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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]

Anxiety is an unpleasant state, which can critically decrease the quality of life is often accompanied by nervous behaviour and rumination. Niranthin is a lignan isolated from various Phyllanthus sources. The literature survey on niranthin highlights wide ranges of the therapeutic potentials. In a present study, based on our previous investigations, we evaluated pure, isolated and characterized niranthin as an anxiolytic agent. The niranthin [6-[(2R,3R)-3-[(3,4-dimethoxyphenyl)methyl]-4-methoxy-2-(methoxymethyl)butyl]-4-methoxy-1,3-benzodioxole] was purchased from commercial source and further subjected for assessment of its anxiolytic potentials using popular animal models including Elevated plus-maze model/test (EPM) and Light & Dark Exploration test (L&D). GABA-A receptor mediation was evaluated by pretreating the mice with the GABA-A receptor antagonist Flumazenil before the EPM task. Molecular docking simulation studies (pdb id: 4COF) carried out by Vlife QSAR software showed that niranthin (docking score: − 62.1714 kcal/mol) have shown comparatively best docking score compared to the standard drug Diazepam (docking score: − 63.1568 kcal/mol). To conclude, Niranthin has probable potential in the management of anxiety disorder. Our in-silico and in-vivo analysis (indirectly) indicated the plausible role of GABA mediation for anxiolytic activity. Although, these studies are preliminary, future in depth experimental explorations will be required to use Niranthin as anti-anxiety drug in near future. [ABSTRACT FROM AUTHOR]

The current study was aimed at evaluating the antihyperalgesic effects of lignans (phyllanthin and hypophyllanthin) and tannin (corilagin) rich three standardized extracts of Phyllanthus amarus in a model of chronic musculoskeletal inflammatory pain. Three percent carrageenan injected in the gastrocnemius muscle produced hyperalgesia to mechanical and heat stimuli ipsilaterally, which spreads to the contralateral side within 7 to 9 days. To investigate the effects on chronic thermal and mechanical hypersensitivity, three extracts of P. amarus in three doses (100, 200, and 400 mg/kg) were administered to animals intraperitoneally from 14th day to 22nd day after intramuscular injection of carrageenan. It was observed that intraperitoneal administrations of Phyllanthus extracts showed antihyperalgesic activity, as they elevated thermal and mechanical threshold, which was supported by histopathological observations along with reduction in prostaglandin E2 (PGE2) concentration. In conclusion, we strongly suggest that the observed antihyperalgesic and antiinflammatory effects of P. amarus in current pain model are mediated via spinal or supraspinal neuronal mechanisms, mainly by inhibition of PGE2. Modulation of chronic muscular inflammation may be due to presence of phytoconstituents like phyllanthin, hypophyllanthin, and corilagin, which offers a promising means for treatment of chronic muscle pain. Copyright © 2015 John Wiley & Sons, Ltd. [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]