Cytotoxicity Analysis and In Silico Studies of Three Plant Extracts with Potential Application in Treatment of Endothelial Dysfunction

Ungureanu, Andreea Roxana; Popovici, Violeta; Oprean, Constantin; Danciu, Corina; Schröder, Verginica; Olaru, Octavian Tudorel; Mihai, Dragoș Paul; Popescu, Liliana; Luță, Emanuela Alice; Chiţescu, Carmen Lidia; Gîrd, Cerasela Elena

doi:10.3390/pharmaceutics15082125

Cited by 5 publications

(4 citation statements)

References 64 publications

(80 reference statements)

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“…The statistically significant differences (at α < 0.05) between various experimental groups were established by Multiple pairwise comparisons using Dunn's procedure from XLSTAT 2023.1.4. by Lumivero (Denver, CO, USA) [44].…”

Section: Discussionmentioning

confidence: 99%

Antioxidant and Cytotoxic Properties of <em>Berberis vulgaris</em> (L.) Stem Bark Dry Extract

Ivan,

Olaru,

Popovici

et al. 2024

Preprint

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Berberis vulgaris (L.) has remarkable ethnopharmacological properties and is widely used in traditional medicine. The present study investigates B. vulgaris stem bark (Berberidis cortex) by extraction with 50% ethanol. The main secondary metabolites were quantified, resulting in a polyphenols content of 17.6780 ± 3.9320 mg Eq Tannic acid / 100 g extract, phenolic acids amount of 3.3886 ± 0.3481 mg Eq Chlorogenic acid / 100 g extract and 78.95 µg/g berberine. The dried hydro-ethanolic extract (BVE) was thoroughly analyzed using Ultra-High Performance Liquid Chromatography coupled with High-Resolution Mass Spectrometry (UHPLC–HRMS/MS) and HPLC and 40 bioactive phenolic constituents were identified. Then, the antioxidant potential of BVE was evaluated using three methods; our results could explain the protective effects of Berberidis cortex EC50FRAP = 0.1398 mg/mL, IC50ABTS = 0.0442 mg/mL, IC50DPPH = 0.2610 mg/mL compared to ascorbic acid (IC50 = 0.0165 mg/mL). Next, the acute toxicity and teratogenicity of BVE and Berberine - Berberine sulfate hydrate (BS) - investigated on Daphnia sp reported significant BS toxicity after 24 h; BVE revealed considerable toxicity after 48 hours and induced embryonic developmental delays. Finally, the anticancer effects of BVE and BS were evaluated on different tumor cell lines after 24 and 48 hours of treatments. The MTS assay evidenced a dose- and time-dependent antiproliferative activity, higher on BS than BVE. The strongest diminution of tumor cell viability was recorded on breast (MDA-MB-231), colon (LoVo) cancer, and OSCC (PE/CA-PJ49) cell lines after 48 h of exposure (IC50 &lt; 100 µg/mL). However, no cytotoxicity was reported on normal epithelial cells (HUVEC) and hepatocellular carcinoma (HT-29) cell lines. Extensive data analysis supports our results, showing a significant correlation between the BVE's concentration, phenolic compounds content, antioxidant activity, exposure time, and the viability rate of various normal cells and cancer cell lines.

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Section: Discussionmentioning

confidence: 99%

Antioxidant and Cytotoxic Properties of <em>Berberis vulgaris</em> (L.) Stem Bark Dry Extract

Ivan,

Olaru,

Popovici

et al. 2024

Preprint

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show abstract

“…The statistically significant differences (at α < 0.05) between the various experimental groups were established by multiple pairwise comparisons using Dunn's procedure from XLSTAT 2023.1.4. by Lumivero (Denver, CO, USA) [48].…”

Section: Discussionmentioning

confidence: 99%

Antioxidant and Cytotoxic Properties of Berberis vulgaris (L.) Stem Bark Dry Extract

