Astragalus membranaceus (Huangqi) and Rhizoma curcumae (Ezhu) decoction suppresses colorectal cancer via downregulation of Wnt5/β-Catenin signal

Background The decoction of Astragalus membranaceus (Huangqi) and Rhizoma curcumae (Ezhu) has been reported as a potential antitumor agent for colorectal cancer (CRC) in experimental and clinical studies, but its underlying mechanism is still unclear. Methods The current research aims to explore the potential of Astragalus membranaceus (Huangqi) and Rhizoma curcumae (Ezhu) decoction (AR decoction) in the treatment of CRC and explore the underlying mechanism. SW620 cells were transient transfection to overexpress or knock down wnt 5 or β-Catenin. Astragalus membranaceus (Huangqi) and Rhizoma curcumae (Ezhu) -containing serum (AR-CS) was used to interfere with SW620 cells. Additional AR-CS, Wnt5 inhibitor (IWP-4), and β-Catenin inhibitor (JW55) were used to intervene in SW620 cells. Furthermore, subcutaneously injection of SW620 cells into the right flank of nude mice replicated xenograft mice, which were treated with AR decoction for 21 days. Results AR-CS significantly reduced the mRNA and protein expression levels of Wnt5, β-Catenin, ARF6, and N-Cadherin in SW620 cells, while inhibiting the proliferation and migration of SW620 cells. In cells overexpressing Wnt5 or β-Catenin, these effects of AR-CS were significantly suppressed. On the contrary, the inhibitory effect of AR-CS on the mRNA and protein levels of ARF6 and N-Cadherin and cell proliferation and migration of SW620 was enhanced, when Wnt5 or β-Catenin were knocked down or suppressed by the inhibitors. Moreover, in the mouse model of xenograft tumors, AR decoction not only reduced the tumor volume and inhibited the mRNA levels and protein levels of Wnt5, β-Catenin, ARF6, and N-Cadherin in the tumor, but also inhibit the protein levels of LRP5, LRP6, TCF-4, and LEF1.The histopathology of mice also showed increased apoptosis in tumor tissues, and AR decoction treatment did not cause pathological damage to the kidney and liver. Conclusions Our results provide evidence that AR decoction inhibits Wnt5/β-catenin signaling and inhibits the development of CRC, which is a promising traditional medicine in the clinical treatment of CRC.

Comparison of curcumin and methylprednisolone in the prevention of epidural fibrosis after spinal surgery: An experimental study

We aimed to compare the effectiveness of curcumin, which has been shown to inhibit cell migration and proliferation, with that of methylprednisolone, which has been shown to have a similar mechanism of action to that of curcumin and to delay tissue repair and wound healing, in the prevention of epidural fibrosis in an experimental laminectomy model in rats. The experiment was conducted with 40 male Wistar rats weighing 250-300 g which were divided into four groups. Laminectomy was performed from L1 to L4 in all groups. Curcumin and methylprednisolone were applied to the other two groups except the control and DMSO groups. The vertebral colon was excised en bloc and each section was examined for epidural fibrosis formation under a light microscope to evaluate histologically using the grading system. Results: The statistical analyses indicated that the treatment groups had a significant effect on the histological grades of epidural fibrosis in rats compared to the control group. Curcumin, derived from the rhizome (Rhizoma Curcumae) of turmeric (Curcuma longa) was found to show a significant effect in the prevention of epidural fibrosis formation with its potent antioxidant and anti-inflammatory properties and by inhibiting further recruitment of fibroblasts to the laminectomy area. In the present study, both histological examination and statistical analyses indicated that the administration of curcumin led to a remarkable reduction in epidural fibrosis after laminectomy.

Inhibition of Fibroblast Activation in Uterine Leiomyoma by Components of Rhizoma Curcumae and Rhizoma Sparganii

Background: The herbs Rhizoma Curcumae and Rhizoma Sparganii (RCRS) are often used in traditional Chinese medicine for the treatment of uterine leiomyoma (UL). The effectiveness of RCRS for the treatment of UL has been confirmed in our previous studies.Purpose: This study aimed to investigate the molecular mechanism by which RCRS inhibits the activation of fibroblast activation protein (FAP) and prevents UL in rats.Study Design and Methods: A Sprague Dawley (SD) rat model of UL was established via estrogen and progesterone load combined with external stimulation. Histological analyses, enzyme-linked immunosorbent assays, and western blotting were performed to evaluate the effect of RCRS on UL and elucidate its mechanism of action.Results: Our data showed that the treatment of SD rats with RCRS significantly reduced the expression of extracellular matrix component collagen, FAP, and transforming growth factor beta (a FAP-activating factor) and the phosphorylation of the cell proliferation pathway-related signaling factors AKT/MEK/ERK.Conclusion: Our results suggest that RCRS is effective in the prevention and treatment of UL in rats, and RCRS may exert its functions by inhibiting the activation of tumor-associated fibroblasts and cell proliferation and by improving the tumor extracellular matrix.

