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Zhishang Chemical

Bee Venom Powder CAS 20449-79-0

Molecular Formula: C131H229N39O31

Formula Weight: 2846.46

ZSpharmac: Bee Venom Powder Supplement

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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?

Mellitin is the major active component of venom. Beevenom is a clear poison with aromatic smell secreted by the venom and accessory glands of worker bees. Among the many components of poison, Bee Venom Powder has the highest possible material, making up regarding 50% of the dry weight of venom, which has high biological activity. Mellittin is a direct peptide made up of 26 amino acids with a family member molecular weight of 2849. Poison Powder has high organic activity. Modern pharmacological research studies have actually shown that it has anti-inflammatory, analgesic, hindering platelet gathering, and also anti-AIDS. sort of impact. Bee Venom Powder can have a strong killing result on a variety of growth cells with various devices, as well as is a very promising anti-tumor all-natural drug.

Bee Venom Powder Property

alpha D21 -89.52° (c = 0.409)
density 1.39
storage temp. -20°C
form White to faint tan powder.

 

Pharmacological Action of Bee Venom Powder

As a monomer, Bee Venom Powder exists in a random coiled structure in a neutral aqueous solution, and with the increase of pH and ionic strength, melittin self-crosslinks to form a helical tetramer structure. Some studies have found that the helical structure region and the angle between the helices of Bee Venom Powder are different in different solutions. The surface of the helix in the helix structure is the first 21 polar amino acids, and the other side of the helix is ​​the non-polar amino acid. This amphipathic nature is characteristic of membrane-bound peptides and membrane protein transmembrane helices.

This feature determines that Bee Venom Powder 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 causes cell death, it does not need to enter the cell, and it can show its tumor cytotoxicity outside the cell. Guo Ju and other scholars studied the inhibitory effect of melittin on LNcap cells and found that melittin had a strong inhibitory effect on LNcap cells, and the higher the concentration of melittin, the higher the inhibition rate of cancer cells.

Apoptosis is a cell suicide program that includes a series of morphological and biochemical changes, and the pathogenesis of most diseases is related to apoptosis. The main ways of inducing apoptosis are endoplasmic reticulum pathway (such as the influence of Ca2+ channel), mitochondrial apoptosis pathway, death receptor pathway and other factors (such as the radiosensitivity of tumor cells).

1 Influence 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 caspase-12 (caspases-12) to activate it and release it into the cytoplasm, thereby inducing apoptosis. Bee Venom Powder can increase the permeability of cell membranes to ions, especially Na+ and Ca2+. Ca2+ can carry signals to activate cells to perform their programmed functions.

The SARIS study found that calcium overload can induce apoptosis and is established by a variety of cells. CHU et al. found that melittin can induce Ca2+ influx through L-type Ca2+ channels in human osteoma cell MG63, which increases the intracellular Ca2+ concentration, leads to cell lysis and causes MG63 cell apoptosis, and Ca2+ influx is independent of protein kinases C and phospholipase A2 activity.

2 Mitochondrial apoptosis pathway

The active center of apoptosis regulation is mitochondria. Mitochondria release pro-apoptotic factors such as cytochrome C under the stimulation of apoptotic factors. In mitochondria, it promotes the release of cytochrome C. Bcl-2 family proteins can regulate the mitochondrial permeability transition pore, which in turn regulates the release of cytochrome C from mitochondria to the cytoplasm, and plays a key role in the regulation of apoptosis.

Li Yumei and others found that Bee Venom Powder can induce apoptosis of U2OS cells, and can promote the changes in the expression of anti-apoptotic proteins Bcl-2 and Bax proteins in U2OS cells, and the Bax/Bcl-2 ratio changes, first activate caspases-9, and then activate caspases-9. caspases-3, and finally induce 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 had a promoting effect on the apoptosis of liver cancer cells .

3 Death receptor pathway

The pathway of death receptor-mediated apoptosis is mainly to transmit signals from extracellular to intracellular through transmembrane receptors. After the adaptor protein binds to the receptor, the executive protein binds to the adaptor protein to induce apoptosis. Its pathways mainly include activation-induced tumor necrosis factor receptor, tumor necrosis factor-related apoptosis-inducing ligand (TNF-related apoptosisinducing ligand, TRAIL) and FAS/FASL. After treating BEL-7402 cells with Bee Venom Powder, Zhang Chen found that melittin had an effect on Fas protein related to apoptosis according to the results of RT-PCR amplification. expression related.

