PMID: 

J Nutr Biochem. 2019 Aug 31 ;74:108228. Epub 2019 Aug 31. PMID: 31678747

Abstract Title: 

Kaempferol stimulates WNT/β-catenin signaling pathway to induce differentiation of osteoblasts.

Abstract: 

Flavonoids, a group of natural compounds found in a variety of vegetables and herbal medicines, have been intensively reported on stimulating bone mineral density and bone formation. Among them, kaempferol has been reported to assist bone formation in vitro and in vivo, but its precise mechanism of action for stimulating bone forming abilities of osteoblasts remained elusive. In SaOS-2 osteoblasts, treatment of kaempferol increased early and late osteogenic parameters significantly, including alkaline phosphatase (ALP) activity, collagen synthesis, and mRNA expression levels of Runx2, osterix, osteopontin and bone sialoprotein. Interestingly, kaempferol promoted osteoblastic differentiation via the activation of the WNT signaling pathway. The stimulation of SaOS-2 cells by kaempferol resulted in an increased activity of WNT signaling responsive reporter construct, Axin-2, and, subsequently, stabilization of WNT signaling mediated transcription factorβ-catenin, probably leading to the activation of WNT-targeted genes for osteogenesis. In corroboration, the kaempferol-induced ALP activity was fully abolished by FH 535, an inhibitor of WNT signaling pathway. Kaempferol mediated activation of WNT signaling pathway through estrogen signaling pathway, as the application of ICI 182,780 (an inhibitor for estrogen receptors) markedly inhibited kaempferol-induced WNT signaling activation and osteogenic marker like ALP activity in SaOS-2 cells. Immunohistochemical studies in drill-hole defect model showed increased expression of Runx2 and β-catenin staining after kaempferol treatment. Thus, it may be concluded that kaempferol stimulates estrogen signaling followed by WNT signaling pathway activation to achieve its potential for bone-sparing effects.

read more

PMID: 

Neurosci Lett. 2019 Nov 16:134633. Epub 2019 Nov 16. PMID: 31743752

Abstract Title: 

Kaempferol protects retinal ganglion ceils from high-glucose-induced injury by regulating vasohibin-1.

Abstract: 

Kaempferol is a medicinal flavonol derived from the roots of Kaempferia galanga L. Kaempferol can affect cell survival, apoptosis, and anti-oxidation, though its role and underlying mechanism in retinal ganglion cells with high-glucose injury remains unclear. In this study, we explored kaempferol's role in high-glucose injury in cells from the retinal ganglion cell (RGC) line. RGC cells were isolated and then cultured in high glucose (55 mmol/L) for 0 hours, 12 hours, 24 hours, 48 hours, or 72 hours, and results showed decreased cell viability at 48 hours and 72 hours. We treated RGC cells with different concentrations of kaempferol (0 µmol/L, 20 µmol/L, 40 µmol/L, 60 µmol/L, 80 µmol/L, or 100 µmol/L) and high-glucose (55 mmol/L) for 48 hours. The data indicated inhibited lactate dehydrogenase leakage, apoptosis, caspase-3 activity, and reactive oxygen species (ROS) levels. Moreover, whereas cell viability increased in RGC cells that were incubated with kaempferol (60 µmol/L, 80 µmol/L, or 100 µmol/L) and glucose (55 mmol/L), compared with glucose alone. Kaempferol (60 µmol/L) elevated ERK phosphorylation and vasohibin-1 (VASH1) expression, and inhibition of ERK phosphorylation reversed the effect of kaempferol (60 µmol/L) on VASH1 expression in RGC cells with high-glucose injury. Additionally, interference of VASH1 by VASH1 siRNA markedly reversed the effects of kaempferol (60 µmol/L) on cell viability, caspase-3 activity, and ROS levels in RGC cells with high glucose injury. Taken together, the results suggest that kaempferol protected retinal ganglion cells from high-glucose-induced injury via ERK and VASH1 signaling.

read more

PMID: 

Food Funct. 2019 Oct 16 ;10(10):6227-6243. PMID: 31591634

Abstract Title: 

Dietary berries, insulin resistance and type 2 diabetes: an overview of human feeding trials.

