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Wang R, Zhang Y, Guo Y, Zeng W, Li J, Wu J, Li N, Zhu A, Li J, Di L, Cao P. Plant-derived nanovesicles: Promising therapeutics and drug delivery nanoplatforms for brain disorders. FUNDAMENTAL RESEARCH 2025; 5:830-850. [PMID: 40242551 PMCID: PMC11997602 DOI: 10.1016/j.fmre.2023.09.007] [Citation(s) in RCA: 5] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/08/2023] [Revised: 08/17/2023] [Accepted: 09/10/2023] [Indexed: 04/18/2025] Open
Abstract
Plant-derived nanovesicles (PDNVs), including plant extracellular vesicles (EVs) and plant exosome-like nanovesicles (ELNs), are natural nano-sized membranous vesicles containing bioactive molecules. PDNVs consist of a bilayer of lipids that can effectively encapsulate hydrophilic and lipophilic drugs, improving drug stability and solubility as well as providing increased bioavailability, reduced systemic toxicity, and enhanced target accumulation. Bioengineering strategies can also be exploited to modify the PDNVs to achieve precise targeting, controlled drug release, and massive production. Meanwhile, they are capable of crossing the blood-brain barrier (BBB) to transport the cargo to the lesion sites without harboring human pathogens, making them excellent therapeutic agents and drug delivery nanoplatform candidates for brain diseases. Herein, this article provides an initial exposition on the fundamental characteristics of PDNVs, including biogenesis, uptake process, isolation, purification, characterization methods, and source. Additionally, it sheds light on the investigation of PDNVs' utilization in brain diseases while also presenting novel perspectives on the obstacles and clinical advancements associated with PDNVs.
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Affiliation(s)
- Ruoning Wang
- School of Pharmacy, Nanjing University of Chinese Medicine, Nanjing 210023, China
- Jiangsu Provincial TCM Engineering Technology Research Center of High Efficient Drug Delivery System, Nanjing 210023, China
| | - Yingjie Zhang
- School of Pharmacy, Nanjing University of Chinese Medicine, Nanjing 210023, China
- Jiangsu Provincial TCM Engineering Technology Research Center of High Efficient Drug Delivery System, Nanjing 210023, China
| | - Yumiao Guo
- School of Pharmacy, Nanjing University of Chinese Medicine, Nanjing 210023, China
- Jiangsu Provincial TCM Engineering Technology Research Center of High Efficient Drug Delivery System, Nanjing 210023, China
| | - Wei Zeng
- School of Pharmacy, Nanjing University of Chinese Medicine, Nanjing 210023, China
- Jiangsu Provincial TCM Engineering Technology Research Center of High Efficient Drug Delivery System, Nanjing 210023, China
| | - Jinge Li
- School of Pharmacy, Nanjing University of Chinese Medicine, Nanjing 210023, China
- Jiangsu Provincial TCM Engineering Technology Research Center of High Efficient Drug Delivery System, Nanjing 210023, China
| | - Jie Wu
- School of Pharmacy, Nanjing University of Chinese Medicine, Nanjing 210023, China
- Jiangsu Provincial TCM Engineering Technology Research Center of High Efficient Drug Delivery System, Nanjing 210023, China
| | - Nengjin Li
- School of Pharmacy, Nanjing University of Chinese Medicine, Nanjing 210023, China
- Jiangsu Provincial TCM Engineering Technology Research Center of High Efficient Drug Delivery System, Nanjing 210023, China
| | - Anran Zhu
- School of Pharmacy, Nanjing University of Chinese Medicine, Nanjing 210023, China
- Jiangsu Provincial TCM Engineering Technology Research Center of High Efficient Drug Delivery System, Nanjing 210023, China
| | - Jiale Li
- School of Pharmacy, Nanjing University of Chinese Medicine, Nanjing 210023, China
- Jiangsu Provincial TCM Engineering Technology Research Center of High Efficient Drug Delivery System, Nanjing 210023, China
| | - Liuqing Di
- School of Pharmacy, Nanjing University of Chinese Medicine, Nanjing 210023, China
- Jiangsu Provincial TCM Engineering Technology Research Center of High Efficient Drug Delivery System, Nanjing 210023, China
| | - Peng Cao
- School of Pharmacy, Nanjing University of Chinese Medicine, Nanjing 210023, China
- Jiangsu Provincial Medical Innovation Center, Affiliated Hospital of Integrated Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing 210028, China
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Lan Y, Wang X, Yan F, Zhang W, Zhao S, Song Y, Wang S, Zhu Z, Wang Y, Liu X. Quinoa Saponin Ameliorates Lipopolysaccharide-Induced Behavioral Disorders in Mice by Inhibiting Neuroinflammation, Modulating Gut Microbiota, and Counterbalancing Intestinal Inflammation. JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY 2025; 73:4700-4715. [PMID: 39948027 DOI: 10.1021/acs.jafc.5c00296] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 02/27/2025]
Abstract
Triterpenoids derived from plants are a promising class of natural antidepressants. This research focused on the therapeutic potential of quinoa saponin (QS) in alleviating lipopolysaccharide (LPS)-induced anxiety and depressive-like behaviors in mice. The most abundant saponin fraction, QS-3, was isolated from QS extracts, and its major saponin components and chemical structure were elucidated. Six pentacyclic triterpene saponins and three tetracyclic triterpene saponins were identified in QS-3, with phytolaccagenin and oleanolic acid being the dominant sapogenins. In vivo studies demonstrated that QS significantly mitigated LPS-induced anxiety and depressive-like behaviors in mice, enhanced the levels of neurotrophic proteins, key synaptic proteins, and neurotransmitters, and restored synaptic function and neuronal damage. Furthermore, QS inhibited neuroinflammation by curtailing the activity of the TLR4/MyD88/NF-κB pathway and modulating microglial phenotypes. Notably, QS also ameliorated colonic inflammation by promoting gut microbiota homeostasis and increasing short-chain fatty acids (SCFAs) production, which contributed to the improvement of anxiety and depressive behaviors in mice. Our findings suggest that QS holds potential as a natural dietary supplement for the treatment and prevention of anxiety and depression, possibly through its modulation of gut-brain axis dynamics and suppression of the activation of the TLR4/MyD88/NF-κB pathway.
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Affiliation(s)
- Yongli Lan
- College of Food Science and Engineering, Northwest A&F University, No. 22 Xinong Road, Yangling, Shaanxi 712100, China
| | - Xinze Wang
- College of Food Science and Engineering, Northwest A&F University, No. 22 Xinong Road, Yangling, Shaanxi 712100, China
| | - Fanghua Yan
- College of Food Science and Engineering, Northwest A&F University, No. 22 Xinong Road, Yangling, Shaanxi 712100, China
| | - Wengang Zhang
- College of Food Science and Engineering, Northwest A&F University, No. 22 Xinong Road, Yangling, Shaanxi 712100, China
- Laboratory for Research and Utilization of Qinghai Tibet Plateau Germplasm Resources, Qinghai University, Xining 810016, China
| | - Shiyang Zhao
- College of Food Science and Engineering, Northwest A&F University, No. 22 Xinong Road, Yangling, Shaanxi 712100, China
| | - Yujie Song
- College of Food Science and Engineering, Northwest A&F University, No. 22 Xinong Road, Yangling, Shaanxi 712100, China
| | - Shuangxi Wang
- Lanzhou Industrial Research Institute, Lanzhou 730050, China
| | - Zhuofan Zhu
- College of Food Science and Engineering, Northwest A&F University, No. 22 Xinong Road, Yangling, Shaanxi 712100, China
| | - Yutang Wang
- College of Food Science and Engineering, Northwest A&F University, No. 22 Xinong Road, Yangling, Shaanxi 712100, China
| | - Xuebo Liu
- College of Food Science and Engineering, Northwest A&F University, No. 22 Xinong Road, Yangling, Shaanxi 712100, China
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Feng Y, Wang W, Zhang Y, Feng Y, Zhao Y, Zhang Z, Wang Y. Xiao-Chai-Hu-Tang Ameliorates Depressive Symptoms via Modulating Neuro-Endocrine Network in Chronic Unpredictable Mild Stress-Induced Mice. CNS Neurosci Ther 2025; 31:e70290. [PMID: 39981856 PMCID: PMC11843474 DOI: 10.1111/cns.70290] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/21/2023] [Revised: 07/11/2024] [Accepted: 12/09/2024] [Indexed: 02/22/2025] Open
Abstract
OBJECTIVE Xiao-Chai-Hu-Tang (XCHT) has been demonstrated to exert an antidepressant effect during long-term clinical practices. However, the potential mechanisms of XCHT remain unknown. This study aims to investigate the effect of XCHT on chronic unpredictable mild stress-induced mice with depressive-like behaviors and to explore the underlying mechanisms. METHODS The active compositions and potential related targets of XCHT in the brain were obtained through UPLC-Q-TOF-MS, network pharmacology, and bioinformatics analyses, verified by experimental validation. Then, the protein-protein interaction (PPI), Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses, and molecular docking were used to predict the core targets and mechanisms of XCHT on depression. After being treated with XCHT standard decoction, based on enzyme-linked immunosorbent assay (ELISA), non-targeted metabolism, targeted LC-MS analyses, RNA-seq, quantitative RT-PCR, immunofluorescence, and western blotting were determined to clarify the mechanism of XCHT in the treatment of anxiety and depression disorder. RESULTS In total, 166 active ingredients and 525 related targets of XCHT were detected and selected from the network databases. The inflammatory response and metabolism of neurotransmitters were the main related signaling pathways predicted by KEGG enrichment analyses. Behavioral testing shows that XCHT has antidepressant effects, and untargeted metabolomic studies showed it significantly reduced levels of the neurotoxic substance quinoline acid. Combining the results of molecular docking, RNA-seq, and western blot revealed that XCHT regulated nerve regeneration via BDNF/TrkB/CREB and PI3K/AKT signaling pathways. Immunofluorescence analysis revealed that XCHT downregulated the chronic stress-induced activation of microglia and astrocytes in the hippocampus. CONCLUSION XCHT exerts antidepressant functions by modulating neuroinflammation and neuroregeneration.
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Affiliation(s)
- Ying Feng
- Department of Medical Oncology, Shuguang HospitalShanghai University of Traditional Chinese MedicineShanghaiChina
- School of Integrative MedicineShanghai University of Traditional Chinese MedicineShanghaiChina
| | - Wenkai Wang
- Department of Medical Oncology, Shuguang HospitalShanghai University of Traditional Chinese MedicineShanghaiChina
| | - Yingru Zhang
- Department of Medical Oncology, Shuguang HospitalShanghai University of Traditional Chinese MedicineShanghaiChina
- School of Integrative MedicineShanghai University of Traditional Chinese MedicineShanghaiChina
- The Second Clinical Medical College of Guizhou University of Traditional Chinese MedicineGuizhou ProvinceChina
| | - Yuanyuan Feng
- Department of Medical Oncology, Shuguang HospitalShanghai University of Traditional Chinese MedicineShanghaiChina
| | - Yiyang Zhao
- Department of Medical Oncology, Shuguang HospitalShanghai University of Traditional Chinese MedicineShanghaiChina
| | - Zhaozhou Zhang
- Department of Medical Oncology, Shuguang HospitalShanghai University of Traditional Chinese MedicineShanghaiChina
- School of Integrative MedicineShanghai University of Traditional Chinese MedicineShanghaiChina
| | - Yan Wang
- Department of Medical Oncology, Shuguang HospitalShanghai University of Traditional Chinese MedicineShanghaiChina
- School of Integrative MedicineShanghai University of Traditional Chinese MedicineShanghaiChina
- The Second Clinical Medical College of Guizhou University of Traditional Chinese MedicineGuizhou ProvinceChina
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Wang H, Liu H, Pan S, Ma Z, Wang Y, Liu J, Wang C, An Z. Effects of lipopolysaccharide infusion on feed intake, apparent digestibility, rumen fermentation and microorganisms of young Holstein bulls fed diets with different ratios of lysine and methionine. Front Vet Sci 2025; 11:1523062. [PMID: 39834924 PMCID: PMC11743472 DOI: 10.3389/fvets.2024.1523062] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/05/2024] [Accepted: 12/11/2024] [Indexed: 01/22/2025] Open
Abstract
The aim of this experiment was to investigate the effects of intravenous infusion of lipopolysaccharide (LPS) and feeding different ratios of lysine (Lys) and methionine (Met) on feed intake, apparent digestibility, rumen fermentation and microorganisms in young Holstein bulls. Five seven-month-old Holstein bulls with similar body weights (279 ± 42 kg) were selected and subjected to a 5 × 5 Latin square experiment. The control group (CON) was fed with basal diet and the ratio of Lys to Met in the diet was adjusted to 3.0: 1. The experimental groups were received LPS infusion while being fed the basal diet (TRT1), along with LPS infusion and the addition of rumen-protected lysine (RPL) and rumen-protected methionine (RPM) to make the ratio of Lys to Met to 2.5:1 (TRT2), 3.0:1 (TRT3) and 3.5: 1 (TRT4), respectively. The LPS jugular infusion dose was set at 0.01 μg/kg body weight on days 1-3 and 0.05 μg/kg body weight on days 4-7. The trial was conducted over five periods, consisting of a 7-day trial period and a 6-day interval. The results indicated that there were no significant effects of LPS infusion on feed intake and apparent digestibility in young Holstein bulls fed different ratios of Lys and Met (p > 0.05). The treatment had no significant effects on the pH and total volatile fatty acids (p > 0.05). Compared with CON, the acetate content in the experimental groups exhibited an increasing trend (p = 0.066), while the content of NH3-N decreased significantly (p < 0.05). LPS infusion had no significant effect on rumen microorganisms at either the species or phylum level (p > 0.05). However, feeding different ratios of Lys and Met could significantly increasing the abundance of Oribacterium (p < 0.05) and tended to increase the abundance of norank_f__norank_o__RF_39 at the genus level (p = 0.087). These findings suggest that adding RPL and RPM into the diet may enhance the rumen environment in young Holstein bulls. Under the conditions of this experiment, adding RPL and RPM can mitigate the negative effects associated with LPS infusion, with an optimal ratio of Lys and Met is 3.0:1.
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Affiliation(s)
- Huiyao Wang
- College of Animal Science and Technology & College of Veterinary Medicine, Key Laboratory of Applied Technology on Green-Eco-Healthy Animal Husbandry of Zhejiang Province, Zhejiang A&F University, Hangzhou, Zhejiang, China
| | - Hongyun Liu
- College of Animal Sciences, Zhejiang University, Hangzhou, Zhejiang, China
| | - Shijia Pan
- College of Animal Science and Technology & College of Veterinary Medicine, Key Laboratory of Applied Technology on Green-Eco-Healthy Animal Husbandry of Zhejiang Province, Zhejiang A&F University, Hangzhou, Zhejiang, China
| | - Zhicong Ma
- College of Animal Science and Technology & College of Veterinary Medicine, Key Laboratory of Applied Technology on Green-Eco-Healthy Animal Husbandry of Zhejiang Province, Zhejiang A&F University, Hangzhou, Zhejiang, China
| | - Yanming Wang
- Kemin (China) Technologies Co. Ltd., Zhuhai, China
| | - Jianxin Liu
- College of Animal Sciences, Zhejiang University, Hangzhou, Zhejiang, China
| | - Chong Wang
- College of Animal Science and Technology & College of Veterinary Medicine, Key Laboratory of Applied Technology on Green-Eco-Healthy Animal Husbandry of Zhejiang Province, Zhejiang A&F University, Hangzhou, Zhejiang, China
| | - Zhigao An
- College of Animal Science and Technology & College of Veterinary Medicine, Key Laboratory of Applied Technology on Green-Eco-Healthy Animal Husbandry of Zhejiang Province, Zhejiang A&F University, Hangzhou, Zhejiang, China
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Wang S, Chen M, Qian Y, Chen X, Xu W. Shexiang Baoxin Pills alleviate doxorubicin-induced cardiotoxicity via the reactive oxygen species-mediated AKT/Bcl-2 pathway. Medicine (Baltimore) 2024; 103:e40287. [PMID: 39969310 PMCID: PMC11688037 DOI: 10.1097/md.0000000000040287] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/26/2024] [Accepted: 10/10/2024] [Indexed: 02/20/2025] Open
Abstract
BACKGROUND Shexiang Baoxin Pill (SBP) is a classical Chinese medicine that improves endothelial function and antioxidant and inflammatory responses. It may also alleviate doxorubicin (DOX)-induced cardiotoxicity. The aim of this study is to explore the potential influence and molecular mechanisms of SBP in DOX-induced cardiotoxicity using network pharmacology. METHODS We established control, SBP, DOX, and DOX + SBP groups to evaluate cell function using a Cell Counting Kit-8 assay, reactive oxygen species (ROS) measurement, cell cycle analysis, and apoptosis assessment. Network pharmacology was employed to predict potential targets and pathways of SBP in DOX-induced cardiotoxicity; the predictions were validated using protein blotting assays. RESULTS SBP (2.5 mg/L) significantly mitigated DOX-induced cardiotoxicity. DOX elevated ROS levels, induced phosphorylation of the AKT pathway, and altered the expression of apoptosis-related proteins Bcl-2 and Bax. SBP attenuated the impact of DOX on cardiomyocytes. Network pharmacology identified 10 candidate targets. CONCLUSION SBP ameliorates DOX-induced cardiomyocyte apoptosis by activating the ROS-mediated AKT/Bcl-2 signaling pathway.
