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Matrine vs Cancer

https://www.youtube.com/watch?v=Ya1PH7gIW-8
Natural Cancer Cure

http://www.itmonline.org/arts/oxymatrine.htm

MATRINE AND OXYMATRINE
Subjects Of Chinese Research
by Subhuti Dharmananda, Ph.D., Director, Institute for Traditional Medicine, Portland, Oregon

Matrine and oxymatrine are the two major alkaloid components found in sophora roots. They are obtained primarily from Sophora japonica (kushen), but also from Sophora subprostrata (shandougen), and from the above ground portion of Sophora alopecuroides. The matrines were first isolated and identified in 1958; they are unique tetracyclo-quinolizindine alkaloids (see Figure 1) found only in Sophora species thus far. An intensive investigation into the pharmacology and clinical applications of these alkaloids has gone on for the past decade and remains one of the focal points of Chinese medical research. The main clinical applications are treatment of people with cancer, viral hepatitis, cardiac diseases (such as viral myocarditis), and skin diseases (such as psoriasis and eczema).

The crude herb and crude hot-water extracts of sophora have been available in the West for more than 25 years. An alkaloid fraction of sophora roots containing a standardized level of oxymatrine and matrine (20%) was first introduced by the Institute for Traditional Medicine, and made available to practitioners in tablet form under the name Oxymatrine (White Tiger) in 1998. It has been used without reported side effects. In China, the alkaloids are often given by injection, but this method of administration is not acceptable in the West, so oral dosing is used here instead. When taken orally, much of the oxymatrine is converted to matrine; to get high blood levels of oxymatrine, it must be given by injection. However, it is unclear whether oxymatrine is clinically more effective than matrine. Chinese researchers have also used the alkaloids in capsule form, with results that appear similar to the injection. Sophora is also administered in complex formulas made as decoctions and taken orally.

Sophora japonica contains about a dozen alkaloids, with matrine and oxymatrine being by far the highest, together comprising about 2% of the dried root stock (most of it in the form of oxymatrine), followed by closely related alkaloids: mainly sophocarpine, but also minute amounts of sophoranol, sophoramine, sophoridine, allomatrine, isomatrine, and others (see Figure 2). These alkaloids were first reported as constituents of kushen in a series of publications from 1958-1978.

An overview of recent research on the pharmacology and clinical applications of the sophora alkaloids is presented below. In general, the dosage of the sophora alkaloids administered clinically is in the range of 400-600 mg per day.

VIRAL HEPATITIS

As described by Chen Yanxi and his colleagues at the Shanghai Second Medical University (1):

In recent years, oxymatrine has been recommended for treating chronic hepatitis B and chronic hepatitis C and has been shown effective in clinical practice. It has been utilized for these applications broadly, but the factors affecting its efficacy have not yet been determined.

Chen and his group gave oxymatrine injection to patients with hepatitis B. He confirmed that the viral load declined by this treatment, suggesting that oxymatrine served to inhibit the viral replication, not just reduce liver damage, which is the primary and more limited effect of many herbs used for hepatitis. Antiviral activity, for hepatitis C virus, was confirmed by the same group in cell culture tests (2). Clinical effectiveness for patients with hepatitis C had been reported earlier, including reduction of viral load (3). Oxymatrine may reduce death of liver cells damaged by means other than by inhibiting viral activity, as indicated in a pharmacology study of liver protective effects in immune-based liver damage (4).

Kang Junjie and Kang Suqiong, at the Treatment Center for Hepatic Diseases of the Amoy Municipal Hospital, reported that oxymatrine injection did not cause side effects other than rare local reactions at the injection site (5). They used this injection along with oral administration of complex Chinese herb formulas designed to match symptom-sign complexes and claimed that the effects were comparable to those attained with interferon therapy, except that adverse reactions were avoided. In particular, they claimed that the use of oxymatrine and Chinese herb formulas inhibited liver fibrosis (for further information on Chinese herbs for this purpose, see: Treatment and prevention of liver fibrosis). The inhibition of fibrosis appears to be a separate for additional function of sophora alkaloids beyond inhibiting viral activity. In laboratory animal studies carried out by Chen Weizhong and his colleagues at the Changzheng Hospital in Shanghai, matrine was shown to reduce the formation of liver fibrosis that was caused by chemical damage to the liver (6).

Thus, in relation to viral hepatitis, the sophora alkaloids appear to inhibit the viral replication, reduce destruction of liver cells, and protect against fibrosis. It has also been suggested that the alkaloids promote the flow of bile.

