PMID: 

Evid Based Complement Alternat Med. 2020 ;2020:2679409. Epub 2020 Mar 28. PMID: 32308701

Abstract Title: 

-Sitosterol Protects against Myocardial Ischemia/Reperfusion Injury via Targeting PPAR/NF-B Signalling.

Abstract: 

Myocardial ischemia/reperfusion (I/R) injury is a clinically severe complication, which can cause high rates of disability and mortality particularly in patients with myocardial infarction, yet the molecular mechanisms underlying this process remain unclear. This study aimed to explore the protective effects of-sitosterol against myocardial I/R injury and to elucidate the underlying molecular mechanisms. Our results showed that hypoxia/reoxygenation (H/R) treatment suppressed cell viability, induced cell apoptosis and reactive oxygen species production, increased caspase-3 and -9 activities, upregulated caspase-3 and -9 protein expressions, downregulated the Bcl-2 protein expression, and reduced the mitochondrial membrane potential.-Sitosterol treatment attenuated H/R-induced cardiomyocyte injury. Moreover,-sitosterol treatment counteracted the inhibitory effects of H/R treatment on the peroxisome proliferator-activated receptor gamma (PPARγ) expression and enhanced effects of H/R treatment on the NF-κB expression in cardiomyocytes. Furthermore, inhibition of PPARγ impaired the protective actions of-sitosterol against H/R-induced cardiomyocyte injury. In the I/R rats,-sitosterol treatment reduced the myocardial infarcted size and apoptosis, which was attenuated by the inhibition of PPARγ. In conclusion, our results demonstrate that-sitosterol protected againstH/R-induced cardiomyocyte injury andmyocardial I/R injury. The-sitosterol-mediated cardioprotective effects may involve the modulation of PPAR/NF-B signalling during myocardial I/R injury. Further studies are required to further explore the clinical application of-sitosterol in the myocardial I/R injury.

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PMID: 

J Biomed Mater Res A. 2020 Apr 21. Epub 2020 Apr 21. PMID: 32319188

Abstract Title: 

β-sitosterol assisted silver nanoparticles activates Nrf2 and triggers mitochondrial apoptosis via oxidative stress in human hepatocellular cancer cell line.

Abstract: 

Cancer nanomedicine is an emerging field of cancer therapeutics. Incidence of hepatocellular carcinoma is increasing worldwide and currently, it is the second leading cause of cancer-related deaths. This study investigates the cytotoxic potential ofβ-sitosterol assisted silver nanoparticles (BSS-SNPs) in HepG2 cells. The silver nanoparticles were synthesized using β-sitosterol as a reducing and stabilizing agent. The characterization of BSS-SNPs was done by UV-visible spectrophotometry and transmission electron microscope (TEM) analysis. HepG2 cells were treated with different concentrations of BSS-SNPs for 24 h and cytotoxicity was evaluated by MTT assay. Intracellular ROS was investigated by 2',7' -dichlorofluorescin diacetate staining. The nuclear factor erythroid 2-related factor 2 (Nrf-2) protein expression was investigated by immunofluorescence staining. Morphology-related to apoptotic changes were analyzed by annexin V staining. Intrinsic apoptosis pathway related molecular markers were investigated by western blotting and PCR analysis. Spectrophotometry analysis confirmed a strong absorption peak at 420 nm, which showed the successful synthesis of BSS-SNPs. The TEM analysis indicated the spherical, rod and hexagonal shaped BSS-SNPs with the size ranges from 5 to 55 nm. BSS-SNPs significantly inhibited the proliferation and induced ROS and Nrf-2 expression in HepG2 cells. BSS-SNPs treatment caused apoptosis-related morphological changes and upregulated the pro-apoptotic markers such as bax, p53, cytochrome c, caspases-9, -3 and downregulated bcl-2 expressions. Our findings suggest that BSS-SNPs might serve as potential drug candidates for hepatocellular carcinoma.

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PMID: 

Antibiotics (Basel). 2020 Apr 15 ;9(4). Epub 2020 Apr 15. PMID: 32326384

Abstract Title: 

Antimicrobial Activity of Silver-Treated Bacteria against other Multi-Drug Resistant Pathogens in Their Environment.

