Comprehensive Bibliometric Analysis of the Kynurenine Pathway in Mood Disorders: Focus on Gut Microbiota Research.

Background: Emerging evidence implicates the dysregulated kynurenine pathway (KP), an immune-inflammatory pathway, in the pathophysiology of mood disorders (MD), including depression and bipolar disorder characterized by a low-grade chronic pro-inflammatory state. The metabolites of the KP, an important part of the microbiota-gut-brain axis, serve as immune system modulators linking the gut microbiota (GM) with the host central nervous system. Aim: This bibliometric analysis aimed to provide a first glimpse into the KP in MD, with a focus on GM research in this field, to guide future research and promote the development of this field. Methods: Publications relating to the KP in MD between the years 2000 and 2020 were retrieved from the Scopus and Web of Science Core Collection (WoSCC), and analyzed in CiteSpace (5.7 R5W), biblioshiny (using R-Studio), and VOSviewer (1.6.16). Results: In total, 1,064 and 948 documents were extracted from the Scopus and WoSCC databases, respectively. The publications have shown rapid growth since 2006, partly owing to the largest research hotspot appearing since then, "quinolinic acid." All the top five most relevant journals were in the neuropsychiatry field, such as Brain Behavior and Immunity. The United States and Innsbruck Medical University were the most influential country and institute, respectively. Journal co-citation analysis showed a strong tendency toward co-citation of research in the psychiatry field. Reference co-citation analysis revealed that the top four most important research focuses were "kynurenine pathway," "psychoneuroimmunology," "indoleamine 2,3-dioxygenase," and "proinflammatory cytokines," and the most recent focus was "gut-brain axis," thus indicating the role of the KP in bridging the GM and the host immune system, and together reflecting the field's research foundations. Overlap analysis between the thematic map of keywords and the keyword burst analysis revealed that the topics "Alzheimer's disease," "prefrontal cortex," and "acid," were research frontiers. Conclusion: This comprehensive bibliometric study provides an updated perspective on research associated with the KP in MD, with a focus on the current status of GM research in this field. This perspective may benefit researchers in choosing suitable journals and collaborators, and aid in the further understanding of the field's hotspots and frontiers, thus facilitating future research.

Luteolin Protects Pheochromocytoma (PC-12) Cells against Aß 25-35-Induced Cell Apoptosis through the ER/ERK/MAPK Signalling Pathway.

The regulatory effect of luteolin on the progression of Alzheimer's disease (AD) remains unclear from the perspective of apoptosis. The present study aimed to investigate the protective effects of luteolin against Aß 25-35-induced cell apoptosis in pheochromocytoma (PC-12) cells. Aß 25-35 was used to induce an in vitro model of AD. Estradiol was used as a positive control. The PC-12 cells were incubated with luteolin alone or in combination with fulvestrant or U0126. The results showed that luteolin treatment significantly prevents Aß 25-35-induced decrease in cell viability and inhibits Aß 25-35-induced cell apoptosis. After the addition of fulvestrant and U0126, the apoptosis rate of PC-12 cells increased significantly. In addition, luteolin treatment significantly upregulated the expression of Bcl-2 and downregulated the expression of Bax and caspase-3, whereas fulvestrant and U0126 partially reversed the effects of luteolin. Moreover, luteolin treatment upregulated the expression of ERß and p-ERK1/2, whereas fulvestrant blocked the expression of p-ERK1/2. The study showed that luteolin could activate the ER/ERK/MAPK signalling pathway to protect PC-12 cells against Aß 25-35-induced cell apoptosis via selectively acting on ERß. Thus, luteolin may be considered as a potential novel therapeutic strategy for AD.

Buyang Huanwu Decoction Ameliorates Poststroke Depression via Promoting Neurotrophic Pathway Mediated Neuroprotection and Neurogenesis.

