Cell proliferation activity delineated by molecular docking of four new compounds isolated from the aerial parts of Suaeda monoica Forssk. ex. J.F. Gmel
“…15135), including their structure elucidations ( Fig. 1 ) have been previously reported by us ( AlSaid et al, 2017 , Siddiqui et al, 2020 ). Fig.…”
Section: Methodssupporting
confidence: 56%
“…The S. monoica derived norsesquaterpenol (NSQ), suaedanortriterpenedione (SND), aromatic monoterpenic ester (AES), norditerpenic xyloside (NDX), alkylated β-naphthol (ABN) and β-methoxy naphthalene (BMN) were first dissolved in 50 μl dimethyl sulfoxide (DMSO, Sigma-Alderich, Germany) and reconstituted in culture media (1 mg/ml, each). Based on our previously assessed non-toxic concentrations on liver cancer cells ( AlSaid et al, 2017 , Siddiqui et al, 2020 ), only three working doses (50, 25 and 12.5 μg/ml; DMSO < 0.5% final) were further prepared in culture media. Likewise, DCF and MGO (Sigma-Alderich, Germany) were prepared to be used as inducers of oxidative and apoptotic cell damage, whereas aminoguanidine (AG; Sigma-Alderich, Germany) served as anti-apoptotic agent (positive control).…”
Section: Methodsmentioning
confidence: 99%
“…In addition, its flavonoids, saponins, alkaloids, polyphenols, resins, tannins, coumarins, cardiac glycosides, and fatty acids are characterized as therapeutic phytoconstituents ( Kokpal et al, 1990 , Lakshmanan et al, 2013 , Muthazhagan et al, 2014 ). Recently, we have reported isolation and preliminary bioactivity of S. monoica derived four new terpenes: a norsesquaterpenol (normonisesquaterpenol), a monocyclic triterpenoid (suaedanortriterpene dione), an aromatic monoterpenic ester, an unknown labdane-type norditerpenic xyloside as well as two new phenols: an alkylated β-naphthol and a β-methoxy naphthalene derivative ( AlSaid et al, 2017 , Siddiqui et al, 2020 ). Notably, a novel pentacyclic triterpenedione from Picea jezoensis with unknown bioactivity has been previously reported ( Tanaka et al, 1997 ).…”
Elevation in hyperglycemia-associated methylglyoxal level can trigger vascular endothelial cells oxidative stress and apoptosis. The present work assesses the cell proliferative, anti-oxidative and anti-apoptotic potential of
Suaeda monoica
derived four new terpenes: a norsesquaterpenol (normonisesquaterpenol), a monocyclic triterpenoid (suaedanortriterpene dione), an aromatic monoterpenic ester and a labdane-type norditerpenic xyloside as well as two new phenols: an alkylated β-naphthol and a β-methoxy naphthalene in cultured human umbilical vein endothelial cells (HUVEC). Of these, suaedanortriterpenedione (53.7%), normonisesquaterpenol (51.4%) and norditerpenic xyloside (48%) showed the most promising cell proliferative activities compared to others. Moreover, normonisesquaterpenol, norditerpenic xyloside and suaedanortriterpenedione efficiently reversed the oxidative and apoptotic cell damage via downregulation of capase-3/7 by 44.3%, 42.2% and 39.4%, respectively against dichlorofluorescin, whereas by 46.2%, 43.5% and 42.5%, respectively against methylglyoxal. Aminoguanidine, the reference drug inhibited caspase-3/7 activity by 56.2% and 54.7% through attenuation of dichlorofluorescin and methylglyoxal, respectively. Further
in silico
molecular docking analysis revealed formation of stable complexes between the tested compounds and caspase-3/7. Conclusively, we for the first time demonstrate the growth stimulatory, anti-oxidative and anti-apoptotic salutations of
S. monoica
derived novel compounds in human endothelial cells. This warrants their further assessment as vascular cell protective and rejuvenating therapeutics, especially in hyperglycemic conditions.
