Anticancer efficacies of persicogenin and homoeriodictyol isolated from Rhus retinorrhoea

Saquib, Quaiser; Ahmed, Sarfaraz; Ahmad, Moaz; Al‐Rehaily, Adnan J.; Siddiqui, Maqsood A.; Faisal, Mohammad; Ahmad, Javed; Alsaleh, Asma N.; Alatar, Abdulrahman A.; Al‐Khedhairy, Abdulaziz A.

doi:10.1016/j.procbio.2020.02.008

Cited by 11 publications

(8 citation statements)

References 55 publications

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“…[60] In addition, homoeriodictyol is known to upregulate the expression of p53, caspase-3, and Bax genes, providing novel insights into its comparative anticancer efficacy and suggesting its underlying clinical applications as anticancer agents. [61] These findings validated the active components screened by network pharmacology and their interactions with BC targets. However, little is known about their effects on BC.…”

Section: Discussionsupporting

confidence: 58%

Uncovering the molecular mechanism of Gynostemma pentaphyllum (Thunb.) Makino against breast cancer using network pharmacology and molecular docking

Wang

et al. 2022

Medicine

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Because of their strong anti-cancer efficacy with fewer side effects, traditional Chinese medicines (TCM) have attracted considerable attention for their potential application in treating breast cancer (BC). However, knowledge about the underlying systematic mechanisms is scarce. Gynostemma pentaphyllum (Thunb.) Makino (GP), a creeping herb, has been regularly used as a TCM to prevent and treat tumors including BC. Again, mechanisms underlying its anti-BC properties have remained elusive. We used network pharmacology and molecular docking to explore the mechanistic details of GP against BC. The TCM systems pharmacology database and analysis platform and PharmMapper Server database were used to retrieve the chemical constituents and potential targets in GP. In addition, targets related to BC were identified using DrugBank and Therapeutic Target Database. Protein-protein interaction network, Gene Ontology, and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses of crucial targets were performed using the Search Tool for the Retrieval of Interacting Genes/Proteins and database for annotation, visualization, and integrated discovery databases, whereas the network visualization analysis was performed using Cytoscape 3.8.2. In addition, the molecular docking technique was used to validate network pharmacology-based predictions. A comparison of the predicted targets of GP with those of BC-related drugs revealed 26 potential key targets related to the treatment of BC, among which ALB, EGFR, ESR1, AR, PGR, and HSP90AA1 were considered the major potential targets. Finally, network pharmacology-based prediction results were preliminarily verified by molecular docking experiments. In addition, chemical constituents and potential target proteins were scored, followed by a comparison with the ligands of the protein. We provide a network of pharmacology-based molecular mechanistic insights on the therapeutic action of GP against BC. We believe that our data will serve as a basis to conduct future studies and promote the clinical applications of GP.Abbreviations: ALB = albumin, AR = androgen receptor, BC = breast cancer, EGFR = Epidermal growth factor receptor, ESR1 = Estrogen receptor, GO = Gene Ontology, GP = Gynostemma pentaphyllum (Thunb.) Makino, HSP90AA1 = heat shock protein HSP 90-alpha, KEGG = Kyoto Encyclopedia of Genes and Genomes, PGR = progesterone receptor, PPI = protein-protein interaction network, STRING = Search Tool for the Retrieval of Interacting Genes database, TCM = traditional Chinese medicines, TTD = Therapeutic Target Database.

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Section: Discussionsupporting

confidence: 58%

Uncovering the molecular mechanism of Gynostemma pentaphyllum (Thunb.) Makino against breast cancer using network pharmacology and molecular docking

Wang

et al. 2022

Medicine

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“…Persicogenin (5, Figure 1) and homoeriodictyol (6, Figure 1) are important flavanones isolated from Rhus retinorrhoea that present similar structures [44]. Whereas persicogenin (5) display anti-mutagenic, antitumor, as well as antibacterial activities, homoeriodictyol ( 6) is relevant to fight osteoporosis and usually used as antioxidant and bitterness masking agent [45][46][47].…”

