{"title":"Supplementing with Vitamin D during Pregnancy Reduces Inflammation and Prevents Autism-Related Behaviors in Offspring Caused by Maternal Immune Activation.","authors":"Xiao Wang, Qingqing Li, Zhihong Lyu, Yingying Wu","doi":"10.1248/bpb.b25-00008","DOIUrl":"https://doi.org/10.1248/bpb.b25-00008","url":null,"abstract":"<p><p>Autism spectrum disorder (ASD), a neurodevelopmental disorder of unknown etiology with limited treatment options, has emerged as a significant public health concern. Studies have demonstrated that prenatal vitamin D deficiency is a risk factor for ASD development in offspring; however, the underlying mechanism remains unclear. In this project, vitamin D was administered orally to pregnant mice with/without the subsequent administration of polyriboinosinic polyribocytidylic acid (Poly(I:C)), which induced the maternal immune activation (MIA). Our results showed that vitamin D supplementation during pregnancy alleviated MIA-induced ASD-like behaviors in offspring. Moreover, vitamin D supplementation reduced the MIA-induced elevation of interleukin-6 (IL-6) and IL-17a levels in both the maternal ileum and fetal brains. It also suppressed signal transducer and activator of transcription 3 (Stat3) activation and the elevated expression of serum amyloid A1 and A2 (SAA1/2) in the ileum of MIA-affected pregnant mice. This study revealed that vitamin D may reduce the expression of IL-17a by inhibiting the IL-6/Stat3/SAA signaling pathway, thereby improving ASD-like behavior in offspring mice, and provide a new theoretical support for the prevention and treatment of ASD by scientific dietary interventions and nutritional supplement during pregnancy.</p>","PeriodicalId":8955,"journal":{"name":"Biological & pharmaceutical bulletin","volume":"48 5","pages":"632-640"},"PeriodicalIF":1.7,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144092590","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Protective Effects of Pleurotus Species on UVB-Induced Skin Disorders at Clinically Relevant Plasma Concentrations of the Antioxidant Ergothioneine in Hairless Mice.","authors":"Motoki Hanayama, Takahiro Ishimoto, Akira Moritomo, Reiya Yamashita, Junya Kawai, Koichiro Mori, Yukio Kato","doi":"10.1248/bpb.b24-00893","DOIUrl":"https://doi.org/10.1248/bpb.b24-00893","url":null,"abstract":"<p><p>Ergothioneine (ERGO) has antioxidant and anti-inflammatory activities in UV-irradiated skin cells in vitro; however, there is no evidence about the effects of dietary ERGO on UV-induced skin damage or ERGO skin distribution in vivo. This study examined the protective effects of ERGO-rich edible mushrooms Pleurotus species against UVB-induced skin damage and the exposure to ERGO in the plasma and skin. Hos : HR-1 hairless mice were fed with or without freeze-dried cross-bred Pleurotus species (PS) or Pleurotus eringii (PE) and were exposed to UVB. Dietary intake of PS or PE significantly alleviated UVB-induced reductions in skin moisture content, increases in transepidermal water loss and oxidative stress markers, and epidermal thickening at plasma ERGO concentrations of 30-40 μM. Additionally, ingestion of PS significantly suppressed UVB-induced expression of pro-inflammatory cytokines. These results suggest that ingesting PS and PE may protect against UVB-induced skin disorders through antioxidant and anti-inflammatory activities at clinically relevant ERGO concentrations. Ingestion of PS and PE led to an increase in epidermal ERGO concentration to levels that were approx. 100 times higher than the ERGO concentration required for significant suppression of UVB-induced intracellular reactive oxygen species in immortalized human keratinocyte HaCaT cells. This suggests that the beneficial effects of PS and PE may be at least partly due to the antioxidant effects of ERGO in murine skin. Overall, ingestion of ERGO-rich Pleurotus species resulted in efficient distribution of ERGO to the skin and protective effects against UVB-induced skin damage, suggesting that these mushrooms may have beneficial effects in humans.