JOURNAL OF ETHNOPHARMACOLOGY
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2023
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IF 5.4
Pan Su,Mengdi Wu,Xiaoting Yin,Mengyuan Li,Yucheng Li,Ming Bai,Baoying Wang,Erping Xu
Ethnopharmacological relevance Modified Xiaoyao San (MXYS), a clinical empirical modified formula based on famous traditional Chinese herbal prescription Xiaoyao San, according to the “yu syndrome” theory of traditional Chinese medicine . MXYS has been shown to be an excellent effective therapy for depression patients in clinic, but the antidepressant mechanisms remain unclear. Aim of the study A growing body of evidence indicates the microglia autophagy and M1 polarized microglia (proinflammatory phenotype)-mediated neuroinflammation act critical roles in the pathogenesis of depression. This study aimed to investigate whether MXYS exerts antidepressant efficacy through inhibition of M1 polarized microglia-mediated neuroinflammation and modulation of autophagy involved in PI3K/Akt/mTOR pathway. Materials and methods In present research, the lipopolysaccharide (LPS)-induced depressive mice and LPS-stimulated N9 microglia cell line were utilized. Behavioral tests (sucrose preference, tail suspension and open field tests) were carried out to evaluate the antidepressant effect of MXYS. The neuronal damage was measured by Nissl's staining in LPS-treated mice. The proinflammatory cytokine levels, the autophagic markers, microglia M1 polarization as well as the PI3K/Akt/mTOR pathway related proteins of MXYS treatment were analyzed by ELISA kits, Western blot and immunofluorescence staining in vivo and vitro . Finally, the influence of autophagy antagonist (3-MA) on the protective effect of MXYS-containing serum in the LPS-stimulated N9 microglia was investigated. Results Treatment of LPS-induced depressive mice with MXYS significantly reversed depression-like behaviors, accompanied by reduction of proinflammatory cytokine levels (TNF-α, IL-1β) and amelioration of neuronal damage in prefrontal cortex. MXYS suppressed microglia M1 polarization and promoted autophagy in prefrontal cortex and LPS-stimulated N9 cells. Importantly, the remarkable inhibitory effect of the MXYS-medicated serum on microglia M1 polarization was blocked by autophagy antagonist 3-MA in LPS-stimulated N9 cells. Meanwhile, the MXYS treatment exhibited an excellent inhibition effect of PI3K/Akt/mTOR pathway in vivo and vitro . Conclusion Our research suggests that the antidepressant effect of MXYS in LPS-induced depressive mice may be related to alleviate neuroinflammation through suppression of microglia M1 polarization via enhancing autophagy involved in inactivation of the PI3K/Akt/mTOR pathway.
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Materials Express
·
2020
·Vol. 10
·期 12
·1978-1985
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IF 1.65
Zhu Jianjin,Sun Changjiao,Yang Huadong,Xu Zhengkuan
Functional motor recovery in spinal cord injury (SCI) is a highly challenging field in biomedical treatment. Minocycline is an effective drug agent for microtubule inhibition and neurite outgrowth of cultured neurons in SCI treatment. In the present report, a facile drug delivery system
was designed using a chitosan-assisted thermoresponsive polymer to provide sustained release of minocycline from the copolymeric matrix. Additionally, curcumin nanoparticles encapsulated with a copolymeric matrix have been shown to stimulate anti-inflammatory, functional recovery, and effective
neuroprotective effects. The distribution of curcumin nanoparticles into a copolymer drug carrier system with thermo-responsive abilities improved sustained delivery, blood bioavailability, stability, and biocompatibility. These results demonstrated that minocycline-loaded Cur-CS/PNIPAM provides
enhanced neuroprotection, axonal growth efficiency, and potentially facilitates functional recovery at the site of SCI injury. Therefore, our data offer a facile combination therapeutic strategy for the treatment and recovery of SCI in humans.
