PMID: 

Cell J. 2020 Jan ;21(4):419-425. Epub 2019 Jul 29. PMID: 31376323

Abstract Title: 

The Use ofß-Elemene to Enhance Radio Sensitization of A375 Human Melanoma Cells.

Abstract: 

Objective: Melanoma is the most malignant and severe type of skin cancer. It is a tumor with a high risk of metastasis and resistant to conventional treatment methods (surgery, radiotherapy, and chemotherapy).β-elemene is the most active constituent of Curcuma wenyujin which is a non-cytotoxic antitumor drug, proved to be effective in different types of cancers. The study aimed to investigate the therapeutic effects of β-elemene in combination with radiotherapy on A375 human melanoma.Materials and Methods: In this experimental study, human melanoma cells were grown in the monolayer culture model. The procedure of the treatment was performed by the addition of different concentrations ofβ-elemene to the cells. Then, the cells were exposed to 2 and 4 Gy X-ray in different incubation times (24, 48, and 72 hours). The MTT assay was used for the determination of the cell viability. To study the rate of apoptosis response to treatments, the Annexin V/PI assay was carried out.Results: The results of the MTT assay showedβ-elemene reduced the cell proliferation in dose- and time-dependent manners in cells exposed to radiation. Flow cytometry analysis indicated that β-elemene was effective in the induction of apoptosis. Furthermore, the combination treatment with radiation remarkably decreased the cells proliferation ability and also enhanced apoptosis. For example, cell viability in a group exposed to 40 μg/ml of β-elemene was 80%, but combination treatment with 6 MV X beam at a dose of 2 Gy reduced the viability to 61%.Conclusion: Our results showed thatβ-elemene reduced the proliferation of human melanoma cancer cell through apoptosis. Also, the results demonstrated that the radio sensitivity of A375 cell line was significantly enhanced by β-elemene. The findings of this study indicated the efficiency of β-elemene in treating melanoma cells andthe necessity for further research in this field.

read more

PMID: 

Nutrients. 2019 Aug 8 ;11(8). Epub 2019 Aug 8. PMID: 31398884

Abstract Title: 

Curcumin and Type 2 Diabetes Mellitus: Prevention and Treatment.

Abstract: 

Type 2 diabetes mellitus (T2DM) is an ensemble of metabolic diseases that has reached pandemic dimensions all over the world. The multifactorial nature of the pathology makes patient management, which includes lifelong drug therapy and lifestyle modification, extremely challenging. It is well known that T2DM is a preventable disease, therefore lowering the incidence of new T2DM cases could be a key strategy to reduce the global impact of diabetes. Currently, there is growing evidence on the efficacy of the use of medicinal plants supplements for T2DM prevention and management. Among these medicinal plants, curcumin is gaining a growing interest in the scientific community. Curcumin is a bioactive molecule present in the rhizome of theplant, also known as turmeric. Curcumin has different pharmacological and biological effects that have been described by both in vitro and in vivo studies, and include antioxidant, cardio-protective, anti-inflammatory, anti-microbial, nephro-protective, anti-neoplastic, hepato-protective, immunomodulatory, hypoglycaemic and anti-rheumatic effects. In animal models, curcumin extract delays diabetes development, improvesβ-cell functions, prevents β-cell death, and decreases insulin resistance. The present review focuses on pre-clinical and clinical trials on curcumin supplementation in T2DM and discusses the peculiar mechanisms by which curcumin might ameliorate diabetes management.

read more

PMID: 

Front Microbiol. 2019 ;10:1466. Epub 2019 Jul 2. PMID: 31333606

Abstract Title: 

Effect of Perillaldehyde on Prophylaxis and Treatment of Vaginal Candidiasis in a Murine Model.

