Curcumin inhibits glial scar formation by suppressing astrocyte-induced inflammation and fibrosis in vitro and in vivo

Yuan, Jianmin; Liu, Wei; Zhu, Haitao; Chen, Yaxing; Zhou, Xuan; Li, Lan; Chu, Weihua; Wen, Zexian; Feng, Hua; Lin, Jiangkai

doi:10.1016/j.brainres.2016.11.002

Cited by 68 publications

(57 citation statements)

References 52 publications

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“…Inhibition of GFAP expression following CNS injury was also observed in several other investigations using Cur 9,13,15 . Cur was able to reduce the expression of both GFAP mRNA and GFAP protein, as well as to induce autophagy and to rescue the filamentous organization of the GFAP mutant protein in an in vitro model of Alexander disease, in which heterozygous mutations of the GFAP gene are responsible for the intracytoplasmic accumulation of fibrous eosinophilic deposits known as Rosenthal fibers in dystrophic astrocytes 28 .…”

Section: Discussionsupporting

confidence: 76%

Section: Discussionmentioning

confidence: 99%

“…The NF-κβ signaling pathway is very important for the effects of pro-inflammatory cytokines TNF-α and IL-1β 15 , which represent important factors in the initial activation of astrocytes and are produced in great numbers in brainstem lesions induced by EB 25 . Under the influence of many relevant factors, astrocytes will lead to dense glial scar formation and will produce large amounts of extracellular matrix components, such as chondroitin sulfate proteoglycan, changing the axonal growth environment and severely inhibiting nerve regeneration 15 . Yuan et al 15 observed that Cur suppressed the NF-κβ signaling pathway, down-regulating the expression of chemokines MCP-1, RANTES and CXCL10 released by astrocytes and decreasing macrophage and T-cell infiltration, thus reducing inflammation in the glial scar environment in an experimental model of spinal cord injury.…”

Section: Discussionmentioning

confidence: 99%

“…Under the influence of many relevant factors, astrocytes will lead to dense glial scar formation and will produce large amounts of extracellular matrix components, such as chondroitin sulfate proteoglycan, changing the axonal growth environment and severely inhibiting nerve regeneration 15 . Yuan et al 15 observed that Cur suppressed the NF-κβ signaling pathway, down-regulating the expression of chemokines MCP-1, RANTES and CXCL10 released by astrocytes and decreasing macrophage and T-cell infiltration, thus reducing inflammation in the glial scar environment in an experimental model of spinal cord injury. Additionally, by silencing the transcription factor SOX9, Cur reduced the deposition of extracellular matrix chondroitin sulfate proteoglycan, contributing to recovery of neurological function.…”

Section: Discussionmentioning

confidence: 99%

“…Recently, Cur has been shown to exhibit proven therapeutic benefits (including antioxidant, anti-inflammatory, anti-cancer and anti-fibrotic effects) in many pathological conditions, such as Alzheimer' s disease, Parkinson' s disease, multiple sclerosis, epilepsy, cerebral injury, cancer, allergy, asthma, bronchitis, colitis, rheumatoid arthritis, renal ischemia, psoriasis, scleroderma, diabetes, obesity, depression, fatigue and acquired immunodeficiency disease 6,7,8 . Specifically regarding the CNS, Cur was capable of providing neuroprotection after spinal cord injury, inhibiting apoptosis and neuron loss and attenuating oxidative stress in astrocytes and reactive astrogliosis 9,10,11,12,13 , suggesting that Cur might beneficially affect astrocyte population in the CNS inflammatory environment by regulating both NF-κβ and SOX9 signaling pathways 14,15 . In this context, the aim of this study was to evaluate whether Cur had the capacity to affect astrocyte response during the process of demyelination and remyelination following gliotoxic injury induced by ethidium bromide (EB).…”

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confidence: 99%

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Curcumin decreases astrocytic reaction after gliotoxic injury in the rat brainstem

Bondan

Cardoso

Martins

2017

Arq. Neuro-Psiquiatr.

