Objective: To evaluate anti-arthritic potential of methanolic extract of rhizome of Costus speciosus Koen. Methods: The powdered drug was extracted with 80% methanol. The crude extract was subjected to phytochemical investigation and was evaluated for its anti-arthritic potential by freund's complete adjuvant induced arthritis model in adult wistar albino rats. Determination of different parameters like arthritic score, arthritic index, paw thickness, body weight, and pain, altered liver enzymes and biochemical estimation like, nitric oxide level and Plasma TNF-α level was done. Finally, radiological estimation and histopathology of tibio tarsal joints was performed. Statistical analysis was performed using one way ANOVA followed by Dunnet's test at different p-values. Results: Phytochemical study revealed the presence of flavonoids, phenolic compound, saponins and carbohydrates. For different parameter mentioned above, anti-arthritic activity shown by prophylactic high dose test extract (200 mg/kg) was as potent as standard drug Indomethacin (10 mg/kg). The effect of Prophylactic low dose extract (100 mg/kg) and therapeutic high dose extract (200 mg/kg) was less than that of Indomethacin (10 mg/kg). Furthermore, Therapeutic low dose extract (100 mg/kg) was not effective. Conclusions: The obtained results indicate that Costus speciosus rhizome extract possess significant anti-arthrtic potential.
Background: The extensive search for a novel therapeutic agent against Alzheimer's Disease (AD) in medical and pharmaceutical research still continues. Despite a lot being explored about its therapeutics, there is still much more to learn in order to achieve promising therapeutic agents against ADAlzheimer's. Phytochemicals, especially secondary metabolites, are the major focus of the investigators for AD treatment. Objective: To describe major therapeutics targets of AD and the role of isothiocyanates (ITCs) in modulating these targets. Methods: Scientific databases, including Elsevier, Science Direct, Pub med, were explored. The explored literature was mainly journal publications on pathogenesis and targets of AD, and the effect of various ITCs in the modulation of these targets. Results: The major targets of AD include the Nrf-2/ARE signaling pathway, MAPKs pathway, GSK-3 signaling, and Ubiquitin-Protease system. ITCs, such as Sulforaphane, Allyl isothiocyanates, Moringin, 6-(methylsulfinyl) hexyl ITC, Phenethyl isothiocyanates, and Erucin, were reported to exert a protective effect against AD via modulating one of the several above mentioned targets. Conclusion: This article gives a detailed description of the therapeutic targets of AD and sheds light that phytochemicals, such as ITCs, can exert a protective effect against AD by targeting those pathways. However, properly designed research and clinical trials are required to include ITCs as a mainstream agent against AD.
The recent study was aimed to investigate in-vitro and in-silico determinations of the 3-hydroxy-3-methyl-glutarylcoenzyme A reductase [HMG-CoA reductase (HMGCR)] inhibition potential of the caffeic acid. The in-vitro assay shown the IC 50 values of caffeic acid and pravastatin by 10.162 µM and 40.6 nM which performed up to 83.29% and 85.83% inhibition of HMGCR, respectively. Consequently, the kinetics of inhibition of HMGCR showed significant values of K m and V max of the caffeic acid (0.360198 ± 0.04251; 11.8% and 91.0863 ± 1.65; 1.811%) and pravastatin (10.325 ± 0.9372) [9.077%; 94.2661 ± 2.458 (2.607%)]. Consequently, the molecular docking revealed significant binding energy, bond length, and H-boding of caffeic acid with target enzyme of HMGCR. Accordingly, the interactions of protein-ligand complexes under cytosolic conditions were validated through root mean score fluctuation of molecular dynamics. Subsequently, the gastrointestinal absorption authenticated by the BOILED egg prediction is further validated by Absorption, Distribution, Metabolism, Excretion, And Toxicity (ADMET) assays and iLogP value. The drug likeness values of caffeic acid and pravastatin were found suitable as per the five rules of the Lipinski. Supportively, the toxicity profiles of the caffeic acid and pravastatin was made by the ProTox-II web server. Hence, it can be concluded that caffeic acid has the capabilities to inhibit HMGCR which provides the hypocholesterolemic potential.
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