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8. Repetitive Administration of Low-Dose Lipopolysaccharide Improves Repeated Social Defeat Stress-Induced Behavioral Abnormalities and Aberrant Immune Response.

Author

Charoensaensuk, Vichuda, Yeh, Wei-Lan, Huang, Bor-Ren, Hsu, Tsung-Che, Xie, Sheng-Yun, Chen, Chao-Wei, Wang, Yu-Wen, Yang, Liang-Yo, Tsai, Cheng-Fang, and Lu, Dah-Yuu

Abstract

Repetitive exposure of innate immune cells to a subthreshold dosage of endotoxin components may modulate inflammatory responses. However, the regulatory mechanisms in the interactions between the central nervous system (CNS) and the immune system remain unclear. This study aimed to investigate the effects of lipopolysaccharide (LPS) preconditioning in repeated social defeat stress (RSDS)-induced abnormal immune responses and behavioral impairments. This study aimed to elucidate the mechanisms that underlie the protective effects of repeated administration of a subthreshold dose LPS on behavioral impairments using the RSDS paradigm. LPS preconditioning improved abnormal behaviors in RSDS-defeated mice, accompanied by decreased monoamine oxidases and increased glucocorticoid receptor expression in the hippocampus. In addition, pre-treated with LPS significantly decreased the recruited peripheral myeloid cells (CD11b+CD45hi), mainly circulating inflammatory monocytes (CD11b+CD45hiLy6ChiCCR2+) into the brain in response to RSDS challenge. Importantly, we found that LPS preconditioning exerts its protective properties by regulating lipocalin-2 (LCN2) expression in microglia, which subsequently induces expressions of chemokine CCL2 and pro-inflammatory cytokine. Subsequently, LPS-preconditioning lessened the resident microglia population (CD11b+CD45intCCL2+) in the brains of the RSDS-defeated mice. Moreover, RSDS-associated expressions of leukocytes (CD11b+CD45+CCR2+) and neutrophils (CD11b+CD45+Ly6G+) in the bone marrow, spleen, and blood were also attenuated by LPS-preconditioning. In particular, LPS preconditioning also promoted the expression of endogenous antioxidants and anti-inflammatory proteins in the hippocampus. Our results demonstrate that LPS preconditioning ameliorates lipocalin 2-associated microglial activation and aberrant immune response and promotes the expression of endogenous antioxidants and anti-inflammatory protein, thereby maintaining the homeostasis of pro-inflammation/anti-inflammation in both the brain and immune system, ultimately protecting the mice from RSDS-induced aberrant immune response and behavioral changes. [ABSTRACT FROM AUTHOR]

Published
2024
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15. Electroacupuncture improves TBI dysfunction by targeting HDAC overexpression and BDNF-associated Akt/GSK-3β signaling

Author

Hung, Shih-Ya, primary, Chung, Hsin-Yi, additional, Luo, Sih-Ting, additional, Chu, Yu-Ting, additional, Chen, Yu-Hsin, additional, MacDonald, Iona J., additional, Chien, Szu-Yu, additional, Kotha, Peddanna, additional, Yang, Liang-Yo, additional, Hwang, Ling-Ling, additional, Dun, Nae J., additional, Chuang, De-Maw, additional, and Chen, Yi-Hung, additional

Published
2022
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22. Edible folic acid and medicinal folinic acid produce cardioprotective effects in late‐stage triple‐transgenic Alzheimer's disease model mice by suppressing cardiac hypertrophy and fibrosis

Author

Huang, Chih‐Yang, primary, Su, Yi‐Chen, additional, Lu, Cheng‐You, additional, Chiu, Ping‐Ling, additional, Chang, Yung‐Ming, additional, Ju, Da‐Tong, additional, Chen, Ray‐Jade, additional, Yang, Liang‐Yo, additional, Ho, Tsung‐Jung, additional, and Kao, Hui‐Chuan, additional

