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Bee Venom Powder CAS 20449-79-0

Molecular Formula: C131H229N39O31

Formula Weight: 2846.46

ZSpharmac: Bee Venom Powder Supplier

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Product Name: Bee Venom Powder
CAS No: 20449-79-0
Purity: 99%

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Basic Info

Product Name:Bee Venom Powder
Other Names:MELITTIN
CAS:20449-79-0
Place of Origin:Shandong, China
Brand Name:ZSpharmac
Type:Cosmetic Raw Materials
Appearance:White to Faint Tan Powder
EINECS No.:629-303-1
Storage:-20°C
Provide:Bee Venom Powder MSDS;
Bee Venom Powder COA

What is Bee Venom Powder?

Melitin is the major energetic ingredient of venom. Beevenom is a clear poison with aromatic smell produced by worker venom glands and accessory glands, which is discharged from the stinger when it is gone against. Amongst the many components of bee poison, melittin has the highest possible content, making up regarding 50% of the completely dry weight of bee venom, and also it has high organic activity. Bee Poison Powder is a straight peptide made up of 26 amino acids, its loved one molecular weight is 2849, as well as the series of amino acids is: Gan-Isoleu-Glyn-C-Val-Leu-Lai-Val-Leu-Three-Three- Gan-liang-preserved-bing-liang-hetero-bright-silk-color-hetero-bright-lai-jing-lai-jing-gu-gu. Melittin has high organic activity, as well as modern-day medicinal research studies have actually shown that it has different results such as anti-inflammatory, analgesic, inhibition of platelet aggregation, as well as anti-AIDS. Poison Powder can produce a strong killing effect on a variety of tumor cells with various devices, as well as is an extremely appealing anti-tumor natural medication.

Bee Venom Powder Property

alpha D21 -89.52° (c = 0.409)
density 1.39
storage temp. -20°C
solubility Soluble to 1 mg/ml in 20% acetonitrile
form White to faint tan powder.

 

Pharmacological Actions of Bee Venom Powder

1 Directly kill tumor cells
As a monomer, Bee Venom Powder exists in a random coil structure in neutral aqueous solution, and as the pH value and ionic strength increase, melittin self-crosslinks to form a helical tetramer structure. Studies have found that the helical region of melittin and the angle between helices are different in different solutions. The surface of the helix in the helical structure is the first 21 polar amino acids, and the other side of the helix is non-polar amino acids. This amphipathic character is characteristic of membrane-bound peptides and transmembrane helices of membrane proteins.

This feature determines that melittin is easy to integrate into and destroy natural and synthetic phospholipid bilayers, thereby inhibiting cell growth and development, and has a strong cytotoxic effect on tumor cells. Because melittin destroys the cell membrane and leads to cell death, it does not need to enter the cell, and it can show its cytotoxicity to destroy tumor cells outside the cell. Guo Ju and other scholars found that melittin has a strong inhibitory effect on LNcap cells in the study of the inhibitory effect of Bee Venom Powder on LNcap cells, and the higher the concentration of melittin, the higher the inhibitory rate on cancer cells.

2 Induce tumor cell apoptosis
Apoptosis is a cell suicide program, including a series of morphological and biochemical changes, and the pathogenesis of most diseases is related to apoptosis. The ways to induce apoptosis mainly include endoplasmic reticulum pathway (such as the influence of Ca2 + channel), mitochondrial apoptosis pathway, death receptor pathway and other factors (such as radiosensitivity of tumor cells).

2.1 Effect of Ca2+ channels

When Ca2 + is released from the endoplasmic reticulum into the cytoplasm, it will activate calpain near the endoplasmic reticulum, and then act on caspases-12 (caspases-12) to activate and release it into the cytoplasm, thereby inducing cell apoptosis. Melittin can increase the permeability of cell membranes to ions, especially Na+ and Ca2+. Ca2+ can carry signals that activate cells to carry out their programmed functions.

The SARIS study found that calcium overload can induce apoptosis, and it is established by a variety of cells. CHU et al. found that Bee Venom Powder can induce Ca2+ influx through L-type Ca2+ channels in human osteoma cells MG63, increasing the intracellular Ca2+ concentration, leading to cell lysis and causing apoptosis of MG63 cells, and Ca2+ influx is not dependent on protein Kinase C and phospholipase A2 activity.

2.2 Mitochondrial apoptosis pathway

The active center of cell apoptosis regulation is the mitochondria. Under the stimulation of apoptosis factors, the mitochondria release pro-apoptotic factors such as cytochrome C, and the pro-apoptotic factors activate the caspases of intracellular caspases, and the activated caspases act in turn. In mitochondria, it promotes the release of cytochrome c. Bcl-2 family proteins can regulate the mitochondrial permeability transition pore, thereby regulating the release of cytochrome c from mitochondria to the cytoplasm, and play a key role in the regulation of apoptosis.