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Recent studies have demonstrated that curcumin (Cur) has antioxidant, anti-inflammatory and anti-fibrotic effects. Ethidium bromide (EB) injections into the central nervous system (CNS) are known to induce local oligodendroglial and astrocytic loss, resulting in primary demyelination and neuroinflammation. Peripheral astrogliosis is seen around the injury site with increased immunoreactivity to glial fibrillary acidic protein (GFAP). This investigation aimed to evaluate the effect of Cur administration on astrocytic response following gliotoxic injury. Wistar rats were injected with EB into the cisterna pontis and treated, or not, with Cur (100 mg/kg/day, intraperitoneal route) during the experimental period. Brainstem sections were collected at 15, 21 and 31 days after EB injection and processed for GFAP immunohistochemical staining. Astrocytic reactivity was measured in a computerized system for image analysis. In Cur-treated rats, the GFAP-stained area around the lesion was significantly smaller in all periods after EB injection compared to untreated animals, showing that Cur reduces glial scar development following injury.Keywords: astrocytes; curcumin; ethidium; gliosis; gliotoxin. RESUMOEstudos recentes têm demonstrado que a curcumina (Cur) possui efeitos antioxidantes, anti-inflamatórios e antifibróticos. Sabe-se que a injeção de brometo de etídio (EB) no sistema nervoso central induz a perda oligodendroglial e astrocitária, resultando em desmielinização primária e neuroinflamação. Astrogliose periférica é observada ao redor da lesão com aumento da imunorreatividade à proteína glial fibrilar ácida (GFAP). A presente investigação objetivou avaliar o efeito da Cur sobre a resposta astrocitária após injúria gliotóxica. Ratos Wistar foram injetados com EB na cisterna basal e tratados ou não com Cur (100 mg/kg/dia, via intraperitoneal) durante o período experimental. Amostras do tronco encefálico foram coletadas aos 15, 21 e 31 dias pós-injeção de EB e processadas para estudo imuno-histoquímico para a GFAP. A reatividade astrocitária foi medida em um sistema computadorizado para análise de imagem. Nos ratos tratados com Cur, a área marcada para GFAP foi significantemente menor em todos os períodos pós-injeção de EB, indicando que a Cur reduz o desenvolvimento da cicatriz glial após injúria.

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Section: Discussionsupporting

confidence: 76%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

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Curcumin decreases astrocytic reaction after gliotoxic injury in the rat brainstem

Bondan

Cardoso

Martins

2017

Arq. Neuro-Psiquiatr.

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Protective effects of curcumin against spinal cord injury

Razavi,

Khayatan,

Najafi Arab

et al. 2024

JOR Spine

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BackgroundIn parallel with population aging, the prevalence of neurological and neurodegenerative diseases has been dramatically increasing over the past few decades. Neurodegenerative diseases reduce the quality of life of patients and impose a high cost on the health system. These slowly progressive diseases can cause functional, perceptual, and behavioral deficits in patients. Therefore, neurodegenerative impairments have always been an interesting subject for scientists and clinicians. One of these diseases is spinal cord injury (SCI). SCI can lead to irreversible damage and is classified into two main subtypes: traumatic and non‐traumatic, each with very different pathophysiological features.AimsThis review aims to gather relevant information about the beneficial effects of curcumin (Cur), with specific emphasis on its anti‐inflammatory properties towards spinal cord injury (SCI) patients.Materials & MethodsThe review collates data from extensive in‐vitro, in‐vivo, and clinical trials documenting the effects of CUR on SCI. It examines the modulation of pathophysiological pathways and regulation of the inflammatory cascades after CUR administration.ResultsVarious pathophysiological processes involving the nuclear factor erythroid 2‐related factor 2 (Nrf2), nuclear factor kappa B (NF‐kB), and transforming growth factor beta (TGF‐β) signaling pathways have been suggested to exacerbate damages resulting from SCI. CUR administration showed to modulate these signaling pathways which lead to attenuation of SCI complications.DiscussionAnti‐inflammatory compounds, particularly CUR, can modulate these pathophysiological pathways and regulate the inflammatory cascades. CUR, a well‐known natural product with significant anti‐inflammatory effects, has been extensively documented in experimental and clinical trials.ConclusionCurcumin's potential to alter key steps in the Nrf2, NF‐kB, and TGF‐β signaling pathways suggests that it may play a role in attenuating SCI complications.

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Ameliorating potential of curcumin and its analogue in central nervous system disorders and related conditions: A review of molecular pathways

Joshi

Bisht

Joshi

et al. 2022

Phytotherapy Research

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Curcumin, isolated from turmeric (Curcuma longa L.) is one of the broadly studied phytomolecule owing to its strong antioxidant and anti‐inflammatory potential and has been considered a promising therapeutic candidate in a wide range of disorders. Considering, its low bioavailability, different curcumin analogs have been developed to afford desired pharmacokinetic profile and therapeutic outcome in varied pathological states. Several preclinical and clinical studies have indicated that curcumin ameliorates mitochondrial dysfunction, inflammation, oxidative stress apoptosis‐mediated neural cell degeneration and could effectively be utilized in the treatment of different neurodegenerative diseases. Hence, in this review, we have summarized key findings of experimental and clinical studies conducted on curcumin and its analogues with special emphasis on molecular pathways, viz. NF‐kB, Nrf2‐ARE, glial activation, apoptosis, angiogenesis, SOCS/JAK/STAT, PI3K/Akt, ERK1/2 /MyD88 /p38 MAPK, JNK, iNOS/NO, and MMP pathways involved in imparting ameliorative effects in the therapy of neurodegenerative disorders and associated conditions.

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Curcumin inhibits glial scar formation by suppressing astrocyte-induced inflammation and fibrosis in vitro and in vivo

Cited by 68 publications

References 52 publications

Curcumin decreases astrocytic reaction after gliotoxic injury in the rat brainstem

Curcumin decreases astrocytic reaction after gliotoxic injury in the rat brainstem

Protective effects of curcumin against spinal cord injury

Ameliorating potential of curcumin and its analogue in central nervous system disorders and related conditions: A review of molecular pathways

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