</p>","PeriodicalId":8955,"journal":{"name":"Biological & pharmaceutical bulletin","volume":"48 5","pages":"672-681"},"PeriodicalIF":1.7,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144118631","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Prospective Analysis of Factors Influencing Inter-Individual Variation in Trough Plasma Voriconazole Concentrations in Older Patients-Impact of High α1-Acid Glycoprotein Levels.","authors":"Yukako Yasui, Hiroyuki Yasui, Yoshiki Yamamoto, Toshihiko Ishizaka, Kazuo Hatanaka, Waki Imoto, Wataru Shibata, Koichi Yamada, Hiroshi Kakeya","doi":"10.1248/bpb.b25-00057","DOIUrl":"https://doi.org/10.1248/bpb.b25-00057","url":null,"abstract":"<p><p>Voriconazole (VRCZ), an azole-based, deep-seated antifungal agent, is used as a 1st-line treatment for aspergillosis in Japan. VRCZ exhibits nonlinear pharmacokinetic (PK) behavior with relatively large inter-individual variability in plasma concentration. Additionally, genetic polymorphisms of CYP2C19 have been reported to influence the metabolic variability of VRCZ. The purpose of this study was to search for and identify clinically relevant potential factors influencing the PK and plasma concentration of VRCZ to better inform VRCZ dosing regimens. Thirty patients receiving VRCZ were enrolled. Total (C<sub>t</sub>) and unbound (C<sub>u</sub>) trough plasma concentrations of VRCZ were determined by the HPLC-UV method. Univariate and multivariate correlation analyses were used to evaluate the relationships between C<sub>t</sub> or C<sub>t</sub>/dose per body weight (C<sub>t</sub>/D) and individual demographic and laboratory characteristics. Since the increasing trend of C-reactive protein (CRP) inversely correlated with the classification of CYP2C19 gene polymorphisms, it was suggested that the inflammation counteracted the trend of C<sub>t</sub> according to CYP2C19 gene polymorphisms. Spearman's rank-order correlation analysis showed significant correlations between C<sub>t</sub> and dose per body weight, CRP, and α1-acid glycoprotein (α1-AGP). Multivariate linear regression analysis showed that age, dose per body weight, CRP, and α1-AGP were significant explanatory factors for C<sub>t</sub>. In particular, elevated α1-AGP levels were found to have significant explanatory value for decreased C<sub>t</sub>. Although the present study has critical limitations, such as the patient sample was small in size and being limited to a single medical institution, this finding may explain some of the inter-individual variability in plasma VRCZ concentration.</p>","PeriodicalId":8955,"journal":{"name":"Biological & pharmaceutical bulletin","volume":"48 5","pages":"694-705"},"PeriodicalIF":1.7,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144141221","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Tokishigyakukagoshuyushokyoto (TSGST) Inhibits Aggression Induced by Isolation Rearing in Mice.","authors":"Honoka Nakajima, Chisato Wakabayashi","doi":"10.1248/bpb.b25-00011","DOIUrl":"https://doi.org/10.1248/bpb.b25-00011","url":null,"abstract":"<p><p>Herbal medicines are widely used in clinical practice. Several herbal medicines are prescribed in clinical practice to improve mental symptoms. Yokukansan is an effective prescription for irritability and aggression, which are behavioral and psychological symptoms of dementia (BPSD) or autism spectrum disorder (ASD). However, because herbal medicines contain many components, their pharmacological effects have not been analyzed in detail. Risperidone and quetiapine are prescribed in severe cases; however, their side effects of oversedation are problematic. Tokishigyakukagoshuyushokyoto (TSGST) is a herbal medicine prescribed to improve blood circulation and relieve headaches, back pain, or chilblains associated with hemodynamic insufficiency. Interestingly, most of the individual components of TSGST are known to exert sedative or analgesic effects. In this study, we investigated whether TSGST ameliorates aggressive behavior induced by social isolation in mice. The mice were isolated for 5 or 6 weeks immediately after weaning and given TSGST via a water bottle during this period. Long-term administration of TSGST suppressed the onset of aggression induced by isolation rearing. This aggressive phenotype was significantly reversed by intraperitoneal (i.p.) administration of the 5-hydroxytryptamine 1A (5-HT<sub>1A</sub>) receptor antagonist WAY-100635 in TSGST-isolated mice. We also showed that TSGST had similar effects as risperidone, a commonly used antipsychotic for irritability and aggression. These results suggest that TSGST may be effective for irritability or aggression in BPSD or ASD.</p>","PeriodicalId":8955,"journal":{"name":"Biological & pharmaceutical bulletin","volume":"48 5","pages":"507-514"},"PeriodicalIF":1.7,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143976249","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Yaru Yang, Lei He, Minghui He, Xu Zhang, Shanggao Liao, Zhu Zeng, Yan Lin, Bo Tu
