Folecitin isolated from hypericum oblongifolium exerts neuroprotection against lipopolysaccharide-induced neuronal synapse and memory dysfunction via p-AKT/Nrf-2/HO-1 signalling pathway

Neurodegenerative diseases, especially Alzheimer's disease (AD), are characterised with neuronal synapse and memory dysfunction, and thus, there is an urgent need to find novel therapeutic medicines that can target different pathways to restore the deficits. In this investigation, we assessed the medicinal potency of folecitin (a flavonoid isolated from Hypericum oblongifolium Wall.) against lipopolysaccharide (LPS)-induced amyloidogenic amyloid beta (Aβ) production pathway-mediated memory impairment in mice. The LPS was administered intraperitonially (i.p.) 250 μg/kg/day for 3 consecutive weeks, followed by the coadministration of folecitin (30 mg/kg/day) with LPS for the last two weeks (2nd and 3rd week). The expression of various proteins involved in synapse, neuronal death, and Aβ generation was evaluated using the Western blot approach. Results indicated that folecitin significantly decreased LPS-induced apoptotic proteins; expressed BAX, PARP-1, and caspase-3 proteins; and inhibited BACE1 that cleaves transmembrane amyloid precursor protein and the amyloidogenic Aβ production pathway. Folecitin restored both preneural and postneuronal synapse, accompanied by the improvement in memory impairment. Moreover, folecitin significantly activated endogenous antioxidant proteins Nrf-2 and HO-1 by stimulating the phosphorylation of Akt proteins. These findings indicate that folecitin might be a promising target for developing novel medication to treat neurodegenerative disorders caused by neurotoxins

Isolation, characterization, pharmacological evaluation and in silico modeling of bioactive secondary metabolites from Ziziphus oxyphylla a member of Rhamnaceae family

Purpose: To investigate the pharmacological properties of the medicinally active metabolites of Ziziphus oxyphylla. Methods: Compound I-IV were isolated form the root of Ziziphus oxyphylla (compound I = Stigmasterol, II = Betulinic acid, III = 1,2,3 benzene triol and IV = 5-Pentadecanoic acid). Various spectroscopic techniques were used to identify and characterize the isolated compounds. DPPH (2,2-diphenyl-1- picrylhydrazyl) and ABTS (2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) assays were employed to determine the antioxidant potentials of these compounds. The acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) inhibition potential of the isolated compounds were also evaluated. Results: Amongst the isolated compounds, compound IV was the most potent antioxidant against DPPH and ABTS free radicals, exhibiting half-maximal concentration (IC50) values of 64 and 65 μg/mL, respectively. All the compounds exhibited good inhibition of acetylcholinesterase and butyrylcholinesterase. However, stigmasterol was more potent than the other isolated compounds, showing IC50 of 85.10 ± 1.45 and 84.81 ± 1.17, respectively, against AChE and BChE. Conclusion: Although, all isolated compounds inhibited the selected free radicals (DPPH and ABTS) and cholinesterases, stigmasterol and 5-penatadecanoic acid were more potent than other two compounds. Thus the former can potentially be used to treat oxidative stress and neurodegenerative diseases. Keywords: Ziziphus oxyphylla, Stigmasterol, 5-Pentadecanoic acid, Antioxidant, Acetyl Cholinesterase, Butyryl cholinesteras

Simulation and modeling of physiological processes of vital organs in organ-on-a-chip biosystem

The limited adequacy of animal cell cultures and models to mimic the complexity of human bodies in laboratory conditions has emphasized researchers to find its quintessential bioelectronic alternative with improved competence. In this regard, tissue engineering has emerged as one of the most precise biomaterial technologies in terms of creating new tissues to model vital organs. An organ-on-a-chip biosystem has shown a plethora of applications in tissue engineering and drug delivery. Organ-on-a-chip is a microfluidic device that provides a completely controlled microenvironment, similar to the natural tissues for the cultured cells of an organ, by amalgamating cell biology and biomaterial science. The device contains several microchambers and microchannels embedded in a layer of a biocompatible polymer, such as polydimethylsiloxane. Microchambers house the cells, while microchannels provide nutrients and growth factors. Over the past few years, organ-on-a-chip technology has displayed ample applications in the field of biomedicine, not only by simulating the normal functions of disparate organs, but also by understanding the inter-relation between diversified systems. In this review, we have spotlighted recent advancements and applications of organ-on-a-chip biosystems to construct physiological models for the heart, lung, kidney, liver, and brain. Part of this review is also concentrated on abridging the desperate essentiality as well as future perspectives of organ-on-a-chip technology in biomedicine, disease modeling, and drug development process

Synthesis, characterization, and pharmacological evaluation of thiourea derivatives

Thioureas and their derivatives are organosulfur compounds having applications in numerous fields such as organic synthesis and pharmaceutical industries. Symmetric thiourea derivatives were synthesized by the reaction of various anilines with CS2. The synthesized compounds were characterized using the UV-visible and nuclear magnetic resonance (NMR) spectroscopic techniques. The compounds were screened for in vitro inhibition of α-amylase, α-glucosidase, acetylcholinesterase (AChE), and butyrylcholinesterase (BuChE) enzymes and for their antibacterial and antioxidant potentials. These compounds were fed to Swiss male albino mice to evaluate their toxicological effects and potential to inhibit glucose-6-phosphatase (G6Pase) inhibition. The antibacterial studies revealed that compound 4 was more active against the selected bacterial strains. Compound 1 was more active against 2,2-diphenyl-1-picrylhydrazyl and 2,2’-Azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) free radicals, AChE, BuChE, and α-glucosidase. Compound 2 was more potent against α-amylase and G6Pase. Toxicity studies showed that compound 4 is safe as it exerted no toxic effect on any of the hematological and biochemical parameters or on liver histology of the experimental animals at any studied dose rate. The synthesized compounds showed promising antibacterial and antioxidant potential and were very active (both in vitro and in vivo) against G6Pase and moderately active against the other selected enzymes used in this study

Antimicrobial, Cytotoxic, and Antioxidant Potential of a Novel Flavone “6,7,4′-Trimethyl Flavone” Isolated from Wulfenia amherstiana

Wulfenia amherstiana belongs to the Scrophulariaceae family and various plants of this family are known for their biological activities. The present study was focused on the isolation of bioactive compounds including a novel flavone 6,7,4′-trimethyl flavone (TMF) along with three known flavonoids such as quercetin, rutin, and a steroid β-sitosterol which were isolated from the ethanolic extract of W. amherstiana (Himalayan Wulfenia) through column chromatography and purified by using HPLC. Their structures were identified and elucidated through electron ionization mass spectroscopy (EIMS), 1DNMR (1H-NMR and 13C-NMR), and 2DNMR (COSY, HMQC, and HMBC) spectroscopy. The antimicrobial activities of this novel compound were evaluated through agar well diffusion method, while antioxidant and cytotoxic activities were assessed through 2,2-diphenyl-1-picrylhydrazyl (DPPH) free-radical scavenging assay and brine shrimp lethality assay, respectively. The NMR data revealed that TMF is a novel compound. TMF showed potential antibacterial and antifungal activities against Staphylococcus aureus (MIC = 128 μg/ml) and Candida albicans (MIC = 128 μg/ml). The cytotoxic potential of TMF was determined from brine shrimp lethality assay with LD50 of 127.01 μg/ml. The free-radical scavenging potential of TMF at various concentrations implicated its strong antioxidant activity in vitro. The results revealed that TMF demonstrated substantial antimicrobial activity against S. aureus and C. albicans, strong antioxidant activity, and moderately cytotoxic activity