Ethnomedicinal Use, Phytochemistry, and Pharmacology of Xylocarpus granatum J. Koenig

The mangrove plants are the potential sources of foods and remedies for people living in the forests and nearby communities. Xylocarpus granatum J. Koenig is traditionally used to treat various diseases including diarrhea, cholera, dysentery, fever, malaria, and viral infections, among others. To summarize critically the taxonomy, ethnomedicinal, phytochemistry, and pharmacological activities of X. granatum, information was collected from different databases. An up-to-date search (till June 2020) was carried out with the help of various scientific web resources from databases such as PubMed, Science Direct, Google Scholar, and various patent offices (e.g., WIPO, CIPO, and USPTO) using the keywords “Xylocarpus granatum” and then paired with ethnomedicinal use and phytochemical, phytochemistry, and pharmacological activity (in vitro, ex vivo, and in vivo studies). Findings revealed that seeds, fruits, stem bark, leaf, and twigs of X. granatum exhibited a wide range of key phytochemicals including limonoids, phragmalin, limonoid-based alkaloids, mexicanolides, protolimonoids, flavonols, and lactones. The plant possessed potent antioxidant, anticancer, antidiabetic, antimicrobial, antimalarial, antifeedant, and neuroprotective activities. No clinical studies have been reported in the databases. Ethnomedicinal assessment indicated the application of X. granatum in various fields of medical science specially to treat various human ailments, and this was attributed to the presence of enormous alkaloids as confirmed by pharmacological studies. However, to understand the mechanism of action in-depth studies are required. In view of these findings, more research is necessary to explore and characterize the chemical compounds and toxicological aspects of this medicinal mangrove plant. Overall, it can be stated that X. granatum may be one of the hopeful medicinal herbs for the treatment of various diseases in human beings.

Download Full-text

Monocytes as Carriers of Magnetic Nanoparticles for Tracking Inflammation in the Epileptic Rat Brain

Current Drug Delivery ◽

10.2174/1567201816666190619122456 ◽

2019 ◽

Vol 16 (7) ◽

pp. 637-644 ◽

Cited By ~ 4

Author(s):

Hadas Han ◽

Sara Eyal ◽

Emma Portnoy ◽

Aniv Mann ◽

Miriam Shmuel ◽

...

Keyword(s):

Brain Tissue ◽

Ex Vivo ◽

In Vivo Studies ◽

Nanoparticle Distribution ◽

Spontaneous Seizures ◽

Systemic Distribution ◽

Hippocampal Ca1 ◽

Pilocarpine Model

Background: Inflammation is a hallmark of epileptogenic brain tissue. Previously, we have shown that inflammation in epilepsy can be delineated using systemically-injected fluorescent and magnetite- laden nanoparticles. Suggested mechanisms included distribution of free nanoparticles across a compromised blood-brain barrier or their transfer by monocytes that infiltrate the epileptic brain. Objective: In the current study, we evaluated monocytes as vehicles that deliver nanoparticles into the epileptic brain. We also assessed the effect of epilepsy on the systemic distribution of nanoparticleloaded monocytes. Methods: The in vitro uptake of 300-nm nanoparticles labeled with magnetite and BODIPY (for optical imaging) was evaluated using rat monocytes and fluorescence detection. For in vivo studies we used the rat lithium-pilocarpine model of temporal lobe epilepsy. In vivo nanoparticle distribution was evaluated using immunohistochemistry. Results: 89% of nanoparticle loading into rat monocytes was accomplished within 8 hours, enabling overnight nanoparticle loading ex vivo. The dose-normalized distribution of nanoparticle-loaded monocytes into the hippocampal CA1 and dentate gyrus of rats with spontaneous seizures was 176-fold and 380-fold higher compared to the free nanoparticles (p<0.05). Seizures were associated with greater nanoparticle accumulation within the liver and the spleen (p<0.05). Conclusion: Nanoparticle-loaded monocytes are attracted to epileptogenic brain tissue and may be used for labeling or targeting it, while significantly reducing the systemic dose of potentially toxic compounds. The effect of seizures on monocyte biodistribution should be further explored to better understand the systemic effects of epilepsy.

Download Full-text

Phenolic Acids Exert Anticholinesterase and Cognition-Improving Effects

Current Alzheimer Research ◽

10.2174/1567205014666171128102557 ◽

2018 ◽

Vol 15 (6) ◽

pp. 531-543 ◽

Cited By ~ 4

Author(s):

Dominik Szwajgier ◽

Ewa Baranowska-Wojcik ◽

Kamila Borowiec

Keyword(s):

Phenolic Acids ◽

Ex Vivo ◽

Amyloid Β ◽

Inhibitory Effect ◽

In Vivo Studies ◽

Amyloid Β Peptide ◽

Beneficial Effects ◽

Aβ Fibrils

Numerous authors have provided evidence regarding the beneficial effects of phenolic acids and their derivatives against Alzheimer's disease (AD). In this review, the role of phenolic acids as inhibitors of acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) is discussed, including the structure-activity relationship. In addition, the inhibitory effect of phenolic acids on the formation of amyloid β-peptide (Aβ) fibrils is presented. We also cover the in vitro, ex vivo, and in vivo studies concerning the prevention and treatment of the cognitive enhancement.