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Affiliation(s)
- Shudan Wang
- The Affiliated Lihuili Hospital, Health Science Center, Ningbo University, Ningbo, China
| | - Mingcai Chen
- The Affiliated Lihuili Hospital, Health Science Center, Ningbo University, Ningbo, China
| | - Yi Qian
- School of Public Health, Health Science Center, Ningbo University, Ningbo, Zhejiang, China
| | - Xiaohan Chen
- The Affiliated Lihuili Hospital, Health Science Center, Ningbo University, Ningbo, China
| | - Weifeng Xu
- The Affiliated Lihuili Hospital, Health Science Center, Ningbo University, Ningbo, China
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Fan W, Fan L, Wang Z, Mei Y, Liu L, Li L, Yang L, Wang Z. Rare ginsenosides: A unique perspective of ginseng research. J Adv Res 2024; 66:303-328. [PMID: 38195040 PMCID: PMC11674801 DOI: 10.1016/j.jare.2024.01.003] [Citation(s) in RCA: 14] [Impact Index Per Article: 14.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/12/2023] [Revised: 12/29/2023] [Accepted: 01/04/2024] [Indexed: 01/11/2024] Open
Abstract
BACKGROUND Rare ginsenosides (Rg3, Rh2, C-K, etc.) refer to a group of dammarane triterpenoids that exist in low natural abundance, mostly produced by deglycosylation or side chain modification via physicochemical processing or metabolic transformation in gut, and last but not least, exhibited potent biological activity comparing to the primary ginsenosides, which lead to a high concern in both the research and development of ginseng and ginsenoside-related nutraceutical and natural products. Nevertheless, a comprehensive review on these promising compounds is not available yet. AIM OF REVIEW In this review, recent advances of Rare ginsenosides (RGs) were summarized dealing with the structurally diverse characteristics, traditional usage, drug discovery situation, clinical application, pharmacological effects and the underlying mechanisms, structure-activity relationship, toxicity, the stereochemistry properties, and production strategies. KEY SCIENTIFIC CONCEPTS OF REVIEW A total of 144 RGs with diverse skeletons and bioactivities were isolated from Panax species. RGs acted as natural ligands on some specific receptors, such as bile acid receptors, steroid hormone receptors, and adenosine diphosphate (ADP) receptors. The RGs showed promising bioactivities including immunoregulatory and adaptogen-like effect, anti-aging effect, anti-tumor effect, as well as their effects on cardiovascular and cerebrovascular system, central nervous system, obesity and diabetes, and interaction with gut microbiota. Clinical trials indicated the potential of RGs, while high quality data remains inadequate, and no obvious side effects was found. The stereochemistry properties induced by deglycosylation at C (20) were also addressed including pharmacodynamics behaviors, together with the state-of-art analytical strategies for the identification of saponin stereoisomers. Finally, the batch preparation of targeted RGs by designated strategies including heating or acid/ alkaline-assisted processes, and enzymatic biotransformation and biosynthesis were discussed. Hopefully, the present review can provide more clues for the extensive understanding and future in-depth research and development of RGs, originated from the worldwide well recognized ginseng plants.
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Affiliation(s)
- Wenxiang Fan
- The MOE Key Laboratory of Standardization of Chinese Medicines, Shanghai Key Laboratory of Compound Chinese Medicines, and SATCM Key Laboratory of New Resources and Quality Evaluation of Chinese Medicines, Institute of Chinese Materia Medica, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China
| | - Linhong Fan
- The MOE Key Laboratory of Standardization of Chinese Medicines, Shanghai Key Laboratory of Compound Chinese Medicines, and SATCM Key Laboratory of New Resources and Quality Evaluation of Chinese Medicines, Institute of Chinese Materia Medica, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China
| | - Ziying Wang
- The MOE Key Laboratory of Standardization of Chinese Medicines, Shanghai Key Laboratory of Compound Chinese Medicines, and SATCM Key Laboratory of New Resources and Quality Evaluation of Chinese Medicines, Institute of Chinese Materia Medica, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China
| | - Yuqi Mei
- The MOE Key Laboratory of Standardization of Chinese Medicines, Shanghai Key Laboratory of Compound Chinese Medicines, and SATCM Key Laboratory of New Resources and Quality Evaluation of Chinese Medicines, Institute of Chinese Materia Medica, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China
| | - Longchan Liu
- The MOE Key Laboratory of Standardization of Chinese Medicines, Shanghai Key Laboratory of Compound Chinese Medicines, and SATCM Key Laboratory of New Resources and Quality Evaluation of Chinese Medicines, Institute of Chinese Materia Medica, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China
| | - Linnan Li
- The MOE Key Laboratory of Standardization of Chinese Medicines, Shanghai Key Laboratory of Compound Chinese Medicines, and SATCM Key Laboratory of New Resources and Quality Evaluation of Chinese Medicines, Institute of Chinese Materia Medica, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China
| | - Li Yang
- The MOE Key Laboratory of Standardization of Chinese Medicines, Shanghai Key Laboratory of Compound Chinese Medicines, and SATCM Key Laboratory of New Resources and Quality Evaluation of Chinese Medicines, Institute of Chinese Materia Medica, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China.
| | - Zhengtao Wang
- The MOE Key Laboratory of Standardization of Chinese Medicines, Shanghai Key Laboratory of Compound Chinese Medicines, and SATCM Key Laboratory of New Resources and Quality Evaluation of Chinese Medicines, Institute of Chinese Materia Medica, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China.
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Chen W, Guo P, Su L, Guo X, Shi M, Geng J, Zong Y, Zhao Y, Du R, He Z. Combining Network Pharmacology and Transcriptomic Strategies to Explore the Pharmacological Mechanism of Total Ginsenoside Ginseng Root and Its Impact on Antidepressant Effects. Int J Mol Sci 2024; 25:12606. [PMID: 39684318 DOI: 10.3390/ijms252312606] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/05/2024] [Revised: 11/20/2024] [Accepted: 11/21/2024] [Indexed: 12/18/2024] Open
Abstract
Depression is one of the most common neurological diseases, which imposes a substantial social and economic burden on modern society. The purpose of this study was to explore the mechanism of total ginsenoside ginseng root (TGGR) in the treatment of depression through a comprehensive strategy combining network pharmacology, transcriptomics, and in vivo experimental validation. The Traditional Chinese Medicine Systematic Pharmacology (TCMSP) database and literature were used to collect the main components and targets of TGGR. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were applied to explore the underlying mechanisms. In addition, the chronic unpredictable mild stress (CUMS)-induced C57BL/6 mouse model was used to evaluate the antidepressant activity of TGGR. The results showed that TGGR improved depression-like behavior in mice and increased the decrease in serum 5-hydroxytryptamine (5-HT) and brain-derived neurotrophic factor (BDNF) levels caused by CUMS. Combined network pharmacology and transcriptomic analysis showed that the AMP-activated kinase (AMPK) signaling pathway mainly enriched the core target. Immunohistochemistry, Western blotting, and reverse transcription quantitative polymerase chain reaction (RT-qPCR) were used to confirm whether TGGR exerts antidepressant effects by regulating this pathway. The results showed that TGGR has a regulatory impact on related proteins in the AMPK pathway, and the regulatory effect of TGGR on proteins was inhibited after the administration of related pathway inhibitors. In summary, total ginsenosides may regulate the AMPK signaling pathway and activate the sirtuin 1 (SIRT1) peroxisome proliferator-activated receptor-gamma coactivator 1-alpha (PGC-1α) pathway to have therapeutic effects on depression.
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Affiliation(s)
- Weijia Chen
- College of Chinese Medicinal Materials, Jilin Agricultural University, Changchun 130118, China
- Jilin Provincial Engineering Research Center for Efficient Breeding and Product Development of Sika Deer, Changchun 130118, China
- Key Laboratory of Animal Production and Product Quality and Security, Ministry of Education, Ministry of National Education, Changchun 130118, China
| | - Pengli Guo
- College of Chinese Medicinal Materials, Jilin Agricultural University, Changchun 130118, China
| | - Lili Su
- College of Chinese Medicinal Materials, Jilin Agricultural University, Changchun 130118, China
| | - Xiangjuan Guo
- College of Chinese Medicinal Materials, Jilin Agricultural University, Changchun 130118, China
| | - Meiling Shi
- College of Chinese Medicinal Materials, Jilin Agricultural University, Changchun 130118, China
| | - Jianan Geng
- College of Chinese Medicinal Materials, Jilin Agricultural University, Changchun 130118, China
- Jilin Provincial Engineering Research Center for Efficient Breeding and Product Development of Sika Deer, Changchun 130118, China
- Key Laboratory of Animal Production and Product Quality and Security, Ministry of Education, Ministry of National Education, Changchun 130118, China
| | - Ying Zong
- College of Chinese Medicinal Materials, Jilin Agricultural University, Changchun 130118, China
- Jilin Provincial Engineering Research Center for Efficient Breeding and Product Development of Sika Deer, Changchun 130118, China
- Key Laboratory of Animal Production and Product Quality and Security, Ministry of Education, Ministry of National Education, Changchun 130118, China
| | - Yan Zhao
- College of Chinese Medicinal Materials, Jilin Agricultural University, Changchun 130118, China
- Jilin Provincial Engineering Research Center for Efficient Breeding and Product Development of Sika Deer, Changchun 130118, China
- Key Laboratory of Animal Production and Product Quality and Security, Ministry of Education, Ministry of National Education, Changchun 130118, China
| | - Rui Du
- College of Chinese Medicinal Materials, Jilin Agricultural University, Changchun 130118, China
- Jilin Provincial Engineering Research Center for Efficient Breeding and Product Development of Sika Deer, Changchun 130118, China
- Key Laboratory of Animal Production and Product Quality and Security, Ministry of Education, Ministry of National Education, Changchun 130118, China
| | - Zhongmei He
- College of Chinese Medicinal Materials, Jilin Agricultural University, Changchun 130118, China
- Jilin Provincial Engineering Research Center for Efficient Breeding and Product Development of Sika Deer, Changchun 130118, China
- Key Laboratory of Animal Production and Product Quality and Security, Ministry of Education, Ministry of National Education, Changchun 130118, China
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Zhang H, Li J, Diao M, Li J, Xie N. Production and pharmaceutical research of minor saponins in Panax notoginseng (Sanqi): Current status and future prospects. PHYTOCHEMISTRY 2024; 223:114099. [PMID: 38641143 DOI: 10.1016/j.phytochem.2024.114099] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 01/10/2024] [Revised: 03/21/2024] [Accepted: 04/14/2024] [Indexed: 04/21/2024]
Abstract
Panax notoginseng (Burk.) F.H. Chen is a traditional medicinal herb known as Sanqi or Tianqi in Asia and is commonly used worldwide. It is one of the main raw ingredients of Yunnan Baiyao, Fu fang dan shen di wan, and San qi shang yao pian. It is also a source of cardiotonic pill used to treat cardiovascular diseases in China, Korea, and Russia. Approximately 270 Panax notoginseng saponins have been isolated and identified as the major active components. Although the absorption and bioavailability of saponins are predominantly dependent on the gastrointestinal biotransformation capacity of an individual, minor saponins are better absorbed into the bloodstream and act as active substances than major saponins. Notably, minor saponins are absent or are present in minimal quantities under natural conditions. In this review, we focus on the strategies for the enrichment and production of minor saponins in P. notoginseng using physical, chemical, enzyme catalytic, and microbial methods. Moreover, pharmacological studies on minor saponins derived from P. notoginseng over the last decade are discussed. This review serves as a meaningful resource and guide, offering scholarly references for delving deeper into the exploration of the minor saponins in P. notoginseng.
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Affiliation(s)
- Hui Zhang
- College of Light Industry and Food Engineering, Guangxi University, 100 Daxue Road, Nanning, 530004, China; National Key Laboratory of Non-Food Biomass Energy Technology, National Engineering Research Center for Non-Food Biorefinery, Guangxi Academy of Sciences, 98 Daling Road, Nanning, 530007, China.
| | - Jianxiu Li
- National Key Laboratory of Non-Food Biomass Energy Technology, National Engineering Research Center for Non-Food Biorefinery, Guangxi Academy of Sciences, 98 Daling Road, Nanning, 530007, China.
| | - Mengxue Diao
- National Key Laboratory of Non-Food Biomass Energy Technology, National Engineering Research Center for Non-Food Biorefinery, Guangxi Academy of Sciences, 98 Daling Road, Nanning, 530007, China.
| | - Jianbin Li
- College of Light Industry and Food Engineering, Guangxi University, 100 Daxue Road, Nanning, 530004, China.
| | - Nengzhong Xie
- National Key Laboratory of Non-Food Biomass Energy Technology, National Engineering Research Center for Non-Food Biorefinery, Guangxi Academy of Sciences, 98 Daling Road, Nanning, 530007, China.
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9
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Ding W, Wang L, Li L, Li H, Wu J, Zhang J, Wang J. Pathogenesis of depression and the potential for traditional Chinese medicine treatment. Front Pharmacol 2024; 15:1407869. [PMID: 38983910 PMCID: PMC11231087 DOI: 10.3389/fphar.2024.1407869] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/27/2024] [Accepted: 06/05/2024] [Indexed: 07/11/2024] Open
Abstract
Depression is a prevalent mental disorder that significantly diminishes quality of life and longevity, ranking as one of the primary causes of disability globally. Contemporary research has explored the potential pathogenesis of depression from various angles, encompassing genetics, neurotransmitter systems, neurotrophic factors, the hypothalamic-pituitary-adrenal axis, inflammation, and intestinal flora, among other contributing factors. In addition, conventional chemical medications are plagued by delayed onset of action, persistent adverse effects, and restricted therapeutic efficacy. In light of these limitations, the therapeutic approach of traditional Chinese medicine (TCM) has gained increasing recognition for its superior effectiveness. Numerous pharmacological and clinical studies have substantiated TCM's capacity to mitigate depressive symptoms through diverse mechanisms. This article attempts to summarize the mechanisms involved in the pathogenesis of depression and to describe the characteristics of herbal medicines (including compounded formulas and active ingredients) for the treatment of depression. It further evaluates their effectiveness by correlating with the multifaceted pathogenesis of depression, thereby furnishing a reference for future research endeavors.
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Affiliation(s)
- Weixing Ding
- College of Traditional Chinese Medicinal Material, Jilin Agricultural University, Changchun, China
| | - Lulu Wang
- School of Medicine, Changchun Sci-Tech University, Changchun, China
| | - Lei Li
- College of Traditional Chinese Medicinal Material, Jilin Agricultural University, Changchun, China
| | - Hongyan Li
- College of Traditional Chinese Medicinal Material, Jilin Agricultural University, Changchun, China
| | - Jianfa Wu
- College of Traditional Chinese Medicinal Material, Jilin Agricultural University, Changchun, China
| | - Jing Zhang
- College of Traditional Chinese Medicinal Material, Jilin Agricultural University, Changchun, China
- Jilin Provincial International Joint Research Center for the Development and Utilization of Authentic Medicinal Materials, Changchun, China
| | - Jing Wang
- Jilin Province Faw General Hospital, Changchun, China
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10
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Zhao W, Ma J, Zhang Q, Zhang H, Ma W, Li S, Piao Y, Zhao S, Dai S, Tang D. Ginsenoside Rg3 overcomes tamoxifen resistance through inhibiting glycolysis in breast cancer cells. Cell Biol Int 2024; 48:496-509. [PMID: 38225685 DOI: 10.1002/cbin.12123] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/11/2023] [Revised: 12/19/2023] [Accepted: 12/30/2023] [Indexed: 01/17/2024]
Abstract
Tamoxifen (TAM) resistance poses a significant clinical challenge in human breast cancer and exhibits high heterogeneity among different patients. Rg3, an original ginsenoside known to inhibit tumor growth, has shown potential for enhancing TAM sensitivity in breast cancer cells. However, the specific role and underlying mechanisms of Rg3 in this context remain unclear. Aerobic glycolysis, a metabolic process, has been implicated in chemotherapeutic resistance. In this study, we demonstrate that elevated glycolysis plays a central role in TAM resistance and can be effectively targeted and overcome by Rg3. Mechanistically, we observed upregulation of 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase 3 (PFKFB3), a key mediator of glycolysis, in TAM-resistant MCF-7/TamR and T-47D/TamR cells. Crucially, PFKFB3 is indispensable for the synergistic effect of TAM and Rg3 combination therapy, which suppresses cell proliferation and glycolysis in MCF-7/TamR and T-47D/TamR cells, both in vitro and in vivo. Moreover, overexpression of PFKFB3 in MCF-7 cells mimicked the TAM resistance phenotype. Importantly, combination treatment significantly reduced TAM-resistant MCF-7 cell proliferation in an in vivo model. In conclusion, this study highlights the contribution of Rg3 in enhancing the therapeutic efficacy of TAM in breast cancer, and suggests that targeting TAM-resistant PFKFB3 overexpression may represent a promising strategy to improve the response to combination therapy in breast cancer.
