Ketamine’s effect on inflammation and kynurenine pathway in depression: A systematic review

Background: Ketamine is a novel rapid-acting antidepressant with high efficacy in treatment-resistant patients. Its exact therapeutic mechanisms of action are unclear; however, in recent years its anti-inflammatory properties and subsequent downstream effects on tryptophan (TRP) metabolism have sparked research interest. Aim: This systematic review examined the effect of ketamine on inflammatory markers and TRP–kynurenine (KYN) pathway metabolites in patients with unipolar and bipolar depression and in animal models of depression. Methods: MEDLINE, Embase, and PsycINFO databases were searched on October 2020 (1806 to 2020). Results: Out of 807 initial results, nine human studies and 22 animal studies on rodents met the inclusion criteria. Rodent studies provided strong support for ketamine-induced decreases in pro-inflammatory cytokines, namely in interleukin (IL)-1β, IL-6, and tumor necrosis factor (TNF)-α and indicated anti-inflammatory effects on TRP metabolism, including decreases in the enzyme indoleamine 2,3-dioxygenase (IDO). Clinical evidence was less robust with high heterogeneity between sample characteristics, but most experiments demonstrated decreases in peripheral inflammation including in IL-1β, IL-6, and TNF-α. Preliminary support was also found for reduced activation of the neurotoxic arm of the KYN pathway. Conclusion: Ketamine appears to induce anti-inflammatory effects in at least a proportion of depressed patients. Suggestions for future research include investigation of markers in the central nervous system and examination of clinical relevance of inflammatory changes.

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Antioxidant and Anti-Inflammatory Effects of Genus Gynura: A Systematic Review

Frontiers in Pharmacology ◽

10.3389/fphar.2020.504624 ◽

2020 ◽

Vol 11 ◽

Author(s):

Jiah Ning Tan ◽

Shamin Mohd Saffian ◽

Fhataheya Buang ◽

Zakiah Jubri ◽

Ibrahim Jantan ◽

...

Keyword(s):

Oxidative Stress ◽

Systematic Review ◽

Clinical Studies ◽

Glycogen Synthase ◽

Chemical Constituents ◽

Future Research ◽

Prostaglandin E ◽

Pharmacokinetic Studies ◽

Related Factor ◽

Anti Inflammatory

Background:Gynura species have been used traditionally to treat various ailments, such as fever, pain, and to control blood glucose level. This systematic review critically discusses studies regarding Gynura species that exhibited antioxidant and anti-inflammatory effects, thus providing perspectives and instructions for future research of the plants as a potential source of new dietary supplements or medicinal agents.Methods: A literature search from internet databases of PubMed, Scopus, Science Direct, e-theses Online Service, and ProQuest was carried out using a combination of keywords such as “Gynura,” “antioxidant,” “anti-inflammatory,” or other related words. Research articles were included in this study if they were experimental (in vitro and in vivo) or clinical studies on the antioxidant or anti-inflammatory effects of Gynura species and if they were articles published in English.Results: Altogether, 27 studies on antioxidant and anti-inflammatory effects of Gynura species were selected. The antioxidant effects of Gynura species were manifested by inhibition of reactive oxygen species production and lipid peroxidation, modulation of glutathione-related parameters, and enzymatic antioxidant production or activities. The anti-inflammatory effects of Gynura species were through the modulation of inflammatory cytokine production, inhibition of prostaglandin E2 and nitric oxide production, cellular inflammatory-related parameters, and inflammation in animal models. The potential anti-inflammatory signaling pathways modulated by Gynura species are glycogen synthase kinase-3, nuclear factor erythroid 2-related factor 2, PPARγ, MAPK, NF-κB, and PI3K/Akt. However, most reports on antioxidant and anti-inflammatory effects of the plants were on crude extracts, and the chemical constituents contributing to bioactivities were not clearly understood. There is a variation in quality of studies in terms of design, conduct, and interpretation, and in-depth studies on the underlying mechanisms involved in antioxidant and anti-inflammatory effects of the plants are in demand. Moreover, there is limited clinical study on antioxidant and anti-inflammatory effects of Gynura species.Conclusion: This review highlighted antioxidant and anti-inflammatory effects of genus Gynura and supported their traditional uses to treat oxidative stress and inflammatory-related diseases. This review is expected to catalyze further studies on genus Gynura. However, extensive preclinical data need to be generated from toxicity and pharmacokinetic studies before clinical studies can be pursued for their development into clinical medicines to treat oxidative stress and inflammatory conditions.