Abstract: 

Dietary berries are a rich source of several nutrients and phytochemicals and in recent years, accumulating evidence suggests they can reduce risks of several chronic diseases, including type 2 diabetes (T2D). The objective of this review is to summarize and discuss the role of dietary berries (taken as fresh, frozen, or other processed forms) on insulin resistance and biomarkers of T2D in human feeding studies. Reported feeding trials involve different berries taken in different forms, and consequently differences in nutritional or polyphenol composition must be considered in their interpretation. Commonly consumed berries, especially cranberries, blueberries, raspberries and strawberries, ameliorate postprandial hyperglycemia and hyperinsulinemia in overweight or obese adults with insulin resistance, and in adults with the metabolic syndrome (MetS). In non-acute long-term studies, these berries either alone, or in combination with other functional foods or dietary interventions, can improve glycemic and lipid profiles, blood pressure and surrogate markers of atherosclerosis. Studies specifically in people with T2D are few, and more knowledge is needed. Nevertheless, existing evidence, although sparse, suggests that berries have an emerging role in dietary strategies for the prevention of diabetes and its complications in adults. Despite the beneficial effects of berries on diabetes prevention and management, they must be consumed as part of a healthy and balanced diet.

read more

PMID: 

Biosci Rep. 2018 12 21 ;38(6). Epub 2018 Nov 15. PMID: 30291211

Abstract Title: 

Protective effects ofmethanolic extract in a rat model of cadmium chloride-induced neurotoxicity.

Abstract: 

Cadmium (Cd) is a common environmental toxicant that has harmful effects on plants, animals, and humans. The present study evaluated the protective effects ofmethanolic extract (SME) on cadmium chloride (CdCl)-induced neuronal toxicity in rats. Male albino rats were intraperitoneally (i.p) injected with CdCl(6.5 mg/kg) for 5 days with or without the SME (250 mg/kg). We measured the levels of Cd, lipid peroxidation (LPO), nitric oxide, glutathione (GSH), and oxidative enzymes such as superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase, and glutathione reductase (GR) in the whole brain homogenate. Compared with the control group, the Cd-intoxicated group showed a marked increase in the brain levels of Cd, LPO, and nitric oxide and a decrease in the levels of GSH and all tested antioxidant enzymes. Compared with Cd-intoxicated rats, the rats pretreated with SME showed restoration of oxidative balance in the brain tissue. While the expression of brain, CAT, glutathione peroxidase 1, and GR was down-regulated in the Cd-treated group, the expression of these enzymes was up-regulated in rats pretreated with SME. In addition, administration of SME before CdClincreased the Bcl-2 expression, but significantly decreased the expression of Bax. Immunohistochemical analysis showed that compared with Cd-intoxicated rats, rats pretreated with SME showed a decrease in the protein expression of tumor necrosis factorα (TNF-α). Our findings indicate that SME protects the brain tissue from Cd-induced neuronal toxicity by improving the antioxidant system and increasing antiapoptotic and anti-inflammatory activities.

read more

In September, The Trump Administration announced a proposed ban on flavored e-cigarettes. Alex Azar, the Health and Human Services Secretary said the FDA will enact the policy soon.

The proposed ban so far does not mention CBD or vitamin vape cartridges, leaving many questions on the fate of non-nicotine vape products.

The ban is a response to 450 cases of lung illness caused by e-cigarettes. Since the ban was proposed in September, that number has grown to 2,290, a 408% increase. 47 of these cases have proven fatal. Medical professionals have not yet determined the direct cause of this illness which includes symptoms such as breathing difficulties, pneumonia, fever, fatigue, and more. One potential cause is the vitamin E infused with the vaped liquids. The CDC has yet to determine a single cause of the illness.

Many patients affected have reported using vaping products that contain either CBD or TCH and wonder if the proposed ban from the Trump administration will include these products as well. The FDA has yet to announce if the ban includes CBD and TCH vape products.

“Unlike tobacco, cannabis isn’t federally legal, so the vast majority of these tragic vape incidents [involving cannabis products] are due to the black market,” says Maggie Connors, founder of Besito, a vaping company in Los Angeles with products that include both CBD and THC. “And when something’s prohibited, it forces consumers to go to extreme measures to create what they want. So a lot of these instances this summer are what I call an extreme measure of people having to mix cartridges at home.”

Several Senators from New York released a report in June said counterfeit and vape products made in China contributed to the lung disease.

Vape and CBD companies fear if the ban includes CBD and TCH products that consumers will turn to counterfeit and black market products which will only increase those affected with illness and add to the death toll.