{"title":"FR429 from Polygonum capitatum Demonstrates Potential as an Anti-hepatic Injury Agent by Modulating PI3K/Akt Signaling Pathway.","authors":"Yaru Yang, Lei He, Minghui He, Xu Zhang, Shanggao Liao, Zhu Zeng, Yan Lin, Bo Tu","doi":"10.1248/bpb.b24-00812","DOIUrl":"https://doi.org/10.1248/bpb.b24-00812","url":null,"abstract":"<p><p>FR429, an ellagitannin isolated and purified from the whole herb Polygonum capitatum (P. capitatum), possesses a robust pharmacological profile, which is particularly noteworthy for its anti-inflammatory and anticancer properties. Despite these established effects, its potential in mitigating hepatic injury remains to be fully explored. The present investigation delineates the hepatoprotective efficacy of FR429 and unveils its underlying molecular mechanisms. Initially, of the tested compounds, 10 compounds (specifically, compounds 2, 4, 5, 6, 7, 8, 9, 12, 13, and 14) exhibited significant protective effects at a concentration of 10 μM, elevating HepG2 (human liver cancer cell) cell viability from 43.4 to 70% following carbon tetrachloride (CCl<sub>4</sub>) exposure. Among them, compounds 2 (FR429, half-maximum effective concentration (EC<sub>50</sub>) = 6.46 μM) and 6 (2\"-O-galloylquercitrin, EC<sub>50</sub> = 5.36 μM) demonstrated the highest cytoprotective activities. In the murine model, FR429 dramatically attenuated serum levels of alanine transaminase, aspartate transaminase, and alkaline phosphatase, indicative of its hepatoprotective potential. Histopathological evaluation further substantiated these findings, as FR429 noticeably mitigated CCl<sub>4</sub>-induced hepatic lesions, involving necrosis, ballooning degeneration, and neutrophil infiltration. Transcriptomic analysis unveiled 178 differentially expressed genes in FR429-treated mice liver tissue, with significant alterations indicative of a hepatoprotective response. Mechanistic investigations revealed that FR429's hepatoprotective effects involve modulation of the phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt) signaling pathway, evidenced by downregulation of toll-like receptor 2, phosphorylated PI3K, phosphorylated Akt, nuclear factor-kappa-B, interleukin-1 beta, and tumor necrosis factor-alpha expression. Furthermore, FR429 modulated the gene and protein expression levels of apoptotic markers (apoptotic protein (Bax) and B-lymphoblastoma-2 gene (Bcl2)), reinforcing its anti-hepatic damage efficacy. This study represents the first report establishing FR429 as an effective hepatoprotective compound, paving the way for further investigation into its therapeutic applications.</p>","PeriodicalId":8955,"journal":{"name":"Biological & pharmaceutical bulletin","volume":"48 4","pages":"372-382"},"PeriodicalIF":1.7,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143956800","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Jin Tian, Ran Huo, Yixuan Wang, Jiepeng Wang, Fang Fang, Chaoyi Fang
{"title":"Astragalus Polysaccharide Alleviates Cognitive Decline in D-Galactose-Induced Aging.","authors":"Jin Tian, Ran Huo, Yixuan Wang, Jiepeng Wang, Fang Fang, Chaoyi Fang","doi":"10.1248/bpb.b24-00524","DOIUrl":"https://doi.org/10.1248/bpb.b24-00524","url":null,"abstract":"<p><p>Astragalus polysaccharide (APS) is a biologically active water-soluble polysaccharide extracted from stems or roots, which has been proven to have antiaging effects. The aim of this study was to investigate the effects of APS on cognitive function in d-galactose (d-gal)-induced aging rats and explore the potential underlying molecular mechanisms. The rats were induced to age by intraperitoneal injection with 400 mg/kg/d d-gal for 8 weeks. Aging of rats was assessed through the Morris water maze test, step-down test, open field test, and grip strength test. Pathological changes in the hippocampal CA3 and CA1 regions were determined by Hematoxylin and eosin and Nissl staining. The superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), malondialdehyde (MDA), and total antioxidant capacity (T-AOC) in the serum were measured. Telomere length, dual oxidase 1 (Duox1), dual oxidase 2 (Duox2), peroxiredoxin 1 (Prdx1), p21, p16, p53, telomerase reverse transcriptase (TERT), phosphatidylinositol 3-kinase (PI3K), protein kinase B (AKT), nicotinamide phosphoribosyl transferase (NAMPT), and sirtuin 1 (SIRT1) were detected via real-time PCR, Western blotting, and immunohistochemical staining. The results indicated that APS ameliorated the general status in d-gal-induced aging rats, mitigated neuronal degeneration in the CA3 and CA1 regions, reduced the oxidative stress levels, modulated senescence-related β-GAL and protein expression, and maintained telomere length. Furthermore, APS significantly reduced p53 expression and increased p-PI3K, p-AKT, NAMPT, SIRT1, and TERT expression. Therefore, d-gal-induced aging and cognitive impairment in rats can be prevented by APS, likely through regulation of the TERT/p53 signaling axis via the PI3K/Akt and NAMPT/SIRT1 signaling pathways.</p>","PeriodicalId":8955,"journal":{"name":"Biological & pharmaceutical bulletin","volume":"48 5","pages":"523-536"},"PeriodicalIF":1.7,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143964600","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Koji Tomita, Ken-Ichi Nakashima, Eiji Yamaguchi, Akichika Itoh, Makoto Inoue
{"title":"Dual Anti-inflammatory Actions of a Novel Retinoid X Receptor Agonist Derived from a Natural Compound in Microglial Cells.","authors":"Koji Tomita, Ken-Ichi Nakashima, Eiji Yamaguchi, Akichika Itoh, Makoto Inoue","doi":"10.1248/bpb.b25-00037","DOIUrl":"https://doi.org/10.1248/bpb.b25-00037","url":null,"abstract":"<p><p>Microglia-mediated neuroinflammation plays a critical role in the onset and progression of Alzheimer's disease. In a previous study, we synthesized 6-hydroxy-3'-propyl-[1,1'-biphenyl]-3-propanoic acid (6OHA) based on the structure of magnaldehyde B, a natural compound that our group identified as a retinoid X receptor (RXR) agonist. However, its potential effects on inflammation in microglial cells remain unexplored. In this study, we specifically focused on the early-phase inflammatory responses to lipopolysaccharide (LPS) and evaluated the inhibitory effects of 6OHA on BV-2 microglial cells following 2 h of LPS exposure. Similar to the existing RXR agonist bexarotene (Bex), 6OHA treatment (0.1 and 1 μM) resulted in a dose-dependent decrease in the mRNA levels of proinflammatory mediators, including interleukin-1β (Il1b), Il6, and inducible nitric oxide synthase. However, these effects on proinflammatory mediators were effectively abolished by the RXR antagonist UVI3003. Additionally, 6OHA promoted M2 microglia polarization after 24 h of treatment, as evidenced by the increased mRNA levels of the M2 marker genes arginase-1 (Arg1), C-C motif chemokine ligand 6 (Ccl6), Ccl17, and Ccl22. Notably, 6OHA induced a distinct set of M2 microglial markers compared with IL-4, a known M2 microglial inducer. Furthermore, the transcription of Arg1, a key M2 marker gene, is regulated by retinoic acid receptor/RXR heterodimers and the IL-4 signaling pathway. Collectively, 6OHA suppressed the early inflammatory responses to LPS and promoted M2 microglial polarization through a mechanism distinct from that of IL-4. Therefore, RXR agonists, including 6OHA and Bex, may exhibit dual anti-inflammatory effects and serve as novel modulators of neuroinflammation.</p>","PeriodicalId":8955,"journal":{"name":"Biological & pharmaceutical bulletin","volume":"48 4","pages":"440-449"},"PeriodicalIF":1.7,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143965820","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"The Tumor Microenvironment Remodeled by Epstein-Barr Virus: From Primary Site to Distant Metastatic Niche.","authors":"Qiuyun Li, Yuping Liu, Yong Chen, Yujuan Huang, Yayan Deng, Qianqing Fan, Lihong Huang, Xue Liu, Jiaxiang Ye, Yongqiang Li, Jiazhang Wei, Jinyan Zhang","doi":"10.1248/bpb.b24-00872","DOIUrl":"https://doi.org/10.1248/bpb.b24-00872","url":null,"abstract":"<p><p>Epstein-Barr virus (EBV) is one of the most pervasive viruses worldwide, and EBV infection is inextricably linked to a multitude of lymphoid and epithelial neoplasms. EBV is responsible for the advancement of malignant disease by modifying the tumor microenvironment (TME), which is a sophisticated and evolving system that facilitates tumor growth, invasion, and metastasis. EBV infection has a profound impact on the cellular and noncellular components that constitute the TME. Our review presents a summary of the composition of the EBV-remodeled TME, with a particular focus on EBV-induced functional phenotypes in non-tumor cells. Furthermore, we discuss the potential for reversing EBV-driven TME remodeling as a therapeutic strategy for treating the malignancies associated with EBV infection.