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Myocardial ischemia-reperfusion injury (MI/RI) seriously restricts the therapeutic effect of reperfusion. It is demonstrated that ferroptosis and apoptosis of cardiomyocytes are widely involved in MI/RI. Therefore, simultaneous inhibition of ferroptosis and apoptosis of cardiomyocytes can be a promising strategy to treat MI/RI. Besides, transferrin receptor 1 (TfR1) is highly expressed in ischemic myocardium, and apoferritin (ApoFn) is a ligand of the transferrin receptor. In this study, CsA@ApoFn was prepared by wrapping cyclosporin A (CsA) with ApoFn and actively accumulated in ischemic cardiomyocytes through TfR1 mediated endoctosis in MI/RI mice. After entering cardiomyocytes, ApoFn in CsA@ApoFn inhibited ferroptosis of ischemic cardiomyocytes by increasing the protein expression of GPX4 and reducing the content of labile iron pool and lipid peroxides. At the same time, CsA in CsA@ApoFn attenuated the apoptosis of ischemic cardiomyocytes through recovering mitochondrial membrane potential and reducing the level of reactive oxygen species, which played a synergistic role with ApoFn in the treatment of MI/RI. In conclusion, CsA@ApoFn restored cardiac function of MI/RI mice by simultaneously blocking ferroptosis and apoptosis of cardiomyocytes. ApoFn itself not only served as a safe carrier to specifically deliver CsA to ischemic cardiomyocytes but also played a therapeutic role on MI/RI. CsA@ApoFn is proved as an effective drug delivery platform for the treatment of MI/RI. STATEMENT OF SIGNIFICANCE: Recent studies have shown that ferroptosis is an important mechanism of myocardial ischemia-reperfusion injury (MI/RI). Therefore, simultaneous inhibition of ferroptosis and apoptosis of cardiomyocytes can be a promising strategy to treat MI/RI. Apoferritin, as a delivery carrier, can actively target to ischemic myocardium through binding with highly expressed transferrin receptor on ischemic cardiomyocytes. At the same time, apoferritin plays a protective role on ischemic cardiomyocytes by inhibiting ferroptosis. This strategy of killing two birds with one stone significantly improves the therapeutic effect on MI/RI while does not need more pharmaceutical excipients, which has the prospect of clinical transformation., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests that could have appeared to influence the work reported in this paper., (Copyright © 2023 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.)

Macrophages, an important component of inflammatory microenvironment and tumor microenvironment, are closely related to tumor development and progression. Our previous studies showed that apple polysaccharide (AP) could prevent from colitis associated colorectal carcinogenesis. Herein, we further our study to observe the effect of AP on the polarization of macrophages in Raw 264.7 cells and a colitis associated colorectal cancer mouse model, and to investigate the possible mechanisms. Forty male ICR mice were administered with azoxymethane (AOM) and dextran sodium sulfate (DSS). Twenty mice were given no further treatment as model mice, the rest twenty were fed basal diet mixed with 5% of AP. Raw 264.7 cells were treated with 0.5 mg/mL AP. AP could protect ICR mice against AOM/DSS-induced carcinogenesis, keep the colon of AOM/DSS-treated mice in a moderative inflammatory state, and shift macrophage polarization toward M1 phenotype. In vitro study showed that AP could upregulate TLR-4 signaling mildly and trigger M1 macrophage transition. Moreover, AP-induced transition of macrophage phenotype was suppressed by a TLR-4 antagonist, TAK-242. These data may provide a novel molecular basis for understanding how apples act to prevent colorectal cancer (CRC) and indicate that AP has a potential to prevent and treat CRC., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Alcoholic fatty liver disease (AFLD), a major public health problem, has drawn clinical and scientific attention. The study aims to investigate the effect of Ganmeijian [crude extract of malt root, phosphoesterase complex (Pho)] on AFLD, and explore the possible mechanisms. An AFLD rat model was made. 30 and 60 mg/kg Pho were administrated through intestinal fistula for 5 weeks. Compared with those in model group, AST, LDL-C and TC in 30 mg/kg Pho group and TC in 60 mg/kg Pho group decreased. The mRNA level of Fas, Gpat1 and Srebp-1c in Pho groups was significantly reduced. The level of GSH-Px was increased, mitochondrial activity was improved, and the level of MDA and ROS was reduced in Pho groups. Pho shows a beneficial effect on AFLD. The mechanisms are possibly related to Pho inhibiting the expression of fat synthesis genes, protecting the function and increasing the activity of mitochondria in hepatocytes, then reducing the accumulation of ROS and the level of oxidative stress in the liver., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier Inc. All rights reserved.)

