Monday, October 22, 2018

Carob Honey Antioxidant Activity Protects Liver, Kidney

Antioxidant Activity and Protective Effect of Carob Honey in CCl4-induced Kidney and Liver Injury

Arch Med Res. 2018 Oct 17. pii: S0188-4409(18)30324-2

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BACKGROUND/AIM:

Various honey samples exhibited protective effect against drug and chemical induced toxicity. The study was designed to determine the antioxidant content and activity of carob honey and to investigate its hepato-renal protective effect in carbon tetrachloride (CCl4) induced kidney and liver injury in rats.

MATERIAL AND METHODS:

Phenolic, flavone and flavonol in carob honey were quantified. DPPH, ABTS•+, ferric reducting antioxidant power, and total antioxidant activity were used to evaluate the antioxidant activity. Rats were used for the experiment, and received either intraperitoneal injection of CCl4 (1 mL/kg.b.wt); honey (orally, 2 g/kg.b.wt) and CCl4; or honey. Liver and kidney function parameters were assessed. Oxidative parameters including lipid peroxidation (MDA), protein carbonyl formation (PCO), advanced protein oxidation products (AOPP), catalase (CAT), glutathione peroxidase (GPx), reduced glutathione (GSH), and ascorbic acid were measured in the kidney and liver tissues.

RESULTS:

CCl4 caused a significant elevation of liver enzymes, lactic acid dehydrogenase, blood glucose, uric acid, blood urea and serum creatinine as compared to the control group. Also, it significantly increased MDA, PCO and AOPP level, and markedly decreased GHS, ascorbic acid, CAT and GPx in the liver and kidney tissues. These changes were significantly ameliorated by carob honey before and after CCl4 administration. Honey alone did not cause significant changes as compared to the control group.

CONCLUSION:

The data showed for the first time that carob honey has high antioxidant content, antioxidant property, and protective effect against CCl4 induced kidney and liver toxicity by maintaining the activity of antioxidant defense system.

Friday, October 19, 2018

Iranian Honey Bee Venom Component May Help Treat Cervical Cancer


Apoptotic Effect of Melittin Purified from Iranian Honey Bee Venom on Human Cervical Cancer HeLa Cell Line
International Journal of Peptide Research and Therapeutics
December 2018, Volume 24, Issue 4, pp 563–570

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Melittin, an amphipathic 26-residue peptide, is the main component of honey bee venom. Studies have been demonstrated that melittin has an inhibitory effect on proliferation of cancer cells. However, the precise mechanism of action is not completely understood. In the present study we have shown that purified melittin from Iranian honey bee venom shows anti-cancer effects on human cervical cancer cell line through induction of apoptosis. The venom was collected from Iranian honey bee (Apis mellifera meda) and melittin isolated using reversed phase HPLC. Biological activity of melittin was analyzed by hemolytic test on human red blood cells.

In order to investigate whether melittin inhibits proliferation of cervical cancer cells, the viability of the melittin treated HeLa cell line was measured via MTT assay. Finally, cell death analysis was performed using Propidum iodide and Annexin V-FITC dual staining. The results showed that the half hemolytic concentration (HD50) induced by mellitin was 0.5 µg/ml in free FBS solution. IC50 obtained after 12 h at 1.8 µg/ml by MTT assay. According to flow cytometric analysis, melittin induced apoptosis at concentrations more than 1 µg/ml.

These results suggest that melittin induces apoptotic cell death in cervical cancerous cells as observed by flow cytometric assay. It is concluded that melittin could be regarded as a potential candidate in future studies to discovery of new anticancer agents.

Thursday, October 18, 2018

Manuka Honey’s Anti-Viral, Anti-Bacterial, Anti-Inflammatory, and Antiseptic Properties


The Health Benefits of Manuka Honey

The Manual

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Manuka honey’s anti-viral, anti-bacterial, anti-inflammatory, and antiseptic properties are thought to be beyond comparison to other foods.

“All honey is said to have some activity level of positive benefits, but Manuka has been studied and sought after for it high non-peroxide and antibacterial activity,” says Blick. “It is dramatically more active than your average honey.”

Manuka is also used in adhesive dressings and wound gels, and as a part of DIY cleansing face masks.

