Neuroprotective Potential of Synthetic Mono-Carbonyl Curcumin Analogs Assessed by Molecular Docking Studies

Hussain, Haya; Ahmad, Shujaat; Shah, Syed Wadood Ali; Ghias, Mehreen; Ullah, Abid; Rahman, Shafiq Ur; Kamal, Zul; Khan, Farman Ali; Khan, Nasir Mehmood; Muhammad, Jan; Almehmadi, Mazen; Abdulaziz, Osama; Alghamdi, Saad

doi:10.3390/molecules26237168

Cited by 23 publications

(26 citation statements)

References 38 publications

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“…Among the fractions, promising effects were produced by SlMo-Chl at 75 and 150 mg/kg body weight doses, compared to the amnesic group that was found to be 65.18 ± 2.61% ( p ˂ 0.001, n = 6) and 69.51 ± 2.71% [F (14.75) = 32.25, p ˂ 0.001, n = 6) correspondingly. The results obtained in this study are in accordance with previously reported studies [ 34 , 35 ]. It could be suggested from the obtained results that the extract at the tested dose could be helpful in reinstating the memory deficit in the experimental animals.…”

Section: Resultssupporting

confidence: 94%

“…Y-maze test was performed following the reported methodology [ 34 , 35 , 36 ]. Y-maze is a Y shaped apparatus having three arms, arbitrarily named A, B, and C. Each arm has a length of 20 cm, with a height of 15.5 cm and 6 cm in width, oriented at an angle of 120° from the two others.…”

Section: Methodsmentioning

confidence: 99%

“…The antiamnesic activity of S. moorcroftiana in the form of extracts was also investigated using novel object recognition test following a reported procedure [ 35 ]. The NORT apparatus was made of plexi glass, with dimension of 40 cm × 40 cm × 30 cm.…”

Section: Methodsmentioning

confidence: 99%

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Amelioration of Scopolamine-Induced Cognitive Dysfunction in Experimental Mice Using the Medicinal Plant Salvia moorcroftiana

et al. 2022

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Salvia moorcroftiana is medicinally used in various parts of the world to treat a number of diseases. In the literature, the antiamnesic activity of this plant has not yet been reported. Therefore, the current study was aimed at evaluating the in vivo antiamnesic (scopolamine-induced) potential of Salvia moorcroftiana. The major phytochemical groups such as total phenolic (TPC), total tannin (TTC), and total flavonoid content (TFC) in methanolic extract (SlMo-Crd) and subsequent fractions of Salvia moorcroftiana were quantified using standard methods. The in vitro anticholinesterase (against butyryl cholinesterase; BChE and acetylcholinesterase; AChE) and antioxidant (against 2,2-diphenyl-1-picrylhydrazyl; DPPH and 2,2′-Azino-bis (3-ethylbenzothiazoline-6-sulfonic acid); ABTS free radicals) potentials of crude (SIMO-Crd) extract and fractions (hexane; SlMo-Hex, chloroform; SlMo-Chl, ethyl acetate; SlMo-Et) were also determined. The SlMo-Crd at doses of 100 and 200 mg/kg body weight compared to fractions of 75 and 150 mg/kg body weight (which were 1/10th of the highest dose tested in acute toxicity tests) were evaluated for their memory enhancement and learning behavior in normal and scopolamine-induced mental dysfunction in mice using behavioral memory tests such as the Y-maze test and novel object recognition test (NORT). Moreover, the samples were further evaluated for acetylcholine contents and biochemical markers such as MDA (malondialdehyde), SOD (superoxide dismutase), CAT (catalase), and GSH (glutathione peroxidase) levels. The maximum TPC with a value of 114.81 ± 1.15 mg GAE/g, TTC with a value of 106.79 ± 1.07 mg GAE/g, and TFC with a value of 194.29 ± 0.83 mg RE/g were recorded for the SlMo-Chl fraction. Against the DPPH free radical, the methanolic extract exhibited an IC50 value of 95.29 ± 1.06 µg/mL whereas, among the fractions, the best activity was observed for the SlMo-Chl fraction with an IC50 of 75.02 ± 0.91 µg/mL, followed by SlMoS-Et with an IC50 value of 88.71 ± 0.87 µg/mL. Among the extracts, the SlMo-Chl and SlMo-Et fractions inverted the amnesic effects of scopolamine in mice effectively. Additionally, the SlMo-Chl and SIMO-Et fractions considerably enhanced the percent spontaneous alteration performance in the Y-maze test with values of 65.18 ± 2.61/69.51 ± 2.71 and 54.92 ± 2.49/60.41 ± 2.69, respectively, for the tested doses. The discrimination index (DI) in experimental mice was considerably enhanced by the SlMo-Chl in the NORT with values of 59.81 ± 1.21/61.22 ± 1.31% DI correspondingly for the tested doses, as mentioned above, followed by the SlMo-Et extract. The selected plant in the form of extracts ameliorated the effects of amnesia in mice and could, therefore, be used as a therapy for amnesia; however, this is subject to further exploration in other animal models and the isolation of the responsible compounds.

