Prudomestin

1 Zanthoxylum sp.

Standardization and xanthine oxidase inhibitory potential of Zanthoxylum armatum fruits.[Pubmed:30342965]

J Ethnopharmacol. 2019 Feb 10;230:1-8.

ETHNOPHARMACOLOGICAL RELEVANCE: Tejovati (Zanthoxylum armatum DC; Family- Rutaceae) popularly known as toothache tree is widely distributed in sub-tropical Himalaya region. Traditionally, The Southeast Asian population of Indo-Nepal origin uses it to treat asthma, gout, pain, and inflammation. The Ayurvedic action of the plant includes the balancing of Vata-Kapha in the body. Which lead to various ailments related to the circulation of blood and water, digestion, immunity, and skin. Therefore, in-vitro xanthine oxidase (XO) inhibition potential of the extract could be worth to explore prospect in the prevention/treatment of gouty affections of the joints and other diseases. AIM OF STUDY: Anti-inflammatory and antioxidant potential of Z. armatum fruit (ZAF) has been reported. To date, no scientific study to validate the claim for gout treatment/management has been attempted so far. The present study deals with the xanthine oxidase inhibitory potential of a various extract of ZAF and marker-based high-performance liquid chromatography (HPLC) standardization of most active fraction. MATERIALS AND METHODS: Liquid-liquid partioning of crude methanol extract of the ZAF followed by repeated column chromatography of most active fraction has resulted in the isolation of seven compounds. Five distinct groups of compounds were isolated, purified, and identified. We have investigated the therapeutic action of ZAF in the management of gout through in-vitro assay of XO, a key enzyme involved in gout pathogenesis. RESULTS: Phytochemical investigation of ZAF has resulted in the isolation of seven compounds of diverse nature. It is noteworthy to mention that out of seven, five compounds have shown the xanthine oxidase inhibitory action. The ethyl acetate fraction was most potent to inhibit XO. The XO inhibitory activity (IC50 values) of isolated marker chemical was ranging from 5.62 to 41.21microM. Three compounds viz. acetyl phenyl acetate (ZA-2), Prudomestin (ZA-6), and tambulin (ZA-7) showed the most potent XO inhibitory activity (IC50 approximately 6microM) comparable with a positive control (Allopurinol, IC50, 3.38microM). This is the first validated HPLC-PDA method for simultaneous analysis and accurate quantification of seven compounds (phenolic acid, acetyl phenyl acetate, xylopyranoside, diphenyl ether and three flavones) in ZAF as well as their distribution in other tissues of the plant. CONCLUSION: Most potent three chemicals (ZA-2, 6 and 7) could be considered as bioactive to ensure the robust quality of the enriched fraction of ZAF with defined XO inhibition potential. Therefore, either single purified component or their enriched fraction could be a better choice for the management of gout than the crude extract of ZAF. Developed HPLC method is suitable for quality assurance analysis and process control of ZAF derived product intended for gout management. XO inhibitory potential exhibited by the characterized compounds validate the traditional use of this ZAF for the treatment of gout. Further, a detailed study is required to assess the effect of ZAF chemicals on serum uric acid and mechanism of XO inhibition.

Characterization and evaluation of bioactive polyphenolic constituents from Zanthoxylum armatum DC., a traditionally used plant.[Pubmed:28242546]

Biomed Pharmacother. 2017 May;89:366-375.

Zanthoxylum armatum or Timoor has been used in different traditional system of medicine due to its aromatic properties and also in the treatment of cancer, diarrhea and cholera. In the present investigation, four chemically distinct compounds namely Tambulin (6), Prudomestin (7), Ombuin (8) and 3, 4, 5, 3', 4', 5'-hexahydroxydiphenyl ether (9) have been isolated and quantified from the fruits. To explore the biological activities, we have further studied the antiproliferative, antimicrobial and antioxidant efficacy. Tambulin which was also found in maximum amount (0.125%) in fruits revealed significant antiproliferative activity (IC50 37.96+/-0.36 to 48.7+/-0.21mug/mL) against breast, liver, colon and skin cancer cell lines corroborated by resilient binding interaction with SDH (-6.76Kcal/mol) and inhibition constant (Ki: 11.02muM). Hexane and ethyl acetate fraction exhibited moderate antibacterial efficacy (MIC: 250-1000mug/mL) against selected pathogenic microbes while Ombuin displayed broad spectrum antibacterial effect with MIC ranges from 125 to 500mug/mL. Total phenolic content (5.27+/-0.06 to 46.12+/-0.40mg/g of gallic acid equivalents), total flavonoids content (6.05+/-0.24 to 14.46+/-0.73mg/g of quercetin equivalents), ferric reducing power (42.35+/-0.85 to 62.52+/-0.66mg/g of ferrous sulfate equivalents) and percent free radical scavenging activity (59.56+/-0.38 to 64.85+/-1.78) were also estimated. Our findings infer that Tambulin exhibited significant antiproliferative activity whereas Ombuin was found to display broad spectrum antibacterial activity which adds one more positive attribute to its traditional usage.

Prudomestin, isolated from the heartwood of Prunus domestica, shows potent xanthine oxidase (XO) inhibitory activity (IC50≈6 µM).

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