Anti-neuropathic pain activity of Ajugarin-I via activation of Nrf2 signaling and inhibition of TRPV1/TRPM8 nociceptors in STZ-induced diabetic neuropathy

Khan, Adnan; Wang, Feng; Shal, Bushra; Khan, Ashraf Ullah; Zahra, Syeda Saniya; Haq, İhsan Ul; Khan, Salman; Rengasamy, Kannan R.R.

doi:10.1016/j.phrs.2022.106392

Cited by 17 publications

(10 citation statements)

References 70 publications

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“…After entering the nucleus, Nrf2 interacts with the antioxidant response element (ARE) to control the production of genes involved in downstream antioxidant defense, including NAD(P)H Dehydrogenase Quinone 1 (NQO1) and HO-1. These downstream effectors play a vital role in neutralizing excessive ROS, thus preserving the cellular redox balance and providing cellular protection [ [23] , [24] , [25] ]. The activation of the Nrf2 pathway stands as a critical antioxidant stress pathway, demonstrating significant neuroprotective effects against oxidative damage in diabetes-related neuropathies.…”

Section: Discussionmentioning

confidence: 99%

Resveratrol protects against diabetic retinal ganglion cell damage by activating the Nrf2 signaling pathway

Yuan,

Xu,

Xue

et al. 2024

Heliyon

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Section: Discussionmentioning

confidence: 99%

Resveratrol protects against diabetic retinal ganglion cell damage by activating the Nrf2 signaling pathway

Yuan,

Xu,

Xue

et al. 2024

Heliyon

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“…Malondialdehyde (MDA) was measured to estimate lipid peroxidation in the brain and spinal cord (L4‐L6), as described previously (Ali et al, 2020; Khan, Khan, Shal, et al, 2022a; Khan, Khan, Khan, Shal, et al, 2022b; Khan, Khan, Zafar, et al, 2022e; Khan, Wang, et al, 2022c; Khan, Zhang et al, 2022d). The quantitative measurement of MDA in the tissue homogenate was an index of lipid peroxidation.…”

Section: Methodsmentioning

confidence: 99%

“…Percentages were used to express the results. The procedure was carried out as directed by the manufacturer (Khan et al, 2013a; Khan, Khan, Khan, Shal, et al, 2021d; Khan, Khan, Shal, et al, 2022a; Khan, Khan, Khan, Shal, et al, 2022b; Khan, Khan, Zafar, et al, 2022e; Khan, Wang, et al, 2022c; Khan, Zhang et al, 2022d).…”

Section: Methodsmentioning

confidence: 99%

Suppression of MAPK/NF‐kB and activation of Nrf2 signaling by Ajugarin‐I in EAE model of multiple sclerosis

Khan

Shal

Khan

et al. 2023

Phytotherapy Research

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Multiple sclerosis (MS) is a debilitating neurodegenerative autoimmune disease of the central nervous system (CNS). The current study aimed to investigate the neuroprotective properties of Ajugarin-I (Aju-I) against the experimental autoimmune encephalomyelitis (EAE) model of MS and explored the underlying mechanism involved. The protective potential of Aju-I was first confirmed against glutamateinduced HT22 cells and hydrogen peroxide (H 2 O 2 )-induced BV2 cells. Next, an EAE model has been established to investigate the mechanisms of MS and identify potential candidates for MS treatment. The behavioral results demonstrated that Aju-I post-immunization treatment markedly reduced the EAE-associated clinical score, motor impairment, and neuropathic pain. Evans blue and fluorescein isothiocyanate extravasation in the brain were markedly reduced by Aju-I. It effectively restored the EAE-associated histopathological changes in the brain and spinal cord. It markedly attenuated EAE-induced inflammation in the CNS by reducing the expression levels of p-38/JNK/NF-κB but increased the expression of IkB-α. It suppressed oxidative stress by increasing the expression of Nrf2 but decreasing the expression of keap-1. It suppressed EAE-induced apoptosis in the CNS by regulating Bax/Bcl-2 and Caspase-3 expression. Taken together, this study suggests that Aju-I treatment exhibits neuroprotective properties in the EAE model of MS via regulation of MAPK/ NF-κB, Nrf2/Keap-1, and Bcl2/Bax signaling.

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“…Aju-I treatment in rats reduced hyperglycemia, pain hypersensitivity, and pancreas damage induced by diabetes. It also mitigated histopathological changes in nerves and the spinal cord, decreasing oxidative stress and modulating TRPV1/TRPM8 nociceptors [145]. The only documented GOF VUS within TRPM8, rs200774365 (Arg30Gln), has been linked to trigeminal neuralgia [25].…”

Section: Trpm8mentioning

confidence: 99%

Ion Channel Genes in Painful Neuropathies

Ślęczkowska,

Misra,

Santoro

et al. 2023

Biomedicines

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Neuropathic pain (NP) is a typical symptom of peripheral nerve disorders, including painful neuropathy. The biological mechanisms that control ion channels are important for many cell activities and are also therapeutic targets. Disruption of the cellular mechanisms that govern ion channel activity can contribute to pain pathophysiology. The voltage-gated sodium channel (VGSC) is the most researched ion channel in terms of NP; however, VGSC impairment is detected in only <20% of painful neuropathy patients. Here, we discuss the potential role of the other peripheral ion channels involved in sensory signaling (transient receptor potential cation channels), neuronal excitation regulation (potassium channels), involuntary action potential generation (hyperpolarization-activated cyclic nucleotide-gated channels), thermal pain (anoctamins), pH modulation (acid sensing ion channels), and neurotransmitter release (calcium channels) related to pain and their prospective role as therapeutic targets for painful neuropathy.

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Anti-neuropathic pain activity of Ajugarin-I via activation of Nrf2 signaling and inhibition of TRPV1/TRPM8 nociceptors in STZ-induced diabetic neuropathy

Cited by 17 publications

References 70 publications

Resveratrol protects against diabetic retinal ganglion cell damage by activating the Nrf2 signaling pathway

Resveratrol protects against diabetic retinal ganglion cell damage by activating the Nrf2 signaling pathway

Suppression of MAPK/NF‐kB and activation of Nrf2 signaling by Ajugarin‐I in EAE model of multiple sclerosis

Ion Channel Genes in Painful Neuropathies

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