Isolation, structure, biological activity and application progress of ginseng polysaccharides from the Araliaceae family.

Phytopolysaccharides are a class of natural macromolecules with a range of biological activities. Ginseng, red ginseng, American ginseng, and Panax notoginseng are all members of the Araliaceae family. They are known to contain a variety of medicinal properties and are typically rich in a wide range of medicinal values. Polysaccharides represent is one of the principal active ingredients in the aforementioned plants. However, there is a paucity of detailed reports on the separation methods, structural characteristics and comparison of various pharmacological effects of these polysaccharides. This paper presents a review of the latest research reports on ginseng, red ginseng, American ginseng and ginseng polysaccharides. The differences in extraction, separation, purification, structural characterization, and pharmacological activities of the four polysaccharides are compared and clarified. Upon examination of the current research literature, it becomes evident that the extraction and separation processes of the four polysaccharides are highly similar. Modern pharmacological studies have corroborated the multiple biological activities of these polysaccharides. These activities encompass a range of beneficial effects, including antioxidant stress injury, fatigue reduction, tumor inhibition, depression alleviation, regulation of intestinal flora, immunomodulation, diabetes management, central nervous system protection, anti-aging, and improvement of skin health. This paper presents a review of studies on the extraction, purification, characterization, and bioactivities of four natural plant ginseng polysaccharides. Furthermore, the review presents the most recent research findings on their pharmacological activities. The information provides a theoretical basis for the future application of natural plant polysaccharides and offers a new perspective for the in-depth development of the medicinal value of ginseng in the clinical practice of traditional Chinese medicine.

Ginkgo biloba leaf extract prevents diabetic nephropathy through the suppression of tissue transglutaminase.

The present study aimed to investigate the preventive effects of Ginkgo biloba leaf extract (GBE) against extracellular matrix (ECM) accumulation in a streptozotocin (STZ)-induced rat model of diabetic nephropathy (DN), and to determine its underlying molecular mechanism. In vivo, a rat model of DN was established by intraperitoneal injection of STZ, and the rats were subsequently administered GBE. The results demonstrated that GBE significantly decreased blood glucose, the urine protein excretion rate and ECM accumulation in DN rats. In addition, the development of DN significantly induced tissue transglutaminase (tTG) protein expression, which was detected by immunohistochemistry, western blotting and PCR analyses, while GBE administration decreased tTG expression in the diabetic kidney. In vitro, rat glomerular mesangial cells (HBZY-1 cells) cultured with high glucose were also treated with GBE. The concentrations of tTG, fibronectin, type IV collagen, transforming growth factor (TGF)-ß and connective tissue growth factor (CTGF) were detected via ELISA. The results demonstrated that GBE notably decreased the concentration of these proteins, and tTG expression was positively associated with TGF-ß. GBE also suppressed tTG expression of high glucose-treated HBZY-1 cells in a concentration-dependent manner. Furthermore, tTG protein expression was detected in high glucose-treated HBZY-1 cells transfected with small interfering RNA (siRNA) oligonucleotides against TGF-ß and CTGF to investigate a possible mechanism of GBE-mediated inhibition of tTG. The results demonstrated that the tTG levels remained unchanged in CTGF siRNA-transfected cells, but were decreased in the GBE + CTGF siRNA group compared with the control siRNA group, suggesting that tTG may not be regulated by CTGF, and the inhibitory effect of GBE on tTG may not be associated with the direct inhibition of CTGF. However, tTG expression was decreased following the transfection with TGF-ß siRNA, in which levels of tTG were similar compared with both the GBE group and GBE + TGF-ß siRNA group, indicating that tTG may be regulated by TGF-ß, and that the GBE-induced repression of tTG expression may be associated with the downregulation of TGF-ß. Taken together, the results of the present study suggest that GBE prevented ECM accumulation by suppressing tTG expression in DN, which was predominantly mediated by TGF-ß.

20(S)-Protopanaxadiol inhibits epithelial-mesenchymal transition by promoting retinoid X receptor alpha in human colorectal carcinoma cells.

