Chun-Feng Zhang

Hesperidin Prevents Retinal and Plasma Abnormalities in Streptozotocin-Induced Diabetic Rats

Diabetic retinopathy is a complex disease that potentially involves increased production of advanced glycosylation end products (AGEs) and elevated aldose reductase (AR) activity, which are related with oxidative stress and inflammation. The aim of this study was to investigate the effects of hesperidin on retinal and plasma abnormalities in streptozotocin-induced diabetic rats. Hesperidin (100, 200 mg/kg daily) was given to diabetic rats for 12 weeks. The blood-retina breakdown (BRB) was determined after 2 weeks of treatment followed by the measurement of related physiological parameters with ELISA kits and immunohistochemistry staining at the end of the study. Elevated AR activity and blood glucose, increased retinal levels of vascular endothelial growth factor (VEGF), ICAM-1, TNF-α, IL-1β and AGEs as well as reduced retina thickness were observed in diabetic rats. Hesperidin treatment significantly suppressed BRB breakdown and increased retina thickness, reduced blood glucose, AR activity and retinal TNF-α, ICAM-1, VEGF, IL-1β and AGEs levels. Furthermore, treatment with hesperidin significantly reduced plasma malondialdehyde (MDA) levels and increased SOD activity in diabetic rats. These data demonstrated that hesperidin attenuates retina and plasma abnormalities via anti-angiogenic, anti-inflammatory and antioxidative effects, as well as the inhibitory effect on polyol pathway and AGEs accumulation.

Echinacoside promotes bone regeneration by increasing OPG/RANKL ratio in MC3T3-E1 cells

Echinacoside (ECH), isolated from Cistanche tubulosa (Schrenk) R. Wight stems, was subjected to in vitro experiments to investigate its bioactivities on proliferation, differentiation and mineralization of the osteoblastic cell line MC3T3-E1. MTT assay, the alkaline phosphatase (ALP) activity and calcium deposition were determined, and the secretion of collagen I (COL I), osteocalcin (OCN), osteoprotegerin (OPG) and receptor activator of nuclear factor-κB ligand (RANKL) were also assayed by enzyme-linked immunosorbent assay (ELISA). The results showed that ECH caused a significant increase in cell proliferation, ALP activity, COL I contents, OCN levels and an enhancement of mineralization in osteoblasts at the concentration range from 0.01 to 10nmol·L(-1) (p<0.05), suggesting that ECH has a stimulatory effect on osteoblastic bone formation or has potential activity against osteoporosis. In addition, the ratio of OPG/RANKL also could be enhanced by ECH. These findings provide the potent evidence that ECH can promote bone regeneration in cultured osteoblastic MC3T3-E1 cells, which might be done by elevating the OPG/RANKL ratio, and potential evidence for echinacoside to be a promising drug or a lead compound in the development of disease-modifying drug to prevent osteoporosis.

Antiosteoporotic activity of echinacoside in ovariectomized rats.

PURPOSE Echinacoside (ECH), isolated from Cistanche tubulosa (Schrenk) R. Wight stems, has been reported to enhance bone regeneration in MC3T3-E1 cells in vitro. The objectives of this study were to investigate the antiosteoporotic effect of ECH on bone metabolism in the ovariectomized (OVX) rat model of osteoporosis in vivo. METHODS Fifty-six aged 6 months female Sprague-Dawley rats were randomly assigned into sham-operated group (SHAM) and six OVX subgroups (n=8 each). The OVX rats were then subdivided into six groups treated with vehicle (OVX), Xian-ling-gu-bao (XLGB, 0.5 g/kg body weight/day, orally), 17β-estradiol (E2, 50 μg/kg body weight/day, orally) or ECH (30, 90, and 270 mg/kg body weight, daily, orally) for 12 weeks respectively. We evaluated the pharmacological effects of E2, XLGB and ECH against osteoporosis by evaluating the body weight, uterus wet weight, serum and urine biochemical parameters, bone mineral density (BMD), bone biomechanical properties, bone microarchitecture, bone histomorphology and uterus immunohistochemistry. RESULTS In OVX rats, the increases of body weight, serum hydroxyproline (HOP) levels, and the decreases of uterus wet weight and BMD were significantly reversed by ECH treatment. Moreover, three dosages of ECH completely corrected the increased urine concentration of calcium (Ca), inorganic phosphorus (P), and HOP observed in OVX rats. Furthermore, Micro-CT analysis results of distal femur showed that all ECH-treated groups notably enhanced bone quality compared to OVX group (p<0.05). Consistent with this finding, total femur BMD and biomechanical strength of tibia were significantly improved (p<0.05) after 12 weeks ECH administration. Histological results also showed the protective activity of ECH through promotion of bone formation and suppression of bone resorption. In addition, the ECH administration also significantly enhanced the expression of ER in the uteri according to immunohistochemical evaluation (p<0.05). Those findings, based on the serum and urine biochemical, BMD, Micro-CT, biomechanical test, histopathological and immunohistochemical parameters, showed that ECH has a notable antiosteoporotic effect, similar to estrogen, especially effective for prevention osteoporosis induced by estrogen deficiency. CONCLUSION These results suggest that ECH, as a new class of phytoestrogen, has a remarkable antiosteoporotic activity, and may be a promising candidate for treatment of postmenopausal osteoporosis induced by estrogen deficiency in a natural way through herbal resources.