Abstract: 

Silver is a potent antimicrobial agent against a variety of microorganisms and once the element has entered the bacterial cell, it accumulates as silver nanoparticles with large surface area causing cell death. At the same time, the bacterial cell becomes a reservoir for silver. This study aims to test the microcidal effect of silver-killedO104: H4 and its supernatant against fresh viable cells of the same bacterium and some other species, includingO157: H7, Multidrug Resistant (MDR)and Methicillin Resistant(MRSA). Silver-killed bacteria were examined by Transmission Electron Microscopy (TEM). Agar well diffusion assay was used to test the antimicrobial efficacy and durability of both pellet suspension and supernatant of silver-killedO104:H4 against other bacteria. Both silver-killed bacteria and supernatant showed prolonged antimicrobial activity against the tested strains that extended to 40 days. The presence of adsorbed silver nanoparticles on the bacterial cell and inside the cells was verified by TEM. Silver-killed bacteria serve as an efficient sustained release reservoir for exporting the lethal silver cations. This promotes its use as a powerful disinfectant for polluted water and as an effective antibacterial which can be included in wound and burn dressings to overcome the problem of wound contamination.

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PMID: 

Evid Based Complement Alternat Med. 2019 ;2019:5486728. Epub 2019 Oct 24. PMID: 31781272

Abstract Title: 

Efficacy of a Peruvian Botanical Remedy (Sabell A4+) for Treating Liver Disease and Protecting Gastric Mucosal Integrity.

Abstract: 

The purpose of this study was to determine the efficacy of a Peruvian botanical formulation for treating disorders of hepatic function and gastric mucosal integrity. The formulation A4+ (Sabell Corporation) contains extracts ofrhizome,flower, andleaf. Individually these plants have been used as traditional remedies for liver disease. We report the efficacy of A4+ and its components using a variety of in vitro and in vivo disease models. The methods used included tests for antioxidant, anti-inflammatory, and antiviral activity as well as mouse models of liver disease, including Concanavalin A-induced immune-mediated hepatitis and a bile duct ligation model for evaluating sickness behaviour associated with liver disease. Rat models were used to evaluate the gastric mucosal protective property of A4+ following indomethacin challenge and to evaluate its anti-inflammatory action in an"air pouch"model. In all tests, A4+ proved to be more effective than placebo. A4+ was antioxidant and anti-inflammatory and diminished Hepatitis C virus replication in vitro. In animal models, A4+ was shown to protect the liver from immune-mediated hepatitis, improve behavioural function in animals with late stage liver disease, and protect the rat gastric mucosa from ulceration following NSAID exposure. We conclude that A4+ ameliorated many aspects of liver injury, inhibited hepatitis C virus replication, and protected the gastric mucosa from NSAIDs. These varied beneficial properties appear to result from positive interactions between the three constituent herbs.

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PMID: 

Zh Nevrol Psikhiatr Im S S Korsakova. 2020 ;120(2):125-131. PMID: 32307422

Abstract Title: 

[Curcumin as an ajuvant treatment of depression: mechanisms of action and application prospects].

Abstract: 

Curcumin, a natural compound found in the rhizomes of turmeric, has a pronounced anti-inflammatory activity. Rodent models of depression show that this activity is similar to the effect of antidepressants (AD). Experimental data indicate that this activity may be related to the effect of curcumin on the monoamine cycle, oxidative and nitrosative stress, neurogenesis, hypothalamic-pituitary-adrenal, and immune systems. A number of meta-analyzes indicate the effectiveness of the combined use of curcumin with antidepressants in the treatment of depression. The mechanism of action of curcumin, as well as the prospects for its further use are considered.

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PMID: 

Fitoterapia. 2020 Apr ;142:104489. Epub 2020 Jan 28. PMID: 32004654

Abstract Title: 

Anti-H1N1 viral activity of three main active ingredients from zedoary oil.

