This study explored how Trigonelline, a form of methylated niacin, impacts spinal cord injury recovery in rats.
Key Points
Several neuroprotective effects of Trigonelline in spinal cord injury were demonstrated:
- Reduced pain and sensitivity following SCI.
- Improved motor coordination and movement control.
- Enhanced nerve signal transmission.
- Improved mitochondrial function and energy production.
- Regulated cell death, reduced inflammation, and promoted nerve growth.
- Protected spinal cord tissue from injury-related damage.
Neuroprotective Effects of Trigonelline Evaluated in Spinal Cord Injury Rat Model
The researchers evaluated the effects of different doses of Trigonelline in rats with a spinal cord injury.
Rats were randomly assigned to seven groups (n=15 per group):
- Normal (N): No surgery, no spinal cord injury (SCI), received control solution (1% DMSO, 10 g/kg).
- Sham (S): Surgery performed but no SCI, received control solution (1% DMSO, 10 g/kg).
- SCI Control (SCI): Surgery with SCI, received control solution (1% DMSO, 10 g/kg).
- MP30: Surgery with SCI, treated with methylprednisolone (30 mg/kg), a standard SCI medication.
- T50: Surgery with SCI, treated with Trigonelline (50 mg/kg).
- T100: Surgery with SCI, treated with Trigonelline (100 mg/kg).
- T200: Surgery with SCI, treated with Trigonelline (200 mg/kg).
Treatments were administered orally once daily for 28 days.
The researchers evaluated the rats using behavioral tests, biochemical tests, and histological analyses to understand the effects of the different treatments.
Reduced Pain and Improved Nerve Function After Spinal Cord Injury
Trigonelline effectively alleviated pain and improved nerve function in rats with a spinal cord injury (SCI):
- Reduced Pain and Sensitivity: Trigonelline significantly reduced sensitivity to touch and heat, addressing pain associated with SCI.
- Improved Motor Coordination: Motor function was significantly improved, indicating better movement control.
- Enhanced Nerve Signal Transmission: Trigonelline helped restore nerve signaling disrupted by the SCI.
“Trigonelline significantly ameliorated the altered behavioral responses linked to impaired neurological functions by mitigating hyperalgesia, allodynia, and deficits in motor activity in SCI-induced rats.”
Improved Mitochondrial Function
The study also showed that Trigonelline helped protect and restore vital energy production processes within cells affected by spinal cord injury:
- Enhanced Energy Production: Trigonelline significantly increased the levels of key mitochondrial enzymes (NADH, SDH, and cytochrome-C), which are essential for cellular energy production.
- Improved Cellular Health: The overall health and function of cells impacted by the injury were improved in rats treated with Trigonelline.
“The current study further supports the protective efficacy of trigonelline against SCI- induced mitochondrial damage in the rat spinal cord.”
Modulated Cell Death, Inflammation, and Nerve Repair Pathways
Trigonelline treatment helped restore a balance of molecules involved in cell death, inflammation, and cell survival after spinal cord injury.
- Reduced Cell Death (Apoptosis): Lowered markers of cell death (Bax and caspase-3) and increased the survival marker, Bcl-2.
- Decreased Inflammation: Reduced levels of the inflammatory marker COX-II.
- Enhanced Nerve Growth Support: Increased expression of BDNF, a key factor for nerve growth and recovery.
“It notably downregulated apoptotic (Bax and caspase-3) and inflammatory (COX-II) markers, while upregulating Bcl-2 and BDNF mRNA expression in the spinal cord.”
Protected Spinal Cord Integrity
Examination of spinal cord tissue showed that Trigonelline significantly reduced injury-related damage, including nerve cell death and inflammation.
The figure above illustrates the extent of nerve cell damage (striped bar), cell death (white bar), inflammation (black bar), and the size of the injured area (checkered bar) in the rats.
- Normal (N): Shows normal levels in rats without spinal cord injury, providing a baseline for comparison.
- Sham (S): Shows results in rats where the spinal cord was exposed but not injured. This helps isolate the effects of the injury itself.
- SCI Control (SCI): Rats with untreated spinal cord injury (SCI) show severe nerve cell damage (striped bar), inflammation (black bar), cell death (white bar), and a large injured area (checkered bar).
- Methylprednisolone (MP30): Shows results after treatment with methylprednisolone (30 mg/kg), a standard steroid treatment for spinal cord injury. Notice some improvement compared to the SCI Control, but still significant damage.
- Trigonelline (T50, T100, T200): Shows results after treatment with Trigonelline at different doses (50, 100, and 200 mg/kg). Notice that the higher doses of Trigonelline (T100 and T200) show significant reduction in all measures of damage.
Author Summary (Above): This summary outlines the study’s objective, findings, and significance, highlighting Trigonelline’s potential to protect against spinal cord injury by reducing inflammation, tissue damage, and promoting cellular repair.
Conclusion
Trigonelline (100 and 200 mg/kg) significantly reduced pain and sensitivity, improved coordination and movement, and enhanced the transmission of nerve signals in rats with spinal cord injuries.
“Trigonelline exerted neuroprotective effects by ameliorating painful mechanical allodynia and hyperalgesia and enhancing motor nerve conduction velocity in experimental SCI rats.”
Disruptions in mitochondrial enzymes critical for energy production, cell survival, and oxidative stress regulation were restored.
“Trigonelline effectively alleviated SCI-induced alterations in mitochondrial complex levels, resulting in enhanced nicotinamide adenine dinucleotide dehydrogenase, succinate dehydrogenase, redox activity, and cytochrome-C levels.”
Pathways related to cell death, inflammation, and nerve growth were enhanced.
“Furthermore, trigonelline improved spinal mitochondrial enzyme activity and neurotrophic factor (BDNF), and attenuated apoptosis (Bax and caspase-3) and inflammation (COX- II).”
Spinal cord tissue in rats treated with Trigonelline showed less damage from the injury compared to those that didn’t receive the treatment.
“Histological examination of spinal cord tissue indicated that trigonelline significantly ameliorated the histological damage caused by SCI, thereby improving neuronal degeneration, inflammatory cell infiltration, and necrosis.”
“Trigonelline shows neuroprotective properties in SCI rats by reducing allodynia, hyperalgesia, and inflammation, stabilizing mitochondrial enzyme complexes, and modulating apoptotic and neurotrophic factors.”
“Based on our findings and reported clinical investigations, trigonelline shows promise as a therapeutic molecule for SCI treatment.”