Malus toringoides (Rehd.) Hughes decoction alleviates ISO-induced cardiac fibrosis by inhibiting cardiomyocyte inflammation and pyroptosis via the HK1/NLRP3-signaling pathway.

Malus toringoides (Rehd.) Hughes leave, called "Eseye (Ese)", is a traditional medicinal plant from the Tibet province of China that has efficiency of anti-inflammatory, antioxidant and anti-apoptosis to treat cardiac conditions. We herein explored the underlying protective mechanisms of Ese decoction in isoproterenol (ISO)-induced cardiac fibrosis (CF). And treatment with an Ese decoction attenuated tissue injury and decreased the release of IL-1ß, IL-18, TNF-α, and caspase-3 and elevated the Bax/Bcl-2 ratio in CF mice. Damage to the mitochondrial ultrastructure of myocardium was alleviated, and the level of ROS was markedly diminished with Ese treatment. Ese inhibited the expression of proteins associated with pyroptosis by the HK1/NLRP3-signaling pathway, and also improved CF. Based on anti-inflammatory, antioxidative and anti-apoptosis activities effects of Ese decoction, we found that Ese protected against ISO-induced CF, which attributed to its inhibition of inflammation and pyroptosis as mediated by the HK1/NLRP3-signaling pathway.

Cichoric acid improves isoproterenol-induced myocardial fibrosis via inhibition of HK1/NLRP3 inflammasome-mediated signaling pathways by reducing oxidative stress, inflammation, and apoptosis.

Cichoric acid (CA), a natural phenolic compound found in many plants, has been reported to have antioxidant, anti-inflammatory, hypoglycemic, and other effects. The aim of this study was to determine the potential role and underlying mechanisms of CA in isoproterenol (ISO)-induced myocardial fibrosis (MF). The MF model was induced by subcutaneous ISO injection in mice. Blood and heart tissue were collected for examination. Hematoxylin and eosin staining and Masson's trichrome staining were used to evaluate the histopathological changes and collagen deposition. The production of reactive oxygen species markers was observed by fluorescence microscopy, the degree of cardiomyocyte microstructure injury was observed by transmission electron microscope, and oxidative stress factors were detected by kit method, and the effect of CA on inflammatory factors was detected by ELISA. The expression levels of collagen proteins and signaling pathways were further investigated by western blotting. The results showed that CA inhibited the expression of ISO-induced proinflammatory factors (TNF-α, IL-1ß, and IL-18) and proteins (HK1, NLRP3, caspase-1, cleaved-caspase-1, and ASC), and regulated the expression of apoptotic factors (caspase-3, cleaved-caspase-3, Bax, and Bcl-2). The results indicated that CA may regulate the HK1/NLRP3 inflammasome pathway by inhibiting HK1 expression and play a protective role in MF.

DNA barcoding identification of grafted Semen Ziziphi Spinosae and transcriptome study of wild Semen Ziziphi Spinosae.

Semen Ziziphi Spinosae (SZS) is the dried and ripe seeds of Ziziphus jujuba var. spinosa. Currently, the yield of naturally grown SZS is unstable owing to environmental factors. Grafting high-quality sour jujube scions onto sour jujube or jujube tree stocks can result in a greater yield. However, the effects of grafting on the quality and gene expression of SZS have rarely been reported. This study used a DNA barcoding technique, high-performance liquid phase-evaporative luminescence detector (HPLC-ELSD), and transcriptomics to investigate the origin and genetic differences between grafted and wild jujube seeds. DNA barcoding identified all samples as Ziziphus jujuba var. spinosa. HPLC-ELSD analysis revealed a higher content of grafted SZS compared to that of the wild SZS. Transcriptome analysis of the metabolic pathways in SZS showed that 22 and 19 differentially expressed gene sequences encoded enzymes related to flavonoids and saponin synthesis, respectively. Weighted correlation network analysis (WGCNA) identified 15 core genes governing the differences in medicinal components between grafted and wild SZS. This study demonstrated the use of DNA barcoding and fingerprint methods to identify jujube seed species and effectively capture ingredient information of medicinal materials. Additionally, transcriptome technology provided data for identifying core differential genes, facilitating studies on quality differences between grafted and wild SZS.

Phlorizin ameliorates myocardial fibrosis by inhibiting pyroptosis through restraining HK1-mediated NLRP3 inflammasome activation.

The specific role of phlorizin (PHL), which has antioxidant, anti-inflammatory, hypoglycemic, antiarrhythmic and antiaging effects, on myocardial fibrosis (MF) and the related pharmacological mechanisms remain unknown. The objective of this study was to determine the protective actions of PHL on isoprenaline (ISO)-induced MF and its molecular mechanisms in mice. PHL was administered at 100 and 200 mg/kg for 15 consecutive days with a subcutaneous injection of ISO (10 mg/kg). MF was induced by ISO and alleviated by treatment with PHL, as shown by reduced fibrin accumulation in the myocardial interstitium and decreased levels of myocardial enzymes, such as creatinine kinase-MB, lactate dehydrogenase, and aspartate transaminase. In addition, PHL significantly decreased the expression of the fibrosis-related factors alpha smooth muscle actin, collagen I, and collagen III induced by ISO. The generation of intracellular reactive oxygen species induced by ISO was attenuated after PHL treatment. The malondialdehyde level was reduced, whereas the levels of superoxide dismutase, catalase, and glutathione were elevated with PHL administration. Moreover, compared to ISO, the level of Bcl-2 was increased and the level of Bax protein was decreased in the PHL groups. PHL relieved elevated TNF-α, IL-1ß, and IL-18 levels as well as cardiac mitochondrial damage resulting from ISO. Further studies showed that PHL downregulated the high expression of hexokinase 1 (HK1), NLRP3, ASC, Caspase-1, and GSDMD-N caused by ISO. In conclusion, our findings suggest that PHL protects against ISO-induced MF due to its antioxidant, anti-apoptotic, and anti-inflammatory activities and via inhibition of pyroptosis mediated by the HK1/NLRP3 signaling pathway in vivo.

In situ detection and mass spectrometry imaging of protein-related metabolites in Bombyx batryticatus before and after frying with wheat bran.

Bombyx batryticatus is derived from the dried larva of Bombyx mori Linnaeus infected by Beauveria bassiana (Bals.) Vuillant. Raw Bombyx batryticatus should be stir-fried before oral administration due to its irritation to the gastrointestinal tract. Nevertheless, it is still an arduous task to uncover the intrinsic mechanism of Bombyx batryticatus processing. In this study, we collected two types of Bombyx batryticatus, one being stir-fried and the other serving as a control. Then, an informative approach, which integrated matrix-assisted laser desorption/ionization mass spectrometry imaging (MALDI-MSI) with chemometrics analysis, was established to screen processing-associated markers and reveal in situ spatial distribution patterns of protein-related metabolites. After optimization of experimental conditions, 21 ions were initially detected from Bombyx batryticatus, including amino acids and peptides. In addition, 15 differential markers were screened by orthogonal projection to potential structure discriminant analysis (OPLS-DA), which were localized and visualized in the transverse section of Bombyx batryticatus by MSI. Eventually, it can be demonstrated that the stir-frying process reduces toxicity while potentially boosting specific biological activities of Bombyx batryticatus. In summary, the established strategy could not only clarify the chemical transformation of protein-related metabolites from Bombyx batryticatus before and after frying with wheat bran, but also reveal the significance of Chinese medicine processing technology.