“Honey has been used topically for centuries for its powerful antibacterial properties … (but) most of the average honey bear honey you see in the grocery stores lack the unique wellness compounds that are really rewarding for your skin,” says Comvita on their blog. “When it comes to beneficial properties, no honey compares to UMF Manuka Honey which contains guaranteed levels of leptosperin, methylglyoxal, and DHA.”

Yep, Manuka honey is so sought out that there have been counterfeit Manuka honey claims against faux Manuka.

And if all that sounds like mumbo jumbo, we’ll cut to the chase and tell you how to use Manuka honey this winter.

HOW TO USE MANUKA HONEY PROPERLY

By the Spoonful

Before heading to work, suck on a spoonful of 5+ Manuka honey. Done. Easy.

In Tea

While spritzers and ice-cold beers reign supreme during the summer, winter calls for a libation switch. Drink some tea, morning, noon, or night and add your Manuka Honey into the cup.

DIY Face Mask

Once or twice a week, do a Manuka face mask to rid dead skin and other impurities. You’ll want to use a high UMF-rated Manuka honey for your masks so mix 15+ or 10+ with raw sugar and a squeezed lemon (not so much that the mixture is runny). Scrub over your face and neck, leave for 20 mins, gently remove with warm water and a washcloth.

In or With Oatmeal, Chicken, or Ham

One of the easiest ways to get a Manuka boost is to mix the honey into everyday dishes. That can include being the sweetener for your steel cut oats, peanut butter banana toast, a glaze for your teriyaki chicken, or even a honey baked ham! Who said ham couldn’t be healthy?...

Wednesday, October 17, 2018

Main Source of Propolis Can Decrease Blood Glucose Levels and Insulin Resistance (Diabetes)


Beneficial Effects of Poplar Buds on Hyperglycemia, Dyslipidemia, Oxidative Stress, and Inflammation in Streptozotocin-Induced Type-2 Diabetes

J Immunol Res. 2018 Sep 18;2018:7245956

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The effects of propolis on blood glucose regulation and the alleviation of various complications caused by diabetes have been widely studied. The main source of propolis in the northern temperate zone is poplar buds. However, there is limited research on the antidiabetic activity of poplar buds.

In order to evaluate the effect of poplar buds on type-2 diabetes, crude extract and 50% fraction of poplar buds were used to feed streptozotocin-induced type-2 diabetic mice.

The results showed that 50% fraction could increase insulin sensitivity and reduce insulin resistance, as well as decrease the levels of fasting blood glucose, glycated hemoglobin, and glycosylated serum proteins in diabetic mice. Compared with the model control group, the 50% fraction-treated group showed significant decreases of malondialdehyde (MDA) and increases of superoxide dismutase (SOD) in serum and liver homogenate.

Moreover, 50% fraction could significantly decrease total cholesterol (TC), alleviate abnormal lipid metabolism, and enhance antioxidant capacity in the serum. For inflammatory factors, feeding of 50% fraction could also reduce the levels of interleukin 6 (IL-6), tumor necrosis factor α (TNF-α), monocyte chemotactic protein 1 (MCP-1), and cyclooxygenase-2 (COX-2) in liver homogenate.

Taken together, our results suggest that crude extract and 50% fraction of poplar buds, particularly the latter, can decrease blood glucose levels and insulin resistance, and 50% fraction can significantly relieve dyslipidemia, oxidative stress, and inflammation caused by type-2 diabetes.

Tuesday, October 16, 2018

Propolis Component May Help Treat Endometriosis


Chrysin leads to cell death in endometriosis by regulation of endoplasmic reticulum stress and cytosolic calcium level

J Cell Physiol. 2018 Oct 9

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Chrysin is a natural compound derived from honey, propolis, or passion flowers and has many functional roles, such as antiinflammatory and antiangiogenesis effects. Although endometriosis is a benign gynecological disease, there is a need to identify the pathology and develop a therapy for endometriosis. Elucidating the biological mechanism of chrysin on endometriosis will improve the understanding of endometriosis.

In this study, we confirmed the apoptotic effects of chrysin in human endometriotic cells using End1/E6E7 (endocervix-derived endometriotic cells) and VK2/E6E7 (vaginal mucosa-derived epithelial endometriotic cells).

The results showed that chrysin suppressed the proliferation of endometriosis and induced programmed cell death through changing the cell cycle proportion and increasing the cytosolic calcium level and generation of reactive oxygen species.

