Identification of plant-based multitargeted leads for Alzheimer's disease: In-vitro and in-vivo validation of Woodfordia fruticosa (L.) Kurz

Raghuvanshi, Rinky; Nuthakki, Vijay K.; Singh, Lovedeep; Singh, Bheeshma Pratap; Bharate, Sonali S.; Bhatti, Rajbir; Bharate, Sandip B.

doi:10.1016/j.phymed.2021.153659

Cited by 11 publications

(7 citation statements)

References 43 publications

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“…There is an incredible contribution of natural products (NPs) to drug discovery in general and particularly in the CNS domain (84% of the marketed drugs in the CNS domain are either pure NPs or NP-inspired molecules). − In continuation to our continuous efforts on exploring natural products for CNS diseases, − herein, the hydroxybenzoquinone natural product, embelin ( 1 ), was pursued for medicinal chemistry lead optimization in search of optimized MTDL for AD. Embelin ( 1 ) is an MTDL showing inhibition of AChE, BChE, and BACE-1 with respective IC 50 values of 2.5, 5.45, and 2.11 μM and also has an ability to bind Aβ and prevent its accumulation. , The ameliorating potential of embelin against scopolamine-induced amnesia and streptozotocin-induced cognitive impairment was proved in rat models.…”

Section: Introductionmentioning

confidence: 99%

Design, Synthesis, and Pharmacological Evaluation of Embelin–Aryl/alkyl Amine Hybrids as Orally Bioavailable Blood–Brain Barrier Permeable Multitargeted Agents with Therapeutic Potential in Alzheimer’s Disease: Discovery of SB-1448

Nuthakki

Choudhary

Reddy

et al. 2023

ACS Chem. Neurosci.

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The complex and multifaceted nature of Alzheimer’s disease has brought about a pressing demand to develop ligands targeting multiple pathways to combat its outrageous prevalence. Embelin is a major secondary metabolite of Embelia ribes Burm f., one of the oldest herbs in Indian traditional medicine. It is a micromolar inhibitor of cholinesterases (ChEs) and β-site amyloid precursor protein cleaving enzyme 1 (BACE-1) with poor absorption, distribution, metabolism, and excretion (ADME) properties. Herein, we synthesize a series of embelin–aryl/alkyl amine hybrids to improve its physicochemical properties and therapeutic potency against targeted enzymes. The most active derivative, 9j (SB-1448), inhibits human acetylcholinesterase (hAChE), human butyrylcholinesterase (hBChE), and human BACE-1 (hBACE-1) with IC50 values of 0.15, 1.6, and 0.6 μM, respectively. It inhibits both ChEs noncompetitively with k i values of 0.21 and 1.3 μM, respectively. It is orally bioavailable, crosses blood–brain barrier (BBB), inhibits Aβ self-aggregation, possesses good ADME properties, and protects neuronal cells from scopolamine-induced cell death. The oral administration of 9j at 30 mg/kg attenuates the scopolamine-induced cognitive impairments in C57BL/6J mice.

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Section: Introductionmentioning

confidence: 99%

Design, Synthesis, and Pharmacological Evaluation of Embelin–Aryl/alkyl Amine Hybrids as Orally Bioavailable Blood–Brain Barrier Permeable Multitargeted Agents with Therapeutic Potential in Alzheimer’s Disease: Discovery of SB-1448

Nuthakki

Choudhary

Reddy

et al. 2023

ACS Chem. Neurosci.

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“…Measurement of the absorbance was taken at 730 nm using distilled water as blank and gallic acid as standard. A Calibration curve was made with gallic acid concentrations in the range of (10,50,100,200,400, and 800 μg/ml). Total phenolic content was stated in mg gallic acid equivalents (GAE) per gram of dry weight 14 .…”

Section: Determination Of Total Phenolic Content (Tpc)mentioning

confidence: 99%

“…The main phytochemicals found in the W. fruticosa are tannins, polyphenolic groups, and flavonoids, and other chemical constituents are saponins, essential oil, carbohydrate etc 5 . According to previous researches W. fruticosa flowers extract has anti-inflammatory 6 , gastroprotective 7 , hepatoprotective 8 , antioxidant 9 , Alzheimer's disease 10 , and wound healing activity 11 . The main objective of this work was to explore the phytochemical profile, antioxidant activity, and in vitro anti-diabetic properties of the W. fruticosa flower.…”