CANCER

Sophora subprostrata has long been regarded an anticancer herb in China. According to cancer specialist Chang Minyi (7), "Sophora subprostrata works through stimulating the anticancer immune mechanism of the patient and reinforcing his resistance against the growth of the tumor." In 1998, Xu Xiangru and Jiang Jikai, working at the Congqing University of Medical Sciences, published a review of anticancer activity of sophora alkaloids (8). They relayed pharmacology studies indicating the alkaloids could inhibit growth of tumor cells directly, and could also affect immune functions. In clinical work, they described the use of sophora alkaloids for treating the side effect of leukopenia caused by cancer chemotherapy or radiation therapy and for treating certain cancers, notably uterine cervical cancer and leukemia. The herb is also considered an important ingredient in treatment of esophageal and laryngeal cancer. In a recent pharmacology study, it was reported that matrine could help leukemia cells differentiate into mature and normal white blood cells (9). Nonetheless, sophora alkaloids should not be relied upon as a sole treatment for cancer, but as an adjunct therapy, as there is no proof that the herb or these compounds are curative.

CARDIAC DISEASES

Sophora and its alkaloids are commonly used in China for treatment of heart arrhythmias (10). A possible mechanism of action is to help block sodium and calcium channels, a mechanism relied on by several antiarrhythmic pharmaceuticals. In a review of sophora alkaloid effects on the heart, Li Yan and He Liren, at the Affiliated Yueyang Hospital of Shanghai University of TCM, reported that:

    sophora total alkaloids or matrine could counteract arrhythmia induced by many causes;
    the total alkaloids or oxymatrine could regulate heart contractility;
    the total alkaloids could dilate the coronary artery, increase blood flow, and improve oxygen delivery to cardiac cells; and
    sophora root could counteract the coxsackie virus that causes myocarditis.

Li and He also relayed a clinical report from the Third Clinical Medical College of Beijing Medical University, about treatment of 167 patients with fast arrhythmia. The patients received each day 3-10 sophora root tablets (extract of 2 grams crude herb/tablet). The results indicated positive effects on various kinds of arrhythmia, such as premature systole, paroxysmal ventricular tachycardia, atrial fibrillation, and sinus tachycardia; the efficacy for premature systole appeared to be the best. This Beijing study and others were described also by Niu Kuizhi in his review (12) of clinical applications of sophora (kushen).

SKIN DISEASES

Sophora is frequently used in treatment of skin diseases, applied topically and consumed orally. One of the primary uses for topical therapy is treatment of vaginitis, particularly that due to candida infection (13). Recently, a topical liniment was developed combining sophora's matrine with the anti-inflammatory flavonoid baicalin from scute (huangqin) for treatment of eczema, neurodermatitis, and psoriasis (14). This treatment was reported to be highly effective, especially for eczema, though the number of cases was small, so that further research must be done. The use of sophora for psoriasis is a promising new area (15). Zhang Junling and his colleagues at the Department of Dermatology, Tianjin Changzheng Hospital, studied the mechanism by which sophora alkaloids reduce psoriasis patches (16). They found that the alkaloids could inhibit keratinocytes, the cells that reproduce continuously to produce the characteristic scales.