Colorectal carcinoma (CRC) recurrence is often accompanied by metastasis. Most metastasis undergo through epithelial-mesenchymal transition (EMT). Studies showed that retinol X receptor alpha (RXRα) and 20(S)-Protopanaxadiol (PPD) have anti-tumour effects. However, the anti-metastasis effect of 20(S)-PPD and the effect of RXRα on EMT-induced metastasis are few studies on. Therefore, the role of RXRα and 20(S)-PPD in CRC cell metastasis remains to be fully elucidated. RXRα with clinicopathological characteristics and EMT-related expression in clinical samples were examined. Then, RXRα and EMT level in SW480 and SW620 cells, overexpressed and silenced RXRα in SW620 cells and SW480 cells, respectively, were evaluated. Finally, 20(S)-PPD effect on SW620 and SW480 cells was evaluated. The results showed that a lower RXRα expression in cancer tissues, and a moderate negative correlation between RXRα and N stage, and tended to higher level of EMT. SW480 and SW620 cells had the highest and lowest RXRα expression among four CRC cell lines. SW480 had lower EMT level than SW620. Furthermore, 20(S)-PPD increased RXRα and inhibited EMT level in SW620 cell. Finally, 20(S)-PPD cannot restore SW480 cells EMT level to normal when RXRα silencing. These findings suggest that 20(S)-PPD may inhibit EMT process in CRC cells by regulating RXRα expression.

Rosuvastatin protects against endothelial cell apoptosis in vitro and alleviates atherosclerosis in ApoE-/- mice by suppressing endoplasmic reticulum stress.

The development of abnormal lipid-induced atherosclerosis is initiated with endothelial cell apoptosis. Vascular endothelial cells possess highly developed endoplasmic reticulum (ER), which is involved in lipid metabolism, indicating that ER stress may contribute chiefly to the induction of endothelial cell apoptosis. Based on its ability to reduce cholesterol levels, rosuvastatin may play an endothelial and vascular protective role by regulating ER stress. In the present study, the involvement of the inhibition of the ER stress-induced endothelial injury was investigated in combination with the lipid lowering effects of rosuvastatin. This compound can be used to inhibit cholesterol synthesis in atherosclerosis. Rosuvastatin decreased the apoptotic rates of human umbilical vascular endothelial cells (HUVECs) that had been stimulated with ox-low density lipoprotein (LDL) in vitro and repressed the mRNA levels of CHOP, sXBP1 and caspase-12, and decreased caspase-12 activity, as well as the content of glucose-regulated protein 78 (GRP78), phosphorylated (p)-protein kinase RNA-like ER kinase (PERK), p-inositol-requiring protein 1α (IRE1α) and p-eIF2α proteins. In addition, ApoE-/- mice were fed with atherogenic chow for 8 weeks for atherosclerosis induction and rosuvastatin was provided by intragastric administration for an additional 4 weeks. Subsequently, the atherosclerotic plaque formation in the aorta was evaluated by Oil Red O and hematoxylin and eosin staining, and the serum LDL, high-density lipoprotein, total cholesterol (TC) and triacylglycerol (TG) levels were measured. In addition, the induction of apoptosis of endothelial cells and the expression levels of GRP78, p-PERK, p-IRE1α and p-eIF2α were assessed in the aorta. Rosuvastatin repressed atherosclerotic plaque formation and endothelial apoptosis in the aorta and decreased LDL and TG levels in the serum, as determined by in vivo results. Furthermore, it downregulated the expression levels of protein chaperone GRP78, p-PERK, p-IRE1α and p-eIF2α in the aortic intima. The data indicated that rosuvastatin could protect HUVECs from ER stress-induced apoptosis triggered by oxidized LDL. It could also inhibit atherosclerosis formation in ApoE-/- mice aorta by regulating the PERK/eIF2α/C/EBPα-homologous protein and IRE1α/sXBP1 signaling pathways. Taken collectively, the present study demonstrated the preventive and therapeutic effects of rosuvastatin in protecting from the development of endothelial cell dysfunction diseases.

Ginsenoside Rg3 Alleviates ox-LDL Induced Endothelial Dysfunction and Prevents Atherosclerosis in ApoE-/- Mice by Regulating PPARγ/FAK Signaling Pathway.