In addition, chrysin activated endoplasmic reticulum (ER) stress by stimulating the unfolded protein response proteins, especially the 78-kDa glucose-regulated protein-PRKR-like ER kinase (PERK)-eukaryotic translation initiation factor 2α (eIF2α) pathway in both endometriotic cell lines.

Furthermore, chrysin inactivated the intracellular phosphoinositide 3-kinase (PI3K)/protein kinase B (PKB, also known as AKT) signaling pathway in a dose-dependent manner. Collectively, the results of this study indicated that chrysin induced programmed cell death by activating the ER stress response and inactivating the PI3K signaling pathways in human endometriotic cells.

Monday, October 15, 2018

Honey Shows Antifungal Activity

Italian acacia honey exhibits lytic effects against the crayfish pathogens Aphanomyces astaci and Fusarium avenaceum

Lett Appl Microbiol. 2018 Oct 13

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This study purpose was to evaluate the in vitro inhibitory properties of Italian acacia honey extracts against pathogenic aquatic oomycete/fungal isolates that cause different diseases in crayfish, resulting in an elevated mortality rate.

The antimycotic activity of acacia honey aqueous extracts were evaluated against the strain UEF88662 of Aphanomyces astaci (oomycete) and the strain SMM2 of Fusarium avenaceum (fungus). The extracts preparation was carried out with water by a cheap, not complex and organic solvent-free procedure, with low environmental impact and the higher possibility of large-scale reproducibility. The anti-oomycete and antifungal activities were quantitatively evaluated by growth, survival and sporulation microbiological assays.

The extracts displayed a dose-dependent inhibitory efficacy on oomycete and fungal growth and survival, as well as on the production of oomycete and fungal spores. Supported by future in vivo studies, our results encourage the use of natural extracts like honey as innovative tools to counteract mycotic infections.

Saturday, October 13, 2018

Propolis Used to Treat Enlarged Prostate, Dandruff, Acne, Nail Fungus, Toothache, Ear Infections, Gastritis, Chronic Rhinitis

BEES-WORKERS TO NO END PRODUCE IT! FEW PEOPLE KNOW HOW TO TAKE…

October 13, 2018

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Бджоли-робітниці без кінця виробляють його! Мало хто знає, як правильно приймати… 

Propolis is a dark resinous substance produced by bees to glossing over cracks and isolation from foreign objects in the hive. Its other name is bee glue, in ancient times it was called the UGA, bee balm bee or plaster.

Bee glue has very strong antimicrobial properties. Thanks to the propolis the bees in the hive is always clean and pristine. Using propolis, bees mummified any insect or animal, such as a mouse, which they can’t get out of his nest, thus preventing rotting and decay.

THE PROPERTIES OF TINCTURE OF PROPOLIS

Due to its unique properties propolis is able to cope with many internal and external diseases. However, to achieve a positive effect, it must apply correctly. Dry propolis is used quite rarely, most often treatment is with the help of his tinctures.

In late February, I began to treat a sore throat, which worried me, no matter what medications I tried. A friend advised me to take tincture of propolis. I really was hoping for a quick result, but after a couple of days of bothersome pain in the throat disappeared.

Tincture of propolis once again proved its effectiveness, and I was curious to know what kind of healing properties it possesses. I already own the experience felt, how she copes with the cold, but how else can I use it?

THE USE OF TINCTURE OF PROPOLIS IN VARIOUS DISEASES

With stomatitis

Stomatitis hurts both children and adults. How to get rid of this disease without going to hospital? Really effective treatment — tincture of propolis.

Help with stomatitis rinse the mouth alcohol tincture of propolis. To start razbaby drug. In 1 Cup of warm liquid (milk, water) you need to add 15-20 grams of solution. Do rinse recommend about 1 month. Alcohol tincture is also used in the form of lotions.

Gastritis

Propolis for gastritis helps to relieve inflammation and pain. Thus it can be used with any acidity, including increased.Treatment of gastritis propolis involves strict control of the doctor and several different regimens, which ideally can be individualized after a complete diagnosis.

Chronic gastritis can be treated with 20% alcohol tincture. For this purpose it is necessary to take 40 drops three times per day. Drinking the extract of bee glue takes about two weeks. This assignment to do in normal and high acidity.

