Optimized New Shengmai Powder modulation of cAMP/Rap1A signaling pathway attenuates myocardial fibrosis in heart failure.

BACKGROUND: Optimized New Shengmai Powder (ONSMP) is a traditional Chinese medicine formula with significant anti-heart failure and myocardial fibrosis effects, but the specific molecular biological mechanisms are not fully understood. METHODS: In this study, we first used network pharmacology to analyze the ONSMP's active ingredients, core signaling pathways, and core targets. Second, calculate the affinity and binding modes of the ONSMP components to the core targets using molecular docking. Finally, the heart failure rat model was established by ligating the left anterior descending branch of the coronary artery and assessing the effect of ONSMP on myocardial fibrosis in heart failure using echocardiography, cardiac organ coefficients, heart failure markers, and pathological sections after 4 weeks of drug intervention. The cAMP level in rat myocardium was determined using Elisa, the α-SMA and FSP-1 positive expression determined by immunohistochemistry, and the protein and mRNA levels of the cAMP/Rap1A signaling pathway were detected by Western Blotting and quantitative real-time PCR, respectively. RESULTS: The result shows that the possible mechanism of ONSMP in reducing myocardial fibrosis also includes the use of 12 active ingredients such as baicalin, vitamin D, resveratrol, tanshinone IIA, emodin, 15,16-dihydrotanshinone-i to regulate ß1-AR, AC6, EPAC1, Rap1 A, STAT3, and CCND1 on the cAMP/Rap1A signaling pathway, thereby inhibiting the proliferation of cardiac fibroblasts and reduce the excessive secretion of collagen, effectively improve cardiac function and ventricular remodeling in heart failure rats. CONCLUSION: This research shows that ONSMP can inhibit myocardial fibrosis and delay heart failure through the cAMP/Rap1A signaling pathway.

Moxibustion for the Treatment of Cancer and its Complications: Efficacies and Mechanisms.

Cancer treatment remains a significant challenge for the medical community, and improved therapies are necessary to treat cancer and its associated complications. Current anticancer therapies often have significant side effects, underscoring the need for new treatment options. Moxibustion is a representative external therapy used in traditional Chinese medicine. This review examines clinical studies demonstrating moxibustion's ability to improve the efficacy of radiotherapy and chemotherapy and control tumor progression. Moxibustion can prevent and treat various complications of cancer, including cancer-related or therapy-induced gastrointestinal symptoms, myelosuppression, fatigue, pain, and postoperative lymphedema. has also been shown to enhance the quality of life for cancer patients. However, very few studies have investigated the underlying mechanisms for these effects, a topic that requires systematic elucidation. Evidence has shown that moxibustion alone or combined with chemotherapy can improve survival and inhibit tumor growth in cancer-bearing animal models. The anticancer effect of moxibustion is associated with alleviating the tumor immunosuppressive and vascular microenvironments. Additionally, the therapeutic effects of moxibustion may originate from the heat and radiation produced during the combustion process on acupoints or lesions. This evidence provides a scientific basis for the clinical application of moxibustion in anticancer treatment and reducing the side effects of cancer therapies and helps promote the precise application of moxibustion in cancer treatment.

Pentoxifylline attenuates nonalcoholic fatty liver by inhibiting hepatic macrophage polarization to the M1 phenotype.

BACKGROUND: Nonalcoholic fatty liver (NAFL), recognized as one of the most common causes of chronic liver diseases, is increasingly prevalent worldwide. Pentoxifylline, a derivative of theobromine extracted from Theobroma cacao and tea, has been studied for effects on blood viscosity, tissue oxygenation and inflammation. However, its effects on hepatic lipid accumulation and the potential mechanisms remain unclear. PURPOSE: This study aimed to investigate the therapeutic effects of pentoxifylline on high-fat diet-induced NAFL and to explore the corresponding molecular mechanisms. METHODS: NAFL mice were injected with or without 25, 50 or 100 mg/kg pentoxifylline for 2 weeks. Hepatic steatosis was observed by haematoxylin-eosin staining and Oil Red O staining, the levels of serum total cholesterol, triglyceride were detected by biochemical kits, and insulin resistance was evaluated by glucose and insulin tolerance tests. In addition, we measured the frequencies of macrophage and its polarization subsets in the liver using flow cytometry and immunofluorescence. The expressions of proteins associated with macrophage polarization signaling pathways were assessed by Western blotting and flow cytometry histograms. Molecular docking and cellular thermal shift assay were conducted to identify and verify the target protein of pentoxifylline in macrophage. RESULTS: Pentoxifylline significantly alleviated hepatic lipid accumulation, reduced blood lipid levels and improved insulin resistance. Strikingly, the excessive M1 macrophages in NAFL development was abolished by pentoxifylline. And pentoxifylline was further evidenced it failed to reduce hepatocyte lipid accumulation in the absence of macrophages in vitro. Mechanistically, pentoxifylline competed with LPS for binding to toll-like receptor 4, dramatically inhibiting the TLR4/MyD88/NF-κB signaling pathway. CONCLUSION: Pentoxifylline attenuated NAFL by inhibiting hepatic macrophage M1 polarization, indicating that pentoxifylline could be a therapeutic candidate for NAFL. This study first observed that M1 macrophages were increased in NAFL mice and then revealed the molecule targeted by pentoxifylline. In addition, we provided evidence that macrophage targeting may be an emerging strategy for NAFL treatment.

Protective effects of Radix Isatidis polysaccharide ameliorates obesity via promotion AMPK pathway in high-fat-diet-induced obese rats and 3T3-L1 adipocyte cells.