It is widely accepted that regulating microbiome could improve human health. We previously observed apple polysaccharide (AP) reversed high-fat-induced microbial dysbiosis, but the mechanism remains to be elucidated. In this study, the function of AP in vitro was evaluated in Bifidobacterium longum (B. longum) and Lactobacillus rhamnosus (L. rhamnosus). The effects of AP on the composition of fecal bacteria of normal SD rats were investigated by qPCR, TA cloning and 16S sequencing. 0.125-2% AP showed no significant effect on the growth of B. longum and L. rhamnosus. DNA concentration of fecal bacteria cultured with 1% AP was significantly higher than that of control group. qPCR revealed that the number of Bifidobacterium and Lactobacillus in fecal flora incubated by 1% AP was significantly higher than that of control group. Three strains of escherichia coli (E. coli) in fecal bacteria were screened out and analyzed. AP can be utilized by one E. coli and the metabolic products of AP could enhance the proliferation of B. longum. These data suggest that AP could promote the growth of B. longum indirectly, and provide another basis to understand the health care function of apple., (Copyright © 2019 Elsevier B.V. All rights reserved.)

The present study tried to assess the effects of modified apple polysaccharide (MAP) on colitis associated carcinogenesis and the expression of Mucin 1(MUC1). One hundred and twenty 5-week-old male ICR mice were used. The control mice were just administrated with saline, and the rest mice were injected intraperitoneally with 1, 2-dimethyl-hydrazine (DMH) and dextran sodium sulfate (DSS). In the 7th week, the mice in MAP-treated groups were bred with the basal diets mixed with different doses of MAP (w/w: 1.25%, 2.5% and 5%) for 13 weeks. The pathological findings demonstrated that: in the 20th week, adenocarcinoma and/or adenoma occurred in the colons of all the mice in model group. MAP treatment decreased the incidence of colorectal cancer significantly. In the early phase of inflammation, MUC1 expression in colonic mucosa had no significant changes. However, when the inflammation developed and tumor formed, MUC1 expression increased remarkably (P < 0.01). And the MAP treatment (especially at the dose of 5%) reduced MUC1 expression significantly. These data suggested that MAP could prevent against colitis associated colorectal cancer in ICR mice effectively, and MUC1 may be a potential therapeutic target in colorectal cancer prevention and treatment., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Chronic intestinal inflammation enhances cell proliferation, angiogenesis, and migration, then promotes the development of colorectal cancer (CRC). Many ingredients of apples have been proven to have anti-inflammatory properties, and show benefits for colitis treatment. In our previous studies, we found modified apple polysaccharide (MAP) could prevent colitis associated colorectal carcinogenesis effectively. Herein, we further our study to observe the effect of MAP on dextran sodium sulfate (DSS)-induced colitis and to investigate the possible mechanisms. IL-22 has both pathogenic and protective effects during intestinal tissue damage. It could be neutralized by the soluble IL-22 receptor, known as the IL-22 binding protein (IL-22BP). A DSS-induced colitis mouse model, a mouse CRC cell line MCA-38 and a mouse dendritic cell line DC2.4 were treated with MAP. Western blot, ELISA, BrdU staining and a co-culture system were used to detect the expression of IL-22 and IL-22BP. MAP significantly protected ICR mice against DSS-induced colitis, and inhibited the growth of MCA-38 cells. The mechanisms may be that MAP down-regulated IL-22 level and up-regulated expression of IL-22BP. These data may provide another molecular basis for understanding how apples act to prevent colitis and suggest that MAP has a potential to treat colitis and prevent CRC., (Copyright © 2017 Elsevier B.V. All rights reserved.)

The saying "An apple a day keeps the doctor away" has been known for over 150 years, and numerous studies have shown that apple consumption is closely associated with reduced risks of chronic diseases. It has been well accepted that dysbiosis is the reflection of various chronic diseases. Therefore, this study investigates the effects of apple polysaccharides (AP) on gut dysbiosis. High-fat diet (HFD) fed rats were treated for 14 weeks with AP. The microbiota composition, microbiota-generated short chain fatty acids (SCFAs), gut permeability and chronic inflammation were analyzed. AP treatment showed higher abundance of Bacteroidetes and Lactobacillus while lower Firmicutes and Fusobacteium. AP significantly increased total SCFAs level that contributed by acetic acid and isobutyric acid. Moreover, AP dramatically alleviated dysbiosis-associated gut permeability and chronic inflammation with decreased plasma LBP, up-regulation of Occludin, down-regulation of tumor necrosis factor a (TNF-a), monocyte chemotactic protein 1 (MCP-1), chemokine ligand 1 (CXCL-1) and interleukin 1 beta (IL-1β). The potential mechanism is due to the fact that AP reduces gut permeability, which involves the induction of autophagy in goblet cells. Therefore, AP exerts health benefits through inhibiting gut dysbiosis and chronic inflammation and modulating gut permeability in HFD-induced dysbiosis rats., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Lateral flow assays (LFAs) hold great promise for point-of-care testing, especially in resource-poor settings. However, the poor sensitivity of LFAs limits their widespread applications. To address this, we developed a novel device by integrating dialysis-based concentration method into LFAs. The device successfully achieved 10-fold signal enhancement in Human Immunodeficiency Virus (HIV) nucleic acid detection with a detection limit of 0.1 nM and 4-fold signal enhancement in myoglobin (MYO) detection with a detection limit of 1.56 ng/mL in less than 25 min. This simple, low-cost and portable integrated device holds great potential for highly sensitive detection of various target analytes for medical diagnostics, food safety analysis and environmental monitoring., (Copyright © 2016 Elsevier B.V. All rights reserved.)

