PMID: 

J Cell Biochem. 2019 Oct 14. Epub 2019 Oct 14. PMID: 31609017

Abstract Title: 

Therapeutic and biological activities of berberine: The involvement of Nrf2 signaling pathway.

Abstract: 

Since the beginning of the 21st century, studies have focused on developing drugs from naturally occurring compounds. Berberine (Brb) as a plant-derived compound is of interest. It is an isoquinone alkaloid which is derived from Berberis aristata, Berberis aquifolium and Berberis vulgaris. This plant-derived compound has a variety of pharmacological effects such as antioxidant, anti-inflammatory, antidiabetic, antidiarrheal, antitumor, antimicrobial, and anti-inflammatory. Various studies have demonstrated the therapeutic and biological activities of Brb, but there is a lack of a precise review to manifest the signaling pathway of action of Brb. The nuclear factor erythroid 2-related factor 2 (Nrf2) is a highly conserved pathway which mainly involves in preservation of redox balance. At the present review, we describe the therapeutic and biological activities of Brb as well as the relevant mechanisms specially focused on the Nrf2 signaling pathway.

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PMID: 

Curr Med Sci. 2019 Oct ;39(5):748-753. Epub 2019 Oct 14. PMID: 31612392

Abstract Title: 

Berberine Attenuates Cigarette Smoke Extract-induced Airway Inflammation in Mice: Involvement of TGF-β1/Smads Signaling Pathway.

Abstract: 

Although several studies confirmed that berberine may attenuate airway inflammation in mice with chronic obstructive pulmonary disease (COPD), its underlying mechanisms were not clear until now. We aimed to establish an experiment mouse model for COPD and to investigate the effects of berberine on airway inflammation and its possible mechanism in COPD model mice induced by cigarette smoke extract (CSE). Twenty SPF C57BL/6 mice were randomly divided into PBS control group, COPD model group, low-dose berberine group and high-dose berberine group, 5 mice in each group. The neutrophils and macrophages were examined by Wright's staining. The levels of inflammatory cytokines TNF-α and IL-6 in bronchoalveolar lavage fluid (BALF) were determined by enzyme-linked immunosorbent assay. The expression levels of TGF-β1, Smad2 and Smad3 mRNA and proteins in lung tissues were respectively detected by quantitative real-time polymerase chain reaction and Western blotting. It was found that CSE increased the number of inflammation cells in BALF, elevated lung inflammation scores, and enhanced the TGF-β1/Smads signaling activity in mice. High-dose berberine restrained the alterations in the COPD mice induced by CSE. It was concluded that high-dose berberine ameliorated CSE-induced airway inflammation in COPD mice. TGF-β1/Smads signaling pathway might be involved in the mechanism. These findings suggested a therapeutic potential of high-dose berberine on the CSE-induced airway inflammation.

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PMID: 

J Sex Med. 2019 Sep 26. Epub 2019 Sep 26. PMID: 31564534

Abstract Title: 

Role of JAK2 in the Pathogenesis of Diabetic Erectile Dysfunction and an Intervention With Berberine.

Abstract: 