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Affiliation(s)
- Wenhui Zhao
- Department of Medical Oncology, Harbin Medical University Cancer Hospital, Harbin, China
| | - Jianli Ma
- Department of Radiation Oncology, Harbin Medical University Cancer Hospital, Harbin, China
| | - Qingyuan Zhang
- Department of Medical Oncology, Harbin Medical University Cancer Hospital, Harbin, China
| | - Han Zhang
- Department of Medical Oncology, Harbin Medical University Cancer Hospital, Harbin, China
| | - Wenjie Ma
- Department of Medical Oncology, Harbin Medical University Cancer Hospital, Harbin, China
| | - Shuo Li
- Department of Medical Oncology, Harbin Medical University Cancer Hospital, Harbin, China
| | - Ying Piao
- Department of Medical Oncology, Harbin Medical University Cancer Hospital, Harbin, China
| | - Shu Zhao
- Department of Medical Oncology, Harbin Medical University Cancer Hospital, Harbin, China
| | - Shaochun Dai
- Department of Ultrasound, Harbin Medical University Cancer Hospital, Harbin, China
| | - Dabei Tang
- Department of Medical Oncology, Harbin Medical University Cancer Hospital, Harbin, China
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11
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Gan H, Ma Q, Hao W, Yang N, Chen ZS, Deng L, Chen J. Targeting autophagy to counteract neuroinflammation: A novel antidepressant strategy. Pharmacol Res 2024; 202:107112. [PMID: 38403256 DOI: 10.1016/j.phrs.2024.107112] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/18/2023] [Revised: 02/01/2024] [Accepted: 02/19/2024] [Indexed: 02/27/2024]
Abstract
Depression is a common disease that affects physical and mental health and imposes a considerable burden on afflicted individuals and their families worldwide. Depression is associated with a high rate of disability and suicide. It causes a severe decline in productivity and quality of life. Unfortunately, the pathophysiological mechanisms underlying depression have not been fully elucidated, and the risk of its treatment is still presented. Studies have shown that the expression of autophagic markers in the brain and peripheral inflammatory mediators are dysregulated in depression. Autophagy-related genes regulate the level of autophagy and change the inflammatory response in depression. Depression is related to several aspects of immunity. The regulation of the immune system and inflammation by autophagy may lead to the development or deterioration of mental disorders. This review highlights the role of autophagy and neuroinflammation in the pathophysiology of depression, sumaries the autophagy-targeting small moleculars, and discusses a novel therapeutic strategy based on anti-inflammatory mechanisms that target autophagy to treat the disease.
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Affiliation(s)
- Hua Gan
- Guangzhou Key Laboratory of Formula-Pattern Research Center, School of Traditional Chinese Medicine, Jinan University, Guangzhou 510632, China
| | - Qingyu Ma
- Guangzhou Key Laboratory of Formula-Pattern Research Center, School of Traditional Chinese Medicine, Jinan University, Guangzhou 510632, China
| | - Wenzhi Hao
- Guangzhou Key Laboratory of Formula-Pattern Research Center, School of Traditional Chinese Medicine, Jinan University, Guangzhou 510632, China
| | - Nating Yang
- Guangzhou Key Laboratory of Formula-Pattern Research Center, School of Traditional Chinese Medicine, Jinan University, Guangzhou 510632, China
| | - Zhe-Sheng Chen
- Department of Pharmaceutical Sciences, College of Pharmacy and Health Sciences, St. John's University, Queens, NY 11439, USA.
| | - Lijuan Deng
- Guangzhou Key Laboratory of Formula-Pattern Research Center, School of Traditional Chinese Medicine, Jinan University, Guangzhou 510632, China.
| | - Jiaxu Chen
- Guangzhou Key Laboratory of Formula-Pattern Research Center, School of Traditional Chinese Medicine, Jinan University, Guangzhou 510632, China; School of Traditional Chinese Medicine, Beijing University of Chinese Medicine, Beijing, China.
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12
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Shi L, Luo J, Wei X, Xu X, Tu L. The protective role of ginsenoside Rg3 in heart diseases and mental disorders. Front Pharmacol 2024; 15:1327033. [PMID: 38469409 PMCID: PMC10926849 DOI: 10.3389/fphar.2024.1327033] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/24/2023] [Accepted: 02/07/2024] [Indexed: 03/13/2024] Open
Abstract
Ginsenoside Rg3, a compound derived from Panax ginseng C. A. Mey., is increasingly recognized for its wide range of pharmacological effects. Under the worldwide healthcare challenges posed by heart diseases, Rg3 stands out as a key subject in modern research on Chinese herbal medicine, offering a novel approach to therapy. Mental illnesses are significant contributors to global disease mortality, and there is a well-established correlation between cardiac and psychiatric conditions. This connection is primarily due to dysfunctions in the sympathetic-adrenomedullary system (SAM), the hypothalamic-pituitary-adrenal axis, inflammation, oxidative stress, and brain-derived neurotrophic factor impairment. This review provides an in-depth analysis of Rg3's therapeutic benefits and its pharmacological actions in treating cardiac and mental health disorders respectively. Highlighting its potential for the management of these conditions, Rg3 emerges as a promising, multifunctional therapeutic agent.
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Affiliation(s)
- Lili Shi
- Department of Geriatric Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
- Hubei Key Laboratory of Genetics and Molecular Mechanisms of Cardiological Disorders, Wuhan, China
| | - Jinlan Luo
- Department of Geriatric Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
- Hubei Key Laboratory of Genetics and Molecular Mechanisms of Cardiological Disorders, Wuhan, China
| | - Xiupan Wei
- Department of Rehabilitation Medicine, Zhongda Hospital, Southeast University, Nanjing, China
| | - Xizhen Xu
- Hubei Key Laboratory of Genetics and Molecular Mechanisms of Cardiological Disorders, Wuhan, China
- Division of Cardiology and Department of Internal Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Ling Tu
- Department of Geriatric Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
- Hubei Key Laboratory of Genetics and Molecular Mechanisms of Cardiological Disorders, Wuhan, China
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13
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Wróbel-Biedrawa D, Podolak I. Anti-Neuroinflammatory Effects of Adaptogens: A Mini-Review. Molecules 2024; 29:866. [PMID: 38398618 PMCID: PMC10891670 DOI: 10.3390/molecules29040866] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/16/2024] [Revised: 02/07/2024] [Accepted: 02/12/2024] [Indexed: 02/25/2024] Open
Abstract
Introduction: Adaptogens are a group of plants that exhibit complex, nonspecific effects on the human body, increasing its ability to adapt, develop resilience, and survive in stress conditions. They are found in many traditional medicinal systems and play a key role in restoring the body's strength and stamina. Research in recent years has attempted to elucidate the mechanisms behind their pharmacological effects, but it appears that these effects are difficult to define precisely and involve multiple molecular pathways. Neuroinflammation: In recent years, chronic inflammation has been recognized as one of the common features of many central nervous system disorders (dementia and other neurodegenerative diseases, depression, anxiety, ischemic stroke, and infections). Because of the specific nature of the brain, this process is called neuroinflammation, and its suppression can result in an improvement of patients' condition and may promote their recovery. Adaptogens as anti-inflammatory agents: As has been discovered, adaptogens display anti-inflammatory effects, which suggests that their application may be broader than previously thought. They regulate gene expression of anti- and proinflammatory cytokines (prostaglandins, leukotriens) and can modulate signaling pathways (e.g., NF-κB). Aim: This mini-review aims to present the anti-neuroinflammatory potential of the most important plants classified as adaptogens: Schisandra chinensis, Eleutherococcus senticosus, Rhodiola rosea and Withania somnifera.
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Affiliation(s)
| | - Irma Podolak
- Department of Pharmacognosy, Jagiellonian University Collegium Medicum, Medyczna 9, 30-688 Cracow, Poland;
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14
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Zhao F, Zhang K, Chen H, Zhang T, Zhao J, Lv Q, Yu Q, Ruan M, Cui R, Li B. Therapeutic potential and possible mechanisms of ginseng for depression associated with COVID-19. Inflammopharmacology 2024; 32:229-247. [PMID: 38012459 PMCID: PMC10907431 DOI: 10.1007/s10787-023-01380-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/19/2023] [Accepted: 10/17/2023] [Indexed: 11/29/2023]
Abstract
Recently, a global outbreak of COVID-19 has rapidly spread to various national regions. As the number of COVID-19 patients has increased, some of those infected with SARS-CoV-2 have developed a variety of psychiatric symptoms, including depression, cognitive impairment, and fatigue. A distinct storm of inflammatory factors that contribute to the initial disease but also a persistent post-acute phase syndrome has been reported in patients with COVID-19. Neuropsychological symptoms including depression, cognitive impairment, and fatigue are closely related to circulating and local (brain) inflammatory factors. Natural products are currently being examined for their ability to treat numerous complications caused by COVID-19. Among them, ginseng has anti-inflammatory, immune system stimulating, neuroendocrine modulating, and other effects, which may help improve psychiatric symptoms. This review summarizes the basic mechanisms of COVID-19 pneumonia, psychiatric symptoms following coronavirus infections, effects of ginseng on depression, restlessness, and other psychiatric symptoms associated with post-COVID syn-dromes, as well as possible mechanisms underlying these effects.
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Affiliation(s)
- Fangyi Zhao
- Jilin Provincial Key Laboratory on Molecular and Chemical Genetics, The Second Hospital of Jilin University, Changchun, People's Republic of China
- Engineering Laboratory for Screening of Antidepressant Drugs, Jilin Province Development and Reform Commission, Changchun, People's Republic of China
- Jilin Provincial Key Laboratory on Target of Traditional Chinese Medicine with Anti-Depressive Effect, Changchun, People's Republic of China
| | - Kai Zhang
- Jilin Provincial Key Laboratory on Molecular and Chemical Genetics, The Second Hospital of Jilin University, Changchun, People's Republic of China
- Engineering Laboratory for Screening of Antidepressant Drugs, Jilin Province Development and Reform Commission, Changchun, People's Republic of China
- Jilin Provincial Key Laboratory on Target of Traditional Chinese Medicine with Anti-Depressive Effect, Changchun, People's Republic of China
| | - Hongyu Chen
- Jilin Provincial Key Laboratory on Molecular and Chemical Genetics, The Second Hospital of Jilin University, Changchun, People's Republic of China
- Engineering Laboratory for Screening of Antidepressant Drugs, Jilin Province Development and Reform Commission, Changchun, People's Republic of China
- Jilin Provincial Key Laboratory on Target of Traditional Chinese Medicine with Anti-Depressive Effect, Changchun, People's Republic of China
| | - Tianqi Zhang
- Jilin Provincial Key Laboratory on Molecular and Chemical Genetics, The Second Hospital of Jilin University, Changchun, People's Republic of China
- Engineering Laboratory for Screening of Antidepressant Drugs, Jilin Province Development and Reform Commission, Changchun, People's Republic of China
- Jilin Provincial Key Laboratory on Target of Traditional Chinese Medicine with Anti-Depressive Effect, Changchun, People's Republic of China
| | - Jiayu Zhao
- Jilin Provincial Key Laboratory on Molecular and Chemical Genetics, The Second Hospital of Jilin University, Changchun, People's Republic of China
- Engineering Laboratory for Screening of Antidepressant Drugs, Jilin Province Development and Reform Commission, Changchun, People's Republic of China
- Jilin Provincial Key Laboratory on Target of Traditional Chinese Medicine with Anti-Depressive Effect, Changchun, People's Republic of China
| | - Qianyu Lv
- Jilin Provincial Key Laboratory on Molecular and Chemical Genetics, The Second Hospital of Jilin University, Changchun, People's Republic of China
- Engineering Laboratory for Screening of Antidepressant Drugs, Jilin Province Development and Reform Commission, Changchun, People's Republic of China
- Jilin Provincial Key Laboratory on Target of Traditional Chinese Medicine with Anti-Depressive Effect, Changchun, People's Republic of China
| | - Qin Yu
- Jilin Provincial Key Laboratory on Molecular and Chemical Genetics, The Second Hospital of Jilin University, Changchun, People's Republic of China
- Engineering Laboratory for Screening of Antidepressant Drugs, Jilin Province Development and Reform Commission, Changchun, People's Republic of China
- Jilin Provincial Key Laboratory on Target of Traditional Chinese Medicine with Anti-Depressive Effect, Changchun, People's Republic of China
| | - Mengyu Ruan
- Jilin Provincial Key Laboratory on Molecular and Chemical Genetics, The Second Hospital of Jilin University, Changchun, People's Republic of China
- Engineering Laboratory for Screening of Antidepressant Drugs, Jilin Province Development and Reform Commission, Changchun, People's Republic of China
- Jilin Provincial Key Laboratory on Target of Traditional Chinese Medicine with Anti-Depressive Effect, Changchun, People's Republic of China
| | - Ranji Cui
- Jilin Provincial Key Laboratory on Molecular and Chemical Genetics, The Second Hospital of Jilin University, Changchun, People's Republic of China
- Engineering Laboratory for Screening of Antidepressant Drugs, Jilin Province Development and Reform Commission, Changchun, People's Republic of China
- Jilin Provincial Key Laboratory on Target of Traditional Chinese Medicine with Anti-Depressive Effect, Changchun, People's Republic of China
| | - Bingjin Li
- Jilin Provincial Key Laboratory on Molecular and Chemical Genetics, The Second Hospital of Jilin University, Changchun, People's Republic of China.
- Engineering Laboratory for Screening of Antidepressant Drugs, Jilin Province Development and Reform Commission, Changchun, People's Republic of China.
- Jilin Provincial Key Laboratory on Target of Traditional Chinese Medicine with Anti-Depressive Effect, Changchun, People's Republic of China.
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15
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Tian Y, Wang S, Tong W, Wang H, Zhang Y, Teng B. Pseudoginsenoside GQ mitigates chronic intermittent hypoxia-induced cognitive damage by modulating microglia polarization. Int Immunopharmacol 2024; 126:111234. [PMID: 37977071 DOI: 10.1016/j.intimp.2023.111234] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/17/2023] [Revised: 11/04/2023] [Accepted: 11/12/2023] [Indexed: 11/19/2023]
Abstract
Obstructive sleep apnea (OSA), a state of sleep disruption, is characterized by recurrent apnea, chronic intermittent hypoxia (CIH) and hypercapnia. Previous studies have showed that CIH-induced neuroinflammatory plays a crucial role in cognitive deficits. Pseudoginsenoside GQ (PGQ) is a new oxytetracycline-type saponin formed by the oxidation and cyclization of the 20(S) Rg3 side chain. Rg3 has been found to afford anti-inflammatory effects, while whether PGQ plays a role of anti-neuroinflammatory remains unclear. The purpose of this study was to investigate whether PGQ attenuates CIH-induced neuroinflammatory and cognitive impairment and the possible mechanism it involves. We found that PGQ significantly ameliorated CIH-induced spatial learning deficits, and inhibited microglial activation, pro-inflammatory cytokine release, and neuronal apoptosis in the hippocampus of CIH mice. In addition, PGQ pretreatment promoted microglial M1 to M2 phenotypic transition in IH-induced BV-2 microglial, as well as indirectly inhibited IH-induced neuronal injury via modulation of microglia polarization. Furthermore, we noted that activation of HMGB1/TLR4/NF-κB signaling pathway induced by IH was inhibited by PGQ. Molecular docking results revealed that PGQ could bind to the active sites of HMGB1 and TLR4. Taken together, this work supports that PGQ inhibits M1 microglial polarization via the HMGB1/TLR4/NF-κB signaling pathway, and indirectly exerts neuroprotective effects, suggesting that PGQ may be a potential therapeutic strategy for cognitive impairment accompanied OSA.
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Affiliation(s)
- Yanhua Tian
- Department of Otorhinolaryngology Head and Neck Surgery, The Second Hospital of Jilin University, Changchun, China
| | - Sanchun Wang
- Department of Otorhinolaryngology Head and Neck Surgery, The Second Hospital of Jilin University, Changchun, China
| | - Weifang Tong
- Department of Otorhinolaryngology Head and Neck Surgery, The Second Hospital of Jilin University, Changchun, China
| | - Hongyan Wang
- Department of Otorhinolaryngology Head and Neck Surgery, The Second Hospital of Jilin University, Changchun, China
| | - Yating Zhang
- Department of Otorhinolaryngology Head and Neck Surgery, The Second Hospital of Jilin University, Changchun, China
| | - Bo Teng
- Department of Otorhinolaryngology Head and Neck Surgery, The Second Hospital of Jilin University, Changchun, China.
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16
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Wu X, Zhang Z, Zhang X, Guo Y, Liu F, Gong J, Li L, Chen X, Li Z. Upregulation of A20 and TAX1BP1 contributes to the anti-neuroinflammatory and antidepressant effects of bavachalcone. Int Immunopharmacol 2023; 122:110552. [PMID: 37393841 DOI: 10.1016/j.intimp.2023.110552] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/05/2023] [Revised: 06/05/2023] [Accepted: 06/19/2023] [Indexed: 07/04/2023]
Abstract
Microglia-mediated neuroinflammation is associated with a variety of disorders, including depression. Bavachalcone is a natural ingredient extracted from Psoralea corylifolia and has various pharmacological effects. However, its anti-neuroinflammatory and antidepressant effects remain unclear. In the present study, we found that bavachalcone improved lipopolysaccharide-induced depressive-like behaviors in mice and exerted an inhibitory effect on the activation of microglia in brain tissue. Further study revealed that bavachalcone inhibited the expression of TRAF6 and the activation of the NF-κB pathway in lipopolysaccharide-induced in vitro and vivo models, while bavachalcone upregulated the expression of A20 and TAX1BP1 and enhanced their interactions. In addition, bavachalcone inhibited the production of pro-inflammatory cytokines TNF-α and IL-6. Transfection with siRNA treatment showed that downregulation of A20 and TAX1BP1 weakened the anti-neuroinflammatory effect of bavachalcone. In conclusion, these results are the first to demonstrate that bavachalcone exerts anti-neuroinflammatory and antidepressant effects via inhibition of the NF-κB pathway mediated by upregulating A20 and TAX1BP1, and may be a potential candidate for the treatment of neuroinflammation-related diseases, including depression.
