One-Pot Synthesis of Glutathione Trisulfide from Oxidized Glutathione.

The excellent medicinal efficacy of glutathione trisulfide, an endogenous compound consisting of sulfane sulfur and two molecules of reduced glutathione, has been reported in recent years. However, no efficient procedure for the synthesis of trisulfide is yet available. Herein, we investigated the optimal conditions for the oxidation reaction of oxidized glutathione to thiosulfinate and its subsequent trisulfidation reaction using commercially available materials.

Solubilization and stabilization of lipoic acid trisulfide by creation of various β-cyclodextrin clathrates.

Lipoic acid trisulfide, a sulfane sulfur-containing trisulfide of α-lipoic acid, holds promise in pharmaceuticals, yet knowledge gaps persist regarding its synthesis, properties, and stability. Here, we synthesized the lipoic acid trisulfide with a purity exceeding 99% from α-lipoic acid on a gram scale and obtained novel β-cyclodextrin clathrates (84%-95% yield). Differential scanning calorimetry confirmed the inclusion of lipoic acid trisulfide in β-cyclodextrins.

Intranasal administration of polysulfide prevents neurodegeneration in spinal cord and rescues mice from delayed paraplegia after spinal cord ischemia.

Background: Delayed paraplegia is a devastating complication of thoracoabdominal aortic surgery. Hydrogen sulfide (HS) was reported to be protective in a mouse model of spinal cord ischemia and the beneficial effect of HS has been attributed to polysulfides. The objective of this study was to investigate the effects of polysulfides on delayed paraplegia after spinal cord ischemia.

Oral Administration of Glutathione Trisulfide Increases Reactive Sulfur Levels in Dorsal Root Ganglion and Ameliorates Paclitaxel-Induced Peripheral Neuropathy in Mice.

Peripheral neuropathy is a dose-limiting side effect of chemotherapy with paclitaxel. Paclitaxel-induced peripheral neuropathy (PIPN) is typically characterized by a predominantly sensory neuropathy presenting with allodynia, hyperalgesia and spontaneous pain. Oxidative mitochondrial damage in peripheral sensory neurons is implicated in the pathogenesis of PIPN.

Internalization of CCR4 and inhibition of chemotaxis by K777, a potent and selective CCR4 antagonist.

CC chemokine receptor 4 (CCR4) is a G protein-coupled receptor that regulates the chemotaxis of Th2 lymphocytes, which are key players in allergic diseases. K777 is a small compound identified in a binding assay using a CCR4 ligand, CCL17. K777 inhibited both CCL17 binding and CCL17-induced chemotaxis in Hut78 cells (IC50: 57 and 8.