BACKGROUND: Oxidative stress is a significant contributor to the poor treatment efficacy on erectile dysfunction induced by diabetes mellitus (DMED). Thus, understanding the mechanism underlying oxidative stress will aid in the identification of novel therapeutic targets.AIM: To define the role of Janus kinase 2 (JAK2) in mediating oxidative stress in the corpus cavernosum smooth muscle cells (CCSMCs) and to investigate the therapeutic effect of monomeric berberine (BB), which inhibits JAK2, in the pathogenesis of DMED.METHODS: Streptozotocin was used to establish type I diabetic rat models and apomorphine tests were conducted to determine DMED rats. Eighteen DMED rats were divided into the DMED group and the DMED+BB group, whereas another 10 age-matched rats formed the control group. CCSMCs were isolated from the corpus cavernosum of rats and were treated with the JAK2 inhibitor alpha cyanano-(3,4-hydroxyl)N-benzophenylamine (AG490) and/or BB.OUTCOMES: Metabolic parameters; erectile function; histologic and molecular alterations.RESULTS: Erectile function was impaired and excessive oxidative stress was found in the DMED group. Excessive oxidative stress led to decreased expression level of phosphorylated endothelial nitric oxide synthase at serine 1177/endothelial nitric oxide synthase and increased expression level of Ras homolog gene family and Rho kinase 1/2. Meanwhile, the relative expression ratio of phosphorylated JAK2/JAK2 was significantly greater in the DMED group than that in the other groups. In vitro, oxidative stress was significantly reduced along with reduced intracellular calcium upon treatment with the JAK2 inhibitor, AG490. Moreover, the CCSMCs treated with BB showed changes similar to those upon treatment with AG490. In vivo experiments also confirmed that the erectile function of the DMED+BB group was improved, accompanied by decreased phosphorylated JAK2/JAK2 and decreased oxidative stress.CLINICAL TRANSLATION: JAK2 can be used as a therapeutic target and BB can be used as a potential drug for the clinical treatment of DMED.STRENGTHS AND LIMITATIONS: This study examines the promoting effect of JAK2 on oxidative stress occurrence in the corpus cavernosum and on the development of DMED in both animal experiments and cell experiments, as well evaluates the inhibitory effect of BB on JAK2 and its therapeutic effect on DMED. The main limitation of our current study is the lack of an appropriate means for activating JAK2.CONCLUSIONS: JAK2 can induce DMED by enhancing oxidative stress and BB can play a role in treating DMED by inhibiting JAK2 and reducing oxidative stress. Our study provides an option and an idea for further studies on the pathogenesis and treatment of DMED. Song J, Tang Z, Li H, et al. Role of JAK2 in the Pathogenesis of Diabetic Erectile Dysfunction and an Intervention With Berberine. J Sex Med 2019;XX:XXX-XXX.

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PMID: 

Sci Rep. 2019 Oct 10 ;9(1):14528. Epub 2019 Oct 10. PMID: 31601842

Abstract Title: 

Pomegranate Juice and Extract Consumption Increases the Resistance to UVB-induced Erythema and Changes the Skin Microbiome in Healthy Women: a Randomized Controlled Trial.

Abstract: 

In vitro and animal studies have demonstrated that topical application and oral consumption of pomegranate reduces UVB-induced skin damage. We therefore investigated if oral pomegranate consumption will reduce photodamage from UVB irradiation and alter the composition of the skin microbiota in a randomized controlled, parallel, three-arm, open label study. Seventy-four female participants (30-45 years) with Fitzpatrick skin type II-IV were randomly assigned (1:1:1) to 1000 mg of pomegranate extract (PomX), 8 oz of pomegranate juice (PomJ) or placebo for 12 weeks. Minimal erythemadose (MED) and melanin index were determined using a cutometer (mexameter probe). Skin microbiota was determined using 16S rRNA sequencing. The MED was significantly increased in the PomX and PomJ group compared to placebo. There was no significant difference on phylum, but on family and genus level bacterial composition of skin samples collected at baseline and after 12 week intervention showed significant differences between PomJ, PomX and placebo. Members of the Methylobacteriaceae family contain pigments absorbing UV irradiation and might contribute to UVB skin protection. However, we were not able to establish a direct correlation between increased MED and bacterial abundance. In summary daily oral pomegranate consumption may lead to enhanced protection from UV photodamage.

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Cannabidiol, or CBD, is a non-psychoactive compound produced by the marijuana plant that seems to be everywhere these days. Maybe you’ve even been asked if you’d like it added to your morning cup of joe! Interestingly, the chemical structure of CBD is very similar to THC, which is the marijuana-derived compound responsible for getting people high and the one screened for by drug tests.

This structural similarity begs the question: Could using CBD make you fail a drug test? In this episode of Reactions, we break down the chemistry behind the possibilities:

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Credits:
Source: https://phys.org/

News Link:  https://phys.org/news/2019-06-video-drug-cbd.html

The post [Video] Could you fail a drug test by taking CBD? appeared first on AlternativeWellness.

PMID: 

J Ethnopharmacol. 2020 Jan 10 ;246:112243. Epub 2019 Sep 18. PMID: 31541722

Abstract Title: 

Ginkgo biloba extract improves brain uptake of ginsenosides by increasing blood-brain barrier permeability via activating A1 adenosine receptor signaling pathway.