Objective. The aim of the present research is to investigate the therapeutic effect of Buyang Huanwu Decoction (BHD) in poststroke depression (PSD) animal model and illustrate its underlying mechanism via promoting neurotrophic pathway mediated neuroprotection and neurogenesis. Methods. To induce PSD rat model, isolation housed rats that received middle cerebral artery occlusion (MCAO) surgery successively suffered from chronic mild stress (CMS) treatment for consecutive twenty-one days. Meanwhile, rats were correspondingly given vehicle, BHD, and fluoxetine. Then, neurologic function was scored and depressive-like behaviors were assessed by sucrose preference test, locomotor activity, novelty-suppressed feeding test, and forced swim test. Thereafter, the neuroprotection and neurogenesis related molecular markers and signaling were detected. Results. We firstly observed a significant neurological function recovery and antidepressants effect of BHD after MCAO together with CMS treatment. Our study also found that treatment with BHD and fluoxetine can significantly rescue neurons from apoptosis and promote neurogenesis in the CA3 and DG regions in the hippocampus. Notably, BHD and fluoxetine treatment can activate BDNF/ERK/CREB signaling. Conclusion. The results suggest that BHD is a promising candidate for treating PSD. Its curative effects can be attributed to neurotrophic pathway mediated neuroprotection and neurogenesis.

Investigation on pharmacokinetics, tissue distribution and excretion of 1-triacontanol in rats by gas chromatography-tandem mass spectrometry (GC-MS/MS).

1. 1-Triacontanol (TA) recently shows promising anti-tumor activity. The present study was aimed to develop a sensitive gas chromatography-tandem mass spectrometry method to explore the pharmacokinetic profiles, distribution and excretion of TA in Sprague-Dawley rats after oral administration of TA. Chromatography separation was performed on a HP-5MS column. 1-Octacosanal was used as the internal standard (IS). Quantification of TA and IS was carried out at m/z 495.6 → 97.0 and m/z 467.5 → 97.0, respectively, in positive electron ionization and multiple reaction monitoring mode. The pharmacokinetic parameters were calculated by non-compartmental analysis. 2. The area under concentration-time curve AUC0-6 h and AUC0-∞ for TA at 60 mg/kg were 87.737 ± 13.574 and 93.617 ± 17.62, respectively. The mean residence time was 3.25 ± 0.17 h. In addition, the elimination half-lives (t1/2) were (2.37 ± 1.23, 1.27 ± 0.49, 2.07 ± 0.93) h after single oral administration of 30, 60 and 120 mg/kg of TA. After oral administration, TA was extensively distributed in stomach and intestine. The majority of TA excreted via feces, and its accumulative excretion ratio during the period of 72 h was 26.68 ± 7.14%, but only 0.0023 ± 0.0015% and 0.0027 ± 0.0006% for urines and bile, respectively. The absolute bioavailability (F, %) of TA was about 2.0%.

Effects of dietary factors on the pharmacokinetics of 58Fe-labeled hemin after oral administration in normal rats and the iron-deficient rats.

Hemin, iron (III) protoporphyrin chloride (IX), as a stable form of heme iron, has been used in iron absorption studies. The aim of the present study was to elucidate the influences of body iron status and three dietary factors (green tea extract, ascorbic acid, and calcium) on the pharmacokinetics of hemin using stable isotope labeling methods followed by ICP-MS measurement. In this study, a rapid, sensitive, and specific ICP-MS method for the determination of (58)Fe originating from hemin in rat plasma was developed and a rat model of iron deficiency anemia was established. It was found that hemin iron absorption increased significantly under iron deficiency anemia status, with AUC0-t and AUC0-∞ showing significant increase in anemic rats compared to normal ones. Green tea extract strongly inhibited hemin iron absorption in both normal rats and iron-deficient rats. In normal rats administered with green tea extract, C max resulted significantly reduced, whereas in anemic rats administered with green tea extract both AUC0-t and AUC0-∞ were reduced. On the other hand, ascorbic acid significantly affected hemin iron absorption only in iron-deficient rats, in which C max showed a significant increase. Interestingly, calcium slowed down the hemin iron absorption rate in normal rats, MRT0-t being significantly different in calcium-treated animals compared to untreated ones. This trend also appeared in the iron-deficient group but it did not reach statistical significance. Our data suggest that the mechanism of hemin iron absorption is regulated by body iron status and dietary factors can influence hemin iron absorption to varying degrees. Moreover, these results may also have general implication in the iron deficiency treatment with iron supplements and fortification of foods.