PMID: 

J Gene Med. 2020 Feb 6:e3169. Epub 2020 Feb 6. PMID: 32028542

Abstract Title: 

Oleanolic acid mitigates interleukin-1β-induced chondrocyte dysfunction by regulating miR-148-3p-modulated FGF2 expression.

Abstract: 

BACKGROUND: microRNAs (miRs)-mediated post-transcriptional repression has been reported in the process of chondrocyte dysfunction. The present study is aimed to investigate the molecular mechanisms underlying in oleanolic acid (OLA)-prevented interleukin-1β (IL-1β)-induced chondrocyte dysfunction via the miR-148-3p/FGF2 signaling pathway.METHODS: Candidate miRs were filtrated using miR microarray assays in chondrocyte with or without IL-1β stimulation. Gene expression of candidate miRs and protein expression of FGF2 were analyzed using RT-qPCR and western blotting, respectively. Cell growth was evaluated using CCK8 assays. Cell apoptosis was detected using Annexin V-FITC double staining.RESULTS: Treatment with OLA counteracted IL-1β-evoked chondrocyte growth inhibition, apoptosis, caspase3 production, MDA and 8-OHdG release. Additionally, FGF2 protein expression levels elevated by IL-1β were down-regulated by OLA and miR-148-3p mimics transfection. IL-1β-induced down-regulation of miR-148-3p in chondrocytes was evaluated by OLA administration. Bioinformatics algorithms and experimental measurements indicated that FGF2 might be a direct target of miR-148-3p. miR-148-3p mimics exhibited equal authenticity of OLA to protect against IL-1β-induced chondrocyte dysfunction.CONCLUSIONS: Our present findings expounded a protective effect of OLA on IL-1β-induced chondrocyte dysfunction, and a novel signal cascade the miR-148-3p/FGF2 signaling pathway might be a potential therapeutic target of OLA to prevent the progression of osteoarthritis (OA).

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PMID: 

IUBMB Life. 2019 Dec 16. Epub 2019 Dec 16. PMID: 31840927

Abstract Title: 

Preventive effect of ursolic acid derivative on particulate matter 2.5-induced chronic obstructive pulmonary disease involves suppression of lung inflammation.

Abstract: 

Respiratory diseases like chronic obstructive pulmonary disease (COPD) are associated with the presence of particulate matter 2.5 (PM2.5) in the air. In the present study, the effect of synthesized ursolic acid derivatives on mice model of PM2.5-induced COPD was investigated in vivo. The mice model of COPD was established by the administration of 25 μL of PM2.5 suspension through intranasal route daily for 1 week. The levels of oxidative stress markers and inflammatory cytokines like tumor necrosis factors-α and interleukin-6 in the mice bronchoalveolar fluids increased markedly on administration with PM2.5. However, treatment with ursolicacid derivative caused a significant suppression in PM2.5-induced increase in oxidative stress markers and inflammatory cytokines in dose-dependent manner. Hematoxylin and eosin staining showed excessive inflammatory cell infiltration in pulmonary tissues in mice with COPD. The inflammatory cell infiltration was inhibited on treatment of the mice with ursolic acid derivative. The ursolic acid derivative treatment increased level of superoxide dismutase in mice with COPD. The lung injury induced by PM2.5 in mice was also prevented on treatment with ursolic acid derivative. Thus, ursolic acid derivative inhibits pulmonary tissues damage in mice through suppression of inflammatory cytokine and oxidative enzymes. Therefore, ursolic acid derivative can be of therapeutic importance for treatment of PM2.5-induced COPD.

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PMID: 

Int J Mol Sci. 2019 Sep 23 ;20(19). Epub 2019 Sep 23. PMID: 31547587

Abstract Title: 

Activating Hippo Pathway via Rassf1 by Ursolic Acid Suppresses the Tumorigenesis of Gastric Cancer.