Protective Effect of p-Cymene on Lipopolysaccharide-Induced Acute Lung Injury in Mice

In the previous study, the anti-inflammatory effect of p-cymene had been found. In this study, we investigated anti-inflammatory effects of p-cymene on acute lung injury using lipopolysaccharide (LPS)-induced acute lung injury (ALI) mouse model. The cell counting in the bronchoalveolar lavage fluid (BALF) was measured. The animal lung edema degree was evaluated by wet/dry weight (W/D) ratio. The superoxidase dismutase (SOD) activity and myeloperoxidase (MPO) activity was assayed by SOD and MPO kits, respectively. The levels of inflammatory mediators including tumor necrosis factor alpha (TNF-α), IL-1β, and IL-6 were assayed by enzyme-linked immunosorbent assay method. The pathological changes of the lung tissues were observed by hematoxylin and eosin staining. The inflammatory signal pathway-related protein levels of NF-κB were measured using Western blotting. The data showed that treatment with the p-cymene markedly attenuated inflammatory cell numbers in the BALF, decreased NF-κB protein level in the lungs, improved SOD activity, and inhibited MPO activity. Histological studies demonstrated that p-cymene substantially inhibited LPS-induced neutrophils in the lung tissue compared with the model group. The results indicated that p-cymene had a protective effect on LPS-induced ALI in mice.

Anti-rheumatoid arthritic activity of flavonoids from Daphne genkwa

The aim of the study was to investigate the anti-rheumatoid arthritic activity of four flavonoids from Daphne genkwa (FFD) in vivo and in vitro. Flavonoids of D. genkwa were extracted by refluxing with ethanol and purified by polyamide resin. An in vivo carrageenan-induced paw edema model, tampon-granuloma model and Freunds complete adjuvant (FCA)-induced arthritis mouse model were used to evaluate the anti-rheumatoid arthritic activities of FFD. Moreover, nitric oxide (NO) release and neutral red uptake (NRU) in lipopolysaccharide (LPS)-induced murine macrophage RAW264.7 cells were used to evaluate the anti-inflammatory effect in vitro. In addition, antioxidant effect of FFD was determined using the 2,2-diphenyl-1-picrylhydrazyl (DPPH) method. A high dose of FFD significantly reduced the degree of acute inflammatory paw edema in mice as a response to carrageenan administration (p<0.01). FFD displayed a dose-dependent inhibition of granuloma formation in mice (p<0.05). FFD also inhibited chronic inflammation in adjuvant-induced arthritis rats when administered orally at the dose of 50mg/kg/day (p<0.001). In addition, FFD suppressed the production of NO and exhibited immunoregulatory function in LPS-activated RAW264.7 cells in a dose-related manner. Simultaneously, FFD revealed conspicuous antioxidant activity with IC50 values of 18.20μg/ml. FFD possesses significant anti-inflammatory and antioxidant activity, which could be a potential therapeutic agent for chronic inflammatory disorders such as rheumatoid arthritis.

Protective effects of timosaponin B-II on high glucose-induced apoptosis in human umbilical vein endothelial cells

This study was designed to investigate the action of timosaponin B-II, a main bioactive compound in Anemarrhena asphodeloides Bunge, on the prevention from high glucose-induced cytotoxicity and apoptosis in human umbilical vein endothelial cells (HUVECs) and the potential mechanisms involved. The results showed that compared with the normal control group, exposure of HUVECs to high glucose media for 72 h resulted in a significant increase in lactates dehydrogenise release, reactive oxygen species production, Caspase-3 activity and the percentage of apoptotic cells (p<0.01). However, pretreatment with timosaponin B-II significantly increased the viability of HUVECs and decreased lactates dehydrogenise release, Caspase-3 activity and the apoptosis rate in a concentration-dependent manner (p<0.05). In addition, timosaponin B-II notably decreased the amount of reactive oxygen species and malondialdehyde, as well as promoted glutathione peroxidase activity, endothelial nitric oxide synthase activity and nitric oxide release (p<0.05). These results suggest that timosaponin B-II has the antiapoptotic effect in endothelial cells through inhibition of high glucose-induced oxidative stress and has the potential for preventing diabetic cardiovascular complications.