Section: Flavonoidsmentioning

confidence: 99%

“…Nevertheless, persicogenin (5) induces a more demarcated apoptotic response which is believed to be related to the presence of an additional methyl group on its structure. Interestingly, the selectivity of persicogenin ( 5) is higher for HeLa cells than for MCF-7 whereas homoeriodictyol ( 6) is more selective towards MCF-7 than for HT-29 cells [44]. Didymin (7, Figure 1) is a dietary flavonoid glycoside widely present in citrus fruits such as orange, mandarin and bergamot [48].…”

Section: Flavonoidsmentioning

confidence: 99%

Chiral Flavonoids as Antitumor Agents

et al. 2021

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Flavonoids are a group of natural products with a great structural diversity, widely distributed in plant kingdom. They play an important role in plant growth, development and defense against aggressors. Flavonoids show a huge variety of biological activities such as antioxidant, anti-inflammatory, anti-mutagenic, antimicrobial and antitumor, being able to modulate a large diversity of cellular enzymatic activities. Among natural flavonoids, some classes comprise chiral molecules including flavanones, flavan-3-ols, isoflavanones, and rotenoids, which have one or more stereogenic centers. Interestingly, in some cases, individual compounds of enantiomeric pairs have shown different antitumor activity. In nature, these compounds are mainly biosynthesized as pure enantiomers. Nevertheless, they are often isolated as racemates, being necessary to carry out their chiral separation to perform enantioselectivity studies. Synthetic chiral flavonoids with promising antitumor activity have also been obtained using diverse synthetic approaches. In fact, several new chiral bioactive flavonoids have been synthesized by enantioselective synthesis. Particularly, flavopiridol was the first cyclin-dependent kinase (CDK) inhibitor which entered clinical trials. The chiral pool approaches using amino acid as chiral building blocks have also been reported to achieve small libraries of chrysin derivatives with more potent in vitro growth inhibitory effect than chrysin, reinforcing the importance of the introduction of chiral moieties to improve antitumor activity. In this work, a literature review of natural and synthetic chiral flavonoids with antitumor activity is reported for the first time.

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“…4 Homoeriodictyol, which is O-methylated in the 3′-position, was previously isolated from Viscum articulatum Burm and has been shown to have anticancer effects in MCF-7, HeLa, and HT-29 cells. 5 Furthermore, it was shown to protect endothelial cells from oxidative stress and mitochondrial dysfunction. 6 Hesperetin, which is O-methylated in the 4′-position, has been reported to ameliorate Alzheimer's disease 7 and inhibit the migration of breast cancer.…”

Section: Introductionmentioning

confidence: 99%

Engineering a Plant Polyketide Synthase for the Biosynthesis of Methylated Flavonoids

Peng,

Zhang,

et al. 2023

J. Agric. Food Chem.

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Homoeriodictyol and hesperetin are naturally occurring O-methylated flavonoids with many health-promoting properties. They are produced in plants in low abundance and as complex mixtures of similar compounds that are difficult to separate. Synthetic biology offers the opportunity to produce various flavonoids in a targeted, bottom-up approach in engineered microbes with high product titers. However, the production of O-methylated flavonoids is currently still highly inefficient. In this study, we investigated and engineered a combination of enzymes that had previously been shown to support homoeriodictyol and hesperetin production in Escherichia coli from fed O-methylated hydroxycinnamic acids. We determined the crystal structures of the enzyme catalyzing the first committed step of the pathway, chalcone synthase from Hordeum vulgare, in three ligand-bound states. Based on these structures and a multiple sequence alignment with other chalcone synthases, we constructed mutant variants and assessed their performance in E. coli toward producing methylated flavonoids. With our best mutant variant, HvCHS (Q232P, D234 V), we were able to produce homoeriodictyol and hesperetin at 2 times and 10 times higher titers than reported previously. Our findings will facilitate further engineering of this enzyme toward higher production of methylated flavonoids.

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Anticancer efficacies of persicogenin and homoeriodictyol isolated from Rhus retinorrhoea

Cited by 11 publications

References 55 publications

Uncovering the molecular mechanism of Gynostemma pentaphyllum (Thunb.) Makino against breast cancer using network pharmacology and molecular docking

Uncovering the molecular mechanism of Gynostemma pentaphyllum (Thunb.) Makino against breast cancer using network pharmacology and molecular docking

Chiral Flavonoids as Antitumor Agents

Engineering a Plant Polyketide Synthase for the Biosynthesis of Methylated Flavonoids

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