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Antioxidant and Inflammatory Effects of Nelumbo nucifera Gaertn. Leaves

Oxidative Medicine and Cellular Longevity ◽

10.1155/2021/8375961 ◽

2021 ◽

Vol 2021 ◽

pp. 1-14

Author(s):

Chong Li ◽

Yongpeng He ◽

Yue Yang ◽

Yuting Gou ◽

Shuting Li ◽

...

Keyword(s):

Oxidative Damage ◽

Animal Studies ◽

Organ Index ◽

Tnf Α ◽

Ifn Γ ◽

Anti Inflammatory ◽

Kidney Liver ◽

Lung And Kidney

This study is aimed at identifying the bioactive components in lotus leaf flavonoid extract (LLFE) and analyzing the antioxidant and anti-inflammatory activities of LLFE in vitro and in vivo. The flavonoids in LLFE were determined by UHPLC-MS/MS. The effect of LLFE on damaged 293T cells (H2O2, 0.3 mmol/L) was determined by MTT assay, and the activity of antioxidant enzymes was measured by kits. We studied the antioxidant and anti-inflammatory effects of LLFE on D-Gal/LPS (30 mg/kg·bw and 3 μg/kg·bw)-induced aging mice. We also evaluated the main organ index, pathological changes in the liver, lung, and kidney, liver function index, biochemical index, cytokine level, and mRNA expression level in serum and liver. The results showed that LLFE contains baicalein, kaempferol, kaempferid, quercetin, isorhamnetin, hyperoside, lespenephryl, and rutin. LLFE reduced the oxidative damage sustained by 293T cells, increased the levels of SOD, CAT, GSH, and GSH-Px, and decreased the level of MDA. The animal studies revealed that LLFE reduced oxidative damage and inflammation in injured mice, inhibited increases in AST, ALT, MDA, and NO, increased SOD, CAT, GSH, and GSH-Px levels, upregulated anti-inflammatory cytokines IL-10 and IL-12, and downregulated proinflammatory cytokines IL-6, IL-1β, TNF-α, and IFN-γ. Furthermore, the expression of antioxidant- and anti-inflammatory-related mRNA was consistent with the above results.

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Neuroendocrine Responses to Stressors in Lactating and Nonlactating Mammals: A Literature Review

Biological Research For Nursing ◽

10.1177/1099800403256494 ◽

2003 ◽

Vol 5 (2) ◽

pp. 79-86 ◽

Cited By ~ 9

Author(s):

Pamela D. Hill ◽

Robert T. Chatterton ◽

Jean C. Aldag

Keyword(s):

Systematic Review ◽

Literature Review ◽

Animal Studies ◽

Physiological Stress ◽

Future Research ◽

Review Of The Literature ◽

Physiological Stress Response ◽

Chronic Stressors ◽

Neuroendocrine Responses ◽

Acute Stressor

Although stress research is a popular topic of study, little is known about the neuroendocrine responses to a stressor in lactating and nonlactating humans. The purpose of this systematic review of the literature was to examine the neuroendocrine responses, specifically the glucocorticoids and catecholamines, in lactating and nonlactating animals and humans to an acute stressor. A brief overview of the physiological stress response in the human is included. Animal studies strongly suggest that lactation is associated with major changes in neuroendocrine responses to a variety of acute stressors. Neuroendocrine responses in humans to stressors are less clear due to the limited research. Future research is needed involving these responses in humans generally, as well as specifically in the patterns of neuroendocrine responses to chronic stressors in lactating and nonlactating women.

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Neuroprotective effect of Lithospermum officinale callus extract on inflamed primary microglial cells

Current Pharmaceutical Biotechnology ◽

10.2174/1389201021666201104145439 ◽

2020 ◽

Vol 21 ◽

Author(s):

Maryam Kheyrollah ◽

Farzaneh Sabouni ◽

Mohsen Farhadpour ◽

Kamahldin Haghbeen

Keyword(s):

