Punicalagin Regulates Signaling Pathways in Inflammation-Associated Chronic Diseases

Inflammation is a complex biological defense system associated with a series of chronic diseases such as cancer, arthritis, diabetes, cardiovascular and neurodegenerative diseases. The extracts of pomegranate fruit and peel have been reported to possess health-beneficial properties in inflammation-associated chronic diseases. Punicalagin is considered to be the major active component of pomegranate extracts. In this review we have focused on recent studies into the therapeutic effects of punicalagin on inflammation-associated chronic diseases and the regulatory roles in NF-κB, MAPK, IL-6/JAK/STAT3 and PI3K/Akt/mTOR signaling pathways. We have concluded that punicalagin may be a promising therapeutic compound in preventing and treating inflammation-associated chronic diseases, although further clinical studies are required.

The Implication of Low Dose Dimethyl Sulfoxide on Mitochondrial Function and Oxidative Damage in Cultured Cardiac and Cancer Cells

Although numerous studies have demonstrated the biological and multifaceted nature of dimethyl sulfoxide (DMSO) across different in vitro models, the direct effect of “non-toxic” low DMSO doses on cardiac and cancer cells has not been clearly explored. In the present study, H9c2 cardiomyoblasts and MCF-7 breast cancer cells were treated with varying concentrations of DMSO (0.001–3.7%) for 6 days. Here, DMSO doses < 0.5% enhanced the cardiomyoblasts respiratory control ratio and cellular viability relative to the control cells. However, 3.7% DMSO exposure enhanced the rate of apoptosis, which was driven by mitochondrial dysfunction and oxidative stress in the cardiomyoblasts. Additionally, in the cancer cells, DMSO (≥0.009) led to a reduction in the cell’s maximal respiratory capacity and ATP-linked respiration and turnover. As a result, the reduced bioenergetics accelerated ROS production whilst increasing early and late apoptosis in these cells. Surprisingly, 0.001% DMSO exposure led to a significant increase in the cancer cells proliferative activity. The latter, therefore, suggests that the use of DMSO, as a solvent or therapeutic compound, should be applied with caution in the cancer cells. Paradoxically, in the cardiomyoblasts, the application of DMSO (≤0.5%) demonstrated no cytotoxic or overt therapeutic benefits.

ACT001 reverses resistance of prolactinomas via AMPK-mediated EGR1 and mTOR pathway

Dopamine agonist (DA) is the first choice for the treatment of prolactinomas and drug resistance is unavoidable during treatment due to the heterogeneity of tumors. The two prolactinoma cell lines (GH3 cells and MMQ cells) were found to have different sensitivity and responding modes to the cabergoline (CAB) and bromocriptine (BRC). In this research, we disclosed the capability of ACT001, a derivative of parthenolide analogues, to activate AMPK by increasing the intracellular reactive oxygen species (ROS) level and AMP/ATP ratio to reverse DA-resistance through dual pathways in prolactinoma cells. The results indicated that ACT001 could reverse the CAB-resistance in GH3 cells by inhibiting the mTOR signaling pathway mainly inducing cell death through autophagy and reverse the BRC-resistance in MMQ cells by activating the EGR1 signaling pathway mainly inducing cell death through apoptosis. Our results suggested that ACT001 is a promising therapeutic compound for treating DA-resistant prolactinomas.

Eugenol Elicits Prolongevity by Increasing Resistance to Oxidative Stress in C. elegans

Aim: To analyze the efficacy of eugenol on longevity by assessing its antioxidant effect using Caenorhabditis elegans as an animal model. Background: Eugenol is a major polyphenolic component of Ocimum sanctum (Tulsi) which attributes wide pharmacological activities and can serve as a biomarker. However, the possible effect of eugenol on longevity in Caenorhabditis elegans has not been reported. Objective: The objective of this investigation was to provide first scientific based results about effect of eugenol on longevity, slowing down of paralysis in Alzheimer’s model and mechanism behind it in Caenorhabditis elegans animal model system. Results: Extract of Ocimum sanctumand eugenol increased lifespan and provided indemnity against pro-oxidants. It also significantly improved healthy ageing and slowed the progression of neurodegeneration in CL4176 Alzheimer’s model of worm by increasing survival against prooxidants and slowing down the paralysis. Longevity effect was independent of the DAF-16 as observed by using DAF-16::GFP and daf-16 null mutant strains. These results implicate eugenol as a potent therapeutic compound which may curtail ageing and age related disorders like- Alzheimer’s disease. Conclusion: The present work demonstrated eugenol as a potential anti-ageing compound which may curtail ageing, improve heath span by enhancing resistance to oxidative stress and exerts its effect independent of DAF-16 pathway. So, it can be assumed that eugenol can be beneficial to humans as well, albeit further research is necessary before declaring it for human consumption.