For toothache

Teeth and gums is generally a sore subject, and when they get sick, want to climb the wall. But if you have propolis, to relieve pain and make your mouth healthier can be a few procedures.Propolis not just temporarily relieves pain, eliminates unpleasant process, prevents the bacteria to continue the destructive influence to tissues of the tooth.

Rinse your mouth with tincture of propolis for tooth pain 3-4 times a day. So you will remove the inflammation of the gums, destroyed a fair amount of harmful bacteria that will get rid of the pain.

For otitis

For otitis media can be instilled 2 drops of the tincture in each ear to relieve inflammation. When purulent inflammation of the middle ear it is necessary to prepare the cords of the bandage, moisten the cloth in the tincture and insert in the ear for 20 minutes, pre gently clearing the ear pus.


In acute or chronic rhinitis

The mucosa of the nasopharynx — a hotbed of pathogenic microorganisms, which increase the symptoms of disease and weaken the immune system. To accelerate the treatment of chronic rhinitis, nasal wash salt solution with tincture of propolis.1 glass of water, take half a teaspoon of salt and half a teaspoon of tincture of propolis. Rinse nose best using special tools (available at pharmacies). You can use a small teapot infuser.

Got up the spout of the pot into your right nostril, tilt your head to the left, the water should be poured through the left nostril. Then do the same thing, washing the left side...

Friday, October 12, 2018

Bee Venom Helps Treat Atopic Dermatitis (Eczema)

Use of Bee Venom for Topical Treatment in Patients With Atopic Dermatitis

Dermatology Advisor

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The use of bee venom (BV) and its major component, melittin, has proven suitable as an epicutaneous application for the treatment of atopic dermatitis (AD), according to the results of an in vivo and in vitro study conducted in an AD-like model, with findings published in the British Journal of Pharmacology.

The investigators sought to explore the potential pharmacologic effects of bee venom and melittin on 1-chloro-2,4-dinitrobenzene (DNCB)-induced in vivo and tumor necrosis factor-alpha (TNF-α)/tumor necrosis factor-gamma (TNF-γ) in vitro AD-like models of skin disease.

Study results showed that bee venom and melittin possess potent anti-atopic activities, as demonstrated by decreased DNCB-induced AD-like skin lesions in an animal model. In vitro studies that used TNF-α/ TNF-γ–stimulated human keratinocytes revealed that bee venom and melittin inhibit the exaggerated expression of such chemokines as TARC/CCL17 and MDC/CCL22, as well as such pro-inflammatory cytokines as interleukin-1-beta (IL-1β), IL-6, and interferon (IFN)-γ, via blockade of the nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) and signal transducers and activators of transcription (STAT) pathways.

The investigators concluded that since the use of topical agents is often recommended for the treatment of AD, bee venom and melittin are suitable for epicutaneous application. The results of this study showed the ameliorating effects of bee venom and melittin on the DNBC-induced AD-like skin lesions in BALB/c mice and TNF-α/ TNF-γ–stimulated human keratinocyte HaCaT cells.

By suppressing production of Th1/Th2–associated and pro-inflammatory cytokines, bee venom and melittin decreased inflammatory symptoms in AD-like skin lesions, resulting in a subsequent reduction in CD4+ T cells, mast cell infiltration, and release of serum immunoglobulin E (IgE). Moreover, bee venom and melittin improved abnormal epidermal differentiation by restoration of filaggrin expression.

'Mad Honey' Heals Infected Wounds

The effect of different types of honey on healing infected wounds

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J Wound Care. 2018 Oct 1;27(Sup10):S18-S25

OBJECTIVE:

To investigate the effects of treatments of 'mad honey', blossom honey and nitrofurazone on infected wound healing.

METHOD:

Male albino Wistar rats were randomly divided into four groups: 'mad honey' (MH), blossom honey (BH), nitrofurazone (N) and control (C). All rats were anaesthetised intraperitoneally. A circular skin incision was made to the back regions. Grafts containing slime-producing Staphylococcus epidermidis were placed on the incision area and then sutured to the skin. Infection in the wound area was confirmed after 48 hours. Wounds were dressed twice daily with the various treatment materials. Rats were randomly euthanised on days 7 or 14, and tissue samples taken. Tissue samples were assessed for hydroxyproline (HP), tensile strength (TS) and macroscopic measurement (area and intensity).

