Protective effects of Ligularia fischeri root extracts against ulcerative colitis in mice through activation of Bcl-2/Bax signalings.

BACKGROUND: Ulcerative colitis (UC) is a chronic inflammatory bowel disease characterized by high levels of proinflammatory cytokines and epithelial barrier dysfunction. The root of Ligularia fischeri (Ledeb.) Turcz. is a traditional Chinese medicinal herb with diverse therapeutic properties, which has been successfully used to treat inflammation-related diseases. However, little is known about its effect and mechanism against UC. PURPOSE: To investigate the efficacy and mechanism of L. fischeri root extracts against UC. METHODS: L. fischeri root samples were prepared using the alcohol extraction method and liquid-liquid extraction method. A dextran sodium sulfate-induced UC mouse model and a lipopolysaccharide (LPS)-induced inflammatory cell model were employed in the present study. Cell apoptosis was detected by TUNEL staining, and an enzyme-linked immunosorbent assay was used to quantify the abundance of inflammatory factors in tissues. Hematoxylin and eosin staining and Masson staining were employed to analyze drug toxicity to the liver and kidney. A myeloperoxidase (MPO) assay kit was used to detect neutrophil infiltration in colon tissues. RT-qPCR was then employed to quantify the transcriptional levels of proinflammatory and apoptotic-related genes, while tight junction and apoptosis-related proteins were quantified via western blotting. Gas Chromatography/Mass Spectrometry analysis was then performed to identify the natural compounds in L. fischeri root extracts. RESULTS: The water decoction extract, methanol extract, and especially the chloroform extract (CE) exerted potent therapeutic effects in UC mice. Similar to the positive control group (5-aminosalicylic acid), oral administration of CE (30, 60, and 90 mg/kg/d) elicited distinct therapeutic effects on UC mice in the medium- and high-dose groups. CE decreased disease activity index, histopathological score, and MPO level significantly, and effectively retained the colon length. Furthermore, CE significantly reduced the levels of proinflammatory cytokines, including interleukin (IL)-1ß, IL-6, and tumor necrosis factor-α and enhanced the expression of tight junction proteins, such as zonula occludens (ZO)-1, ZO-2, claudin-1, and occludin, as well as the transcriptional levels of mucins, such as MUC-1 and MUC-2, in UC mice. Notably, CE prevented apoptosis of colonic epithelial cells by up-regulating Bcl-2 and down-regulating Bax. Also, CE inhibited the secretion of pro-inflammatory cytokines and apoptosis in LPS-induced RAW264.7 macrophages via the activation of Bcl-2/Bax signals. CONCLUSIONS: Collectively, L. fischeri root extracts, especially CE, have obvious therapeutic effects against UC. CE reduces inflammation and protects the intestinal epithelial cells and intestinal epithelial barrier via activation of the Bcl-2/Bax signaling pathway, and may be a promising therapeutic agent for UC treatment.

Osteoinductive activity of bisdemethoxycurcumin and its synergistic protective effect with human amniotic mesenchymal stem cells against ovariectomy-induced osteoporosis mouse model.

Osteoporosis is a common disease characterized by skeletal fragility and microarchitectural deterioration. However, existing conventional drugs exhibit limited efficacy and can elicit severe adverse effects; moreover, and novel stem cell-based therapies have not exhibited sufficient therapeutic efficacy. Our hypothesis is that an appropriate osteogenic inducer may improve their therapeutic efficacy. In this study, we found that bisdemethoxycurcumin (BDMC) stimulates the differentiation of human amniotic mesenchymal stem cells (hAMSCs) into osteoblasts without inducing cytotoxicity. Here BDMC enhances calcium deposition in hAMSCs, while promoting the expression of early and late markers of osteoblast differentiation, including ALP, runt-related transcription factor 2, osterix, COL1-α1, osteocalcin, and osteopontin at the transcriptional and translational levels. Mechanistically, BDMC was found to activate the JAK2/STAT3 pathway; whereas AG490 (JAK2/STAT3 pathway inhibitor) inhibited BDMC functioning. Subsequently, we found that the combinatorial therapy of BDMC and hAMSC had a positive synergistic effect on osteoporotic mouse model induced by bilateral ovariectomy, including inhibiting bone loss and bone resorption and improving bone micro-architecture. Moreover, BDMC inhibited production of the bone resorption markers C-terminal telopeptide of type I collagen, and tartrate resistant acid phosphatase, while promoting serum levels of bone formation markers OCN, and procollagen I N-terminal propeptide. BDMC also improved liver and kidney function in osteoporotic mouse model. Collectively, BDMC improved osteoporosis by enhancing hAMSC osteogenesis and exhibited a protective effect on liver and kidney function in an osteoporotic mouse model. Hence, BDMC may serve as an effective adjuvant, and combined therapy with hAMSCs is a promising new approach toward osteoporosis treatment.