</p>","PeriodicalId":8955,"journal":{"name":"Biological & pharmaceutical bulletin","volume":"48 5","pages":"495-506"},"PeriodicalIF":1.7,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143958842","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Pentadecyl, an Active Component of Microalgae, Ameliorates Endoplasmic Reticulum Stress and Blue Light-Induced Cell Death in Mouse Retina-Derived 661W Cells.","authors":"Mayuna Obayashi, Wataru Otsu, Kanta Yamazaki, Shinsuke Nakamura, Hideaki Ishikawa, Yasuko Sakata, Makoto Tsuboi, Hideshi Tsusaki, Masamitsu Shimazawa","doi":"10.1248/bpb.b24-00889","DOIUrl":"https://doi.org/10.1248/bpb.b24-00889","url":null,"abstract":"<p><p>Light stress is a risk factor leading to retinal diseases such as age-related macular degeneration. However, the mechanism underlying the stress response to light in the retina has yet to be elucidated. We have reported that exposure to blue light-emitting diode light induces excessive production of reactive oxygen species and activates the unfolded protein response, robustly increasing activating transcription factor 4 (ATF4) expression. These processes result in photoreceptor cell death. This study investigates the effects of Pentadecyl, a bioactive product obtained from Aurantiochytrium limacinum, on either chemical-induced or blue light-induced endoplasmic reticulum (ER) stress. Pentadecyl suppressed cell death induced by either thapsigargin or tunicamycin in a concentration-dependent manner. Pentadecyl also suppressed the expression of unfolded protein response target genes, including Atf4 and ER chaperones. Consistently, immunoblotting revealed that Pentadecyl suppressed the increased expression of ATF4 at the protein level. Pentadecyl also protected 661W cells from blue light-induced damage but did not protect against hydrogen peroxide (H<sub>2</sub>O<sub>2</sub>)-induced oxidative stress. These results indicated that Pentadecyl has a novel function that protects against ER stress induced by photodamage.</p>","PeriodicalId":8955,"journal":{"name":"Biological & pharmaceutical bulletin","volume":"48 6","pages":"791-800"},"PeriodicalIF":1.7,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144246249","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Preventive and Therapeutic Effects of Intracerebroventricular Administration of Maresin-1 on Lipopolysaccharide-Induced Depression-Like Behaviors in Mice.","authors":"Satoshi Deyama, Katsuyuki Kaneda, Masabumi Minami","doi":"10.1248/bpb.b24-00743","DOIUrl":"10.1248/bpb.b24-00743","url":null,"abstract":"<p><p>Enhanced inflammatory and immune responses have been observed in patients with major depressive disorder, pointing to anti-inflammatory substances as potential seeds for developing novel antidepressants. Omega-3 polyunsaturated fatty acid metabolites, such as resolvin D and E series, maresins, and protectins (collectively known as specialized pro-resolving mediators) demonstrate anti-inflammatory effects. This study examined the antidepressant-like effects of maresin-1 (MaR1) on lipopolysaccharide (LPS)-induced depression-like behaviors in mice. Using the tail suspension test (TST) and the forced swim test (FST), we assessed depression-like behaviors 26 and 28 h after intraperitoneal injection of LPS (0.8 mg/kg), respectively. An open field test (OFT) was also conducted to evaluate locomotor activity 24 h after LPS injection. Intracerebroventricular (i.c.v.) injection of MaR1 (10 ng/mouse) immediately after the LPS challenge mitigated the increased immobility time in the TST and FST, without affecting locomotor activity in the OFT, indicating the preventive effects of MaR1 on LPS-induced depression-like behaviors. Furthermore, i.c.v. injection of MaR1 23 h after the LPS challenge reduced the immobility time in both tests, underscoring its therapeutic potential. These findings suggest that MaR1 could be a promising seed for developing novel antidepressants.</p>","PeriodicalId":8955,"journal":{"name":"Biological & pharmaceutical bulletin","volume":"48 1","pages":"6-10"},"PeriodicalIF":1.7,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142977401","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}