(Combretaceae): Pharmacological Effects, LC-ESI-MS/MS Profiling and In Silico Attributes

Overview

Journal Metabolites

Publisher MDPI

Date 2023 Jul 29

PMID 37512501

Authors

Muhammad Khurm

Yuting Guo

QingQing Wu

Xinxin Zhang

Muhammad Umer Ghori

Muhammad Fawad Rasool

Imran Imran

Fatima Saqib

Muqeet Wahid

Zengjun Guo

Affiliations

Soon will be listed here.

Abstract

In folklore medicine, is used to treat various illnesses. The main objective of this study was a comprehensive investigation of leaf aqueous extract (CLAE) for its antioxidant, cardioprotective, anxiolytic, antidepressant and memory-enhancing capabilities by using different in vitro, in vivo and in silico models. The in vitro experimentation revealed that CLAE consumed an ample amount of total phenolics (67.70 ± 0.15 µg GAE/mg) and flavonoids (47.54 ± 0.45 µg QE/mg) with stronger antiradical effects through DPPH (IC = 16.66 ± 0.42 µg/mL), TAC (77.33 ± 0.41 µg AAE/mg) and TRP (79.11 ± 0.67 µg GAE/mg) assays. The extract also displayed suitable acetylcholinesterase (AChE) inhibitory (IC = 110.13 ± 1.71 µg/mL) activity through a modified Ellman's method. The toxicology examination presented no mortality or any signs of clinical toxicity in both single-dose and repeated-dose tests. In line with the cardioprotective study, the pretreatment of CLAE was found to be effective in relieving the isoproterenol (ISO)-induced myocardial injury in rats by normalizing the heart weight index, serum cardiac biomarkers, lipid profile and various histopathological variations. In the noise-stress-induced model for behavior attributes, the results demonstrated that CLAE has the tendency to increase the time spent in the central zone and elevated open arms in the open field and elevated plus maze tests (examined for anxiety assessment), reduced periods of immobility in the forced swimming test (for depression) and improved recognition and working memory in the novel object recognition and Morris water maze tests, respectively. Moreover, the LC-ESI-MS/MS profiling predicted 53 phytocompounds in CLAE. The drug-likeness and ADMET analysis exhibited that the majority of the identified compounds have reasonable physicochemical and pharmacokinetic profiles. The co-expression of molecular docking and network analysis indicated that top-ranked CLAE phytoconstituents act efficiently against the key proteins and target multiple signaling pathways to exert its cardiovascular-protectant, anxiolytic, antidepressant and memory-enhancing activity. Hence, this artifact illustrates that the observed biological properties of CLAE elucidate its significance as a sustainable source of bioactive phytochemicals, which appears to be advantageous for pursuing further studies for the development of new therapeutic agents of desired interest.

Citing Articles

Unlocking the hepatoprotective potential of the parasitic plant Poir. aqueous extract against CCl-induced liver injury in rat.

Bedoui A, Mufti A, Feriani A, Baccari H, Bouallegue A, Kharrat M Front Pharmacol. 2024; 14:1320062.

PMID: 38239200 PMC: 10794580. DOI: 10.3389/fphar.2023.1320062.

References

Afifi H, Al Marzooqi H, Tabbaa M, Arran A . Phytochemicals of spp. as a Natural and Safe Source of Phenolic Compounds and Antioxidants. Molecules. 2021; 26(4). PMC: 7922956. DOI: 10.3390/molecules26041069. View

Endo T, Nakagawa T, Iguchi F, Kita T, Okano T, Sha S . Elevation of superoxide dismutase increases acoustic trauma from noise exposure. Free Radic Biol Med. 2005; 38(4):492-8. DOI: 10.1016/j.freeradbiomed.2004.11.008. View

Chen Y, Pan R, Zhang J, Liang T, Guo J, Sun T . Pinoresinol diglucoside (PDG) attenuates cardiac hypertrophy via AKT/mTOR/NF-κB signaling in pressure overload-induced rats. J Ethnopharmacol. 2021; 272:113920. DOI: 10.1016/j.jep.2021.113920. View

Eladwy R, Mantawy E, El-Bakly W, Fares M, Ramadan L, Azab S . Mechanistic insights to the cardioprotective effect of blueberry nutraceutical extract in isoprenaline-induced cardiac hypertrophy. Phytomedicine. 2018; 51:84-93. DOI: 10.1016/j.phymed.2018.10.009. View

Wang S, Yu Y, Feng Y, Zou F, Zhang X, Huang J . Protective effect of the orientin on noise-induced cognitive impairments in mice. Behav Brain Res. 2015; 296:290-300. DOI: 10.1016/j.bbr.2015.09.024. View

