Berberis lyceum and Fumaria indica: in vitro cytotoxicity, antioxidant activity, and in silico screening of their selected phytochemicals as novel hepatitis C virus nonstructural protein 5A inhibitors

Landry, Koloko Brice; Tariq, Somayya; Malik, Ayesha; Sufyan, Muhammad; Ashfaq, Usman Ali; Ijaz, Bushra; Shahid, Ahmad Ali

doi:10.1080/07391102.2021.1902395

Cited by 11 publications

(2 citation statements)

References 56 publications

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“…Pugsley hydromethanolic extract revealed the predominant presence of alkaloids, coumarins, phenylpropanoids, flavonoids, and other identified chemicals were sinapic acid, bergenin, (methylsulfanyl)butyl glucosinolate, p-coumaraldehyde, dehydrosalsolidine, hydrocotarnine, ellipticine, hulupinic acid, isocorydine, koumine, serotonin, and linoleic acid. The previous phytochemical research indicated comparable results. − …”

Section: Discussionsupporting

confidence: 52%

Fumaria indica (Hausskn.) Pugsley Hydromethanolic Extract: Bioactive Compounds Identification, Hypotensive Mechanism, and Cardioprotective Potential Exploration

Shah,

Rana,

Mohany

et al. 2024

ACS Omega

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Fumaria indica (Hausskn.) Pugsley (FIP), a member of the Papaveraceae family, has a documented history of use in traditional medicine to treat cardiovascular ailments, particularly hypertension, and has shown substantial therapeutic efficacy among native cultures worldwide. However, the identification of bioactive compounds and the mechanism of hypotensive effect with the cardioprotective potential investigations are yet to be determined. The study aimed to identify bioactive compounds, explore the hypotensive mechanism and cardioprotective potential, and assess the safety of Fumaria indica (Hausskn.) Pugsley hydromethanolic extract (Fip.Cr). LC ESI-MS/MS analysis was performed to identify the bioactive compounds. In vitro experiments were conducted on isolated rat aorta and atria, and an in vivo invasive BP measurement model was used. Acute and subacute toxicities were assessed for 14 and 28 days, respectively. Isoproterenol (ISO) was used to develop the rats' myocardial infarction damage model. The mRNA levels of NLRP3 inflammasome and the abundance level of Firmicutes and Lactobacillus were measured by qRT-PCR. The hypotensive effect of FIP bioactive compounds was also investigated using in silico methods. Fip. Cr LC ESI−MS/MS analysis discovered 33 bioactive compounds, including alkaloids and flavonoids. In isolated rat aorta, Fip.Cr reversed contractions induced by K + (80 mM), demonstrating a calcium entry-blocking function, and had a vasorelaxant impact on phenylephrine (PE) (1 μM)-induced contractions unaffected by L-NAME, ruling out endothelial NO participation. Fip.Cr caused negative chronotropic and inotropic effects in isolated rat atria unaffected by atropine pretreatment, eliminating cardiac muscarinic receptor involvement. Safety evaluation showed no major adverse effects. In vivo, invasive BP measurement demonstrated a hypotensive effect comparable to verapamil. Fip.Cr protected the rats from ISO-induced MI interventions significantly in biometrical and cardiac serum biochemical indicators and histological examinations by reducing inflammation via inhibiting NLRP3 inflammasome and elevating Firmicutes and Lactobacillus levels. The network pharmacology study revealed that the FIP hypotensive mechanism might involve MMP9, JAK2, HMOX1, NOS2, NOS3, TEK, SERPINE1, CCL2, and VEGFA. The molecular docking study revealed that FIP bioactive compounds docked better with CAC1C_ HUMAN than verapamil. These findings demonstrated that Fip.Cr's hypotensive mechanism may include calcium channel blocker activity. Fip.Cr ameliorated ISO-induced myocardial infarction in rats by attenuating inflammation, which might be via inhibiting NLRP3 inflammasome and may prove beneficial for treating MI.

