PMID: 

Int J Biol Sci. 2020 ;16(9):1536-1550. Epub 2020 Mar 5. PMID: 32226300

Abstract Title: 

Bisdemethoxycurcumin Enhances the Sensitivity of Non-small Cell Lung Cancer Cells to Icotinib via Dual Induction of Autophagy and Apoptosis.

Abstract: 

Non-small cell lung cancer (NSCLC) with epidermal growth factor receptor (EGFR) wild-type is intrinsic resistance to EGFR-tyrosine kinase inhibitors (TKIs). In this study, we assessed whether the combination of bisdemethoxycurcumin (BDMC) and icotinib could surmount primary EGFR-TKI resistance in NSCLC cells and investigated its molecular mechanism. Results showed that the combination of BDMC and icotinib produced potently synergistic growth inhibitory effect on primary EGFR-TKI-resistant NSCLC cell lines H460 (EGFR wild-type and K-ras mutation) and H1781 (EGFR wild-type and Her2 mutation). Compared with BDMC or icotinib alone, the two drug combination induced more significant apoptosis and autophagy via suppressing EGFR activity and interaction of Sp1 and HDCA1/HDCA2, which was accompanied by accumulation of reactive oxygen species (ROS), induction of DNA damage, and inhibition of cell migration and invasion. ROS inhibitor (NAC) and autophagy inhibitors (CQ or 3-MA) partially reversed BDMC plus icotinib-induced growth inhibitory effect on the NSCLC cells. Meanwhile, co-treatment with NAC attenuated the two drug combination-induced autophagy, apoptosis, DNA damage and decrease of cell migration and invasion ability. Also, 3-MA or CQ can abate the combination treatment-induced apoptosis and DNA damage, suggesting that there is crosstalk between different signaling pathways in the effect produced by the combination treatment. Our data indicate that BMDC has the potential to improve the treatment of primary EGFR-TKI resistant NISCLC that cannot be controlled with single-target agent, such as icotinib.

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PMID: 

Pestic Biochem Physiol. 2019 Sep ;159:59-67. Epub 2019 May 24. PMID: 31400785

Abstract Title: 

Antifungal activity of zedoary turmeric oil against Phytophthora capsici through damaging cell membrane.

Abstract: 

Phytophthora capsici is a plant oomycete pathogen, which causes many devastating diseases on a broad range of hosts. Zedoary turmeric oil (ZTO) is a kind of natural plant essential oil that has been widely used in pharmaceutical applications. However, the antifungal activity of ZTO against phytopathogens remains unknown. In this study, we found ZTO could inhibit P. capsici growth and development in vitro and in detached cucumber and Nicotiana benthamiana leaves. Besides, ZTO treatment resulted in severe damage to the cell membrane of P. capsici, leading to the leakage of intracellular contents. ZTO also induced a significant increase in relative conductivity, malondialdehyde concentration and glycerol content. Furthermore, we identified 50 volatile organic compounds from ZTO, and uncovered Curcumol,β-elemene, curdione and curcumenol with strong inhibitory activities against mycelial growth of P. capsici. Overall, our results not only shed new light on the antifungal mechanism of ZTO, but also imply a promising alternative for the control of phytophthora blight caused by P. capsici.

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PMID: 

Nutr Cancer. 2020 Apr 14:1-15. Epub 2020 Apr 14. PMID: 32285707

Abstract Title: 

Therapeutic Effects of Curcumol in Several Diseases; An Overview.