Abstract: 

ETHNOPHARMACOLOGICAL RELEVANCE: Ginkgo biloba leaves and Panax ginseng are Chinese medicine commonly used in combination for cerebral disease.AIM OF THE STUDY: To investigate the effect of standard extract of Ginkgo biloba leaves (EGb) on facilitating brain uptake of ginsenoside and its underlying mechanisms.MATERIALS AND METHODS: The increasing uptake of ginsenosides in the brain of rats by EGb were detected by LC-MS/MS analysis. Evans blue and FITC-dextran leakage were determined to evaluate blood-brain barrier (BBB) permeability in vivo. Transendothelial electrical resistance (TEER) and Na-F penetration rate were measured with a co-culture of the human cerebral microvascular endothelial cell line (hCMEC/D3) and human normal glial cell line (HEB) in vitro BBB model. WB were used to analyzed the expression of BBB tight junctions (TJs) related protein (ZO-1, Occludin, Claudin-3, p-ERM, and p-MLC), ultrastructure of TJs was determined by transmission electron microscope.RESULTS: LC-MS/MS analysis demonstrated that EGb could improve brain uptake of ginsenoside Rg1, Re, Rd and Rb1. In vivo study showed that, BBB permeability was significantly increased after EGb administration, evidenced by the markedly increased penetration of FITC-dextran and Evans Blue into the mice brain parenchyma. In the in vitro BBB model, reduced TEER and increased Na-F penetration rate was observed in EGb group, which was associated with alteration of TJs ultrastructure. Furthermore, the expression of p-ERM and p-MLC in hCMEC/D3 as well as mice brain microvessels were significantly upregulated, but no significant change on the expression of TJs proteins (ZO-1, Occludin and Claudin-3). Moreover, the effect of EGb on in vitro BBB permeability and ERM, MLC phosphorylation was counteracted by DPCPX, an A1 adenosine receptor (A1R) antagonist.CONCLUSIONS: EGb might induce ERM/MLC phosphorylation and increase the cell-cell junction gaps to cause a reversible increase of the BBB permeability via A1R signaling pathway. Our results may contribute to better use of EGb in the treatment of brain diseases.

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PMID: 

Iran J Pharm Res. 2019 ;18(2):803-811. PMID: 31531063

Abstract Title: 

Anti-tumor Effect ofExocarp Extracts on B16 Melanoma Bearing Mice Involving P I3K/Akt/HIF-1α/VEGF Signaling Pathways.

Abstract: 

The objective of this study is to investigate the anti-tumor effect ofexocarp extracts (GBEE) on B16 melanoma bearing mice and its related molecular mechanisms. The B16-F10 melanoma solid tumor model was established in CBL/6J mice. The tumor-bearing mice were treated with GBEE (50, 100, 200 mg/kg), taking cis-Dichlorodiamineplatinum (Ⅱ) (DDP, 3 mg/kg) as positive control and normal saline (NS) as model control. After 17 days of administration, the transplanted tumors was stripped and weighed, and the inhibition rate was calculated. Quantitative Reverse Transcription Polymerase chain reaction (qRT-PCR), Western Blot and immunohistochemistry were applied to detect mRNA and protein levels of related factors in B16 transplanted tumor tissues. The results indicated that GBEE (50, 100, 200 mg/kg) inhibited the growth of B16 transplanted solid tumor in CBL/6J mice. Meanwhile, it inhibited the expression of CD34 and reduced microvessel density (MVD) in a dose-dependent manner. Moreover, GBEE dose-dependently down-regulated the mRNA and protein levels of hypoxia inducible factor-1α (HIF-1α), vascular endothelial growth factor (VEGF), and vascular endothelial growth factor receptor 2 (VEGFR2). The phosphoinositide 3-kinase (PI3K) and protein kinase B (Akt) proteins were not changed obviously, but the protein levels of p-PI3K and p-Akt were down-regulated. Overall, the inhibitory effect of GBEE on the growth of B16 melanoma transplant tumor in mice is related to inhibiting angiogenesis, and the mechanism involves the regulation of PI3K/Akt/ HIF-lα/VEGF signaling pathway.

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PMID: 

Med Sci Monit. 2019 Sep 11 ;25:6836-6845. Epub 2019 Sep 11. PMID: 31509521

Abstract Title: 

Ginkgo Biloba Extract Inhibits Metastasis and ERK/Nuclear Factor kappa B (NF-κB) Signaling Pathway in Gastric Cancer.