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Affiliation(s)
- Xintong Wu
- School of Pharmacy, Binzhou Medical University, Yantai, Shandong, China
| | - Zhonghong Zhang
- School of Pharmacy, Binzhou Medical University, Yantai, Shandong, China
| | - Xiao Zhang
- School of Pharmacy, Binzhou Medical University, Yantai, Shandong, China
| | - Yaping Guo
- School of Pharmacy, Binzhou Medical University, Yantai, Shandong, China
| | - Feng Liu
- Department of Neurosurgery, Ankang Central Hospital, Ankang, China
| | - Jianwei Gong
- School of Rehabilitation Medicine, Binzhou Medical University, Yantai, Shandong, China
| | - Li Li
- Zhejiang Hospital, Hangzhou 310013, Zhejiang, China
| | - Xinyu Chen
- Zhejiang Hospital, Hangzhou 310013, Zhejiang, China.
| | - Zhipeng Li
- School of Pharmacy, Binzhou Medical University, Yantai, Shandong, China.
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Li B, Xu M, Wang Y, Feng L, Xing H, Zhang K. Gut microbiota: A new target for traditional Chinese medicine in the treatment of depression. JOURNAL OF ETHNOPHARMACOLOGY 2023; 303:116038. [PMID: 36529248 DOI: 10.1016/j.jep.2022.116038] [Citation(s) in RCA: 8] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 09/22/2022] [Revised: 11/20/2022] [Accepted: 12/06/2022] [Indexed: 06/17/2023]
Abstract
ETHNIC PHARMACOLOGICAL RELEVANCE The causes of depression are complex. Many factors are involved in its pathogenesis, including the individual's biological and social environment. Although numerous studies have reported that the gut microbiota plays a significant role in depression, drugs that regulate the gut microbiota to treat depression have not yet been comprehensively reviewed. At the same time, more and more attention has been paid to the characteristics of traditional Chinese medicine (TCM) in improving depression by regulating gut microbiota. In ancient times, fecal microbiota transplantation was recorded in TCM for the treatment of severe diseases. There are also records in Chinese ancient books about the use of TCM to adjust gut microbiota to treat diseases, which has opened up a unique research field in TCM. Therefore, this article focuses on the pharmacological effects, targets, and mechanisms of TCM in improving depression by mediating the influence of gut microbiota. AIM OF THIS REVIEW To summarize the role the gut microbiota plays in depression, highlight potential regulatory targets, and elucidate the anti-depression mechanisms of TCMs through regulation of the gut microbiota. METHODS A systematic review of 256 clinical trials and pharmaceutical studies published until June 2022 was conducted in eight electronic databases (Web of Science, PubMed, SciFinder, Research Gate, ScienceDirect, Google Scholar, Scopus, and China Knowledge Infrastructure), according to the implemented PRISMA criteria, using the search terms "traditional Chinese medicine," "depression," and "gut microbiota." RESULTS Numerous studies reported the effects of different gut bacteria on depression and that antidepressants work through the gut microbiota. TCM preparations based on compound Chinese medicine, the Chinese Materia Medica, and major bioactive components exerted antidepressant-like effects by improving levels of neurotransmitters, short-chain fatty acids, brain-derived neurotrophic factor, kynurenine, and cytokines via regulation of the gut microbiota. CONCLUSION This review summarized the anti-depression effects of TCM on the gut microbiota, providing evidence that TCMs are safe and effective in the treatment of depression and may provide a new therapeutic approach.
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Affiliation(s)
- Boru Li
- Department of Pharmacology, Shenyang Pharmaceutical University, Shenyang, 110016, China
| | - Meijing Xu
- Department of Pharmacology, Shenyang Pharmaceutical University, Shenyang, 110016, China
| | - Yu Wang
- Department of Pharmacology, Shenyang Pharmaceutical University, Shenyang, 110016, China
| | - Lijin Feng
- Department of Pharmacology, Shenyang Pharmaceutical University, Shenyang, 110016, China
| | - Hang Xing
- Department of Pharmacology, Shenyang Pharmaceutical University, Shenyang, 110016, China; Jiangsu Kanion Pharmaceutical Co, Ltd, Lianyungang, 222001, China.
| | - Kuo Zhang
- Department of Pharmacology, Shenyang Pharmaceutical University, Shenyang, 110016, China; Tianjin UBasio Biotechnology Group, Tianjin, 300457, China.
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Shin YJ, Lee DY, Kim JY, Heo K, Shim JJ, Lee JL, Kim DH. Effect of fermented red ginseng on gut microbiota dysbiosis- or immobilization stress-induced anxiety, depression, and colitis in mice. J Ginseng Res 2023; 47:255-264. [PMID: 36926604 PMCID: PMC10014181 DOI: 10.1016/j.jgr.2022.08.004] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/17/2021] [Revised: 06/06/2022] [Accepted: 08/16/2022] [Indexed: 11/26/2022] Open
Abstract
Background Red ginseng (RG) alleviates psychiatric disorders. Fermented red ginseng (fRG) alleviates stress-induced gut inflammation. Gut dysbiosis causes psychiatric disorders with gut inflammation. To understand the gut microbiota-mediated action mechanism of RG and fRG against anxiety/depression (AD), we investigated the effects of RG, fRG, ginsenoside Rd, and 20(S)-β-D-glucopyranosyl protopanaxadiol (CK) on gut microbiota dysbiosis-induced AD and colitis in mice. Methods Mice with AD and colitis were prepared by exposing to immobilization stress (IS) or transplanting the feces of patients with ulcerative colitis and depression (UCDF). AD-like behaviors were measured in the elevated plus maze, light/dark transition, forced swimming, and tail suspension tests. Results Oral gavage of UCDF increased AD-like behaviors and induced neuroinflammation, gastrointestinal inflammation, and gut microbiota fluctuation in mice. Oral administration of fRG or RG treatment reduced UCDF-induced AD-like behaviors, hippocampal and hypothalamic IL-6 expression, and blood corticosterone level, whereas UCDF-suppressed hippocampal BDNF+NeuN+ cell population and dopamine and hypothalamic serotonin levels increased. Furthermore, their treatments suppressed UCDF-induced colonic inflammation and partially restored UCDF-induced gut microbiota fluctuation. Oral administration of fRG, RG, Rd, or CK also decreased IS-induced AD-like behaviors, blood IL-6 and corticosterone and colonic IL-6 and TNF-α levels, and gut dysbiosis, while IS-suppressed hypothalamic dopamine and serotonin levels increased. Conclusion Oral gavage of UCDF caused AD, neuroinflammation, and gastrointestinal inflammation in mice. fRG mitigated AD and colitis in UCDF-exposed mice by the regulation of the microbiota-gut-brain axis and IS-exposed mice by the regulation of the hypothalamic-pituitary-adrenal axis.
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Key Words
- AD, anxiety/depression
- BDNF, brain-derived neurotropic factor
- CK, 20(S)-β-D-glucopyranosyl protopanaxadiol
- ELISA, enzyme-linked immunoassay
- EPMT, elevated plus maze task
- FMT, fecal microbiota transplantation
- FST, forced swimming test
- HPA, hypothalamic–pituitary–adrenal
- IL, interleukin
- IS, immobilization stress
- LDTT, light/dark transition task
- RG, red ginseng
- TNBS, 2,4,6-trinitrobenzenesulfonic acid
- TNF, tumor necrosis factor
- TST, tail suspension test
- UCD, ulcerative colitis and depression
- UCDF, the feces of patients with ulcerative colitis and depression
- depression
- fRG, fermented red ginseng
- fermentation
- ginsenoside Rd
- gut microbiota
- red ginseng
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Affiliation(s)
- Yoon-Jung Shin
- Neurobiota Research Center, College of Pharmacy, Kyung Hee University, Seoul, Republic of Korea
| | - Dong-Yun Lee
- Neurobiota Research Center, College of Pharmacy, Kyung Hee University, Seoul, Republic of Korea
| | - Joo Yun Kim
- R&BD Center, hy Co.Ltd., Yongin, Republic of Korea
| | - Keon Heo
- R&BD Center, hy Co.Ltd., Yongin, Republic of Korea
| | | | | | - Dong-Hyun Kim
- Neurobiota Research Center, College of Pharmacy, Kyung Hee University, Seoul, Republic of Korea
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19
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Rg3-enriched Korean red ginseng alleviates chloroquine-induced itch and dry skin pruritus in an MrgprA3-dependent manner in mice. Integr Med Res 2023; 12:100916. [PMID: 36632132 PMCID: PMC9826840 DOI: 10.1016/j.imr.2022.100916] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/16/2022] [Revised: 11/11/2022] [Accepted: 12/14/2022] [Indexed: 12/24/2022] Open
Abstract
Background Previous studies have found that Korean red ginseng extract (KRG) has antipruritic effects, which can be attributed to the presence of Rg3, one of the most potent ginsenosides. Therefore, Rg3-enriched KRG extract (Rg3EKRG) is anticipated to have enhanced antipruritic effects. The present study was conducted to examine the effects of Rg3EKRG in acute chloroquine (CQ)-induced and chronic dry skin pruritus. Methods Calcium imaging technique was used in HE293T cells expressing MrgprA3 and TRPA1 ("MrgprA3/TRPA1") and in primary cultures of mouse dorsal root ganglia (DRG) neurons. Mouse scratching behavior tests were performed on dry skin models. To verify the altered expression of itch-related genes, real-time RNA sequencing analysis and PCR were performed on DRG sections obtained from dry skin models. Results Rg3EKRG suppressed CQ-induced intracellular calcium changes to a greater degree than KRG. Rg3EKRG dose-dependently inhibited CQ-induced responses in MrgprA3/TRPA1 cells. Rg3EKRG likely targeted MrgprA3 rather than TRPA1 to exert its inhibitory effect. Further, Rg3EKRG strongly inhibited the scratching behavior in mice induced by acute CQ injection. Importantly, DRG neurons obtained from dry skin mice models showed increased mRNA levels of MrgprA3, and treatment with Rg3EKRG alleviated chronic dry skin conditions and suppressed spontaneous scratching behaviors. Conclusion The results of the present study imply that Rg3EKRG has a stronger antipruritic effect than KRG, inhibiting both acute CQ-induced and chronic dry skin pruritus in an MrgprA3-dependent manner. Therefore, Rg3EKRG is a potential antipruritic agent that can suppress acute and chronic itching at the peripheral sensory neuronal level.
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20
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Ren SY, Sun ZL, Yang J. The use of biochemical indexes in hair for clinical studies of psychiatric diseases: What can we learn about mental disease from hair? J Psychiatr Res 2023; 158:305-313. [PMID: 36628872 DOI: 10.1016/j.jpsychires.2023.01.004] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/13/2022] [Revised: 12/25/2022] [Accepted: 01/03/2023] [Indexed: 01/06/2023]
Abstract
Analysis of hair samples provides unique advantages, including non-invasive sampling, sample stability, and the possibility of additional optimization of high sensitivity detection methods. Hair sample analysis is often used in psychiatric disease research to evaluate previous periods of stress encountered by patients. Glucocorticoid analysis is the most frequently tested indicator of stress. Furthermore, the hypothalamus-pituitary-gonad axis and endocannabinoid system also are involved in the occurrence and development of mental disorders. The endocannabinoid and sex hormone levels in patients experiencing mental illness are considerably different from levels observed in healthy individuals. Nevertheless, due to the different methods used to assess the degree of disease and the range of analytical methods involved in clinical research, the trends in changes for these biomarkers are not uniform. The correlations between changes in biomarker concentrations and illness severity also are not clear. The observed alterations suggest these biochemical substances in hair have potential as biomarkers for diagnosis or predictive treatment. However, the variable results obtained thus far could hamper further development of hair samples for clinical assessment in psychiatric disorders. This article summarizes the published reports documenting the changes in the content of relevant substances in hair in individuals experiencing mental illness and the degree of correlation. In the discussion section, we proposed several issues that should be considered in future studies of hair samples obtained from patients with mental disorders to promote the use of hair sample assessment as an aid in diagnosis or predictive treatment.
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Affiliation(s)
- Si-Yu Ren
- The National Clinical Research Center for Mental Disorders & Beijing Key Laboratory of Mental Disorders, Beijing Anding Hospital, Capital Medical University, Beijing, China; Advanced Innovation Center for Human Brain Protection, Capital Medical University, Beijing, China
| | - Zuo-Li Sun
- The National Clinical Research Center for Mental Disorders & Beijing Key Laboratory of Mental Disorders, Beijing Anding Hospital, Capital Medical University, Beijing, China; Advanced Innovation Center for Human Brain Protection, Capital Medical University, Beijing, China
| | - Jian Yang
- The National Clinical Research Center for Mental Disorders & Beijing Key Laboratory of Mental Disorders, Beijing Anding Hospital, Capital Medical University, Beijing, China; Advanced Innovation Center for Human Brain Protection, Capital Medical University, Beijing, China.
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21
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Korean red ginseng water extract produces antidepressant-like effects through involving monoamines and brain-derived neurotrophic factor in rats. J Ginseng Res 2023. [DOI: 10.1016/j.jgr.2023.01.003] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/11/2023] Open
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22
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Phytochemistry, Pharmacology and Molecular Mechanisms of Herbal Bioactive Compounds for Sickness Behaviour. Metabolites 2022; 12:metabo12121215. [PMID: 36557252 PMCID: PMC9782141 DOI: 10.3390/metabo12121215] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/10/2022] [Revised: 11/24/2022] [Accepted: 11/25/2022] [Indexed: 12/07/2022] Open
Abstract
The host's response to acute infections or tissue injury is a sophisticated and coordinated adaptive modification called sickness behaviour. Many herbs have been studied for their ability to protect animals against experimentally induced sickness behaviour. However, there is a lack of knowledge and experimental evidence on the use of herbal bioactive compounds (HBACs) in the management of sick behaviour. The goal of this review is to provide a concise summary of the protective benefits and putative mechanisms of action of phytochemicals on the reduction of lipopolysaccharide (LPS)-induced sickness behaviour. Relevant studies were gathered from the search engines Scopus, ScienceDirect, PubMed, Google Scholar, and other scientific databases (between 2000 and to date). The keywords used for the search included "Lipopolysaccharide" OR "LPS" OR "Sickness behaviour" OR "Sickness" AND "Bioactive compounds" OR "Herbal medicine" OR "Herbal drug" OR "Natural products" OR "Isolated compounds". A total of 41 published articles that represented data on the effect of HBACs in LPS-induced sickness behaviour were reviewed and summarised systemically. There were 33 studies that were conducted in mice and 8 studies in rats. A total of 34 HBACs have had their effects against LPS-induced changes in behaviour and biochemistry investigated. In this review, we examined 34 herbal bioactive components that have been tested in animal models to see if they can fight LPS-induced sickness behaviour. Future research should concentrate on the efficacy, safety, and dosage needed to protect against illness behaviour in humans, because there is a critical shortage of data in this area.
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23
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Neurological disorders of COVID-19: insights to applications of natural products from plants and microorganisms. Arch Pharm Res 2022; 45:909-937. [PMCID: PMC9702705 DOI: 10.1007/s12272-022-01420-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/04/2022] [Accepted: 11/22/2022] [Indexed: 11/29/2022]
Abstract
In addition to the typical respiratory manifestations, various disorders including involvement of the nerve system have been detected in COVID-19 ranging from 22 to 36%. Although growing records are focusing on neurological aspects of COVID-19, the pathophysiological mechanisms and related therapeutic methods remain obscure. Considering the increased concerns of SARS-CoV-2 potential for more serious neuroinvasion conditions, the present review attempts to focus on the neuroprotective effects of natural compounds as the principle source of therapeutics inhibiting multiple steps of the SARS-CoV-2 infection cycle. The great majority of the natural products with anti-SARS-CoV-2 activity mainly inhibit the attachment, entry and gene expression rather than the replication, assembly, or release. Although microbial-derived natural products comprise 38.5% of the known natural products with neuroprotective effects following viral infection, the neuroprotective potential of the majority of microorganisms is still undiscovered. Among natural products, chrysin, huperzine A, ginsenoside Rg1, pterostilbene, and terrein have shown potent in vitro neuroprotective activity and can be promising for new or repurpose drugs for neurological complications of SARS-CoV-2.
