Renal fibrosis is a common cause of renal dysfunction with chronic kidney disease. Central to this process is epithelial-mesenchymal transformation (EMT) of proximal tubular epithelial cells driven by transforming growth factor-β1 (TGF-β1) signaling. The present study aimed to investigate the effect of Ferulic acid (FA) on EMT of renal proximal tubular epithelial cell line (NRK-52E) induced by TGF-β1 and to elucidate its underlying mechanism against EMT related to TGF-β1/Smads pathway. The NRK-52E cells were treated for 48 h with TGF-β1 (5 ng/mL) in different concentrations of FA (0 to 200 µM). Fibronectin, a mesenchymal marker, was assessed by western blotting. Western blotting was also used to examine the EMT markers (E-cadherin, andα-smooth muscle actin (α-SMA)), signal transducer (p-Smad2/3), and EMT initiator (Snail). ILK was also assayed by western blotting. The results showed that TGF-β1 induced spindle-like morphological transition in NRK-52E cells. Smad2/3 signaling pathway activation, increased fibronectin,α-SMA, ILK, and Snail expression, and decreased E-cadherin expression in TGF-β1-treated NRK-52E cells. FA efficiently blocked P-Smad2/3 activation and attenuated all these EMT changes induced by TGF-β1. These findings suggest that FA may serve as a potential fibrosis antagonist for renal proximal tubule cells by inhibiting EMT process.

Astragaloside IV is a compound isolated from the Traditional Chinese Medicine Astragalus membranaceus, that has been reported to have bioactivities against cardiovascular disease and kidney disease. There is limited information on the metabolism of astragaloside IV, which impedes comprehension of its biological actions and pharmacology. In the present study, an ultra-performance liquid chromatography coupled with quadrupole/time-of-flight mass spectrometry (UPLC-Q-TOF-MS/MS)-based approach was developed to profile the metabolites of astragaloside IV in rat plasma, bile, urine and feces samples. Twenty-two major metabolites were detected. The major components found in plasma, bile, urine and feces included the parent chemical and phases I and II metabolites. The major metabolic reactions of astragaloside IV were hydrolysis, glucuronidation, sulfation and dehydrogenation. These results will help to improve understanding the metabolism and reveal the biotransformation profiling of astragaloside IV in vivo. The metabolic information obtained from our study will guide studies into the pharmacological activity and clinical safety of astragaloside IV.

To verify the effects of perilla oil on the regulation of blood lipid levels in patients with hyperlipidemia. Blood was taken from patients prior to and 8 weeks following treatment with perilla oil. Different ways to test for indexes which correlate to hyperlipidemia were performed. Some indexes, which correlate with inflammation and injury to endothelial cells, were tested using enzyme linked immunosorbent assays. Serum lipid levels [triglyceride (TG), total cholesterol (TC), and low-density lipoprotein-cholesterol (LDL-C)] changed significantly after 56 days of treatment. Differences were noted as early as 28 days after treatment began (P < 0.05). Treatment with perilla oil showed statistically significant recovery levels of high-density lipoprotein-cholesterol (HDL-C) after 28 and 56 days of treatment. Plasma lipids levels were significantly lower after 56 days of treatment (P < 0.05). Perilla oil reduced blood lipid levels in patients, and the regulation of cell signaling factor levels had no adverse effects on patients' liver or kidney function, or blood routine examinations. Perilla oil treatment is safe in clinical use, can regulate blood lipid levels and protects the function of endothelial cells.

