There is a substantial unmet need for the treatment of skeletal muscle mass loss that is associated with aging and obesity-related increases in FFA. Unsaturated FFAs stimulate the inflammatory gene expression in human skeletal myoblasts (SkMs). Farnesol is a hydrophobic acyclic sesquiterpene alcohol with potential anti-inflammatory effects. Here, we created farnesol-loaded small unilamellar (SUVs) or multilamellar lipid-based vesicles (MLVs), and investigated their effects on inflammatory gene expression in primary human skeletal myoblasts. The attachment of SUVs or MLVs to SkMs was tracked using BODIPY, a fluorescent lipid dye. The data showed that farnesol-loaded SUVs reduced FFA-induced IL6 and LIF expression by 77% and 70% in SkMs, respectively. Farnesol-loaded MLVs were less potent in inhibiting FFA-induced IL6 and LIF expression. In all experiments, equal concentrations of free farnesol did not exert significant effects on SkMs. This report suggests that farnesol, if efficiently directed into myoblasts through liposomes, may curb FFA-induced inflammation in human skeletal muscle.
7 November 2021 in Journal of Veterinary Pharmacology and Therapeutics
Chronic inflammation and elevated cytokine levels are closely associated with the progression of chronic kidney disease (CKD), which is responsible for the manifestation of numerous complications and mortality. In addition to conventional CKD therapies, the possibility of using natural compounds with anti-inflammatory potential has attracted widespread attention in scientific research. This study aimed to study the potential anti-inflammatory effects of a natural oil compound, farnesol, in primary human renal proximal tubule epithelial cell (RPTEC) culture. Farnesol was encapsulated in lipid-based small unilamellar vesicles (SUVs) to overcome its insolubility in cell culture medium. The cell attachment of empty vesicles (SUVs) and farnesol-loaded vesicles (farnesol-SUVs) was examined using BODIPY, a fluorescent dye with hydrophobic properties. Next, we used multiple protein, RNA, and protein phosphorylation arrays to investigate the impact of farnesol on inflammatory signaling in RPTECs. The results indicated that farnesol inhibits TNF-α/IL-1β-induced phosphorylation of the PI3 kinase p85 subunit and subsequent transcriptional activation of the inflammatory genes TNFRSF9, CD27, TNFRSF8, DR6, FAS, IL-7, and CCL2. Therefore, farnesol may be a promising natural compound for treating CKD.
18 June 2024 in Veterinary Anaesthesia and Analgesia
Background: Neuroprotective strategies as primary or ancillary treatment could ameliorate the significant mortality and disability associated with ischemic stroke. Nanoliposomes composed of monosialoganglioside, phosphatidylcholine, and cholesterol (NLGM1) were previously shown to ameliorate brain injury when given before arterial occlusion in mice. We aimed to test the hypothesis that NLGM1 given following transient intraluminal filament and photothrombotic (PT) middle cerebral artery occlusion (MCAO) will attenuate acute and chronic stroke injury in mice. Methods: Twelve‐week‐old C57BL/6 mice underwent MCAO for 45 minutes and were then injected with 1 or 3 doses of saline or NLGM1 (1 or 2 mg IV) after occlusion. Neurologic deficit score and brain infarct area were measured after 48 hours. Separate mice underwent PT occlusion of the distal lateral middle cerebral artery trunk followed by injection of 1 or 2 doses saline or NLGM1 (1 or 2 mg IV) postocclusion. Motor and behavior testing was performed at 21, 30, 45, and 90 days after PT MCAO. Results: Following intraluminal MCAO, single‐dose NLGM1‐treated mice exhibited reduced neurological impairment (neurologic deficit score 3.6±0.2, 2.6±0.3, 2.4±0.3 at 0, 1, 2 mg, respectively; P <0.05 versus control) and reduced infarct area (29.8±2.9%, 15.0±1.5%, 13.0±1.2%; P <0.001 versus control) with similar results with multiple dosing. Following PT MCAO, day 21 latency to fall (rotarod test), day 30 corner test, day 45 adhesive tape removal, and day 90 novel object recognition were improved in single‐dose NLGM1‐treated mice versus controls with improved corner and adhesive tape removal tests with multiple dosing. There were no significant differences in outcomes between 1 versus 2 mg NLGM1 treatments. Conclusions: Treatment of mice with NLGM1 resulted in reduced brain infarct size acutely following intraluminal MCAO and improved motor and behavior function acutely and chronically following intraluminal and PT MCAO. NLGM1 represents a promising novel neuroprotective agent in stroke.
Patients at a dental school were observed to self-medicate for dental pain and presumed infection with nonprescribed ornamental fish antibiotics, thereby circumventing professional health care. This study determined if the human-approved antibiotics, amoxicillin and cephalexin, were present in the nonprescribed, over-the-counter fish antibiotics. Human-grade prescribed and over-the-counter commercially-available fish antimicrobials (amoxicillin, cephalexin) were analyzed by using high-performance liquid chromatography ultraviolet-visible detection following US Pharmacopeia (USP) protocols. The contents of 20 capsules of each type were combined and dissolved in a carrier fluid to a concentration of 1 mg/mL. Samples were analyzed using high-performance liquid chromatography at a flow rate of 1.5 mL/min using isocratic mobile phase conditions. All products contained the equivalent of not less than 90.0% and not more than 120.0% of their labeled contents, within the USP standards. Although no major impurities were identified, there was evidence of several as-yet unidentified excipient ingredients. Results confirm that the human-grade prescribed and nonprescribed over-the-counter fish antibiotics tested match USP standards and are pharmacologically indistinguishable. The results of this study showed that the major component of the amoxicillin and cephalexin capsules marketed for fish contain their purported levels of antibiotics.