The novel protective effects of loganin against 1‐methyl‐4‐phenylpyridinium‐induced neurotoxicity: Enhancement of neurotrophic signaling, activation of IGF‐1R/GLP‐1R, and inhibition of RhoA/ROCK pathway

Abstract

Loganin, a major iridoid glycoside obtained from fruits of Cornus officinalis, possesses anti‐inflammatory, antitumor, antidiabetic, and osteoporosis prevention effects. Loganin has been linked to neuroprotection in several models of neurodegeneration, including Parkinson's disease (PD). However, mechanisms underlying the neuroprotective effects of loganin are still mostly unknown. Here, we demonstrated the protective effects of loganin against PD mimetic toxin 1‐methyl‐4‐phenylpyridinium (MPP+) and the important roles of insulin‐like growth factor 1 receptor (IGF‐1R) and glucagon‐like peptide 1 receptor (GLP‐1R) in the neuroprotective mechanisms of loganin. In primary mesencephalic neuronal cultures treated with or without MPP+, loganin up‐regulated expressions of neurotrophic signals including IGF‐1R, GLP‐1R, p‐Akt, BDNF, and tyrosine hydroxylase. Loganin protected against MPP+‐induced apoptosis by up‐regulating antiapoptotic protein and down‐regulating proapoptotic protein. Moreover, loganin attenuated MPP+‐induced neurite damage via up‐regulation of GAP43 and down‐regulation of membrane‐RhoA/ROCK2/p‐LIMK/p‐cofilin. Loganin also attenuated MPP+‐induced reactive oxygen species (ROS) production. However, both AG1024, an IGF‐1R antagonist, and exendin 9‐39, a GLP‐1R antagonist, attenuated the protective effects of loganin on MPP+‐induced cytotoxicity, apoptosis, neurite length decrease, and ROS production. Our results suggest that loganin attenuates MPP+‐induced apoptotic death, neurite damage, and oxidative stress through enhancement of neurotrophic signaling, activation of IGF‐1R/GLP‐1R, and inhibition of RhoA/ROCK pathway, providing the evidence that loganin possesses novel neuroprotective effects.

Devil's claw (Harpagophytum procumbens) and chronic inflammatory diseases: A concise overview on preclinical and clinical data

“…This extract was able to decrease the burden of oxidative stress and protect from the decline in cortical dopamine (DA), norepinephrine (NE), and serotonin (5‐hydroxytriptamine, 5‐HT) levels induced by amyloid β‐peptide, in rat cortex synaptosomes (Ferrante et al, ). Intriguingly, the multitarget mechanisms showed by both devil's claw extracts and harpagoside corroborate recent in vitro studies regarding the neuroprotective effects induced by iridoid compounds such as loganin and genipin (Liu, Chen, Lu, Fang, & Yu, ; Tseng, Lin, Chang, & Lo, ), thus supporting future in vivo investigations in order to confirm the efficacy and safety in the management of neurodegenerative diseases.…”

Determination of bioactive compounds in the nonmedicinal parts of Scrophularia ningpoensis using ultra‐high‐performance liquid chromatography coupled with tandem mass spectrometry and chemometric analysis

“…It is worth noting that the total content of compounds in the flowers was much higher than that in the other parts, especially that of iridoids, which was three times higher in the flowers than in the medicinal part (i.e., the roots). Modern pharmacological studies have shown that iridoids have antitumoral [28], hepatoprotective [29], neuroprotective [30], and other biological effects [6,31]. Therefore, S. ningpoensis flowers might provide a supplementary source of iridoids, be used as a source for the extraction of important bioactive compounds, and reduce the waste of nonmedical parts and environmental pollution.…”

Iridoids: Research Advances in Their Phytochemistry, Biological Activities, and Pharmacokinetics

“…Furthermore, the presence of IGF-1R antagonists (AG1024) or GLP-1R antagonists (exendin 9-39) weakened the protective effect of loganin on MPP+ -induced cytotoxicity and apoptosis, and decreased neuron length and ROS production. A series of experiments showed that loganin could enhance neurotrophic signals, activate IGF-1R/GLP-1R, inhibit RhoA/ROCK pathway, and alleviate MPP+ induced apoptosis and death, neuron damage, oxidative stress, and other mechanisms to achieve neuroprotective effect [53].…”