Neurodegenerative Diseases Prevented by Bee Venom

Bee venom and its numerous components are revealing many uses in treating health conditions. Incorporating other bee products during such a treatment would generate additional benefits, namely "synergistic effects", whereby each product enhances the properties of the others, such as royal jelly & propolis.

Neuroprotective effects of melittin on hydrogen peroxide-induced apoptotic cell death in neuroblastoma SH-SY5Y cells

BMC Complementary and Alternative Medicine 2014, 14:286, Published: 5 August 2014

Background

Free radicals are involved in neuronal cell death in human neurodegenerative diseases. Since ancient times, honeybee venom has been used in a complementary medicine to treat various diseases and neurologic disorders. Melittin, the main component of honeybee venom, has various biologic effects, including anti-bacterial, anti-viral, and anti-inflammatory activities.

Methods

We investigated the neuroprotective effects of melittin against H2O2-induced apoptosis in the human neuroblastoma cell line SH-SY5Y. The neuroprotective effects of melittin on H2O2-induced apoptosis were investigated using a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenylterazolium bromide assay, caspase 3 activity, 4,6-diamidino-2-phenylindole staining, a lactate dehydrogenase release assay, Western blots, and reverse transcription-polymerase chain reaction.

Results

The H2O2-treated cells had decreased cell viability with apoptotic features and increased production of caspase-3. On the other hand, melittin treatment increased cell viability and decreased apoptotic DNA fragmentation. Melittin attenuated the H2O2-induced decrease in mRNA and protein production of the anti-apoptotic factor Bcl-2. In addition, melittin inhibited both the H2O2-induced mRNA and protein expression of Bax-associated pro-apoptotic factor and caspase-3.

Conclusions

These findings suggest that melittin has potential therapeutic effects as an agent for the prevention of neurodegenerative diseases.

Bee Venom Enhances Anti-Cancer Effect of Multimodal Approach

Important news from a study which finds the anti-cancer capacity of bee venom is effectively enhanced when mixed at a lower dosage in a culture of white blood cells. Interestingly enough, this anti-apoptopic effect (cell death) is also found true in propolis. Bee products are definitely pro-life... 

Co-culture with NK-92MI cells enhanced the anti-cancer effect of bee venom on NSCLC cells by inactivation of NF-Κb

Arch Pharm Res, 2014 Jan 1

In the present study we experimented on a multimodal therapeutic approach, such as combining chemotherapy agent (Bee venom) with cellular (NK-92MI) immunotherapy. Previously bee venom has been found to show anti-cancer effect in various cancer cell lines. In lung cancer cells bee venom showed an IC50 value of 3 μg/ml in both cell lines. The co-culture of NK-92MI cell lines with lung cancer cells also show a decrease in viability up to 50 % at 48 h time point. Hence we used bee venom treated NK-92MI cells to co-culture with NSCLC cells and found that there is a further decrease in cell viability up to 70 and 75 % in A549 and NCI-H460 cell lines respectively.

We further investigated the expression of various apoptotic and anti-apoptotic proteins and found that Bax, cleaved caspase-3 and -8 were increasing where as Bcl-2 and cIAP-2 was decreasing. The expression of various death receptor proteins like DR3, DR6 and Fas was also increasing. Concomitantly the expression of various death receptor ligands (TNFalpha, Apo3L and FasL) was also increasing of NK-92MI cells after co-culture. Further the DNA binding activity and luciferase activity of NF-κB was also inhibited after co-culture with bee venom treated NK-92MI cell lines. The knock down of death receptors with si-RNA has reversed the decrease in cell viability and NF-κB activity after co-culture with bee venom treated NK-92MI cells.

Thus this new approach can enhance the anti-cancer effect of bee venom at a much lower concentration.

Bee Venom Component Prevents Atherosclerosis

Interestingly enough, propolis also shows strong apoptotic (programmed cell death) activity. As a beekeeper, I welcome bee stings as a natural booster shot for my immune system. Fortunately, bee stings stimulate the body locally and systemically...

Apamin Inhibits THP-1-Derived Macrophage Apoptosis Via Mitochondria-Related Apoptotic Pathway

Exp MolPathol, 2012 Apr 17

The development of atherosclerotic lesions is mainly due to macrophage death. The oxidative stresses of monocytes/macrophages play a vital role in the initiation and amplification of atherosclerosis.