Herba Epimedii is an important medicinal plant which has been used in various traditional Chinese formulations for thousands of years as well as in modern proprietary traditional Chinese medicine products. It has extensive clinical indications, especially for the treatment of sexual dysfunction and osteoporosis. There have been more than 260 chemical moieties identified in the genus Epimedium most of which belong to flavonoids. Icariin is the most abundant constituent in Herba Epimedii. Icariin is pharmacologically bioactive and demonstrates extensive therapeutic capacities such as osteoprotective effect, neuroprotective effect, cardiovascular protective effect, anti-cancer effect, anti-inflammation effect, immunoprotective effect and reproductive function. Particularly, the significant osteogenic effect of icariin made it a promising drug candidate in bone tissue engineering. The current review paper aims to summarize the literatures reporting the pharmacological effects of icariin. The pharmacokinetic properties of bioactive ingredients in Herba Epimedii have also been discussed., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Colorectal cancer (CRC) is one of the most common cancers and a leading cause of cancer-related mortality in developed countries. Many ingredients of apples have been proven to have anti-inflammatory and anti-carcinogenic characteristics, and show benefits for CRC prevention. The aim of this study, therefore, was to evaluate inhibitory effect of an apple oligogalactan (AOG) on pro-inflammatory endotoxin lipopolysaccharide (LPS)-activated human colon carcinoma cells HT-29 and SW-620 and investigate the possible mechanisms. The two cell lines were pretreated with AOG (0.1-1 g/L) for 30 min and then treated with 10 μg/mL LPS. Real time PCR, Western blot, electrophoretic mobility shift assay (EMSA), and ELISA were used to detect the expression and activity of cyclooxygenase-2 (COX-2), NF-κB and MAPKs pathways. AOG significantly inhibited the expression and activity of COX-2 in LPS-activated human colon carcinoma cells HT-29 and SW-620. The mechanisms of AOG-suppressed COX-2 expression may be through inhibiting the phosphorylation of MAPKs and the activation of NF-κB and AP-1. These data may provide another molecular basis for understanding how apples act to prevent CRC and indicate that AOG may be useful for treatment of colitis and prevention of carcinogenesis., (Copyright © 2013 Elsevier B.V. All rights reserved.)

It is reported that apple polysaccharide can prevent colon cancer growth and impede colon cancer progression. Apple oligosaccharide was prepared by the combination of alkaline hydrolysis and enzymolysis of apple polysaccharides, and purified by anion column chromatography. The aim of this study is to explore the effect of apple oligosaccharide on the cellular viability of human colon carcinoma cells (HT29 cells) and its mechanism. The results showed that apple oligosaccharide decreased the cellular viability of HT29 cells in dose-dependent manner. Meanwhile it enhanced the expression of Bax; and decreased the levels of Bcl-2 and Bcl-xl. Apple oligosaccharide induced cell cycle arrest in S phase, which correlated with the decreased expression of Cdk 2 and cyclin B1. These results indicated that apple oligosaccharide attenuated HT29 cell viability by inducing cell apoptosis and cell cycle arrest. Apple oligosaccharide is a potential chemoprevention agent or anti-tumor agent and is worthy of further study., (Copyright © 2013 Elsevier B.V. All rights reserved.)

This study is to investigate the synergistic effect of Anglica polysaccharide sulfate (APS-1) and Combivir, an anti-AIDS drug, on murine leukemia virus in vivo. As the results shown, the virus replication was significantly decreased by the combination of APS-1 and Combivir, which tended to be further decreased (58% inhibition) when compared with that of Combivir alone (51% inhibition). Furthermore, both the percentage of CD4(+) cells and CD4(+)/CD8(+) ratio in peripheral blood cells were significantly enhanced by this combined administration, while the CD4(+) cells was only slightly increased and CD4(+)/CD8(+) ratio was not affected by Combivir alone. Additionally, combination of APS-1 and Combivir also alleviated the toxicity of Combivir. APS-1 not only increased the survival rate of mice administered with LD(50) dose of Combivir, but also reduced the hematologic toxicity induced by Combivir, RBC, HGB and PLT were restored to normal level. These results suggest that APS-1 had synergistic effect with Combivir, which provided new insight into the potential clinical use of polysaccharide sulfate in anti-AIDS field., (Copyright © 2012 Elsevier B.V. All rights reserved.)