Section: Introductionmentioning

confidence: 99%

Antioxidant and Antidiabetic activity of hydroalcoholic flower extract of Woodfordia fruticosa (L.) Kurz

Giri

Dey

Dua

2022

J. Drug Delivery Ther.

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Woodfordia fruticosa (L.) Kurz, (W. fruticosa) a member of the Lythraceae family, commonly known as dhaiphul, has been used in traditional medicine to cure common illnesses since ancient times. The most effective part of this plant is the flower which has a high demand in the national as well as the international market of the eastern south part of Asian countries. The present study focuses on exploring the presence of phytochemicals, antioxidants, and antidiabetic potential of hydroalcoholic extract of flower of W. fruticosa. Phytochemical test showed the presence of saponin, flavonoid, carbohydrates, alkaloids, tannin, anthraquinone, and triterpenoids in the extract, and it showed an effective result of total phenolic content, total flavonoid Content with the value of 371.96 ± 2.86 mg of gallic acid equivalent per gram of the extract and 113.82 ± 0.178 mg of quercetin equivalent per gram of dry weight. In vitro antioxidant assay, for the DPPH assay, the IC50 values were found 30.85 ± 0.36 μg/ml and 22.35 ± 0.54 μg/ml for the extract of W. fruticosa flower and ascorbic acid respectively and for the FRAP Assay, the reducing power assay of plant extract is lesser than standard (Ascorbic acid). W. fruticosa also showed significant hyperglycemic activity. In accordance with results, we can conclude that plant consists of a high polyphenolic and flavonoid group which help in antioxidant activity as well as the hydroalcoholic extract shows mild activity against diabetes. Keywords: Woodfordia fruticosa, phytochemical, hydroalchoholic, antioxidants, antidiabetic, DPPH.

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“…Turmeric (Curcuma longa) is a ginger family rhizomatous herbaceous perennial plant. It's a spice that's important in both medical and scientific circles, as well as in the kitchen.These are potential phytochemical substances that can be used in molecular docking experiments (Miziak et al, 2021;Raghuvanshi et al, 2021) (Miziak et al, 2021). This research contributes to our understanding of the structural effects of these phytochemicals on the MAPT Protein, which is thought to be the primary cause of familial forms of Alzheimer's disease.…”

Section: Introductionmentioning

confidence: 99%

Identifying Novel Compound against the Mutational Impact on the Mapt Protein via Molecular Docking Studies

2022

pnr

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Aim. Molecular docking experiments employing a molecular docking server will be used to find novel drugs against mutant structures of the MAPT protein linked to Alzheimer's disease. Materials and Methods. In this study, we used SWISS-Attach to dock phytochemicals Curcumin and Resveratrol with mutant structures of MAPT protein V287I mutation, which were predicted to have destabilizing effects on the MAPT protein by Dynamut.Alzheimer's disease, EOAD, PSEN2, Mutant structures, Novel compounds, Molecular Docking, SWISS-DOCK. Sample size chosen for this study was 1 mutation for the MAPT gene. Results. The binding energies of the docked molecules were investigated. Conclusion. Using the molecular docking online tool that we employed in our investigation, we performed molecular docking of mutant MAPT protein structures with putative phytochemicals. These docked chemicals could help with medication development investigations and uncover a possible AD treatment.

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Identification of plant-based multitargeted leads for Alzheimer's disease: In-vitro and in-vivo validation of Woodfordia fruticosa (L.) Kurz

Cited by 11 publications

References 43 publications

Design, Synthesis, and Pharmacological Evaluation of Embelin–Aryl/alkyl Amine Hybrids as Orally Bioavailable Blood–Brain Barrier Permeable Multitargeted Agents with Therapeutic Potential in Alzheimer’s Disease: Discovery of SB-1448

Design, Synthesis, and Pharmacological Evaluation of Embelin–Aryl/alkyl Amine Hybrids as Orally Bioavailable Blood–Brain Barrier Permeable Multitargeted Agents with Therapeutic Potential in Alzheimer’s Disease: Discovery of SB-1448

Antioxidant and Antidiabetic activity of hydroalcoholic flower extract of Woodfordia fruticosa (L.) Kurz

Identifying Novel Compound against the Mutational Impact on the Mapt Protein via Molecular Docking Studies

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