Abstract: 

Vulvovaginal candidiasis is a common fungal infection afflicting women which is primarily caused by the yeast(). It is imperative to introduce new drug classes to counter this threat due to the continuous emergence of drug-resistant cases in recent years. The purpose of this study was to clarify theantifungal activity of perillaldehyde (PAE) againstand to prove that PAE is a promising candidate for the control of vaginal candidiasis. An animal model of vaginitis was developed to demonstrate the therapeutic and preventive effects of PAE on vaginal candidiasis, and these were evaluated through fungal and histopathological examinations. In clarifying the mechanism of PAE, standard hematological test results indicated that white blood cells (WBC) were elevated abnormally in mice infected with, whereas when the mice were treated with various concentrations of PAE, the number of WBC in the blood was reduced. Flow cytometry was used to detect the populations of neutrophils, macrophages and CD4 T cells in the vaginal tissue of the mice. PAE was found to reduce these immune cells, which all play a key role in the inflammatory response, and the related interleukin and pro-inflammatory cytokines, including IL-17, IL-22 and TNF-α. These were detected using ELISA. Finally, we detected the expression levels of E-cadherin in the PAE treatment mouse group and discovered that it had recovered to its normal levels, but in the infection mouse group, the E-cadherin expression was clearly suppressed by the presence of. Our data demonstrated that PAE targets these cytokines and possesses the ability to fight the fungal infection while also reducing the levels of the inflammatory factors identified. Our results demonstrated that PAE has a significant preventative and therapeutic effect on vaginal candidiasis and is a potential candidate for the treatment of vaginalinfections.

read more

PMID: 

R Soc Open Sci. 2019 Jun ;6(6):190360. Epub 2019 Jun 12. PMID: 31312498

Abstract Title: 

Piceatannol attenuates RANKL-induced osteoclast differentiation and bone resorption by suppressing MAPK, NF-κB and AKT signalling pathways and promotes Caspase3-mediated apoptosis of mature osteoclasts.

Abstract: 

Osteoclasts are multinuclear giant cells that have unique ability to degrade bone. The search for new medicines that modulate the formation and function of osteoclasts is a potential approach for treating osteoclast-related bone diseases. Piceatannol (PIC) is a natural organic polyphenolic stilbene compound found in diverse plants with a strong antioxidant and anti-inflammatory effect. However, the effect of PIC on bone health has not been scrutinized systematically. In this study, we used RAW264.7, an osteoclast lineage of cells of murine macrophages, to investigate the effects and the underlying mechanisms of PIC on osteoclasts. Here, we demonstrated that PIC treatment ranging from 0 to 40µM strongly inhibited osteoclast formation and bone resorption in a dose-dependent manner. Furthermore, the inhibitory effect of PIC was accompanied by the decrease of osteoclast-specific genes. At the molecular level, PIC suppressed the phosphorylation of c-Jun N-terminal kinase (JNK), extracellular signal-regulated kinase (ERK1/2), NF-κB p65, IκBα and AKT. Besides, PIC promoted the apoptosis of mature osteoclasts by inducing caspase-3 expression. In conclusion, our results suggested that PIC inhibited RANKL-induced osteoclastogenesis and bone resorption by suppressing MAPK, NF-κB and AKT signalling pathways and promoted caspase3-mediated apoptosis of mature osteoclasts, which might contribute to the treatment of bone diseases characterized by excessive bone resorption.

read more

PMID: 

Neurotherapeutics. 2019 Jul 2. Epub 2019 Jul 2. PMID: 31267473

Abstract Title: 

Long-Term Pantethine Treatment Counteracts Pathologic Gene Dysregulation and Decreases Alzheimer's Disease Pathogenesis in a Transgenic Mouse Model.

Abstract: 

The low-molecular weight thiol pantethine, known as a hypolipidemic and hypocholesterolemic agent, is the major precursor of co-enzyme A. We have previously shown that pantethine treatment reduces amyloid-β (Aβ)-induced IL-1β release and alleviates pathological metabolic changes in primary astrocyte cultures. These properties of pantethine prompted us to investigate its potential benefits in vivo in the 5XFAD (Tg) mouse model of Alzheimer's disease (AD).1.5-month-old Tg and wild-type (WT) male mice were submitted to intraperitoneal administration of pantethine or saline control solution for 5.5 months. The effects of such treatments were investigated by performing behavioral tests and evaluating astrogliosis, microgliosis, Αβ deposition, and whole genome expression arrays, using RNAs extracted from the mice hippocampi. We observed that long-term pantethine treatment significantly reduced glial reactivity and Αβ deposition, and abrogated behavioral alteration in Tg mice. Moreover, the transcriptomic profiles revealed that after pantethine treatment, the expression of genes differentially expressed in Tg mice, and in particular those known to be related to AD, were significantly alleviated. Most of the genes overexpressed in Tg compared to WT were involved in inflammation, complement activation, and phagocytosis and were found repressed upon pantethine treatment. In contrast,pantethine restored the expression of a significant number of genes involved in the regulation of Αβ processing and synaptic activities, which were downregulated in Tg mice. Altogether, our data support a beneficial role for long-term pantethine treatment in preserving CNS crucial functions altered by Aβ pathogenesis in Tg mice and highlight the potential efficiency of pantethine to alleviate AD pathology.

