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Mangiferin, which is a C-glucosylxanthone (1,3,6,7-tetrahydroxyxanthone-C2-β-D-glucoside) purified from plant sources, has recently gained attention due to its various biological activities. The present study aimed to determine the apoptotic effects of mangiferin on A549 human lung adenocarcinoma cells. In vitro studies demonstrated that mangiferin exerted growth-inhibitory and apoptosis-inducing effects against A549 cells. In addition, mangiferin exhibited anti-tumor properties in A549 xenograft mice in vivo. Mangiferin triggered G2/M phase cell cycle arrest via down-regulating the cyclin-dependent kinase 1-cyclin B1 signaling pathway, and induced apoptotic cell death by inhibiting the protein kinase C-nuclear factor-κB pathway. In addition, mangiferin was able to enhance the antiproliferative effects of cisplatin on A549 cells, thus indicating the potential for a combined therapy. Notably, mangiferin exerted anticancer effects in vivo, where it was able to markedly decrease the volume and weight of subcutaneous tumor mass, and expand the lifespan of xenograft mice. The present study clarified the molecular mechanisms underlying mangiferin-induced antitumor activities, and suggested that mangiferin may be considered a potential antineoplastic drug for the future treatment of cancer.

The present study was designed to examine the protective effect of notoginsenoside R1 (NR1) on podocytes in a rat model of streptozotocin (STZ)-induced diabetic nephropathy (DN), and to explore the mechanism responsible for NR1-induced renal protection. Diabetes was induced by a single injection of STZ, and NR1 was administered daily at a dose of 5 mg/kg (low dose), 10 mg/kg (medium) and 20 mg/kg (high) for 16 weeks in Sprague-Dawley rats. Blood glucose levels, body weight and proteinuria were measured every 4 weeks, starting on the day that the rats received NR1. Furthermore, on the day of sacrifice, blood, urine and kidneys were collected in order to assess renal function according to general parameters. Pathological staining was performed to evaluate the renal protective effect of NR1, and the expression of the key slit diaphragm proteins, namely neprhin, podocin and desmin, were evaluated. In addition, the serum levels of inflammatory cytokines [tumor necrosis factor-α (TNF-α), tumor growth factor-β1 (TGF-β1), interleukin (IL)-1 and IL-6] as well as an anti-inflammatory cytokine (IL-10) were assessed, and the apoptosis of podocytes was quantified. Finally, the phosphoinositide 3-kinase (PI3K)/Akt signaling pathway and the involvement of nuclear factor-κB (NF-κB) inactivation was further analyzed. In this study, NR1 improved renal function by ameliorating histological alterations, increasing the expression of nephrin and podocin, decreasing the expression of desmin, and inhibiting both the inflammatory response as well as the apoptosis of podocytes. Furthermore, NR1 treatment increased the phosphorylation of both PI3K (p85) and Akt, indicating that activation of the PI3K/Akt signaling pathway was involved. Moreover, NR1 treatment decreased the phosphorylation of NF-κB (p65), suggesting the downregulation of NF-κB. This is the first study to the best of our knowledge, to clearly demonstrate that NR1 treatment ameliorates podocyte injury by inhibiting both inflammation and apoptosis through the PI3K/Akt signaling pathway.

Injury to terminally differentiated podocytes contributes ignificantly to proteinuria and glomerulosclerosis. The aim of this study was to examine the protective effects of notoginsenoside R1 (NR1) on the maintenance of podocyte number and foot process architecture via the inhibition of apoptosis, the induction of autophagy and the maintenance pf podocyte biology in target cells. The effects of NR1 on conditionally immortalized human podocytes under high glucose conditions were evaluated by determining the percentage apoptosis, the percentage autophagy and the expression levels of slit diaphragm proteins. Our results revealed that NR1 protected the podocytes against high glucose-induced injury by decreasing apoptosis, increasing autophagy and by promoting cytoskeletal recovery. The phosphoinositide 3-kinase (PI3K)/Akt/mammalian target of rapamycin (mTOR) signaling pathway was further investigated in order to elucidate the mechanisms responsible for the protective effects of NR1 on podocytes. Our data indicated that treatment with NR increased the phosphorylation levels of PI3K, Akt and mTOR, leading to the activation of the PI3K/Akt/mTOR signaling pathway in podocytes. To the best of our knowledge, this is the first in vitro study to demonstrate that NR1 protects podocytes by activating the PI3K/Akt/mTOR pathway.

Previous studies have demonstrated that regulatory T cells (Tregs) are pivotal in the regulation of T cell-mediated immune responses in atherosclerosis, a chronic autoimmune-like disease. In the authors' previous studies, it was demonstrated that amygdalin ameliorated atherosclerosis by the regulation of Tregs in apolipoprotein E-deficient (ApoE−/−) mice. Therefore, the aim of the present study was to investigate the therapeutic effect of amygdalin on low-density lipoprotein (LDL) receptor deficient (LDLR−/−) mice, and to examine its immune regulatory function by the stimulation of Tregs. To establish an atherosclerosis mouse model, the LDLR−/− mice were fed a high fat and high cholesterol diet then the total plasma cholesterol, triglyceride, LDL and chemokines levels were measured by an ELISA. Following sacrificing the mice, the upper sections of the aorta were stained by hematoxylin and eosin, and Oil red O to assess the plaque area. Then western blotting and reverse transcription polymerase chain reactions were performed to analysis the expression levels of cluster of differentiation 68, monocyte chemoattractant protein-1, matrix metalloproteinase (MMP)-2, MMP-9 and forkhead box P3 (Foxp3). To further confirm the activation of FOXP3 by amygdalin, lentiviruses carrying Foxp3 shRNA were injected into the mice, and the serum cytokines levels were measured by ELISA. Following feeding of the mice with a high-fat/high-cholesterol diet, the LDLR−/− mice demonstrated comparatively higher levels of triglyceride, total cholesterol and LDL, compared with levels in the amygdalin-treated mice. By comparing the vessel area, lumen area, plaque area, and percentage aortic plaque coverage, the effects of amygdalin on pre-existing lesions were assessed. In addition, the levels of CD68, monocyte chemoattractant protein-1, MMP-2 and MMP-9 were analyzed, and analysis of the expression of interleukin (IL)-1β, IL-6 and tumor necrosis factor (TNF)-α indicated that the mice treated with amygdalin had decreased expression of pro-inflammatory cytokines. The mRNA and protein levels of Foxp3 were also quantified, and the mice treated with amygdalin demonstrated an increased number of Tregs. The knockdown of Foxp3mRNA resulted in the increased secretion of IL-1β, IL-6 and TNF-α. Therefore, the data indicated that amygdalin regulated the formation of atherosclerosis and stabilized the plaque by suppressing inflammatory responses and promoting the immune-modulation function of Tregs. Taken together, the results demonstrated the therapeutic effect of amygdalin on atherosclerosis.

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C–H bonds are common in organic molecules, and the functionalization of these inactive C–H bonds has become one of the most powerful methods used to assemble complicated bioactive molecules from readily available starting materials. However, a central challenge in these reactions is controlling their stereoselectivity. Recently, significant progress has been made in the development of enantioselective C–H activation enabled by different chiral ligands for the formation of C–C and C–X bonds bearing a chiral center. In this paper, we focus on some archetypal chiral ligands for enantioselective C–H functionalization developed in recent years and analyze the mechanism of these methods, aiming to accelerate related research and to search for more efficient strategies.