Search

Tithonia diversifolia (Hemsl.) A. Gray leaves have long been used to manage neurodegenerative diseases without scientific basis. This study characterized the phenolic constituents, evaluated the antioxidant properties of phenolic extracts from T. diversifolia leaves used as traditional medicine in Africa and its inhibition of key enzymes linked to Alzheimer’s disease. The extract was rich in phenolic acids (gallic acid, chlorogenic acid, caffeic acid and p-coumaric acid) and flavonoids (apigenin) and had 1,1-diphenyl-2-picryl-hydrazil radical scavenging abilities (IC50 = 41.05 μg. mL−1), 2,2-Azino-bis3-ethylbenthiazoline-6sulphonic acid radical scavenging ability (IC50 = 33.51 μg. mL−1), iron chelation (IC50 = 38.50 μg. mL−1), reducing power (Fe3+- Fe2+) (7.34 AAEmg/100 g), inhibited acetylcholinesterase (IC50 = 39.27 μg mL−1) and butyrylcholinesterase (IC50 = 35.01 μg mL−1) activities. These results reveal the leaf as a rich source of phenolic compounds with antioxidant and cholinesterase inhibitory activity. Keywords: Tithonia diversifolia leaves, Antioxidant activity, Cholinergic enzymes, Alzheimer’s disease

Highlights • Novel organic selenium compounds presented low toxicity over C. elegans survival. • Defecation cycles were decreased by Novel organic selenium compounds, except C1. • Novel organic selenium compounds, except C1 decreased AChE enzyme activity. • All compounds tested prevented from juglone stress. • C2 selenium compound decreased GST-4::GFP fluorescence under juglone stress., Organic selenium compounds possess numerous biological properties, including antioxidant activity. Yet, the high toxicity of some of them, such as diphenyl diselenide (DPDS), is a limiting factor in their current usage. Accordingly, we tested four novel organic selenium compounds in the non-parasite nematode Caenorhabditis elegans and compared their efficacy to DPDS. The novel organic selenium compounds are β-selenoamines 1-phenyl-3-(p-tolylselanyl)propan-2-amine (C1) and 1-(2-methoxyphenylselanyl)-3-phenylpropan-2-amine (C2) and analogs of DPDS 1,2-bis(2-methoxyphenyl)diselenide (C3) and 1,2-bisp-tolyldiselenide (C4). Synchronized worms at the L4 larval stage were exposed for one hour in M9 buffer to these compounds. Oxidative stress conditions were induced by juglone (200 μM) and heat shock (35 °C). Moreover, we evaluated C. elegans behavior, GST-4::GFP (glutathione S-transferase) expression and the activity of acetylcholinesterase (AChE). All tested compounds efficiently restored viability in juglone stressed worms. However, DPDS, C2, C3 and C4 significantly decreased the defecation cycle time. Juglone-induced GST-4::GFP expression was not attenuated in worms pretreated with the novel compounds, except with C2. Finally, AChE activity was reduced by DPDS, C2, C3 and C4. To our knowledge, this is study firstly showed the effects of C1, C2, C3 and C4 selenium-derived compounds in C. elegans. Low toxic effects were noted, except for reduction in the defecation cycle, which is likely associated with AChE inhibition. The juglone-induced stress (reduced viability) was fully reversed by compounds to control animal levels. C2 was also efficient in reducing the juglone-induced GST-4::GFP expression, suggesting the latter may mediate the stress induced by this compound. Future studies could be profitably directed at addressing additional molecular mechanisms that mediate the protective effects of these novel organic selenium compounds.

Graphical abstract, Highlights • Current study supports antioxidant activity of Tithonia diversifolia leaves. • Current study also supports anti cholinesterase activity of Tithonia diversifolia leaves. • Current investigation adequately characterized the phenolic compounds of Tithonia diversifolia leaves., Tithonia diversifolia (Hemsl.) A. Gray leaves have long been used to manage neurodegenerative diseases without scientific basis. This study characterized the phenolic constituents, evaluated the antioxidant properties of phenolic extracts from T. diversifolia leaves used as traditional medicine in Africa and its inhibition of key enzymes linked to Alzheimer’s disease. The extract was rich in phenolic acids (gallic acid, chlorogenic acid, caffeic acid and p-coumaric acid) and flavonoids (apigenin) and had 1,1-diphenyl-2-picryl-hydrazil radical scavenging abilities (IC50 = 41.05 μg. mL−1), 2,2-Azino-bis3-ethylbenthiazoline-6sulphonic acid radical scavenging ability (IC50 = 33.51 μg. mL−1), iron chelation (IC50 = 38.50 μg. mL−1), reducing power (Fe3+- Fe2+) (7.34 AAEmg/100 g), inhibited acetylcholinesterase (IC50 = 39.27 μg mL−1) and butyrylcholinesterase (IC50 = 35.01 μg mL−1) activities. These results reveal the leaf as a rich source of phenolic compounds with antioxidant and cholinesterase inhibitory activity.