This study is to synthesize sulfated Angelica polysaccharides (APSs) and investigate the activity of one of the sulfated derivatives APS-1 on murine leukemia virus in vivo. Six sulfated derivatives with degree of sulfation ranging from 0.68 to 1.91 were obtained. And the virus replication was inhibited by APS-1 at the dose of 10 and 30 mg/kg (26% and 30% inhibition respectively). Furthermore, both the percentage of CD4(+) cells and CD4(+)/CD8(+) ratio in peripheral blood cells were significantly enhanced by APS-1 at 3-30 mg/kg. In addition, the reduced thymus/body weight index by murine leukemia virus infection was increased by ASP-1 in a dose dependent manner. These results suggest that APS-1 could not only inhibit virus replication, but also improve the immune function. APS-1 may be a potential new and better antiviral drug., (Copyright © 2011 Elsevier B.V. All rights reserved.)

Colon-specific drug delivery systems are clinically necessary to treat colon diseases locally while minimizing systemic side effects. In this study, we extracted angelica polysaccharide from fresh roots of Angelica sinensis Diels and analyzed the monosaccharide components. With succinate as a cross-linker and angelica polysaccharide as a drug carrier, a dexamethasone-polysaccharide conjugate was synthesized. The amount of dexamethasone (Dex) loaded in the dexamethasone-polysaccharide conjugate was 14.13/100 mg. The newly synthesized dexamethasone-polysaccharide conjugate was found to greatly reduce systemic absorption of Dex and effectively deliver Dex to the large intestine. When dexamethasone-polysaccharide conjugate was used to treat TNBS-induced ulcerative colitis in rats by gavage, the ulcerative area of the colon and the colonic myeloperoxidase (MPO) activity was reduced in a dose-dependent manner. There was no effects on spleen weight, thymus weight, or peripheral blood lymphocyte count (0.25 micromol kg(-1) day(-1)). These results indicate that the dexamethasone-polysaccharide conjugate has a therapeutic effect on TNBS-induced ulcerative colitis in rats, while simultaneously reducing the systemic immunosuppression caused by Dex. Thus, the angelica polysaccharide was a promising colon-specific drug carrier, and the new dexamethasone-polysaccharide conjugate may yield a potential drug for the treatment of human inflammatory bowel disease., (2009 Wiley-Liss, Inc. and the American Pharmacists Association)

The immunomodulatory activities of an Angelica sinensis polysaccharide (AP), purified from the fresh root of A. sinensis Diels, were investigated in vitro in relation to the specificity to immune cells. AP consisted of rhamnose, arabinose, mannose, glucose, galactose with the molar ratio of 1.00:4.54:2.98:11.09:7.45. Cell proliferation results showed that proliferation of total spleen cells, macrophages and T cells were promoted by the action of AP. The treatment of AP increased the production of IL-2 and IFN-gamma, while that of IL-4 was decreased. RT-PCR analysis displayed that the IL-2 and IFN-gamma gene expression were enhanced but the IL-4 gene expression was decreased. Some differences in cytokines secretion pattern were also detected, the expression of IFN-gamma was rapidly augmented while that of IL-2 responded later. The flow cytometry results showed that the percentage of CD4(+)T cell in total spleen cells was remarkably increased by AP, while that of CD8(+)T cell was slightly decreased. In conclusion, AP has immunomodulatory activity by regulating expression of Th1 and Th2 related cytokines. The time-effect relation of cytokines response also suggests that macrophages and natural killer cells involved in nonspecific immunity were primary activated, and helper T cell were secondarily affected by AP.

Two water-soluble glucans (designated APS-1cI and APS-1cII) were extracted from the roots of Angelica sinensis (Oliv.) Diels and further purified by anion-exchange and gel-filtration chromatography. Their molecular weights were determined to be 1.7 x 10(5) and 3.9 x 10(4)Da, respectively. The structures of the purified glucans were investigated by a combination of chemical and instrumental analysis, such as methylation analysis, periodate oxidation, GC-MS, as well as FTIR and NMR spectroscopy ((1)H, (13)C, H-H COSY, HSQC, HMBC, TOCSY and NOESY). The data obtained indicated that APS-1cI was a linear alpha-glucan composed of only (1-->6)-alpha-D-Glcp, and APS-1cII had a repeating unit consisting of (1-->4)-alpha-D-Glcp and (1-->6)-alpha-D-Glcp in a molar ratio of 4:1. Such glucans isolated from A. sinensis (Oliv.) Diels have not been previously reported.