Curcumin Ameliorates Cardiac Fibrosis by Regulating Macrophage-Fibroblast Crosstalk via IL18-P-SMAD2/3 Signaling Pathway Inhibition.

Ethnopharmacological relevance: Curcumin is a bright yellow chemical produced by plants of the Curcuma longa species. Chemically, curcumin is a diarylheptanoid, belonging to the group of curcuminoids. The therapeutic potential of curcumin has been widely investigated, including its utilization in various of cardiovascular diseases. However, its effect in cardiac remodeling post myocardial infarction and underlying mechanism remains to be uncover. Aim: To evaluate the therapeutic effect and underlying mechanism of curcumin on cardiac fibrosis after myocardial infarction via macrophage-fibroblast crosstalk. Methods: Male C57BL/6 (C57) mice were subjected to left anterior descending coronary artery ligation to establish myocardial infarction and intragastrically fed vehicle or curcumin (50 mg/kg or 100 mg/kg) for 4 weeks. In parallel, neonatal rat cardiac fibroblasts were isolated and co-cultured with liposaccharide (LPS- or LPS+) curcumin-treated macrophages, followed by TGF-ß stimulation for 24 h. Cardiac function was determined by 2-dimensional echocardiography, and cardiac fibrosis was measured by picrosirius red staining. Apoptosis of macrophages was investigated by flow cytometry; all pro-fibrotic protein expression (EDA-Fibronectin, Periostin, Vimentin, and α-SMA) as well as TGF-ßR1 downstream signaling activation reflected by phosphorylated SMAD2/3 (p-SMAD2 and p-SMAD3) were demonstrated by western blotting. Results: Curcumin significantly ameliorated the inflammation process subsequent to myocardial infarction, reflected by decreased expression of CD68+ and CD3+ cells, accompanied by dramatically improved cardiac function compared with the placebo group. In addition, cardiac fibrosis is inhibited by curcumin administration. Interestingly, no significant reduction in fibrotic gene expression was observed when isolated cardiac fibroblasts were directly treated with curcumin in vitro; however, pro-fibrotic protein expression was significantly attenuated in CF, which was co-cultured with LPS-stimulated macrophages under curcumin treatment compared with the placebo group. Mechanistically, we discovered that curcumin significantly downregulated pro-inflammatory cytokines in macrophages, which in turn inhibited IL18 expression in co-cultured cardiac fibroblasts using bulk RNA sequencing, and the TGF-ß1-p-SMAD2/3 signaling network was also discovered as the eventual target downstream of IL18 in curcumin-mediated anti-fibrosis signaling. Conclusion: Curcumin improves cardiac function and reduces cardiac fibrosis after myocardial infarction. This effect is mediated by the inhibition of macrophage-fibroblast crosstalk in the acute phase post-MI and retrained activation of IL18-TGFß1-p-SMAD2/3 signaling in cardiac fibroblasts.

Inhibitory effect of chitooligosaccharides on retinol metabolism and bioavailability in mice.

This study investigated the intervention effects of chitooligosaccharides (COS) on retinol metabolism and included comparisons of the retinol level, retinol binding protein 4 (RBP4) content, key genes, and protein expression between mice on a COS-enriched diet and a normal diet. The results showed that COS markedly decreased the retinol and RBP4 concentrations in the serum and liver. Furthermore, COS suppressed the mRNA and protein expression of RBP4, cellular retinol binding protein 1 (CRBP1), lecithin: retinol acyltransferase (LRAT) and cytochrome P45026A1 (CYP26A1). In addition, COS inhibited the mRNA expression of stimulated by retinoic acid 6 (STRA6). However, the protein expression of STRA6 was not significantly decreased. Thus, COS reduced the retinol concentration in the serum and disrupted the metabolism of retinol. The intervention mechanism of COS on retinol metabolism may be attributed to the modulation of RBP4, CRBP1, LRAT, STRA6, and CYP26A1 expression at the mRNA and protein levels. PRACTICAL APPLICATIONS: Chitooligosaccharides (COS), known to be the degradation products of chitosan, have been found to induce pinkeye in industrial workers who participate in the manufacturing of COS. Meanwhile, 5% population with COS dietary supplement also have similar phenomenon. The aim of this study is to explore the possible mechanism underlay of this potential risk. The results of this study showed that high exposure to COS during manufacture influences retinol metabolism and leads to a decrease in retinol content, ultimately causing pinkeye. These findings provide new evidence for understanding COS-induced retinol metabolism alteration and drawing attention toward the prevention of potential risk in high-exposure populations.