Apamin, a component of bee venom, exerts an anti-inflammatory effect, and selectively inhibits the Ca(2+)-activated K(+) channels. The mechanisms involved in the inhibition of macrophage apoptosis have been fully elucidated.

We induced oxidized low-density lipoprotein (oxLDL) in THP-1-derived macrophage and studied the effect of apamin on intercellular lipid levels, mitochondria-related apoptotic pathway and numbers of apoptotic cells. Oil-red O staining indicates that the inhibition of apamin in the condition significantly prevents intracellular lipid deposition.

Treatment with apamin significantly decreased the apoptotic macrophages by decreasing the expression of pro-apoptotic genes Bax, caspase-3 and PARP protein levels, as well as through increasing expression of anti-apoptotic genes Bcl-2 and Bcl-xL protein levels in the absence and presence of oxLDL. In vivo, with apamin treatment reduced apoptotic cells death by TUNEL staining.

These results indicate that apamin plays an important role in monocyte/macrophage apoptotic processing, which may provide a potential drug for preventing atherosclerosis.

Bee Venom May Help Treat Parkinson's Disease

Clinical trials are currently ongoing in Parisian Hospitals using Bee Venom in the treatment of Parkinson's Disease... 

Bee Venom Protects SH-SY5Y Human Neuroblastoma Cells from 1-Methyl-4-Phenylpyridinium-Induced Apoptotic Cell Death

Brain Research, 2011 Oct 6

Parkinson's disease (PD) is a progressive neurodegenerative disorder characterized by progressive selective loss of dopaminergic neurons in the substantia nigra. Recently, bee venom was reported to protect dopaminergic neurons in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine induced mice PD model, however, the underlying mechanism is not fully understood.

The objective of the present study is to investigate the neuroprotective mechanism of bee venom against Parkinsonian toxin, 1-methyl-4-phenylpyridine (MPP(+)), in SH-SY5Y human neuroblastoma cells.

Our results revealed that bee venom pretreatment (1-100ng/ml) increased the cell viability and decreased apoptosis assessed by DNA fragmentation and caspase-3 activity assays in MPP(+)-induced cytotoxicity in SH-SY5Y cells. Bee venom increased the anti-apoptotic Bcl-2 expression and decreased the pro-apoptotic Bax, cleaved PARP expressions.

In addition, bee venom prevented the MPP(+)-induced suppression of Akt phosphorylation, and the neuroprotective effect of bee venom against MPP(+)-induced cytotoxicity was inhibited by a phosphatidylinositol 3-kinase (PI3K) inhibitor, LY294002.

These results suggest that the anti-apoptotic effect of bee venom is mediated by the cell survival signaling, the PI3K/Akt pathway. These results provide new evidence for elucidating the mechanism of neuroprotection of bee venom against PD.

Propolis Extracts May Allow Inexpensive Cancer Treatment

a very concise peer-reviewed article, confirming ONCE AGAIN, that propolis has very real potential to save lives. In the meantime, take your propolis regularly!!!

Cytotoxic Constituents of Propolis Inducing Anticancer Effects: A Review

J Pharm Pharmacol, 2011 Nov;63(11):1378-86

Objectives:
Propolis is a honeybee product used extensively in traditional medicine for its antioxidant, anti-inflammatory, immunomodulatory and anticancer effects. Propolis exhibits a broad spectrum of biological activities because it is a complex mixture of natural substances. In this review, the antitumour effects of propolis extracts and its constituents (e.g. flavonoids, terpenes and caffeic acid phenethyl ester) are discussed.

Key findings:
The effect of propolis on experimental carcinogenesis is discussed, as well as its possible mechanisms of action against tumours, involving apoptosis, cell cycle arrest and interference on metabolic pathways. Propolis seems to be efficient against different tumour cells both in vitro and in vivo, which suggests its potential in the development of new anticancer drugs.

Summary:
Propolis extracts may be important economically and would allow a relatively inexpensive cancer treatment. Preclinical investigations are needed to further elucidate the benefits of propolis and its anti-tumour properties.

Red Propolis Extract Kills More Leukemia Cancer Cells

the unrelenting power of propolis, proving once again its anti-carcinogenic properties...