Adulteration and cultivation region identification of American ginseng using HPLC coupled with multivariate analysis.

American ginseng (Panax quinquefolius) is originally grown in North America. Due to price difference and supply shortage, American ginseng recently has been cultivated in northern China. Further, in the market, some Asian ginsengs are labeled as American ginseng. In this study, forty-three American ginseng samples cultivated in the USA, Canada or China were collected and 14 ginseng saponins were determined using HPLC. HPLC coupled with hierarchical cluster analysis and principal component analysis was developed to identify the species. Subsequently, an HPLC-linear discriminant analysis was established to discriminate cultivation regions of American ginseng. This method was successfully applied to identify the sources of 6 commercial American ginseng samples. Two of them were identified as Asian ginseng, while 4 others were identified as American ginseng, which were cultivated in the USA (3) and China (1). Our newly developed method can be used to identify American ginseng with different cultivation regions.

Colon cancer chemopreventive effects of baicalein, an active enteric microbiome metabolite from baicalin

Baicalin is a major constituent of Scutellaria baicalensis, which is a commonly used herbal medicine in many Asian countries. After oral ingestion, intestinal micro-biota metabolism may change parent compounds structure and its biological activities. However, whether baicalin can be metabolized by enteric microbiota and the related anti-cancer activity is not clear. In this study, using human enteric microbiome incubation and HPLC analysis, we observed that baicalin can be quickly converted to baicalein. We compared the antiproliferative effects of baicalin and baicalein using a panel of human cancer cell lines, including three human colorectal cancer (CRC) cell lines. In vitro antiproliferative effects on CRC cells were verified using an in vivo xenograft nude mouse model. Baicalin showed limited antiproliferative effects on some of these cancer cell lines. Baicalein, however, showed significant antiproliferative effects in all the tested cancer cell lines, especially on HCT-116 human colorectal cancer cells. In vivo antitumor results supported our in vitro data. We demonstrated that baicalein exerts potent S phase cell cycle arrest and pro-apoptotic effects in HCT-116 cells. Baicalein induced the activation of caspase 3 and 9. The in silico modeling suggested that baicalein forms hydrogen bonds with residues Ser251 and Asp253 at the active site of caspase 3, while interactions with residues Leu227 and Asp228 in caspase 9 through its hydroxyl groups. Data from this study suggested that baicalein is a potent anticancer metabolite derived from S. baicalensis. Enteric microbiota play a key role in the colon cancer chemoprevention of S. baicalensis.

Hypoglycemic and hypolipidemic effects of oxymatrine in high-fat diet and streptozotocin-induced diabetic rats

Oxymatrine, a quinolizidine alkaloid, has been widely used for the treatment of hepatitis. In this study, we investigated the hypoglycemic and hypolipidemic effects and new pharmacological activities of oxymatrine, in a high-fat diet and streptozotocin (STZ)-induced diabetic rats. The results demonstrated that oxymatrine could significantly decrease fasting blood glucose, glycosylated hemoglobin (GHb), food and water intake, non-esterified fatty acid (NEFA), total cholesterol (TC), triglyceride (TG), low density lipoprotein cholesterol levels (LDL-c), and increase serum insulin, liver and muscle glycogen, high density lipoprotein cholesterol (HDL-c), glucagon-like peptide-1 (GLP-1) and muscle glucose transporter-4 (GLUT-4) content in diabetic rats. The results of the histological examinations of the pancreas and liver show that oxymatrine protected the islet architecture and prevented disordered structure of the liver. This study displays that oxymatrine can alleviate hyperglycemia and hyperlipemia in a high-fat diet and STZ-induced diabetic rats might by improving insulin secretion and sensitivity.

Ginseng on Cancer: Potential Role in Modulating Inflammation-Mediated Angiogenesis

Angiogenesis is a regulated process integral to many physiological and pathological situations, including carcinogenesis and tumor growth. The majority of the angiogenic processes are related to inflammation. The interplay is not only important in the case of pathogen entry but also influential in chronic inflammatory diseases, tumor growth and tissue regeneration. Modulating the interaction between inflammation and angiogenesis could be an important target for cancer treatment and wound healing alike. Ginseng has a wide range of pharmacological effects, including anti-inflammatory and angiogenesis-modulating activities. This paper presents the recent research progresses on the inhibition of angiogenesis by ginseng and its active constituents, with a particular focus on processes mediated by inflammation. The modulatory role of ginseng compounds in inflammation-mediated angiogenesis involving hypoxia and microRNAs are also discussed. With the potential to modulate the angiogenesis at the transcriptional, translational and protein signaling level via various different mechanisms, ginseng could prove to be effective in cancer therapeutics.