read more

PMID: 

J BUON. 2019 Mar-Apr;24(2):549-554. PMID: 31128004

Abstract Title: 

Root extract of Prunella vulgaris inhibits in vitro and in vivo carcinogenesis in MCF-5 human breast carcinoma via suppression of angiogenesis, induction of apoptosis, cell cycle arrest and modulation of PI3K/AKT signalling pathway.

Abstract: 

PURPOSE: In this study we examined the anticancer effects of methanolic root extract of Prunella Vulgaris (PVE) against the MCF-5 breast cancer (BC) cell line along with its mode of action.METHODS: The proliferation rate of the MCF-5 cells was assessed by MTT assay. Apoptosis was confirmed by acridine orange (AO)/ethidium bromide (EB) and annexin V/propidium iodide (PI) staining. DNA damage was checked by comet assay. Cell cycle analysis was performed by flow cytometry. Protein expression was determined by western blotting. In vivo evaluation of the extract was carried out in xenografted tumor mice models.RESULTS: PVE inhibited the growth of the MCF-5 cells and exhibited an IC50 value of 25µg/ml. The investigation of underlying mechanism revealed that PVE triggered apoptotic cell death of the MCF-5 cells which was also associated with enhancement of the expression of Bax and decrease in the expression of Bcl-2. PVE also caused arrest of the cells in the G2/M phase of the cell cycle and also exerted the anti-angiogenic effects. In vivo evaluation of PVE showed that it could inhibit the tumor weight and volume, suggestive of the anticancer potential of PVE.CONCLUSION: The root extract of Prunella vulgaris in this study was shown to exert potent anticancer effects in MCF-7 human BC cells both in vitro and in vivo, accompanied with apoptosis induction, inhibition of angiogenesis, cell cycle arrest, and modulation of PI3K/AKT signaling pathway.

read more

PMID: 

J Agric Food Chem. 2019 Aug 16. Epub 2019 Aug 16. PMID: 31419115

Abstract Title: 

Pterostilbene inhibits adipocyte conditioned-medium-induced colorectal cancer cell migration through targeting FABP5-related signaling pathway.

Abstract: 

Pterostilbene (PTS) is a phenolic compound with diverse pharmacologic activities. However, its potential for inhibiting obesity-related CRC remains unclear. Our study evaluated the mechanism of inhibitory effects of PTS on adipocyte conditioned-medium (aCM)-induced malignant transformation in HT-29 colorectal adenocarcinoma cells. The results demonstrated that PTS could downregulate the expression of aCM-induced fatty acid-binding protein 5 (FABP5) and pro-metastasis factors such as vascular endothelial growth factor (VEGF), matrix metalloproteinase-2 (MMP2), MMP9, and extracellular tumor necrosis factor alpha (TNF-α) via inhibiting aCM-induced nuclear factor-kappa B (NF-κB), β-catenin, and peroxisome proliferator-activated receptor γ (PPAR-γ). Moreover, PTS can suppress aCM-stimulated phosphoinositide 3-kinase (PI3K), protein kinase B (Akt), p38 mitogen-activated protein kinase (p38 MAPK), extracellularsignal-regulated kinase (ERK), and c-Jun N-terminal kinases 1/2 (JNK 1/2) signaling pathways activation that are upstream of NF-B, β-catenin, and PPAR-γ. Therefore, we suggest that PTS could alleviate adiposity-induced cachexia in CRC via inhibiting cell migration through downregulating FABP5 gene expression.

read more

PMID: 

Complement Ther Med. 2019 Aug ;45:89-97. Epub 2019 May 23. PMID: 31331588

Abstract Title: 

Policosanol supplementation significantly improves blood pressure among adults: A systematic review and meta-analysis of randomized controlled trials.