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Qu D, Ye Z, Zhang W, Dai B, Chen G, Wang L, Shao X, Xiang A, Lu Z, Shi J. Cyanidin Chloride Improves LPS-Induced Depression-Like Behavior in Mice by Ameliorating Hippocampal Inflammation and Excitotoxicity. ACS Chem Neurosci 2022; 13:3023-3033. [PMID: 36254458 DOI: 10.1021/acschemneuro.2c00087] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/20/2023] Open
Abstract
Depression is a global disease that places a significant burden on human health. Neuroinflammation and disturbance of glutamate metabolism in brain regions, such as the hippocampus, play vital roles in the development of depression. Previous studies have shown that cyanidin chloride (Cycl) has anti-inflammatory and antioxidant properties with neuroprotective effects in peripheral tissues. However, the effects of Cycl on depression and the possible mechanism by which this compound targets brain regions remain less elucidated. We investigated the role of Cycl in lipopolysaccharide (LPS)-induced depression and examined the influence of the drug on central inflammation and the expression of excitatory amino acid transporters in the hippocampus. We found that prophylactic i.p. application of Cycl at 20 or 40 mg/kg for 5 days significantly reduced the immobility time assessed by the tail suspension test (TST) and forced swim test (FST) in LPS-challenged mice, suggesting an effective antidepressant activity of the drug. Western blotting and immunofluorescence staining in the hippocampus revealed that Cycl inhibited the upregulation of proinflammatory cytokines, including TNF-α and IL-6, and suppressed the hyperactivity of microglia induced by LPS, indicating an anti-inflammatory role in the hippocampus. Moreover, treatment with Cycl also recovered the downregulated expression of glial fibrillary acidic protein (GFAP), brain-derived neurotrophic factor (BDNF), and glutamate-aspartate transporter (GLAST) and excitatory amino acid transporter 2 (EAAT2), two members in the excitatory amino acid transporter family. The role of Cycl was also verified in cultured BV2 and U251 cells. In conclusion, the present in vivo and in vitro studies demonstrate that Cycl exerts potent antidepressant action in an LPS-induced depression model and the underlying mechanism is associated with reduced hippocampal inflammation, improved neurotrophic function, and attenuated excitotoxicity induced by glutamate.
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Affiliation(s)
- Di Qu
- The College of Life Sciences, Northwest University, Xi'an 710127, Shaanxi Province, China.,State Key Laboratory of Cancer Biology, Department of Biopharmaceutics, Air Force Medical University, Xi'an 710032, Shaanxi Province, China
| | - Zichen Ye
- Department of Health Service, Health Service Training Base, Air Force Medical University, Xi'an 710032, Shaanxi Province, China
| | - Wenli Zhang
- The College of Life Sciences, Northwest University, Xi'an 710127, Shaanxi Province, China.,State Key Laboratory of Cancer Biology, Department of Biopharmaceutics, Air Force Medical University, Xi'an 710032, Shaanxi Province, China
| | - Bing Dai
- The College of Life Sciences, Northwest University, Xi'an 710127, Shaanxi Province, China.,State Key Laboratory of Cancer Biology, Department of Biopharmaceutics, Air Force Medical University, Xi'an 710032, Shaanxi Province, China
| | - Guo Chen
- State Key Laboratory of Cancer Biology, Department of Biopharmaceutics, Air Force Medical University, Xi'an 710032, Shaanxi Province, China
| | - Li Wang
- State Key Laboratory of Cancer Biology, Department of Biopharmaceutics, Air Force Medical University, Xi'an 710032, Shaanxi Province, China
| | - Xiaolong Shao
- State Key Laboratory of Cancer Biology, Department of Biopharmaceutics, Air Force Medical University, Xi'an 710032, Shaanxi Province, China
| | - An Xiang
- State Key Laboratory of Cancer Biology, Department of Biopharmaceutics, Air Force Medical University, Xi'an 710032, Shaanxi Province, China
| | - Zifan Lu
- State Key Laboratory of Cancer Biology, Department of Biopharmaceutics, Air Force Medical University, Xi'an 710032, Shaanxi Province, China
| | - Juan Shi
- Department of Human Anatomy, Histology and Embryology & K. K. Leung Brain Research Centre, Preclinical School of Medicine, Air Force Medical University, Xi'an 710032, Shaanxi Province, China
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Ginsenosides Rg1 and CK Control Temozolomide Resistance in Glioblastoma Cells by Modulating Cholesterol Efflux and Lipid Raft Distribution. EVIDENCE-BASED COMPLEMENTARY AND ALTERNATIVE MEDICINE 2022; 2022:1897508. [PMID: 36276866 PMCID: PMC9583863 DOI: 10.1155/2022/1897508] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 05/30/2022] [Revised: 08/16/2022] [Accepted: 08/26/2022] [Indexed: 11/07/2022]
Abstract
Background Cholesterol efflux and lipid raft redistribution contribute to attenuating temozolomide resistance of glioblastoma. Ginsenosides are demonstrated to modify cholesterol metabolism and lipid raft distribution, and the brain distribution and central nervous effects of whose isoforms Rb1, Rg1, Rg3, and CK have been identified. This study aimed to reveal the role of Rb1, Rg1, Rg3, and CK in the drug resistance of glioblastoma. Methods The effects of ginsenosides on cholesterol metabolism in temozolomide-resistant U251 glioblastoma cells were evaluated by cholesterol content and efflux assay, confocal laser, qRT-PCR, and Western blot. The roles of cholesterol and ginsenosides in temozolomide resistance were studied by CCK-8, flow cytometry, and Western blot, and the mechanism of ginsenosides attenuating resistance was confirmed by inhibitors. Results Cholesterol protected the survival of resistant U251 cells from temozolomide stress and upregulated multidrug resistance protein (MDR)1, which localizes in lipid rafts. Resistant cells tended to store cholesterol intracellularly, with limited cholesterol efflux and LXRα expression to maintain the distribution of lipid rafts. Ginsenosides Rb1, Rg1, Rg3, and CK reduced intracellular cholesterol and promoted cholesterol efflux in resistant cells, causing lipid rafts to accumulate in specific regions of the membrane. Rg1 and CK also upregulated LXRα expression and increased the cytotoxicity of temozolomide in the presence of cholesterol. We further found that cholesterol efflux induction, lipid raft redistribution, and temozolomide sensitization by Rg1 and CK were induced by stimulating LXRα. Conclusions Ginsenosides Rg1 and CK controlled temozolomide resistance in glioblastoma cells by regulating cholesterol metabolism, which are potential synergists for temozolomide therapy.
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Liang XQ, Mai PY, Qin H, Li S, Ou WJ, Liang J, Zhong J, Liang MK. Integrated 16S rRNA sequencing and metabolomics analysis to investigate the antidepressant role of Yang-Xin-Jie-Yu decoction on microbe-gut-metabolite in chronic unpredictable mild stress-induced depression rat model. Front Pharmacol 2022; 13:972351. [PMID: 36249818 PMCID: PMC9565485 DOI: 10.3389/fphar.2022.972351] [Citation(s) in RCA: 12] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/18/2022] [Accepted: 08/30/2022] [Indexed: 11/13/2022] Open
Abstract
Objectives: Our goals were to evaluate the antidepressant efficacy of Yang-Xin-Jie-Yu Decoction (YXJYD) in Chronic Unpredictable Mild Stress (CUMS)-induced depression rat model and to investigate the underlying mechanisms.Design: We used CUMS-induced depression rat model to evaluate whether oral administration of YXJYD with different doses (2.1 g/kg, 1.05 g/kg and 0.525 g/kg, respectively) improve the depressive-like symptoms, and then performed UHPLC-Q-TOF-MS to explore the active ingredients of YXJYD. Subsequently, rat’s cecal contents, serum, and urine were collected from the control group, CUMS model group, and YXJYD high-dose (2.1 g/kg) treatment group. The 16S rRNA sequencing was performed on the cecal contents, based on Illumina MiSeq platform, and ANOVA analysis were used to analyze the composition variety and screen differential expression of gut bacteria in the three groups. 1H Nuclear Magnetic Resonance (NMR) analysis was used for analyzing the metabolites obtained from cecal contents, serum, and urine, and KEGG enrichment analysis was used to identify pathways of differential metabolites. An integrated 16S rRNA sequencing and metabolomic data were conducted to characterize the underlying mechanisms of YXJYDResults: The gut microbial communities, and serum, cecal content, urine metabolic compositions were significantly significantly altered in CUMS-induced depressive rats, while YXJYD effectively ameliorated the CUMS-associated gut microbiota dysbiosis, especially of Monoglobus, and alleviated the disturbance of serum, cecal content, urine metabolome and reversed the changes of key depressive and gut microbiota-related metabolites, such as succinic acid, taurine, hippuric acid, melatonin. With an integrated study of the gut microbiota and metabolomes, we identified the pathway of tricarboxylic acid cycle (TCA cycle) and propanoate metabolism as the regulated target of YXJYD on host-microbiome interaction.Conclusion: Our findings further confirmed the imbalance of metabolism and intestinal microbial is closely related to CUMS-induced depression. YXJYD regulates gut microbiome to affect body metabolomes and then produce antidepressant-like effect in CUMS-induced depressive rats while its molecular mechanism possibly be increased Monoglobus abundance in gut microbiota and regulated the TCA cycle pathway and propanoate metabolism in host.
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Affiliation(s)
- Xing-Qiu Liang
- Medical College, Guangxi University, Nanning, China
- Department of Science and Technology, Ruikang Hospital Affiliated to Guangxi University of Chinese Medicine, Nanning, China
| | - Peng-Yu Mai
- Department of Science and Technology, Ruikang Hospital Affiliated to Guangxi University of Chinese Medicine, Nanning, China
| | - Hui Qin
- Guangxi International Zhuang Medicine Hospital, Nanning, China
| | - Sen Li
- School of Basic Medical Sciences, Guangxi University of Chinese Medicine, Nanning, China
| | - Wen-Juan Ou
- School of Basic Medical Sciences, Guangxi University of Chinese Medicine, Nanning, China
| | - Jian Liang
- Medical College, Guangxi University, Nanning, China
- *Correspondence: Jian Liang, ; Jing Zhong, ; Ming-Kun Liang,
| | - Jing Zhong
- School of Basic Medical Sciences, Guangxi University of Chinese Medicine, Nanning, China
- *Correspondence: Jian Liang, ; Jing Zhong, ; Ming-Kun Liang,
| | - Ming-Kun Liang
- Department of Science and Technology, Ruikang Hospital Affiliated to Guangxi University of Chinese Medicine, Nanning, China
- *Correspondence: Jian Liang, ; Jing Zhong, ; Ming-Kun Liang,
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Tsoi B, Gao C, Yan S, Du Q, Yu H, Li P, Deng J, Shen J. Camellia nitidissima Chi extract promotes adult hippocampal neurogenesis and attenuates chronic corticosterone-induced depressive behaviours through regulating Akt/GSK3β/CREB signaling pathway. J Funct Foods 2022. [DOI: 10.1016/j.jff.2022.105199] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022] Open
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Li Y, Guo Q, Huang J, Wang Z. Antidepressant Active Ingredients From Chinese Traditional Herb Panax Notoginseng: A Pharmacological Mechanism Review. Front Pharmacol 2022; 13:922337. [PMID: 35795547 PMCID: PMC9252462 DOI: 10.3389/fphar.2022.922337] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/17/2022] [Accepted: 05/31/2022] [Indexed: 11/13/2022] Open
Abstract
Depression is one of the most common mental illnesses in the world and is highly disabling, lethal, and seriously endangers social stability. The side effects of clinical drugs used to treat depression are obvious, and the onset time is longer. Therefore, there is a great demand for antidepressant drugs with better curative effects, fewer side effects, and shorter onset time. Panax notoginseng, a Chinese herbal medication, has been used to treat depression for thousands of years and shown to have a therapeutic effect on depression. This review surveyed PubMed’s most recent 20 years of research on Panax notoginseng’s use for treating depression. We mainly highlight animal model research and outlined the pathways influenced by medicines. We provide a narrative review of recent empirical evidence of the anti-depressive effects of Panax Notoginseng and novel ideas for developing innovative clinical antidepressants with fewer side effects.
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Affiliation(s)
- Yanwei Li
- Guangzhou Key Laboratory of Formula-pattern Research Center, School of Traditional Chinese Medicine, Jinan University, Guangzhou, China
| | - Qingwan Guo
- Interdisciplinary Institute for Personalized Medicine, School of Traditional Chinese Medicine, Jinan University, Guangzhou, China
| | - Junqing Huang
- Guangzhou Key Laboratory of Formula-pattern Research Center, School of Traditional Chinese Medicine, Jinan University, Guangzhou, China
- *Correspondence: Junqing Huang, ; Ziying Wang,
| | - Ziying Wang
- Interdisciplinary Institute for Personalized Medicine, School of Traditional Chinese Medicine, Jinan University, Guangzhou, China
- *Correspondence: Junqing Huang, ; Ziying Wang,
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Cespedes M, Jacobs KR, Maruff P, Rembach A, Fowler CJ, Trounson B, Pertile KK, Rumble RL, Rainey-Smithe SR, Rowe CC, Villemagne VL, Bourgeat P, Lim CK, Chatterjee P, Martins RN, Ittner A, Masters CL, Doecke JD, Guillemin GJ, Lovejoy DB. Systemic perturbations of the kynurenine pathway precede progression to dementia independently of amyloid-β. Neurobiol Dis 2022; 171:105783. [DOI: 10.1016/j.nbd.2022.105783] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/24/2021] [Revised: 05/30/2022] [Accepted: 06/01/2022] [Indexed: 11/16/2022] Open
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Liu HT, Lin YN, Tsai MC, Wu YC, Lee MC. Baicalein Exerts Therapeutic Effects against Endotoxin-Induced Depression-like Behavior in Mice by Decreasing Inflammatory Cytokines and Increasing Brain-Derived Neurotrophic Factor Levels. Antioxidants (Basel) 2022; 11:antiox11050947. [PMID: 35624812 PMCID: PMC9137772 DOI: 10.3390/antiox11050947] [Citation(s) in RCA: 18] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/02/2022] [Revised: 05/06/2022] [Accepted: 05/07/2022] [Indexed: 12/07/2022] Open
Abstract
Inflammation plays an important role in the pathophysiology of depression. This study aims to elucidate the antidepressant effect of baicalein, an anti-inflammatory component of a traditional Chinese herbal medicine (Scutellaria baicalensis), on lipopolysaccharide (LPS)-induced depression-like behavior in mice, and to investigate the underlying mechanisms. In vitro, baicalein exhibited antioxidant activity and protected macrophages from LPS-induced damage. The results of the tail suspension test and forced swimming test (tests for despair potential in mice) showed the antidepressant effect of baicalein on LPS-treated mice. It also substantially decreased the production of pro-inflammatory cytokines, including IL-6, TNF-α, MCP-1, and eotaxin, elicited by LPS in the plasma. Baicalein downregulated NF-κB-p65 and iNOS protein levels in the hippocampus, demonstrated its ability to mitigate neuroinflammation. Additionally, baicalein increased the levels of the mature brain-derived neurotrophic factor (mBDNF) in the hippocampus of LPS-treated mice, and elevated the ratio of mBDNF/proBDNF, which regulates neuronal survival and synaptic plasticity. Baicalein also promoted the expression of CREB, which plays a role in a variety of signaling pathways. In summary, the findings of this study demonstrate that the administration of baicalein can attenuate LPS-induced depression-like behavior by suppressing neuroinflammation and inflammation induced by the peripheral immune response.
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Affiliation(s)
- Hsin-Tzu Liu
- Department of Medical Research, Hualien Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Hualien 970, Taiwan; (H.-T.L.); (Y.-C.W.)
| | - Yu-Ning Lin
- Department of Chinese Medicine, Hualien Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Hualien 970, Taiwan;
| | - Ming-Cheng Tsai
- Department of Neurosurgery, Shin-Kong Wu Ho-Su Memorial Hospital, Taipei 111, Taiwan;
| | - Ya-Chi Wu
- Department of Medical Research, Hualien Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Hualien 970, Taiwan; (H.-T.L.); (Y.-C.W.)
| | - Ming-Chung Lee
- Department of Life Science, National Taiwan Normal University, Taipei 116, Taiwan
- School of Life Science, National Taiwan Normal University, No. 88, Sec. 4, Ting-Zhou Road, Taipei 116, Taiwan
- Correspondence: ; Tel.: +886-2-7749-6254; Fax: +886-2-29312904
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Yang F, Li J, Lan Y, Lei Y, Zeng F, Huang X, Luo X, Liu R. Potential application of ginseng in sepsis. J Ginseng Res 2022; 47:353-358. [DOI: 10.1016/j.jgr.2022.05.003] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/15/2022] [Revised: 04/11/2022] [Accepted: 05/02/2022] [Indexed: 10/18/2022] Open
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Bi S, Qu Y, Shao J, Zhang J, Li W, Zhang L, Ni J, Cao L. Ginsenoside Rg3 Ameliorates Stress of Broiler Chicks Induced by Escherichia coli Lipopolysaccharide. Front Vet Sci 2022; 9:878018. [PMID: 35464384 PMCID: PMC9024239 DOI: 10.3389/fvets.2022.878018] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/17/2022] [Accepted: 03/09/2022] [Indexed: 11/30/2022] Open
Abstract
In broiler chicks, Escherichia coli lipopolysaccharide is a prominent cause for inflammatory damage and loss of immune homeostasis in broiler chicks. Ginsenosides have been shown to have anti-inflammatory and antioxidant effects. However, it has not been demonstrated that ginsenosides protect broiler chicks against stress induced by Escherichia coli lipopolysaccharide challenge. The aim of this is to investigate the protective effect of ginsenosides Rg1, Re, and Rg3 on Escherichia coli lipopolysaccharide-induced stress. Our results showed that Rg3 ameliorated growth inhibition and fever, as well as decreased the production of stress-related hormones in broilers with stress. The protective effect of Rg3 on the stressed chicks may be largely mediated by regulating inflammatory response and oxidative damage. Moreover, real-time quantitative-polymerase chain reaction (RT-qPCR) results demonstrated that Rg3 upregulated mRNA expression of mTOR, HO-1, and SOD-1. These results suggested that ginsenoside Rg3 and ginsenoside products contains Rg3 deserve further study for the control of immunological stress and inflammation in broiler chicks.