Comparison of Effects of the Ethanolic Extracts of Brazilian Propolis on Human Leukemic Cells As Assessed with the MTT Assay

Evidence-BasedComplementary and Alternative Medicine, Volume 2012

Propolis is a resinous product collected by honey bees. It was also reported that propolis has a wide variety of biological actions, including antimicrobial activity and antioxidant, anti-inflammatory, and suppressive effects of dioxin toxicity activities.

The aim of this study was to compare the in vitro cytotoxic activities of green propolis (G12) and red propolis (G13) in human leukemia cells. These cells were incubated with different concentrations of propolis and 48 hours after the IC50 was calculated for each cell.

The results showed that the red propolis has cytotoxic effect in vitro higher than green propolis. Red propolis was showed to be cytostatic in K562 cells and caused the same amount of apoptosis as its control Gleevec.

In conclusion, these results showed that red propolis is more cytotoxic than the green propolis in a variety of human cell lines of leukemia. Red propolis may contain drugs capable of inhibiting cancer cell growth. Therefore, further isolation of respective chemical ingredients from the red propolis (G13) for identification of the activities is necessary.

Royal Jelly Protects Kidneys, Liver from Anti-Cancer Treatments

New research from Turkish researchers confirm the protective properties of Royal Jelly against damage caused by anti-cancer therapies. Could this be new ground towards complementary alternative therapies? 

Royal Jelly Modulates Oxidative Stress and Apoptosis in Liver and Kidneys of Rats Treated with Cisplatin

Oxidative Medicine and Cell Longevity, Volume 2011 (2011)

Abstract:

Cisplatin (CDDP) is one of the most active cytotoxic agents in the treatment of cancer and has adverse side effects such as nephrotoxicity and hepatotoxicity. The present study was designed to determine the effects of royal jelly (RJ) against oxidative stress caused by CDDP injury of the kidneys and liver, by measuring tissue biochemical and antioxidant parameters and investigating apoptosis immunohistochemically.

Twenty-four Sprague Dawley rats were divided into four groups, group C: control group received 0.9% saline; group CDDP: injected i.p. with cisplatin (CDDP, 7 mg kg(-1) body weight i.p., single dose); group RJ: treated for 15 consecutive days by gavage with RJ (300 mg/kg/day); group RJ + CDDP: treated by gavage with RJ 15 days following a single injection of CDDP. Malondialdehyde (MDA) and glutathione (GSH) levels, glutathione S-transferase (GST), glutathione peroxidase (GSH-Px), and superoxide dismutase (SOD) activities were determined in liver and kidney homogenates, and the liver and kidney were also histologically examined.

RJ elicited a significant protective effect towards liver and kidney by decreasing the level of lipid peroxidation (MDA), elevating the level of GSH, and increasing the activities of GST, GSH-Px, and SOD. In the immunohistochemical examinations were observed significantly enhanced apoptotic cell numbers and degenerative changes by cisplatin, but these histological changes were lower in the liver and kidney tissues of RJ + CDDP group. Besides, treatment with RJ lead to an increase in antiapoptotic activity hepatocytes and tubular epithelium.

In conclusion, RJ may be used in combination with cisplatin in chemotherapy to improve cisplatin-induced oxidative stress parameters and apoptotic activity...

excerpt:

Recently, royal jelly (RJ) has received particular attention because of studies that have reported that it is a highly efficient antioxidant and has free radical scavenging capacity [4, 15]. Royal jelly is a secretion produced by the hypopharyngeal and mandibular glands of worker honeybees (Apis mellifera). It contains many important compounds with biological activity such as free amino acids, proteins, sugars, fatty acids, minerals, and vitamins [16]. So far, RJ has been demonstrated to possess several physiological activities in experimental animals, including vasodilative and hypotensive activities [17], the induction of decrease in serum cholesterol levels [18], antimicrobial [19], antiallergic [20], anti-inflammatory [21], immunomodulatory [22, 23], and antioxidant properties [16]. In addition, Kanbur et al. [24] revealed the protective effect of RJ against paracetamol-induced liver damage in mice.

Bee Venom Component Protects Liver Cells Against Injury

Is there anything from honey bees that isn't good?!?!?!

Protective Effects of Melittin on Transforming Growth Factor-β1 Injury to Hepatocytes Via Anti-Apoptotic Mechanism

Toxicology and Applied Pharmacology, 17-Aug 2011

Melittin is a cationic, hemolytic peptide that is the main toxic component in the venom of the honey bee (Apis mellifera). Melittin has multiple effects, including anti-bacterial, anti-viral and anti-inflammatory, in various cell types. However, the anti-apoptotic mechanisms of melittin have not been fully elucidated in hepatocytes.