OBJECTIVES: The purpose of this paper is to ascertain the effect and mechanism of Radix Isatidis polysaccharide (RIP) on obesity. METHODS: High fat diet (HFD)-induced obese rats and the MDI-induced 3T3-L1 adipocyte cells were established to evaluate the ameliorated obesity effect and mechanism from RIP. KEY FINDINGS: Experiments in vivo show that oral administration of RIP has significant preventive effects on HFD-induced obesity and metabolic disorders in rats. With treatment of RIP (20, 40 and 80 mg/kg BW), the body weight, fat accumulation, adipocyte cell size, serum lipid levels and antioxidant enzyme activity were progressively improved. On the other hand, the treatment of 3T3-L1 cells with RIP (25, 50 and 100 mg/L) led to a decrease in lipid accumulation and glucose consumption. In addition, during adipogenesis in 3T3-L1 cells, RIP remarkably down-regulated mRNA levels of peroxisome proliferator-activated receptor-γ (PPARγ), CCAAT/enhancer binding protein-α (C/EBPα), sterol regulatory element-binding protein-1c (SREBP-1c), fatty acid synthase (FAS), acetyl-CoA carboxylase and glycerol-3-phosphate dehydrogenase. Furthermore, after RIP treatment, the protein expression of PPARγ, C/EBPα, FAS, HMG-CoA reductase and acetyl-CoA synthetase-1 (AceCS1) were significantly decreased and the expression of p-AMPK was increased. CONCLUSION: These results highlight the potential of RIP for obesity interventions and suggest that RIP inhibited adipocyte differentiation and lipid synthesis by activating adenosine 5'-monophosphate (AMP)-activated protein kinase (AMPK) signalling pathway and down-regulating the expression of major adipogenic transcription factors, PPARγ, C/EBPα, etc.

Preparation of corn ACE inhibitory peptide-ferrous chelate by dual-frequency ultrasound and its structure and stability analyses.

In order to improve iron chelating ability and retain the activity of functional peptide, corn peptide was chelated with iron to form corn ACE inhibitory peptide-ferrous chelate (CP-Fe) treated by dual-frequency ultrasound. Furthermore, the chelating mechanism was revealed by analyzing various structural changes, and the stability was further evaluated. Under this study condition, the iron-binding capacity of corn ACE inhibitory peptide (CP) and chelate yield reached 66.39% and 82.87%, respectively. Ultrasound-treated CP exhibited a high iron chelating ability, meanwhile, chelation reaction had no significant effect on the ACE inhibition activity (82.21%) of the peptide. CP-Fe was formed by binding the peptides amino, carbonyl and carboxyl groups with Fe2+ demonstrated by Ultra-violet spectroscopy, Fourier transform infrared characterization, X-ray diffraction, energy dispersion spectrum, zeta potential, amino acid composition and other multi-angle analyses. Moreover, ultrasound-treated CP-Fe chelate exhibited porous surface and uniform nanoparticle shape. Furthermore, ultrasound-treated CP-Fe chelate exhibited an excellent stability towards various pH (retention rate ≥ 95.47% at pH 6-10), temperatures (retention rate ≥ 85.10% at 25-70 °C), and gastrointestinal digestion (retention rate 79.18%). Overall, ultrasound-treated CP-Fe chelate possessed high iron-chelating ability, ACE inhibition activity and stability. This study provides a novel synthesis method of the iron-chelating corn ACE inhibitory peptide, which is promising to be applied as iron supplements with high efficiency, bioactivity, and stability.

Effect of Radix isatidis polysaccharide on alleviating insulin resistance in type 2 diabetes mellitus cells and rats.

OBJECTIVES: The objective of this paper was to explore the effects of Radix isatidis polysaccharide (RIP) extracted from Radix isatis on alleviating insulin resistance. METHODS: The insulin resistance models of 3T3-L1 preadipocytes and type 2 diabetic rats were established to evaluate the insulin resistance activity of RIP. KEY FINDINGS: Radix isatidis polysaccharide within the concentration range of 25-100 µg/ml could reduce cell supernatant glucose and TNF-α levels (P < 0.01) and increase the expression of PI-3K P85, Glut4, IRS-1 and Akt protein in symptoms of IR 3T3-L1 preadipocytes. In the meantime, RIP contributed to relieve the weight loss of diabetic rats whose liver weight and liver index were decreased due to the effects of RIP. Experiments in rats also showed that RIP had capacity in reduced serum TC, TG, LDL-C, FFA, FBG, FINS, MDA, ALT, AST activities and increased serum HDL-C, SOD, ISI (P < 0.05 or 0.01). In addition, the oral glucose tolerance in rats was improved (P < 0.05) and liver damage was restored due to RIP. CONCLUSIONS: Radix isatidis polysaccharide significantly alleviates insulin resistance in 3T3-L1 preadipocytes and type 2 diabetic rats. These beneficial effects of RIP may associate with their roles in improving the glucose metabolism, lipid metabolism and oxidative stress.

Biocompatible graphene-based nanoagent with NIR and magnetism dual-responses for effective bacterial killing and removal.

Antibiotics have been widely used in clinical applications to treat pathogenic infections at present, but the problem of drug-resistance associated with the abuse of antibiotics has become a large threat to human beings. Herein, we developed an antibacterial nanoagent by coating quaternized chitosan (QCS) on the surface of Fe3O4 nanoparticles-anchored graphene oxide (GO), which enabled QCS and GO to achieve synergistic effects on killing the drug-resistant bacteria. Systematical antibacterial experiments showed that the prepared nanoagent had antibacterial ability, which was significantly enhanced after the introduction of near-infrared (NIR). Importantly, the nanoagent could be easily recycled and reused without the reduction of the antibacterial ability. During the test time, this nanoagent exhibited no obviously toxic side effect to cells. Given the above advantages, we anticipate that the nanoagent has a promising future in various applications such as wound disinfection, water purification, and surface sterilization of medical devices.