PMID: 

Phytomedicine. 2019 Jun 20:152996. Epub 2019 Jun 20. PMID: 31272819

Abstract Title: 

Therapeutic potential of Aloe vera-A miracle gift of nature.

Abstract: 

BACKGROUND: Aloe vera is commonly used in the primary health care of human beings since time immemorial. It is an herb widely used in various traditional systems of medicine worldwide. Systematic and scientific investigation on A. vera as a medicinal plant has drawn considerable attention, and many laboratories are involved in isolation, characterization and evaluation of phytoconstituents for their nutraceutical and pharmaceutical applications.PURPOSE: The aim of this study was to provide an overview of the phytochemical, biological and medicinal attributes of A. vera against various diseases with special emphasis on underlying mechanisms of action.METHODS: PubMed, EBOSCO host, Science Direct, Scopus, and Cochrane library databases were utilized to search literature published between1977 and 2019 (till March). Major keywords used in various combinations included: Aloe vera, phytochemistry, metabolism, pharmacological activity, prevention, treatment, health, disease, in vivo, in vitro, and clinical studies.RESULTS: Various biological and pharmacological activities of A. vera, such as antioxidant, anti-inflammatory, immuno-modulatory, antimicrobial, antiviral, antidiabetic, hepatoprotective, anticancer, and skin-protective and wound-healing responses, have been attributed to the presence of many active compounds, including anthraquinones, anthrones, chromones, flavonoids, amino acids, lipids, carbohydrates, vitamins and minerals.CONCLUSION: Based on various preclinical studies, A. vera constituents have enormous potential to prevent and treat various diseases. Randomized clinical trials are needed to understand the full therapeutic potential of this unique medicinal plant.

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PMID: 

Phytother Res. 2019 Jul 1. Epub 2019 Jul 1. PMID: 31264313

Abstract Title: 

Hesperidin improves hepatic steatosis, hepatic enzymes, and metabolic and inflammatory parameters in patients with nonalcoholic fatty liver disease: A randomized, placebo-controlled, double-blind clinical trial.

Abstract: 

This study aimed to evaluate the effects of hesperidin on nonalcoholic fatty liver disease (NAFLD) characteristics. In this randomized, double-blind, controlled clinical trial, 50 NAFLD patients were supplemented with either 1-g hesperidin capsule or identical placebo capsule for 12 weeks. During the intervention, both groups were advised to follow healthy lifestyle habits including dietary and physical activity recommendations. At the end of the study, hesperidin supplementation, compared with placebo, was associated with a significant reduction in alanine aminotransferase (p = .005), γ-glutamyltransferase (p = .004), total cholesterol (p = .016), triglyceride (p = .049), hepatic steatosis (p = .041), high-sensitivity C-reactive protein (p = .029), tumor necrosis factor-α, and nuclear factor-κB (NF-κB). In conclusion, our results indicate that hesperidin supplementation accompanied with lifestyle modification is superior to lifestyle modification alone in management of NAFLD at least partially through inhibiting NF-κB activation and improving lipid profile. Further studies with higher dose of hesperidin are required to find the optimal dose.

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PMID: 

Nutr Rev. 2019 Jul 4. Epub 2019 Jul 4. PMID: 31271436

Abstract Title: 

Effects of hesperidin consumption on cardiovascular risk biomarkers: a systematic review of animal studies and human randomized clinical trials.

Abstract: 