The initiation of atherosclerosis (AS) induced by dyslipidemia is accompanied by endothelial dysfunction, including decreased healing ability and increased recruitment of monocytes. Studies showed ginsenoside Rg3 has potential to treat diseases associated with endothelial dysfunction which can protects against antineoplastic drugs induced cardiotoxicity by repairing endothelial function, while the effect and mechanism of Rg3 on dyslipidemia induced endothelial dysfunction and AS are not clear. Therefore, we investigated the effects of Rg3 on oxidized low-density lipoprotein (ox-LDL) induced human umbilical vein endothelial cells (HUVECs) dysfunction and high-fat diets (HFD) induced atherosclerosis in ApoE-/- mice, as well as the mechanism. For in vitro assay, Rg3 enhanced healing of HUVECs and inhibited human monocytes (THP-1) adhesion to HUVECs disturbed by ox-LDL, down-regulated focal adhesion kinase (FAK)-mediated expression of vascular cell adhesion molecule 1 (VCAM-1) and intercellular adhesion molecule 1 (ICAM-1); restrained the FAK-mediated non-adherent dependent pathway containing matrix metalloproteinase (MMP)-2/9 expression, activation of nuclear factor-kappa B (NF-κB), high mRNA levels of monocyte chemotactic protein 1 (MCP-1) and interleukin 6 (IL-6), besides Rg3 up-regulated peroxisome proliferators-activated receptor γ (PPARγ) in ox-LDL-stimulated HUVECs. GW9662, the PPARγ-specific inhibitor, can repressed the effects of Rg3 on ox-LDL-stimulated HUVECs. For in vivo assay, Rg3 significantly reduced atherosclerotic pathological changes in ApoE-/- mice fed with HFD, up-regulated PPARγ, and inhibited activation FAK in aorta, thus inhibited expression of VCAM-1, ICAM-1 in intima. We conclude that Rg3 may protect endothelial cells and inhibit atherosclerosis by up-regulating PPARγ via repressing FAK-mediated pathways, indicating that Rg3 have good potential in preventing dyslipidemia induced atherosclerosis.

MiR-92b-3p is Induced by Advanced Glycation End Products and Involved in the Pathogenesis of Diabetic Nephropathy.

PURPOSE: The current study aims to examine the effects of advanced glycation end products (AGEs) on the microRNA (miRNA) expression profile in the kidney tissues of rats. METHODS: Wistar rats were randomly divided into three equal experiment groups: the AGE group, the RSA group, and the control group. The rats in the AGE group and the RSA group were administered with advanced glycation end products (AGEs) and rat serum albumin (RSA) via the tail vein, respectively, whereas the control group received PBS. Total RNA was prepared from the rat kidney tissues, and the miRNA expression profiles in different experiment groups were compared by microarray analysis. The expression levels of selected differential miRNAs were verified by RT-qPCR. Target gene prediction was conducted using algorithms such as TargetScan, miRanda, and PICTar. Functional analysis was performed to determine the putative biological roles of the validated miRNAs. RESULTS: The microarray study revealed 451 upregulated and 320 downregulated miRNAs in the AGE group compared with the RSA group (p < 0.05). Seven miRNAs, including miR-21-5p, miR-92b-3p, miR-140-3p, miR-196a-5p, miR-181b-5p, miR-186-5p, and miR-192-5p, were screened and verified using RT-qPCR, of which, the change of miR-92b-3p was the most obvious according to the miRNA expression different multiple and p < 0.05). Seven miRNAs, including miR-21-5p, miR-92b-3p, miR-140-3p, miR-196a-5p, miR-181b-5p, miR-186-5p, and miR-192-5p, were screened and verified using RT-qPCR, of which, the change of miR-92b-3p was the most obvious according to the miRNA expression different multiple and. CONCLUSION: The results of the current study suggested that miR-92b-3p could mediate AGE-induced development of renal abnormalities through targeting Smad7 in rats with DN.

Expression analysis of microRNAs and their target genes during experimental diabetic renal lesions in rats administered with ginsenoside Rb1 and trigonelline.