Research by Li Yumei et al. found that Bee Venom Powder can induce U2OS cell apoptosis, and can promote changes in the expression of anti-apoptotic proteins Bcl-2 and Bax proteins in U2OS cells, and changes in the ratio of Bax/Bcl-2, first activate caspases-9, and then activate caspases-3, finally induces apoptosis. After Zhang Chen treated BEL-7402 cells with different concentrations of melittin, the expression rate of mitochondrial membrane protein 7A6 increased, and the expression rate increased with the increase of melittin concentration, which can promote the apoptosis of liver cancer cells .

2.3 Death receptor pathway

The death receptor-mediated apoptosis pathway is mainly through transmembrane receptors to transmit signals from extracellular to intracellular, after the adapter protein binds to the receptor, the execution protein binds to the adapter protein again, thereby inducing cell apoptosis. Its pathway mainly includes activation-induced tumor necrosis factor receptor, tumor necrosis factor-related apoptosis-inducing ligand (TNF-related apoptosis-inducing ligand, TRAIL) and FAS/FASL. After Zhang Chen treated BEL-7402 cells with Bee Venom Powder, according to the results of RT-PCR amplification, it was found that melittin had an effect on Fas protein related to cell apoptosis. expression related.

Scholars such as Wang Chen found that melittin can promote the sensitivity of human liver cancer cells to TRAIL by constructing a mouse tumor-bearing model, and can enhance the activation of calcium/calmodulin-dependent protein kinase Ⅱ-transforming growth factor β-activated kinase 1-mitogen Proactivation of the protein kinase kinase-JNK/p38 signaling pathway and inhibition of nuclear factor-κB inhibiting the protein kinase-nuclear factor-κB signaling pathway synergistically with TRAIL to induce apoptosis in human hepatocellular carcinoma cells.

2.4 Improving the radiosensitivity of tumor cells

Radiation therapy and chemotherapy are important means of treating tumors. Generally speaking, the effect of tumor radiotherapy is related to radiosensitivity, that is, those with strong radiosensitivity have better therapeutic effect, and those with poor radiosensitivity have poor therapeutic effect. Foreign scholars have found that melittin can enhance the radiosensitivity of esophageal cancer, resulting in enhanced apoptosis in vitro and in vivo. Scholars believe that melittin and radiation-induced apoptosis may be activated through the Bax / Bcl-2 pathway, and thus conclude that melittin-mediated radiosensitization may be partly due to the regulation of Bcl-2 protein.

After Yang Xi received different doses of X-ray radiation on nasopharyngeal carcinoma CNE-2 cells, he found that the cell survival scores in the normoxia group and the hypoxia group were significantly lower than before when melittin was combined. The sensitization ratios of melittin in CNE-2 normoxic and hypoxic cells were 1.07 and 1.13, respectively, and melittin could increase the total apoptosis rate of normoxic and hypoxic CNE-2 cells after irradiation. Therefore, melittin can effectively increase the radiosensitivity of tumor cells and promote the induction of apoptosis of tumor cells.

3 Inhibit the invasion and metastasis of tumor cells
Blood vessels are one of the important channels for tumor cell invasion and metastasis, and tumor cells can flow to all parts of the body through blood vessels. Therefore, we can inhibit tumor cell invasion and metastasis by inhibiting tumor-associated angiogenesis. Foreign scholars have found that melittin can inhibit tumor growth and tumor-associated angiogenesis in vivo induced by vascular endothelial growth factor A in Lewis lung cancer, and this inhibition of vascular endothelial growth factor A-induced proliferation and capillary differentiation has no cytotoxicity, which is consistent with vascular endothelial growth Factor 2 and cyclooxygenase-2 are associated with mitogen-activated protein kinase signaling. The biological processes of invasion and metastasis require disruption of the extracellular matrix.

Therefore, extracellular matrix degrading enzymes such as matrix metalloproteinases have become important drug targets for the regulation of tumor invasion and metastasis. PARK studies have shown that melittin can inhibit phorbol ester-stimulated cancer cell invasion by inhibiting the expression of matrix metalloproteinase-9, and the inhibition of matrix metalloproteinase-9 expression is due to the inhibition of phosphorylation of extracellular regulated protein kinase ( extracellular regulated protein kinase (ERK) and phosphorylated Jun levels resulted in effects on AP-1 and nuclear factor κB.