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Section: Resultssupporting

confidence: 94%

Section: Methodsmentioning

confidence: 99%

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Amelioration of Scopolamine-Induced Cognitive Dysfunction in Experimental Mice Using the Medicinal Plant Salvia moorcroftiana

et al. 2022

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“…Behavioral tasks on the Y-Maze Paradigm and “NOD” tasks were conducted in the 5th week of study to determine learning and memory functions. The apparatus arena was cleaned with 70% ethanol during the inter-trial interval to prevent a confounding error due to the influence of odor [ 20 , 21 ].…”

Section: Methodsmentioning

confidence: 99%

Flavonoid Derivatives as Potential Cholinesterase Inhibitors in Scopolamine-Induced Amnesic Mice: An In Vitro, In Vivo and Integrated Computational Approach

et al. 2022

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Flavonoids are one of the most exciting types of phenolic compounds with a wide range of bioactive benefits. A series of flavone derivatives (F1–F5) were previously synthesized from substituted O-hydroxy acetophenone and substituted chloro-benzaldehydes. The titled compounds F1–F5 in the present study were evaluated for their anticholinesterase potential (against AChE and BuChE). The obtained results were then validated through a molecular docking approach. Compound F5 was found to be the most potent inhibitor of AChE (IC50 = 98.42 ± 0.97 µg/mL) followed by compound F4, whereas compound F2 was found to be the most promising inhibitor of BuChE (IC50 = 105.20 ± 1.43 µg/mL) among the tested compounds. The molecular docking analysis revealed a similar trend in the binding affinity of compounds with the targeted enzymes and found them to be capable of forming highly stable complexes with both receptors. The selected compounds were further subjected to in vivo assessment of cognitive function in a scopolamine-induced amnesic animal model, in which almost all compounds F1–F5 significantly attenuated the amnesic effects as evaluated through Y-Maze Paradigm and novel object discrimination (NOD) tasks, findings that were further supported by ex vivo experimental results. Among (F1–F5), F5 showed significant anti-amnesic effects in scopolamine-induced amnesic models and ameliorated the memory loss in behavioral model studies as compared to counterparts. In ex vivo study, noteworthy protection from oxidative stress in the brains of scopolamine-induced amnesic mice was also recorded for F5. These findings also confirmed that there were no significant differences among the in vivo and ex vivo results after administration of F1–F5 (7.5 or 15 mg/kg) or donepezil (2 mg/kg). These synthesized flavonoids could serve as potential candidates for new neuroprotective and nootropic drugs. However, further studies are needed to validate their observed potential in other animal models as well.

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“…Neurodegenerative disorders are a growing public health problem due the rising incidence and low effectiveness of current treatments [ 1 , 2 ]. Alzheimer’s disease is one of the most common age-related irreversible and progressive neurodegenerative disorders characterized by dementia, memory loss, a decline in language skills, and cognitive impairment with aging.…”

Section: Introductionmentioning

confidence: 99%

Isoquinoline Alkaloid Contents in Macleaya cordata Extracts and Their Acetylcholinesterase and Butyrylcholinesterase Inhibition

et al. 2022

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An important strategy for treating neurodegenerative disorders is to maintain the levels of acetylcholine in the synaptic cleft by blocking the cholinesterases. Searching for new effective compounds with inhibited acetylcholinesterase and butyrylcholinesterase activity is one of the most significant challenges of the modern scientific research. The aim of this study was the optimization of the condition for cholinesterase activity determination by high-performance liquid chromatography coupled with diode array detector (HPLC-DAD) in terms of concentrations of enzymatic reaction mixture components, temperature of incubation, and incubation time. In vitro investigation of acetylcholinesterase and butyrylcholinesterase activity inhibition by some isoquinoline alkaloids and extracts obtained from the aerial part and roots of Macleaya cordata collected in May, July, and September. Acetylcholinesterase and butyrylcholinesterase activity inhibition of the extracts obtained from the plant had not been tested previously. The application of the HPLC method allowed eliminating absorption of interfering components, for example, alkaloids such as sanguinarine and berberine. The HPLC method was successfully applied for the evaluation of the acetylcholinesterase inhibitory activity in samples such as plant extracts, especially those containing colored components adsorbing at the same wavelength as the adsorption wavelength of 5-thio-2-nitro-benzoic acid, which is the product of the reaction between thiocholine (product of the hydrolysis of acetyl/butyrylthiocholine reaction) with Ellman’s reagent. Moreover, liquid chromatography coupled with a triple quadrupole mass spectrometer (LC–QqQ–ESI–MS/MS) analysis allowed evaluating the identification of relevant bioactive compounds in the obtained plant extracts. The investigated alkaloids, especially sanguinarine and chelerythrine, and all the Macleaya cordata extracts, especially the extract obtained from the aerial part collected in May, exhibited very high cholinesterase activity inhibition. HPLC-DAD was also applied for the kinetics study of the most active alkaloids sanguinarine and chelerythrine. Our investigations demonstrated that these plant extracts can be recommended for further in vivo experiments to confirm their cholinesterase inhibition activity.

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Neuroprotective Potential of Synthetic Mono-Carbonyl Curcumin Analogs Assessed by Molecular Docking Studies

Cited by 23 publications

References 38 publications

Amelioration of Scopolamine-Induced Cognitive Dysfunction in Experimental Mice Using the Medicinal Plant Salvia moorcroftiana

Amelioration of Scopolamine-Induced Cognitive Dysfunction in Experimental Mice Using the Medicinal Plant Salvia moorcroftiana

Flavonoid Derivatives as Potential Cholinesterase Inhibitors in Scopolamine-Induced Amnesic Mice: An In Vitro, In Vivo and Integrated Computational Approach

Isoquinoline Alkaloid Contents in Macleaya cordata Extracts and Their Acetylcholinesterase and Butyrylcholinesterase Inhibition

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