“…15135), including their structure elucidations ( Fig. 1 ) have been previously reported by us ( AlSaid et al, 2017 , Siddiqui et al, 2020 ). Fig.…”
Section: Methodssupporting
confidence: 56%
“…The S. monoica derived norsesquaterpenol (NSQ), suaedanortriterpenedione (SND), aromatic monoterpenic ester (AES), norditerpenic xyloside (NDX), alkylated β-naphthol (ABN) and β-methoxy naphthalene (BMN) were first dissolved in 50 μl dimethyl sulfoxide (DMSO, Sigma-Alderich, Germany) and reconstituted in culture media (1 mg/ml, each). Based on our previously assessed non-toxic concentrations on liver cancer cells ( AlSaid et al, 2017 , Siddiqui et al, 2020 ), only three working doses (50, 25 and 12.5 μg/ml; DMSO < 0.5% final) were further prepared in culture media. Likewise, DCF and MGO (Sigma-Alderich, Germany) were prepared to be used as inducers of oxidative and apoptotic cell damage, whereas aminoguanidine (AG; Sigma-Alderich, Germany) served as anti-apoptotic agent (positive control).…”
Section: Methodsmentioning
confidence: 99%
“…In addition, its flavonoids, saponins, alkaloids, polyphenols, resins, tannins, coumarins, cardiac glycosides, and fatty acids are characterized as therapeutic phytoconstituents ( Kokpal et al, 1990 , Lakshmanan et al, 2013 , Muthazhagan et al, 2014 ). Recently, we have reported isolation and preliminary bioactivity of S. monoica derived four new terpenes: a norsesquaterpenol (normonisesquaterpenol), a monocyclic triterpenoid (suaedanortriterpene dione), an aromatic monoterpenic ester, an unknown labdane-type norditerpenic xyloside as well as two new phenols: an alkylated β-naphthol and a β-methoxy naphthalene derivative ( AlSaid et al, 2017 , Siddiqui et al, 2020 ). Notably, a novel pentacyclic triterpenedione from Picea jezoensis with unknown bioactivity has been previously reported ( Tanaka et al, 1997 ).…”
Elevation in hyperglycemia-associated methylglyoxal level can trigger vascular endothelial cells oxidative stress and apoptosis. The present work assesses the cell proliferative, anti-oxidative and anti-apoptotic potential of
Suaeda monoica
derived four new terpenes: a norsesquaterpenol (normonisesquaterpenol), a monocyclic triterpenoid (suaedanortriterpene dione), an aromatic monoterpenic ester and a labdane-type norditerpenic xyloside as well as two new phenols: an alkylated β-naphthol and a β-methoxy naphthalene in cultured human umbilical vein endothelial cells (HUVEC). Of these, suaedanortriterpenedione (53.7%), normonisesquaterpenol (51.4%) and norditerpenic xyloside (48%) showed the most promising cell proliferative activities compared to others. Moreover, normonisesquaterpenol, norditerpenic xyloside and suaedanortriterpenedione efficiently reversed the oxidative and apoptotic cell damage via downregulation of capase-3/7 by 44.3%, 42.2% and 39.4%, respectively against dichlorofluorescin, whereas by 46.2%, 43.5% and 42.5%, respectively against methylglyoxal. Aminoguanidine, the reference drug inhibited caspase-3/7 activity by 56.2% and 54.7% through attenuation of dichlorofluorescin and methylglyoxal, respectively. Further
in silico
molecular docking analysis revealed formation of stable complexes between the tested compounds and caspase-3/7. Conclusively, we for the first time demonstrate the growth stimulatory, anti-oxidative and anti-apoptotic salutations of
S. monoica
derived novel compounds in human endothelial cells. This warrants their further assessment as vascular cell protective and rejuvenating therapeutics, especially in hyperglycemic conditions.