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Stem Cell Research & Therapy
·
2025
·Vol. 16
·期 1
·1-18
·
IF 7.3
Mao Shihui,Lan Ting,Sun Yimei,Li Lin,Jiang Weifeng,Xu Jiadong,Feng Yan,Hu Huiqin,Fang Yan,Xu Lanxi,Chu Lisheng
Background Bone marrow mesenchymal stem cell-derived extracellular vesicles (BMSC-EVs) show therapeutic promise for ischemic stroke (IS). Preconditioning MSCs with drugs can modulate the cargo composition and function of their derived EVs. This study investigated the therapeutic effects and underlying mechanisms of EVs derived from tetramethylpyrazine (TMP)-preconditioned BMSCs (TMP-BMSC-EVs) in IS.Methods EVs were isolated from BMSCs pretreated with or without TMP by differential centrifugation. The therapeutic efficacy of EVs was evaluated in a rat model of middle cerebral artery occlusion (MCAO) through neurological function assessments and infarct volume quantification. The expression of miR-486 and its roles in regulating microglia/macrophage polarization and neurogenesis, as well as the mechanistic targets, were examined by real-time quantitative polymerase chain reaction (RT-qPCR), immunofluorescence staining, and Western blotting.Results TMP-BMSC-EVs exerted superior therapeutic efficacy compared to BMSC-EVs. Mechanistically, TMP-BMSC-EVs were enriched with miR-486, which promoted microglia/macrophage M2 polarization and neurogenesis, while downregulating phosphatase and tensin homolog (PTEN) and phosphorylated NF-κB (p-NF-κB) protein levels, and upregulating phosphorylated Akt (p-Akt) expression. Transfection with a miR-486 inhibitor abolished the beneficial effects of TMP-BMSC-EVs, which could be counteracted by the PTEN inhibitor bisperoxovanadium (bpV).Conclusion sTMP-BMSC-EVs could significantly promote neural repair by driving microglia/macrophage M2 polarization and enhancing neurogenesis through miR-486-mediated PTEN inhibition, thereby offering a promising treatment strategy for IS.
研究领域:
神经科学
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干细胞研究
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分子生物学
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药理学
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EUROPEAN JOURNAL OF HISTOCHEMISTRY
·
2024
·Vol. 68
·期 3
·4034
·
IF 2.1
Lan Wang,Zhenyu Fan,Haijin Wang,Shougui Xiang
Subarachnoid hemorrhage (SAH) is a devastating stroke caused by ruptured intracranial aneurysms, leading to blood accumulation around the brain. Early brain injury (EBI) within 72 h post-SAH worsens prognosis, primarily due to intense neuroinflammation. Microglia, pivotal in central nervous system defense and repair, undergo M1 to M2 polarization post-SAH, with M1 exacerbating neuroinflammation. Propofol (PPF), an anesthetic with anti-inflammatory properties, shows promise in mitigating neuroinflammation in SAH by modulating microglial activation. It likely acts through microRNAs like miR-140-5p, which attenuates microglial activation and inflammation by targeting TREM-1 and the NF-κB pathway. Understanding these mechanisms could lead to new therapeutic approaches for SAH-related EBI. In this study, BV-2 cell was used to establish in vitro model of SAH, and the expression of miR-140-5p and TREM-1 was detected after modeling. Microglial activity, apoptosis, the inflammatory pathway and response, oxidative damage, and M1/M2 polarization of microglia were evaluated by drug administration or transfection according to experimental groups. Finally, the targeting relationship between miR-140-5p and TREM-1 was verified by dual luciferase reporter assays, and the effect of PPF on the miR-140-5p/TREM-1/NF-κB signaling cascade was evaluated by RT ‒ qPCR or Western blotting. PPF effectively mitigates apoptosis, neuroinflammation, oxidative damage, and M1 microglial polarization in SAH. In SAH cells, PPF upregulates miR-140-5p and downregulates TREM-1. Mechanistically, PPF boosts miR-140-5p expression, while TREM-1, a downstream target of miR-140-5p, inhibits NF-κB signaling by regulating TREM-1, promoting M1 to M2 microglial polarization. Reduced miR-140-5p or increased TREM-1 counters PPF's therapeutic impact on SAH cells. In conclusion, PPF plays a neuroprotective role in SAH by regulating the miR-140-5p/TREM-1/NF-κB signaling axis to inhibit neuroinflammation and M1 polarization of microglia.