Abstract: 

also known asis a traditional Chinese medicine that has been used for many centuries against several diseases. The rhizome of the plant is composed of curcuminoids (curcumin, demethoxycurcumin, and bisdemethoxycurcumin), and essential volatile oils including curcumol, curdione, and germacrone. While curcuminoids have been extensively studied for their antimicrobial, antioxidant, anti-inflammatory and anticancer properties, the therapeutic efficacy of curcumol is still emerging. Recent studies have shown anticancer properties of curcumol against multiple solid tumors such as breast, colorectal, head and neck, and lung adenocarcinomas. The underlying anti-tumor mechanisms revealed inhibition of several signaling pathways (NF-κB, MAPK, PI-3K/AKT, and GSK-3β) associated with cell proliferation, survival, anti-apoptosis, invasion and metastasis. Besides curcumol, extracts from theroots possess many other terpenoids such asβ-elemene, δ-elemene, germacrone, furanodiene and furanodienone with known anticancer properties. In this review, we comprehensively focused on the composition ofessential oils, their structure, isolation and therapeutic uses of curcumol to aid in the improvement and development of novel drugs with minimal cytotoxicity, enhanced efficacy, and less cost.

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PMID: 

Phytomedicine. 2020 Feb 10 ;69:153184. Epub 2020 Feb 10. PMID: 32199253

Abstract Title: 

β-Elemene inhibits the metastasis of multidrug-resistant gastric cancer cells through miR-1323/Cbl-b/EGFR pathway.

Abstract: 

BACKGROUND: β-Elemene is a natural agent extracted from the traditional Chinese herbal medicine Curcuma wenyujin that is a promising novel plant-derived drug with broad-spectrum anticancer activity. Our previous study identified an enhanced capacity for metastasis in multidrug resistant (MDR) gastric cancer and breast cancer cells. However, the anti-metastatic effects of β-Elemene on MDR cancer cells remain unknown.PURPOSE: In this study, we posit the hypothesis thatβ-elemene possesses antimetastatic effects on MDR cancer cells.METHODS: Cell viability assay was used to assess the resistance of SGC7901/ADR cells and the cytotoxic effects ofβ-Elemene. Wound healing, transwell assay and lung metastatic mice model were used to the anti-metastasis effects of β-Elemene. MicroRNA microarray analysis was used to explore potential regulated miRNAs. Luciferase reporter assay was used to identify the direct target. Human MMP antibody array, western blot, immunoprecipitation, qRT-PCR analyses and immunohistochemistry were conducted to investigate the underlying anti-metastasis mechanism of β-Elemene.RESULTS: In this study, we found thatβ-Elemene significantly inhibited the metastatic capacity of MDR gastric cells in vivo and in vitro. Mechanistically, we found that β-Elemene regulated MMP-2/9 expression and reversed epithelial-mesenchymal transition. Further studies showed that β-Elemene upregulated Cbl-b expression, resultingin inhibition of the EGFR-ERK/AKT pathways, which regulate MMP-2/9. Additionally, we confirmed that β-Elemene upregulated Cbl-b by inhibiting miR-1323 expression. Finally, we found that numbers of metastatic tumor nodules were significantly decreased in the lungs of nude mice after β-Elemene treatment.CONCLUSION: Our results suggested thatβ-Elemene inhibits the metastasis of MDR gastric cancer cells by modulating the miR-1323/Cbl-b/EGFR signaling axis.

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PMID: 

Acta Histochem. 2020 Mar 14:151538. Epub 2020 Mar 14. PMID: 32183989

Abstract Title: 

β-elemene suppresses the malignant behavior of esophageal cancer cells by regulating the phosphorylation of AKT.

Abstract: 