Glucose-lowering and hypolipidemic activities of polysaccharides from Cordyceps taii in streptozotocin-induced diabetic mice.

BACKGROUND: Hyperglycemia and dyslipidemia are classic features of patients with diabetes mellitus (DM). Cordyceps taii, a folk medicinal fungus native to southern China, possesses various pharmacological activities. This study aimed to assess the glucose-lowering and hypolipidemic effects of polysaccharides from C. taii (CTP) in streptozotocin (STZ)-induced diabetic mice. METHODS: Kunming mice were intraperitoneally injected with STZ at a dose of 100 mg/kg body weight. After induction of diabetes, diabetic mice were randomly divided into five groups: diabetic mellitus group (DM), metformin-treated group, low, medium, and high-dose CTP-treated group (CTP-L, CTP-M, and CTP-H). Normal mice served as the control group. After treatment for 28 days, body weight, fasting serum insulin (FSI), fasting blood glucose (FBG), homeostasis model assessment-insulin resistance (HOMA-IR), triglyceride (TG), total cholesterol (TC), low-density lipoprotein-cholesterol (LDL-C), high-density lipoprotein-cholesterol (HDL-C), tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and C-reactive protein (CRP) levels were measured. Histological analysis of pancreatic tissue and immune organ indices was also performed to evaluate the anti-diabetes effect of CTP. SPSS (version 21.0) software was used for statistical analysis, and statistical differences were considered significant at p < 0.05. RESULTS: Compared with the DM group, the body weight and FSI level of CTP-H group increased by 36.13 and 32.47%, whereas the FBG and HOMA-IR decreased by 56.79 and 42.78%, respectively (p < 0.05). Histopathological examination of the pancreas revealed that CTP improved and repaired the impaired islet ß-cells in pancreatic tissue. Compared with the DM group, the levels of TC, TG, and LDL-C decreased by 13.84, 31.87, and 36.61%, whereas that of HDL-C increased by 28.60% in CTP-H (p < 0.05). Further study showed that the thymus index in CTP-H was elevated by approximately 54.96%, and the secretion of pro-inflammatory cytokines TNF-α, IL-6, and CRP was inhibited by approximately 19.97, 34.46, and 35.41%, respectively (p < 0.05). CONCLUSION: The anti-diabetes effect of CTP is closely associated with immunoregulation and anti-inflammation, and CTP may be considered as a therapeutic drug or functional food for DM intervention.

Antitumor and antimetastatic activities of chloroform extract of medicinal mushroom Cordyceps taii in mouse models.