Apoptosis contributes to liver inflammation and fibrosis. Knowledge of the apoptotic mechanisms is important to develop new and effective therapies for treatment of cirrhosis, portal hypertension, liver cancer, and other liver diseases.

In the present study, we investigated the anti-apoptotic effect of melittin on transforming growth factor (TGF)-β1-induced apoptosis in hepatocytes. TGF-β1-treated hepatocytes were exposed to low doses (0.5 and 1 μg/mL) and high dose (2 μg/mL) of melittin. The low doses significantly protected these cells from DNA damage in TGF-β1-induced apoptosis compared to the high dose. Also, melittin suppressed TGF-β1-induced apoptotic activation of the Bcl-2 family and caspase family of proteins, which resulted in the inhibition of poly–ADP–ribose polymerase (PARP) cleavage.

These results demonstrate that TGF-β1 induces hepatocyte apoptosis and that an optimal dose of melittin exerts anti-apoptotic effects against TGF-β1-induced injury to hepatocytes via the mitochondrial pathway. These results suggest that an optimal dose of melittin can serve to protect cells against TGF-β1-mediated injury.

Highlights

► We investigated the anti-apoptotic effect of melittin on TGF-β1-induced apoptosis in hepatocytes.

► TGF-β1 induces hepatocyte apoptosis.

► TGF-β1-treated hepatocytes were exposed to low doses (0.5 and 1 μg/mL) and high dose (2 μg/mL) of melittin.

► An optimal dose of melittin exerts anti-apoptotic effects to hepatocytes via the mitochondrial pathway.

Algerian Propolis Extract Protects Against Kidney Damage

Another plus from the powerhouse of protection - Propolis!

Polyphenolic fraction of Algerian propolis protects rat kidney against acute oxidative stress induced by doxorubicin

Indian Journal of Nephrology, June 28, 2011

Introduction
Propolis is a complex resinous hive product, a mixture of wax, sugars and plant exudates collected by bees from plants sources. [1],[2],[3],[4] Its chemical and constituents composition depends on its floral origin, and varies according to climatic and geographical conditions. [5],[6] Flavonoids and phenolic compounds appear to be the principal components responsible for the biological activities. [6] By their antioxidant activity, flavonoids are able to attenuate the development of cancer and inflammatory diseases. [7] Indeed, one of the most exciting recent findings about propolis is its efficacy in cancer prevention and treatment. [8],[9] Propolis inhibits cancer cell growth by increasing the process of apoptosis by a pro-oxidant effect inducing apoptosis in human melanoma cells or by oxygen species production. In addition, propolis can prevent drug side-effects and reduce drug resistance.

Propolis has many anti-oxidant and antiapoptotic properties. Phenolic compounds (flavonoids and phenolic acid derivatives) are the most important pharmacologically active constituents in propolis. However, the constituents of propolis vary widely with climate and location. The major flavonoids detected from the extracts in our study were, pinostrobin chalcone, tectochrysin. We observed some similarities in the qualitative composition between the Algerian and Turkish propolis...

We evaluated the effects of propolis extract on renal oxidative stress induced by doxorubicin throughout an analytical and pharmacological study of the eastern Algerian propolis using thin layer chromatography, ultra-violet-high-performance liquid chromatography) and gas chromatography-mass spectrometry.


Materials and Methods
The pharmacological study was carried out in vivo on Wistar rat pre-treated with propolis extract 100 mg/kg/day for seven days. Doxorubicin at 10 mg/kg of body weight was administered intravenously on Day 7. Serum creatinine concentration, scavenging effect of flavonoids, lipid peroxidation and glutathione concentration were measured. Chemical analysis allowed identification and quantification of the phenolic compounds including pinostrombin chalcone (38.91%), galangin (18.95%), naringenin (14.27%), tectochrysin (25.09%), methoxychrysin (1.14%) and a prenylated coumarin compound suberosin (1.65%). The total flavonoid concentration in the propolis extract was 370 mg (quercetin equivalents QE) /g dry weight (QE/g DWPE)...


Conclusions
Propolis extract (EEP) restored the renal functions and reduced the toxic effect of doxorubicin. These data show a protective effect of Algerian propolis extract (EEP) against doxorubicin-induced oxidative stress.