A 75 kDa glycoprotein isolated from Cudrania tricuspidata Bureau induces colonic epithelial proliferation and ameliorates mouse colitis induced by dextran sulfate sodium / 中国天然药物

Cudrania tricuspidata Bureau (CTB), a species of the Moraceae plant, has been used as a bruise recovery treatment. This study aimed to determine whether the 75 kDa phytoglycoprotein extracted from CTB has a regulatory effect on the proliferation of human colon epithelial cells and the pathological process of inflammatory bowel disease (IBD). We found that CTB glycoprotein significantly induces the proliferation of human colon epithelial HT-29 cells by activating protein kinase C. CTB glycoprotein stimulated the phosphorylation of c-Jun N-terminal kinase and transcription factor nuclear factor-κB, which are responsible for the expression of cell-cycle-related proteins (CDK2, CDK4, cyclin D1 and cyclin E) during its promotion of cell proliferation. Experimental colitis was induced in mice by adding dextran sulfate sodium to their drinking water at a concentration of 4% (W/V) for seven days. We found that CTB glycoprotein ameliorates the pathological process of IBD and lowers the disease activity index score, which was composed of body weight change, diarrhea, and hematochezia in ICR mice treated with dextran sulfate sodium. Hence, we suggest that CTB glycoprotein has the ability to prevent IBD by promoting cell proliferation signaling events via the activation of PKC, JNK and NF-κB in colon epithelial cells.

Inhibition of Total Flavonids from Cudrania tricuspidata Bun on Lewis Lung Cancer and the Effect of Its Component Compatibility on Autophagy of LLC Cells / 中国药学杂志

OBJECTIVE: To explorethe effect of total flavonoids from Cudrania tricuspidata Bun on Lewis lung cancer mice and its new component compatibility on the autophagy of LLC cells. METHODS: A mouse model of Lewis lung cancer xenografts was constructed. The body weight, tumor weight, tumor volume and organ index were measured before and after taking total flavonoids of Cudrania tricuspidata Bun. The HE staining of the xenograft pathological sections were also observed. The TNF-α, IL-2, IL-6 and IL-12 levels in the serum were calculated by ELISA. The content of the main active ingredient and its ratio in the flavonoid extract were measured by UPLC. Western blot was used to detect the effect of the new component compatibility on the expression of autophagy protein in LLC cells, and the ultra structural changes of LLC cells were observed by transmission electron microscopy. Flow cytometry was used to detect the effect of the new component compatibility on autophagy of LLC cells. RESULTS: The high-dose group of total flavonoids from Cudrania tricuspidata Bun can significantly inhibit the growth of tumor in mice and enhance the organ index of tumor-bearing mice, and the survival rate of mice could be improved in all groups of total flavonoids from Cudrania tricuspidata Bun. The serum levels of TNF-α, IL-2, IL-6 and IL-12 in the tumor-bearing mice of each group were higher than those in the model group, and there was significant difference in the high dose group of total flavonoids (P<0.01). The main active ingredients were taxifolin, kaempferol and naringenin by UPLC. The ratio of taxifolin to kaempferol was 60:1. Western blot assay showed that its new component compatibility significantly increased the expression of autophagic protein in LLC cells (P<0.01). The autophagosomes in the cytoplasm were observed by transmission electron microscopy. The results of flow experiments showed that the average fluorescence intensity of its new component compatibility was significantly higher than that of the control group. CONCLUSION: Total flavonoids of Cudrania tricuspidata Bun can effectively inhibit tumor growth and have less harm to immune organs. Its mechanism may be related to up-regulation of cytokines TNF-α, IL-2, IL-6 and IL-12 levels and improve immune function in the body. Moreover, its main active ingredient promotes the increase of autophagy protein expression in LLC cells and induces autophagy in LLC cells.

Isolation and content determination of taxifolin, orobol and quercetin in Cudrania tricuspidata / 国际中医中药杂志

Objective To isolate and identify 3 flavonoids (taxifolin, orobol and quercetin) from Cudrania tricuspidata, and develop a method for determining 3 flavonoid constituents in Cudrania tricuspidata. Methods Three flavonoids was isolated from ethanol extract of Cudrania tricuspidata by chromatography, and its structure was identified by nuclear magnetic resonance. The analysis was conducted on an Aglient C18 column (4.6 mm ×250 mm, 5 μm) eluted with 1％ acetic acid and methanol as mobile phases in gradient mode. The flow rate was 1 ml/min and the detection wavelength was set at 310 nm. The column temperature was 25 ℃. Results Taxifolin, orobol and quercetin were isolated from ethanol extract of Cudrania tricuspidata by chromatography. The content of taxifolin, orobol and quercetin were 0.850 mg/g, 0.518 mg/g, 0.103 mg/g. Conclusion The method can be used for the quality control of Cudrania tricuspidata as a reference.

