Ampelopsis japonica aqueous extract improves ovulatory dysfunction in PCOS by modulating lipid metabolism.

Polycystic ovary syndrome (PCOS) is a highly prevalent endocrine and metabolic disorder that is closely associated with the proliferation and apoptosis of ovarian granulosa cells (GCs). Ampelopsis japonica (AJ) is the dried tuberous root of Ampelopsis japonica (Thunb.) Makino (A. japonica), with anti-inflammatory, antioxidant, antibacterial, antiviral, wound-healing, and antitumor properties; however, it is unclear whether this herb has a therapeutic effect on PCOS. Therefore, this study aimed to investigate the pharmacological effect of AJ on PCOS and reveal its potential mechanism of action. A PCOS rat model was established using letrozole. After establishing the PCOS model, the rats received oral treatment of AJ and Diane-35 (Positive drug: ethinylestradiol + cyproterone tablets) for 2 weeks. Lipidomics was conducted using liquid-phase mass spectrometry and chromatography. AJ significantly regulated serum hormone levels and attenuated pathological variants in the ovaries of rats with PCOS. Furthermore, AJ significantly reduced the apoptotic rate of ovarian GCs. Lipidomic analysis revealed that AJ modulated glycerolipid and glycerophospholipid metabolic pathways mediated by lipoprotein lipase (Lpl), diacylglycerol choline phosphotransferase (Chpt1), and choline/ethanolamine phosphotransferase (Cept1). Therefore, we established that AJ may reduce ovarian GC apoptosis by modulating lipid metabolism, ultimately improving ovulatory dysfunction in PCOS. Therefore, AJ is a novel candidate for PCOS treatment.

Brugada Pattern, Tall Peaked T Waves, Absence of P Waves, and Broad QRS Complexes.

This case report presents the electrocardiogram findings of a patient in their 70s with chest tightness and shortness of breath for 5 hours and loss of consciousness for 10 minutes.

A green and highly efficient method to deliver hydrophilic polyphenols of Salvia miltiorrhiza and Carthamus tinctorius for enhanced anti-atherosclerotic effect via metal-phenolic network.

Salvia miltiorrhiza and Carthamus tinctorius are traditional Chinese medicines that have been widely used for the treatment of cardiovascular disease. Salvianic acid A (SAA), salvianic acid B (SAB), protocatechuic aldehyde (PCA) and hydroxysafflor yellow A (HSYA) are the major hydrophilic polyphenols of Salvia miltiorrhiza and Carthamus tinctorius, all of which have been documented as active compounds for the prevention and treatment of atherosclerosis (AS). However, high aqueous solubility, low permeability and poor stability properties of the four hydrophilic polyphenols might influence their bioavailability and thus hinder their clinical potential. In this work, we introduced a green and highly efficient method for the efficient delivery of the four hydrophilic components via metal-phenolic network. The four coordination polymers of SAA, SAB, PCA and HSYA were successfully fabricated, and confirmed by UV-vis, FTIR, XPS, ICP-MS and dynamic light scattering analysis. We found all of them displayed potent antioxidant activity, good biocompatibility and stability. Impressively, the four coordination polymers showed remarkably enhanced anti-atherosclerotic effect compared with free drugs. Collectively, metal-phenolic network-based coordination polymer might show great potential for safe and efficient delivery of the hydrophilic polyphenols of Salvia miltiorrhiza and Carthamus tinctorius for anti-atherosclerotic therapy.

Network pharmacology integrated with experimental validation reveals the regulatory mechanism of action of Hehuan Yin decoction in polycystic ovary syndrome with insulin resistance.

ETHNOPHARMACOLOGICAL RELEVANCE: Hehuan Yin decoction (HHY), first recorded in the Jingyue Quanshu (published in 1624 A.D.), is composed of Albizia julibrissin Durazz. and Ampelopsis japonica (Thunb.) Makino. AIM OF THE STUDY: This study aimed to investigate the mechanism of action of HHY in treating polycystic ovary syndrome with insulin resistance (PCOS-IR). MATERIALS AND METHODS: Network pharmacology and molecular docking were used to predict active compounds, potential targets, and pathways for PCOS-IR treatment using HHY. Female Sprague-Dawley rats were administered letrozole (1 mg/kg) with a high-fat diet to establish a PCOS-IR model. Thereafter, symptoms, ovarian pathology, serum insulin resistance, and sex hormone levels were determined. Western blotting was used to determine the levels of PI3Kp85α, AKT, phospho (p)-AKT, and GSK3ß in the ovaries of rats. RESULTS: Network pharmacology revealed 58 components in HHY and 182 potential targets that were shared between HHY and PCOS-IR. HHY could potentially treat PCOS-IR via the insulin resistance, PI3K/AKT, HIF-1, and steroid hormone biosynthesis pathways. Molecular docking revealed that PI3K, AKT1, GSK3ß, IRS1, and EGFR had high affinities to HHY compounds. In the PCOS-IR rats, HHY significantly normalised the symptoms and ovarian pathology, increased follicle-stimulating hormone (FSH) and oestradiol levels in the serum, and decreased the levels of fasting plasma glucose and fasting insulin, as well as the insulin resistance index. HHY also decreased the luteinising hormone (LH) and testosterone levels and the LH/FSH ratio in the PCOS-IR rats and increased the levels of PI3K, p-AKT, and GSK3ß in ovary tissue, which indicated the activation of the PI3K/AKT pathway. CONCLUSIONS: HHY can improve PCOS-IR symptoms via multiple pharmacological pathways and may be a potential alternative therapy for the treatment of PCOS-IR.

ATP-Responsive Multifunctional Supramolecular Polymer as a Nonviral Vector for Boosting Cholesterol Removal from Lipid-Laden Macrophages.

Specific delivery of NCEH1 plasmid is a promising approach to boost the cholesterol removal from lipid-laden macrophages for antiatherosclerosis. Polyethylenimine (PEI) is one of the most efficient gene carriers among nonviral vectors. However, the high transfection activity of PEI is always accompanied by profound cytotoxicity. To tackle the paradox between transfection efficiency and safety, we constructed a novel ATP-responsive multifunctional supramolecular polymer by cross-linking functionalized low-molecular-weight PEI via a boronic ester bond for NCEH1 plasmid delivery. The supramolecular polymer could condense NCEH1 plasmids to form stable nanosized polyplexes when the w/w ratios of the polymer and gene were higher than 2. ATP-triggered degradation of the polymer and pDNA release were characterized by a series of studies, including 1H NMR, 31P NMR, XPS, agarose gel electrophoresis, and ethidium bromide exclusion tests. In addition, the changes in particle size and morphology were observed in the presence of ATP. Interestingly, the supramolecular polymer showed broad spectrum antioxidant activities by measuring the elimination rates of different reactive oxygen species. In addition, the supramolecular polymer displayed a high buffering capability and good cytocompatibility as demonstrated by the results of the buffering capacity, a hemolysis assay, and a cytotoxicity test. Importantly, it was revealed that the supramolecular polymer/NCEH1 plasmid polyplex formulated at a w/w ratio of 20 was most effective in enhancing cholesterol removal from lipid-laden macrophages and reducing the accumulation of lipid droplets as evidenced by transfection study, cholesterol efflux assay, and oil red O staining studies. Collectively, the ATP-responsive multifunctional supramolecular polymer holds great potential for safe and efficient gene delivery for antiatherosclerosis.