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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]

Introduction: Leishmaniasis is caused by protozoa of the genus Leishmania, classified as tegumentary and visceral. The disease treatment is still a serious problem, due to the toxic effects of available drugs, the costly treatment and reports of parasitic resistance, making the search for therapeutic alternatives urgent. This study assessed the in vitro anti-leishmanial potential of the extract, fractions, and isoeleutherin from Eleutherine plicata, as well as the in silico interactions of isoeleutherin and its analogs with Trypanothione Reductase (TR), in addition to predicting pharmacokinetic parameters. Methods: From the ethanolic extract of E. plicata (EEEp) the dichloromethane fraction (FDEp) was obtained, and isoeleutherin isolated. All samples were tested against promastigotes, and parasite viability was evaluated. Isoeleutherin analogues were selected based on similarity in databases (ZINK and eMolecules) to verify the impact on structural change. Results and Discussion: The extract and its fractions were not active against the promastigote form (IC50 > 200 μg/mL), while isoeleutherin was active (IC50 = 25 μg/mL). All analogues have high intestinal absorption (HIA), cell permeability was moderate in Caco2 and low to moderate in MDCK. Structural changes interfered with plasma protein binding and blood-brain barrier permeability. Regarding metabolism, all molecules appear to be CYP3A4 metabolized and inhibited 2-3 CYPs. Molecular docking and molecular dynamics assessed the interactions between the most stable configurations of isoeleutherin, analogue compound 17, and quinacrine (control drug). Molecular dynamics simulations demonstrated stability and favorable interactions with TR. In summary, fractionation contributed to antileishmanial activity and isoleutherin seems to be promising. Structural alterations did not contribute to improve pharmacokinetic aspects and analogue 17 proved to be more promising than isoeleutherin, presenting better stabilization in TR. [ABSTRACT FROM AUTHOR]

Lamiaceae (Labiatae) is a medicinally significant plant family featuring key species like Salvia aegyptiaca, S. cabulica, S. coccinea, S. glutinosa, S. officinalis, S. haematodes, S. hians, S. lanata, S. macrosiphon, S. moorcroftiana, S. spinosa, S. sclarea, and S. plebeia. These species exhibit diverse pharmacological activities attributed to essential oils and phytochemi-cals, including antioxidant, antiasthmatic, antitumor, anti-inflammatory, analgesic, etc. This re-view covers extensive phytomedicinal aspects of some important plants of the genus Salvia., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)