Abstract: 

Influenza virus is one of the most widespread infectious diseases in the world. It poses a serious public health threat to humans. With the emergence of drug-resistant virus strains, antiviral drugs are urgently needed to control virus transmission and disease progression. In this study, three main active substances-curcumol, curdione and germacrone-were isolated from the traditional Chinese medicine zedoary. They inhibited the replication of influenza A (H1N1) virus in a dose-dependent manner. After treatment with these compounds, the expression of viral protein and RNA synthesis were inhibited. In vivo, these compounds also reduced H1N1-induced lung damage and the load of virus in serum as well as whole blood cells. In a proteomic analysis, after treatment with germacrone, the expression of antiviral protein and the amount of intracellular virus were significantly reduced, further proving that germacrone can inhibit viral replication. Our experiments have shown that curcumol, curdione and germacrone can inhibit the replication of H1N1 virus; in particular, germacrone shows potential both in vitro and in vivo as a therapeutic drug.

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PMID: 

Cell Prolif. 2020 Mar ;53(3):e12762. Epub 2020 Mar 2. PMID: 32119185

Abstract Title: 

Curcumol attenuates liver sinusoidal endothelial cell angiogenesis via regulating Glis-PROX1-HIF-1α in liver fibrosis.

Abstract: 

OBJECTIVE: Hepatic sinusoidal angiogenesis owing to dysfunctional liver sinusoidal endothelial cells (LSECs) accompanied by an abnormal angioarchitecture is a symbol related to liver fibrogenesis, which indicates a potential target for therapeutic interventions. However, there are few researches connecting angiogenesis with liver fibrosis, and the deeper mechanism remains to be explored.MATERIALS AND METHODS: Cell angiogenesis and angiogenic protein were examined in primary LSECs of rats, and multifarious cellular and molecular assays revealed the efficiency of curcumol intervention in fibrotic mice.RESULTS: We found that curcumol inhibited angiogenic properties through regulating their upstream mediator hypoxia-inducible factor-1α (HIF-1α). The transcription activation of HIF-1α was regulated by hedgehog signalling on the one hand, and the protein stabilization of HIF-1α was under the control of Prospero-related homeobox 1 (PROX1) on the other. A deubiquitinase called USP19 could be recruited by PROX1 and involved in ubiquitin-dependent degradation of HIF-1α. Furthermore, our researches revealed that hedgehog signalling participated in the activation of PROX1 transcription probably in vitro. Besides, curcumol was found to ameliorate liver fibrosis and sinusoid angiogenesis via hedgehog pathway in carbon tetrachloride (CCl) induced liver fibrotic mice. The protein expression of key regulatory factors, PROX1 and HIF-1α, was consistent with the Smo, the marker protein of Hh signalling pathway.CONCLUSIONS: In this article, we evidenced that curcumol controlling LSEC-mediated angiogenesis could be a promising therapeutic approach for liver fibrosis.

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PMID: 

J Cancer. 2020 ;11(7):1679-1692. Epub 2020 Jan 14. PMID: 32194780

Abstract Title: 

Curcumol inhibits the proliferation and metastasis of melanoma via the miR-152-3p/PI3K/AKT and ERK/NF-κB signaling pathways.

Abstract: 

Melanoma is the most aggressive and treatment-resistant form of skin cancer. Curcumol is a Chinese medicinal herb traditionally used as a cancer remedy. However, the molecular mechanisms underlying the anticancer activity of curcumol in melanoma remains largely unknown. In the present study, we observed that Curcumol decreased mouse melanoma B16 cell proliferation and migration. The xenograft tumor assay showed that curcumol reduced melanoma volume and lung metastasis. Curcumol upregulated the expression of E-cadherin and downregulated the expression of N-cadherin, MMP2 and MMP9 in mouse melanoma B16 cell. Western blot analysis revealed that curcumol reduced the translocation of p65 to the nucleus and decreased p-ERK. Furthermore, curcumol attenuated c-MET, P13K and p-AKT protein expression and upregulated miR-152-3p gene expression. The dual-luciferase reporter assay indicated that c-MET was a target gene of miR-152-3p. Reduced expression of miR-152-3p partially attenuated the effect of curcumol on mouse melanoma B16 cell proliferation and migration. The decrease in c-MET, P13K and p-AKT protein expression following curcumol treatment in mouse melanoma B16 cells was notably attenuated by the miR-152-3p inhibitor. Taken together, our findings suggested that curcumol attenuated melanoma progression and concomitantly suppressed ERK/NF-κB signaling and promoted miR-152-3p expression to inactivate the c-MET/PI3K/AKT signaling pathway.