Neuroprotective Effect ◽

Wistar Rat ◽

Microglial Cells ◽

Root Extract ◽

Primary Microglia ◽

Methanolic Extracts ◽

Tnf Α ◽

The Central Nervous System ◽

Anti Inflammatory ◽

Lithospermum Officinale

Background and Objective: Lithospermum officinale is a famous medicinal herb in the traditional medicine of India. However, the medicinal use of its root extract is limited due to the presence of pyrrolizidine alkaloids (PzAl). It was recently shown that PzAl are not accumulated in the cell culture of L. officinale while the biosynthetic pathway of phenolic acids remains active so that rosmarinic acid (RsA) is the main product in the proliferated callus. Considering the existing literature on the anti-inflammatory effects of caffeic acid (CfA) and its derivatives, this research was devoted to the evaluation of the anti-inflammatory capacity of methanolic extracts of L. officinale callus (LoE) on the rat microglial cells as the immune cells of the Central Nervous System, which play an essential role in the responses to neuroinflammation. Methods: primary microglia were obtained from Wistar rat, then they were subjected to various amounts of CfA and methanolic extracts of 17 and 31-day L. officinale callus prior to stimulation by LPS. In addition to HPLC analysis of the extracts, viability, nitric oxide production, evaluation of the pro-inflammatory genes and cytokines in the inflamed microglia were investigated. Results: Methanolic extract of the 17-day old callus of L. officinale exhibited anti-inflammatory effects on the LPS- stimulated microglial cells much higher than that was observed for CfA. The data was further supported by the decreased expression of NOS2, TNF-α, and Cox-2 mRNA and the suppression of TNF-α and IL-1β release in the activated microglial cells pretreated with the effective dose of LoE (0.8 mg mL-1). Conclusion: It was assumed that better anti-neuroinflammatory performance of LoE than CfA in LPS-activated primary microglia could be a result of synergism of the components of the extract and the lipophilic nature of RsA as the main phenolic acid of LoE. Considering the fact that LoE shows high antioxidant capacity and lacks PzAl, it is anticipated that LoE is considered as a reliable substitute to the extract of the natural root of L. officinale and plays a key role in the preparation of neuroprotective pharmaceutical formula.

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Systematic Review of the Kynurenine Pathway and Psychoneurological Symptoms Among Adult Cancer Survivors

Biological Research For Nursing ◽

10.1177/1099800420938141 ◽

2020 ◽

Vol 22 (4) ◽

pp. 472-484

Author(s):

Hongjin Li ◽

Tingting Liu ◽

Lacey W. Heinsberg ◽

Mark B. Lockwood ◽

Derek A. Wainwright ◽

...

Keyword(s):

Systematic Review ◽

Cancer Survivors ◽

Kynurenic Acid ◽

Kynurenine Pathway ◽

Future Research ◽

Pathway Activation ◽

Adult Cancer Survivors ◽

Psychoneurological Symptoms ◽

Cognitive Disturbance

The co-occurrence of multiple psychoneurological symptoms, including pain, sleep disturbance, fatigue, depression, anxiety, and cognitive disturbance among adult cancer survivors led us to question which common biological mechanisms are shared among these conditions. Variances in tryptophan (Trp) levels and downstream metabolites of the kynurenine (Kyn) metabolic pathway are known to affect immune response and psychoneurological symptoms. The objective of this systematic review was to help us (a) better understand the role of the Kyn pathway in psychoneurological symptoms among adult cancer survivors and (b) identify common significant biomarkers across psychoneurological symptoms as a guide for future research. Some evidence has shown that decreased Trp levels and increased Kyn, Trp/Kyn ratio, and kynurenic acid/Trp ratio in parallel with immune activation are correlated with some psychoneurological symptoms among people undergoing cancer treatment, although discrepancies exist between studies. Kyn pathway activation could also be associated with psychoneurological symptoms among adult cancer survivors, but further research is needed to confirm its exact etiological role with respect to psychoneurological symptoms.

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Non-steroidal anti-inflammatory drugs in chronic kidney disease: a systematic review of prescription practices and use in primary care

Clinical Kidney Journal ◽

10.1093/ckj/sfz054 ◽

2019 ◽

Vol 13 (1) ◽

pp. 63-71 ◽

Cited By ~ 4

Author(s):

Claire Lefebvre ◽

Jade Hindié ◽

Michael Zappitelli ◽

Robert W Platt ◽

Kristian B Filion

Keyword(s):