Wang Chen and other scholars found that melittin can promote the sensitivity of human hepatoma cells to TRAIL by constructing a mouse tumor-bearing model, and it can promote the activation of calcium/calmodulin-dependent protein kinase II-transforming growth factor β-activated kinase 1-mitogen. Pro-activated protein kinase kinase-JNK/p38 signaling pathway and inhibition of nuclear factor κB inhibited protein kinase-nuclear factor κB signaling pathway synergistically TRAIL-induced apoptosis of human hepatoma cells.

4 Improve 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, the treatment effect of strong radiosensitivity is good, and the treatment effect of poor radiosensitivity is poor. Foreign scholars have found that Bee Venom Powder 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 concluded that melittin-mediated radiosensitization may be partly due to the regulation of Bcl-2 protein.

Yang Xi received different doses of X-ray radiation on nasopharyngeal carcinoma CNE-2 cells, and found that both the normoxia group and the hypoxia group after combined melittin were significantly lower than the previous cell survival scores. The sensitization ratios of melittin in CNE-2 normoxic and hypoxic cells were 1.07 and 1.13, respectively, and melittin was able to increase the overall apoptosis rate of normoxic and hypoxic CNE-2 cells after irradiation. Therefore, melittin can effectively improve the radiosensitivity of tumor cells and promote the induction of apoptosis 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 Bee Venom Powder can inhibit vascular endothelial growth factor A-induced Lewis lung cancer tumor growth and tumor-related angiogenesis in vivo, and this inhibition of vascular endothelial growth factor A-induced proliferation and capillary differentiation has no cytotoxicity, and vascular endothelial growth. Factor 2 and cyclooxygenase-2 are involved in the mitogen-activated protein kinase signaling pathway. The biological process of invasion and metastasis requires destruction 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 matrix metalloproteinase-9 expression, which is due to the inhibition of phosphorylated extracellular regulated protein kinase (extracellular regulated protein kinase) by melittin. Regulated protein kinase, ERK) and phosphorylated Jun levels resulted in the effects of 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 the extracellular matrix. LIU studies demonstrate that Rac1 is a key regulator of liver cancer cell metastasis in vivo and in vitro. Jun pathway is one of Rac1-dependent pathways, and melittin can largely inhibit cell movement by inhibiting Jun pathway, thereby preventing the metastasis of liver cancer cells in vivo.

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 1 (Th1)/Th2. The γ-interferon secreted by Th1 cells has anti-inflammatory effects. Tumor effect, and interleukin-4 (interleukin, IL-4) secreted by Th2 cells has the effect of promoting inflammation. If the Th1/Th2 balance is tilted towards Th1, the antitumor effect of T cells can be enhanced.

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

Wang Qiubo found that the body’s IL-2 content was significantly increased and the IL-4 content was decreased after bee therapy on volunteers, which led to the enhancement of Th1 cell function and played a positive role in regulating the body’s cellular immune function. Scholars such as Xiong Langping and others found that Bee Venom Powder can up-regulate Th1 ratio and γ-interferon concentration when immune cells are activated, and down-regulate IL-4 concentration to affect immune cells, thereby improving the anti-tumor effect.

Bee Venom Powder Chemical Structure

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 was 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 Bee Venom Powder is an alpha helical structure. They are the α-helix structure of 1-10 amino acid residues and the α-helix structure of 13-20 amino acid residues, respectively.
3. Tertiary structure
The spatial structure of Bee Venom Powder 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) Positively charged regions at the C-terminus. Such four monomers are connected by hydrophobic groups to form a stable tetramer structure. The angle between the two α-helix structures will change due to the different forms of melittin.

Preparation of Bee Venom Powder

Use solvent extraction, three-column chromatography, solvent extraction and three-column chromatography to prepare melittin, the product preparation process is loaded down with trivial details, the production cycle is long, and the amount of organic solvent used is large. Kreil reported a method for preparing Bee Venom Powder by solvent extraction. The yield of melittin was about 20% (mass fraction), and the purity was 60.3% (mass fraction). The demand for n-butanol is large, causing serious environmental pollution.

Liu Ling and Yang Wenchao reported that Bee Venom Powder was prepared 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 the combination of solvent extraction and chromatography to prepare melittin. The yield of melittin 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 of the present invention, the use amount of n-butanol is reduced, but a large amount of n-butanol is still required in the extraction process, which is not conducive to environmental protection.

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

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

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

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

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: Additive , Chemical Auxiliary & Catalyst , Organic Chemicals
  • Products/Service: Organic Intermediate,Inorganic Chemistry, APIs, Dyestuffs And Pigments, Fragrance And Spices, Food 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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