Search bioRxiv⌕ Search
Home/Archive/bioRxiv

bioRxiv · 10.1101/2020.03.29.013839

Human keratinocyte (HaCaT) stimulation and healing effect of the methanol fraction from the decoction from leaf from Sideroxylon obtusifolium (Roem. & Schult.) T.D. Penn on experimental burn wound model

Souza, T. d. F. G. d.·Pierdona, T. M.·Macedo, F. S.·de Aquino, P. E. A.·Rangel, G. d. F. P.·Duarte, R. S.·Viana, G. S. d. B.·Alves, A. P. N. N.·Montenegro, R. C.·Wilke, D. V.·Silveira, E. R.·Alencar, N. M. N. d.
View original source ↗Export metadata ↓

Abstract

The larger number of plants, with therapeutic potential, popularly used in Northeastern Brazil is due to their easy access and the great Brazilian biodiversity. Previously, was demonstrated that the methanol fraction from Sideroxylon obtusifolium (MFSOL) promoted an anti-inflammatory and healing activity in excisional wounds. Thus, this work aimed to investigate the healing effects of MFSOL on human keratinocytes cells (HaCaT) and experimental burn model injuries. HaCaT cells were used to investigate migration and proliferation of cell rates. Female Swiss mice were subjected to second-degree superficial burn protocol and divided into four treatment groups: Vehicle (cream-base), 1.0% Silver Sulfadiazine (Sulfa), and 0.5% or 1.0% MFSOL cream (CrMFSOL). Samples were collected for quantification of the inflammatory mediators and histological analyses after 3, 7 and 14 days on evaluation. As result, MFSOL (50 g/ml) stimulated HaCaT cells by increasing proliferation and migration rates. Moreover, CrMFSOL 0.5% attenuated myeloperoxidase (MPO) activity and also stimulated the release of IL-1{beta} and IL-10, after 3 days with treatment. CrMFSOL 0.5% enhanced wound contraction, promoted tissue remodeling improvement and highest collagen production after 7 days, and VEGF release after 14 days. Therefore, MFSOL evidenced the stimulation of human keratinocyte (HaCaT) cells and improvements on wound healing via inflammatory modulation on burn injuries.

Explore related subjects

pharmacology and toxicologyPreprint

Keep this discovery

Explore connections, maps & timelines

BibTeXRIS

Souza, T. d. F. G. d., Pierdona, T. M., Macedo, F. S., de Aquino, P. E. A., Rangel, G. d. F. P., Duarte, R. S., Viana, G. S. d. B., Alves, A. P. N. N., Montenegro, R. C., Wilke, D. V., Silveira, E. R., Alencar, N. M. N. d.. 2020-03-30. Human keratinocyte (HaCaT) stimulation and healing effect of the methanol fraction from the decoction from leaf from Sideroxylon obtusifolium (Roem. & Schult.) T.D. Penn on experimental burn wound model. https://doi.org/10.1101/2020.03.29.013839

Cite the original work for its findings. Save a collection to share your selection of sources.

KEEP EXPLORING

Related preprints

bioRxiv2026

Lipid-ASO therapeutics exhibit differential tissue targeted delivery upon systemic or local CNS administration

