Neuroprotective mechanism of Ajugarin-I against Vincristine-Induced neuropathic pain via regulation of Nrf2/NF-κB and Bcl2 signalling

Khan, Adnan; Shal, Bushra; Khan, Ashraf Ullah; Shah, Kifayat Ullah; Zahra, Syeda Saniya; Haq, İhsan Ul; Din, Fakhar ud; Ali, Hussain; Khan, Salman

doi:10.1016/j.intimp.2023.110046

Cited by 8 publications

(4 citation statements)

References 104 publications

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“… 33 Ajugarin-I inhibits vincristine-induced NP by modulating Nrf2/NF-κB and BCL2 signaling. 34 AKT is a key downstream substrate of the PI3K pathway and is involved in various biological processes. 35 It is reported that, activation of PI3K/AKT pathway in spinal cord contributes to activation of the transcription factor NF-κB and release of inflammatory mediators, ultimately leading to the development of NP.…”

Section: Discussionmentioning

confidence: 99%

Ligusticum chuanxiong Hort. Ameliorates Neuropathic Pain by Regulating Microglial M1 Polarization: A Study Based on Network Pharmacology

Cui,

Feng,

Xia

2024

JPR

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Background In traditional Chinese medicine, Ligusticum chuanxiong Hort . (LCH) is used to treat neuropathic pain (NP). This study was performed to investigate the underlying pharmacological mechanisms. Methods The main components of the LCH were obtained from the TCMSP database. The targets of the active components were obtained using the Swiss Target Prediction database and HERB database. The NP-related genes were obtained from the CTD database and GeneCard database. Protein-protein interaction (PPI) network was constructed using the STRING platform and Cytoscape 3.9.0 software. GO and KEGG enrichment analyses were performed using the DAVID database. Interactions between the key components and hub target proteins were verified using molecular docking and molecular dynamics simulation. In addition, microglial cell line HMC3 was induced to polarize to the M1 phenotype using 100 ng/mL lipopolysaccharide (LPS). Quantitative real-time polymerase chain reaction (qRT-PCR), Western blot and enzyme-linked immunosorbent assays were used to detect the expression levels of M1 markers and inflammatory factors, respectively. Results Seven LCH active components of LCH were identified, corresponding to 387 target genes. 2019 NP-related genes were obtained, and a total of 174 NP-related genes were identified as target genes that could be modulated by LCH. Beta-sitosterol, senkyunone, wallichilide, myricanone, and mandenol were considered as the key components of LCH in the treatment of NP. SRC, BCL2, AKT1, HIF1A and HSP90AA1 were identified as the hub target proteins. GO analysis showed that 328 biological processes, 61 cell components, and 85 molecular functions were likely modulated by the components of LCH, and KEGG enrichment analysis showed that 132 signaling pathways were likely modulated by the components of LCH. Beta-sitosterol, senkyunone, wallichilide, myricanone, and mandenol showed good binding activity with hub target proteins including SRC, BCL2, AKT1, and HSP90AA1. In addition, beta-sitosterol inhibited LPS-induced M1 polarization in HMC3 in vitro. Conclusion This study provides a theoretical basis for the application of LCH in the treatment of NP through multicomponent, multitarget, and multiple pathways.

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Section: Discussionmentioning

confidence: 99%

Ligusticum chuanxiong Hort. Ameliorates Neuropathic Pain by Regulating Microglial M1 Polarization: A Study Based on Network Pharmacology

Cui,

Feng,

Xia

2024

JPR

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“…This hypothesis was further tested in in-vitro release assay. It is worth mention that drug release and the pattern of drug release form a nano system is important to produce the desired therapeutic effect, which is associated with the drug solubilization and release from the system [ 75 , 76 ]. Moreover, it ensure the availability of drug at desired concentration at a specific period of time [ 77 , 78 ].…”

Section: Discussionmentioning

confidence: 99%

Investigation of the treatment potential of Raloxifene-loaded polymeric nanoparticles in osteoporosis: In-vitro and in-vivo analyses

Guo,

Afza,

Moneeb Khan

et al. 2023

Heliyon

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“…Ajugarin-I, a phytoconstituent, has been found to possess neuroprotective properties against vincristine-induced neuropathic pain. The potential mechanism underlying the anti-neuropathic effect of Aju-I may involve the activation of the nuclear factor erythroid 2-related factor 2/heme oxygenase 1 (Nrf2-HO-1 axis), the inhibition of Nuclear factor-kappaB (NF-kappaB)/cyclooxygenase-2 (NF-κB/COX-2), and apoptotic signalling in nociceptors located in the spinal cord [ 193 ]. This section presents a comprehensive analysis of nanocarrier systems that incorporate phytoconstituents or phytochemicals for the purpose of neuroprotection against NDs.…”

Section: Strategies Of Gene Therapymentioning

confidence: 99%

Nano biomaterials based strategies for enhanced brain targeting in the treatment of neurodegenerative diseases: an up-to-date perspective

Nayab,

Din,

Ali

et al. 2023

J Nanobiotechnol

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Neurons and their connecting axons gradually degenerate in neurodegenerative diseases (NDs), leading to dysfunctionality of the neuronal cells and eventually their death. Drug delivery for the treatment of effected nervous system is notoriously complicated because of the presence of natural barriers, i.e., the blood-brain barrier and the blood cerebrospinal fluid barrier. Palliative care is currently the standard care for many diseases. Therefore, treatment programs that target the disease’s origin rather than its symptoms are recommended. Nanotechnology-based drug delivery platforms offer an innovative way to circumvent these obstacles and deliver medications directly to the central nervous system, thereby enabling treatment of several common neurological problems, i.e., Alzheimer’s, Parkinson’s, Huntington’s, and amyotrophic lateral sclerosis. Interestingly, the combination of nanomedicine and gene therapy enables targeting of selective mutant genes responsible for the progression of NDs, which may provide a much-needed boost in the struggle against these diseases. Herein, we discussed various central nervous system delivery obstacles, followed by a detailed insight into the recently developed techniques to restore neurological function via the differentiation of neural stem cells. Moreover, a comprehensive background on the role of nanomedicine in controlling neurogenesis via differentiation of neural stem cells is explained. Additionally, numerous phytoconstituents with their neuroprotective properties and molecular targets in the identification and management of NDs are also deliberated. Furthermore, a detailed insight of the ongoing clinical trials and currently marketed products for the treatment of NDs is provided in this manuscript. Graphical abstract

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Neuroprotective mechanism of Ajugarin-I against Vincristine-Induced neuropathic pain via regulation of Nrf2/NF-κB and Bcl2 signalling

Cited by 8 publications

References 104 publications

Ligusticum chuanxiong Hort. Ameliorates Neuropathic Pain by Regulating Microglial M1 Polarization: A Study Based on Network Pharmacology

Ligusticum chuanxiong Hort. Ameliorates Neuropathic Pain by Regulating Microglial M1 Polarization: A Study Based on Network Pharmacology

Investigation of the treatment potential of Raloxifene-loaded polymeric nanoparticles in osteoporosis: In-vitro and in-vivo analyses

Nano biomaterials based strategies for enhanced brain targeting in the treatment of neurodegenerative diseases: an up-to-date perspective

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