curcumin and triptolide

Autosomal dominant polycystic kidney disease (ADPKD) is a monogenic kidney disorder that impairs renal functions progressively leading to kidney failure. The disease affects between 1:400 and 1:1000 ratio of the people worldwide. It is caused by the mutated PKD1 and PKD2 genes which encode for the defective polycystins. Polycystins mimic the receptor protein or protein channel and mediate aberrant cell signaling that causes cystic development in the renal parenchyma. The cystic development is driven by the increased cyclic AMP stimulating fluid secretion and infinite cell growth. In recent years, natural product-derived small molecules or drugs targeting specific signaling pathways have caught attention in the drug discovery discipline. The advantages of natural products over synthetic drugs enthusiast researchers to utilize the medicinal benefits in various diseases including ADPKD.. Overall, this review discusses some of the previously studied and reported natural products and their mechanisms of action which may potentially be redirected into ADPKD.

Topics: Antioxidants; Chalcones; Curcumin; Diterpenes; Diterpenes, Kaurane; Emodin; Epoxy Compounds; Estrogen Antagonists; Flavanones; Humans; Hypoglycemic Agents; Metformin; Phenanthrenes; Plant Extracts; Polycystic Kidney, Autosomal Dominant; Protein Kinase Inhibitors; Quercetin; Resveratrol

The proteasome is a multicatalytic protease complex whose activity is required for the growth of normal or tumor cells. It has been shown that human cancer cells are more sensitive to proteasome inhibition than normal cells, indicating that the proteasome could be a target of chemotherapy. Studies suggest that traditional Chinese medicine (TCM) is an effective approach for cancer treatment. Here we reviewed several TCMs for their potential in treatment of cancer. This short review focuses mainly on the TCMs that potentially target the tumor cellular proteasome and NF-kappaB pathway whose activation is dependent on the proteasome activity.

Topics: Animals; Antineoplastic Agents, Phytogenic; Benzyl Compounds; Curcumin; Diterpenes; Drug Delivery Systems; Drug Screening Assays, Antitumor; Drugs, Chinese Herbal; Epoxy Compounds; Humans; Medicine, Chinese Traditional; Molecular Structure; Naphthoquinones; Neoplasms; Pentacyclic Triterpenes; Phenanthrenes; Phenols; Proteasome Endopeptidase Complex; Signal Transduction; Triterpenes

Triptolide has proven to possess anticancer potential and been widely used for anti-cancer research. However, the liver and kidney toxicity has limited its application in cancer treatment. In this study, a drug delivery system based on mPEG-DPPE/calcium phosphate was developed to co-load triptolide and curcumin (TP and Curc-NPs). The coefficient of drug interaction (CDI) was calculated to determine the optimal concentration of the two drugs. When the concentration of triptolide was 25.22 ng/mL and the concentration of curcumin was 6.62 μg/mL, the two drugs reached the maximum synergistic killing effects on SKOV-3 tumor cells. The TP and Curc-NPs was prepared using ultrasonic emulsification. Flow cytometry results revealed that the TP and Curc-NPs arrested cell-cycle in the S and G2/M phases and exhibited a strong ability to induce apoptosis. Intracellular reactive oxygen species (ROS) results indicated that curcumin could reduce the intracellular ROS level caused by triptolide. The mRNA levels of heat shock protein (HSP) were detected by qTR-PCR and the results showed that the TP and Curc-NPs could lower the HSP70 mRNA level while could not reduce the HSP90 mRNA level. The animal experiments demonstrated the favorable curative effects of the TP and Curc-NPs, and the tumor inhibition rate reached 68.78%. The results of the pathological examinations demonstrated that the nanoparticles had no significant toxic effects on important organs. In conclusion, the TP and Curc-NPs exerted synergistic effects on ovarian cancer in vitro and in vivo, and the toxicity caused by triptolide may be reduced by curcumin through anti-oxidative stress effects. The TP and Curc-NPs could be a promising strategy for ovarian cancer.

