract of leaves (200 and 400 mg/kg, for 21 days) from three species of amaranth: *A. caudatus, A. spinosus,* and *A. viridis* [30]. Experiments were conducted in streptozotocin-induced diabetic rats. Methanol extracts of all three species of amaranth showed significant glucose and cholesterol-lowering activity at a dose of 400 mg/kg [30]. Similar issues are presented in another paper published in 2011. Antihyperglycemic and hypolipidemic activity of the methanolic extract of leaves of *Amaranthus viridis* was investigated. Normal and streptozotocin-induced diabetic rats were fed with 200 mg/kg and 400 mg/kg of extract *per os* for 21 days. The authors of this study proved that the tested extract showed antiglycemic activity and improved the lipid profile in rats [29]. Studies on the activity of selected proteins from amaranth (*Amaranthus cruentus*) sugges<sup>t</sup> hypocholesterolemic activity of this plant. Manolio Soares and colleagues showed that proteins from the plant affect the action of a key enzyme in cholesterol biosynthesis, 3-hydroxy-3-methyl-glutaryl-CoA reductase [31]. The hypolipemic effect of amaranth oil is associated with its significant squalene content. The mechanism of activity of squalene relies on the inhibition of HMG-CoA activity—a liver enzyme responsible for cholesterogenesis. Such activity has been demonstrated in both rat and clinical studies [7]. In another paper, the effects of consumption of the *Amaranthus mangostanus* on lipid metabolism and gu<sup>t</sup> microbiota in high-fat diet-fed mice were examined. Amaranth powder supplementation significantly reduced the levels of triglycerides, total cholesterol, and phospholipids in the liver of rats and also downregulated the expression of a few lipogenesis-related genes [32]. Recent research findings sugges<sup>t</sup> that the aqueous extract obtained from steamed red amaranth leaves might be used as a potent nutritional supplement to prevent diabetic retinopathy. Anti-glycative and anti-oxidative action of that extract against a high glucoseinduced injury was examined in a human lens epithelial cell line HLE-B3 [33].

#### *6.5. Neuroprotective and Antidepressant Action*

An attempt was made to determine the neuroprotective effect of *A. lividus* L. and *A. tricolor* L. extracts against AGEs-induced cytotoxicity and oxidative stress. Advanced glycation end-products (AGEs) caused oxidative stress and cytotoxicity in neuronal cells. It was found that examined extracts protect human neuroblastoma SH-SY5Y cells against AGEs-induced cytotoxicity [34]. The authors sugges<sup>t</sup> that amaranth may be useful for treating chronic inflammation associated with neurodegenerative disorders [34]. In another paper by the same authors, the neuroprotective effect of amaranth was again described. The methanol extracts of *A. lividus* and *A. tricolor* leaves were found to decrease cell toxicity and intracellular ROS production in human neuronal immortalized SH-SY5Y cells. Examined extracts decreased oxidative stress by suppressing gene expression of HMOX-1, RAGE, and RelA. Because of such activity and the high content of antioxidant substances, amaranth extracts may be a potential neuroprotective factor [35]. The methanol extract of *Amaranthus spinosus* (100 and 200 mg/kg, orally) was investigated for antidepressant activity. In the study, forced swimming test (FST) and tail suspension test (TST) models were used in experimental rats. The results of the tests prove the antidepressive potential of the methanol extract of this plant. The authors indicate that the mechanism of this activity has not ye<sup>t</sup> been understood and its explanation requires further in-depth studies [36].