Systematic Review ◽

Primary Care ◽

Chronic Kidney Disease ◽

Kidney Disease ◽

Observational Research ◽

Quality Improvement Intervention ◽

Future Research ◽

Cross Sectional ◽

Inflammatory Drugs ◽

Anti Inflammatory

Abstract Background Chronic kidney disease (CKD) management focuses on limiting further renal injury, including avoiding nephrotoxic medications such as non-steroidal anti-inflammatory drugs (NSAIDs). We performed a systematic review to evaluate the prevalence of primary care NSAID prescribing in this population. Methods We systematically searched MEDLINE and Embase from inception to October 2017 for observational studies examining NSAID prescribing practices or use in CKD patients in a primary care setting. The methodological quality of included studies was assessed independently by two authors using a modified version of the Agency for Healthcare Research and Quality’s Methodological Evaluation of Observational Research checklist. Results Our search generated 8055 potentially relevant publications, 304 of which were retrieved for full-text review. A total of 14 studies from 13 publications met our inclusion criteria. There were eight cohort and three cross-sectional studies, two quality improvement intervention studies and one prospective survey, representing a total of 49 209 CKD patients. Cross-sectional point prevalence of NSAID use in CKD patients ranged from 8 to 21%. Annual period prevalence rates ranged from 3 to 33%. Meta-analysis was not performed due to important clinical heterogeneity across study populations. Conclusions Evidence suggests that NSAID prescriptions/use in primary care among patients with CKD is variable and relatively high. Future research should explore reasons for this to better focus knowledge translation interventions aimed at reducing NSAID use in this patient population.

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Military Sexual Trauma and Risky Behaviors: A Systematic Review

Trauma Violence & Abuse ◽

10.1177/1524838019897338 ◽

2020 ◽

pp. 152483801989733 ◽

Cited By ~ 1

Author(s):

Shannon R. Forkus ◽

Nicole H. Weiss ◽

Svetlana Goncharenko ◽

Joseph Mammay ◽

Michael Church ◽

...

Keyword(s):

Systematic Review ◽

Sexual Behaviors ◽

Technology Use ◽

Sexual Trauma ◽

Strong Support ◽

Risky Behaviors ◽

Future Research ◽

Military Sexual Trauma ◽

Men And Women ◽

Wide Range

Introduction: Military sexual trauma (MST) is a serious and pervasive problem among military men and women. Recent findings have linked MST with various negative outcomes including risky, self-destructive, and health-compromising behaviors. Objective: The current review summarizes the existing literature on the association between MST and risky behaviors among military men and women who have served in the U.S. Armed Forces. Method: We systematically searched five electronic databases (PubMed, EMBASE, PSYCINFO, PILOTS, and CINAHL Plus) using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Results: Of the initial 2,021 articles, 47 met the inclusion criteria. Reviewed studies revealed three patterns of findings: (1) largely studied and consistent (i.e., suicidal behaviors, disordered eating), (2) mixed and in need of future research (i.e., alcohol and drug use, smoking), and (3) underexamined (i.e., sexual behaviors, illegal/aggressive behaviors) or completely neglected (e.g., problematic technology use, gambling). Discussion: The current systematic review advances literature by providing strong support for an association between MST and a wide range of risky behaviors. Moreover, it highlights important areas for future research.

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Lurasidone in the Treatment of Bipolar Depression: Systematic Review of Systematic Reviews

BioMed Research International ◽

10.1155/2017/3084859 ◽

2017 ◽

Vol 2017 ◽

pp. 1-17 ◽

Cited By ~ 13

Author(s):

Michele Fornaro ◽

Domenico De Berardis ◽

Giampaolo Perna ◽

Marco Solmi ◽

Nicola Veronese ◽

...

Keyword(s):

Systematic Review ◽

Systematic Reviews ◽

Bipolar Depression ◽

Meta Analysis ◽

Future Research ◽

Tolerability Profile ◽

Type I ◽

Essential Information ◽

Quantitative Evidence ◽

Measurement Biases

Introduction. A burgeoning number of systematic reviews considering lurasidone in the treatment of bipolar depression have occurred since its Food and Drug Administration extended approval in 2013. While a paucity of available quantitative evidence still precludes preliminary meta-analysis on the matter, the present quality assessment of systematic review of systematic reviews, nonetheless, aims at highlighting current essential information on the topic. Methods. Both published and unpublished systematic reviews about lurasidone mono- or adjunctive therapy in the treatment of bipolar depression were searched by two independent authors inquiring PubMed/Cochrane/Embase/Scopus from inception until October 2016. Results. Twelve included systematic reviews were of moderate-to-high quality and consistent in covering the handful of RCTs available to date, suggesting the promising efficacy, safety, and tolerability profile of lurasidone. Concordance on the drug profile seems to be corroborated by a steadily increasing number of convergent qualitative reports on the matter. Limitations. Publication, sponsorship, language, citation, and measurement biases. Conclusions. Despite being preliminary in nature, this overview stipulates the effectiveness of lurasidone in the acute treatment of Type I bipolar depression overall. As outlined by most of the reviewed evidence, recommendations for future research should include further controlled trials of extended duration.

