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On valorization of solvent extracts of Terminalia arjuna (arjuna) upon DNA scission and free radical scavenging improves coupling responses and cognitive functions under in vitro conditions.

ABSTRACT: Chronic diseases have been treated using the phytochemical concepts of ethnomedicinal plant-derived herbal products. Terminalia arjuna, a significant ethnomedicinal plant, was revisited and reconnoitred for antioxidant, free radical scavenging, and DNA nicking inhibiting activity under H_2O2 conditions using 21 solvent extracts. Ferric reducing antioxidant power (FRAP), 2,2-diphenyl-1-picrylhydrazyl (DPPH), 2,2'-azino-bis-3-ethylbenzothiazoline-6-sulphonic acid, and nitrous oxide scavenging (%) were found to have a strong positive association and interaction (PCA 1 explains 84.54% variation) with ethanol bark (Etoh-AB) (Meoh-AF). TPC (144.67-1794 µg/mL GAE) and TFC (2.5-34 µM Fe(II)/g were highest in Etoh-AB. In a pattern of combined solvent extracts, Etoh-AB had the highest antioxidant capacity, accompanied by Etoh-AL ≥ Meoh-AB ≥ Dw-AF. With R² = 0.94, the DNA nicking inhibition behaviour parameters relative front, relative quantity, band (%), and lane (%) formed a positive significant (p < 0.01) connection. For the first time, we show that Etoh-AB nicks supercoiled, circular plasmid DNA in a way that is comparable to normal antioxidants. Normal antioxidants with the ability to prevent DNA nicking include Butylated hydroxy anisole < Butylated hydroxy toluene < ascorbic acid < and Gallic acid. Gallic acid (m/z 170.0208 g/mol) and Ellagic acid (m/z 302.0063 g/mol were present in high concentrations in solvent extracts. 0.48 mg was found to be the effective concentration for inhibiting relative DNA nicking. The current study is the first of its kind to show that steroid concentrations are higher in bark fractions of acetone, ethanol, and methanol. Furthermore, T. arjuna solvent extracts provide a wealth of information on phytochemical profiling, antioxidant ability, and DNA nicking inhibition, which may be useful for exploring the natural way and further research to develop a remedy against geriatric chronic disease. Despite the fact that ethanol is very close to methanol in terms of solvent toxicity, the current study identified it as the preferred solvent. Thus, the current research revisits previous studies and explores the potentiality of non-polar and polar aprotic and polar protic solvent systems, which lend credence to bioactive compounds that may be useful in isolating and formulating safe and cost effective herbal medicament for livestocks and aquaculture, and drugs for deoxygenerative human diseases, and can also be investigated further to instil environmental frugality.

SUBMITTER: Meena DK

PROVIDER: S-EPMC8137696 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:Kidney stone formation during hyperoxaluric condition is inherently dependent on the interaction between renal epithelial cells and calcium oxalate (CaOx) crystals. Although modern medicine has progressed in terms of removal of these stones, recurrence and persistent side effects restricts their use. Strategies involving plant based agents which could be used as adjunct therapy is an area which needs to be explored. Plant proteins having antilithiatic activity is a hitherto unexplored area and therefore, we conducted a detailed identification and characterization of antilithiatic proteins from Terminalia arjuna (T. arjuna). Proteins were isolated from the dried bark of T. arjuna and those having molecular weights > 3 kDa were subjected to anion exchange chromatography followed by gel filtration chromatography. Four proteins were identified exhibiting inhibitory activity against CaOx crystallization and crystal growth kinetics The cytoprotective and anti-apoptotic efficacy of these purified proteins was further investigated on oxalate injured renal epithelial cells (MDCK and NRK-52E) wherein, injury due to oxalate was significantly attenuated and led to a dose dependent increase in viability of these cells. These proteins also prevented the interaction of the CaOx crystals to the cell surface and reduced the number of apoptotic cells. Identification of these 4 anionic proteins from the bark of T. arjuna was carried out by Matrix-assisted laser desorption/ionization-time of flight Mass spectrometry (MALDI-TOF MS). This was followed by database search with the MASCOT server and sequence similarity was found with Nuclear pore anchor, DEAD Box ATP-dependent RNA helicase 45, Lon protease homolog 1 and Heat shock protein 90-3. These novel proteins isolated from T. arjuna have the potential to inhibit CaOx crystallization and promote cell survival and therefore, offer novel avenues which need to be explored further for the medical management of urolithiasis.