BACKGROUND: Esophageal cancer is a digestive tract malignancy, ranking sixth among the world's deadliest tumor incidence. However, the pathogenesis of esophageal cancer is complex and the prognosis remains poor. Therefore, in-depth study of the pathogenesis and developing effective treatments are of great value for esophageal cancer.β-elemene is a natural monomeric compound derived from the Chinese herbal Curcuma wenyujin. β-elemene has been reported to have anti-tumor effects and used as an adjunct to clinical therapy for multiple cancers. This study aims to explore the effects of β-elemene on esophageal cancer and its related molecular mechanisms.METHODS: TE-1 and KYSE-150 cells were used to evaluate the activity ofβ-elemene on esophageal cancerin vitro and in vivo. Western blot was performed for protein expression assessment. CCK8 assay and cell cycle analysis were used for proliferation testing. Flow cytometry was performed for apoptosis detection. Wound healing assay was subjected to assess the migration ability. Transwell chamber assay was applied to assess the invasion ability. HE staining, TUNEL staining and immunohistochemical staining were used to evaluate the changes in tumor tissues.RESULTS: We found thatβ-elemene treatment suppressed proliferation, as well as induced apoptosis of esophageal cancer cells. In addition, β-elemene inhibited the migration and invasion ability of esophageal cancer cells. Furthermore, β-elemene exerted its effects against esophageal cancer by specifically regulating AKT signaling, thereby controlling the expression of PD-L1.CONCLUSION: β-elemene inhibits proliferation and metastasis of esophageal cancer cells by regulating the phosphorylation of AKT.

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PMID: 

Biomed Res Int. 2020 ;2020:6892961. Epub 2020 Feb 19. PMID: 32149121

Abstract Title: 

The Antitumor Efficacy of-Elemene by Changing Tumor Inflammatory Environment and Tumor Microenvironment.

Abstract: 

Inflammatory mediators and inflammatory cells in the inflammatory microenvironment promote the transformation of normal cells to cancer cells in the early stage of cancer, promote the growth and development of cancer cells, and induce tumor immune escape. The monomeric active ingredient-elemene is extracted from the traditional Chinese medicineand has been proven to have good anti-inflammatory and antitumor activities in clinical applications for more than 20 years in China. Recent studies have found that this traditional Chinese medicine plays a vital role in macrophage infiltration and M2 polarization, as well as in regulating immune disorders, and it even regulates the transcription factors NF-B and STAT3 to alter inflammation, tumorigenesis, and development. In addition,-elemene regulates not only different inflammatory factors (such as TNF-, IFN, TGF-, and IL-6/10) but also oxidative stress in vivo and in vitro. The excellent anti-inflammatory and antitumor effects of-elemene and its ability to alter the inflammatory microenvironment of tumors have been gradually elaborated. Although the study of monomeric active ingredients in traditional Chinese medicines is insufficient in terms of quality and quantity, the pharmacological effects of more active ingredients of traditional Chinese medicines will be revealed after-elemene.

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PMID: 

Int J Mol Sci. 2020 Mar 26 ;21(7). Epub 2020 Mar 26. PMID: 32225104

Abstract Title: 

The Emerging Role of Curcumin in the Modulation of TLR-4 Signaling Pathway: Focus on Neuroprotective and Anti-Rheumatic Properties.

Abstract: 

Natural products have been used in medicine for thousands of years. Given their potential health benefits, they have gained significant popularity in recent times. The administration of phytochemicals existed shown to regulate differential gene expression and modulate various cellular pathways implicated in cell protection. Curcumin is a natural dietary polyphenol extracted fromwith different biological and pharmacological effects. One of the important targets of curcumin is Toll-like receptor-4 (TLR-4), the receptor which plays a key role in the modulation of the immune responses and the stimulation of inflammatory chemokines and cytokines production. Different studies have demonstrated that curcumin attenuates inflammatory response via TLR-4 acting directly on receptor, or by its downstream pathway. Curcumin bioavailability is low, so the use of exosomes, as nano drug delivery, could improve the efficacy of curcumin in inflammatory diseases. The focus of this review is to explore the therapeutic effect of curcumin interacting with TLR-4 receptor and how this modulation could improve the prognosis of neuroinflammatory and rheumatic diseases.

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A double-blind, placebo-controlled, randomized study finds flaxseed oil equally beneficial to fish oil supplementation in reducing myocardial disease risk in patients with Type 2 diabetes

PMID: 

Mol Med Rep. 2019 Oct ;20(4):3215-3223. Epub 2019 Aug 6. PMID: 31432168

Abstract Title: 

Allium hookeri root extract regulates asthmatic changes through immunological modulation of Th1/Th2‑related factors in an ovalbumin‑induced asthma mouse model.