Abstract: 

The Hippo pathway is often dysregulated in many carcinomas, which results in various stages of tumor progression. Ursolic acid (UA), a natural compound that exists in many herbal plants, is known to obstruct cancer progression and exerts anti-carcinogenic effect on a number of human cancers. In this study, we aimed to examine the biological mechanisms of action of UA through the Hippo pathway in gastric cancer cells. MTT assay showed a decreased viability of gastric cancer cells after treatment with UA. Following treatment with UA, colony numbers and the sizes of gastric cancer cells were significantly diminished and apoptosis was observed in SNU484 and SNU638 cells. The invasion and migration rates of gastric cancer cells were suppressed by UA in a dose-dependent manner. To further determine the gene expression patterns that are related to the effects of UA, a microarray analysis was performed. Gene ontology analysis revealed that several genes, such as the Hippo pathway upstream target gene, ras association domain family (), and its downstream target genes (MST1, MST2, and LATS1) were significantly upregulated by UA, while the expression of YAP1 gene, together with oncogenes (FOXM1, KRAS, and BATF), were significantly decreased. Similar to the gene expression profiling results, the protein levels of RASSF1, MST1, MST2, LATS1, and p-YAP were increased, whereas those of CTGF were decreased by UA in gastric cancer cells. The p-YAP expression induced in gastric cancer cells by UA was reversed with RASSF1 silencing. In addition, the protein levels in the Hippo pathway were increased in the UA-treated xenograft tumor tissues as compared with that in the control tumor tissues; thus, UA significantly inhibited the tumorigenesis of gastric cancer in vivo in xenograft animals. Collectively, UA diminishes the proliferation and metastasis of gastric cancer via the regulation of Hippo pathway through Rassf1, which suggests that UA can be used as a potential chemopreventive and therapeutic agent for gastric cancer.

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PMID: 

Int J Mol Sci. 2020 Jan 13 ;21(2). Epub 2020 Jan 13. PMID: 31941116

Abstract Title: 

Licochalcone A InhibitsandGene Expression and Hypoxic Growth of Human Tumor Cell Lines.

Abstract: 

Hypoxic cellular proliferation is a common feature of tumor cells and is associated with tumor progression. Therefore, the inhibition of hypoxic cellular proliferation is expected to regulate malignancy processes. Licochalcone A (LicA) is known to show inhibitory effects on cell growth in normoxia, but it is unclear whether LicA exerts similar effects in hypoxia. Here, we studied the inhibitory activity of LicA in the hypoxic cellular proliferation of tumor cells and its molecular mechanism using human cell lines derived from various tumors including neuroblastoma and colorectal cancer. LicA inhibited cell growth at a 50% inhibitory concentration between 7.0 and 31.1µM in hypoxia. LicA significantly suppressed hypoxic induction of tropomyosin receptor kinase B () gene expression at the transcription level. LicA also downregulated mRNA levels of the TrkB high-affinity ligand brain-derived neurotrophic factor, but not neurotrophin-4, another TrkB ligand, or glyceraldehyde-3-phosphate dehydrogenase, indicating that the inhibitory activity of LicA is selective. Since both LicA-treatment and-knockdown decreased activation of protein kinase B in hypoxia, LicA exerts its inhibitory effect against hypoxic cell growth through inhibition of the TrkB-AKT axis. These results suggest that LicA has therapeutic potential for malignant tumors including neuroblastoma and colorectal cancer.

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Can CBD cause liver damage?  If you watch the news you may have seen reports that CBD can cause liver damage.  This was very concerning to me, since I truly believe in the healing powers that CBD can provide.  So, I started doing some digging to find out why these news reports were popping up suddenly.

What does the FDA say?

First, the FDA states on their website that CBD can cause liver damage.  So, I looked for the study where they determined that to be true.  And guess what?  There is no study!!  What the FDA is referring to is studies that were done for the approval of the drug Epidiolex – a purified form of CBD that the FDA approved in 2018 for use in the treatment of two rare and severe seizure disorder.  In these studies, they noted that the risks were increased when taken with other drugs that can impact the liver.  The FDA states that there is also other “published literature” that show liver damage with CBD use.  However, there is no link to that literature and there are no studies to show that.

What do other studies say?

