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<p>Nuclear erythroid 2-related factor (Nrf-2) activators have been used in previous research in inhibiting the multifaceted pathophysiology of traumatic brain injury (TBI). Moreover, combinatorial treatment strategies provide an additive pharmacological effect when compared with single treatment against brain injury. Therefore, the current study aimed to evaluate the neuroprotective effect of a Nrf-2 activator, kinetin (plant cytokinin, 6-Furfurylaminopurine) and zinc along with their combination on pre-clinical TBI. The acute injury was induced in male Wistar rats by controlled cortical impact and kinetin (5&#xa0;mg/kg and 10&#xa0;mg/kg) along with zinc picolinate (6&#xa0;mg/kg) was administered. Several neurobehavioral tests like open field, beam balance and grip strength were performed post injury. Biochemical, histopathological and immunohistochemical analysis were also carried out. The expression of NLRP3-NF-ԟB pathway proteins were evaluated using techniques like ELISA and immunohistochemistry. Histopathological analysis was performed through H &amp; E staining method. The results showed less exploration and grip strength in injured rats which was improved after treatment with kinetin. Injured rats showed a slight increase in brain and serum Nrf-2 levels which was profoundly increased by treatment. We also found an increase in brain and serum levels of an antioxidant defence system and a decrease in levels of inflammatory cytokines after treatment with both kinetin and zinc picolinate. There was a significant decrease in levels of NF-ԟB and NLRP3 inflammasome. Further, histopathological and immunohistochemistry analysis revealed neuroprotective effect of both the compounds on TBI. We can conclude that kinetin and zinc, alone and their combination show neuroprotective effects in TBI by activating Nrf-2 anti-oxidant defence and inhibiting NLRP3-NF-ԟB pathways. These findings support future evaluation of plant cytokinin in combination with a bio metal in attenuating secondary injury in TBI.</p> Graphical Abstract <p></p>

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A combination of Nrf-2 activator, kinetin and zinc provides neuroprotection through NLRP3-NF-ԟB signaling in traumatic brain injury

  • 期刊论文

  • 发表日期：

    2026年7月14日

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  • Shivani Agarwal,
  • Mohd. Shahrukh,
  • Divya Vohora,
  • Suhel Parvez,
  • Abul Kalam Najmi,
  • Mohd. Akhtar

摘要

Nuclear erythroid 2-related factor (Nrf-2) activators have been used in previous research in inhibiting the multifaceted pathophysiology of traumatic brain injury (TBI). Moreover, combinatorial treatment strategies provide an additive pharmacological effect when compared with single treatment against brain injury. Therefore, the current study aimed to evaluate the neuroprotective effect of a Nrf-2 activator, kinetin (plant cytokinin, 6-Furfurylaminopurine) and zinc along with their combination on pre-clinical TBI. The acute injury was induced in male Wistar rats by controlled cortical impact and kinetin (5 mg/kg and 10 mg/kg) along with zinc picolinate (6 mg/kg) was administered. Several neurobehavioral tests like open field, beam balance and grip strength were performed post injury. Biochemical, histopathological and immunohistochemical analysis were also carried out. The expression of NLRP3-NF-ԟB pathway proteins were evaluated using techniques like ELISA and immunohistochemistry. Histopathological analysis was performed through H & E staining method. The results showed less exploration and grip strength in injured rats which was improved after treatment with kinetin. Injured rats showed a slight increase in brain and serum Nrf-2 levels which was profoundly increased by treatment. We also found an increase in brain and serum levels of an antioxidant defence system and a decrease in levels of inflammatory cytokines after treatment with both kinetin and zinc picolinate. There was a significant decrease in levels of NF-ԟB and NLRP3 inflammasome. Further, histopathological and immunohistochemistry analysis revealed neuroprotective effect of both the compounds on TBI. We can conclude that kinetin and zinc, alone and their combination show neuroprotective effects in TBI by activating Nrf-2 anti-oxidant defence and inhibiting NLRP3-NF-ԟB pathways. These findings support future evaluation of plant cytokinin in combination with a bio metal in attenuating secondary injury in TBI.

Graphical Abstract