Adverse drug reactions after taking the extract of Cudrania tricuspidata

Cudrania tricuspidata is a deciduous tree belonging to the Moraceae plant, which has been widely used as a folk remedy or health supplements in the Asian countries including Korea. As far as we know, side effects from taking the extract of C. tricuspidata has not yet been reported. We reviewed the electronic medical records of 2 patients who had adverse drug reactions to C. tricuspidata. The first case was a 30-year-old woman without a specific medical history. She was admitted with a 2-week history of jaundice and dyspepsia after taking extract of C. tricuspidata for 3 days. Initial laboratory findings were as follows: aspartate aminotransferase, 364 IU/L; alanine aminotransferase, 574 IU/L; total bilirubin, 36.3 mg/dL; and direct bilirubin, 18.3 mg/dL. She was conservatively treated for liver and renal failure while awaiting liver transplantation. However, she was expired due to combined pneumonia and progressed hepatic and renal failure. The second case was a 42-year-old woman who has chronic urticaria without other medical history. She was admitted with a 3-month history of whole body rash with small pustular vesicle after taking extract of C. tricuspidata. She was treated with intravenous steroids and antihistamines. Skin lesions were improved after 1 week. Here, we report 2 cases of adverse drug reaction to C. tricuspidata. It should be considered that C. tricuspidata ingestion could cause severe adverse drug reactions such as liver failure and acute generalized exanthematous pustulosis.

Ethyl acetate fraction from Cudrania tricuspidata inhibts IL-1β-induced rheumatoid synovial fibroblast proliferation and MMPs, COX-2 and PGE2 production

Objectives: The objective of this study is to determine the effects of Ethyl acetate fraction from Cudrania tricuspidata (EACT) on the interleukin-1b (IL-1b)-induced proliferation of rheumatoid synovial fbroblasts (RASFs) and production of matrix metalloproteinases (MMPs), cyclooxygenase (COX) and prostaglandin E2 (PGE2) by RASFs. Materials and Methods: The proliferation of RASFs was evaluated with CCK-8 reagent in the presence of IL-1b with/without EACT. The expression of MMPs, TIMP-1, COXs, PGE2 and intracellular MAPK signalings, including p-ERK, p-p38, p-JNK and NF-kB were examined by immunoblotting or semi-quantitative reverse transcription-polymerase chain reaction (RT-PCR) and ELISA in conditions as described above. Results: EACT inhibits IL-1β-induced proliferation of RASFs and MMP-1, 3, COX-2 mRNA and protein expression, PGE2 production induced with IL-1b. EACT also inhibits the phosphorylation of ERK-1/2, p38, JNK and activation of NF-kB by IL-1b. Conclusions: These results suggest that EACT might be involved in synovial fbroblast proliferation and MMPs, COX-2, and PGE2 production, which are involved in joint destruction in rheumatoid arthritis (RA), indicating that this might be a new therapeutic modality for management of rheumatoid arthritis.

Expression of HSP70,c-fos following focal cerebral ischemic reperfusion in rats and neuroprotective effect of Cudrania tricuspidata / 临床神经病学杂志

Objective To investigate the expression of heat shock protein 70(HSP70) and c-fos,the presence of apoptosis and the neuroprotective effects of Cudrania tricuspidata root extrate(Ecr) after focal cerebral ischemic reperfusion in rats.Methods Models of middle cerebral artery occlusion(MCAO) were used in this study.The rats in Ecr pretreated ischemia reperfusion(IR) group were fed with Ecr(2 ml tid) for 5 days before MCAO.The brain specimen were took at different reperfusion times: 1 h,6 h,12 h,24 h,3 d and 7 d after recirculation.Then immunohistochemistry,insitu hybridization,terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling(TUNEL) were used to detect the expression of HSP70,c-fos gene and cell apoptosis in the brains.Positive results were semiquantitatively analyzed.Results IR could induce the expression of HSP70 and c-fos.HSP70 was detected at 6 h following reperfusion and peaked at 24 h both in cortical and basal ganglia regions.c-fos was markedly expressed at 1 h and the level peaked at 6 h in the ischemic hemispheres,and then reduced gradually.The TUNEL positive cells were markedly observed at 6 h.After treatment with Ecr,the positive reaction cells both of HSP70 and c-fos were significantly increased(all(P

Studies on the chemical constituents of Cudrania tricuspidata / 中成药

Objective: To study chemical constituents of Cudrania tricuspidata . Method: The 80% ethanolic extract of Cudrania tricuspidata was analyzed by column chromatography of silica gel and Sephadex LH 20. Result: Six compounds were extracted from the ethanolic extract part. Conclusion: They were elucidated as syringaresinol, schizandrin, gomisin A, gomisin H, ? sitosterol and ? sitosterol 3 O ? D glucopyranoside respectively. Among them, syringaresinol, schizandrin, gomisin A, gomisin H were obtained from this species for the first time.