CONTEXT: The cardioprotective effects of the flavonoid hesperidin, which is present in citrus products, are controversial and unclear. This systematic review was conducted in accordance with the PRISMA 2015 guidelines.OBJECTIVE: To evaluate the current evidence from animal and human clinical studies and thus determine whether the consumption of hesperidin exerts beneficial effects on cardiovascular risk factors.DATA SOURCES: PICOS (Population, Intervention, Comparison, Outcome, and Study Design) criteria defined the research question. Searches of the PubMed and Cochrane Plus databases were conducted and studies that met the inclusion criteria and were published in English in the last 15 years were included.DATA EXTRACTION: The first author, year of publication, study design, characteristics of animals and humans, intervention groups, dose of hesperidin, route of administration, duration of the intervention, cardiovascular risk biomarkers assessed, and results observed were extracted from the included articles.RESULTS: A total of 12 animal studies and 11 randomized clinical trials met the inclusion criteria. In the animal studies, the glucose, total and LDL cholesterol, and triglyceride levels decreased with chronic flavonoid consumption. In the human studies, endothelial function improved with flavonoid consumption, whereas no conclusive results were observed for the other biomarkers.CONCLUSIONS: Animal studies have revealed that hesperidin and hesperetin consumption reduces glucose levels and various lipid profile parameters. However, a definitive conclusion cannot be drawn from the existing human clinical trials. Further research is needed to confirm whether the findings observed in animal models can also be observed in humans.SYSTEMATIC REVIEW REGISTRATION: Prospero registration number CRD42018088942.

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PMID: 

Eur Rev Med Pharmacol Sci. 2019 Jun ;23(12):5468-5476. PMID: 31298400

Abstract Title: 

The protective effects of Berberine and Hesperidin on inflammatory factor-stimulating cardiac fibroblasts.

Abstract: 

OBJECTIVE: The previous work has shown that Berberine and Hesperidin have beneficial effects on cardiovascular diseases. However, the underlying mechanisms remain unknown. This study aimed to investigate the effect of Berberine and Hesperidin on inflammatory cytokine secretion, proliferation, differentiation, and collagen synthesis of cardiac fibroblasts stimulated by the transforming growth factor-β1 (TGF-β1), and the potential of these drugs to regulate the Notch1 signaling pathway.PATIENTS AND METHODS: Neonatal rat primary cardiac fibroblasts were stimulated with 5 ng/mL TGF-β1 as model (TGF) group. In the Berberine (TGF+B) group cells were given TGF-β1, along with 1.25/2.5/5/10 mg/L Berberine, while the Hesperidin (TGF+H) group was treated with TGF-β1 and 12.5/25/50/100 µmmol/L Hesperidin. Cellular proliferation, differentiation, and collagen synthesis were evaluated. The role of the Notch1 signaling pathway in the protective effects of Berberine and Hesperidin was analyzed by using γ-secretase inhibitor (DAPT) to block the Notch1 pathway.RESULTS: 5/10 mg/L Berberine intervention could noticeably decrease both TGF-β1 and IL-1β levels, 25/50/100 µmol/L Hesperidin could reduce IL-1β secretion from TGF-β1 stimulated cardiac fibroblasts. Both Berberine and Hesperidin decreased the expression of α-SMA and cell viability in a concentration-dependent manner; however, the apoptosis of cardiac fibroblasts was not influenced. 10 mg/L Berberine or at least 50 µmol/L Hesperidin could noticeably decrease MMP-1 expression, and at least 5 mg/L Berberine or 100 µmol/L Hesperidin could markedly reduce MMP-9 expression. Using DAPT to block Notch1 signaling could reverse the protective effects of Berberine and Hesperidin.CONCLUSIONS: Berberine and Hesperidin can reduce the secretion of inflammatory cytokines, differentiation, and proliferation, and increase the collagen synthesis of cardiac fibroblasts stimulated by TGF-β1 via the Notch1 signaling pathway.

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PMID: 

Nutr Cancer. 2019 Jul 9:1-12. Epub 2019 Jul 9. PMID: 31287738

Abstract Title: 

The Role of Polyphenol (Flavonoids) Compounds in the Treatment of Cancer Cells.

Abstract: 

