harmine and Inflammation

Peri-prosthetic osteolysis (PPO) and following aseptic loosening are regarded as the prime reasons for implant failure after joint replacement. Increasing evidence indicated that wear-debris-irritated inflammatory response and macrophage polarization state play essential roles in this osteolytic process. Harmine, a β-carboline alkaloid primitively extracted from the

Topics: Animals; Biomarkers; Bone Diseases; Cell Survival; Disease Models, Animal; Fluorescent Antibody Technique; Harmine; Immunohistochemistry; Inflammation; Macrophage Activation; Macrophages; Male; Mice; Nitric Oxide; Osteoclasts; Osteogenesis; Osteolysis; RAW 264.7 Cells; Titanium; X-Ray Microtomography

Harmine (HAR) is a β-carboline alkaloid with anti-inflammatory and antipruritic effect. However, the low bioavailability and side effects of HAR severely limited its clinical application. The main objective of this study was to develop harmine-loaded ethosomes (HLE) drug delivery system for topical application to treat inflammation. HLE were obtained by ethanol injection method and characterized. The morphology of HLE was evaluated by transmission electron microscopy (TEM). HLE exhibited a good biocompatibility with human embryonic skin fibroblasts and rat skin. The

Topics: Administration, Cutaneous; Animals; Anti-Inflammatory Agents; Area Under Curve; Disease Models, Animal; Drug Delivery Systems; Edema; Fibroblasts; Harmine; Humans; Inflammation; Liposomes; Rats; Rats, Sprague-Dawley; Skin; Skin Absorption

Harmine is a major constituent in a hallucinogenic botanical mixture ayahuasca and medical plant Peganum harmala L. The plant is used for various illnesses and exhibits anti-inflammatory activity. However, the active constituents remain unclear. Here, we screened the seven alkaloids in P. harmala for their anti-inflammatory activity using an nuclear factor-κB (NF-κB) reporter assay. We found that harmine and harmol could inhibit NF-κB transactivity. As the most abundant compound, harmine inhibited tumor necrosis factor-α (TNF-α)- and lipopolysaccharides (LPS)-induced NF-κB transactivity and nuclear translocation in mouse macrophage RAW 264.7 cells. The mRNA and protein levels of NF-κB downstream inflammatory cytokines also reduced. In an LPS-challenged mouse model, harmine markedly averted inflammatory damage of the lung, and decreased serum TNF-α, interleukin-1β (IL-1β) and IL-6 levels. Our data indicate that harmine may exert the anti-inflammatory effect by inhibition of the NF-κB signaling pathway and harmine is probably responsible for the anti-inflammatory effects of P. harmala.

Topics: Animals; Anti-Inflammatory Agents; Dose-Response Relationship, Drug; Harmine; HEK293 Cells; Humans; Inflammation; Lipopolysaccharides; Mice; Molecular Structure; NF-kappa B; Nitric Oxide; Protein Transport; RAW 264.7 Cells; Signal Transduction; Structure-Activity Relationship; Tumor Necrosis Factor-alpha

In our study, a series of new harmine derivatives has been prepared by cycloaddition reaction using various arylnitrile oxides and evaluated in vitro against acetylcholinesterase and 5-lipoxygenase enzymes, MCF7 and HCT116 cancer cell lines. Some of these molecules have been shown to be potent inhibitors of acetylcholinesterase and MCF7 cell line. The greatest activity against acetylcholinesterase (IC50 = 10.4 µM) was obtained for harmine 1 and cytotoxic activities (IC50 = 0.2 µM) for compound 3a. Two derivatives 3e and 3f with the thiophene and furan systems, respectively, showed good activity against 5- lipoxygenase enzyme (IC50 = 29.2 and 55.5 µM, respectively).

Topics: Acetylcholinesterase; Alzheimer Disease; Anti-Inflammatory Agents; Antineoplastic Agents; Arachidonate 5-Lipoxygenase; Cell Proliferation; Cholinesterase Inhibitors; Dose-Response Relationship, Drug; Drug Screening Assays, Antitumor; Harmine; HCT116 Cells; Humans; Inflammation; Isoxazoles; Lipoxygenase Inhibitors; MCF-7 Cells; Molecular Structure; Structure-Activity Relationship