PMID: 

Front Oncol. 2019 ;9:501. Epub 2019 Jun 14. PMID: 31259152

Abstract Title: 

Ursolic Acid Reverses the Chemoresistance of Breast Cancer Cells to Paclitaxel by Targeting MiRNA-149-5p/MyD88.

Abstract: 

Paclitaxel (PTX) is widely used as a front-line chemotherapy for breast cancer treatment. However, its clinical applications are limited by the development of chemoresistance. The objective of this study was to investigate the reversal effects of ursolic acid (UA) on PTX resistance and the possible mechanisms in breast cancer. The role of miRNA-149-5p/MyD88 in the regulation of PTX resistance was investigated by the transfection of breast cancer cells with MDA-MB-231 (231) and MDA-MB-231/PTX-resistance (231/PTX) with lentiviruses carrying the MyD88 gene, shRNA specific for MyD88, the miR-149-5p gene, and shRNA specific for miR-149-5p. The PTX sensitivity was assessed by a CCK-8 assay. qRT-PCR and Western blot analyses were used to detect changes in the mRNA and protein levels. Flow cytometry was used to measure the rate of cell apoptosis. A luciferase activity assay was used to detect the binding site of miR-149-5p on the 3'UTR of MyD88. 231/PTX cells were injected into the flanks of female athymic nude mice, and the mice were randomly divided into the five following groups: PBS, PTX (low), PTX (high), UA, and PTX+UA. Our data show that UA reversed the resistance of breast cancer 231/PTX cells to PTXand. UA treatment significantly increased the expression of miR-149-5p, which was lower in 231/PTX cells than in 231 cells. Furthermore, the overexpression of miR-149-5p increased the sensitivity of 231/PTX cells to PTX treatment, whereas the knockdown of the miR-149-5p gene attenuated the effects of UA on the regulation of PTX sensitivity. A luciferase assay demonstrated that miR-149-5p could directly regulate the transcriptional activity of MyD88, a known PTX-resistance gene, by targeting the 3'UTR of MyD88. Meanwhile, the downregulation of MyD88 through the overexpression of miR-149-5p or UA treatment inhibited the activation of the Akt signaling pathway in 231/PTX cells. Thus, our data indicate that UA can reverse PTX resistance by targeting the miRNA-149-5p/MyD88 axis in breast cancer cells.

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PMID: 

Toxicon. 2019 Jul 26. Epub 2019 Jul 26. PMID: 31356822

Abstract Title: 

Ameliorative effect of ursolic acid on ochratoxin A-induced renal cytotoxicity mediated by Lonp1/Aco2/Hsp75.

Abstract: 

Ochratoxin A (OTA) is a mycotoxin ubiquitous in feeds and foodstuffs. The water-insoluble pentacyclic triterpene bioactive compound, ursolic acid (UA), is widespread in various cuticular waxes of edible fruits, food materials, and medicinal plants. Although studies have reported that oxidative stress was involved in both the nephrotoxicity of OTA and the renoprotective function of UA, the role of stress-responsive Lon protease 1 (Lonp1) in the renoprotection of UA against OTA is still unknown. In this study, cell viability, reactive oxygen species (ROS) production, and several proteins' expressions of human embryonic kidney 293T (HEK293T) cells in response to UA, OTA, and/or Lonp1 inhibitor CDDO-me treatment were detected to reveal the protective mechanism of UA against OTA-induced renal cytotoxicity. Results indicated that a 2 h-treatment of 1 μM UA could significantly alleviate the ROS production and cell death induced by a 24 h-treatment of 8 μM OTA in HEK293T cells (P 

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PMID: 

Cardiovasc Toxicol. 2019 Jun 11. Epub 2019 Jun 11. PMID: 31183600

Abstract Title: 

The Protective Effect of Crataegus aronia Against High-Fat Diet-Induced Vascular Inflammation in Rats Entails Inhibition of the NLRP-3 Inflammasome Pathway.

