Gastrodin prevents myocardial injury in sleep-deprived mice by suppressing ferroptosis through SIRT6.

Gastrodin (GAS), a bioactive compound derived from the orchid plant Gastrodia elata, exhibits numerous pharmacological effects. However, its effect on sleep deprivation (SD)-induced cardiac injury and the mechanisms are unknown. This study established SD mice model using a modified multiple platform water method and induced ferroptosis model in H9c2 cells using Erastin. The heart rate of mice was measured, and myocardial and mitochondrial structures were visualized using hematoxylin and eosin (H&E) staining and transmission electron microscopy (TEM). Myocardial injury, oxidative stress indicators, and Fe2+ levels were detected by the kit method. The reactive oxygen species (ROS) levels were detected by immunofluorescence, and SIRT6 and ferroptosis-associated protein expression levels were detected by Western blot. Reduced heart rate and abnormalities in myocardial tissue and mitochondrial structure were ameliorated in the SD group of mice after GAS treatment. GAS treatment reduced ROS levels in Erastin-induced H9c2 cells. GAS treatment reduced atrial natriuretic peptide (ANP), creatine kinase (CK), lactate dehydrogenase (LDH), malondialdehyde (MAD), and Fe2+ levels, and increased superoxide dismutase (SOD) and glutathione (GSH) levels in the SD and Erastin groups. Western blot showed that GAS treatment increased the expression of sirtuin 6 (SIRT6), solute carrier family 7 member 11 (SLC7A11), and glutathione peroxidase 4 (GPX4) and decreased the expression of P53 in SD and Erastin groups. The SIRT6 inhibitor OSS_128167 (OSS) reversed GAS treatment of Erastin-induced ferroptosis in H9c2 cells. These observations propose that GAS prevents myocardial injury in sleep-deprived mice by suppressing ferroptosis through SIRT6.

Chinese traditional formula Kaixin San suppressed ferroptosis of hippocampal neurons and cardiomyocytes in mice with paradoxical sleep deprivation.

ETHNOPHARMACOLOGICAL RELEVANCE: Kaixin San (KXS) is one of the most famous traditional Chinese formulas prescribed by Sun Simiao in 652 Christian era. It is composed of Panax ginseng C.A.Mey, Polygala tenuifolia, Poria cocos and Acorus calamus var. angustatus Besser. KXS is widely used for the treatment of emotion-thought disease, such as settling fright, quieting the spirit and nourishing the heart. However, whether KXS benefits hippocampal neurons and myocardial cells of mice impaired by paradoxical sleep deprivation (PSD) and its mechanism remains unclear. AIM OF THE STUDY: This study was aimed to investigate the effect of KXS on hippocampal neuron and cardiac ferroptosis in rapid-eye-movement (REM) sleep deprived mice and clarify its potential mechanism. MATERIALS AND METHODS: PSD was induced by a modified multi-platform method. Morris water maze (MWM) was used to detect the ability of learning and memory. Cardiac morphological changes were assessed by hematoxylin and eosin (HE) staining. Heart rate was detected by a PowerLab multichannel physiological recorder. Serum levels of atrial natriuretic peptide (ANP) and lactate dehydrogenase (LDH) were measured with biochemical kits. Transmission electron microscopy (TEM), immunofluorescent, and Western blotting analysis were used to observe the process and pathway of ferrotosis in hippocampus tissue and heart tissue of PSD mice. RESULTS: KXS administration improved the impaired learning and memory of PSD mice. It prevented the damage of mitochondria in the hippocampus and heart of PSD mice. KXS also alleviated the myocardial injury, such as morphological damage, abnormal heart rate, serum ANP, and serum LDH induced by PSD. Further study disclosed that KXS reversed the expressions of proteins involved in ferroptosis such as TFRC, SLC7A11/xCT, GPX-4, ACSL4, and FTH1 in hippocampus and heart tissues. CONCLUSIONS: KXS improved learning and memory of mice with REM sleep deprivation, which was closely associated with suppressed ferroptosis in hippocampal neurons and myocardiocytes.

Synthesis and antioxidative activity of 2-substituted phenyl-5-(3'-indolyl)-oxazole derivatives.

AIM: To study the synthesis of 5-(3'-indolyl)-oxazoles and their antioxidative activity. METHODS: The amides were prepared from tryptophan and different acid derivatives by the catalytic dehydration of dicyclohexyl carbodiimide (DCC). The characteristic heterocyclic ring system of 5-(3'-indolyl)-oxazoles was constructed by oxidative cyclization of amide, using dicholorodicyanoquinone (DDQ). Their antioxidative activity in vitro was tested using DPPH system. RESULTS: Eleven 2-substituted phenyl-5-(3'-indolyl)-oxazoles were prepared, the compounds 21 and 22 have shown antioxidative activity 3-4 times stronger than that of Vit E, and the compound 29 showed antioxidative activity almost as same as Vit E. CONCLUSION: Three 5-(3'-indoyl)-oxazole compounds synthesized showed potent antioxidative effect and they would be a good antioxidants.

[Isolation and purification of gonyautoxins from Alexandrium mimutum Halim].

AIM: To isolate and purify gonyautoxins from Alexandrium mimutum Halim Amtk2 strain. METHODS: The ethanol extracts of culture Alexandriun minutum Halim Amtk2 were isolated by means of gel filtration chromatography, the toxin fraction obtained was then purified by ion exchange chromatography. RESULTS: From 100 liter of cultivation liquid of Alexandrium mimutum Halim Amtk2 (6.74 +/- 0.31) x 10(9) cells were obtained. The ethanol extracts of Alexandriun minutum Halim purified by gel filtration chromatography obtained gonyautoxins mixture 29.59 mg. 4.06 mg of the mixture was further purified by two steps of ion exchange chromatography, and obtained pure GTX-4 (0.40 +/- 0.002) mg, GTX-1 (5.95 +/- 0.03) x 10(-2) mg, GTX-3 (6.92 +/- 0.05) x 10(-4) mg and GTX-2 (0.11 +/- 0.005) mg. CONCLUSION: Pure gonyautoxins can be obtained by means of gel filtration chromatography and ion exchange chromatography from ethanol extracts of cultured Alexandriun minutum Halim Amtk2 strain.