Current Bioactive Compounds - Volume 20, Issue 5, 2024

Background: Lack of control in voluntary movements, resting tremor, postural instability, and stiffness are the hallmarks of Parkinson's disease (PD). Objective: The current work's objective is to assess naringin isolated from Citrus aurantium L. peels as an anti-parkinsonism agent in rats. Methods: The HPLC and LC-ESI-MS analysis of Citrus aurantium L. peels methanol extract was done. The behavioral, biochemical, genetic, and histopathological analysis were evaluated in parkinsonism rats. Results: Fourteen phenolics and nine flavonoids were found in the extract, according to the HPLC analysis, while LC-ESI-MS analysis revealed the presence of twenty-six flavonoids. The dominant flavonoid subclasses were 4 aglycones, 11 monoglycosides, 5 diglycosides, and 6 polymethoxy flavonoids, beside 4 coumarines, 4 alkaloids and a limonin triterpene. Adenosine A2A receptor (A2AR) gene expression, malondialdehyde (MDA), interleukin-6 (IL-6), caspase-3 (Cas-3) and DNA fragmentation levels significantly increased in rotenone-induced rats. Dopamine (DA), norepinephrine (NE), serotonin (5-HT), reduced glutathione (GSH), succinate, and lactate dehydrogenase (SDH ) levels all significantly decreased. Treatment with naringin and A2AR antagonists enhanced the animals’ behavior and improved all the selected parameters. The brain hippocampal features confirmed our results. Conclusion: Naringin could be considered a nutraceutical agent by attenuating the neurodegeneration associated with PD via blocking adenosine A2AR.

Background: Anemia is a global hematological disorder. Earthworms have antimicrobial, antispasmodic, antihypertensive, antiallergic, anti-inflammatory, and anticoagulant properties. Objective: Our study aimed to investigate the anti-anemic activity of the earthworm Allolobophora caliginosa extract (AcE) on phenylhydrazine-induced hemolytic anemia in rats. Methods: Eighteen adult male albino rats were randomly divided into 3 groups (n = 6 per group) as follows: Control, PHZ, and AcE-treated groups. Induction of anemia was done by intraperitoneal administration of phenylhydrazine (40 mg/kg) for 2 consecutive days. Treatment of AcE by intraperitoneal injection (45 mg/kg) for six successive days. Results: Treatment of anemic rats with AcE extract caused significant increases in red blood cells (RBCs), hemoglobin (HB), hematocrit (HCT), total protein (TP), albumin, glutathione reduced (GSH), catalase (CAT), and glutathione-S-transferase (GST), as compared to the PHZ group. While, mean corpuscular haemoglobin (MCH), mean corpuscular hemoglobin concentration (MCHC), alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), malondialdehyde (MDA), and nitric oxide (NO) levels significantly decreased after intraperitoneal administration of AcE, when compared to the PHZ group. Liver sections from the AcE-treated group restored the normal micromorphological features of the liver. The expression of caspase-3 was weak and/or there was no expression in the liver sections from AcE groups. AcE caused a significant reduction in the incidence of DNA damage, which appeared as less DNA in the tails. Conclusion: The present research sheds light on the antianemic efficacy of AcE in rats. This study reveals that AcE has antianemic activity, which can be linked to its iron and branched-chain amino acid content, as well as antioxidant and anti-apoptotic properties.

Background: Green tea extract is a hydrophilic antioxidant. The challenge associated with its cutaneous administration is its poor penetration. A system of solid-liquid lipids formulated in the form of a nanostructured lipid carrier (NLC), can improve the penetration. In addition, Vitamin E oil used as a liquid lipid will aid in skin hydration, reduce particle size, and enhance penetration. Objective: The objective of this study was to formulate the NLC-based sunscreen gel of green tea extract. Methods: Nanostructured lipid carriers (NLC) were prepared by melt emulsion ultrafiltration technique and were evaluated for particle size, zeta potential, polydispersity index (PDI), drug loading (DL), encapsulation efficacy (EE), and in vitro drug release. The optimised formula was incorporated into a suitable gel base and an in vitro sun protection factor (SPF) was determined. Beeswax and Vitamin E oil were chosen as solid and liquid lipids for NLC formulation. Results: The particle size, PDI, zeta potential, entrapment efficiency, and in vitro drug release of optimised formulation (NLC4) were found to be 139.4 nm, 0.236, -11.0 mV, 84.20%, and 85% respectively. The SPF value of green tea extract-NLC-loaded gel was found to be 20.035. Conclusion: The result of the current investigation depicted that lipid nanoparticles are suitable carriers for green tea extract to be delivered as sunscreen gel.