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Section: Discussionsupporting

confidence: 52%

Fumaria indica (Hausskn.) Pugsley Hydromethanolic Extract: Bioactive Compounds Identification, Hypotensive Mechanism, and Cardioprotective Potential Exploration

Shah,

Rana,

Mohany

et al. 2024

ACS Omega

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“…Molecular dynamics (MD) simulation was executed by the Desmond v3.6 molecular dynamics program according to a previously reported method [ 32 ]. In brief, a boundary was prepared with an orthorhombic-shaped box, and a TIP3P solvent model was applied.…”

Section: Methodsmentioning

confidence: 99%

Identification of Lignan Compounds as New 6-Phosphogluconate Dehydrogenase Inhibitors for Lung Cancer

et al. 2022

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Targeting pentose phosphate pathway (PPP) enzymes has emerged as a promising strategy to combat cancer. 6-Phosphogluconate dehydrogenase (6-PGD), the third critical enzyme of the PPP, catalyzes oxidative decarboxylation of 6-phosphogluconate (6-PG) to produce ribulose-5-phosphate (Ru-5-P) and CO2. Overexpression of 6-PGD has been reported in multiple cancers and is recognized as a potential anticancer drug target. The current study is focused on the utilization of indispensable virtual screening tools for structure-based drug discovery. During the study, 17,000 natural compounds were screened against the 3-phosphoglycerate (3-PG) binding site of 6-PGD through a molecular operating environment (MOE), which revealed 115 inhibitors with higher selectivity and binding affinity. Out of the 115 best-fit compounds within the 6-PGD binding cavity, 15 compounds were selected and optimized through stringent in silico ADMET assessment models that justified the desirable pharmacokinetic, pharmacodynamic and physicochemical profiles of 5 ligands. Further protein–ligand stability assessment through molecular dynamics (MD) simulation illustrated three potential hits, secoisolariciresinol, syringaresinol and cleomiscosin A, with stable confirmation. Moreover, 6-PGD inhibitor validation was performed by an in vitro enzymatic assay using human erythrocytes purified 6-PGD protein and A549 cell lysate protein. The results of the in vitro assays supported the in silico findings. In order to gain insight into the anticancer activity of the aforementioned compounds, they were subjected to CLC-Pred, an in silico cytotoxicity browsing tool, which proved their anticancer activity against several cancer cell lines at Pa > 0.5. Additionally, a confirmation for in silico cytotoxicity was made by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay for commercially available hits syringaresinol and cleomiscosin A against lung cancer (A549) cells. The results demonstrated that syringaresinol has an IC50 value of 36.9 μg/mL, while cleomiscosin A has an IC50 value of 133 μg/mL. After MTT, flow cytometry analysis confirmed that compounds induced apoptosis in A549 cells in a dose-dependent manner. This study suggested that the respective lignan compounds can serve as lead candidates for lung cancer therapy via 6-PGD inhibition. Furthermore, in vivo experiments need to be conducted to confirm their efficacy.

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Fumaria vaillantii extract protects PC12 cells against neurotoxicity induced by 6-OHDA

Javid,

Rahimian,

Salimi

et al. 2024

Mol Biol Rep

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Berberis lyceum and Fumaria indica: in vitro cytotoxicity, antioxidant activity, and in silico screening of their selected phytochemicals as novel hepatitis C virus nonstructural protein 5A inhibitors

Cited by 11 publications

References 56 publications

Fumaria indica (Hausskn.) Pugsley Hydromethanolic Extract: Bioactive Compounds Identification, Hypotensive Mechanism, and Cardioprotective Potential Exploration

Fumaria indica (Hausskn.) Pugsley Hydromethanolic Extract: Bioactive Compounds Identification, Hypotensive Mechanism, and Cardioprotective Potential Exploration

Identification of Lignan Compounds as New 6-Phosphogluconate Dehydrogenase Inhibitors for Lung Cancer

Fumaria vaillantii extract protects PC12 cells against neurotoxicity induced by 6-OHDA

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