Arctigenin protects against depression by inhibiting microglial activation and neuroinflammation via HMGB1/TLR4/NF-κB and TNF-α/TNFR1/NF-κB pathways.

BACKGROUND AND PURPOSE: Arctigenin, a major bioactive component of Fructus arctii, has been reported to have antidepressant-like effects. However, the mechanisms underlying these effects are still unclear. Neuroinflammation can be caused by excessive production of proinflammatory cytokines in microglia via high-mobility group box 1 (HMGB1)/TLR4/NF-κB and TNF-α/TNFR1/NF-κB signalling pathways, leading to depression. In this study, we have investigated the antidepressant mechanism of arctigenin by conducting in vitro and in vivo studies. EXPERIMENTAL APPROACH: The effects of chronic unpredictable mild stress (CUMS) on wild-type (WT) and TLR4-/- mice were examined. Antidepressant-like effects of arctigenin were tested using the CUMS-induced model of depression in WT mice. The effects of arctigenin were assessed on the HMGB1/TLR4/NF-κB and TNF-α/TNFR1/NF-κB signalling pathways in the prefrontal cortex (PFC) of mouse brain and HMGB1- or TNF-α-stimulated primary cultured microglia. The interaction between HMGB1 and TLR4 or TNF-α and TNFR1 with or without arctigenin was examined by localized surface plasmon resonance (LSPR) and co-immunoprecipitation assays. KEY RESULTS: The immobility times in the tail suspension test (TST) and forced swimming test (FST) were reduced in TLR4-/- mice, compared with WT mice. Arctigenin exhibited antidepressant-like effects. Arctigenin also inhibited microglia activation and inflammatory responses in the PFC of mouse brain. Arctigenin inhibited HMGB1 and TLR4 or TNF-α and TNFR1 interactions, and suppressed both HMGB1/TLR4/NF-κB and TNF-α/TNFR1/NF-κB signalling pathways. CONCLUSIONS AND IMPLICATIONS: Arctigenin has antidepressant-like effects by attenuating excessive microglial activation and neuroinflammation through the HMGB1/TLR4/NF-κB and TNF-α/TNFR1/NF-κB signalling pathways. This suggests that arctigenin has potential as a new drug candidate suitable for clinical trials to treat depression.

Antidepressive Effect of Arctiin by Attenuating Neuroinflammation via HMGB1/TLR4- and TNF-α/TNFR1-Mediated NF-κB Activation.

Inflammation is a potential factor in the pathophysiology of depression. A traditional Chinese herbal medicine, arctiin, and its aglycone, arctigenin, are the major bioactive components in Fructus arctii and exhibit neuroprotective and anti-inflammatory activities. Arctigenin has been reported to have antidepressant-like effects. However, the antidepressant-like effects of arctiin, its precursor, remain unknown. In this study, we investigated the antidepressant-like effects of arctiin and its underlying mechanisms by in vivo and in vitro experiments in mice. Our results showed that arctiin significantly attenuated sucrose consumption and increased the immobility time in tail suspension and forced swimming tests. Arctiin decreased neuronal damage in the prefrontal cortex (PFC) of the brain. Arctiin also attenuated the levels of three inflammatory mediators, indoleamine 2,3-dioxygenase, 5-hydroxytryptamine, and dopamine, that were elevated in the PFC or serum of chronic unpredictable mild stress (CUMS)-exposed mice. Arctiin reduced excessive activation of microglia and neuroinflammation by reducing high mobility group box 1 (HMGB1)/toll-like receptor 4 (TLR4)- and tumor necrosis factor-α (TNF-α)/TNF receptor 1 (TNFR1)-mediated nuclear factor-kappa B (NF-κB) activation in the PFC of CUMS-exposed mice and HMGB1- or TNF-α-stimulated primary cultured microglia. These findings demonstrate that arctiin ameliorates depression by inhibiting the activation of microglia and inflammation via the HMGB1/TLR4 and TNF-α/TNFR1 signaling pathways.

Effects of posterior corneal astigmatism on the accuracy of AcrySof toric intraocular lens astigmatism correction.

AIM: To evaluate the effects of posterior corneal surface measurements on the accuracy of total estimated corneal astigmatism. METHODS: Fifty-seven patients with toric intraocular lens (IOL) implantation and posterior corneal astigmatism exceeding 0.5 diopter were enrolled in this retrospective study. The keratometric astigmatism (KA) and total corneal astigmatism (TA) were measured using a Pentacam rotating Scheimpflug camera to assess the outcomes of AcrySof IOL implantation. Toric IOLs were evaluated in 26 eyes using KA measurements and in 31 eyes using TA measurements. Preoperative corneal astigmatism and postoperative refractive astigmatism were recorded for statistical analysis. The cylindrical power of toric IOLs was estimated in all eyes. RESULTS: In all cases, the difference of toric IOL astigmatism magnitude between KA and TA measurements for the estimation of preoperative corneal astigmatism was statistically significant. Of a total of 57 cases, the 50.88% decreased from Tn to Tn-1, and 10.53% decreased from Tn to Tn-2. In all cases, 5.26% increased from Tn to Tn+1. The mean postoperative astigmatism within the TA group was significantly lower than that in the KA group. CONCLUSION: The accuracy of total corneal astigmatism calculations and the efficacy of toric IOL correction can be enhanced by measuring both the anterior and posterior corneal surfaces using a Pentacam rotating Scheimpflug camera.

Optical performance of toric intraocular lenses in the presence of decentration.

AIM: To evaluate the optical performance of toric intraocular lenses (IOLs) after decentration and with different pupil diameters, but with the IOL astigmatic axis aligned. METHODS: Optical performances of toric T5 and SN60AT spherical IOLs after decentration were tested on a theoretical pseudophakic model eye based on the Hwey-Lan Liou schematic eye using the Zemax ray-tracing program. Changes in optical performance were analyzed in model eyes with 3-mm, 4-mm, and 5-mm pupil diameters and decentered from 0.25 mm to 0.75 mm with an interval of 5° at the meridian direction from 0° to 90°. The ratio of the modulation transfer function (MTF) between a decentered and a centered IOL (MTFDecentration/MTFCentration) was calculated to analyze the decrease in optical performance. RESULTS: Optical performance of the toric IOL remained unchanged when IOLs were decentered in any meridian direction. The MTFs of the two IOLs decreased, whereas optical performance remained equivalent after decentration. The MTFDecentration/MTFCentration ratios of the IOLs at a decentration from 0.25 mm to 0.75 mm were comparable in the toric and SN60AT IOLs. After decentration, MTF decreased further, with the MTF of the toric IOL being slightly lower than that of the SN60AT IOL. Imaging qualities of the two IOLs decreased when the pupil diameter and the degree of decentration increased, but the decrease was similar in the toric and spherical IOLs. CONCLUSIONS: Toric IOLs were comparable to spherical IOLs in terms of tolerance to decentration at the correct axial position.