Molecular docking, DFT studies, and anti-inflammatory evaluation of peshawaraquinone isolated from Fernandoa adenophylla.

In recent years, there has been growing interest in exploring natural compounds with anti-inflammatory properties for potential therapeutic applications. This study focuses on investigating the anti-inflammatory potential of peshawaraquinone (PAQ), a compound isolated from Fernandoa adenophylla, which is known for its local use in pain relief. We aim to evaluate the efficacy of peshawaraquinone in both in vitro and in vivo models and gain insights into its mode of action. In the in vitro Human red blood cell (HRBC) assay, various concentrations of peshawaraquinone were tested for their ability to inhibit the hemolysis of red blood cells, a well-established indicator of anti-inflammatory activity. The results demonstrated a maximum percent inhibition of 79.69 at a concentration of 100 µM, indicating significant anti-inflammatory potential. Furthermore, the in vivo xylene-induced ear edema model was employed to assess the compound's efficacy in reducing inflammation. Xylene was topically applied to the ear to induce edema, and peshawaraquinone was administered to evaluate its inhibitory effects. The findings revealed a substantial 74.19% reduction in ear edema, accompanied by decreased ear thickness and histopathological improvements, such as inhibited cell infiltration and epidermal hyperplasia. To gain further insights into the compound's mechanism of action, density functional theory (DFT) calculations were performed to investigate its spectroscopic characteristics and geometric properties. Additionally, docking studies were conducted on key targets involved in inflammation, including COX-1 and COX-2. In conclusion, this study showcases the significant anti-inflammatory potential of peshawaraquinone, offering promising prospects for its use as a natural anti-inflammatory agent. The results from both in vitro and in vivo models, as well as the mechanistic insights gained from computational analyses, provide a solid basis for further exploration of peshawaraquinone's therapeutic applications.Communicated by Ramaswamy H. Sarma.

Metabolic and pharmacological profiling of Penicillium claviforme by a combination of experimental and bioinformatic approaches.

BACKGROUND: Penicillium produces a wide range of structurally diverse metabolites with significant pharmacological impacts in medicine and agriculture. For the first time, a complete metabolome of Penicillium claviforme (P. claviforme) (FBP-DNA-1205) was studied alongside pharmacological research in this study. METHODS: The metabolic profile of P. claviforme fermented on Potato Dextrose Broth (PDB) was investigated in this work. The complete metabolomics studies of fungus were performed using GC-MS and LC-MS-QTOF techniques. An in vitro model was utilised to study the cytotoxic and antioxidant activities, while an in vivo model was employed to investigate the antinociceptive and acute toxicity activities. Molecular Operating Environment (MOE) software was used for molecular docking analysis. RESULTS: GC-MS study showed the presence of alkanes, fatty acids, esters, azo and alcoholic compounds. Maculosin, obtain, phalluside, quinoline, 4,4'-diaminostilbene, funaltrexamine, amobarbital, and fraxetin were among the secondary metabolites identified using the LC-MS-QTOF technique. The n-hexane fraction of P. claviforme displayed significant cytotoxic activity in vitro, with an LD50 value of 92.22 µgml-1. The antinociceptive effects in vivo were dose-dependent significantly (p < .001). Interestingly, during the 72 h of investigation, no acute toxicity was demonstrated. In addition, a docking study of tentatively identified metabolites against the inflammatory enzyme (COX-2) supported the antinociceptive effect in an in silico model. CONCLUSION: Metabolic profile of P. claviforme shows the presence of biologically relevant compounds in ethyl acetate extract. In addition, P. claviforme exhibits substantial antioxidant and cytotoxic activities in an in vitro model as well as antinociceptive activity in an in vivo model. The antinociceptive action is also supported by a molecular docking study. This research has opened up new possibilities in the disciplines of mycology, agriculture, and pharmaceutics. Key messagesThe first time explored complete metabolome through GC-MS and LC-MS-QTOF.Both in vivo & in vitro pharmacological investigation of P. claviforme.In silico molecular docking of LC-MS-QTOF metabolites.

Density functional theory, molecular docking and in vivo muscle relaxant, sedative, and analgesic studies of indanone derivatives isolated from Heterophragma adenophyllum.

Heterophragma adenophyllum (HA) is an important medicinal plant which is used in traditional medicine for the treatment of muscular tension and pain. Herein, we report the isolation of methyl,1,2-dihydroxy-2-(3-methylbut-2-en-1-yl)-3-oxo-2,3-dihydro-1H-indene-1-carboxylate (1), from the roots of H. adenophyllum. The isolated compound 1 was evaluated for in vivo muscle relaxant, sedative, and analgesic potential in Swiss albino mice. Results revealed that the isolated compound 1 exhibited a dose- and time-dependent muscle coordination (51%) and a significant (p < 01) sedative effect. It also showed a considerable (p < 0.5) analgesia after 30 min of post treatment and was maintained for up-to 120 min of experimental duration. In acute toxicity studies, no mortality was observed which indicates a preliminary safety of compound 1. Furthermore, the experimental results were compared with the theoretical studies by using density functional theory (DFT). The stability of the compound as well as the flow of electrons was determined by the calculated Frontier orbital analysis. The calculated stretching frequencies, 1H-NMR/13C-NMR chemical shift values and UV-visible spectra were found to be in agreement with experimental values. The results obtained from molecular docking studies were used to explore the mechanism of analgesic and muscle relaxant activity.Communicated by Ramaswamy H. Sarma.