Thus it was shown that melittin can inhibit the invasion and metastasis of cancer cells by preventing the degradation of extracellular matrix. LIU studies revealed that Rac1 is a key regulator of liver cancer cell metastasis in vivo and in vitro. The Jun pathway is one of the Rac1-dependent pathways, and Bee Venom Powder can largely inhibit the movement of cells by inhibiting the Jun pathway, thereby preventing the metastasis of liver cancer cells in vivo.

4 Immunomodulatory effects
T cell regulation is an important part of cellular immune regulation in the human body. There is an important balance in T cell regulation, that is, the balance of helper T cell (Th1)/Th2. The γ-interferon secreted by Th1 cells has anti- Tumor function, while interleukin-4 (interleukin, IL-4) secreted by Th2 cells can promote inflammation. If the Th1/Th2 balance is tilted towards Th1, the anti-tumor effect of T cells can be enhanced.

NAM et al. found that bee venom can selectively induce the development of Th1 cell lineage by up-regulating Tbet and increase the expression of Th1 cell-specific cytokine γ-interferon. Moreover, this effect is mediated by directly affecting CD4+ T cells, independent of any antigen-presenting cells.

Wang Qiubo found that the IL-2 content of the body increased significantly and the IL-4 content decreased after treating volunteers with bees, which led to the enhancement of Th1 cell function and played a positive role in regulating the body’s cellular immune function. Scholar Xiong Langping and other scholars found that Bee Venom Powder can up-regulate the Th1 ratio and γ-interferon concentration in the state of immune cell activation, and down-regulate the IL-4 concentration to affect immune cells, thereby improving the anti-tumor effect.

Preparation of Bee Venom Powder

Preparation of melittin by methods such as solvent extraction, three-column chromatography, and combination of solvent extraction and three-column chromatography, the product preparation process is cumbersome, the production cycle is long, and the amount of organic solvent used is large. Kreil reported the method of preparing melittin by solvent extraction. The yield of Bee Venom Powder is about 20% (mass fraction), and the purity is 60.3% (mass fraction). The preparation method is simple. It takes 200mL n-butanol to extract 1g melittin The demand for n-butanol is large, causing serious pollution to the environment.

Liu Ling and Yang Wenchao reported the preparation of melittin by three-column chromatography. The yield of melittin was about 48.67% (mass fraction), and the purity was 97.32% (mass fraction). problem, but the extraction process is complicated and the extraction time is long. Zhang Wenli and Xu Peng reported that melittin was prepared by combining solvent extraction and chromatography. The yield of Bee Venom Powder was about 47% (mass fraction), and the purity was electrophoretic pure, which shortened the time required for three-column chromatography. Compared with the preparation method, the usage amount of n-butanol is reduced, but a large amount of n-butanol is still needed in the extraction process, which is not conducive to environmental protection.

The above separation and purification method has complex production process, long production cycle, low yield, low purity and serious pollution. CN201710169095.3 provides a method for rapidly preparing Bee Venom Powder. The melittin prepared by the method has high yield, high purity, short cycle, low energy consumption, and less pollution. The method for preparing melittin.

The extraction rate mass fraction of Bee Venom Powder obtained by the present invention is 49%, and the purity mass fraction is 98%. A kind of method for preparing melittin of the present invention, the steps are as follows:

① Removal of impurities from bee venom Add crude bee venom into a buffer solution with a pH of 4.0-5.5 to make the concentration 0.5-1.5mg/mL, and centrifuge at 2500-3500r/min for 3-7min to remove insoluble impurities. Clear liquid; the crude bee venom is obtained by dissolving the venom discharged from bee stings with distilled water and freeze-drying; the buffer is acetic acid-sodium acetate buffer solution; the impurity removal is to remove insoluble substances in the buffer solution.

②Separation of melittin Pass the supernatant obtained in ① through a Sephadex G-25 column, elute with distilled water, control the flow rate at 25-30mL/h, and measure the molecular weight of each separated component. The chromatographic fraction with a molecular weight of 2840 Da was collected under the gel column and freeze-dried to obtain a solid sample. The production of melittin by this method simplifies the extraction process of melittin, reduces the production cycle by 1-2 days compared with the existing method, improves the yield by 1-2%, reduces the preparation cost, and the purity of Bee Venom Powder can reach Electrophoretic pure.