RESULTS:

HP levels were higher in the treatment groups (MH, BH, N) at days 7 and 14 compared with the control group. 'Group x day' interaction was found in the HP levels (p = 0.015). Increases in HP levels in the MH and N groups between days 7 and 14 were significantly higher than those in the other groups (p < 0.05). Intensity was significantly lower in the control group and significantly higher in group MH compared with the other groups. Significant 'group x day' interaction was observed in intensity (p = 0.006). TS was significantly lower on day 7 than on day 14 (p = 0.022). No marked difference was observed between the groups, nor any 'group x day' interaction, in terms of TS.

CONCLUSION:

Honey administration successfully healed infected wounds. However, there was no significant difference between the effect of MH and that of N in terms of wound healing.

Thursday, October 11, 2018

Propolis Accelerates Diabetic Wound Healing


Polysaccharide-based film loaded with vitamin C and propolis: A promising device to accelerate diabetic wound healing

Int J Pharm. 2018 Oct 6. pii: S0378-5173(18)30745-2

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Wound healing can be a painful and time-consuming process in patients with diabetes mellitus. In light of this, the use of wound healing devices could help to accelerate this process. Here, cellulose-based films loaded with vitamin C (VitC) and/or propolis (Prop), two natural compounds with attractive properties were engineered.

The starting materials and the cellulose-based films were characterized in detail. As assessed, vitamin C can be released from the Cel-PVA/VitC and Cel-PVA/VitC/Prop films in a controlled manner. In vitro antibacterial activity studies showed a reduction of bacteria counts (Escherichia coli and Staphylococcus aureus) after Cel-PVA/VitC, Cel-PVA/Prop, and Cel-PVA/VitC/Prop treatments. Moreover, we examined the antibacterial and wound healing properties of the cellulose-based films in a streptozotocin (STZ)-induced diabetic animal model. Diabetic mice exhibited impaired wound healing while the Cel-PVA/VitC/Prop treatment increased the wound closure.

A marked reduction in bacterial counts present in the wound environment of diabetic mice was observed after Cel-PVA/VitC, Cel-PVA/Prop and Cel-PVA/VitC/Prop treatment. Histological analysis demonstrated that the non-treated diabetic mice group did not exhibit adequate wound healing while the treated group with Cel-PVA/VitC and Cel-PVA/VitC/Prop films presented good cicatricial response. Furthermore, these novel eco-friendly films may represent a new therapeutic approach to accelerate diabetic wound healing.

Wednesday, October 10, 2018

6 Ways Manuka Honey Benefits Your Skin, Gut Health, and More (Probiotics, Acne, Wound Healing, Sinus, Diabetes)

Its potent antibacterial properties can treat cuts, calm acne, and bolster probiotics.

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By Maria Masters, Oct 9, 2018

Honey is one of those products that seems to do it all. It can sweeten any meal, hydrate parched skin, and soothe a sore throat when you’re feeling sick—but one particular honey stands out from the rest. Manuka honey, which is native to New Zealand and parts of Australia, has been gaining lots of buzz in the wellness world for its potent healing properties.

While some celebrities (like Kourtney Kardashian) are huge fans of the stuff, it’s also being researched by otolaryngologists, dermatologists, and nutritionists, many of whom are (at least cautiously) optimistic. Curious? Here’s everything you need to know about Manuka honey, its body-wide health benefits, and where to find it if you want to try it out for yourself.

Manuka is a special type of honey that’s made from bees that pollenate the Manuka plant, a shrub or small tree that’s native to New Zealand and eastern Australia. The Manuka flower produces a nectar that has unique compounds that aren’t as concentrated in other types of honey, including methylglyoxal, which is known for its antibacterial properties.

All genuine Manuka honey products have a Unique Manuka Factor (UMF) placed on the label, a trademark that rates the honey to signify the strength and quality of its signature properties, which is determined through independent testing. It’s these various compounds that have been linked to the health benefits of Manuka honey...

Tuesday, October 09, 2018

Bee Venom Can Kill HIV (AIDS)


Bee venom can kill virus, heals wounds faster

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By AbdulAzeez Bello

Dr Mkabwa Manoko of the University of Dar es Salaam, Tanzania, said bee venom could be used to kill deadly viruses in the body.