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Affiliation(s)
- Shicheng Bi
- Department of Traditional Chinese Veterinary Medicine, College of Veterinary Medicine, Southwest University, Chongqing, China
- *Correspondence: Shicheng Bi
| | - Yiwen Qu
- Department of Traditional Chinese Veterinary Medicine, College of Veterinary Medicine, Southwest University, Chongqing, China
| | - Jianjian Shao
- Department of Traditional Chinese Veterinary Medicine, College of Veterinary Medicine, Southwest University, Chongqing, China
| | - Jianrong Zhang
- Department of Traditional Chinese Veterinary Medicine, College of Veterinary Medicine, Southwest University, Chongqing, China
| | - Weihao Li
- Department of Traditional Chinese Veterinary Medicine, College of Veterinary Medicine, Southwest University, Chongqing, China
| | - Li Zhang
- Department of Traditional Chinese Veterinary Medicine, College of Veterinary Medicine, Southwest University, Chongqing, China
| | - Jingxuan Ni
- Department of Traditional Chinese Veterinary Medicine, College of Veterinary Medicine, Southwest University, Chongqing, China
| | - Liting Cao
- Immunology Research Center, Medical Research Institute, Southwest University, Chongqing, China
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Feng L, Xing H, Zhang K. The therapeutic potential of traditional Chinese medicine in depression: Targeting adult hippocampal neurogenesis. PHYTOMEDICINE : INTERNATIONAL JOURNAL OF PHYTOTHERAPY AND PHYTOPHARMACOLOGY 2022; 98:153980. [PMID: 35152089 DOI: 10.1016/j.phymed.2022.153980] [Citation(s) in RCA: 19] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 06/19/2021] [Revised: 01/22/2022] [Accepted: 02/02/2022] [Indexed: 06/14/2023]
Abstract
BACKGROUND Depression is a common mental disorder characterized by persistent sadness and lack of interest or pleasure in previously rewarding or enjoyable activities. Understandably, the causes of depression are complex. Nevertheless, the understanding of depression pathophysiology has progressed considerably and numerous studies indicate that hippocampal neurogenesis plays a pivotal role. However, no drugs specifically targeting hippocampal neurogenesis yet exist. Meanwhile, the effects of traditional Chinese medicine (TCM) on hippocampal neurogenesis have received increasing attention in the field of antidepressant treatment because of its multi-ingredient, multi-target, and holistic view. However, the effects and mechanisms of TCM on hippocampal neurogenesis in clinical trials and pharmaceutical studies remain to be comprehensively delineated. PURPOSE To summarize the importance of hippocampal neurogenesis in depression and illustrate the targets and mechanisms of hippocampal neurogenesis regulation that underlie the antidepressant effects of TCM. METHOD A systematic review of clinical trials and studies ending by January 2022 was performed across eight electronic databases (Web of Science, PubMed, SciFinder, Research Gate, ScienceDirect, Google Scholar, Scopus and China Knowledge Infrastructure) according to the PRISMA criteria, using the search terms 'traditional Chinese medicine' "AND" 'depression' "OR" 'hippocampal neurogenesis' "OR" 'multi-ingredient' "OR" 'multi-target'. RESULTS Numerous studies show that hippocampal neurogenesis is attenuated in depression, and that antidepressants act by enhancing hippocampal neurogenesis. Moreover, compound Chinese medicine (CCM), Chinese meteria medica (CMM), and major bioactive components (MBCs) can promote hippocampal neurogenesis exerting antidepressant effects through modulation of neurotransmitters and receptors, neurotrophins, the hypothalamic-pituitary-adrenal axis, inflammatory factors, autophagy, and gut microbiota. CONCLUSION We have comprehensively summarized the effect and mechanism of TCM on hippocampal neurogenesis in depression providing a unique perspective on the use of TCM in the antidepressant field. TCM has the characteristics and advantages of multiple targets and high efficacy, showing great potential in the field of depression treatment.
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Affiliation(s)
- Lijin Feng
- Department of Pharmacology, Shenyang Pharmaceutical University, Shenyang 110016, China
| | - Hang Xing
- Department of Pharmacology, Shenyang Pharmaceutical University, Shenyang 110016, China.
| | - Kuo Zhang
- Department of Pharmacology, Shenyang Pharmaceutical University, Shenyang 110016, China; Tianjin UBasio Biotechnology Group, Tianjin 300457, China.
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Wu Q, Duan WZ, Chen JB, Zhao XP, Li XJ, Liu YY, Ma QY, Xue Z, Chen JX. Extracellular Vesicles: Emerging Roles in Developing Therapeutic Approach and Delivery Tool of Chinese Herbal Medicine for the Treatment of Depressive Disorder. Front Pharmacol 2022; 13:843412. [PMID: 35401216 PMCID: PMC8988068 DOI: 10.3389/fphar.2022.843412] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/25/2021] [Accepted: 02/28/2022] [Indexed: 01/29/2023] Open
Abstract
Extracellular vesicles (EVs) are lipid bilayer-delimited particles released by cells, which play an essential role in intercellular communication by delivering cellular components including DNA, RNA, lipids, metabolites, cytoplasm, and cell surface proteins into recipient cells. EVs play a vital role in the pathogenesis of depression by transporting miRNA and effector molecules such as BDNF, IL34. Considering that some herbal therapies exhibit antidepressant effects, EVs might be a practical delivery approach for herbal medicine. Since EVs can cross the blood-brain barrier (BBB), one of the advantages of EV-mediated herbal drug delivery for treating depression with Chinese herbal medicine (CHM) is that EVs can transfer herbal medicine into the brain cells. This review focuses on discussing the roles of EVs in the pathophysiology of depression and outlines the emerging application of EVs in delivering CHM for the treatment of depression.
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Affiliation(s)
- Qian Wu
- School of Traditional Chinese Medicine, Beijing University of Chinese Medicine, Beijing, China
- Division of Neurobiology, Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, MD, United States
| | - Wen-Zhen Duan
- Division of Neurobiology, Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, MD, United States
- The Solomon H Snyder Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, MD, United States
- Program in Cellular and Molecular Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, United States
| | - Jian-Bei Chen
- School of Traditional Chinese Medicine, Beijing University of Chinese Medicine, Beijing, China
| | - Xiao-Peng Zhao
- School of Traditional Chinese Medicine, Beijing University of Chinese Medicine, Beijing, China
| | - Xiao-Juan Li
- Guangzhou Key Laboratory of Formula-Pattern of Traditional Chinese Medicine, School of Traditional Chinese Medicine, Jinan University, Guangzhou, China
| | - Yue-Yun Liu
- School of Traditional Chinese Medicine, Beijing University of Chinese Medicine, Beijing, China
| | - Qing-Yu Ma
- Guangzhou Key Laboratory of Formula-Pattern of Traditional Chinese Medicine, School of Traditional Chinese Medicine, Jinan University, Guangzhou, China
| | - Zhe Xue
- School of Traditional Chinese Medicine, Beijing University of Chinese Medicine, Beijing, China
| | - Jia-Xu Chen
- School of Traditional Chinese Medicine, Beijing University of Chinese Medicine, Beijing, China
- Guangzhou Key Laboratory of Formula-Pattern of Traditional Chinese Medicine, School of Traditional Chinese Medicine, Jinan University, Guangzhou, China
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Lu J, Wang X, Wu A, Cao Y, Dai X, Liang Y, Li X. Ginsenosides in central nervous system diseases: Pharmacological actions, mechanisms, and therapeutics. Phytother Res 2022; 36:1523-1544. [PMID: 35084783 DOI: 10.1002/ptr.7395] [Citation(s) in RCA: 22] [Impact Index Per Article: 7.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/21/2021] [Revised: 01/04/2022] [Accepted: 01/08/2022] [Indexed: 12/11/2022]
Abstract
The nervous system is one of the most complex physiological systems, and central nervous system diseases (CNSDs) are serious diseases that affect human health. Ginseng (Panax L.), the root of Panax species, are famous Chinese herbs that have been used for various diseases in China, Japan, and Korea since ancient times, and remain a popular natural medicine used worldwide in modern times. Ginsenosides are the main active components of ginseng, and increasing evidence has demonstrated that ginsenosides can prevent CNSDs, including neurodegenerative diseases, memory and cognitive impairment, cerebral ischemia injury, depression, brain glioma, multiple sclerosis, which has been confirmed in numerous studies. Therefore, this review summarizes the potential pathways by which ginsenosides affect the pathogenesis of CNSDs mainly including antioxidant effects, anti-inflammatory effects, anti-apoptotic effects, and nerve protection, which provides novel ideas for the treatment of CNSDs.
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Affiliation(s)
- Jing Lu
- School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, China
| | - Xian Wang
- School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, China
| | - Anxin Wu
- School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, China
| | - Yi Cao
- School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, China
| | - Xiaolin Dai
- School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, China
| | - Youdan Liang
- School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, China
| | - Xiaofang Li
- School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, China
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Wang X, Yuan W, Xu M, Su X, Li F. Visualization of Acute Inflammation through a Macrophage-Camouflaged Afterglow Nanocomplex. ACS APPLIED MATERIALS & INTERFACES 2022; 14:259-267. [PMID: 34957836 DOI: 10.1021/acsami.1c19388] [Citation(s) in RCA: 10] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/14/2023]
Abstract
Acute inflammation is a basic innate, immediate, and stereotyped immune response to injury, which is characterized by rapid recruitment of immune cells to the vasculature and extravasation into the damaged parenchyma. Visualization of acute inflammation plays an important role in monitoring the disease course and understanding pathogenesis, which lacks specific targeted and observing tools in vivo. Here, we report a Trojan horse strategy of a macrophage-camouflaged afterglow nanocomplex (UCANPs@RAW) to specifically visualize acute inflammation. Due to the advantages of optical antibackground interference elimination, as well as particular immune homing and long-term tracking capacity, UCANPs@RAW demonstrates an excellent acute inflammatory recognition ability. In an arthritis model, previously intravenously injected UCANPs@RAW could directionally migrate from the liver to the inflammation site as soon as 3 h after the model was induced, which could be continuously lighted for at least 36 h with the highest imaging signal-to-background ratio (SBR) as 382 at the time point of 9 h. Additionally, UCANPs@RAW is observed to penetrate the blood-brain barrier and image the deep brain inflamed region covered by the thick skull in an acute brain inflammation model with an SBRmax of 258, which is based on the strong recruiting ability of macrophages to immune response. In view of this smart nanocomplex, our strategy holds great potential for inflammatory detection and treatments.
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Affiliation(s)
- Xiu Wang
- Department of Chemistry, Fudan University, 2005 Songhu Road, Shanghai 200438, P. R. China
| | - Wei Yuan
- Department of Chemistry, Fudan University, 2005 Songhu Road, Shanghai 200438, P. R. China
| | - Ming Xu
- Department of Chemistry, Fudan University, 2005 Songhu Road, Shanghai 200438, P. R. China
| | - Xianlong Su
- Department of Chemistry, Fudan University, 2005 Songhu Road, Shanghai 200438, P. R. China
| | - Fuyou Li
- Department of Chemistry, Fudan University, 2005 Songhu Road, Shanghai 200438, P. R. China
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Li M, Wang X, Wang Y, Bao S, Chang Q, Liu L, Zhang S, Sun L. Strategies for Remodeling the Tumor Microenvironment Using Active Ingredients of Ginseng-A Promising Approach for Cancer Therapy. Front Pharmacol 2022; 12:797634. [PMID: 35002732 PMCID: PMC8727883 DOI: 10.3389/fphar.2021.797634] [Citation(s) in RCA: 18] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/21/2021] [Accepted: 12/06/2021] [Indexed: 12/21/2022] Open
Abstract
The tumor microenvironment (TME) plays a key role in promoting the initiation and progression of tumors, leading to chemoradiotherapy resistance and immunotherapy failure. Targeting of the TME is a novel anti-tumor therapeutic approach and is currently a focus of anti-tumor research. Panax ginseng C. A. Meyer (ginseng), an ingredient of well-known traditional Asia medicines, exerts beneficial anti-tumor effects and can regulate the TME. Here, we present a systematic review that describes the current status of research efforts to elucidate the functions and mechanisms of ginseng active components (including ginsenosides and ginseng polysaccharides) for achieving TME regulation. Ginsenosides have variety effects on TME, such as Rg3, Rd and Rk3 can inhibit tumor angiogenesis; Rg3, Rh2 and M4 can regulate the function of immune cells; Rg3, Rd and Rg5 can restrain the stemness of cancer stem cells. Ginseng polysaccharides (such as red ginseng acidic polysaccharides and polysaccharides extracted from ginseng berry and ginseng leaves) can regulate TME mainly by stimulating immune cells. In addition, we propose a potential mechanistic link between ginseng-associated restoration of gut microbiota and the tumor immune microenvironment. Finally, we describe recent advances for improving ginseng efficacy, including the development of a nano-drug delivery system. Taken together, this review provides novel perspectives on potential applications for ginseng active ingredients as anti-cancer adjuvants that achieve anti-cancer effects by reshaping the tumor microenvironment.
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Affiliation(s)
- Mo Li
- Department of Radiotherapy, The Second Hospital of Jilin University, Changchun, China.,Department of Thyroid Surgery, The Second Hospital of Jilin University, Changchun, China
| | - Xin Wang
- Department of Neurology, China-Japan Union Hospital of Jilin University, Changchun, China
| | - Ying Wang
- Department of Breast Surgery, The Second Hospital of Jilin University, Changchun, China
| | - Shunchao Bao
- Department of Radiotherapy, The Second Hospital of Jilin University, Changchun, China
| | - Qing Chang
- Department of Radiotherapy, The Second Hospital of Jilin University, Changchun, China
| | - Linlin Liu
- Department of Radiotherapy, The Second Hospital of Jilin University, Changchun, China
| | - Shuai Zhang
- Jilin Ginseng Academy, Changchun University of Chinese Medicine, Changchun, China
| | - Liwei Sun
- Research Center of Traditional Chinese Medicine, The Affiliated Hospital to Changchun University of Chinese Medicine, Changchun, China
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Abstract
The gut microbiome produces chemically diverse small molecules to interact with the host, conveying signals from the gut to the whole system. The microbial metabolites feature several unique modes of interaction with host targets, which fits well into the balanced and networked fashion of biological regulation. Hence, fully unveiling the targetome of signaling microbial metabolites may offer new insights into host health and disease, expand the repertoire of druggable targets, and enlighten a bioinspired path to drug design and discovery. In this review, we present an updated understanding of how microbial metabolite interaction with host targets finely orchestrates and integrates multiple signals to pathophysiological phenotypes, contributing new insights into organ crosstalk and holistic homeostasis maintenance in biological systems. We discuss strategies and open questions for mining and biomimicking the microbial metabolite-targetome interactions for pharmacological manipulation, which may lead to a new paradigm of drug discovery.
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Affiliation(s)
- Xiao Zheng
- State Key Laboratory of Natural Medicines, School of Pharmacy, China Pharmaceutical University, Nanjing 210009, China
| | - Xiaoying Cai
- State Key Laboratory of Natural Medicines, School of Pharmacy, China Pharmaceutical University, Nanjing 210009, China
| | - Haiping Hao
- State Key Laboratory of Natural Medicines, School of Pharmacy, China Pharmaceutical University, Nanjing 210009, China.
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Sng KS, Li G, Zhou LY, Song YJ, Chen XQ, Wang YJ, Yao M, Cui XJ. Ginseng extract and ginsenosides improve neurological function and promote antioxidant effects in rats with spinal cord injury: A meta-analysis and systematic review. J Ginseng Res 2022; 46:11-22. [PMID: 35058723 PMCID: PMC8753526 DOI: 10.1016/j.jgr.2021.05.009] [Citation(s) in RCA: 19] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/30/2020] [Revised: 04/26/2021] [Accepted: 05/31/2021] [Indexed: 02/07/2023] Open
Abstract
Spinal cord injury (SCI) is defined as damage to the spinal cord that temporarily or permanently changes its function. There is no definite treatment established for neurological complete injury patients. This study investigated the effect of ginseng extract and ginsenosides on neurological recovery and antioxidant efficacies in rat models following SCI and explore the appropriate dosage. Searches were done on PubMed, Embase, and Chinese databases, and animal studies matches the inclusion criteria were selected. Pair-wise meta-analysis and subgroup analysis were performed. Ten studies were included, and the overall methodological qualities were low quality. The result showed ginseng extract and ginsenosides significantly improve neurological function, through the Basso, Beattie, and Bresnahan (BBB) locomotor rating scale (pooled MD = 4.40; 95% CI = 3.92 to 4.88; p < 0.00001), significantly decrease malondialdehyde (MDA) (n = 290; pooled MD = −2.19; 95% CI = −3.16 to −1.22; p < 0.0001) and increase superoxide dismutase (SOD) levels (n = 290; pooled MD = 2.14; 95% CI = 1.45 to 2.83; p < 0.00001). Both low (<25 mg/kg) and high dosage (≥25 mg/kg) showed significant improvement in the motor function recovery in SCI rats. Collectively, this review suggests ginseng extract and ginsenosides has a protective effect on SCI, with good safety and a clear mechanism of action and may be suitable for future clinical trials and applications.
