A new ellagic acid rhamnoside and other biologically active compounds from roots and stems of Synadenium Glaucescens pax

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Date

2023-05

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Sokoine University of Agriculture

Abstract

Medicinal plants have been used as a source of drugs and drug templates. The extracts of Synadenium glaucescens Pax (SG) from roots and stems contain bioactive secondary metabolites against bacterial and viral infections. However, majority of its pure compounds were uncharacterized and their phytochemical profiles in different phytogeographical regions were unknown. Therefore, this study aimed at characterization of more compounds which are promising drug leads. Furthermore, the study investigated the phytochemical profiles of SG from three regions of Tanzania. Samples of SG were collected from Njombe, Morogoro and Tanga regions as representatives of three phytogeographical zones of Tanzania. All sample were dried in a cold and dark room between 15 to 18 oC at the Tanzania Tree Seed Agency-Morogoro. Samples were pulverized using a laboratory milling machine (Christy Hunt Engineering Ltd, England) to afford approximately 1 mm particles’ size. The isolation of pure compounds involved root barks and stem barks of SG from Njombe. Phytochemical profiling involved five parts (root barks, root wood, stem barks, stem wood and leaves). Sample extraction was done by total maceration using either methanol or ethanol. Fractionation of the crude extracts was done through vacuum Liquid chromatography in solvent gradient systems from Hexane, ethyl acetate/ dichloromethane and finally methanol/ ethanol. Concentration of extracts was done using rotary evaporator at <60 oC. Isolation of pure compounds was done by column chromatography in a solvent gradient system. A single spot on the thin layer chromatography plate in both treatments was an indicator for a pure compound. Structures of compounds were elucidated through (1D and 2D) of a 600 MHz Bruker Avance III HD nuclear magnetic resonance (NMR) machine. Confirmation of structures involved LC/GCMS, FTMS-ESI, NIST library and in comparison, to the literature. The SciFinder database was used for reference of a new compound. The processing NMR spectral data was performed using Bruker TopSpin 3.6.2 while compound structures were drawn in ChemDraw Professional 16.0. Biological activities involved cytotoxicity and antibacterial tests of pure compounds. Cytotoxicity studies were done using Brine shrimp assay involving Artemia salina cysts which were hatched and used within 24 hours of incubation. The varying concentrations (2400- ȝJ PO LQ P/ RI % v/v DMSO were employed in duplicate. 7KH FRPSRXQGV¶ concentration killing 50 % of the nauplii larvae was determined. An In vitro antibacterial efficacy of pure compounds was done by using microtitre plate assay. Four standard strains of bacteria were used (Staphylococcus aureus ATCC 25923, Enterococcus faecalis ATCC51559, Escherichia coli ATCC25922 and Pseudomonas aeruginosa ATCC 27853. The activities of the compounds were evaluated using the observed MIC values. Determination of the phytochemical profiles on the thin layer FKURPDWRJUDSK\ SODWHV XVHG DQ RSWLPDO ȝ/ YROXPH RI mg/mL. The number of compounds were recorded at 254nm, 365nm of an ultraviolet lamp and after colour reaction. Data from the thin layer chromatography were analysed in JMP statistical software. A total of fifteen (15) compounds were isolated and elucidated. A new ellagic acid rhamnoside 3',4'-di-O- methylellagic acid-4-Į-L-rhamnopyranoside, 28 mg (32) was isolated as greyish powder. it showed high res. FTMS-ESI- of 476.0921 and melting point of 251.0~ 252.7 oC. Other known phenolics 3,4,3'-tri-O-methylellagic acid, 14 mg (33), hemicosanylferulate,65 mg (34) and octacosylferulate, 19 mg (35) were also isolated. The study also led to isolation of two hydrocarbons from the root barks: 1-nonacosene, 11 mg (38), and hexacosane,173 mg (39) and one fatty acid from the stem barks; hexacosanoic acid, 26 mg (40). The isolated triterpenoids include Lupeol, 65 mg (18) from the stem barks, euphol, 1855.5 mg (28) from both roots and stem barks, epifriedelanol, 167 mg (36) from both roots and stem barks and a steroid ȕ-sitosterol 64 mg (30) from the root barks. Cytotoxicity tests indicated that all the tested compounds were non-toxic (LC50 ! ȝJ P/) up to a maximum tested FRQFHQWUDWLRQ RI ȝJ P/ Octacosylferulate demonstrated strong activity against S. aureus (MIC= 0.125 mg/mL) Phytochemical screening by TLC indicated a significant variation in concentration and distribution of compounds in SG among the three regions (p< 0.0001). Njombe registered the highest number of compounds (mean= 12.4000) while Morogoro had the least of all (mean= 9.7000). Euphol, a triterpenoid in root barks was detected to be at the highest concentration in Tanga and the lowest in Morogoro. Derivatives of ellagic acid were detected in root barks at all ages and locations. The results also indicated continuous disappearance of red fluorescing compounds in stems barks and leaves as the plant age increased. The number of compounds increased with age while the optimal age for a maximum number of phytochemicals was 3 to 4.5 years. Furthermore, the stem barks registered the highest number of phytochemicals (>15). A new compound: 3',4'-di-O-methylellagic acid-4-Į-L- rhamnopyranoside along with 14 other known compounds were isolated from root and stem barks of SG. The isolated compounds during this study represent six major groups of secondary metabolites of pharmacological importance which are Phenolics, triterpenoids, steroids, long chain hydrocarbons, long chain amine and Fatty acids. This new compound is suggested to serve as a marker for standardization and quality control of any formulation from the root barks of S. glaucescens Pax.

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Keywords

Ellagic acid rhamnoside, Biologically active, Compounds from roots, Stems synadenium, Glaucescens pax

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