Cancer remains a second leading cause of deaths and major public health problem. It occurs due to extensive DNA damage caused by ultraviolet radiations, ionizing radiations, environmental agents, therapeutic agents, etc. Among all cancers, the most frequently diagnosed cancers are lung (12.7%), breast (10.9%), colorectal (9.7%), and gastric cancer (7.81%). Natural compounds are most favorable against cancer on the count of their anti-cancerous ability, easy to avail and efficient. Among natural compounds, polyphenols (flavonoids, catechin, hesperetin, flavones, quercetin, phenolic acids, ellagic acid, lignans, stilbenes, etc.) represent a large and diverse group used in the prevention and treatment of cancer. Natural flavonoids are derived from different plant sources and from various medicinal plants including,,,, etc. Natural flavonoids possess antioxidant, anti-inflammation, as well as anti-cancerous activities through multiple pathways, they induce apoptosis in breast, colorectal, and prostate cancers, lower the nucleoside diphosphate kinase-B activity in lung, bladder and colon cancers, inhibit cell-proliferation and cell cycle arrest by suppressing the NF-kB pathway in various cancers, etc. The current review summarized the anticancer activities of natural polyphenols and their mechanisms of action. Abbreviations Akt pathway A Serine/Threonine-Protein Kinase pathway COX-2 Cyclooxygenase-2 HaCaT Cultured Human Keratinocyte HDAC Histone Deacetylase MAPK pathway Mitogen-Activated Protein Kinases pathway (Oestrogen Receptor); NF-kBkappa-light-chain-enhancer of activated B cell PARP Poly ADP Ribose Polymerase ROS Reactive oxygen Speciese STAT-1 Signal Transducer and Activator of Transcription 1.

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PMID: 

AAPS J. 2019 Jun 28 ;21(5):83. Epub 2019 Jun 28. PMID: 31254216

Abstract Title: 

Anthocyanin Delphinidin Prevents Neoplastic Transformation of Mouse Skin JB6 P+ Cells: Epigenetic Re-activation of Nrf2-ARE Pathway.

Abstract: 

Redox imbalance is a major contributor to the pathogenesis of melanoma and nonmelanoma skin cancer. Activation of the nuclear factor E2-related factor 2 (Nrf2) antioxidant responsive element (ARE) pathway is an intrinsic defense mechanism against oxidative stress. Flavonoids such as anthocyanidins, which are found abundantly in fruits and vegetables, have been shown to activate Nrf2. However, the epigenetic and genetic mechanisms by which anthocyanidins modulate the Nrf2-ARE pathway remain poorly understood in the context of skin cancer. In this study, delphinidin, one of the most potent and abundant anthocyanidins in berries, significantly inhibited 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced neoplastic cell transformation in mouse epidermal JB6 P+ cells by 69.4 to 99.4%. The mechanism was elucidated based on observations of increased ARE-driven luciferase activity and elevated mRNA and protein expression of Nrf2 downstream genes, such as heme oxygenase-1 (Ho-1), in JB6 P+ cells. Activation of the Nrf2-ARE pathway was correlated with demethylation of 15 CpG sites in the mouse Nrf2 promoter region between nt - 1226 and - 863 from the transcription start site. The reduced CpG methylation ratio in the Nrf2 promoter region was consistent with observed decreases in the protein expression of DNA methyltransferases 1 (DNMT1), DNMT3a, and class I/II histone deacetylases (HDACs). Overall, our results suggestthat delphinidin, an epigenetic demethylating agent of the Nrf2 promoter, can activate the Nrf2-ARE pathway, which can be applied as a potential skin cancer chemopreventive agent.

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PMID: 

Biol Res Nurs. 2019 Jul 9:1099800419857812. Epub 2019 Jul 9. PMID: 31288563

Abstract Title: 

The Effects of Exercise on Pain and Reproductive Performance in Female Pregnant Mice With Neuropathic Pain.

Abstract: 

Pain can have negative, physiological and psychological impacts on pregnancy. Pregnant women are fearful of using pain medication because of teratogenic effects. In this study, we evaluated whether exercise could lower pain sensitivity in pregnant mice with neuropathic pain and reduce the negative effects of maternal pain on newborns. We randomly assigned 32 female mice to one of four groups (eight mice/group): Sham surgery with standard environment (SE) or enriched environment (EE) or spare nerve injury (SNI) with SE or EE. Mice in EE groups had access to an exercise wheel. Mothers were evaluated for mechanical sensitivity with Von Frey filaments and for exercise performance with computerized running wheels. Mice were impregnated 2 weeks after the initiation of EE. Pups were weighed and measured for length at birth and evaluated for negative geotaxis, righting, forelimb grasping, rooting, and crawling at 3 days postpartum and for crawling at 6 days postpartum. Following euthanasia, mothers' frontal cortexes were analyzed for selected neuropeptides. After exercise exposure, only SNI-SE females remained neuropathic. Exercise levels were similar between EE groups. Some brain neuropeptides (endorphins, enkephalins, and oxytocin) from SNI females showed significant differences with exercise. Number of pups was significantly smaller in the SNI-SE group. Significantly more pups died at birth in the SNI-SE group, but pup behavior tests (except righting) were similar across groups. Exercise can reduce neuropathic pain in pregnant mice. Neuropathic pain does not impact motor neurodevelopment of mice pups but does appear to affect litter size and neonatal mortality.