Download Full-text

Antimalarial drugs—are they beneficial in rheumatic and viral diseases?—considerations in COVID-19 pandemic

Clinical Rheumatology ◽

10.1007/s10067-021-05805-5 ◽

2021 ◽

Author(s):

Bogna Grygiel-Górniak

Keyword(s):

Connective Tissue ◽

Viral Infections ◽

Current Knowledge ◽

Inflammatory Diseases ◽

Antiviral Drugs ◽

In Vivo Studies ◽

Viral Diseases ◽

Cardiac Complications

AbstractThe majority of the medical fraternity is continuously involved in finding new therapeutic schemes, including antimalarial medications (AMDs), which can be useful in combating the 2019-nCoV: coronavirus disease (COVID-19). For many decades, AMDs have been widely used in the treatment of malaria and various other anti-inflammatory diseases, particularly to treat autoimmune disorders of the connective tissue. The review comprises in vitro and in vivo studies, original studies, clinical trials, and consensus reports for the analysis, which were available in medical databases (e.g., PubMed). This manuscript summarizes the current knowledge about chloroquine (CQ)/hydroxychloroquine (HCQ) and shows the difference between their use, activity, recommendation, doses, and adverse effects on two groups of patients: those with rheumatic and viral diseases (including COVID-19). In the case of connective tissue disorders, AMDs are prescribed for a prolonged duration in small doses, and their effect is observed after few weeks, whereas in the case of viral infections, they are prescribed in larger doses for a short duration to achieve a quick saturation effect. In rheumatic diseases, AMDs are well tolerated, and their side effects are rare. However, in some viral diseases, the effect of AMDs is questionable or not so noticeable as suggested during the initial prognosis. They are mainly used as an additive therapy to antiviral drugs, but recent studies have shown that AMDs can diminish the efficacy of some antiviral drugs and may cause respiratory, kidney, liver, and cardiac complications.

Download Full-text

Pharmacokinetic and toxicology assessment of INTERCEPT (S-59 and UVA treated) platelets

Human & Experimental Toxicology ◽

10.1191/096032701718120319 ◽

2001 ◽

Vol 20 (10) ◽

pp. 533-550 ◽

Cited By ~ 55

Author(s):

V Ciaravino ◽

T McCullough ◽

A D Dayan

Keyword(s):

Ex Vivo ◽

Reproductive Toxicity ◽

In Vivo Studies ◽

Pathogen Inactivation ◽

Platelet Concentrates ◽

Baxter Healthcare ◽

Safety Margins ◽

Toxicology Assessment

The pathogen inactivation process developed by Cerus and Baxter Healthcare Corporations uses the psoralen, S-59 (amotosalen) in an ex vivo photochemical treatment (PCT) process to inactivate viruses, bacteria, protozoans, and leukocytes in platelet concentrates and plasma. Studies were performed by intravenous infusion of S-59 PCT formulations-compound adsorption device (CAD) treatment and with non-UVA illuminated S-59, using doses that were multiples of potential clinical exposures. The studies comprised full pharmacokinetic, single and repeated-dose (up to 13 weeks duration) toxicity, safety pharmacology (CNS, renal, and cardiovascular), reproductive toxicity, genotoxicity, carcinogenicity testing in the p53- mouse, vein irritation, and phototoxicity. No specific target organ toxicity (clinical or histopathological), reproductive toxicity, or carcinogenicity was observed. S-59 and/or PCT formulations demonstrated CNS, ECG, and phototoxicity only at supraclinical doses. Based on the extremely large safety margins (>30,000 fold expected clinical exposures), the CNS and ECG observations are not considered to have any toxicological relevance. Additionally, after a complete assessment, mutagenicity and phototoxicity results are not considered relevant for the proposed use of INTERCEPT platelets. Thus, the results of an extensive series of in vitro and in vivo studies have not demonstrated any toxicologically relevant effects of platelet concentrates prepared by the INTERCEPT system.

Download Full-text

Phytochemistry and Pharmacology of the Genus Pedicularis Used in Traditional Chinese Medicine

The American Journal of Chinese Medicine ◽

10.1142/s0192415x14500670 ◽

2014 ◽

Vol 42 (05) ◽

pp. 1071-1098 ◽

Cited By ~ 13

Author(s):

Mao-Xing Li ◽

Xi-Rui He ◽

Rui Tao ◽

Xinyuan Cao

Keyword(s):

Chinese Medicine ◽

Traditional Chinese Medicine ◽

Chemical Constituents ◽

Iridoid Glycosides ◽

In Vivo Studies ◽

Chemical Components ◽

Wide Range ◽

Phenylpropanoid Glycosides

In the present review, the literature data on the chemical constituents and biological investigations of the genus Pedicularis are summarized. Some species of Pedicularis have been widely applied in traditional Chinese medicine. A wide range of chemical components including iridoid glycosides, phenylpropanoid glycosides (PhGs), lignans glycosides, flavonoids, alkaloids and other compounds have been isolated and identified from the genus Pedicularis. In vitro and in vivo studies indicated some monomer compounds and extracts from the genus Pedicularis have been found to possess antitumor, hepatoprotective, anti-oxidative, antihaemolysis, antibacterial activity, fatigue relief of skeletal muscle, nootropic effect and other activities.