On November 19, The American Medical Association (AMA), called for a total ban on vaping products.

PMID: 

Oncol Lett. 2019 Nov ;18(5):4735-4743. Epub 2019 Sep 5. PMID: 31611983

Abstract Title: 

Artesunate and sorafenib: Combinatorial inhibition of liver cancer cell growth.

Abstract: 

An antimalarial medication, artesunate (Art), has exhibited promising anticancer effects with excellent tolerability in various types of cancer, suggesting that it has the potential to be used in combination with sorafenib (Sora) in hepatocellular carcinoma (HCC) treatment. To determine the potency of this combination, the present study attempted to quantitatively measure the dose-effect relationship of each drug alone and in combination in liver cancer cellsusing Calcusyn software. Cell growth inhibition was determined using the CyQUANT proliferation assay in two liver cancer cell lines, HepG2 and Huh7. Drug combination and reduction indices and isobologram plots were used to assess drug interactions. Cell apoptosis was evaluated by measurements of the proportion of cells in the sub G/Gphase of the cell cycle, and determination of protein expression levels of cleaved poly ADP ribose polymerase and caspase-9. Additionally, a cell migration assay was conducted using Essen ImageLock plates with an IncuCyte Zoom imaging system. The results of the present study revealed that the inhibitory effect of Sora on cell growth was synergistically enhanced by the combination with Art in HepG2 and Huh7 cells. The combination index and dose reduction index were specific to each cell line. Furthermore, combination at a fixed ratio presented mutual enhancement with respect to apoptosis induction and suppression ofliver cancer cell migration. Therefore, considering the low toxicity and well-defined clinical characteristics of Art, combination of Sora and Art may present an attractive therapeutic option in the development of clinical trials for HCC treatment.

read more

PMID: 

Cell Death Dis. 2019 Nov 13 ;10(11):862. Epub 2019 Nov 13. PMID: 31723124

Abstract Title: 

Artesunate induces mitochondria-mediated apoptosis of human retinoblastoma cells by upregulating Kruppel-like factor 6.

Abstract: 

Retinoblastoma (RB) is the most common primary intraocular malignancy in children. Intravitreal chemotherapy achieves favorable clinical outcomes in controlling RB vitreous seeds, which are a common reason for treatment failure. Thus, a novel, effective and safe intravitreal chemotherapeutic drug is urgently required. The malaria drug artesunate (ART) recently demonstrated remarkable anticancer effects with mild side effects. The purpose of this study is to investigate the anti-RB efficacy, the underlying mechanism and the intraocular safety of ART. Herein, we verified that ART inhibits RB cell viability and induces cell apoptosis in a dose- and time-dependent manner. Microarray analysis revealed that Kruppel-like factor 6 (KLF6) was upregulated after ART treatment, and this was further confirmed by real-time PCR and western blot assays. Silencing of KLF6 expression significantly reversed ART-induced RB cell growth inhibition and apoptosis. Furthermore, ART activated mitochondria-mediated apoptosis of RB cells, while silencing KLF6 expression significantly inhibited this effect. In murine xenotransplantation models of RB, we further confirmed that ART inhibits RB tumor growth, induces tumor cell apoptosis and upregulates KLF6 expression. In addition, KLF6 silencing attenuates ART-mediated inhibition of tumor growth in vivo. Furthermore, we proved that intravitreal injection of ART in Sprague-Dawley (SD) rats is safe, with no obvious retinal function damage or structural disorders observed by electrophysiology (ERG), fundal photographs, fundus fluorescein angiography (FFA) or optical coherence tomography (OCT) examinations. Collectively, our study revealed that ART induces mitochondrial apoptosis of RB cells via upregulating KLF6, and our results may extend the application of ART to the clinic as an effective and safe intravitreal chemotherapeutic drug to treat RB, especially RB with vitreous seeds.

read more

PMID: 

J Cell Mol Med. 2019 Nov 20. Epub 2019 Nov 20. PMID: 31746143

Abstract Title: 

Artesunate inhibits the mevalonate pathway and promotes glioma cell senescence.