Matrine


Oxymatrine


REFERENCES

    Chen Yanxi, et al., Relationship between serum load of HBV-DNA and therapeutic effect of oxymatrine in patients with chronic hepatitis B, Chinese Journal of Integrated Traditional Chinese and Western Medicine 2002; 22 (5): 335-336.
    Chen YX, et al., The inhibitory effect of oxymatrine on hepatitis C virus in vitro, Chinese Journal of Liver Diseases 2001; 9 (Supplement): 12-14.
    Li Jiqiang, et al., A preliminary study on therapeutic effect of oxymatrine in treating patients with chronic hepatitis C, Chinese Journal of Integrated Traditional and Western Medicine, 1998; 18(4): 227-229.
    Xiang X, et al., Effect of oxymatrine on murine fulminant hepatitis and hepatocye apoptosis, Chinese Journal of Medicine, 2002; 115(4); 593-596.
    Kang Junjie and Kang Suqiong, 30 cases of chronic hepatitis B treated with oxymatrine injection combined with syndrome differentiation of Traditional Chinese Medicine, Journal of Traditional Chinese Medicine, 2002; 43(1): 53.
    Chen Weizhong, et al., Effect of matrine on experiment rat liver fibrosis, Chin Journal of New Drugs, 2000; 19(5): 410-412.
    Chang Minyi, Anticancer Medicinal Herbs, 1992 Hunan Science and Technology Publishing House, Changsha.
    Xu Xiangru and Jiang Jikai, Recent progress in anticancer bioactivity study of Sophora flavescens and its alkaloids, Chinese Journal of Integrated Traditional Chinese and Western Medicine 1998; 4 (3): 235-239.
    Zhu Ningxi, et al., Study on inducing and differentiating function and mechanism of matrine on leukemia cells, ACTA Traditional Chinese Medicine and Pharmacology (Shanghai), 2001; 15(1): 43-44.
    Ding Guangsheng, Anti-arrhythmia agents in traditional Chinese medicines, Abstracts of Chinese Medicine 1987; 1(2): 287-308.
    Li Yan and He Liren, Pharmacological study of Sophora alkaloid actions on the cardiovascular system, Chinese Traditional and Herbal Drugs, 2000; 31(3): 227-229.
    Niu Kuizhi, Pharmacology and clinical application of sophora flavescentis, International Journal of Oriental Medicine 1997; 22(1): 75-81.
    Li Xiuying, et al., Treatment of 50 patients with candida albicans vaginitis by cortex sophorae, Chinese Journal of Integrated Traditional Chinese and Western Medicine 2000; 6 (2): 146-147.
    Ding Ting, et al., The preparing and clinical applications of Complex Matrine Liniment, ACTA Chinese Medicine and Pharmacology, 2002; 30(2): 47-48.
    Zhang Yaolong, Clinical study on matrine for the treatment of psoriasis, Hebei Journal of Medical Science, 1996; 69 (2): 590-591.
    Zhang Junling, et al., Study on Apoptosis induced by oxymatrine in cultured keratinocytes, Chinese Journal of Dermatology and Venereology, 2000; 14(6): 367-368.



http://www.ncbi.nlm.nih.gov/pubmed/21061465
PMID:21061465
DOI:10.1142/S0192415X10008512
Am J Chin Med. 2010;38(6):1115-30.

Therapeutic effects of matrine on primary and metastatic breast cancer.

Li H, Tan G, Jiang X, Qiao H, Pan S, Jiang H, Kanwar JR, Sun X.

Abstract

Matrine, one of the main components extracted from a traditional Chinese herb, Sophora flavescens Ait, has displayed anti-cancer activity in several types of cancer cells. This study aims to evaluate the therapeutic benefits of matrine on primary and metastatic breast cancer. Matrine inhibited the viability of and induced apoptosis in human MCF-7 and mouse 4T1 breast cancer cells in a dose-dependent manner in vitro as shown by MTT assay, flow cytometry and laser scanning confocal microscopy. Administration of matrine inhibited the growth of primary tumors and their metastases to lungs and livers, in a dose-dependent manner, in a highly metastatic model of 4T1 breast cancer established in syngeneic Balb/c mice. Tumors from matrine-treated mice had a smaller proliferation index, shown by immunostaining with an anti-Ki-67 antibody, a greater apoptosis index, shown by TUNEL-staining, and a less microvessel density, shown by immunostaining with an anti-CD31 A antibody, compared to the controls. Western blot analysis of tumoral homogenates indicated that matrine therapy reduced the ratio of Bcl-2/Bax, downregulated the expressions of VEGF and VEGFR-2, and increased the activation of caspase-3 and caspase-9. This study suggests matrine may be a potent agent, from a natural resource, for treating metastatic breast cancer because of its anti-apoptotic, anti-proliferative and anti-angiogenic activities.



http://www.ncbi.nlm.nih.gov/pubmed/20930385
Biol Pharm Bull. 2010;33(10):1740-5.

Matrine inhibits proliferation and induces apoptosis of pancreatic cancer cells in vitro and in vivo.

Liu T1, Song Y, Chen H, Pan S, Sun X.

Abstract

Matrine, an alkaloid extracted from a Chinese herb, Sophora flavescens AIT., has exhibited anti-proliferative and pro-apoptotic abilities against various types of cancer cells. This study aims to investigate its anti-cancer activity and underlying mechanisms in human pancreatic cancer cells in vitro and in vivo. Human BxPC-3 and PANC-1 pancreatic cancer cells, and human HL-7702 liver cells were incubated with matrine at different concentrations. Cell viability was assessed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, and cell apoptosis, by flow cytometry. Subcutaneous BxPC-3 xenograft tumors were established in nude BALB/c mice, and matrine was intraperitoneally (i.p.) administered. The tumors were monitored and harvested. Tumor sections were immunostained with an anti-Ki-67 antibody (Ab) to examine cell proliferation, or stained with terminal deoxynucleotidyl transferase mediated deoxyuridine triphosphate (dUTP) nick-end labeling (TUNEL) to evaluate in situ cell apoptosis. The expression of proliferating cell nuclear antigen (PCNA) and several apoptosis-related proteins in cells and tumor tissues were evaluated by Western blot analysis. In in vitro assays, matrine inhibited cell viability by downregulating the expression of PCNA, and induced cell apoptosis by reducing the ratio of Bcl-2/Bax, upregulating Fas, and increasing activation of caspases-8,-3 and -9, in a dose-dependent manner. Administration of matrine inhibited tumor growth in a dose-dependent manner, and regulated tumoral gene expression consistent with the in vitro results. But matrine had no significant effects on the viability of HL-7702 cells or the bodyweight of mice compared to controls. These results indicate matrine may be a potential and promising agent of natural resource to treat pancreatic cancer.