Carbon Monoxide Therapy Using Hybrid Carbon Monoxide-Releasing/Nrf2-Inducing Molecules through a Neuroprotective Lens

Carbon monoxide (CO) has long been known for its toxicity. However, in recent decades, new applications for CO as a therapeutic compound have been proposed, and multiple forms of CO therapy have since been developed and studied. Previous research has found that CO has a role as a gasotransmitter and promotes anti-inflammatory and antioxidant effects, making it an avenue of interest for medicine. Such effects are possible because of the Nrf2/HO1 pathway, which has become a target for therapy development because its activation also leads to CO release. Currently, different forms of treatment involving CO include inhaled CO (iCO), carbon monoxide-releasing molecules (CORMs), and hybrid carbon monoxide-releasing molecules (HYCOs). In this article, we review the progression of CO studies to develop possible therapies, the possible mechanisms involved in the effects of CO, and the current forms of therapy using CO.

Integrating Multi-Datasets Analysis with Molecular Docking To Explore Potential Therapeutic Compound and Its Mechanism and Target Sites in Gastric Carcinoma

Background Gastric carcinoma still threatens public health with high morbidity and mortality, especially in Eastern Asia. Target therapy possesses a vast value and makes significant progress in cancer treatment, and it is essential to explore more potential target drugs in gastric carcinoma. Methods Gene expression data was obtained from TCGA (The Cancer Genome Atlas) and GEO (Gene Expression Omnibus) datasets and the interaction networks of chemical-genes was obtained from CTD (Comparative Toxicogenomics Database). Then, GSEA (Gene Set Enrichment Analysis) was utilized to identify the significant compounds, which related to gene expression in gastric carcinoma. Moreover, PPI (Protein-Protein Interaction) network, screening of hub-genes, KEGG (Kyoto Encyclopedia of Genes and Genomes), and GO (Gene Ontology) analysis were employed to explore potential mechanisms and potential targets of these compounds. Finally, molecular docking was used to analyze the stable binding between the compounds and target proteins. Results Bazedoxifene was selected by integrating datasets and bioinformatics analysis as a potential therapeutic compound. UHRF1, MCM10, HELLS, and DTL with high expression in cancer tissues may be new targets in gastric carcinoma. Furthermore, Bazedoxifene may target UHRF1 and the pathway of ubiquitin-like protein transferase in gastric carcinoma and has potential therapeutic value. Conclusion It is infered that Bazedoxifene may target on UHRF1 in gastric carcinoma and has the therapeutic potential.

Lipid Peroxidation and the Redox Effects of Polyherbal

The use of more than one herb in a medicinal preparation also known as polyherbal has increased geometrically in recent times. Over a hundred thousand scientists have cited “herbal” to strengthen its ethnopharmacological relevance in literature. Polyherbal (PH) is effective potential therapeutic compound used globally to treat oxidative stress-induced injuries which give credence for their traditional applications. However, some issues related to safety and adverse reactions due to PH have raised important public health debates. Lipid peroxidation (LPO) assay is widely used to assess the toxic endpoint of PH. This paper discusses some important roles that PH plays during oxidation–reduction processes.

Withaferin A – A natural multifaceted therapeutic compound

COVID 19, which has lead to the death of millions of people, is still spreading worldwide. The development of any new drug after proper trial is much time consuming. This present global pandemic situation has lead the researchers around the world to run behind various existing antiviral and immunomodulatory natural compounds to overcome this contagious disease. Withania somnifera (ashwagandha) that is being used in Ayurvedic medicine for several ailments since several years is also said to pocess anti viral activity. Thus many of its metabolites are being studied individually for its efficacy against the dreadful disease. Withaferin A, a steroidal lactone from ashwagandha is one such prime metabolite which beyond acting as an antioxidant or antimicrobial agent, is also said to pocess anti-inflammatory to anti carcinogenic properties. Thus because of its wide spectrum of medicinal properties it has now become an attractive drug candidate for several preclinical studies. This increase in the demand for withaferin A has chanelled its way towards in vitro propagation of the plant Withania somnifera and trials on various strategies to increase the yield in terms of plant biomass as well as the withaferin content in the plants thus making it a better alternative to field grown plants. Thus this article reviews in depth on the important medicinal properties of withaferin A, its demand in Ayurveda industry and the in vitro strategies being carried out to overcome the demand.

Zebrafish as an animal model for biomedical research

Zebrafish have several advantages compared to other vertebrate models used in modeling human diseases, particularly for large-scale genetic mutant and therapeutic compound screenings, and other biomedical research applications. With the impactful developments of CRISPR and next-generation sequencing technology, disease modeling in zebrafish is accelerating the understanding of the molecular mechanisms of human genetic diseases. These efforts are fundamental for the future of precision medicine because they provide new diagnostic and therapeutic solutions. This review focuses on zebrafish disease models for biomedical research, mainly in developmental disorders, mental disorders, and metabolic diseases.