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Zheng QL, Zhu HY, Xu X, Chu SF, Cui LY, Dong YX, Liu YJ, Zhan JH, Wang ZZ, Chen NH. Korean red ginseng alleviate depressive disorder by improving astrocyte gap junction function. JOURNAL OF ETHNOPHARMACOLOGY 2021; 281:114466. [PMID: 34332064 DOI: 10.1016/j.jep.2021.114466] [Citation(s) in RCA: 12] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 12/12/2019] [Revised: 06/28/2021] [Accepted: 07/25/2021] [Indexed: 06/13/2023]
Abstract
ETHNOPHARMACOLOGICAL RELEVANCE Korean red ginseng (KRG), a processed product of Panax ginseng C. A. Mey, show significant anti-depressive effect in clinic. However, its mechanism is still unclear. AIM OF THE STUDY Gap junction intercellular communication (GJIC) dysfunction is a potential pathogenesis of depression. Therefore, this study's objective is to investigate whether the antidepressant effect of KRG is related to GJIC. MATERIALS AND METHODS Rat were restraint 8 h every day for 28 consecutive days to prepare depression models, and meanwhile, rats were intragastrically administrated with normal saline, KRG solutions (25, 50 or 100 mg/kg) or fluoxetine (10 mg/kg) 1 h before stress. The behavioral performance was determined by forced swimming test, sucrose preference test and open field test. GJIC was determined by the Lucifer yellow (LY) diffusion distance in prelimb cortex (PLC). In addition, the level of Cx43, one of executors of GJIC, was tested by Western blot. To find out the protective effect of KRG against GJIC dysfunction directly, rats were intracranially injected with carbenoxolone (CBX, blocker of GJIC), and meanwhile normal saline, KRG (100 mg/kg) or fluoxetine (10 mg/kg) was administered daily. The behavioral performance of these rats was detected, and the LY localization injection PLC area was used to detect the gap junction function. RESULTS Chronic resistant stress (CRS) induced depressive symptoms, as manifested by prolonged immobility time in forced swimming test and decreased sucrose consumption ratio. Administration of KRG alleviated these depressive symptoms significantly. GJIC determination showed that KRG improved the LY diffusion and increased Cx43 level in prefrontal cortex (PFC) significantly, indicated that GJIC dysfunction was alleviated by the treatment of KRG. However, the astrocytes number was also increased by the treatment of KRG, which maybe alleviate depression-like symptoms by increasing the number of astrocytes rather than improving GJIC. Injection of CBX produced depressive symptoms and GJIC dysfunction, as manifested by decreased sucrose consumption ratio and prolonged immobility time in forced swimming test, but no astrocytes number changes, KRG also reversed depressive symptoms and GJIC dysfunction, suggested that the improvement of depressive-like symptoms was improved by GJIC. CONCLUSIONS KRG alleviate depressive disorder by improving astrocytic gap junction function.
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Affiliation(s)
- Qing-Lian Zheng
- Institute for Brain Research and Rehabilitation (IBRR), South China Normal University (SCNU), Guangzhou, 510631, China.
| | - Hao-Yu Zhu
- State Key Laboratory of Bioactive Substances and Functions of Natural Medicines, Institute of Materia Medica & Neuroscience Center, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100050, China.
| | - Xin Xu
- Institute for Brain Research and Rehabilitation (IBRR), South China Normal University (SCNU), Guangzhou, 510631, China.
| | - Shi-Feng Chu
- State Key Laboratory of Bioactive Substances and Functions of Natural Medicines, Institute of Materia Medica & Neuroscience Center, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100050, China.
| | - Li-Yuan Cui
- State Key Laboratory of Bioactive Substances and Functions of Natural Medicines, Institute of Materia Medica & Neuroscience Center, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100050, China.
| | - Yi-Xiao Dong
- State Key Laboratory of Bioactive Substances and Functions of Natural Medicines, Institute of Materia Medica & Neuroscience Center, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100050, China.
| | - Ying-Jiao Liu
- Hunan University of Chinese Medicine & Hunan Engineering Technology Center of Standardization and Function of Chinese Herbal Decoction Pieces, Changsha 410208 Hunan, China.
| | - Jia-Hong Zhan
- DME Center, Clinical Pharmacology Institute, Guangzhou University of Chinese Medicine, Guangzhou, 510405, China.
| | - Zhen-Zhen Wang
- State Key Laboratory of Bioactive Substances and Functions of Natural Medicines, Institute of Materia Medica & Neuroscience Center, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100050, China.
| | - Nai-Hong Chen
- Institute for Brain Research and Rehabilitation (IBRR), South China Normal University (SCNU), Guangzhou, 510631, China; State Key Laboratory of Bioactive Substances and Functions of Natural Medicines, Institute of Materia Medica & Neuroscience Center, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100050, China; Hunan University of Chinese Medicine & Hunan Engineering Technology Center of Standardization and Function of Chinese Herbal Decoction Pieces, Changsha 410208 Hunan, China; DME Center, Clinical Pharmacology Institute, Guangzhou University of Chinese Medicine, Guangzhou, 510405, China.
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miR-182 mediated the inhibitory effects of NF-κB on the GPR39/CREB/BDNF pathway in the hippocampus of mice with depressive-like behaviors. Behav Brain Res 2021; 418:113647. [PMID: 34743948 DOI: 10.1016/j.bbr.2021.113647] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/01/2021] [Revised: 09/26/2021] [Accepted: 10/27/2021] [Indexed: 12/17/2022]
Abstract
BACKGROUND Chronic stress is one of the most important causes of depression, accompanied by neuroinflammation and hippocampal injuries. Long-term elevation of glucocorticoid leads to activation of NF-κB and inhibition of GPR39/CREB/BDNF pathway, which is pivotal for neuroprotection and neurogenesis. The present study thus was designed to determine the relationship between NF-κB and GPR39/CREB/BDNF pathway. METHODS Depressive-like behaviors were induced by chronic unpredictable mild stress (CUMS) and chronic restraint stress (CRS) in mice. Corticosterone, inflammatory cytokines, and GPR39/CREB/BDNF pathway were determined by ELISA and Western Blot assays. The activation of NF-κB and inhibition of GPR39 were connected by bioinformatic analysis and experimentally validated in hippocampus cells by knock-in and knock-down techniques. RESULTS CUMS and CRS led to an elevation of serum corticosterone and depressive-like behaviors in mice, with activation of NF-κB subunit p65 in the hippocampus and elevations of TNFα and IL-6. The expression of GPR39/CREB/BDNF pathway in the hippocampus was inhibited. Bioinformatic analysis revealed that four miRNAs, miR-96, miR-143, miR-150, and miR-182, were potentially transcribed by NF-κB and bound with GPR39 mRNA. NF-κB overexpression increased miR-182 expression and decreased GPR39 expression in hippocampus cells. Its inhibitor led to reverse effects. miR-182 mimics or inhibitors also regulated GPR39 expression in hippocampus cells and more importantly, blocked the regulation of NF-κB on GPR39. CONCLUSIONS The results suggested that activation of NF-κB inhibited GPR39/CREB/BDNF pathway through increasing miR-182 in chronic stress-induced depressive-like behaviors. The negative-regulation features of miRNAs might be important for neuroinflammation-induced inhibition of neurofunction in depression.
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Song L, Wu X, Wang J, Guan Y, Zhang Y, Gong M, Wang Y, Li B. Antidepressant effect of catalpol on corticosterone-induced depressive-like behavior involves the inhibition of HPA axis hyperactivity, central inflammation and oxidative damage probably via dual regulation of NF-κB and Nrf2. Brain Res Bull 2021; 177:81-91. [PMID: 34500039 DOI: 10.1016/j.brainresbull.2021.09.002] [Citation(s) in RCA: 30] [Impact Index Per Article: 7.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/25/2021] [Revised: 09/02/2021] [Accepted: 09/03/2021] [Indexed: 12/24/2022]
Abstract
This study aimed to investigate the antidepressant effect and mechanism of catalpol on corticosterone (CORT)-induced depressive-like behavior in mice for the first time. As a result, CORT injection induced depressive-like behaviors of mice in behavioral tests, aggravated the serum CORT, adrenocorticotropic hormone, and corticotropin-releasing hormone levels, and conspicuously elevated the phosphorylations of nuclear factor kappa-B (NF-κB) in the hippocampus and frontal cortex, and down-regulated the expression levels of nuclear factor erythroid-2-related factor 2 (Nrf2). Furthermore, CORT exposure dramatically augmented the levels of inflammatory factors (interleukin-1β, tumor necrosis factor-α, nitric oxide synthase, and nitric oxide) and lipid peroxidation product malondialdehyde, and attenuated the levels of antioxidants including reduced glutathione, glutathione S-transferase, total superoxide dismutase, and heme oxygenase-1 in the mouse hippocampus and frontal cortex. On the contrary, catalpol administration markedly suppressed the abnormalities of the above indicators. From the overall results, this study displayed that catalpol exerted a beneficial effect on CORT-induced depressive-like behavior in mice possibly via the inhibition of hypothalamus-pituitary-adrenal (HPA) axis hyperactivity, central inflammation and oxidative damage at least partially through dual regulation of NF-κB and Nrf2.
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Affiliation(s)
- Lingling Song
- College of Pharmacy, Henan University of Chinese Medicine, Zhengzhou, 450046, China
| | - Xiaohui Wu
- College of Pharmacy, Henan University of Chinese Medicine, Zhengzhou, 450046, China
| | - Junming Wang
- College of Pharmacy, Henan University of Chinese Medicine, Zhengzhou, 450046, China; Co-construction Collaborative Innovation Center for Chinese Medicine and Respiratory Diseases by Henan & Education Ministry of P.R. China, Henan University of Chinese Medicine, Zhengzhou, 450046, China.
| | - Yuechen Guan
- College of Pharmacy, Henan University of Chinese Medicine, Zhengzhou, 450046, China
| | - Yueyue Zhang
- College of Pharmacy, Henan University of Chinese Medicine, Zhengzhou, 450046, China
| | - Mingzhu Gong
- College of Pharmacy, Henan University of Chinese Medicine, Zhengzhou, 450046, China
| | - Yanmei Wang
- College of Pharmacy, Henan University of Chinese Medicine, Zhengzhou, 450046, China
| | - Bingyin Li
- College of Pharmacy, Henan University of Chinese Medicine, Zhengzhou, 450046, China
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Han Y, Wang T, Li C, Wang Z, Zhao Y, He J, Fu L, Han B. Ginsenoside Rg3 exerts a neuroprotective effect in rotenone-induced Parkinson's disease mice via its anti-oxidative properties. Eur J Pharmacol 2021; 909:174413. [PMID: 34391769 DOI: 10.1016/j.ejphar.2021.174413] [Citation(s) in RCA: 25] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/05/2021] [Revised: 07/24/2021] [Accepted: 08/06/2021] [Indexed: 01/05/2023]
Abstract
Ginsenoside Rg3, extracted from Panax ginseng C.A. Meyer, has been shown to possess neuroprotective properties. The present study aims to investigate the neuroprotective effects of ginsenoside Rg3 on rotenone-induced Parkinson's disease mice. Rotenone, a mitochondrial complex I inhibitor, leads to the augmentation of reactive oxygen species production in cells. Male C57/BL6 mice were intragastrically administered rotenone (30 mg/kg) and then treated with ginsenoside Rg3 (5, 10, or 20 mg/kg). Pole, rotarod, and open field tests were performed to evaluate motor function. Ginsenoside Rg3 decreased the climbing time in the pole test (p < 0.01), whereas it increased the latency in the rotarod test (p < 0.01) and the total distance (p < 0.01) and mean speed in the open field test (p < 0.01). Ginsenoside Rg3 treatment augmented the number of tyrosine hydroxylase-positive neurons in the substantia nigra (p < 0.01), mean density of tyrosine hydroxylase-positive nerve fibers (p < 0.01), and dopamine content (p < 0.01) in the striatum and reduced the reactive oxygen species level in the substantia nigra (p < 0.01). Glutathione cysteine ligase regulatory subunit and glutathione cysteine ligase modulatory subunit expression levels were elevated in the ginsenoside Rg3 groups. Ginsenoside Rg3 also improved motor function in rotenone-induced Parkinson's disease mice. The neuroprotective effects of ginsenoside Rg3 are at least partly associated with its anti-oxidative properties via regulation of glutathione cysteine ligase modulatory subunit and glutathione cysteine ligase regulatory subunit expression.
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Affiliation(s)
- Yingjie Han
- Center for Mitochondria and Healthy Aging, College of Life Science, Yantai University, Yantai, 264005, PR China
| | - Tian Wang
- School of Pharmacy, Yantai University, Yantai, Shandong, 264005, PR China
| | - Chunyan Li
- Center for Mitochondria and Healthy Aging, College of Life Science, Yantai University, Yantai, 264005, PR China
| | - Zhenhua Wang
- Center for Mitochondria and Healthy Aging, College of Life Science, Yantai University, Yantai, 264005, PR China
| | - Yue Zhao
- Center for Mitochondria and Healthy Aging, College of Life Science, Yantai University, Yantai, 264005, PR China
| | - Jie He
- Center for Mitochondria and Healthy Aging, College of Life Science, Yantai University, Yantai, 264005, PR China
| | - Li Fu
- Dalian Fusheng Natural Medicine Development Co., Ltd, Dalian, 116600, PR China.
| | - Bing Han
- Center for Mitochondria and Healthy Aging, College of Life Science, Yantai University, Yantai, 264005, PR China.
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Ren B, Feng J, Yang N, Guo Y, Chen C, Qin Q. Ginsenoside Rg3 attenuates angiotensin II-induced myocardial hypertrophy through repressing NLRP3 inflammasome and oxidative stress via modulating SIRT1/NF-κB pathway. Int Immunopharmacol 2021; 98:107841. [PMID: 34153662 DOI: 10.1016/j.intimp.2021.107841] [Citation(s) in RCA: 45] [Impact Index Per Article: 11.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/28/2020] [Revised: 05/09/2021] [Accepted: 05/30/2021] [Indexed: 10/21/2022]
Abstract
BACKGROUND Ginsenoside Rg3 (Rg3), one of the most potent components extracted from the roots of the traditional Chinese herb Panax ginseng, has prominent roles in anti-tumor and anti-inflammation. However, the applications of Rg3 against myocardial hypertrophy are not fully revealed. METHODS Transverse aortic constriction (TAC) was adopted to build the myocardial hypertrophy model in rats. The in vitro model of myocardial hypertrophy was induced by angiotensin II (Ang II) in the human cardiomyocyte cell line AC16 and HCM, which were then treated with different doses of Rg3. The levels of myocardial hypertrophy markers (ANP, BNP, and β-MHC) were detected by quantitative real-time polymerase chain reaction (qRT-PCR). Western blot (WB) was conducted to verify the expressions of myocardial fibrosis-associated proteins (MyHc, Collagen Ⅰ, and TGF-β1) and oxidative stress (OS) proteins (HO-1 and Nrf2). The markers of fibrosis, hypertrophy, NLRP3 inflammasome and OS in cardiomyocytes were evaluated by qRT-PCR, western blot (WB), enzyme-linked immunosorbent assay (ELISA), and cellular immunofluorescence, respectively. Furthermore, pharmacological intervention on sirtuin-1 (SIRT1) was performed to clarify the function of SIRT1 in Rg3-mediated effects. RESULTS Rg3 dose-dependently attenuated the Ang II-induced myocardial hypertrophy and fibrosis. What's more, Rg3 markedly inhibited NLRP3-ASC-Caspase1 inflammasome and OS (reflected by SOD, MDA, HO-1, and Nrf2) in cardiomyocytes treated with Ang II. Mechanistically, Rg3 attenuated NF-κB activation and promoted SIRT1 expression. Inhibiting SIRT1 (by AGK2) mostly reversed Rg3-mediated effects against Ang II-induced myocardial hypertrophy and fibrosis. In the TAC rat model, administration of Rg3 mitigated myocardial hypertrophy and fibrosis through pressing overproduced inflammation and OS. CONCLUSION Rg3 prevents Ang II-induced myocardial hypertrophy via inactivating NLRP3 inflammasome and oxidative stress by modulating the SIRT1/NF-κB pathway.
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Affiliation(s)
- Bei Ren
- Department of Cardiology, Tianjin Chest Hospital, Tianjin, China
| | - Jinping Feng
- Department of Cardiology, Tianjin Chest Hospital, Tianjin, China
| | - Ning Yang
- Department of Cardiology, Tianjin Chest Hospital, Tianjin, China
| | - Yujun Guo
- Department of Cardiology, Tianjin Chest Hospital, Tianjin, China
| | - Cheng Chen
- Chengde Medical College Physiology Department, Tianjin, China
| | - Qin Qin
- Department of Cardiology, Tianjin Chest Hospital, Tianjin, China.