Antisense oligonucleotides (ASOs) are a powerful therapeutic modality, but their full potential is hindered by pharmacokinetic properties that affect tissue and cellular delivery. Lipid conjugation is increasingly used to modulate ASO's biodistribution and promote extrahepatic activity, yet lipid dependent effects on in vivo functional delivery, particularly in the central nervous system (CNS), remain less explored. Here, we performed a side by side in vivo comparison of cholesterol, palmitic acid (C16:0), docosanoic acid (C22:0), and eicosapentaenoic acid (C20:5) conjugated to a fully phosphorothioated 3 10 3 LNA gapmer ASO targeting the Malat1 long non coding RNA. Lipid-ASO conjugates were administered systemically or locally in the brain of mice and evaluated for tissue level and cellular level distribution by imaging, qPCR and single-cell RNA sequencing, simultaneously annotating cell origin and global transcriptional changes within the cell. Following systemic administration in mice, lipid conjugation improved overall multi organ efficacy compared to unconjugated ASO, but with pronounced tissue specific differences. Single cell sequencing of liver and heart transcriptomes revealed lipid dependent cellular uptake patterns and transcriptional responses distinct from administration of unconjugated ASO. After intracerebroventricular administration, selected fatty acid conjugates enhanced silencing in deep brain regions such as the striatum, whereas cholesterol conjugation impaired functional delivery despite increased CNS retention. Light-sheet microscopy showed restricted parenchymal penetration of cholesterol ASOs compared with broader but heterogeneous distribution of palmitic acid conjugate. Together, these findings demonstrate that lipid identity critically determines ASO efficacy, productive cellular uptake, and regional CNS engagement, emphasizing the need for context specific lipid design in ASO therapeutic development.

pharmacology and toxicology↗
bioRxiv2026

Novel Dissymmetric Ionizable Lipid-Assembled Lipid Nanoparticles for Delivery of Ferroptosis-Related siRNA in Diabetic Treatment

Small interfering RNA (siRNA) enables precise post-transcriptional gene silencing for refractory diseases, yet its clinical translation remains limited by the lack of safe and efficient delivery vectors. Inspired by the dissymmetric alkyl chain architecture of natural membrane phospholipids, we designed and synthesized 34 novel ionizable lipids with dissymmetric hydrophobic tails and formulated them into lipid nanoparticles (LNPs). Through systematic physicochemical and biological assessments, we established clear structure-activity relationships and identified two lead LNPs (O14-LNP, H18a-LNP) with superior endosomal escape capacity, enhanced in vivo gene silencing potency, and favorable biosafety relative to the clinical benchmark MC3-LNP. In both streptozotocin-induced and spontaneous db/db type 2 diabetes (T2D) mouse models, lead LNPs delivering ferroptosis-related siRNAs effectively ameliorated glucose and lipid metabolic disorders, restored islet function, and alleviated hepatic steatosis. This study not only lays a theoretical foundation for the rational design of novel ionizable lipids, but also validates the therapeutic potential of siRNA therapy targeting ferroptosis, providing a versatile delivery platform and targeted therapeutic strategy for the treatment of T2D.

pharmacology and toxicology↗
bioRxiv2020

Self-administration of heroin by vapor inhalation in female Wistar rats

Over the last two decades the United States has experienced a significant increase in the medical and non-medical use of opioid drugs, resulting in record numbers of opioid-related overdoses and deaths. There was an initial increase in non-medical use of prescription opioids around 2002, followed later by increased heroin use and then most recently fentanyl. Inhalation is a common route of administration for opioids, with a documented history spanning back to Mediterranean antiquity and up through modern use with e-cigarette devices. Unfortunately, preclinical studies using inhalation as the route of administration remain relatively few. This study was conducted to determine the efficacy of e-cigarette vapor inhalation of heroin in rats. Non-contingent exposure to heroin or methadone vapor produced anti-nociceptive efficacy in male and female rats. Female rats were trained to self-administer heroin vapor; the most-preferring half of the distribution obtained more vapor reinforcers when the concentration of heroin was reduced in the vapor vehicle and when pre-treated with the opioid receptor antagonist naloxone. The anti-nociceptive effect of heroin self-administered by vapor was identical in magnitude to that produced by intravenous self-administration. Finally, anxiety-like behavior increased 24-48 hours after last heroin vapor access, consistent with withdrawal signs observed after intravenous self-administration. In sum, these studies show that rewarding and anti-nociceptive effects of heroin are produced in rats by vapor inhalation using e-cigarette technology. Importantly, self-administration models by this route can be deployed to determine health effects of inhaled heroin or other opioids.

pharmacology and toxicology↗