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Effect of Cynara cardunculus L. var. altilis (DC) in Inflammatory Bowel Disease

Applied Sciences ◽

10.3390/app11041629 ◽

2021 ◽

Vol 11 (4) ◽

pp. 1629

Author(s):

Vanessa Mateus ◽

João Estarreja ◽

Inês Silva ◽

Paulo Barracosa ◽

Edite Teixeira-Lemos ◽

...

Keyword(s):

Inflammatory Bowel Disease ◽

Bowel Disease ◽

Animal Studies ◽

Inflammatory Disorder ◽

Cynara Cardunculus ◽

Trinitrobenzenesulfonic Acid ◽

Chronic Inflammatory Disorder ◽

Tnf Α ◽

Inflammatory Bowel ◽

Anti Inflammatory

Background: Cynara cardunculus L. var. altilis (DC) is a plant generally associated as an ingredient in the Mediterranean diet. The polyphenols present in this plant provide pharmacological and nutritional properties. C. cardunculus L. has been used throughout animal studies, which demonstrated an anti-inflammatory effect. Inflammatory bowel disease (IBD) is a chronic inflammatory disorder of the gastrointestinal tract. Since there is not a known cure, the research of new possible pharmacological approaches is essential. This study aims to evaluate the effect of an aqueous extract of C. cardunculus L. dry leaves in a 2,4,6-Trinitrobenzenesulfonic acid (TNBS)-induced colitis model. Methods: CD-1 mice with TNBS-induced colitis received an intraperitoneal (IP) administration of C. cardunculus L. once per day for 4 days. Results: The C. cardunculus L. demonstrated a beneficial effect in this experimental model of IBD with anti-inflammatory action through the reduction of tumor necrosis factor (TNF)-α levels. It also demonstrated a beneficial influence on the extra-intestinal manifestations related to IBD, with the absence of significant side effects of its use. Conclusions: The extract of C. cardunculus L. dry leaves can become an interesting tool for new possible pharmacological approaches in the management of IBD.

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Lichen-Derived Compounds and Extracts as Biologically Active Substances with Anticancer and Neuroprotective Properties

Pharmaceuticals ◽

10.3390/ph14121293 ◽

2021 ◽

Vol 14 (12) ◽

pp. 1293

Author(s):

Elżbieta Studzińska-Sroka ◽

Aleksandra Majchrzak-Celińska ◽

Przemysław Zalewski ◽

Dominik Szwajgier ◽

Ewa Baranowska-Wójcik ◽

...

Keyword(s):

Usnic Acid ◽

Biological Properties ◽

Kynurenine Pathway ◽

Biologically Active ◽

Evernia Prunastri ◽

Biological Potential ◽

The Central Nervous System ◽

Anti Inflammatory ◽

Butyrylcholinesterase Activity ◽

Pharmacologically Active

Lichens are a source of chemical compounds with valuable biological properties, structurally predisposed to penetration into the central nervous system (CNS). Hence, our research aimed to examine the biological potential of lipophilic extracts of Parmelia sulcata, Evernia prunastri, Cladonia uncialis, and their major secondary metabolites, in the context of searching for new therapies for CNS diseases, mainly glioblastoma multiforme (GBM). The extracts selected for the study were standardized for their content of salazinic acid, evernic acid, and (−)-usnic acid, respectively. The extracts and lichen metabolites were evaluated in terms of their anti-tumor activity, i.e. cytotoxicity against A-172 and T98G cell lines and anti-IDO1, IDO2, TDO activity, their anti-inflammatory properties exerted by anti-COX-2 and anti-hyaluronidase activity, antioxidant activity, and anti-acetylcholinesterase and anti-butyrylcholinesterase activity. The results of this study indicate that lichen-derived compounds and extracts exert significant cytotoxicity against GBM cells, inhibit the kynurenine pathway enzymes, and have anti-inflammatory properties and weak antioxidant and anti-cholinesterase properties. Moreover, evernic acid and (−)-usnic acid were shown to be able to cross the blood-brain barrier. These results demonstrate that lichen-derived extracts and compounds, especially (−)-usnic acid, can be regarded as prototypes of pharmacologically active compounds within the CNS, especially suitable for the treatment of GBM.

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