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Catorce MN, Gevorkian G. Evaluation of Anti-inflammatory Nutraceuticals in LPS-induced Mouse Neuroinflammation Model: An Update. Curr Neuropharmacol 2021; 18:636-654. [PMID: 31934839 PMCID: PMC7457421 DOI: 10.2174/1570159x18666200114125628] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/11/2019] [Revised: 11/26/2019] [Accepted: 01/11/2020] [Indexed: 02/08/2023] Open
Abstract
It is known that peripheral infections, accompanied by inflammation, represent significant risk factors for the development of neurological disorders by modifying brain development or affecting normal brain aging. The acute effects of systemic inflammation on progressive and persistent brain damage and cognitive impairment are well documented. Anti-inflammatory therapies may have beneficial effects on the brain, and the protective properties of a wide range of synthetic and natural compounds have been extensively explored in recent years. In our previous review, we provided an extensive analysis of one of the most important and widely-used animal models of peripherally induced neuroinflammation and neurodegeneration - lipopolysaccharide (LPS)-treated mice. We addressed the data reproducibility in published research and summarized basic features and data on the therapeutic potential of various natural products, nutraceuticals, with known anti-inflammatory effects, for reducing neuroinflammation in this model. Here, recent data on the suitability of the LPS-induced murine neuroinflammation model for preclinical assessment of a large number of nutraceuticals belonging to different groups of natural products such as flavonoids, terpenes, non-flavonoid polyphenols, glycosides, heterocyclic compounds, organic acids, organosulfur compounds and xanthophylls, are summarized. Also, the proposed mechanisms of action of these molecules are discussed.
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Affiliation(s)
- Miryam Nava Catorce
- Instituto de Investigaciones Biomedicas, Universidad Nacional Autonoma de Mexico (UNAM), Mexico DF, Mexico
| | - Goar Gevorkian
- Instituto de Investigaciones Biomedicas, Universidad Nacional Autonoma de Mexico (UNAM), Mexico DF, Mexico
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Analysis of the hotspots and trends in traditional Chinese medicine immunomodulation research based on bibliometrics. DIGITAL CHINESE MEDICINE 2021. [DOI: 10.1016/j.dcmed.2021.06.002] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/29/2022] Open
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Kim Y, Cho SH. The effect of ginsenosides on depression in preclinical studies: A systematic review and meta-analysis. J Ginseng Res 2021; 45:420-432. [PMID: 34025135 PMCID: PMC8134838 DOI: 10.1016/j.jgr.2020.08.006] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/16/2020] [Revised: 08/15/2020] [Accepted: 08/31/2020] [Indexed: 01/27/2023] Open
Abstract
BACKGROUND Many ginsenosides have been shown to be efficacious for major depressive disorder (MDD), which is a highly recurrent disorder, through several preclinical studies. We aimed to review the literature assessing the antidepressant effects of ginsenosides on MDD animal models, to establish systematic scientific evidence in a rigorous manner. METHODS We performed a systematic review on the antidepressant effects of ginsenoside evaluated in in vivo studies. We searched for preclinical trials from inception to July 2019 in electronic databases such as Pubmed and Embase. In vivo studies examining the effect of a single ginsenoside on animal models of primary depression were included. Items of each study were evaluated by two independent reviewers. A meta-analysis was conducted to assess behavioral changes induced by ginsenoside Rg1, which was the most studied ginsenoside. Data were pooled using the random-effects models. RESULTS A total of 517 studies were identified, and 23 studies were included in the final analysis. They reported on many ginsenosides with different antidepressant effects and biological mechanisms of action. Of the 12 included articles assessing ginsenoside Rg1, pooled results of forced swimming test from 9 articles (mean difference (MD): 20.50, 95% CI: 16.13-24.87), and sucrose preference test from 11 articles (MD: 28.29, 95% CI: 22.90-33.69) showed significant differences compared with vehicle treatment. The risk of bias of each study was moderate, but there was significant heterogeneity across studies. CONCLUSION These estimates suggest that ginsenosides, including ginsenoside Rg1, reduces symptoms of depression, modulates underlying mechanisms, and can be a promising antidepressant.
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Affiliation(s)
- Yunna Kim
- College of Korean Medicine, Kyung Hee University, Seoul, Republic of Korea
- Research group of Neuroscience, East-West Medical Research Institute, WHO Collaborating Center, Kyung Hee University, Seoul, Republic of Korea
- Department of Clinical Korean Medicine, Graduate School, Kyung Hee University, Seoul, Republic of Korea
| | - Seung-Hun Cho
- College of Korean Medicine, Kyung Hee University, Seoul, Republic of Korea
- Research group of Neuroscience, East-West Medical Research Institute, WHO Collaborating Center, Kyung Hee University, Seoul, Republic of Korea
- Department of Clinical Korean Medicine, Graduate School, Kyung Hee University, Seoul, Republic of Korea
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Dal-Pizzol F, de Medeiros GF, Michels M, Mazeraud A, Bozza FA, Ritter C, Sharshar T. What Animal Models Can Tell Us About Long-Term Psychiatric Symptoms in Sepsis Survivors: a Systematic Review. Neurotherapeutics 2021; 18:1393-1413. [PMID: 33410107 PMCID: PMC8423874 DOI: 10.1007/s13311-020-00981-9] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 11/23/2020] [Indexed: 02/06/2023] Open
Abstract
Lower sepsis mortality rates imply that more patients are discharged from the hospital, but sepsis survivors often experience sequelae, such as functional disability, cognitive impairment, and psychiatric morbidity. Nevertheless, the mechanisms underlying these long-term disabilities are not fully understood. Considering the extensive use of animal models in the study of the pathogenesis of neuropsychiatric disorders, it seems adopting this approach to improve our knowledge of postseptic psychiatric symptoms is a logical approach. With the purpose of gathering and summarizing the main findings of studies using animal models of sepsis-induced psychiatric symptoms, we performed a systematic review of the literature on this topic. Thus, 140 references were reviewed, and most of the published studies suggested a time-dependent recovery from behavior alterations, despite the fact that some molecular alterations persist in the brain. This review reveals that animal models can be used to understand the mechanisms that underlie anxiety and depression in animals recovering from sepsis.
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Affiliation(s)
- Felipe Dal-Pizzol
- Laboratório de Fisiopatologia Experimental, Programa de Pós-Graduação em Ciências da Saúde, Universidade do Extremo Sul Catarinense, 88806-000 Criciúma, Brazil
| | | | - Monique Michels
- Laboratório de Fisiopatologia Experimental, Programa de Pós-Graduação em Ciências da Saúde, Universidade do Extremo Sul Catarinense, 88806-000 Criciúma, Brazil
| | - Aurélien Mazeraud
- Laboratory of Experimental Neuropathology, Institut Pasteur, 75015 Paris, France
| | - Fernando Augusto Bozza
- Laboratório de Medicina Intensiva, Instituto Nacional de Infectologia Evandro Chagas (INI), Fundação Oswaldo Cruz (FIOCRUZ), 21040-360 Rio de Janeiro, Brazil
| | - Cristiane Ritter
- Laboratório de Fisiopatologia Experimental, Programa de Pós-Graduação em Ciências da Saúde, Universidade do Extremo Sul Catarinense, 88806-000 Criciúma, Brazil
| | - Tarek Sharshar
- Laboratoire de Neuropathologie Expérimentale, Institut Pasteur, 75015 Paris, France
- Laboratory of Experimental Neuropathology, Institut Pasteur, 75015 Paris, France
- Department of Neuro-Intensive Care Medicine, Sainte-Anne Hospital, Paris-Descartes University, 75015 Paris, France
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Qu S, Liu M, Cao C, Wei C, Meng XE, Lou Q, Wang B, Li X, She Y, Wang Q, Song Z, Han Z, Zhu Y, Huang F, Duan JA. Chinese Medicine Formula Kai-Xin-San Ameliorates Neuronal Inflammation of CUMS-Induced Depression-like Mice and Reduces the Expressions of Inflammatory Factors via Inhibiting TLR4/IKK/NF-κB Pathways on BV2 Cells. Front Pharmacol 2021; 12:626949. [PMID: 33790789 PMCID: PMC8006317 DOI: 10.3389/fphar.2021.626949] [Citation(s) in RCA: 37] [Impact Index Per Article: 9.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/07/2020] [Accepted: 01/25/2021] [Indexed: 12/12/2022] Open
Abstract
Kai-Xin-San (KXS) is a traditional Chinese medicinal formula composed of Ginseng Radix et Rhizoma, Polygalae Radix, Acori Tatarinowii Rhizoma, and Poria for relieving major depressive disorder and Alzheimer's disease in traditional Chinese medicine (TCM) clinics. Previous studies on the antidepressant mechanism of KXS mainly focused on neurotransmitter and neurotrophic factor regulation, but few reports exist on neuronal inflammation regulation. In the current study, we found that KXS exerted antidepressant effects in chronic unpredictable mild stress-induced depression-like mice according to the results of behavioral tests. Meanwhile, KXS also inhibited the activation of microglia and significantly reduced the expression of pro-inflammatory cytokines such as IL-1β, IL-2, and TNF-α in the hippocampus of mice. In mice BV2 microglia cell lines, KXS extract reduced the expression of inflammatory factors in BV2 cells induced by lipopolysaccharide via inhibiting TLR4/IKK/NF-κB pathways, which was also validated by the treatment of signaling pathway inhibitors such as TAK-242 and JSH-23. T0hese data implied that the regulation of pro-inflammatory cytokines in microglia might account for the antidepressant effect of KXS, thereby providing more scientific information for the development of KXS as an alternative therapy for major depressive disorder.
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Affiliation(s)
- Suchen Qu
- Jiangsu Key Laboratory for High Technology Research of TCM Formulae and Jiangsu Collaborative Innovation Center of Chinese Medicinal Resources Industrialization, Nanjing University of Chinese Medicine, Nanjing, China
| | - Mengqiu Liu
- Jiangsu Key Laboratory for High Technology Research of TCM Formulae and Jiangsu Collaborative Innovation Center of Chinese Medicinal Resources Industrialization, Nanjing University of Chinese Medicine, Nanjing, China
| | - Cheng Cao
- Jiangsu Key Laboratory for High Technology Research of TCM Formulae and Jiangsu Collaborative Innovation Center of Chinese Medicinal Resources Industrialization, Nanjing University of Chinese Medicine, Nanjing, China
| | - Chongqi Wei
- Jiangsu Key Laboratory for High Technology Research of TCM Formulae and Jiangsu Collaborative Innovation Center of Chinese Medicinal Resources Industrialization, Nanjing University of Chinese Medicine, Nanjing, China
| | - Xue-Er Meng
- Jiangsu Key Laboratory for High Technology Research of TCM Formulae and Jiangsu Collaborative Innovation Center of Chinese Medicinal Resources Industrialization, Nanjing University of Chinese Medicine, Nanjing, China
| | - Qianyin Lou
- Jiangsu Key Laboratory for High Technology Research of TCM Formulae and Jiangsu Collaborative Innovation Center of Chinese Medicinal Resources Industrialization, Nanjing University of Chinese Medicine, Nanjing, China
| | - Bin Wang
- Jiangsu Key Laboratory for High Technology Research of TCM Formulae and Jiangsu Collaborative Innovation Center of Chinese Medicinal Resources Industrialization, Nanjing University of Chinese Medicine, Nanjing, China
| | - Xuan Li
- Jiangsu Key Laboratory for High Technology Research of TCM Formulae and Jiangsu Collaborative Innovation Center of Chinese Medicinal Resources Industrialization, Nanjing University of Chinese Medicine, Nanjing, China
| | - Yuyan She
- Jiangsu Key Laboratory for High Technology Research of TCM Formulae and Jiangsu Collaborative Innovation Center of Chinese Medicinal Resources Industrialization, Nanjing University of Chinese Medicine, Nanjing, China
| | - Qingqing Wang
- Jiangsu Key Laboratory for High Technology Research of TCM Formulae and Jiangsu Collaborative Innovation Center of Chinese Medicinal Resources Industrialization, Nanjing University of Chinese Medicine, Nanjing, China
| | - Zhichao Song
- Jiangsu Key Laboratory for High Technology Research of TCM Formulae and Jiangsu Collaborative Innovation Center of Chinese Medicinal Resources Industrialization, Nanjing University of Chinese Medicine, Nanjing, China
| | - Zhengxiang Han
- Department of Neurology and Rehabilitation, Shanghai Seventh People's Hospital, Shanghai University of TCM, Shanghai, China
| | - Yue Zhu
- Jiangsu Key Laboratory for High Technology Research of TCM Formulae and Jiangsu Collaborative Innovation Center of Chinese Medicinal Resources Industrialization, Nanjing University of Chinese Medicine, Nanjing, China
| | - Fei Huang
- Department of Endocrinology, Suzhou TCM Hospital Affiliated to Nanjing University of Chinese Medicine, Suzhou, China
| | - Jin-Ao Duan
- Jiangsu Key Laboratory for High Technology Research of TCM Formulae and Jiangsu Collaborative Innovation Center of Chinese Medicinal Resources Industrialization, Nanjing University of Chinese Medicine, Nanjing, China
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Liu QF, Park SW, Kim YM, Song SJ, Chin YW, Pak SC, Jeon S, Koo BS. Administration of Kyung-Ok-Ko reduces stress-induced depressive behaviors in mice through inhibition of inflammation pathway. JOURNAL OF ETHNOPHARMACOLOGY 2021; 265:113441. [PMID: 33027642 DOI: 10.1016/j.jep.2020.113441] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 04/07/2020] [Revised: 09/24/2020] [Accepted: 09/29/2020] [Indexed: 06/11/2023]
Abstract
ETHNOPHARMACOLOGICAL RELEVANCE Kyung-Ok-Ko (KOK), a traditional medicinal formula composed of Rehmannia glutinosa (Gaertn.) DC, Poria cocos (Schw.) Wolf, Korean Red Panax ginseng C.A.Mey, and honey, has been used to treat amnesia and dementia. KOK has also been shown to ameliorate transient cerebral global ischemia-induced brain damage, but the antidepressant-like effect of KOK has not been examined. AIM OF THE STUDY This study examined the antidepressant-like effect of KOK in an immobilization-induced stress mouse and its mechanisms of action. MATERIALS AND METHODS The animals in the stress group were immobilized for two hours a day for two weeks. KOK at a dose of 1 g/kg/day was administered orally to the stressed mice for two weeks in advance of their immobilization. A forced swimming test was performed to analyze their depressive behaviors. To examine the anti-inflammatory or antioxidative effects of KOK, the murine macrophage cell line, RAW 264.7 cells and human neuroblastoma cell, SH-SY5Y cells, were treated with lipopolysaccharide (LPS) and hydrogen peroxide, respectively. RESULT The KOK extract showed no significant toxicity when the cells were treated with a KOK extract at 5, 10, 25, 50, and 100 μg/mL. The KOK ethanol extract reduced LPS-induced TNF-α production, inducible nitric oxide (iNOS) mRNA level, and the levels of MAPK and p38 phosphorylation in RAW 264.7 cells. KOK also suppressed H2O2-induced cell death and the production of reactive oxygen species (ROS) in SH-SY5Y cells. In the forced swimming test, KOK induced a decrease in immobility and an increase in climbing activity. Finally, the administration of KOK reversed the up-regulation of IkB-α phosphorylation in the stressed mouse cortex. CONCLUSION KOK might be useful for the treatment of depression caused by environmental and lifestyle-related stress.
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Affiliation(s)
- Quan Feng Liu
- Department of Oriental Neuropsychiatry, Graduate School of Oriental Medicine, Dongguk University, 814 Siksa-dong, Goyang-si, Gyeonggi-do, 10326, Republic of Korea
| | - Sun-Woo Park
- Yaksan Korean Medical Clinic 302, Dongyang-plaza 533-3, Yatap-dong, Bundang-gu, Seongnam-si, Gyeonggi-do, South Korea
| | - Young-Mi Kim
- College of Pharmacy, Seoul National University, Gwanak-ro, Gwanak-gu, Seoul, 08826, Republic of Korea
| | - Sue-Jin Song
- Department of Oriental Neuropsychiatry, Graduate School of Oriental Medicine, Dongguk University, 814 Siksa-dong, Goyang-si, Gyeonggi-do, 10326, Republic of Korea
| | - Young-Won Chin
- College of Pharmacy, Seoul National University, Gwanak-ro, Gwanak-gu, Seoul, 08826, Republic of Korea
| | - Sok Cheon Pak
- School of Biomedical Sciences, Charles Sturt University, Bathurst, NSW, 2795, Australia
| | - Songhee Jeon
- Department of Biomedical Sciences, Center for Creative Biomedical Scientists at Chonnam National University, Gwangju, 61469, Republic of Korea.
| | - Byung-Soo Koo
- Department of Oriental Neuropsychiatry, Graduate School of Oriental Medicine, Dongguk University, 814 Siksa-dong, Goyang-si, Gyeonggi-do, 10326, Republic of Korea; Department of Korean Neuropsychiatry, Dongguk University Ilsan Hospital, 32, Dongguk-lo, Ilsandong-gu, Goyang, Gyeonggi-do, 10326, Republic of Korea.
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