Background: Cancer is a leading cause of death worldwide and is anticipated to reach 28,4 million fresh cases globally by 2040. Despite all the progress made in cancer prevention, diagnosis, and treatment, mortality by cancer is in second place. Objectives: The design of novel 2-substituted benzimidazole modelled by QSAR study. Molecular docking studies on the novel derivatives and synthesis characterization and evaluation of the anticancer activity of the novel derivatives against breast cancer cell line MCF 7. Methods: We designed 10 novel benzimidazole derivatives modeled by 2D QSAR. From the ten compounds by applying in silico tools of ADME properties and toxicity and through molecular docking on Tyrosine Kinase (PDB ID: 2SRC). Compound 2AD showed the highest dock score of -9.5 kcal/mol followed by 2 BD and 2GD (-9.3 kcal/mol) Molecular dynamic simulation studies were conducted using CABSflex an online molecular dynamic simulation tool. Six compounds were selected for synthesis. The synthesized compounds were characterized and the invitro pharmacological activity was tested on MCF-7 cell line by MTT assay. Results: The compounds 2AD and 2GD showed good percentage inhibition on MCF-7 cell line with IC50 values of 2.757 μg/ml and 2.875 μg/ml respectively. Conclusion: The novel 2-substituted benzimidazole derivatives are good lead compounds for cancer therapy. Optimization of these compounds will be providing more target-specific anticancer agents.

Introduction: Memecylon umbellatum is a perennial plant of the Melastomataceae family that grows in abundance in the Western Ghats and has been used traditionally to treat cancer and inflammatory conditions. Methods: From the literature survey, it was found that no substantial work has been carried out to identify the bioactive compounds by HPTLC method and to screen the antioxidant and anticancer activity of M. umbellatum. Hence, an effort has been made to carry out the phytochemical investigation by HPTLC method and to screen the antioxidant activity by ABTS assay, DPPH assay, Nitric oxide antioxidant assay, Iron chelating activity and Total antioxidant activity. Results: Total phenolics and flavonoids were carried out by using suitable methods. MCF-7 as well as MDA-MB-231 cells were used to test anticancer activities in vitro. Cell cycle analysis demonstrated that ethyl acetate extract caused G0/G1 phase arrest in MCF-7 cells. HPTLC analysis led to the identification of Lupeol from ethyl acetate extract. Conclusion: The anticancer activity of ethyl acetate extract of M. umbellatum was significant. The antioxidant and anticancer activity may attributed to Lupeol, Phenolic compounds and Flavonoids.

Background: Alzheimer’s disease (AD) is a complex neurodegenerative condition for which a single protein-targeting medication is not enough to provide a cure. All the medications now available for AD are palliative. FDA has approved five medications for the treatment of AD, i.e., tacrine, donepezil, galantamine, rivastigmine, and memantine. Due to hepatotoxicity, tacrine is no longer utilized in clinical practice. Due to the lack of therapeutic efficiency of single-target medications and the multifaceted etiology of AD, multitarget-directed ligands have been developed. Objectives: The present research focused on incorporating a flavone nucleus into the amino group of 9-amino acridine nucleus to make it an acetylcholinesterase (AChE) and butyryl cholinesterase inhibitor (BuChE) with less toxicity. Methods: We designed and synthesized ten flavone-substituted acridine derivatives and evaluated them for in vitro AChE and BuChE inhibitory activity. Molecular modeling studies were conducted using AutoDock Vina with hAChE (PDB ID: 4EY7) and hBuChE (PDB ID: 4TPK). The toxicity profile of the most active novel compound tested on zebrafish larvae for determining the liver and cardiac toxicity and LD50 value of the compound were determined. Results: In vitro AChE and BuChE inhibitory study by Ellman assay showed acceptable results. The compound AF2 showed the highest activity with an IC50 value of 0.99 ± 0.1 μM for AChE and 1.78 ± 0.19 for BuChE. The in vivo acute toxicity studies conducted on zebra fish larvae did not show cardiac and hepatotoxicity, and the LD50 value was found to be 1000 μL. Conclusion: The results highlighted the AChE and BuChE inhibitory effects of the novel acridine- flavone hybrids, and they can be promising multitarget-directed ligands for AD.

The existence of the blood-brain barrier (BBB), a densely woven network of blood vessels and endothelial cells designed to prevent the infiltration of foreign substances into the brain, the methods employed in developing treatments for neurodegenerative disorders (NDs) such as Alzheimer's disease, Parkinson's disease, Huntington's disease, Multiple sclerosis, Amyotrophic lateral sclerosis, and others, pose significant challenges and complexities. These illnesses have had a terrible impact on the human population's health. Because early detection of these problems is poor and no good therapy has been established, they have emerged as the biggest lifethreatening healthcare burden worldwide compared to other significant illnesses. Traditional drug delivery techniques do not offer efficient treatment for NDs due to constraints in the BBB design, efflux pumps, and metabolic enzyme expression. Nanotechnology has the potential to significantly enhance ND therapy by utilizing systems that have been bioengineered to engage with living organisms at the cellular range. Compared to traditional techniques, nanotechnological technologies have several potential ways for crossing the BBB and increasing therapeutic efficacy in the brain. The introduction and growth of nanotechnology indicate promising potential for overcoming this issue. Engineered nanoparticles coupled with therapeutic moieties and imaging agents with dimensions ranging from 1-100 nm can improve effectiveness, cellular uptake, selective transport, and drug delivery to the brain due to their changed physicochemical properties. Conjugates of nanoparticles and medicinal plants, or their constituents known as nano phytomedicine, have recently gained importance in developing cutting-edge neuro-therapeutics due to their abundant natural supply, promising targeted delivery to the brain, and lower potential for adverse effects. This study summarizes the common NDs, their prevalence and pathogenesis, and potential herbal nanoformulation for treating NDs.