Effects of dietary arginine levels on growth performance, body composition, serum biochemical indices and resistance ability against ammonia-nitrogen stress in juvenile yellow catfish (Pelteobagrus fulvidraco).

This experiment was conducted to investigate the effects of dietary arginine levels on growth performance, body composition, serum biochemical indices and resistance ability against ammonia-nitrogen stress in juvenile yellow catfish (Pelteobagrus fulvidraco). Five isonitrogenous and isolipidic diets (42% protein and 9% lipid) were formulated to contain graded levels of arginine (2.44%, 2.64%, 2.81%, 3.01% and 3.23% of diet), by supplementing L-Arginine HCl. Seven hundred juvenile yellow catfish with an initial average body weight of 1.13 ± 0.02 g were randomly divided into 5 groups with 4 replicates of 35 fish each and each group was fed one of the diets. After 56 d feeding, fish were exposed to 100 mg/L of ammonia-nitrogen for 72 h. The results showed that weight gain (WG) and specific growth rate (SGR) in 2.64% and 2.81% groups were significantly higher than those in 3.23% group (P < 0.05). The feed conversation ratio (FCR) in 2.64%, 2.81% and 3.01% groups was significantly decreased when compared with 3.23% group. The protein efficiency ratio (PER) in 2.64% group was significantly higher than that in 2.44% and 3.23% groups (P < 0.05). The condition factor (CF) of fish was significantly higher in 2.81% group than that in 2.44% group (P < 0.05). Dietary arginine levels had no significant effect on hepatosomatic index (HSI), viscerosomatic index (VSI), and whole-body dry matter, crude protein, crude lipid, ash contents, as well as serum total protein (TP), triglyceride (TG), glucose (GLU), urea nitrogen (UN) contents and aspartate aminotransferase (AST), alanine aminotransferase (ALT) activities (P > 0.05). After the fish were challenged to ammonia-nitrogen for 72 h, their cumulative mortality rate in 2.81% group was significantly lower than that in 2.44% group (P < 0.05). The results suggested that dietary arginine level at 2.81% could optimize anti-ammonia-nitrogen stress ability of juvenile yellow catfish and a level of 3.23% arginine seemed to depress the growth performance of fish and decreased their tolerance to the ammonia-nitrogen stress under current study. A quadratic regression analysis based on WG indicated that the optimal dietary arginine requirement of juvenile yellow catfish was estimated to be 2.74% of the diet (6.45% of dietary protein) under current culture conditions.

Clinical observations on 46 cases of globus hystericus treated with modified Banxia Houpu decoction.

OBJECTIVE: To observe the therapeutic effect and mechanism of modified Banxia Houpu decoction on globus hystericus. METHODS: The 95 patients with globus hystericus were randomly divided into a treatment group of 46 cases treated with modified Banxia Houpu decoction and a control group of 49 cases treated with Manyanshuning (Granula for Clearing the Throat). In addition, a normal group of 24 healthy people was set up. SCL-90 scale was adopted to observe the therapeutic effect, evaluate the psychological state of patients and build a database on combination of four diagnoses. RESULTS: The effect of the modified Banxia Houpo decoction was better than that of the control group in relieving depression, anxiety and improving the psychological state (P<0.05 or P<0.01). CONCLUSION: Modified Banxia Houpu decoction has definite therapeutic effect on globus hystericus. Its mechanism may be related to its function in relieving depression and anxiety and regulating the psychological state.