BACKGROUND: Cordyceps taii, an entomogenous fungus native to south China, is a folk medicine with varieties of pharmacological activities including anticancer effect. To validate the ethnopharmacological claim against cancer, the antitumor and antimetastatic activities of chloroform extract of C. taii (CFCT) were investigated in vivo. METHODS: The in vitro cytotoxic activities of CFCT against human lung cancer (A549) and gastric cancer (SGC-7901) cells were evaluated using the Sulforhodamine B (SRB) assay. In vivo anti tumor and antimetastatic activities, Kunming mice bearing sarcoma 180 and C57BL/6 mice bearing melanoma B16F10 were employed, respectively. The antitumor effects of CFCT were completely evaluated on the basis of the tumor weight, survival time, histologic analysis, and immune organ indices. The histopathological change, metastatic foci and malignant melanoma specific marker HMB45 in the lung tissue were detected for the evaluation of the antimetastatic activity of CFCT. RESULTS: CFCT exhibited dose- and time-dependent cytotoxicities against A549 and SGC-7901 cells with the IC50 values of 30.2 and 65.7 µg/mL, respectively. Furthermore, CFCT at a dose of 50 or 100 mg/kg could significantly inhibit the tumor growth in vivo and prolonged the survival time in two different models as compared with the model group, especially when combined with the CTX at a low dose rate. And it also increased spleen index of Kunming mice and thymus index of C57BL/6 mice. Meanwhile, histologic analysis illustrated that CFCT alone or in combination with CTX could induce tumor tissue necrosis of both models. In addition, CFCT at a dose of 50 or 100 mg/kg inhibited the lung metastasis of melanoma B16F10 in tumor-bearing C57BL/6 mice. The antimetastatic effect was also observed when CFCT was used in combination with CTX. In comparison to any other groups, CFCT at a dose of 100 mg/kg could effectively enhance the GSH-Px activities of various tissues in tumor-bearing C57BL/6 mice. CONCLUSIONS: These findings demonstrate that CFCT has potent in vivo antitumor and antimetastatic activities, and may be helpful to the development of anticancer chemopreventive agents from C. taii.

[Research progress on hypoglycemic effect and its mechanism of action of medicinal fungal polysaccharides].

Due to substantial morbidity and high complications, diabetes mellitus is considered as the third "killer" in the world. Medicinal fungal polysaccharides, as water-soluble macromolecular substances with low toxicity, exhibit diversified pharmacological actions such as immune regulation, anti-tumor, antivirus, antioxidant, anti-aging, hypoglycemic effect and improving liver and kidney function. In recent year, a number of investigators reported medicinal fungal polysaccharides showed good anti-diabetes and hypoglycemic activity, and their acting mechanisms involved in glycometabolism and ß cell function, e. g. promoting glycogen synthesis, promoting glycolysis, inhibiting the activity of α-glucosidase, promoting insulin secretion, increasing insulin sensitivity, enhancing antioxidation. Therefore, the hypoglycemic activity and its mechanisms of action of medicinal fungal polysaccharides showed characteristics of multiple effects, multi-target, and multi-pathway regulation. These finding suggest that medicinal fungal polysaccharides are a promising source for the development of discovery of anti-diabetic agent.

Nucleosides, a valuable chemical marker for quality control in traditional Chinese medicine Cordyceps.

Cordyceps, a well-known traditional Chinese medicine, is an endoparasitic and/or symbiotic macrofungus in the body of insect and other arthropod, and has received increasing attention worldwide due to its rarity and outstanding curative effects for different diseases. Recent years, however, the counterfeits and mimics of Cordyceps are frequently found in markets because of its scarce in nature and high in price. Therefore, quality control of Cordyceps and its bioproducts is very important to ensure their safety and efficacy. Nucleoside is recognized as a major active component of Cordyceps, and even is used as chemical marker for quality control of Cordyceps. In this present review, recent studies and associated patents, with regard to the chemical marker nucleosides for quality control of Cordyceps and its bioproducts, including nucleoside components, pharmacological activities, and analytical methods were reviewed and discussed thereof. Also, developing trends in the field have been appraised.

[Advance and prospect of studies on bioactivity and mechanism of Cordyceps fungi].

Cordyceps is a precious medical fungi resource, with diverse metabolites and bioactive. There is huge prospect for its applicaiton in functional food and biomedicine fields. Cordyceps has abundant species resources, particularly Cordyceps sinensis is one of three most precious traditional Chinese restoratives in China. The essay summarizes the latest studies on bioactivity and mechanism of Cordyceps and its metabolites, and analyzes problems during R&D of the resources, in order to bring forth new ideas to future development.