Abstract: 

BACKGROUND Ginkgo biloba extract (EGb761), a standard extract of the Chinese traditional medicine Ginkgo biloba, plays an anti-tumor role in various cancers. However, whether EGb761 is involved in the invasion and metastasis of gastric cancer remains unclear. MATERIAL AND METHODS In the current study, cell viability assay, Western blotting, wound-healing assay, Transwell invasion assay, and orthotopic transplantation model were performed to explore the effects of EGb761 on gastric cancer. RESULTS In vitro, the results showed that EGb761 suppressed the proliferation of gastric cancer cells in a dose-dependent manner. Furthermore, the migration and invasiveness were weakened and the protein levels of p-ERK1/2, NF-kappaB P65, NF-kappaB p-P65, and MMP2 were decreased by EGb761 or U0126 (an inhibitor of ERK signaling pathway) exposure in gastric cancer cells. Moreover, the combined treatment with EGb761 and U0126 significantly inhibited ERK, NF-kappaB signaling pathway, and the expression of MMP2 than those of single drug. In vivo, EGb761 inhibited the tumor growth and hepatic metastasis of gastric cancer in the mouse model. Results of immunohistochemistry indicated that the expression of ERK1/2, NF-kappaB P65 and MMP2 were decreased by EGb761 in the tumor tissues. CONCLUSIONS EGb761 plays a vital role in the suppression of metastasis and ERK/NF-kappaB signaling pathway in gastric cancer.

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PMID: 

Res Pharm Sci. 2019 Apr ;14(2):146-154. Epub 2019 Mar 8. PMID: 31620191

Abstract Title: 

Hemp seed/evening primrose oil affects expression of STAT3, IL-17, and FOXP3in experimental autoimmune encephalomyelitis.

Abstract: 

T helper (Th)-17 mediate inflammation in both peripheral tissues and the central nervous system. Signal transducer and activator of transcription factor3 (STAT3) is required for Th-cell pathogenicity and its activation in the brain has been demonstrated during the acute phase of experimental autoimmune encephalomyelitis (EAE) through the mammalian target of rapamycin (mTOR) signaling. Rapamycin (RAPA), an inhibitor of mTOR, can drive Forkhead box P3 (FOXP3) induction as a regulatory factor. The aim of this study was to determine the effects of hemp seed/evening primrose oils (HSO/EPO) supplement on the expression of FOXP3, STAT3, and interleukin (IL)-17 genes in EAE lymph nodes. EAE was induced by myelin oligodendrocyte glycoprotein peptide in mice, and then the mice were assigned to three treatment groups compared to two control groups (EAE and naive). The histological findings of the spinal cord were evaluated. To determine the expression of FOXP3, STAT3, and IL-17 genes in the lymphocytes, qRT-PCR was used. Our results showed that EAE severity was reduced in HSO/EPO mice by reducing the expression of STAT3 and IL-17 genes and increasing the expression of FOXP3gene, which was confirmed by slight inflammation in the spinal cord. Histological findings showed a significant improvement in the HSO/EPO group. Our findings suggest that the HSO/EPO treatment can be used to ameliorate the demyelination of spinal cord, which was confirmed by immunological and histological findings.

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PMID: 

ACS Omega. 2019 Oct 8 ;4(15):16517-16523. Epub 2019 Sep 26. PMID: 31616830

Abstract Title: 

CLG from Hemp Seed Inhibits LPS-Stimulated Neuroinflammation in BV2 Microglia by Regulating NF-κB and Nrf-2 Pathways.

Abstract: 

The healthy benefits of hemp (L.) seed have often been attributed to its oils and proteins. Recent studies reveal that hemp seed phenylpropionamides could also show various bioactivities. Continuation of our study on hemp seed provided a phenylpropionamide, coumaroylaminobutanol glucopyranoside (CLG). This work investigated the neuroprotective effect of CLG and its underlying mechanism using lipopolysaccharide-induced BV2 microglia. Our study demonstrated that CLG increased adenosine monophosphate-activated protein kinase (AMPK) expression, suppressed the nuclear factor-kappa B (NF-κB) signaling pathway by inhibiting the phosphorylation of IκBα and NF-κB p65 and decreased proinflammatory cytokine levels in a concentration-dependent manner. Furthermore, CLG reduced the production of cellular reactive oxygen species and stimulated the nuclear factor erythroid 2-related factor 2 (Nrf-2) signaling pathway. Collectively, these results suggested that CLG effectively and simultaneously inhibited inflammatory responses and oxidative stress through the NF-κB and Nrf-2 signaling pathways. AMPK was also involved in the anti-inflammatory effect of CLG. This study provides new insights into the diverse bioactive constituents of hemp seed.

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