Abstract: 

Glioma is a common brain malignancy for which new drug development is urgently needed because of radiotherapy and drug resistance. Recent studies have demonstrated that artemisinin (ARS) compounds can display antiglioma activity, but the mechanisms are poorly understood. Using cell lines and mouse models, we investigated the effects of the most soluble ARS analogue artesunate (ART) on glioma cell growth, migration, distant seeding and senescence and elucidated the underlying mechanisms. Artemisinin effectively inhibited glioma cell growth, migration and distant seeding. Further investigation of the mechanisms showed that ART can influence glioma cell metabolism by affecting the nuclear localization of SREBP2 (sterol regulatory element-binding protein 2) and the expression of its target gene HMGCR (3-hydroxy-3-methylglutaryl coenzyme A reductase), the rate-limiting enzyme of the mevalonate (MVA) pathway. Moreover, ART affected the interaction between SREBP2 and P53 and restored the expression of P21 in cells expressing wild-type P53, thus playing a key role in cell senescence induction. In conclusion, our study demonstrated the new therapeutic potential of ART in glioma cells and showed the novel anticancer mechanisms of ARS compounds of regulating MVA metabolism and cell senescence.

read more

PMID: 

Food Funct. 2018 Dec 13 ;9(12):6218-6226. PMID: 30382270

Abstract Title: 

Strawberries decrease circulating levels of tumor necrosis factor and lipid peroxides in obese adults with knee osteoarthritis.

Abstract: 

OBJECTIVE: Knee osteoarthritis (OA) is increasingly prevalent in obese people, who often have high cardio-metabolic risk factors. Among the few available non-surgical approaches, nutraceuticals have gained popularity, and dietary berries have mitigated arthritis symptoms in observational and animal studies. Clinical studies in OA are sparse, but recently we reported that strawberry supplementation can mitigate pain and reduce inflammatory markers in adults with knee OA. This study extends those observations.METHODS: We conducted a randomized cross-over double-blind placebo-controlled trial on the effects of dietary freeze-dried strawberries on obesity-related hormones, biomarkers of inflammation and lipid peroxidation. Seventeen subjects (4 men, 13 women; age 57± 3 year) were randomized to strawberry supplements (50 g day-1 for 12 weeks) vs. placebo (50 g day-1, matched for calories and fiber), for two 12-week intervention periods, separated by 2-week washout phase.RESULTS: Among 24 biomarkers of inflammation examined (Bioplex-Pro human inflammation panel), 12 were detectable in all samples. Among these, high-sensitivity TNF-α (hs-TNF-α) and the soluble tumor necrosis factor receptor (sTNF-R2) were significantly decreased after strawberry consumption (p

read more

PMID: 

J Autoimmun. 2014 May ;50:99-106. Epub 2014 Jan 29. PMID: 24485154

Abstract Title: 

A/H1N1 antibodies and TRIB2 autoantibodies in narcolepsy patients diagnosed in conjunction with the Pandemrix vaccination campaign in Sweden 2009-2010.

Abstract: 

Narcolepsy is a lifelong sleep disorder related to hypocretin deficiency resulting from a specific loss of hypocretin-producing neurons in the lateral hypothalamic area. The disease is thought to be autoimmune due to a strong association with HLA-DQB1*06:02. In 2009 the World Health Organization (WHO) declared the H1N1 2009 flu pandemic (A/H1N1PDM09). In response to this, the Swedish vaccination campaign began in October of the same year, using the influenza vaccine Pandemrix(®). A few months later an excess of narcolepsy cases was observed. It is still unclear to what extent the vaccination campaign affected humoral autoimmunity associated with narcolepsy. We studied 47 patients with narcolepsy (6-69 years of age) and 80 healthy controls (3-61 years of age) selected after the Pandemrix vaccination campaign. The first aim was to determine antibodies against A/H1N1 and autoantibodies to Tribbles homolog 2 (TRIB2), a narcolepsy autoantigen candidate as well as to GAD65 and IA-2 as disease specificity controls. The second aim was to test if levels and frequencies ofthese antibodies and autoantibodies were associated with HLA-DQB1*06:02. In vitro transcribed and translated [(35)S]-methionine and -cysteine-labeled influenza A virus (A/California/04/2009/(H1N1)) segment 4 hemagglutinin was used to detect antibodies in a radiobinding assay. Autoantibodies to TRIB2, GAD65 and IA-2 were similarly detected in standard radiobinding assays. The narcolepsy patients had higher median levels of A/H1N1 antibodies than the controls (p = 0.006). A/H1N1 antibody levels were higher among the

read more