rexresearch.com
Matrine vs Cancer
https://www.youtube.com/watch?v=Ya1PH7gIW-8
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.
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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.
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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
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chemical bonds, and matrine is dissolved into a water solution
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matrine water solution is dripped into the organic phase to form
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The present invention is concerned with a process for the
manufacture of a herbal composition, said process comprising: a.
subjecting a matrine containing plant material, in the absence of
a plant material derived from the species Dictamnus, to an
extraction with an aqueous solvent, optionally followed by a
concentration step, to produce a herbal extract I; b. subjecting a
plant material derived from the species Dictamnus, to an
extraction with an aqueous solvent, optionally followed by a
concentration step, to produce a herbal extract II; c. mixing the
herbal extracts I and II; d. provided the resulting mixture
contains a significant amount of water, drying the mixture to a
water content of less than 6 wt. %. The herbal composition
according to the present invention may advantageously be used in a
method of treating or preventing cancer, H. pylori infections,
chronic inflammatory conditions, cardiovascular diseases or
cerebral vascular diseases in mammals.
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and biosynthesis. The present invention disclosed that HHT
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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
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Lipopolysaccharide of Kelp (LIK), Puerarin (PUN) and Indirubin
(IND) for diverting human cancer cells to closely normal cells,
inducing apoptosis of cancer cells and inhibiting cancer cells.
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HHT and other ingredients
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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
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pH=7 to obtain magnetic fluid, using acetic acid to prepare
chitosan solution, using distilled water to prepare polyphosphate,
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concentration; merging extracted solution, regulating pH value,
sterilizing, cold storing, suction filtering, and adding matrine
dissolved in injection water to obtain the medicine liquid. The
medicine liquid may be prepared into various forms, including
injection, transfusion fluid, powder for injection, tablet,
capsule, etc. The present invention can raise the immunity of
cancer patient and inhibit tumor.
Medicinal composition for treating liver disease
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compound of arasaponin and the kuhseng alkaloid chosen from the
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sophora, common alkaloid of sophora alopecuroids, matrine and
kurannol.
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.