http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4713592/
Int J Clin Exp Pathol. 2015; 8(11): 14793–14799.
http://www.ncbi.nlm.nih.gov/pubmed/26823806
Int J Clin Exp Pathol. 2015 Nov 1;8(11):14793-9

Matrine inhibited proliferation and increased apoptosis in human breast cancer MCF-7 cells via upregulation of Bax and downregulation of Bcl-2.

Li H, Li X, Bai M, Suo Y, Zhang G, Cao X.

Abstract

PURPOSE:

The aim of the present study was to investigate the effects of matrine on proliferation and apoptosis in human breast cancer MCF-7 cells and its relevant molecular mechanisms.

METHODS:

Breast carcinoma cell line MCF-7 was cultured with series concentrations of Matrine in vitro. The proliferation and apoptosis of MCF-7 cells were investigated by 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT) assay, flow cytometry, and Mitochondrial membrane potential (MMP) measurements. The expression levels of Bax and Bcl-2 proteins were detected by Annexin V/propidium iodide coupled staining. The morphological changes of MCF-7 cell were examined.

RESULTS:

The inhibition rates of MCF-7 cells were 6.01%-37.01%, 7.56%-53.92%, and 10.86%-70.23% for 24, 48, and 72 hours after Matrine treatment, respectively. The proliferation of MCF-7 cells was significantly inhibited by Matrine administration, with a time and dose dependent manner. The rates apoptotic cells was between 4.17±0.25% and 19.63±0.17% in 0.25-2.0 mg/ml Matrine groups, which had significant increased compare with the control groups (1.10±0.08%, P<0.05). Meanwhile, increased Bax expression, but decreased Bcl-2 expression was observed in MCF-7 cell line. MMP were significantly decreased by Matrine treatment.

CONCLUSIONS:

Matrine significantly inhibited the growth and induced apoptosis in breast carcinoma MCF-7 cells, which is related to Bax, Bcl-2 signaling and MMP.



Patents
https://worldwide.espacenet.com

Anti-cancer Chinese traditional patent medicine and production method thereof
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The invention relates to an anti-cancer Chinese traditional patent medicine, which is obtained by processing Chinese herbs. The anti-cancer Chinese traditional patent medicine is characterized in that the product mainly contains steroidal saponin, volatile oil, colchicine, matrine and puerarin, the traditional Chinese medicine smilax glabra roxb is adopted as the main raw material to prepare the product, and the pharmaceutically acceptable dosage form or carrier is used.

Method for analysis of matrine inhibited human pancreatic cancer cell migration
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The present invention discloses a method for analysis of matrine inhibited human pancreatic cancer cell migration. The method comprises the steps of: human pancreatic cancer cell culture, single cell migration analysis, cell infiltration analysis, ELISA adsorption analysis and immunoblotting analysis. Analysis by using the method demonstrates that action by matrine for a certain time can significantly reduce the migration and invasion ability of human pancreatic cancer cells, and the expression of human pancreatic cancer cell migration-related proteins, MT1-MMP and Wnt, beta-Catenin is significantly decreased. Further detection finds that MT1-MMP transcriptional activity is also significantly reduced, which is consistent with the Wnt signaling pathway activity; the matrine reduces the transcription and expression of MT1-MMP by regulating Wnt pathway activity, thereby further inhibiting migration and infiltration of pancreatic cancer cells.