研究领域:
神经科学
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药理学
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炎症
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细胞生物学
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JOURNAL OF ETHNOPHARMACOLOGY
·
2023
·
IF 5.4
Shan Luo,Yuanchun Chen,Ruoxi Zhao,Donglai Ma,Yanmeng Zhao,Ying Zhang,Jianming Jiang,Wentao Yu
Ethnopharmacology relevance San Hua Tang (SHT) was first mentioned in the book "The Collection of Plain Questions about Pathogenesis, Qi, and Life." SHT has the effect of dispelling wind and dredging collaterals, dredging viscera, and guiding stagnation, and is used in the treatment of ischemic stroke (IS). SHT is composed of Rheum palmatum L., Magnolia officinalis Rehder & E.H.Wilson, Citrus assamensis S.Dutta & S.C.Bhattacharya, and Notopterygium tenuifolium M.L.Sheh & F.T.Pu, which is the traditional prescription of the Tongxia method for the treatment of stroke. Tongxia is one of the "eight methods" used in traditional Chinese medicine, which plays a role in treating diseases by promoting gastrointestinal peristalsis and defecation. Studies have demonstrated a close relationship between gut microbiota metabolism and cerebral stroke; however, the role of SHT in IS treatment through gut microbiota or intestinal metabolites is unclear. Aim of the study : To explore the connotation of the Xuanfu theory and clarify the mechanism underlying SHT-mediated opening Xuanfu methods. Through metabolomics, 16S rRNA gene sequencing, and molecular biology techniques, research on the changes in the gut microbiota and blood-brain barrier (BBB) will highlight greater strategies for the treatment of stroke. Materials and methods We used pseudo-germ-free (PGF) rats combined with an ischemia/reperfusion (I/R) rat model for the follow-up experimental research. PGF rats were prepared by the intragastric administration of an antibiotic cocktail for 6 days, following which SHT was administered for 5 consecutive days. The I/R model was performed 1 day following the concluding administration of SHT. We detected the neurological deficit score, cerebral infarct volume, serum inflammatory factor levels (interleukin IL-6, IL-10, IL-17, and tumor necrosis factor alpha), tight junction-related proteins (Zonula occludens-1, Occludin, and Claudin-5), and small glue plasma cell-associated proteins (Cluster of Differentiation 16/Cluster of Differentiation 206, Matrix metalloproteinase, ionized calcium-binding adapter molecule 1, and C-X3-C Motif Chemokine Ligand 1) 24 h following I/R. Using 16S rRNA gene sequencing and non-targeted metabolomics analysis, we explored the relationship between fecal microecology and serum metabolites. Eventually, we analyzed the correlation between the gut microbiota and plasma metabolic profile as well as the mechanism underlying the SHT-mediated regulation of gut microbiota to protect the BBB following stroke. Results In IS treatment, SHT is principally involved in reducing neurological injury and the volume of cerebral infarction; protecting the intestinal mucosal barrier; increasing the levels of acetic acid, butyric acid, and propionic acid; promoting the transformation of microglia to the M2 state; reducing inflammatory reactions; and enhancing tight junctions. These therapeutic effects were not observed in the group treated with antibiotics alone or that treated with SHT in combination with antibiotics, thereby indicating SHT plays a therapeutic role through the gut microbiota. Conclusion SHT regulates the gut microbiota, inhibits pro-inflammatory factors in rats with IS, alleviates an inflammatory injury of the BBB, and plays a protective role in the brain .
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Heliyon
·
2024
·
IF 3.4
Chongchong Liu,Jiangyan Sun,Xiaoming Shen,Shefang Li,Sha Luo,Na Chen,Yunke Zhang
Epilepsy is a chronic neurological disorder. Drug-resistant epilepsy (DRE) accounts for about one-third of epilepsy patients worldwide. Peimine, a main active component of Fritillaria, has been reported to show anti-inflammatory effects. However, its potential therapeutic role in DRE is not yet fully understood. In this work, a DRE rat model was established by injecting 1 μg kainic acid (KA), followed by a 250 mg/kg administration of valproic acid (VPA) from day 4–31. Rats were treated with different doses of peimine (2.5 mg/kg, 5 mg/kg and 10 mg/kg) daily from day 32–62. In vitro, BV-2 microglia were exposed to different doses of peimine (7.5 μg/ml, 15 μg/ml, and 30 μg/ml) in presence of LPS. The aim of this study was to investigate the potential therapeutic effects of peimine on DRE. The results showed that peimine efficiently suppressed the KA-induced epileptic behaviors of rats in a dose-dependent manner, as recorded by electroencephalography. Furthermore, peimine ameliorated hippocampal neuron injury in DRE rats, and promoted an M1-to-M2 microglial phenotype shift in a dose-dependent manner. Mechanistically, peimine inhibited the TLR4/NF-κB/HIF-1α signaling pathway both in vivo and in vitro. Additionally, peimine suppressed the apoptosis of primary neurons induced by LPS-treated microglia. In conclusion, peimine augments the microglial polarization towards an M2 phenotype by inhibiting the TLR4/NF-κB/HIF-1α signaling pathway, thereby attenuating DRE.
研究领域:
神经病学
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药理学
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免疫学
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细胞生物学
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