The essential oil from the raw and vinegar processed Rhizoma Curcumae ameliorate CCl4-incuded liver fibrosis: integrating network pharmacology and molecular mechanism evaluation

Liver fibrosis caused by multiple chronic liver injuries, is a known contributor to cirrhosis, and even liver cancer. Rhizoma Curcumae as a Traditional Chinese Medicine (TCM) has been extensively used...

Comparison of Curcumin and Methylprednisolone in Preventing Epidural Fibrosis After Spinal Surgery: An Experimental Study

Aim:We aimed to compare the effectiveness of curcumin, which has been shown to inhibit cell migration and proliferation, with that of methylprednisolone, which has been shown to have a similar mechanism of action to that of curcumin and to delay tissue repair and wound healing, in the prevention of epidural fibrosis in an experimental laminectomy model in rats.Material and methods:The experiment was conducted with 40 male Wistar rats weighing 250-300 g which were divided into four groups. Laminectomy was performed from L1 to L4 in all groups. Curcumin and methylprednisolone were applied to the other two groups except the control and Dmso groups. The vertebral colon was excised en bloc and each section was examined for epidural fibrosis formation under a light microscope to evaluate histologically using the grading system.Results:The statistical analyses indicated that the treatment groups had a significant effect on the histological grades of epidural fibrosis in rats compared to the control group.Discussion:Curcumin, derived from the rhizome (Rhizoma Curcumae) of turmeric (Curcuma longa) was found to show a significant effect in the prevention of epidural fibrosis formation with its potent antioxidant and anti-inflammatory properties and by inhibiting further recruitment of fibroblasts to the laminectomy area.Conclusions:In the present study, both histological examination and statistical analyses indicated that the administration of curcumin led to a remarkable reduction in epidural fibrosis after laminectomy.

Transcriptome analysis of Curcuma wenyujin from Haikou and Wenzhou, and a comparison of the main constituents and related genes of Rhizoma Curcumae

For more than a thousand years, Rhizoma Curcumae (known as E zhu), a Chinese herbal medicine, has been used to eradicate blood stasis and relieve aches. The plant Curcuma wenyujin, which is grown primarily in Wenzhou, China, is considered the best source of Rhizoma Curcumae. In this study, we sought to ascertain differences in transcript profiles of C. wenyujin grown in traditional (Wenzhou) and recently established (Haikou) production areas based on Illumina and RNA (RNA-seq) sequencing. We also examined differences in the main components of the volatile oil terpene; curcumin, polysaccharide, and starch constituents and related genes in the corresponding pathways, in C. wenyujin cultivated in the two production areas. We accordingly found that the essential oil (2.05%), curcumin (1.46%), and polysaccharide (8.90%) content in Wenzhou rhizomes was higher than that in the rhizomes of plants from Haikou (1.60%, 0.91%, and 6.15%, respectively). In contrast, the starch content of Wenzhou rhizomes (17.0%) was lower than that of Haikou rhizomes (23.8%). Furthermore, we detected significant differences in the oil components of Haikou and Wenzhou rhizomes, with curzerene (32.34%), curdione (21.35%), and germacrene B (9.39%) being the primary components of the essential oil derived from Wenzhou rhizomes, and curzerene (20.13%), curdione (14.73%), and cineole (9.76%) being the main constituents in Haikou rhizomes. Transcriptome and qPCR analyses revealed considerable differences in gene expression between Wenzhou and Haikou rhizomes. The expression of terpene, curcumin, and polysaccharide pathway-related genes in Wenzhou rhizomes was significantly up-regulated, whereas the expression of starch-associated genes was significantly down-regulated, compared with those in Haikou rhizomes. Difference in the content of terpene, curcumin, polysaccharides, and starch in rhizomes from the two production areas could be explained in terms of differences in expression of the related genes.

Inhibition of Fibroblast Activation by Components of Rhizoma Curcumae and Rhizoma Sparganii in A Rat Model of Uterine Leiomyoma

Background: Traditional Chinese medicine (TCM) often uses Rhizoma Curcumae and Rhizoma Sparganii (RCRS) ，the natural herbs for the treatment of UL. RCRS has been shown to be effective in the treatment of UL in our previous study. This study was to investigate the molecular mechanism by which RCRS inhibits fibroblast activation protein (FAP) activation and prevents uterine leiomyoma in rats. Methods: The SD rat model of uterine leiomyoma was established by estrogen and progesterone load combined with external stimulation. Subsequently, histological analyses, enzyme-Linked immunosorbent assays, western blotting were performed to evaluate the effect of the drug on uterine leiomyoma and its mechanism. Results: Our data showed that treatment of rats with RCRS significantly reduced the expression of FAP, TGF-β (the FAP activating factor), and significantly decreased the phosphorylation of cell proliferation pathway-related signaling factors AKT/MEK/ERK, as well as the expression of the extracellular matrix component collagen. Conclusions: Our results showed that RCRS is very effective in prevention and treatment of uterine leiomyoma in rats, and RCRS may exert its actions by inhibiting the activation of tumor-associated fibroblasts, inhibiting the cell proliferation, and improving tumor extracellular matrix.