Abstract: 

This study investigated whether the whole-plant aqueous extract of Crataegus aronia (C. aronia) could protect against or alleviate high-fat diet (HFD)-induced aortic vascular inflammation in rats by inhibiting the NLRP-3 inflammasome pathway and examined some mechanisms of action with respect to its antioxidant and hypolipidemic effects. Adult male Wistar rats were divided into five groups (n = 6/each): standard diet (10% fat) fed to control rats, control + C. aronia (200 mg/kg), HFD (40% fat), HFD + C. aronia, and HFD post-treated with C. aronia. The HFD was fed for 8 weeks and C. aronia was administered orally for 4 weeks. In addition, isolated macrophages from controlrats were pre-incubated with two doses of C. aronia (25 and 50 μg/mL) with or without lipopolysaccharide (LPS) stimulation. Only in HFD-fed rats, co- and post-C. aronia therapy lowered circulatory levels of LDL-C and ox-LDL-c and aortic protein levels of LOX-1 and CD36. C. aronia also inhibited the nuclear accumulation of NF-κB and lowered protein levels of NLRP-3, caspase-1, and mature IL-1β. In vitro, in the absence of ox-LDL-c, C. aronia led to reduced nuclear levels of NF-κB, ROS generation, and protein NLRP-3 levels, in both LPS-stimulated and unstimulated macrophages, in a dose-dependent manner. However, protein levels of LOX-1 were not affected by C. aronia in unstimulated cells. In conclusion, C. aronia inhibits the NLRP-3 inflammasome pathway, induced by HFD feeding in the aorta of rats, mainly by its hypolipidemic effect and in vitro, in LPS-stimulated macrophages, by itsantioxidant effect.

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PMID: 

Oxid Med Cell Longev. 2019 ;2019:8512048. Epub 2019 May 16. PMID: 31223427

Abstract Title: 

Antioxidant and Anti-inflammatory Mechanisms of Neuroprotection by Ursolic Acid: Addressing Brain Injury, Cerebral Ischemia, Cognition Deficit, Anxiety, and Depression.

Abstract: 

Ursolic acid (UA) is a pentacyclic triterpene which is found in common herbs and medicinal plants that are reputed for a variety of pharmacological effects. Both as an active principle of these plants and as a nutraceutical ingredient, the pharmacology of UA in the CNS and other organs and systems has been extensively reported in recent years. In this communication, the antioxidant and anti-inflammatory axis of UA's pharmacology is appraised for its therapeutic potential in some common CNS disorders. Classic examples include the traumatic brain injury (TBI), cerebral ischemia, cognition deficit, anxiety, and depression. The pharmacological efficacy for UA is demonstrated through the therapeutic principle of one drug→ multitargets → one/many disease(s). Both specific enzymes and receptor targets along with diverse pharmacological effects associated with oxidative stress and inflammatory signalling are scrutinised.

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PMID: 

J Ethnopharmacol. 2019 Jul 23 ;243:112107. Epub 2019 Jul 23. PMID: 31349027

Abstract Title: 

The fruit of Crataegus pinnatifida ameliorates memory deficits inβ-amyloid protein-induced Alzheimer's disease mouse model.

Abstract: 

ETHNOPHARMACOLOGICAL RELEVANCE: The fruit of Crataegus pinnatifida is a traditional medicine widely used as digestive drug in East Asia. Although Chinese herbal medicine used it for mental health, scientific evidence does not exist, yet.AIMS OF STUDY: The aim of this study is to show that the ethanol extract of the fruit of Crataegus pinnatifida (CPE) has neuroprotective effect on Alzheimer' disease model mice.MATERIALS AND METHODS: Intracerebroventricular injection of Aβ was used to induce Alzheimer's disease-like pathology. Passive avoidance and Y-maze tasks were used to examine the effect of CPE on memory impairments by Aβ. Immunohistochemistry was used to examine the effect of CPE on glial activation. ThT assay was used to observe the effect of CPE on Aβ aggregation. MTT and LDH release assays were utilized to examine effects of CPE on Aβ-induced cytotoxicity.RESULTS: CPE prevented memory deficit in Aβ-induced memory impairment model. Moreover, CPE prevented glial activation in the hippocampus of Aβ-injected model. In in vitro test, CPE inhibited Aβ fibril formation in a concentration-dependent manner. CPE also caused disaggregation of Aβ fibrils. Along with this, CPE blocked neuronal cell death induced by Aβ.CONCLUSIONS: Collectively, these experimental findings demonstrated that CPE could be a candidate for development of AD therapy.