Chemical Structure of Bee Venom Powder

1. Primary structure
In 1967, melittin consisting of 26 amino acids was isolated from bee venom, and the amino acid sequence was analyzed to prove that there is no disulfide bond in its structure. The relative molecular weight of melittin is 2849, strong alkaline, facultative molecule, soluble in water.
2. Secondary structure
The secondary structure of melittin is α-helical structure. α-helix structure of 1-10 amino acid residues and α-helix structure of 13-20 amino acid residues, respectively.
3. Tertiary structure
The spatial structure of melittin can be divided into four regions (1-10) N-terminal α-helix structure, (11-12) hinge structure connecting two helices at an angle of 120°, (13-20) α-helix structure, ( 21-26) The positively charged region at the C-terminus. These four monomers are linked by hydrophobic groups to form a stable structure of tetramer. The angle between the two α-helical structures will change due to the different forms of melittin.

About Products:
If you need Bee Venom Powder, the cosmetic raw material, please contact our service staff directly, we will provide you with high-quality products at the best price.
As an experienced Bee Venom Powder manufacturer and supplier, ZSpharmac will provide Bee Venom Powder raw materials to customers all over the world for a long time.
Over the years, the company has been adhering to the spirit of “integrity management, strict quality control, customer first”, and has won unanimous praise from domestic and foreign customers.

Company Profile and Corporate Culture

Company Profile:

ZhiShang Chemical is owned by ZhiShang Group is a professional new-type chemicals enterprise combined into research and development, production and sales .

The company’s competitive product is pharmaceutical raw materials and intermediates (especially carbohydrate derivatives Series), In recent years, the company has made a major breakthrough in food and feed additives, plant extraction, industrial chemicals industry .

The company insists on the spirit of “sincere management, strict quality control, customer as god” , get consistent high praise from customers at home and abroad.

Corporate Culture:

OUR MISSION
Help China Chemicals to benefit the happiness of human life
OUR VISSION
Become the most trusted chemical supplier in the world
OUR BUSINESS PHILOSOPHY
Striver – oriented, enrich employees, customer first, deep service, seek development
OUR VALUES
Be prepared for danger in times of peace, forge ahead actively, unity and cooperation, and be brave to fight

About Us

The production base is located in Zhangqiu chemical industry park and Tai’an high-tech chemical industry park. laboratory and workshop in strict accordance with the GMP standard and the product fit national ISO9001 and ISO2000 standards.

“Zhishang” products are exported to Europe, North and South America, the Middle East, Asia Pacific and Africa area, so as to establish a long-term and stable cooperation relationship with customer in the world.

Company Info
  • Business Type: Manufacturer
  • Product Range: Cosmetic raw materials
  • Products/Service:Cosmetic raw materials (flavors and fragrances,antioxidant products, moisturizing and hydrating, whitening agents, cosmetic additives)
  • Total Employees: 51~100
  • Capital (Million US $): 10000000RMB
  • Year Established: 2016
Production Capacity
  • No. of Production Lines : 8
  • No. of QC Staff : 5 -10 People
  • OEM Services Provided : yes
  • Factory Size (Sq.meters) : 3,000-5,000 square meters
  • Certificate: ISO9001 , CE , GMP , API , MSDS
  • Factory Location : Diao Town Industry Park, Zhangqiu City, Jinan City, Shandong Province, China.

Service

Pre-Sales Service

* Prompt reply and 24 hours online, professional team to provide best price and high quality product.

* Sample testing support.

* Every batch of products will be tested to ensureits quality.

*The packing also can be according the customers` requirment.

*Any inquiries will be replied within 24 hours.

*we provide Commerical Invoice, Packing List, Bill of loading, COA , Health certificate and Origin certificate. If your markets have any special requirements, let us know.

 

After-Sales Service

*The fact of logistics information monitoring.

* Any questions about the product can be consulted at any time.

*Product has any problem can return.

FAQ

Do you accept sample order?

We will make samples before mass production, and after sample approved, we’ll begin mass production. Doing 100% inspection during production, then do random inspection before packing.

 

HOW TO CONFIRM THE PRODUCT QUALITY BEFORE PLACING ORDERS?

You can get free samples for some products,you only need to pay the shipping cost or arrange a courier to us and take the samples. You can send us your product specifications and requests,we will manufacture the products according to your requests.

What’s your MOQ?

Our MOQ is 1kg. But usually we accept less quantity such as 100g on the condition that sample charge is 100% paid.

Do you supply product report?

Yes. We’ll give you product analysis report before shipping.

  Is there a discount?

Different quantity has different discount.

Shipping

1. ≤50kg, Express delivery recommended, usually called as DDU service;

2. ≤500kg, Air shipping recommended, usually called as FOB, CFR, or CIF service;

3. >500kg, sea shipping recommended, usually called as FOB, CFR, or CIF service;

4. For high value products, please select air shipping and express delivery for safe.

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