[Current studies and prospect of anti-thrombotic effect of Cordyceps fungi].

Cordyceps is an entomogenous fungi developed after being infected by insects or arthropods. Many varieties of entomogenous fungus show a huge application prospect in functional food and biological medicine fields. Among them, famous herb C. sinensis is their most excellent representative, and mainly used to replenish kidneys and moisten lungs, treating fatigue, night sweating, cardiovascular diseases, respiratory diseases, hypertension, hyperlipidemia, hyperglycemia, renal failure and so on. Currently, as a medicinal resource, C. sinensis has aroused attention from the world. In the past 20 years, many studies found that Cordyceps fungi show the anti-thrombotic effect, as well as a good potential for becoming a patent medicine. This article summarizes studies on Cordyceps fungi's effects in reducing blood viscosity and resisting platelet aggregation and anticoagulant, so as to provide thought for developing and utilizing these resources as anti-thrombotic medicines.

Jiangxienone, a new compound with potent cytotoxicity against tumor cells from traditional Chinese medicinal mushroom Cordyceps jiangxiensis.

A new compound, named jiangxienone, has been isolated from a culture of the traditional Chinese medicinal mushroom Cordyceps jiangxiensis, and its chemical structure was established on the basis of spectroscopic and chemical techniques. Jiangxienone showed potent cytotoxic effects against human gastric adenocarcinoma SGC-7901 cell and human lung carcinoma A549 cell with IC(50) values ranging from 1.38 to 2.93 µM, i.e., with at least approximately six-fold stronger cytotoxicity than cisplatin, a first-line chemotherapy drug for cancer patients.

Polysaccharides from the Medicinal Mushroom Cordyceps taii Show Antioxidant and Immunoenhancing Activities in a D-Galactose-Induced Aging Mouse Model.

Cordyceps taii, an edible medicinal mushroom native to south China, is recognized as an unparalleled resource of healthy foods and drug discovery. In the present study, the antioxidant pharmacological properties of C. taii were systematically investigated. In vitro assays revealed the scavenging activities of the aqueous extract and polysaccharides of C. taii against various free radicals, that is, 1,1-diphenyl-2-picrylhydrazyl radical, hydroxyl radical, and superoxide anion radical. The EC(50) values for superoxide anion-free radical ranged from 2.04 mg/mL to 2.49 mg/mL, which was at least 2.6-fold stronger than that of antioxidant thiourea. The polysaccharides also significantly enhanced the antioxidant enzyme activities (superoxide dismutase, catalase, and glutathione peroxidase) and markedly decreased the malondialdehyde production of lipid peroxidation in a D-galactose-induced aging mouse model. Interestingly, the immune function of the administration group was significantly boosted compared with the D-galactose-induced aging model group. Therefore, the C. taii polysaccharides possessed potent antioxidant activity closely associated with immune function enhancement and free radical scavenging. These findings suggest that the polysaccharides are a promising source of natural antioxidants and antiaging drugs. Consequently, a preliminary chemical investigation was performed using gas chromatography-mass spectroscopy and revealed that the polysaccharides studied were mainly composed of glucose, mannose, and galactose. Fourier-transform infrared spectra also showed characteristic polysaccharide absorption bands.

Secondary metabolites from Cordyceps species and their antitumor activity studies.

Cordyceps, an entomopathogenic mushroom, is a famous traditional Chinese medicinal herb (TCM). This higher fungus contains various known and untapped bioactive metabolites, and is looked at as an important source of natural drugs while simultaneously provides good opportunities for discovering new drugs with immunomodulatory, antitumor, hypoglycemic and hypocholesterolemic functions. Therefore, the Cordyceps spp. has been receiving an increasing interest around the world as an interesting natural drug resource. Various secondary metabolites from Cordyceps fungi were reported to have antitumor activities, and antitumor mechanism of those bioactive compounds possesses multi-target, multi-level and multi-pathway characteristics. Challenges in investigations on Cordyceps fungi include the further elucidation of antitumor molecular mechanism and relationship between structure and function of their secondary metabolites.