Shi L, Du X, Zuo B, Hu J, Cao W . Qige Huxin Formula Attenuates Isoprenaline-Induced Cardiac Fibrosis in Mice via Modulating Gut Microbiota and Protecting Intestinal Integrity. Evid Based Complement Alternat Med. 2022; 2022:2894659. PMC: 9328975. DOI: 10.1155/2022/2894659. View

Hornick A, Lieb A, Vo N, Rollinger J, Stuppner H, Prast H . The coumarin scopoletin potentiates acetylcholine release from synaptosomes, amplifies hippocampal long-term potentiation and ameliorates anticholinergic- and age-impaired memory. Neuroscience. 2011; 197:280-92. PMC: 3212650. DOI: 10.1016/j.neuroscience.2011.09.006. View

Liu W, Shi X, Yang Y, Cheng X, Liu Q, Han H . In vitro and in vivo metabolism and inhibitory activities of vasicine, a potent acetylcholinesterase and butyrylcholinesterase inhibitor. PLoS One. 2015; 10(4):e0122366. PMC: 4388757. DOI: 10.1371/journal.pone.0122366. View

Liu L, Shen P, He T, Chang Y, Shi L, Tao S . Noise induced hearing loss impairs spatial learning/memory and hippocampal neurogenesis in mice. Sci Rep. 2016; 6:20374. PMC: 4740884. DOI: 10.1038/srep20374. View

10.

Luo L, Sun T, Yang L, Liu A, Liu Q, Tian Q . Scopoletin ameliorates anxiety-like behaviors in complete Freund's adjuvant-induced mouse model. Mol Brain. 2020; 13(1):15. PMC: 7001522. DOI: 10.1186/s13041-020-0560-2. View

11.

Zholobenko A, Modriansky M . Silymarin and its constituents in cardiac preconditioning. Fitoterapia. 2014; 97:122-32. DOI: 10.1016/j.fitote.2014.05.016. View

12.

Qi C, Liu X, Xiong T, Wang D . Tempol prevents isoprenaline-induced takotsubo syndrome via the reactive oxygen species/mitochondrial/anti-apoptosis /p38 MAPK pathway. Eur J Pharmacol. 2020; 886:173439. DOI: 10.1016/j.ejphar.2020.173439. View

13.

Paul R, Borah A . Global loss of acetylcholinesterase activity with mitochondrial complexes inhibition and inflammation in brain of hypercholesterolemic mice. Sci Rep. 2017; 7(1):17922. PMC: 5738385. DOI: 10.1038/s41598-017-17911-z. View

14.

Nalban N, Sangaraju R, Alavala S, Mir S, Jerald M, Sistla R . Arbutin Attenuates Isoproterenol-Induced Cardiac Hypertrophy by Inhibiting TLR-4/NF-κB Pathway in Mice. Cardiovasc Toxicol. 2019; 20(3):235-248. DOI: 10.1007/s12012-019-09548-3. View

15.

Zhou Y, Li M, Song J, Shi Y, Qin X, Gao Z . The cardioprotective effects of the new crystal form of puerarin in isoproterenol-induced myocardial ischemia rats based on metabolomics. Sci Rep. 2020; 10(1):17787. PMC: 7575583. DOI: 10.1038/s41598-020-74246-y. View

16.

Ayaz M, Sadiq A, Junaid M, Ullah F, Ovais M, Ullah I . Flavonoids as Prospective Neuroprotectants and Their Therapeutic Propensity in Aging Associated Neurological Disorders. Front Aging Neurosci. 2019; 11:155. PMC: 6606780. DOI: 10.3389/fnagi.2019.00155. View

17.

Berry C, Hare J . Xanthine oxidoreductase and cardiovascular disease: molecular mechanisms and pathophysiological implications. J Physiol. 2003; 555(Pt 3):589-606. PMC: 1664875. DOI: 10.1113/jphysiol.2003.055913. View

18.

Beserra A, Vilegas W, Tangerina M, Ascencio S, Soares I, Pavan E . Chemical characterisation and toxicity assessment in vitro and in vivo of the hydroethanolic extract of Terminalia argentea Mart. leaves. J Ethnopharmacol. 2018; 227:56-68. DOI: 10.1016/j.jep.2018.08.025. View

19.

Shah S, Akram M, Riaz M, Munir N, Rasool G . Cardioprotective Potential of Plant-Derived Molecules: A Scientific and Medicinal Approach. Dose Response. 2019; 17(2):1559325819852243. PMC: 6537262. DOI: 10.1177/1559325819852243. View

20.

Ul-Haq I, Ullah N, Bibi G, Kanwal S, Ahmad M, Mirza B . Antioxidant and Cytotoxic Activities and Phytochemical Analysis of Euphorbia wallichii Root Extract and its Fractions. Iran J Pharm Res. 2013; 11(1):241-9. PMC: 3813110. View