Surface modified multifaceted nanocarriers for oral non-conventional cancer therapy; synthesis and evaluation

Mazhar, Kehkashan; Malik, Annum; Naz, Shazia; Shah, Kifayat Ullah; Khan, Adnan; Khan, Salman; Ahmed, Rizwan; Qaisar, Sara

doi:10.1016/j.msec.2021.111940

Cited by 13 publications

(3 citation statements)

References 93 publications

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“…A 30-s cutoff time was used to prevent any paw or body damage. In the hot plate, the paw latency reaction (paw licking, flinching, or jumping) time was measured [ 53 , 54 ].…”

Section: Methodsmentioning

confidence: 99%

Suppression of TRPV1/TRPM8/P2Y Nociceptors by Withametelin via Downregulating MAPK Signaling in Mouse Model of Vincristine-Induced Neuropathic Pain

Khan

Shal

Khan

et al. 2021

IJMS

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Vincristine (VCR) is a widely used chemotherapy drug that induced peripheral painful neuropathy. Yet, it still lacks an ideal therapeutic strategy. The transient receptor potential (TRP) channels, purinergic receptor (P2Y), and mitogen-activated protein kinase (MAPK) signaling play a crucial role in the pathogenesis of neuropathic pain. Withametelin (WMT), a potential Phytosteroid isolated from datura innoxa, exhibits remarkable neuroprotective properties. The present investigation was designed to explore the effect of withametelin on VCR-induced neuropathic pain and its underlying molecular mechanism. Initially, the neuroprotective potential of WMT was confirmed against hydrogen peroxide (H2O2)-induced PC12 cells. To develop potential candidates for neuropathic pain treatment, a VCR-induced neuropathic pain model was established. Vincristine (75 μg/kg) was administered intraperitoneally (i.p.) for 10 consecutive days (day 1–10) for the induction of neuropathic pain. Gabapentin (GBP) (60 mg/kg, i.p.) and withametelin (0.1 and 1 mg/kg i.p.) treatments were given after the completion of VCR injection on the 11th day up to 21 days. The results revealed that WMT significantly reduced VCR-induced pain hypersensitivity, including mechanical allodynia, cold allodynia, and thermal hyperalgesia. It reversed the VCR-induced histopathological changes in the brain, spinal cord, and sciatic nerve. It inhibited VCR-induced changes in the biochemical composition of the myelin sheath of the sciatic nerve. It markedly downregulated the expression levels of TRPV1 (transient receptor potential vanilloid 1); TRPM8 (Transient receptor potential melastatin 8); and P2Y nociceptors and MAPKs signaling, including ERK (Extracellular Signal-Regulated Kinase), JNK (c-Jun N-terminal kinase), and p-38 in the spinal cord. It suppressed apoptosis by regulating Bax (Bcl2-associated X-protein), Bcl-2 (B-cell-lymphoma-2), and Caspase-3 expression. It considerably attenuated inflammatory cytokines, oxidative stress, and genotoxicity. This study suggests that WMT treatment suppressed vincristine-induced neuropathic pain by targeting the TRPV1/TRPM8/P2Y nociceptors and MAPK signaling.

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“…A 30-s cutoff time was used to prevent any paw or body damage. In the hot plate, the paw latency reaction (paw licking, flinching, or jumping) time was measured [ 53 , 54 ].…”

Section: Methodsmentioning

confidence: 99%

Suppression of TRPV1/TRPM8/P2Y Nociceptors by Withametelin via Downregulating MAPK Signaling in Mouse Model of Vincristine-Induced Neuropathic Pain

Khan

Shal

Khan

et al. 2021

IJMS

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“…Thermal hyperalgesia was measured using a hot‐plate apparatus (Khalid et al, 2019; Ur Rehman et al, 2021). The temperature was calibrated at 55 ± 1°C, and the latency of paw licking was used to determine pain sensitivity.…”

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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“…To evaluate further the analgesic effect of Compound 1 in PTX-induced rats, a hot plate test was performed according to the previously reported protocols [26][27][28]. The once-daily dosing of Compound 1 was examined for antihyperalgesic effect on days 0, 2, 4, 6, and 8.…”

Section: Evaluation Of Thermal Hyperalgesiamentioning

confidence: 99%

Anti-neuropathic pain activity of a cationic palladium (II) dithiocarbamate by suppressing the inflammatory mediators in paclitaxel-induced neuropathic pain model

et al. 2021

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Surface modified multifaceted nanocarriers for oral non-conventional cancer therapy; synthesis and evaluation

Cited by 13 publications

References 93 publications

Suppression of TRPV1/TRPM8/P2Y Nociceptors by Withametelin via Downregulating MAPK Signaling in Mouse Model of Vincristine-Induced Neuropathic Pain

Suppression of TRPV1/TRPM8/P2Y Nociceptors by Withametelin via Downregulating MAPK Signaling in Mouse Model of Vincristine-Induced Neuropathic Pain

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

Anti-neuropathic pain activity of a cationic palladium (II) dithiocarbamate by suppressing the inflammatory mediators in paclitaxel-induced neuropathic pain model

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