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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]

The study of inflammatory pain has been one of the most rapidly advancing and expanding areas of pain research in recent years. Studies from our lab have demonstrated the chronic pain-modulating potential of the Phyllanthus species and their probable interaction with various inflammatory mediators involving enzymes like COX-2 and PGE synthase, cytokines like TNF-alpha and IL-1 beta, and with the NMDA receptor. Inflammatory mediators which play a crucial role in chronic inflammatory hyperalgesia and its subsequent modulation were selected for their interactions with 86 structurally diverse phytoconstituents identified from the Phyllanthus species. The docking analysis of the target proteins with the phytochemical ligands was performed using VLifeMDS software. The docking scores and analysis of the interactions of the phytocompounds with target proteins suggest that important molecules like lupeol, phyllanthin, hypopyllanthin, corilagin, epicatechin, and most of the other compounds have the ability to bind to multiple targets involved in inflammatory hyperalgesia. Our study strongly suggests that the findings of the present study could be exploited in the future for designing ligands in order to obtain novel molecules for the treatment and management of chronic pain. [ABSTRACT FROM AUTHOR]

Context: Alocasia indica Schott (Araceae) is used in several regions of India, especially in rural communities, by traditional medicine practitioners to treat diarrhea. However, no scientific data are available to justify the traditional potentials of the plant species in gastrointestinal disorders. Objective: To evaluate the antidiarrheal and in vitro antiprotozoal activities of extracts of leaves of Alocasia indica using various pharmacological models. Materials and methods: In vitro antidiarrheal activity of aqueous and ethanol extracts of Alocasia indica was evaluated against Escherichia coli, Salmonella typhimurium, Shigella flexneri and Staphylococcus aureus by agar well diffusion method. In vivo antidiarrheal activity of the extracts was studied against recinolic acid-induced diarrhea and magnesium sulfate-induced diarrhea. The effect of the extracts on normal intestinal transit, recinolic acid-induced intestinal transit, recinolic acid-induced intestinal fluid accumulation (enteropooling) and gastric emptying was assessed. In vitro antiprotozoal activity of aqueous and ethanol extracts of Alocasia indica was studied against Entamoeba histolytica and Giardia intestinalis. Results: The aqueous and ethanol extracts exhibited significant in vitro antidiarrheal activity compared to the standard drug ciprofloxacine (10 µµg/mL). The plant extracts showed significant (P <0.05) and dose-dependent antidiarrheal activity comparable to that of the reference drug, loperamide (10 mg/kg). The plant extracts exhibited significant in vitro antiprotozoal activity against both protozoa compared to the standard amebicidal and giardicidal drugs, metronidazole and emetine. Discussion and conclusion: The results showed that the extracts of Alocasia indica have significant antidiarrheal and in vitro antiprotozoal activities which support its use in traditional herbal medicine practice. [ABSTRACT FROM AUTHOR]

The study of inflammatory pain has been one of the most rapidly advancing and expanding areas of pain research in recent years. Studies from our lab have demonstrated the chronic pain-modulating potential of the Phyllanthus species and their probable interaction with various inflammatory mediators involving enzymes like COX-2 and PGE synthase, cytokines like TNF-alpha and IL-1 beta, and with the NMDA receptor. Inflammatory mediators which play a crucial role in chronic inflammatory hyperalgesia and its subsequent modulation were selected for their interactions with 86 structurally diverse phytoconstituents identified from the Phyllanthus species. The docking analysis of the target proteins with the phytochemical ligands was performed using VLifeMDS software. The docking scores and analysis of the interactions of the phytocompounds with target proteins suggest that important molecules like lupeol, phyllanthin, hypopyllanthin, corilagin, epicatechin, and most of the other compounds have the ability to bind to multiple targets involved in inflammatory hyperalgesia. Our study strongly suggests that the findings of the present study could be exploited in the future for designing ligands in order to obtain novel molecules for the treatment and management of chronic pain.