Purpose: To appraise the curative effect of ginsenoside Rb1 and trigonelline in diabetic nephropathy and to analyze the expression analysis of microRNAs and their target genes during experimental diabetic renal lesions in rats. Methods: Wistar rats were made diabetic by intraperitoneal injection of 55 mg/kg streptozotocin. According to their fasting blood glucose values and initial body weight, diabetic rats were assigned to specific groups and treated as follows: DN group (tap water, n = 10), A group (ginsenoside Rb1, 40 mg/kg, n = 10), B group (trigonelline, 20 mg/kg, n = 10) and the C group (ginsenoside Rb1 and trigonelline, 60 mg/kg, m(ginsenoside Rb1) : m (trigonelline) = 2:1, n = 10). The control group was treated with tap water (n = 10). All rats were gavaged with drugs or tap water once daily for 12 weeks. Results: Renal dysfunction, oxidative stress, and pathological alteration were significantly alleviated by a combination of ginsenoside Rb1 and trigonellin (C group). Some miRNAs were expressed differentially in Con, DN, A and C groups. Results of immunohistochemistry and western blotting showed that Wnt and ß-catenin were expressed differentially in Con, DN, and C groups. Conclusion: Ginsenoside Rb1 and trigonelline could prevent the development of diabetic renal lesions by regulating the expression of miR-3550 and further associating with the Wnt/ß-catenin signaling.

Rosuvastatin protects against oxidized low­density lipoprotein­induced endothelial cell injury of atherosclerosis in vitro.

Atherosclerosis­induced cardiovascular diseases (CVDs) are accompanied by substantial morbidity and mortality. The loss and injury of endothelial cells is the primary cause of atherosclerosis. Rosuvastatin is an alternative agent used to reduce the risk of cardiovascular disease. Subsequently, the present study aimed to investigate the protective effects of rosuvastatin on oxidized­low­density lipoprotein (ox­LDL)­induced human umbilical vein endothelial cell (HUVEC) injury. The viability of ox­LDL­cultured HUVECs with or without rosuvastatin (0.01, 0.1 and 1 µmol/l) pretreatment, and pretreatment at different time points (3, 6, 12 and 24 h) was determined using an MTT assay. Morphological changes and the extent of apoptosis were detected; the anti­oxidase activity, including superoxide dismutase (SOD) and catalase (CAT), was examined, and the contents of malondiahdehyde (MDA) and nitric oxide (NO) were measured. The phosphorylation levels of endothelial nitric oxide synthase (eNOS), protein kinase B (Akt) and phosphoinositide 3 kinase (PI3K) were detected using western blot analysis. The results demonstrated that pretreatment with 0.01­1 µmol/l rosuvastatin decreased cell apoptosis caused by ox­LDL. Notably, pretreatment with 1 µmol/l rosuvastatin for >12 h increased cell viability. Additionally, DAPI staining revealed that rosuvastatin inhibited HUVEC apoptosis. Rosuvastatin treatment also resulted in increased SOD and CAT activities and decreased MDA content in ox­LDL­stimulated HUVECs. Furthermore, pretreatment with 0.01­1 µmol/l rosuvastatin significantly increased` the NO content compared with HUVECs treated with ox­LDL alone. Western blot analyses demonstrated that rosuvastatin upregulated the phosphorylation of eNOS, Akt and PI3K. These findings indicated that rosuvastatin could protect HUVECs against ox­LDL­induced injury through its anti­oxidant effect and its ability to upregulate the expression of vascular endotheliocyte­protecting factors.

Herba Artemisiae Capillaris Extract Prevents the Development of Streptozotocin-Induced Diabetic Nephropathy of Rat.

Diabetic nephropathy (DN) is a major cause of end-stage renal disease throughout the world; until now there is no specific drug available. In this work, we use herba artemisiae capillaris extract (HACE) to alleviate renal fibrosis characterized by the excessive accumulation of extracellular matrix (ECM) in rats, aiming to investigate the protective effect of the HACE on DN. We found that the intragastric treatment of high-dose HACE could reverse the effect of streptozotocin not only to decrease the level of blood glucose and blood lipid in different degree but also further to improve renal functions. It is worth mentioning that the effect of HACE treatment was comparable to the positive drug benazepril. Moreover, we found that HACE treatment could on one hand inhibit oxidative stress in DN rats through regulating enzymatic activity for scavenging reactive oxygen species and on the other hand increase the ECM degradation through regulating the activity of metalloproteinase-2 (MMP-2) and the expression of tissue transglutaminase (tTG), which explained why HACE treatment inhibited ECM accumulation. On the basis of above experimental results, we conclude that HACE prevents DN development in a streptozotocin-induced DN rat model, and HACE is a promising candidate to cure DN in clinic.