Preparing method of matrine nanoparticles modified by wheat germ agglutinin and application of matrine nanoparticles
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The invention relates to a preparing method of matrine nanoparticles modified by wheat germ agglutinin and application of the matrine nanoparticles. The method and application effectively solve the problems that preparing of the matrine nanoparticles modified by the wheat germ agglutinin and matrine are low in targeting and poor in using effect. According to the matrine nanoparticles modified by the wheat germ agglutinin, the matrine nanoparticles are connected with wheat germ agglutinin through chemical bonds, and matrine is dissolved into a water solution through water bath; polylactic acid-hydroxyacetic acid copolymer acetone is dissolved into an organic phase through water bath; the matrine water solution is dripped into the organic phase to form colostrums, the colostrums is injected into a polyving akohol water solution, acetone is volatilized, centrifugation is conducted, sediment and drying are conducted, and matrine nanoparticles are obtained; the matrine nanoparticles are dissolved through a PBS solution, carbodiimide and N-hydroxy succinimide is added, activation and centrifugation are conducted, supernate is added into a solution containing wheat germ agglutinin, incubation and centrifugation are conducted, sediment and drying are conducted, and the final matrine nanoparticles is prepared. According to the preparing method, the preparation condition is met easily, the raw material source is rich, the cost is low, and the preparing method is innovation of cancer therapeutic drug.

Matrine containing composition for treatment or prevention of mammal cancer and other diseases
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Application of matrine compounds in preparing anti-hepatic fibrosis and anti-liver cancer medicament
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The invention relates to application of compounds and salt thereof, and particularly relates to application of matrine compounds and salt thereof in preparation of anti-hepatic fibrosis and anti-liver cancer medicaments. The compounds have the advantages of remarkably inhibiting the proliferation of hepatoma cell lines Hep-G2, Hun-7, MHCC-97L, SMMC-7721 and Hep-3B and proliferation activities of fibroblast BJ, human hepatic stellate cells LX-2 and hepatic stellate cells HSC-T6, and can be used for preparing medicaments for treating hepatic fibrosis and liver cancer.

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Application of compounds inhibiting cell cycle progression in preparation of drug inhibiting or removing double minute chromosomes in tumor cells
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Medicinal composition with anti-tumor effect and application thereof
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Medicine composition containing silymarin and kurainone or matrine and use thereof
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Composition and its use as effective constituent of a medicine having anti-angiogenesis synergy effect
US2008108642
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The present invention provides a new method for extracting Homoharringtonine (HHT) by culture cells or culture plant tissues. Also, disclosed are methods of obtaining HHT from semi-synthesis and biosynthesis. The present invention disclosed that HHT combined with some botanical drugs could induce cancer cells to resemble normal cells. To add some botanical drugs combined with HHT can significantly increase anticancer effects of HHT. These drugs include Matrine (MAT), Guanzhongsu (GU), Maidongsu (MU), and Indirubin (IND). The experimental data showed that above drugs have strong synergisms effects for treating leukemia and other cancer cells and more safe.

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Pure Chinese medicine compound preparation for preventing and treating cancer and malignant tumor
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http://www.missouribotanicalgarden.org/PlantFinder/PlantFinderDetails.aspx?kempercode=c149

Sophora Japonica

Common Name: Japanese pagoda tree
Type: Tree
Family: Fabaceae
Native Range: China, Korea
Zone: 4 to 8
Height: 50.00 to 75.00 feet
Spread: 50.00 to 75.00 feet
Bloom Time: July to August
Bloom Description: Creamy white
Sun: Full sun to part shade
Water: Medium
Maintenance: Low
Suggested Use: Shade Tree, Street Tree
Flower: Showy
Fruit: Showy
Tolerate: Drought, Air Pollution

 

Culture

Best grown in rich, medium moisture, well-drained sandy loams in full sun to part shade. Best in full sun. Tolerant of common city pollutants and conditions. Once established, it is also tolerant of heat and some drought. Newly planted saplings may not flower for as long as the first 10 years.
Noteworthy Characteristics

Japanese pagoda tree is native to China and Korea, but not Japan. It is a medium to large deciduous tree that typically matures to 50-75’ (less frequently to 100’) tall with a broad rounded crown. It is generally cultivated for its attractive compound foliage and fragrant late summer flowers. Pinnate leaves (to 10” long), each with 7-17 oval, lustrous, dark green leaflets, remain attractive throughout the growing season. Leaves retain green color late into fall, resulting in no fall color or at best an undistinguished greenish yellow. Small, fragrant, pea-like, creamy white flowers (each 1/2” long) bloom in late summer in sweeping terminal panicles to 12” long and to 12” wide. Flowers fall to the ground around the tree after bloom covering the ground with a blanket of white. Flowers give way to slender, 1- to 6-seeded, knobby, bean-like pods (to 3-8” long) that mature to brown in fall and persist into winter. Although not native to Japan, the specific epithet and common name seem to recognize the early use of the tree in Japan around Buddhist temples. This tree is also commonly known as Chinese scholar tree.
Problems

No serious insect or disease problems. Twig blight, verticillium wilt, canker, powdery mildew and rust may occur. Watch for leaf hoppers.