Download Full-text

The pathophysiologic role of the protein kinase Cδ pathway in the intervertebral discs of rabbits and mice: In vitro, ex vivo, and in vivo studies

Arthritis & Rheumatism ◽

10.1002/art.34337 ◽

2012 ◽

Vol 64 (6) ◽

pp. 1950-1959 ◽

Cited By ~ 25

Author(s):

Michael B. Ellman ◽

Jae-Sung Kim ◽

Howard S. An ◽

Jeffrey S. Kroin ◽

Xin Li ◽

...

Keyword(s):

Protein Kinase ◽

Ex Vivo ◽

Intervertebral Discs ◽

In Vivo Studies ◽

Protein Kinase Cδ

Download Full-text

hPSC-Derived Enteric Ganglioids Model Human ENS Development and Function

10.1101/2022.01.04.474746 ◽

2022 ◽

Author(s):

Homa Majd ◽

Ryan M Samuel ◽

Jonathan T Ramirez ◽

Ali Kalantari ◽

Kevin Barber ◽

...

Keyword(s):

Ex Vivo ◽

Xenograft Model ◽

Developmental Relationships ◽

Drug Candidates ◽

Effective Strategies ◽

Wide Range ◽

Functional Features ◽

And Function

The enteric nervous system (ENS) plays a central role in gut physiology and mediating the crosstalk between the gastrointestinal (GI) tract and other organs. The human ENS has remained elusive, highlighting the need for an in vitro modeling and mapping blueprint. Here we map out the developmental and functional features of the human ENS, by establishing robust and scalable 2D ENS cultures and 3D enteric ganglioids from human pluripotent stem cells (hPSCs). These models recapitulate the remarkable neuronal and glial diversity found in primary tissue and enable comprehensive molecular analyses that uncover functional and developmental relationships within these lineages. As a salient example of the power of this system, we performed in-depth characterization of enteric nitrergic neurons (NO neurons) which are implicated in a wide range of GI motility disorders. We conducted an unbiased screen and identified drug candidates that modulate the activity of NO neurons and demonstrated their potential in promoting motility in mouse colonic tissue ex vivo. We established a high-throughput strategy to define the developmental programs involved in NO neuron specification and discovered that PDGFR inhibition boosts the induction of NO neurons in enteric ganglioids. Transplantation of these ganglioids in the colon of NO neuron-deficient mice results in extensive tissue engraftment, providing a xenograft model for the study of human ENS in vivo and the development of cell-based therapies for neurodegenerative GI disorders. These studies provide a framework for deciphering fundamental features of the human ENS and designing effective strategies to treat enteric neuropathies.

Download Full-text

Non-Toxic Virucidal Macromolecules Show High Efficacy Against Influenza Virus Ex Vivo and In Vivo

10.1101/2020.03.18.996678 ◽

2020 ◽

Author(s):

Ozgun Kocabiyik ◽

Valeria Cagno ◽

Paulo Jacob Silva ◽

Yong Zhu ◽

Laura Sedano ◽

...

Keyword(s):

Broad Spectrum ◽

Viral Infections ◽

Ex Vivo ◽

Public Health Problem ◽

Major Public Health Problem ◽

New Class ◽

Influenza Strain ◽

Low Toxicity

AbstractInfluenza is one of the most widespread viral infections worldwide and represents a major public health problem. The risk that one of the next pandemics is caused by an influenza strain is very high. It is very important to develop broad-spectrum influenza antivirals to be ready for any possible vaccine shortcomings. Anti-influenza drugs are available but they are far from ideal. Arguably, an ideal antiviral should target conserved viral domains and be virucidal, i.e. irreversibly inhibit viral infectivity. Here, we describe a new class of broad-spectrum anti-influenza macromolecules that meets these criteria and displays exceedingly low toxicity. These compounds are based on a cyclodextrin core modified on its primary face with long hydrophobic linkers terminated in 6’sialyl-N-acetyllactosamine (6’SLN) or 3’SLN. SLN enables nanomolar inhibition of the viruses while the hydrophobic linkers confer irreversibility to the inhibition. The combination of these two properties allows for efficacy in vitro against several human or avian influenza strains, as well as against a 2009 pandemic influenza strain ex vivo. Importantly, we show that, in mice, the compounds provide therapeutic efficacy when administered 24h post-infection allowing 90% survival as opposed to no survival for the placebo and oseltamivir..

Download Full-text