Abstract: 

BACKGROUND AND AIMS: Policosanol contains a mixture of concentrated primary aliphatic alcohols extracted from sugar cane wax and is recognized as a cholesterol-lowering drug but previous studies reported that it could be helpful for reducing blood pressure as well. We aimed to systematically review all randomized control trials (RCTs) evaluating the efficacy of policosanol supplementation for lowering high blood pressure.METHODS AND RESULTS: The following databases were searched up to March 2019: PubMed, Scopus, ISI Web of Science and the Cochrane library. Eligible RCTs were included if they investigate the effects of policosanol supplementation on systolic (SBP) and diastolic (DBP) blood pressure. Pooled effect size was measured using random effect model (DerSimmonon method). A total of nineteen studies with twenty-four arms were considered. Pooled effect size showed that SBP (WMD: -3.423 mmHg, 95% CI: -5.315, -1.531; p 

read more

PMID: 

J Asian Nat Prod Res. 2019 Jul 25:1-14. Epub 2019 Jul 25. PMID: 31345059

Abstract Title: 

Endoplasmic reticulum stress mediated the xanthohumol induced murine melanoma B16-F10 cell death.

Abstract: 

Xanthohumol (XN) exerts a specific cytotoxicity in B16-F10 melanoma cells with cytoplasmic vacuoles formation. Further investigation showed XN inhibited cell proliferation in a time- and dose-dependent manner along with down-regulation of mitogen-activated protein kinase and up-regulation of the endoplasmic reticulum (ER) stress marker Bip, CHOP and protein ubiquitination, which was relieved by the ER-stress inhibitor 4-PBA. Whereas no early apoptosis characteristics was identified during XN induced cell death.

read more

PMID: 

Biochim Biophys Acta Gen Subj. 2019 Aug 3. Epub 2019 Aug 3. PMID: 31386885

Abstract Title: 

Xanthohumol exhibits anti-myeloma activity in vitro through inhibition of cell proliferation, induction of apoptosis via the ERK and JNK-dependent mechanism, and suppression of sIL-6R and VEGF production.

Abstract: 

BACKGROUND: Xanthohumol (XN, a hop-derived prenylflavonoid) was found to exert anticancer effects on various cancer types. However, the mechanisms by which XN affects the survival of multiple myeloma cells (MM) are little known. Therefore, our study was undertaken to address this issue.METHODS: Anti-proliferative activity of XN towards two phenotypically distinct MM cell lines U266 and RPMI8226 was evaluated with the MTT and BrdU assays. Cytotoxicity was determined with the LDH method, whereas apoptosis was assessed by flow cytometry and fluorescence staining. The expression of cell cycle- and apoptosis-related proteins and the activation status of signaling pathways were estimated by immunoblotting and ELISA assays.RESULTS: XN reduced the viability of RPMI8226 cells more potently than in U266 cells. It blocked cell cycle progression through downregulation of cyclin D1 and increased p21 expression. The marked apoptosis induction in the XN-treated RPMI8226 cells was related to initiation of mitochondrial and extrinsic pathways, as indicated by the altered p53, Bax, and Bcl-2 protein expression, cleavage of procaspase 8 and 9, and elevated caspase-3 activity. The apoptotic process was probably mediated via ROS overproduction and MAPK (ERK and JNK) activation as N-acetylcysteine, or specific inhibitors of these kinases prevented the XN-induced caspase-3 activity and, hence, apoptosis. Moreover, XN decreased sIL-6R and VEGF production in the studied cells.CONCLUSIONS: ERK and JNK signaling pathways are involved in XN-induced cytotoxicity against MM cells.GENERAL SIGNIFICANCE: The advanced understanding of the molecular mechanisms of XN action can be useful in developing therapeutic strategies to treat multiple myeloma.

read more