Herniarin, Dimethylfraxetin and Extracts from Tagetes lucida, in Psychosis Secondary to Ketamine and Its Interaction with Haloperidol

Abstract

Tagetes lucida Cav., is a medicinal plant used in Mexico to alleviate different disorders related to alterations of the central nervous system, such as behaviors associated with psychosis. The present work evaluated the effect of different extracts separated from this plant, TlHex, TlEA, TlMet, and TlAq, and of two isolated coumarins, herniarin (HN) and dimethylfraxetin (DF), on haloperidol-induced catalepsy (HAL), and psychotic behaviors provoked with a glutamatergic antagonist, ketamine (KET) on ICR mice. The extracts TlEA, TlAq, and the isolated compounds HN and DF, induced an increment of the cataleptic effect of HAL. Schizophrenia-like symptoms caused by KET were analyzed through the behavior of the animals in the open field (OFT), forced swimming (FST), passive avoidance test (PAT), and social interaction test (SIT). Treatments derived from T. lucida could interact with this substance in all tests except for FST, in which only TlMet blocks its activity. Mainly, TlEA, TlAq, HN, and DF, blocked the effects of KET on stereotyped behavior, hyperlocomotion, cognitive impairment, and detriment in the social interaction of rodents. T. lucida interacted with dopaminergic and glutamatergic systems.

Effect of Herniarin on Cell Viability, Cell Cycle, and Erk Protein Levels in Different Stages of Bladder Cancer Cells

“…Herniarin, a compound found in several groups of plants, has a broad range of activities that includes anti‐cancer, anti‐genotoxic, anti‐diabetic, anti‐anxiety, anti‐depressant, anti‐inflammatory, and immunomodulatory effects [27] . Studies conducted by Silvan et al.…”

“…Herniarin, a compound found in several groups of plants, has a broad range of activities that includes anti-cancer, antigenotoxic, anti-diabetic, anti-anxiety, anti-depressant, anti-inflammatory, and immunomodulatory effects. [27] Studies conducted by Silvan et al showed that herniarin has in vitro antiinflammatory properties [28] and suggested its potential to act as an anti-nociceptive agent in mice. [29] Barchestani et al demonstrated that herniarin has the ability to reduce memory loss and pain thresholds by counteracting oxidative stress in an animal model of ischemia.…”

Effects of Five Coumarins and Standardized Extracts from Tagetes lucida Cav. on Motor Impairment and Neuroinflammation Induced with Cuprizone

“…In the same work, the interaction of these natural treatments with haloperidol was identified since a potentiation of catalepsy in mice induced by that drug was observed. The results of both trials indicate that these T. lucida products modify glutamatergic and dopaminergic neurotransmission; both are involved in the pathophysiology of neurological diseases such as schizophrenia [27]. This finding is interesting since ketamine, also used as an antidepressant, can reverse the effects caused by CPZ.…”

“…Recent research has shown that different extracts of T. lucida have properties such as anti-inflammatory and antioxidant activities and mainly have a potential use against illnesses related to the CNS, providing antinociceptive and sedative effects, and treatment for disorders of depression and anxiety [17][18][19]21,23,[25][26][27][28][29]. The HPLC analysis of the TlHx and TlAcOEt extracts allowed the identification of five coumarins with biological activity: IC, HN, DF, SC, and PE.…”

“…For example, repeated treatment with (R)-ketamine (10 mg/kg/ daily, twice a week, for six weeks) significantly improved demyelination and activated microglia in the brain compared with saline-treated mice [40]. Thus, it can be deduced that T. lucida could be exerting its protective effect against the actions of cuprizone due to its ability to interact with the glutamatergic system as ketamine does [27], since the products of the plant interact with that drug. More studies are necessary to establish the relationship between this neurotransmission system and coumarins.…”