Next, there was an article written in Forbes back in June, 2019 that referenced a study from the University of Arkansas at Little Rock on CBD given to mice.  In this study the mice that were given extremely high doses of CBD showed signs of liver damage within 24 hours.  The problem with this study is that it was not done on humans.  And the high amounts of CBD given to the mice exceed any equivalent amount that a human would ever take.

 

The bottom line is there is much to be learned about the effects CBD has on humans.  But the FDA and big pharma have made it difficult to do any research and get studies published.  Those of us that take CBD regularly know of the benefits it is having on our health and quality of life.  I’m sure that every one of you did your own research on CBD before you decided to start using it and came to the same conclusion that I did – the rewards of taking CBD far out way any risks that may come from taking it.

 

If you haven’t started taking CBD and are still in the “research phase”, please check out our website.  Read our blogs and FAQs.  And if you still aren’t convinced, email me with your concerns.  I will be happy to talk with you and help you the best way that I can.

PMID: 

Inflammation. 2017 Dec ;40(6):1894-1902. PMID: 28756519

Abstract Title: 

Anti-Inflammatory Effects of Licochalcone A on IL-1β-Stimulated Human Osteoarthritis Chondrocytes.

Abstract: 

Licochalcone A (Lico A), a flavonoid found in licorice root (Glycyrrhiza glabra), has been reported to have anti-inflammatory activity. In this study, we evaluated the anti-inflammatory effects of Lico A on IL-1β-stimulated human osteoarthritis chondrocytes and investigated the possible mechanism. Results demonstrated that Lico A treatment significantly inhibited PGE2 and NO production induced by IL-1β. IL-1β-induced iNOS and COX-2 expression were also inhibited by Lico A. Lico A inhibited MMP1, MMP3, and MMP13 production in IL-1β-stimulated chondrocytes. Lico A also inhibited IL-1β-induced phosphorylation of NF-κB p65 and IκBα. Meanwhile, Lico A was found to upregulate the expression of Nrf2 and HO-1. However, Nrf2 siRNA reversed the anti-inflammatory effects of Lico A. In conclusion, our results suggested that Lico A showed anti-inflammatory effects in IL-1β-stimulated chondrocytes by activating Nrf2 signaling pathway.

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PMID: 

Int J Mol Sci. 2017 Aug 12 ;18(8). Epub 2017 Aug 12. PMID: 28805696

Abstract Title: 

Licochalcone A Inhibits the Proliferation of Human Lung Cancer Cell Lines A549 and H460 by Inducing G2/M Cell Cycle Arrest and ER Stress.

Abstract: 

Licochalcone A (LicA), a flavonoid isolated from the famous Chinese medicinal herb Glycyrrhiza uralensis Fisch, has wide spectrum of pharmacological activities. In this study, the anti-cancer effects and potential mechanisms of LicA in non-small cell lung cancer (NSCLC) cells were studied. LicA decreased cell viability and induced apoptosis in a dose-dependent manner in NSCLC cells. LicA inhibited lung cancer cells growth by blocking cell cycle progression at the G2/M transition and inducing apoptosis. LicA treatment decreased the expression of MDM2, Cyclin B1, Cdc2 and Cdc25C in H460 and A549 cancer cell lines. In addition, LicA induced caspase-3 activation and poly-ADP-ribose polymerase (PARP) cleavage, which displayed features of apoptotic signals. Furthermore, LicA increased the expression of endoplasmic reticulum (ER) stress related proteins, such as p-EIF2α and ATF4. These data provide evidence that LicA has the potential to be used in the treatment of lung cancer.

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PMID: 

Int J Mol Sci. 2017 Sep 22 ;18(10). Epub 2017 Sep 22. PMID: 28937602

Abstract Title: 

Licochalcone A Prevents the Loss of Dopaminergic Neurons by Inhibiting Microglial Activation in Lipopolysaccharide (LPS)-Induced Parkinson's Disease Models.