Abstract: 

In 2013, WHO estimated that approximately 235 million people suffered from asthma worldwide. Asthma is a hyper responsive disorder, which is related to an imbalance between the T‑helper type 1 and 2 cells (henceforth, Th1 and Th2, respectively). Allium hookeri is a plant that is widely used for culinary purposes and also in traditionalAsian medicine. The present study was conducted to elucidate the anti‑asthmatic effects and mechanism of action of A. hookeri root extracts (AHRE) in an ovalbumin (OVA)‑induced asthma mouse model. The mice were divided into five groups, namely, the control, the OVA‑treated group, the dexamethasone‑treated group, the 30 mg/kg AHRE‑treated group, and the 300 mg/kg AHRE‑treated group. The total WBC count and the differential cell count in the bronchoalveolar fluid, the level of serum IgE, the histopathological changes in the lung, and changes in the cell surface molecules, the asthma‑related cytokine levels, and Th cell transcription factors were evaluated. AHRE significantly ameliorated asthmatic changes, such as the total WBC count, eosinophil count, and the level of IgE; in addition, it reduced mucus hypersecretion, epithelial hyperplasia, and eosinophil infiltration inthe lungs. AHRE significantly inhibited the expression of CD68+ cells and MHC class II+ molecules, Th1 cell transcription factor (T‑bet) activation, Th2 cell transcription factor (GATA‑3) activation, and TNF‑α in the lung tissue. Furthermore, it suppressed cell surface molecules, such as CD4+and CD8+; Th1‑related cytokines, such as IFN‑γ and IL‑12p40; Th2‑related cytokines, such as IL‑4 and IL‑5; and Th17‑related cytokines, such as IL‑6 and TNF‑α, in a dose‑dependent manner. Thus, AHRE may be considered a promising anti‑asthmatic drug.

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PMID: 

Nutrients. 2019 Sep 20 ;11(10). Epub 2019 Sep 20. PMID: 31547031

Abstract Title: 

Root Extract Inhibits Adipogenesis by Promoting Lipolysis in High Fat Diet-Induced Obese Mice.

Abstract: 

(AH) is widely consumed as a herbal medicine. It possesses biological activity against metabolic diseases. The objective of this study was to investigate effects of AH root water extract (AHR) on adipogenesis in 3T3-L1 cells and in high-fat diet (HFD)-induced obese mice. AHR inhibited lipid accumulation during adipocyte differentiation by downregulation of gene expression, such as hormone sensitive lipase (HSL), lipoprotein lipase (LPL) and an adipogenic gene, CCAAT/enhancer binding protein-α in 3T3-L1 preadipocytes. Oral administration of AHR significantly suppressed body weight gain, adipose tissue weight, serum leptin levels, and adipocyte cell size in HFD-induced obese mice. Moreover, AHR significantly decreased hepatic mRNA expression levels of cholesterol synthesis genes, such as 3-hydroxy-3-methylglutaryl CoA reductase, sterol regulatory element-binding transcription factor (SREBP)-2, and low-density lipoprotein receptor, as well as fatty acid synthesis genes, such as SREBP-1c and fatty acid synthase. Serum triglyceride levels were also lowered by AHR, likely as a resultof the upregulating gene involved in fatty acid β-oxidation, carnitine palmitoyltransferase 1a, in the liver. AHR treatment activated gene expression of peroxisome proliferator-activated receptor-γ, which might have promoted HSL and LPL-medicated lipolysis, thereby reducing white adipose tissue weight. In conclusion, AHR treatment can improve metabolic alterations induced by HFD in mice by modifying expression levels of genes involved in adipogenesis, lipogenesis, and lipolysis in the white adipose tissue and liver.

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