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PMID: 

Neurorehabil Neural Repair. 2019 Jul 9:1545968319860485. Epub 2019 Jul 9. PMID: 31286830

Abstract Title: 

Neuroprotective Effects of Exercise on the Morphology of Somatic Motoneurons Following the Death of Neighboring Motoneurons.

Abstract: 

. Motoneuron loss is a severe medical problem that can result in loss of motor control and eventually death. We have previously demonstrated that partial motoneuron loss can result in dendritic atrophy and functional deficits in nearby surviving motoneurons, and that treatment with androgens can be neuroprotective against this dendritic atrophy. Exercise has also been shown to be protective following a variety of neural injury models and, in some cases, is dependent on androgen action.. In this study, we explored whether exercise shows the same neuroprotective effect on induced dendritic atrophy as that seen with androgen treatment.. Motoneurons innervating the vastus medialis muscles of adult male rats were selectively killed by intramuscular injection of cholera toxin-conjugated saporin. Following saporin injections, some animals were allowed free access to a running wheel attached to their home cages. Four weeks later, motoneurons innervating the ipsilateral vastus lateralis muscle were labeled with cholera toxin-conjugated horseradish peroxidase, and dendritic arbors were reconstructed in 3 dimensions.. Dendritic arbor lengths of animals allowed to exercise were significantly longer than those not allowed to exercise.. These findings indicate that exercise following neural injury exerts a protective effect on motoneuron dendrites comparable to that seen with exogenous androgen treatment.

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Cooking Habits That Can Make You Sick – https://weil.ws/2zhdqm0 

PMID: 

J Appl Physiol (1985). 2019 Jul 11. Epub 2019 Jul 11. PMID: 31295062

Abstract Title: 

Chronic exercise training prevents coronary artery stiffening in aortic-banded miniswine: Role of perivascular adipose-derived advanced glycation end products.

Abstract: 

Aims Heart failure (HF) is associated with increased large conduit artery stiffness and afterload resulting in stiffening of the coronary arteries. Perivascular adipose tissue (PVAT) and advanced glycation end products (AGE) both promote arterial stiffness, yet the mechanisms by which coronary PVAT promotes arterial stiffness and the efficacy of exercise to prevent coronary stiffness are unknown. We hypothesized both chronic continuous and interval exercise training would prevent coronary PVAT-mediated AGE secretion and arterial stiffness. Methods and Results Yucatan mininature swine were divided into four groups: control-sedentary (CON), aortic-banded sedentary heart failure (HF), aortic-banded HF continuous exercise trained (HF+CONT), and aortic-banded HF interval exercise trained (HF+IT). The left circumflex (LCX) and right coronary artery (RCA) underwent ex vivo mechanical testing, and arterial AGE, elastin and collagen were assessed. Coronary elastin elastic modulus (EEM) and elastin protein were lower, and AGE was increased with HF compared to CON that was prevented by both HF+CONT and HF+IT. Mouse aortic segments treated with swine coronary PVAT-conditioned media had lower EEM, elastin content, greater AGE secretion and arterial AGE accumulation in HF compared with CON, which was prevented by both HF+CONT and HF+IT. Aminoguanidine (AMG), an AGE inhibitor, prevented the reduction in the EEM, arterial elastin content and AGE accumulation in mouse aortic segments treated with PVAT conditioned media in the HF group. Conclusions Our data demonstrate efficacy for chronic continuous and interval exercise to prevent coronary artery stiffness via inhibition of PVAT-derived AGE secretion in a pre-clinical mini-swine model of pressure overload-induced HF.

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