Abstract: 

The neuroprotective effects of Licochalcone A (Lico.A), a flavonoid isolated from the herb licorice, in Parkinson's disease (PD) have not been elucidated. The prominent pathological feature of PD is the loss of dopaminergic neurons. The crucial role of neuroinflammation induced by activated microglia in dopaminergic neurodegeneration has been validated. In this study, we explore the therapeutic effects of Lico.A in lipopolysaccharide (LPS)-induced PD models in vivo and in vitro. We find that Lico.A significantly inhibits LPS-stimulated production of pro-inflammatory mediators and microglial activation by blocking the phosphorylation of extracellular signal-regulated kinase (ERK1/2) and nuclear factorκB (NF-κB) p65 in BV-2 cells. In addition, through cultured primary mesencephalic neuron-glia cell experiments, we illustrate that Lico.A attenuates the decrease in [³H] dopamine (DA) uptake and the loss of tyrosine hydroxylase-immunoreactive (TH-ir) neurons in LPS-induced PD models in vitro. Furthermore, LPS intoxication in rats results in microglial activation, dopaminergic neurodegeneration and significant behavioral deficits in vivo. Lico.A treatment prevents microglial activation and reduction of dopaminergic neuron and ameliorates PD-like behavioral impairments. Thus, these results demonstrate for the first time that the neuroprotective effects of Lico.A are associated with microglia and anti-inflammatory effects in PD models.

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PMID: 

Cell Physiol Biochem. 2017 ;43(3):937-944. Epub 2017 Sep 29. PMID: 28957807

Abstract Title: 

Licochalcone A Inhibits MMPs and ADAMTSs via the NF-κB and Wnt/β-Catenin Signaling Pathways in Rat Chondrocytes.

Abstract: 

BACKGROUND: Osteoarthritis (OA) is a joint disease in which cartilage degradation is the central pathological change. In this study, we investigated the anti-osteoarthritic effects of licochalcone A (Lico A) in rat chondrocytes.METHODS: Polymerase chain reaction and Western blotting were performed to evaluate the expression of a disintegrin and metalloproteinase with thrombospondin motifs (ADAMTS)-5, ADAMTS-4, collagen II, matrix metalloproteinase (MMP)-13 and MMP-1 at both the gene and protein levels, respectively. In addition, the wnt/β-catenin and nuclear factor kappa B (NF-κB) signaling pathways were also analyzed by Western blotting.RESULTS: Lico A downregulated ADAMTS-5, ADAMTS-4,MMP-13 and MMP-1 expression, and diminished the IL-1β-induced inhibition of collagen II. In addition, the activation of β-catenin and phosphorylation of p65 and IKKα/β were suppressed by Lico A.CONCLUSIONS: Our results suggest that Lico A inhibits MMPs and ADAMTS partly via the NF-κB and wnt/β-catenin signaling pathways in rat chondrocytes. Thus, Lico A may have therapeutic effects in OA.

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PMID: 

Biomed Pharmacother. 2017 Dec ;96:64-71. Epub 2017 Nov 24. PMID: 28965009

Abstract Title: 

Licochalcone A induces morphological and biochemical alterations in Schistosoma mansoni adult worms.

Abstract: 

This paper is the first report on the in vitro effects of licochalcone A, a chalcone isolated from Glycyrrhiza inflate Batalin (Leguminosae), on Schistosoma mansoni adult worms. In vitro, licochalcone A afforded lethal concentrations for 50% of parasites (LC) of 9.12±1.1 and 9.52±0.9μM against female and male adult worms, respectively, at 24h. Additionally, the compound reduced the total number of S. mansoni eggs and affected the development of eggs produced by S. mansoni adult worms. Together, the results achieved after 24h showed that licochalcone A was 55.7- and 53.3-fold more toxic to S. mansoni female and male adult worms than to Chinese hamster ovary fibroblasts cells, respectively. Treatment with licochalcone A elicited drastic changes in the tegument of S. mansoni adult worms, as well as mitochondrial alteration and chromatin condensation. Licochalcone A also increased the superoxide anion level and decreased the superoxide dismutase activity in S. mansoni adult worms. Overall, our results indicated that licochalcone A displays in vitro schistosomicidal activity. This effect may result from increased production of reactive oxygen species(ROS) induced by the action of licochalcone A. The resulting ROS could act on the S. mansoni tegument and membranes and help induce the death of S. mansoni adult worms.

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