Ivan,

Olaru,

Popovici

et al. 2024

Molecules

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Berberis vulgaris (L.) has remarkable ethnopharmacological properties and is widely used in traditional medicine. The present study investigated B. vulgaris stem bark (Berberidis cortex) by extraction with 50% ethanol. The main secondary metabolites were quantified, resulting in a polyphenols content of 17.6780 ± 3.9320 mg Eq tannic acid/100 g extract, phenolic acids amount of 3.3886 ± 0.3481 mg Eq chlorogenic acid/100 g extract and 78.95 µg/g berberine. The dried hydro-ethanolic extract (BVE) was thoroughly analyzed using Ultra-High-Performance Liquid Chromatography coupled with High-Resolution Mass Spectrometry (UHPLC–HRMS/MS) and HPLC, and 40 bioactive phenolic constituents were identified. Then, the antioxidant potential of BVE was evaluated using three methods. Our results could explain the protective effects of Berberidis cortex EC50FRAP = 0.1398 mg/mL, IC50ABTS = 0.0442 mg/mL, IC50DPPH = 0.2610 mg/mL compared to ascorbic acid (IC50 = 0.0165 mg/mL). Next, the acute toxicity and teratogenicity of BVE and berberine—berberine sulfate hydrate (BS)—investigated on Daphnia sp. revealed significant BS toxicity after 24 h, while BVE revealed considerable toxicity after 48 h and induced embryonic developmental delays. Finally, the anticancer effects of BVE and BS were evaluated in different tumor cell lines after 24 and 48 h of treatments. The MTS assay evidenced dose- and time-dependent antiproliferative activity, which was higher for BS than BVE. The strongest diminution of tumor cell viability was recorded in the breast (MDA-MB-231), colon (LoVo) cancer, and OSCC (PE/CA-PJ49) cell lines after 48 h of exposure (IC50 < 100 µg/mL). However, no cytotoxicity was reported in the normal epithelial cells (HUVEC) and hepatocellular carcinoma (HT-29) cell lines. Extensive data analysis supports our results, showing a significant correlation between the BVE concentration, phenolic compounds content, antioxidant activity, exposure time, and the viability rate of various normal cells and cancer cell lines.

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“…It is based on the premise that toxicology can be considered as pharmacology at higher doses, suggesting that if toxic compounds are found, lower nontoxic doses might exhibit useful pharmacological effects. This assay is widely used to detect a broad range of biological activities and chemical structures, making it a versatile method for the preliminary screening of bioactive substances in plant extracts [ 56 ].…”

Section: Discussionmentioning

confidence: 99%

Preliminary Investigation of Astragalus arpilobus subsp. hauarensis: LC-MS/MS Chemical Profiling, In Vitro Evaluation of Antioxidant, Anti-Inflammatory Properties, Cytotoxicity, and In Silico Analysis against COX-2

Lekmine,

Benslama,

Kadi

et al. 2024

Antioxidants

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The search results offer comprehensive insights into the phenolic compounds, antioxidant, anti-inflammatory, cytotoxic effects, LC-MS/MS analysis, molecular docking, and MD simulation of the identified phenolic compounds in the Astragalus arpilobus subsp. hauarensis extract (AAH). The analysis revealed substantial levels of total phenolic content (TPC), with a measured value of 191 ± 0.03 mg GAE/g DM. This high TPC was primarily attributed to two key phenolic compounds: total flavonoid content (TFC) and total tannin content (TTC), quantified at 80.82 ± 0.02 mg QE/g DM and 51.91 ± 0.01 mg CE/g DM, respectively. LC-MS/MS analysis identified 28 phenolic compounds, with gallic acid, protocatechuic acid, catechin, and others. In the DPPH scavenging assay, the IC50 value for the extract was determined to be 19.44 ± 0.04 μg/mL, comparable to standard antioxidants like BHA, BHT, ascorbic acid, and α-tocopherol. Regarding anti-inflammatory activity, the extract demonstrated a notably lower IC50 value compared to both diclofenac and ketoprofen, with values of 35.73 µg/mL, 63.78 µg/mL, and 164.79 µg/mL, respectively. Cytotoxicity analysis revealed significant cytotoxicity of the A. arpilobus extract, with an LC50 value of 28.84 µg/mL, which exceeded that of potassium dichromate (15.73 µg/mL), indicating its potential as a safer alternative for various applications. Molecular docking studies have highlighted chrysin as a promising COX-2 inhibitor, with favorable binding energies and interactions. Molecular dynamic simulations further support chrysin’s potential, showing stable interactions with COX-2, comparable to the reference ligand S58. Overall, the study underscores the pharmacological potential of A. arpilobus extract, particularly chrysin, as a source of bioactive compounds with antioxidant and anti-inflammatory properties. Further research is warranted to elucidate the therapeutic mechanisms and clinical implications of these natural compounds.

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Cytotoxicity Analysis and In Silico Studies of Three Plant Extracts with Potential Application in Treatment of Endothelial Dysfunction

Cited by 5 publications

References 64 publications

Antioxidant and Cytotoxic Properties of <em>Berberis vulgaris</em> (L.) Stem Bark Dry Extract

Antioxidant and Cytotoxic Properties of <em>Berberis vulgaris</em> (L.) Stem Bark Dry Extract

Antioxidant and Cytotoxic Properties of Berberis vulgaris (L.) Stem Bark Dry Extract

Preliminary Investigation of Astragalus arpilobus subsp. hauarensis: LC-MS/MS Chemical Profiling, In Vitro Evaluation of Antioxidant, Anti-Inflammatory Properties, Cytotoxicity, and In Silico Analysis against COX-2

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