Dr. Manoko, also Head of the Department of Crop Sciences and Beekeeping Technology in the university, said this in an interview with the News Agency of Nigeria (NAN) on the sidelines of the just concluded ApiExpo Africa in Abuja.

He noted that honey also had a medicinal value that could be used for wound management without side effect.

The don said more studies and research implementation were required to tap into other potentialities of bees.

“Bees produce a lot of products that have industrial use in the pharmaceutical, food and beverage industries.

“Honey has medicinal property. It can be used for wound management, it is cheap, it takes a short time to heal and has no side effect like other chemicals.

“Bees produce propolis, venom, pollen, and all these are  valuable,” Manoko said.

He added that it was clearly established in research that bee venom had the ability to kill HIV, but not human cells. So it is something that research can explore to see how it can be used in the cure of HIV/AIDS....

Monday, October 08, 2018

Propolis Shows Anti-Inflammatory, Antibiotic, Antioxidative, Anticancer, Antifungal, Anesthetic, and Cytostatic Effects

3.3. Propolis

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Propolis or bee glue is a resinous substance that bees collect from various living plants for construction and adaptation of their nests, consisting of three major components: flavonoids, phenolic compounds, and caffeic acid phenethyl ester (CAPE). As a functional food, it has a range of biological activities such as anti-inflammatory, antibiotic, antioxidative, anticancer, antifungal, anesthetic, and cytostatic effects. In Caco-2 cells and in rats, propolis protects intestinal barrier function by increasing expression of tight junction loci occludin and zonula occluden and activating AMP-activated protein kinase and extracellular regulated protein kinase signaling. In intestinal epithelial cells, CAPE, as an active constituent of honeybee propolis, inhibits nuclear factor- (NF-) κB signaling and TNF-induced and IFN-induced protein- (IP-) 10 expression, independently of p38 mitogen-activated protein kinase (MAPK) and HO-1 signaling pathways, revealing its anti-inflammatory effect.

Sunday, October 07, 2018

Flavanones and Flavones from Bashkir Propolis


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Chemistry of Natural Compounds
September 2018, Volume 54, Issue 5, pp 975–977

Propolis is a product of the honey bee Apis mellifera and has a broad spectrum of biological activity (antimicrobial, antifungal, antitumor, antineurodegenerative, anti-inflammatory, antioxidant, cytotoxic, antituberculosis, antiviral, and immunomodulating) that is widely employed in traditional and folk medicine.

Greater than 500 compounds, of which more than 150 were flavonoids, were identified in the constituents of propolis depending on the geographic location, bee species, and plants.

The chemical composition of Bashkir propolis produced by A. mellifera from plants of the southern Urals (Bashkiria) was studied by us for the first time. Pure flavanones 1–4 and flavones 5 and 6 were isolated and identified.

Saturday, October 06, 2018

Propolis Component May Help Treat Brain Cancers Glioblastoma and Melanoma

Two Deadly Brain Cancers May Have Met Their Match

09/27/2018

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Glioblastoma and Melanoma metastasized to the brain are incredibly deadly brain cancers. However, pharmaceutical company Moleculin Biotech, Inc. hopes the diseases have met their match in a small molecule compound known as WP1066.

The company has initiated a Phase 1 clinical trial of the new first-in-class cancer drug candidate discovered by Professor Waldemar Priebe at The University of Texas MD Anderson Cancer Center. In animal models, WP1066 has shown to both inhibit an important cell signaling protein STAT3 that is involved in cell growth and proliferation, and also stimulate an immune response.

The first glioblastoma patient has received the initial doses of the compound at MD Anderson Cancer Center, and is said to have tolerated the dose well.

“Treating the first brain tumor patient with WP1066 is the start of a very exciting and encouraging program for doctors treating the worst types of brain cancers. There has been very little progress in recent years toward improved therapies for glioblastoma and other aggressive primary or metastatic brain tumors.  WP1066 has shown extremely promising results based on animal studies where we have seen inhibition of tumor growth and improvements in survival,” said Dr. Sandra Silberman, an oncologist and Moleculin’s CMO.

WP1066, which is built from the chemical backbone of the active ingredient in propolis, a natural product of honey bees, not only directly kills tumor cells, but also has the ability to overcome the tumor’s ability to evade the natural immune response, which would otherwise be working to eliminate the cancerous activity....