Hydroxy Pentacyclic Triterpene Acid, Kaempferol, Inhibits the Human 5-Hydroxytryptamine Type 3A Receptor Activity

Abstract

Monoamine serotonin is a major neurotransmitter that acts on a wide range of central nervous system and peripheral nervous system functions and is known to have a role in various processes. Recently, it has been found that 5-HT is involved in cognitive and memory functions through interaction with cholinergic pathways. The natural flavonoid kaempferol (KAE) extracted from Cudrania tricuspidata is a secondary metabolite of the plant. Recently studies have confirmed that KAE possesses a neuroprotective effect because of its strong antioxidant activity. It has been confirmed that KAE is involved in the serotonergic pathway through an in vivo test. However, these results need to be confirmed at the molecular level, because the exact mechanism that is involved in such effects of KAE has not yet been elucidated. Therefore, the objective of this study is to confirm the interaction of KAE with 5-HT3A through electrophysiological studies at the molecular level using KAE extracted from Cudrania tricuspidata. This study confirmed the interaction between 5-HT3A and KAE at the molecular level. KAE inhibited 5-HT3A receptors in a concentration-dependent and voltage-independent manner. Site-directed mutagenesis and molecular-docking studies confirmed that the binding sites D177 and F199 are the major binding sites of human 5-HT3A receptors of KAE.

Transcriptome and metabolome reveal the accumulation of secondary metabolites in different varieties of Cinnamomum longepaniculatum

“…Flavonoids, which include, flavones, flavonols, flavan-3-ols, flavanones, isoflavanones, isoflavans, and pterocarpans, have diverse structures. Previous studies suggest that apigenin [ 35 ], chrysin [ 36 ], neohesperidin [ 37 ], epicatechin [ 38 ], catechin [ 39 ], and kaempferol [ 40 , 41 ] are bioactive substances that have antioxidant, antibacterial, antifungal, and antitumor activities and anti-inflammatory properties. Therefore, we believe that the flavonoids in C .…”

Chronic-Exposure Low-Frequency Magnetic Fields (Magnetotherapy and Magnetic Stimulation) Influence Serum Serotonin Concentrations in Patients with Low Back Pain—Clinical Observation Study

“…Its precursor is tryptophan; out of which, hydroxytryptophan is synthesized by the tryptophan hydroxylase (TPH) enzyme by means of hydroxylation. After decarboxylation, hydroxytryptophan is converted into serotonin [ 1 , 2 , 3 ].…”

“…Serotonin is involved in cognitive processes, and regulates eating habits, sexual activity, mood and anxiety [ 4 ], aggression and pain (through substance P inter alia), sleep and wakefulness, and other biological rhythms. It acts as a hormone and a cytokine [ 2 , 3 , 5 ]. All of these processes are associated with membrane receptors that are classified into seven families (5HT1-7) with 21 subtypes.…”

“…The concentration of serotonin rises in preeclampsia as it is released from the breakdown of platelets [ 3 ]. Marktl et al [ 11 ] observed a decrease in the concentration of serotonin in patients with ischemic heart disease during the day, whereas its concentrations remained steady at night.…”

“…In peripheral tissues, serotonin plays a role in immune processes (proinflammatory agent) [ 3 ], the physiology of digestion, the development of mammary glands, coagulation, and fibrinolysis. In stress, by affecting the adrenal cortex, serotonin regulates cell proliferation, and their migration and differentiation [ 2 ].…”