Published
2022
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33. Aqueous extract of Solanum nigrum attenuates Angiotensin-II induced cardiac hypertrophy and improves cardiac function by repressing protein kinase C-ζ to restore HSF2 deSUMOlyation and Mel-18-IGF-IIR signaling suppression

Author

Hung-Jen Lin, Chih Yang Huang, Ping-Ling Chiu, Yung-Ming Chang, Yang Liang-Yo, Ray-Jade Chen, Wei Wen Kuo, Hsiang-Yen Huang, Cecilia Hsuan Day, Ramasamy Mahendran, and V. Vijaya Padma

Subjects
Male, Cardiac function curve, Cardiotonic Agents, Cardiomegaly, Hydrophobia, Pharmacology, Rats, Inbred WKY, Receptor, IGF Type 2, Cell Line, Muscle hypertrophy, chemistry.chemical_compound, Rats, Inbred SHR, Drug Discovery, medicine, Animals, cvg, Protein kinase A, Heat-Shock Proteins, Protein Kinase C, Protein kinase C, Solanum nigrum, Dose-Response Relationship, Drug, Plant Extracts, business.industry, Angiotensin II, cvg.computer_videogame, medicine.disease, Rats, Disease Models, Animal, Calphostin C, chemistry, Heart failure, Hypertension, business, Myoblasts, Cardiac, Transcription Factors
Abstract

Ethnopharmacological relevance Solanum nigrum, commonly known as Makoi or black shade has been traditionally used in Asian countries and other regions of world to treat liver disorders, diarrhoea, inflammatory conditions, chronic skin ailments (psoriasis and ringworm), fever, hydrophobia, painful periods, eye diseases, etc. It has been observed that S. nigrum contains substances, like steroidal saponins, total alkaloid, steroid alkaloid, and glycoprotein, which show anti-tumor activity. However; there is no scientific evidence of the efficacy of S. nigrum in the treatment of cardiac hypertrophy. Aim To investigate the ability of S. nigrum to attenuate Angiotensin II - induced cardiac hypertrophy and improve cardiac function through the suppression of protein kinase PKC-ζ and Mel-18-IGF-IIR signaling leading to the restoration of HSF2 desumolyation. Materials and methods Cardiomyoblast cells (H9c2) were challenged with 100 nM Angiotensin-II (AngII) for 24 h and were then treated with different concentration of S.nigrum or Calphostin C for 24 h. The hypertrophic effect in cardiomyoblast cells were determined by immunofluorescence staining and the modulations in hypertrophic protein marker along with Protein Kinase C-ζ, MEL18, HSF2, and Insulin like growth factor II (IGFIIR), markers were analyzed by western blotting. In vivo experiments were performed using 12 week old male Wistar Kyoto rats (WKY) and Spontaneously hypertensive rats (SHR) separated into five groups. [1]Control WKY, [2] WKY –100 mg/kg of S.nigrum treatment, [3] SHR, [4] SHR-100 mg/kg of S.nigrum treatment, [5] SHR-300 mg/kg of S.nigrum treatment. S. nigrum was administered intraperitoneally for 8 week time interval. Results Western blotting results indicate that S. nigrum significantly attenuates AngII induced cardiac hypertrophy. Furthermore, actin staining confirmed the ability of S. nigrum to ameliorate AngII induced cardiac hypertrophy. Moreover, S. nigrum administration suppressed the hypertrophic signaling mediators like Protein Kinase C-ζ, Mel-18, and IGFIIR in a dose-dependent manner and HSF2 activation (restore deSUMOlyation) that leads to downregulation of IGF-IIR expression. Additionally in vivo experiments demonstrate the reduced heart sizes of S. nigrum treated SHRs rats when compared to control WKY rats. Conclusion Collectively, the data reveals the cardioprotective effect of S. nigrum inhibiting PKC-ζ with alleviated IGF IIR level in the heart that profoundly remits cardiac hypertrophy for hypertension-induced heart failure.

Published
2022

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