Topics: Animals; Apoptosis; Calcium Phosphates; Cell Line, Tumor; Curcumin; Diterpenes; Epoxy Compounds; Female; Nanoparticles; Ovarian Neoplasms; Phenanthrenes; Phenyl Ethers; Polyethylene Glycols

As natural medicines in Asia, curcumin and triptolide extracted from different drug plants have proven to possess anticancer potential and widely used for anti-cancer research. The present study attempted to clarify that curcumin and triptolide synergistically suppress ovarian cancer cell growth in vitro.. To test synergic effects, cell viability and apoptosis were analyzed after curcumin and triptolide combination treatment on ovarian cancer cell lines. Synergistic effects on apoptosis induction were determined by lactate dehydrogenase (LDH) leakage assay, intracellular reactive oxygen species (ROS) assay, mitochondrial membrane potential (MMP) loss assay and flow cytometry analysis. Critical regulators of cell proliferation and apoptosis related were analyzed by qRT-PCR and Western blotting.. We showed that the combination of curcumin and triptolide could synergistically inhibit ovarian cancer cell growth, and induce apoptosis, which is accompanied by HSP27 and HSP70, indicating that HSP27 and HSP70 play the important role in the synergic effect.. From the result present here, curcumin and triptolide combination with lower concentration have a synergistic anti-tumor effect on ovarian cancer and which will have a good potential in clinical applications.

Topics: Antineoplastic Agents, Hormonal; Apoptosis; Blotting, Western; Cell Proliferation; Curcumin; Diterpenes; Drug Synergism; Epoxy Compounds; Female; HSP27 Heat-Shock Proteins; HSP70 Heat-Shock Proteins; Humans; L-Lactate Dehydrogenase; Membrane Potential, Mitochondrial; Ovarian Neoplasms; Phenanthrenes; Reactive Oxygen Species; Real-Time Polymerase Chain Reaction; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger; Tumor Cells, Cultured

Traditional medicines provide fertile ground for modern drug development, but first they must pass along a pathway of discovery, isolation, and mechanistic studies before eventual deployment in the clinic. Here, we highlight the challenges along this route, focusing on the compounds artemisinin, triptolide, celastrol, capsaicin, and curcumin.

Topics: Animals; Artemisinins; Capsaicin; Curcumin; Diterpenes; Drug Approval; Drug Evaluation, Preclinical; Epoxy Compounds; Humans; Medicine, Traditional; Pentacyclic Triterpenes; Phenanthrenes; Plant Preparations; Technology, Pharmaceutical; Triterpenes

Crohn's disease (CD) patients have an abnormal increase in intestinal epithelial permeability. The defect in intestinal tight junction (TJ) barrier has been proposed as an important etiologic factor of CD. TNF-alpha increases intestinal TJ permeability. Because TNF-alpha levels are markedly increased in CD, TNF-alpha increase in intestinal TJ permeability could be a contributing factor of intestinal permeability defect in CD. Our purpose was to determine some of the intracellular mechanisms involved in TNF-alpha modulation of intestinal epithelial TJ permeability by using an in vitro intestinal epithelial system consisting of filter-grown Caco-2 monolayers. TNF-alpha produced a concentration- and time-dependent increase in Caco-2 TJ permeability. TNF-alpha-induced increase in Caco-2 TJ permeability correlated with Caco-2 NF-kappa B activation. Inhibition of TNF-alpha-induced NF-kappa B activation by selected NF-kappa B inhibitors, curcumin and triptolide, prevented the increase in Caco-2 TJ permeability, indicating that NF-kappa B activation was required for the TNF-alpha-induced increase in Caco-2 TJ permeability. This increase in Caco-2 TJ permeability was accompanied by down-regulation of zonula occludens (ZO)-1 proteins and alteration in junctional localization of ZO-1 proteins. TNF-alpha modulation of ZO-1 protein expression and junctional localization were also prevented by NF-kappa B inhibitors. TNF-alpha did not induce apoptosis in Caco-2 cells, suggesting that apoptosis was not the mechanism involved in TNF-alpha-induced increase in Caco-2 TJ permeability. These results demonstrate for the first time that TNF-alpha-induced increase in Caco-2 TJ permeability was mediated by NF-kappa B activation. The increase in permeability was associated with NF-kappa B-dependent downregulation of ZO-1 protein expression and alteration in junctional localization.

Topics: Apoptosis; Binding Sites; Biotransformation; Blotting, Western; Caco-2 Cells; Cell Membrane Permeability; Curcumin; Diterpenes; DNA; Down-Regulation; Electrophoretic Mobility Shift Assay; Epoxy Compounds; Fluorescein; Humans; Intestinal Mucosa; Membrane Proteins; NF-kappa B; Phenanthrenes; Phosphoproteins; Precipitin Tests; Tight Junctions; Tumor Necrosis Factor-alpha; Zonula Occludens-1 Protein