Livogrit prevents Amiodarone-induced toxicity in experimental model of human liver (HepG2) cells and Caenorhabditis elegans by regulating redox homeostasis.

Treatment with cationic amphiphilic drugs like Amiodarone leads to development of phospholipidosis, a type of lysosomal storage disorder characterized by excessive deposition of phospholipids. Such disorder in liver enhances accumulation of drugs and its metabolites, and dysregulates lipid profiles, which subsequently leads to hepatotoxicity. In the present study, we assessed pharmacological effects of herbal medicine, Livogrit, against hepatic phospholipidosis-induced toxicity. Human liver (HepG2) cells and in vivo model of Caenorhabditis elegans (N2 and CF1553 strains) were used to study effect of Livogrit on Amiodarone-induced phospholipidosis. In HepG2 cells, Livogrit treatment displayed enhanced uptake of acidic pH-based stains and reduced phospholipid accumulation, oxidative stress, AST, ALT, cholesterol levels, and gene expression of SCD-1 and LSS. Protein levels of LPLA2 were also normalized. Livogrit treatment restored Pgp functionality which led to decreased cellular accumulation of Amiodarone as observed by UHPLC analysis. In C. elegans, Livogrit prevented ROS generation, fat-6/7 gene overexpression, and lysosomal trapping of Amiodarone in N2 strain. SOD-3::GFP expression in CF1553 strain normalized by Livogrit treatment. Livogrit regulates phospholipidosis by regulation of redox homeostasis, phospholipid anabolism, and Pgp functionality hindered by lysosomal trapping of Amiodarone. Livogrit could be a potential therapeutic intervention for amelioration of drug-induced phospholipidosis and prevent hepatotoxicity.

Anti-oxidant response of lipidom modulates lipid metabolism in Caenorhabditis elegans and in OxLDL-induced human macrophages by tuning inflammatory mediators.

Atherosclerosis is the main pathological process of several cardiovascular diseases. It may begin early in life and stay latent and asymptomatic for an extended period before its clinical manifestation. The formation of foamy macrophages due to dysregulated lipid metabolism is a key event in the development and progression of atherosclerotic plaque. The current pharmacotherapy for atherosclerosis is not able to address multiple aetiologies associated with the disease. Lipidom, an herbal prescription medicine, has anti-oxidant, lipid lowering and anti-inflammatory properties that lead to multifaceted treatment benefits against chronic inflammation, dyslipidaemia, and oxidative stress. The present study aimed to characterize the pharmacological effects of Lipidom using various experimental models. The phytochemical analysis of Lipidom was performed on ultra-high performance liquid chromatography (UHPLC) platform. Lipidom was evaluated for cytosafety, IL-1ß and MCP-1 release, modulation of NLRP3 pathway, NFκB activity, ROS generation, lipid accumulation and gene expression in THP1 macrophages. Furthermore, Lipidom evaluation was also performed in the N2, CF1553, and TJ356 strains of Caenorhabditis elegans (C. elegans). The evaluation of brood size, adult (%), lipid accumulation, triglyceride levels, SOD-3 GFP signal, MDA formation, DAF-16 nuclear translocation, and gene expression was performed in C. elegans. Lipidom treatment significantly reduced the inflammatory mediators, lipid accumulation, oxidative stress, and normalized genes involved in the development of foamy macrophages. Lipidom treated C. elegans showed a significant decline in lipid accumulation and oxidative stress. Taken together, Lipidom treatment showed a multifaceted approach in the modulation of several mediators responsible for the development and progression of atherosclerotic plaque.

Exploring the Impact of Onobrychis cornuta and Veratrum lobelianum Extracts on C. elegans: Implications for MAPK Modulation, Germline Development, and Antitumor Properties.

In an era of increasing interest in the potential health benefits of medicinal foods, the need to assess their safety and potential toxicity remains a critical concern. While these natural remedies have garnered substantial attention for their therapeutic potential, a comprehensive understanding of their effects on living organisms is essential. We examined 316 herbal extracts to determine their potential nematocidal attributes in Caenorhabditis elegans. Approximately 16% of these extracts exhibited the capacity to induce diminished survival rates and larval arrest, establishing a correlation between larval arrest and overall worm viability. Certain extracts led to an unexpected increase in male nematodes, accompanied by a discernible reduction in DAPI-stained bivalent structures and perturbed meiotic advancement, thereby disrupting the conventional developmental processes. Notably, Onobrychis cornuta and Veratrum lobelianum extracts activated a DNA damage checkpoint response via the ATM/ATR and CHK-1 pathways, thus hindering germline development. Our LC-MS analysis revealed jervine in V. lobelianum and nine antitumor compounds in O. cornuta. Interestingly, linoleic acid replicated phenotypes induced by O. cornuta exposure, including an increased level of pCHK-1 foci, apoptosis, and the MAPK pathway. Mutants in the MAPK pathway mitigated the decline in worm survival, underscoring its importance in promoting worm viability. This study reveals complex interactions between herbal extracts and C. elegans processes, shedding light on potential antitumor effects and mechanisms. The findings provide insights into the complex landscape of herbal medicine's impact on a model organism, offering implications for broader applications.