Guben Xiezhuo Decoction (GBXZD) is an herbal compound used to treat chronic kidney disease (CKD) under the guidance of traditional Chinese medicine (TCM). Its main components are Astragalus membranaceus (Fisch.) Bunge, Codonopsis pilosula (Franch.) Nannf., Centella asiatica (L.) Urb., Salvia miltiorrhiza Bunge, Cuscuta chinensis Lam., and Rheum palmatum L.. Clinical studies have shown that it can relieve fatigue, nausea and other symptoms and improve kidney function in patients; however, its specific mechanism of action requires further study. Renal interstitial fibrosis (RIF) is the ultimate characteristic manifestation of various CKD, that cannot be cured, and appropriate treatments to delay its progression require further exploration. GBXZD, widely used in clinical practice for RIF treatment, can effectively relieve the syndrome in patients with CKD. However, the specific mechanism of action of GBXZD in RIF is unknown and requires further study. This study aimed to explore the specific effects of GBXZD on RIF through the regulation of M1 macrophages. An in vivo RIF model was obtained through unilateral ureteral obstruction (UUO), and the Sprague-Dawley (SD) rats were randomly divided into sham operation, UUO, UUO + GBXZD-low dose (GBXZD-L) and UUO + GBXZD-high dose (GBXZD-H) groups. Pathological changes in rat kidney specimens were observed using hematoxylin and eosin (HE) and Masson staining. The expression of collagen I (COL I), fibronectin (FN), α-smooth muscle actin (α-SMA), interleukin-1β (IL-1β), interleukin-6 (IL-6), and tumour necrosis factor-α (TNF-α) was detected using immunohistochemistry, and immunofluorescence was used to detect the expression of CD86 and inducible nitric-oxide synthase (iNOS) in kidney tissue. An in vitro experiment was performed using M1 polarization model in RAW264.7 macrophages induced by lipopolysaccharide (LPS). Cells were divided into control, LPS, LPS + GBXZD-low dose (GBXZD-L) and LPS + GBXZD-high dose (GBXZD-H) groups. The changes in expression of CD86, iNOS, IL-1β, IL-6, and TNF-α were measured using western blotting, flow cytometry, immunofluorescence and enzyme-linked immunosorbent assay (ELISA). We analyzed the action pathway of GBXZD in regulating M1 polarization of macrophages using antibody microarray and verified the results using western blotting. Histopathological results showed that the UUO group exhibited significant fibrotic injury compared to the sham group. After GBXZD treatment, the degree of kidney injury, RIF, and inflammatory factor expression were lower than those in the UUO group. Compared with LPS-treated cells, the expression of the M1 markers CD86, iNOS, and pathway proteins Raf1 and p-Elk1 was down-regulated in RAW 264.7 cells treated with LPS and GBXZD. The secretion of the inflammatory factors IL-1β, IL-6, and TNF-α in the LPS group was more than that in the control group. However, the levels of these factors were significantly reduced in the GBXZD-H group compared to those in the LPS group. This study indicates that GBXZD ameliorates RIF and inhibits the inflammatory response and macrophage M1 polarization by a potential mechanism related to the downregulation of Raf1 and p-Elk1. GBXZD therefore has therapeutic potential value for patients with CKD.

Periprosthetic osteolysis (PPO) and subsequent aseptic loosening are the main causes of implant failure and revision surgery. Emerging evidence has suggested that wear-particle-induced chronic inflammation, osteoblast inhibition and osteoclast formation at the biointerface of implant materials are responsible for PPO. Punicalagin (PCG), a polyphenolic compound molecularly extracted from pomegranate rinds, plays a critical role in antioxidant, anticancer and anti-inflammatory activities. However, whether PCG could attenuate chronic inflammation and bone destruction at sites of titanium (Ti)-particle-induced osteolysis remains to be determined. In this study, we explored the effect of PCG on Ti-particle-induced osteolysis in vivo and osteoblast and osteoclast differentiation in vitro. We found that PCG could relieve wear-particle-induced bone destruction in a murine calvarial osteolysis model by increasing bone formation activity and suppressing bone resorption activity. PCG treatment also reduced the Ti-particle-induced inflammatory response in vivo and vitro. In addition, we also observed that PCG promotes osteogenic differentiation of MC3T3-E1 cells under inflammatory conditions and inhibits RANKL-induced osteoclast formation of bone marrow-derived macrophages (BMMs). Meanwhile, the induction of the RANKL to OPG ratio was reversed by PCG treatment in vivo and in vitro, which demonstrated that PCG could also indirectly inhibit osteoclastogenesis. Collectively, our findings suggest that PCG represents a potential approach for the treatment of wear-particle-induced inflammatory osteolysis.