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PMID: 

J Ethnopharmacol. 2020 Apr 9 ;257:112835. Epub 2020 Apr 9. PMID: 32278762

Abstract Title: 

Curcumol inhibits the expression of programmed cell death-ligand 1 through crosstalk between hypoxia-inducible factor-1α and STAT3 (T705) signaling pathways in hepatic cancer.

Abstract: 

ETHNOPHARMACOLOGICAL RELEVANCE: Curcuma wenyujin is a Chinese traditional herbal medicine that is commonly used as an anti-oxidant, anti-proliferative, and anti-tumorigenic agent. Curcumol is a representative index component for the quality control of the essential oil of Curcuma wenyujin, which is currently used as an anti-cancer drug, and is included in the State Pharmacopoeia Commission of the People's Republic of China (2005). However, the mechanisms of action and molecular functions of curcumol are not yet fully elucidated.AIM OF THE STUDY: This study aimed to identify new effects of curcumol from the perspective of cancer immunotherapy.MATERIALS AND METHODS: The underlying mechanism of the inhibition of programmed cell death-ligand 1 (PD-L1) activation by curcumol was investigated in vitro via homology modeling, molecular docking experiments, luciferase reporter assays, MTT assays, RT-PCR, western blotting, and immunofluorescence assays. Changes in cellular proliferation, angiogenesis, and the tumor-killing activity of T-cells were analyzed via EdU labeling, colony formation, flow cytometry, wound-healing, Matrigel Transwell invasion, tube formation, and T-cell killing. The anti-tumor activity of curcumol was assessed in vivo in a murine xenograft model using Hep3B cells.RESULTS: Curcumol reduced the expression of phosphorylated signal transducer and activator of transcription 3 (p-STAT3) via JAK1, JAK2, and Src pathways and inhibited hypoxia-inducible factor-1α (HIF-1α) protein synthesis via mTOR/p70S6K/eIF4E and MAPK pathways. Furthermore, we revealed crosstalk between STAT3 and HIF-1α pathways, which collaboratively regulated PD-L1 activation, and that curcumol played a role in this regulation. Curcumol inhibited cell proliferation, S-phase progression, tube formation, invasion, and metastasis by inhibiting PD-L1. In addition, curcumol restored the activity of cytotoxic T-cells and their capacity for tumor cell killing by inhibiting PD-L1. In vivo experiments confirmed that curcumol inhibited tumor growth in a xenograft model.CONCLUSIONS: These results illustrated that curcumol inhibits the expression of PD-L1 through crosstalk between HIF-1α and p-STAT3 (T705) signaling pathways in hepatic cancer. Thus, curcumol might represent a promising lead compound for the development of new targeted anti-cancer therapeutics.

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PMID: 

Curr Dev Nutr. 2020 Apr ;4(4):nzaa038. Epub 2020 Mar 18. PMID: 32337476

Abstract Title: 

Gender Differences in Plasma Vitamin C Concentrations and Cognitive Function: A Pilot Cross-Sectional Study in Healthy Adults.

Abstract: 

Background: A number of investigations have highlighted the importance of vitamin C in maintaining brain health. Biologically, vitamin C has exhibited roles in neuromodulation, neurodevelopment, vascular support, and neuroprotection. Vitamin C's contribution to cognitive function in both cognitively intact and impaired cohorts has previously been assessed, with little focus on gender variability.Objective: The present study explored the interaction between gender and plasma vitamin C on cognitive performance, and the effect of different amounts of plasma vitamin C (adequate/inadequate) on various cognitive tasks by gender.Methods: This retrospective analysis was conducted in healthy adults ( = 80, female = 52, male = 28, 24-96 y) with a range of blood plasma vitamin C concentrations. Cognitive assessments included the Swinburne University Computerized Cognitive Assessment Battery (SUCCAB) and 2 pen-and-paper tests, the Symbol Digits Modalities Test (SDMT) and the Hopkins Verbal Learning Test-Revised (HVLT-R). Food-frequency questionnaires were used to elucidate dietary consumption.Results: After adjusting for a number of potential covariates such as age, number of prescribed medications and dose of vitamin C supplementation, results indicated a significant interaction ( 

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