Project description:Background:Plants belonging to the genus Terminalia such as Terminalia bellirica and Terminalia sericea are used traditionally to treat several diseases and health disorders. Up to this date, the roots of Terminalia sericea and the fruits of Terminalia bellirica are the mostly studied plant parts. The phytochemical composition and the biological activities of the leaves of both species are not well identified so far. Methods:The secondary metabolites of Terminalia bellirica and Terminalia sericea leaves were identified using HPLC-PDA-MS/MS. The antioxidant activities of the leaves extracts were determined by DPPH and FRAP assays. The hepatoprotective potential was evaluated in rats with D-galactosamine induced liver damage. The effect of the extracts on the expression of the anti-apoptotic marker Bcl-2 was measured in an immunohistochemical study. The most abundant compounds identified in the studied extracts were docked into Bcl-2: Bim (BH3) interaction surface using molecular operating environment software. Results:A total of 85 secondary metabolites were identified in the leaf extracts of both species. Ellagitannins such as corilagin, chebulagic acid, galloylpunicalagin, and digalloyl-hexahydroxydiphenoyl-hexoside were found to be the major components in Terminalia bellirica whereas flavonoid glycosides including quercetin rutinoside and quercetin galloyl-glucoside were highly abundant in Terminalia sericea. The studied extracts exhibited pronounced antioxidant activities, moderate anti-apoptotic and hepatoprotective potential. In silico docking experiments revealed that the compounds abundant in the extracts were able to bind to Bcl-2: Bim (BH3) interaction surface with an appreciable binding free energy. Discussion:The antioxidant and hepatoprotective activities exhibited by the studied extracts might be attributed to the high content of the polyphenols. The anti-apoptotic activity could be due to the interference with the apoptotic pathway mediated by Bcl-2: Bim interaction. These findings support the medicinal relevance of Terminalia bellirica and Terminalia sericea and provide a rational base for their utilization in folk medicine.

Project description:Aqueous extract of the bark of Terminalia arjuna (TA) is used by a large population in the Indian subcontinent for treating various cardiovascular conditions. Animal experiments have shown its anti-atherogenic, anti-hypertensive, and anti-inflammatory effects. It has several bioactive ingredients with hemodynamic, ROS scavenging, and anti-inflammatory properties. Earlier we have done limited proteomic and transcriptomic analysis to show its efficacy in ameliorating cardiac hypertrophy induced by isoproterenol (ISO) in rats. In the present study we have used high-throughput sequencing of the mRNA from control and treated rat heart to further establish its efficacy. ISO (5 mg/kg/day s.c.) was administered in male adult rats for 14 days to induce cardiac hypertrophy. Standardized aqueous extract TA bark extract was administered orally. Total RNA were isolated from control, ISO, ISO + TA, and TA treated rat hearts and subjected to high throughput sequence analysis. The modulations of the transcript levels were then subjected to bio-informatics analyses using established software. Treatment with ISO downregulated 1,129 genes and upregulated 204 others. Pre-treatment with the TA bark extracts markedly restored that expression pattern with only 97 genes upregulated and 85 genes downregulated. The TA alone group had only 88 upregulated and 26 downregulated genes. The overall profile of expression in ISO + TA and TA alone groups closely matched with the control group. The genes that were modulated included those involved in metabolism, activation of receptors and cell signaling, and cardiovascular and other diseases. Networks associated with those genes included those involved in angiogenesis, extracellular matrix organization, integrin binding, inflammation, drug metabolism, redox metabolism, oxidative phosphorylation, and organization of myofibril. Overlaying of the networks in ISO and ISO_TA group showed that those activated in ISO group were mostly absent in ISO_TA and TA group, suggesting a global effect of the TA extracts. This study for the first time reveals that TA partially or completely restores the gene regulatory network perturbed by ISO treatment in rat heart; signifying its efficacy in checking ISO-induced cardiac hypertrophy.

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On valorization of solvent extracts of Terminalia arjuna (arjuna) upon DNA scission and free radical scavenging improves coupling responses and cognitive functions under in vitro conditions.

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