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PMID: 

J Food Biochem. 2019 Feb ;43(2):e12708. Epub 2018 Nov 11. PMID: 31353662

Abstract Title: 

Protective effects of hawthorn (Crataegus pinnatifida) polyphenol extract against UVB-induced skin damage by modulating the p53 mitochondrial pathway in vitro and in vivo.

Abstract: 

This study investigated the effect of a hawthorn polyphenol extract (HPE) on ultraviolet B (UVB)-induced damage in HaCaT cells and mice. High-performance liquid chromatography/electrospray ionization tandem mass spectrometry was used to analyze the phenolic composition of HPE. The protective effects of HPE and its main components were compared in HaCaT cells. An enzyme-linked immunosorbent assay was used to detect DNA damage (8-hydroxydeoxyguanosine levels). Flow cytometry and western blotting were used to measure the extent of apoptosis and the levels of apoptosis-related proteins, respectively. Treatment with HPE or its polyphenol components inhibited the UVB-induced damage by removing an excess of reactive oxygen species (ROS), reducing DNA damage and p53 activation, regulating the protein expression of B-cell lymphoma 2 family members toward antiapoptotic ratios, and reducing caspase activation. Similar effects were observed in a UVB-irradiated mouse skin, as detected using terminal deoxynucleotidyl transferase dUTP nick-end labeling, immunohistochemistry, and western blotting assays. These results suggest that HPE can be used as a natural dietary supplement for the prevention and treatment of UVB radiation-induced skin damage. PRACTICAL APPLICATIONS: Hawthorn (Crataegus pinnatifida) shows antioxidant, anti-inflammatory, and lipid-lowering effects. As natural, healthy, and effective additives, HPEs have been widely used in food and health products. The results of this study reveal the molecular mechanisms underlying HPE effects, showing that HPE reverses the effects of UVB irradiation via removal of an excess of ROS and reduction of DNA damage and p53 expression in vitro and in vivo. Consequently, HPE upregulates the expression of antiapoptotic BCL-2 and downregulates that of proapoptotic BAX, thereby reducing the activation of caspase-3/9 and inhibiting apoptosis. These findings suggest that HPE can be used as the base ingredient for antiphotoaging food products. This study provides both theoretical and experimental background for hawthorn deep processing and utilization.

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PMID: 

Iran J Basic Med Sci. 2019 May ;22(5):460-468. PMID: 31217924

Abstract Title: 

The effects of(Chinese hawthorn) on metabolic syndrome: A review.

Abstract: 

Metabolic syndrome is described as a group of risk factors in which at least three unhealthy medical conditions, including obesity, high blood sugar, hypertension or dyslipidemia occur simultaneously in a patient. These conditions raise the risk for diabetes mellitus and cardiovascular diseases. Many recent studies have focused on herbal remedies and their pharmacological effects on metabolic syndrome.or Chinese hawthorn has been widely used in the treatment of hyperlipidemia and cardiovascular diseases. Its leaves, fruits and seeds have various active substances such as, flavonoids, triterpenic acids and sesquiterpenes, which through different mechanisms can be beneficial in metabolic syndrome. Flavonoids found in the leaves of hawthorn can significantly reduce atherosclerotic lesion areas, the fruit extracts contain two triterpenic acids (oleanolic acid and ursolic acid), that have the ability to inhibit the acyl-coA-cholesterol acyltransferase (ACAT) enzyme and as a result reduce very low-density lipoprotein (VLDL) and low-density lipoprotein (LDL) cholesterol levels. Another example regards a sesquiterpene found in the seeds of, which exhibits the ability to inhibit platelet aggregation, thus showing antithrombotic activity. Various studies have shown thatcan have beneficial effects on controlling and treating high blood sugar, dyslipidemia, obesity and atherosclerosis. The aim of this review is to highlight the interesting effects ofon metabolic syndrome.

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PMID: 

Oncol Lett. 2019 Jun ;17(6):4761-4767. Epub 2019 Mar 19. PMID: 31186681

Abstract Title: 

Anticancer effect of ursolic acid via mitochondria-dependent pathways.