“…Gmel. was also reported with the identification of a couple of active compounds (Al-Said et al, 2017;Siddiqui et al, 2020). In India, since local people use this halophytic succulent herb as fodder for wound healing, burn the leaves to repel mosquitoes, use as antidiuretic compound and drink the juice of the leaves in diarrhea as electrolytes, a proper validation of a variety of ethnomedicinal properties of this plant is fairly warranted.…”
Suaeda monoica Forssk. ex J.F.Gmel. (Amaranthaceae), a mangrove associate and ethno-medicinal herb of Indian Sundarbans, was investigated as a promising source of bioactive compounds. Various polar and nonpolar solvent extracts of the leaf and root-shoot parts of the plant exhibited antioxidant, antibacterial, antifungal, allelopathic, mosquitocidal, antihaemolytic and antidiuretic potential. Moreover, to meet pharmacological requirements, the antioxidant ability of the plant was validated by both chemical and biological analyses. Extraction yield and presence of different phytochemicals like phenolics, flavonoids, tannins and saponins were compared in various solvent-extracted fractions. Principle component analysis revealed that the antioxidant property present in different extracts maintained a positive correlation with the occurrence of polyphenols (phenolics, tannins and flavonoids). Biochemical evaluation, HPLC examination and GC–MS analysis showed a differential level of the presence of various phytochemicals in different solvent extracts. In contrast to mosquitocidal, antioxidant, antihaemolytic and phytotoxic properties which were observed to be dominant in polar solvent extracts, maximum antibacterial potency was detected in nonpolar n-hexane fractions. Overall, the plant extract is nontoxic in nature and a dose amounting to 3,000 mg/kg was well tolerated by Swiss albino mice. A combination of HPLC and GC–MS analyses showed the presence of a large number of structurally diverse phytochemicals, many of which had already been reported as insecticidal, mosquitocidal, antibacterial, herbicidal, antidiuretic, antioxidant and anti-haemolytic compounds. All these findings support that the least explored traditional edible medicinal mangrove associate S.monoica is enriched with multiple bioactive molecules and may be considered as one of the richest sources of various lead molecules of pharmaceutical importance.
“…65 PTEN is a 403 amino acid long protein consisting of two major domains namely N-terminal phosphatase domain (residues 7-185) by PI3K and can activate downstream effectors AKT/PKB kinase, [66][67][68] and additionally active site residues His123, Cys124, Lys125, Ala126, Gly127, Lys128, Gly129, and Arg130 form a P loop located at the bottom of the active site pocket, especially His123 and Gly127 that are important for the conformation of the P loop, which has two basic residues (Lys125 and Lys128) in its center, and His93 gives the PTEN active site pocket a highly basic character. Several studies reported that flavonoids can bind to the PTEN, leading to the activation of PI3K/AKT signaling pathway, 69,70 in particular, the flavonoid naringin inhibit dephosphorylation activity of PTEN through Tyr16, Asp24, Arg47, Gly44, Val45, Asp92, His93, Ala126, Lys128, Asp162, Lys164, Asp326, and Lys330. 69 In agree with these reports, we found seven amino acids (Asp92, His93, Cys124, Lys125, Ala126, Lys128, and…”
Dibutyl phthalate (DBP) is a phthalic acid ester (PAE) that has posed a health hazard to the organisms. Naringenin (NRG) is a flavanone compound that has shown protection against several environmental chemicals through suppression of oxidative stress and activation of phosphatidylinositol 3-kinase/threonine kinase (PI3K/AKT) signaling pathway. Herein, swine testis (ST) cells were treated with 1.8 μM of DBP or/and 25.39 nM of NRG for 24 h, we described the discovery path of NRG inhibition on apoptosis in DBP-exposed ST cells through targeting phosphatase and tensin homologue deleted on chromosome 10 (PTEN). We first found that the anti-apoptosis effect of NRG is dependent on mitochondrial pathway through flow cytometry and related gene/protein expression, and then we detected PI3K/AKT pathway-related gene/protein expression, and established a computational docking assay between NRG and PTEN. We found that NRG specifically binds to three basic residues (His93, Lys125, Lys128) of P loop in PTEN, as well as phosphatase domains (Asp92, His93, Cys124, Lys125, Ala126, Lys128, and Arg130) in active dephosphorylation pockets, thereby reducing PTEN level and activating PI3K/AKT signaling pathway, and further inhibiting oxidative stress and mitochondrial pathway apoptosis. Taken together, our results push forward that NRG deserves further attention as a potential antagonistic therapy against DBP through targeting PTEN to inhibit oxidative stress and activate PI3K/AKT signaling pathway.
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