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Fibromyalgia (FM) is characterized by chronic pain and heightened sensitivity to painful stimuli. This study investigated the potential of Niranthin (NR), a natural compound derived from Phyllanthus species, in a rat model of FM. We employed a multifaceted approach to comprehensively assess the potential benefits of NR as a treatment for FM, including in-vivo analysis, molecular docking studies, and molecular dynamics (MD) simulations, and Density Functional Theory (DFT) calculations. Three doses of NR (5 mg/kg, 10 mg/kg and 20 mg/kg) significantly reduced mechanical allodynia induced by acidic saline injections. In an acute study, NR dosing increased the mechanical threshold in both ipsilateral and contralateral paws. In a four-day study, twice-daily NR treatment further elevated the mechanical threshold. Temporary treatment interruption led to a re-establishment of allodynia, but subsequent reinitiation of NR treatment remained effective, ruling out tolerance development. MD simulations were conducted to investigate the stability and dynamics of NR-target complexes, revealing stable binding interactions and conformational changes associated with NR binding. Docking calculations indicated that the NR molecule had a similar binding affinity to the drug Amiloride towards Acid-sensing ion channels (ASICs). NR showed interactions with amino acid residues, including LYS 373, ARG 370, GLU 374 and GLN 277. DFT calculations provided insights into the electronic and structural properties of NR and its interactions with FM-related molecular target ASICs. We propose that NR may modulate ASICs, leading to decreased pain sensitivity in FM rats. However, further research is required to fully understand the mechanism of action and explore NRs therapeutic potential for the treatment of FM. Fibromyalgia, a condition characterized by chronic pain and heightened pain sensitivity, was studied with Niranthin (NR), a natural compound from Phyllanthus species. Various NR doses reduced mechanical allodynia in a rat model of fibromyalgia, and NR doses improved mechanical thresholds. NR exhibited strong binding affinity to ASICs, similar to the drug Amiloride. NR interacted with specific amino acid residues, suggesting its potential role in modulating ASICs. Therapeutic Potential: NR shows promise in decreasing pain sensitivity in fibromyalgia rats, but further research is required to understand the mechanism fully and assess its therapeutic potential. [ABSTRACT FROM AUTHOR]

Objective(s) This study planned to assess antidepressant like activity of aqueous extract from leaves of Citrus maxima Merr. (Rutaceae). Materials and Methods Boiling was used for aqueous extraction. Acute toxicity study was performed in mice. Antidepressant activity was studied using locomotor activity test, modified forced swimming test (FST) and tail suspension test (TST). Three doses 100, 200 and 300 mg/kg of aqueous extract of leaves were selected for testing. Fluoxetine (20 mg/kg, i.p.) and imipramine (30 mg/kg, i.p.) were used as the standard drugs. Results Aqueous extract of Citrus maxima leaves significantly reduced immobility time in both TST and FST. In locomotor activity testing it showed psychostimulant effect. Extract increased the climbing behavior in FST, which is similar to effect observed with imipramine. Conclusion The results of this study suggest that antidepressant like effect of Citrus maxima seems to be mediated by an increase in norepinephrine level in synapses. [ABSTRACT FROM AUTHOR]