Abstract: 

Ursolic acid is a plant-derived pentacyclic triterpenoid found in various medicinal herbs and fruits. It has generated clinical interest due to its anti-inflammatory, antioxidative, antiapoptotic and anticarcinogenic effects. An increasing amount of evidence supports the anticancer effect of ursolic acid in various cancer cells. One of the hallmarks of malignant transformation is metabolic reprogramming that sustains macromolecule synthesis, bioenergetic demand and tumor cell survival. Mitochondria are important regulators of tumorigenes is as well as a major site of the metabolic reactions that facilitate this reprogramming and adaption to cellular and environmental changes. The current review explored the close association between the anticancer effect of ursolic acid and the activation of mitochondrial-dependent signaling pathways.

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PMID: 

BMC Pulm Med. 2019 Jun 6 ;19(1):103. Epub 2019 Jun 6. PMID: 31170951

Abstract Title: 

Ursolic acid alleviates airway-vessel remodeling and muscle consumption in cigarette smoke-induced emphysema rats.

Abstract: 

BACKGROUND: This study assessed the effects of ursolic acid (UA) on airway-vessel remodeling and muscle atrophy in cigarette smoke (CS)-induced emphysema rats and investigated potential underlying mechanisms.METHODS: Emphysema was induced in a rat model with 3 months of CS exposure. Histology and immunohistochemistry (IHC) stains were used to assess airway-vessel remodeling and muscle atrophy-associated changes. Levels of cleaved-caspase3, 8-OHdG, and S100A4 were measured in airways and associated vessels to evaluate cell apoptosis, oxidant stress, epithelial-to-mesenchymal transition (EMT), and endothelial-to-mesenchymal transition (EndMT)-associated factors. Western blot and/or IHC analyses were performed to measure transforming growth factor-beta 1(TGF-β1)/Smad2.3, alpha-smooth muscle actin (α-SMA), and insulin-like growth factor 1 (IGF1) expression. We also gave cultured HBE and HUVEC cells Cigarette Smoke Extract (CSE) administration and UA intervention. Using Western blot method to measure TGF-β1/Smad2.3, α-SMA, S100A4, and IGF1 molecules expression.RESULTS: UA decreased oxidant stress and cell apoptosis in airway and accompanying vascular walls of cigarette smoke-induced emphysema model rats. UA alleviated EMT, EndMT, changes associated with airway-vessel remodeling and muscle atrophy. The UA effects were associated with IGF1 and TGF-β1/Smad2.3 pathways.CONCLUSIONS: UA reduced EMT, EndMT, airway-vessel remodeling, and musculi soleus atrophy in CS-induced emphysema model rats at least partly through IGF1 and TGF-β1/Smad2.3 signaling pathways.

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PMID: 

Clin Rehabil. 2019 Jun 24:269215519856675. Epub 2019 Jun 24. PMID: 31230466

Abstract Title: 

Pilates method in the treatment of patients with Chikungunya fever: a randomized controlled trial.

Abstract: 

OBJECTIVE: The aim of this study was to evaluate the effects of the Pilates method on the reduction of pain, improvement of joint function, and quality of life of patients with chronic Chikungunya fever.DESIGN: This is a randomized, controlled, blind trial for the evaluators.SETTING: The study was conducted at the Advanced Laboratory in Physical Education and Health at Federal University of Pernambuco, Brazil.SUBJECTS: A total of 51 patients were allocated randomly and divided into 2 groups: a Pilates group (26 patients) and a control group (25 patients). After 12 weeks, 4 patients in the Pilates group and 5 in the control group were lost to follow-up.INTERVENTION: The Pilates group performed 24 Pilates method intervention sessions; the control group continued to receive standard clinical treatment at the outpatient clinic.MAIN MEASURES: The main measures were as follows: visual analogue scale (VAS) for pain, functional capacity evaluated by Health Assessment Questionaire (HAQ), quality of life measured by the 12-Item Short-Form Health Survey (SF-12), and range of joint motion by goniometry.RESULTS: After 12 weeks, patients in the Pilates group presented lower VAS ( 

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