Study on the Drug Targets and Molecular Mechanisms of Rhizoma Curcumae in the Treatment of Nasopharyngeal Carcinoma Based on Network Pharmacology

Aim. To analyse the target of Rhizoma Curcumae in nasopharyngeal carcinoma by using network pharmacological techniques and to explore the associated molecular mechanism. Methods. The targets of nasopharyngeal carcinoma were retrieved from the GeneCards database. At the same time, the drug therapeutic targets of Rhizoma Curcumae were obtained from the TCMSP and SymMap databases. The data were imported into the STRING database and Cytoscape 3.7.1 to construct a network of “Chinese medicine component-target-disease” interactions; then, the intersection was screened as the core Rhizoma Curcumae antinasopharyngeal cancer targets. Through GO target function and KEGG pathway enrichment analyses of the core targets, we predicted the biological processes and key signalling pathways involved in the Rhizoma Curcumae treatment of nasopharyngeal carcinoma. Results. Twenty-five core targets of Rhizoma Curcumae in nasopharyngeal carcinoma were mined: TP53, BCL2 ICAM1 RXRA, TLR3 and TLR9, TNF, PTGS2, IL-6, CTSD, MMP2, MMP9, MMP14, TIMP2, ABCC1, ABCB1, ABCG2, and so on. The results of visual analysis showed that the Rhizoma Curcumae treatment of nasopharyngeal carcinoma mainly involves leukocyte adhesion to vascular endothelial cells, positive regulation of NF-κB import into the nucleus, regulation of the reactive oxygen species biosynthetic and metabolic process, regulation of the chemokine biosynthetic and metabolic process, various cancer-related signalling pathways, and a variety of cytokine signal transduction pathways, such as the NF-κB, TLR, IL-17, and TNF signalling pathways. Conclusion. The core targets predicted by our research can be used as molecular markers for the treatment and prediction of nasopharyngeal carcinoma. The mechanism of Rhizoma Curcumae treatment in NPC may be related to immune regulatory pathways, the inhibition of cancer cell proliferation, metastasis, and angiogenesis, as well as the regulation of tumour microenvironment. Combined with the prediction of its associated mechanism of action, the core targets can provide targeted reference value for subsequent drug development related to Curcuma.

Curcumol inhibits lung adenocarcinoma growth and metastasis via inactivation of PI3K/AKT and Wnt/ß-catenin pathway

Curcumol (Cur), isolated from the Traditional Chinese Medical plant Rhizoma Curcumae, is the bioactive component of sesquiterpene reported to possess anti-tumor activity. However, its bioactivity and mechanisms against lung adenocarcinoma are still unclear. We investigated its effect on lung adenocarcinoma and elucidated its underlying molecular mechanisms. <I>In vitro</I>, Cur effectively suppressed proliferation, migration and invasion of lung adenocarcinoma cells A549 and H460, which were associated with the altered expressions of signaling molecules, including p-AKT, p-PI3K, p-LRP5/6, AXIN, APC, GSK3 &szlig; and p- &szlig;-catenin, matrix metalloproteinase (MMP)-2 and MMP-9. Furthermore, Cur significantly induced cell apoptosis of A549 and H460 by promoting the expression of Bax, caspase-3 and caspase-9 and suppressing the expression of Bcl-2, and arrested the cell cycle at the G0/G1 phase by lowering the levels of cyclin D1, CDK1 and CDK4. In vivo experiment revealed that Cur could inhibit lung tumor growth and lung metastasis, which were consistent with these in vitro results. In xenograft model mice, Cur strongly decreased tumor weight and tumor volume, which may were related to the down-regulation of p-AKT and p-PI3K by immunofluorescence analysis. In addition, lung metastasis model experiment suggested that Cur dramatically decreased the ratio of lung/total weight, tumor metastatic nodules, and the expressions of MMP-2 and MMP-9 in lung tissues compared with the control. Overall, these data suggested that the inhibitory activity of Cur on lung adenocarcinoma via the inactivation of PI3K/Akt and Wnt/ &szlig;-catenin pathways, at least in part, indicating that curcumol may be a potential anti-tumor agent for lung adenocarcinoma therapy.