Bergapten Attenuates Nitroglycerin-Induced Migraine Headaches through Inhibition of Oxidative Stress and Inflammatory Mediators

Abstract

The present study intended to examine the effect of bergapten and possible mechanisms involved in the treatment of migraine-associated symptoms in the rat model. Five doses of nitroglycerin (10 mg/kg) were injected intraperitoneal to induce migraine headaches in rats with a one-day break between each dose. Treatment groups received nitroglycerin followed after 1 day by bergapten (50 or 100 mg/kg), saline (10 mL/kg), or sumatriptan (50 mg/kg) once daily for 10 days. Behavioral observations were analyzed 2 h after nitroglycerin injections and 1 h 40 min after treatment. The animals were sacrificed 24 h after the last treatment dose. Samples of trigeminal nucleus caudalis (TNC) and cerebral cortex were collected and analyzed for antioxidant activity and expression of inflammatory markers by immunohistochemistry and enzyme-linked immunosorbent assay. Our findings revealed that bergapten notably decreases headache by altering mechanical allodynia, thermal allodynia, light phobicity, and the number of head-scratching incidence in rats. In the cortex and TNC regions, antioxidant factors were restored, and lipid peroxidation was significantly reduced. Furthermore, bergapten decreased the expression of inflammatory markers, such as nuclear factor kappa B (NF-Kb) and tumor necrosis factor-alpha (TNF-α), as evidenced by immunohistochemistry and ELISA. These results suggest that bergapten exhibits headache-relieving activity, possibly mediated through antioxidant and anti-inflammatory pathways.

Nephroprotective Effect of Bergapten Against Cyclophosphamide-Mediated Renal Stress, Inflammation, and Fibrosis in Wistar Rats: Probable Role of NF-kB and TGF-β1 Signaling Molecules

“…BGP-3, however, failed to reduce the marker of oxidative stress compared to CPM 200, as shown in Figure . Findings of our study correlate with the previously published study where BGP exhibited significant antioxidant activity in various preclinical models. , …”

“…Findings of our study correlate with the previously published study where BGP exhibited significant antioxidant activity in various preclinical models. 19,20 CPM-mediated renal toxicity is not only a manifestation of oxidative stress, but induced inflammation also plays a pivotal role in its toxicological attributes. 16 Among various mediators of inflammation caused by CPM, NF-kB is one of the extensively explored regulators of renal inflammation.…”

“…Findings of our study correlate with the previously published study where BGP exhibited significant antioxidant activity in various preclinical models. 18 , 19 …”

Regulating Neuroinflammatory Biomarkers in Nitroglycerine induced Migraine in Rats: A Therapeutic role of Chrysanthemum indicum extract

“…Our results suggesting that the CIHE attenuates the biomarkers such as MMP9[16], TNF-α[26], NFkB [27], IL-1β[28], CGRP [29], and iNOS [30] are involved in the migraine attack which represented in (Fig. 1).…”

A role of NLRP3 and MMP9 in migraine progression: a systematic review of translational study

“…Scientists have yet to find a medication that treats migraine for ten decades. They started targeting different biomarkers such as NFkB (2)(3)(4), interleukins (5-7), serotonin (8)(9)(10)(11), etc. which was released immensely in the migraineurs but unable to find a way to cure.…”