Protective effect of flavonoids from Astragalus complanatus on radiation induced damages in mice
Graphical Abstract
Introduction
The development of a technological society is associated with increasing environmental pollution and reduced immunity to disease. Radiation, oxidation, and toxic substances are all potentially damaging factors. Radiation is one of the most important environmental factors because of its hazardous health effects, which include oxidative stress, hematopoietic system dysfunction, genetic mutations and immune dysfunction [1]. It has become imperative to safeguard human populations against high background radiation.
A number of preventive and therapeutic chemical and biological agents can combat radiation injury. However, some can also result in a series of side effects [2], and people have therefore investigated the anti-radiation effects of natural products [3]. At present, almost 70% of the world's population use medicinal plants, and an increasing number of medicinal plants have been proven to protect against radiation injury [4], including flavonoids. Herbal medicines have attracted considerable interest as alternative remedies because of their low toxicity and costs. Flavonoids are the active ingredients of many Chinese herbal medicines which can exhibit anti-inflammatory, analgesic properties, immunoregulatory, anti-tumor and anti-radiation effects. For example, low-doses of Ginkgo biloba flavonoids significantly improved the survival rate and average survival time of irradiated mice [5].
Shayuanzi comprises the dry mature seeds of Astragalus complanatus (AC), which mainly grows in Shaanxi, Gansu, Shanxi, Hebei and Inner Mongolia in China. It is believed that AC which is warm and sweet had the functions of hepatoprotection, tonifying kidney, improving acuity of vision in the most authoritative medical book of Ancient China “Compendium of Materia Medica”. AC has been extensively used for clinical treatment of reinforcing liver benefiting kidney and gynecological disease for more than a thousand years in China. Thus the method of reinforcing liver benefiting kidney is also one of the basic therapeutics which is called “Fuzheng-peiben” in traditional Chinese medicine to treat tumor. Therefore, nowadays AC is used as an antineoplastic traditional Chinese drug in the clinic of traditional Chinese medicine. AC has been widely used in clinical therapy. “The Pharmacopoeia of the PRC” records the clinical usage of drug composing with AC. AC was a drug by means of various kinds of decoctions and over-the-counter to cure dizziness induced by the liver or kidney's debility, such as Shayuanzi grains and jinsuo gujing pills in China.
Since the 1980s, many researchers have studied the chemical composition and pharmacological effects of AC. AC contains flavonoids, triterpenes, organic acids, amino acids, peptides, proteins, tannin, polysaccharides and microelements. It is certified that AC has the functions of anti-liver fibrosis, restraining platelet aggregation, modifying haemorheology, anti-inflammatory, and anti-tumor [6]. In the past 10 years, members of the group focus on the pharmacological activity and the identification of the active component of AC. It is certified that the flavonoid fraction of AC seeds (FAC) is mainly an active constituent and has least side effects and toxicity. FAC was isolated and chemical analysis of the extract indicated that it accounted for 78% of the seeds by weight. FAC was shown to upregulate the body's own immune system, and to have anti-tumor, anti-lipid peroxidation, blood pressure lowering, and liver protective effects [7], [8], [9], [10], [11], [12], [13]. The antineoplastic mechanism of FAC is related to inducing apoptosis of tumor cells, inhibiting tumor angiogenesis and enhancing the immune function, and the mechanism reflects the multitargeted characteristic of traditional Chinese medicine. Otherwise there are literatures to report the anti-radioprotective properties of flavonoids [5]. The hepatoprotective effect of FAC was confirmed by histopathology, which demonstrated improved liver architecture, absence of parenchymal congestion, and reduced cellular swelling, compared with untreated animals. Preliminary investigations suggested that the hepatoprotective mechanism was related to improved immune function. Flavones have been shown to improve immune function, and we therefore investigated the protective effects of FAC on immune and hematopoietic function. In order to further research the anti-liver tumor and hepatoprotective mechanism of FAC, we study the radioresistant effects of FAC.
The mammalian liver is a highly radiosensitive organ that contains enzymes and antioxidants responsible for drug metabolism [14]. In this study, we investigated the possibility that FAC was able to protect the body from radiation injury through improving immune function and reducing DNA damage to reduce the risk of developing radiation-related diseases. With the development of the study, FAC may become a more available new drug to accord with international medicine standardization and has better therapeutic value in clinic.
Section snippets
Plant material
Dried seeds of AC R.Br. (Family: Leguminosae) were obtained from Shanxi Weinan Pharmaceutical Corporation (Shanxi, China) in December 2004 and identified by chief pharmacist, Wu Yin-Sheng (Suzhou Drug Administration Bureau). The voucher specimen (No.SAC/200504) was deposited in the Herbarium of the College of Pharmacology, Suzhou University, China.
Preparation of flavonoids from AC
Dry seeds from AC were pulverized in an electric grinder and the fine powder was defatted using ligarine in a Soxhlet apparatus. The defatted portion
Acute toxicity
FAC administration was not associated with any mortality throughout the whole observation period, though there was some reduction in activity. External appearance, respiration, heart rate, appetite, BW and excretion were all normal. No pathological changes were visible at autopsy. We concluded that the maximum dose suitable to administer to mice was 15 g/kg BW.
Effect of FAC on survival rate of irradiated mice
60Co γ-ray total body irradiation at 6 Gy reduced the survival rate of mice to 70.8% after 21 days, indicating a deleterious effect of
Discussion
In China, the seeds of AC for the clinical treatment of diseases could be traced back to the Tang Dynasty more than a thousand years ago. It is recorded as an important medicine and tonic food for China's royal family in the 2005 version of the “Chinese Pharmacopoeia”. In modern times AC is used for clinical treatment of liver and kidney complaints. There are recent reports that the prescription drugs with the component of AC, for example granular formulation (De Tian Medicine Co. Ltd., Xian,
Acknowledgment
This study was supported by the Natural Science Fund for Colleges and Universities in Jiangsu Province (No. 06KJB360105) in 2006.
References (32)
- et al.
Short-term injection of antiapoptotic cytokine combinations soon after lethal gamma irradiation promotes survival
Blood
(2003) - et al.
Induction of apoptosisin human hepatocarcinoma SMMC-7721cells in vitro by flavonoids from Astragalus complanatus
J Ethnopharmacol
(2009) - et al.
Arabinoxylans and endoxylanases in wheat flour
J Cereal Sci
(2002) DNA double stand break repair in mammalian cell
Curr Opin Genet Dev
(2000)- et al.
Radiation-induced bystander effects:are they good, bad or both? Medicine
Med Confl Surviv
(2005) - et al.
Radiomodulatory influence of Rajgira (Amaranthus paniculatus) leaf extract in Swiss albino mice
Phytother Res
(2003) - et al.
Radioprotective effects of ginsa, an immunomodulator
Radiat Res
(2003) Drug Discov. Hosseinimehr Foundation review: trends in the development of radioprotective agents
Today
(2007)- et al.
Grape seed extract reduces oxidative stress and fibrosis in experimental biliary obstruction
J Gastroenterol Hepatol
(2007) - et al.
Anti-hyperglycemic effect of diacylated anthocyanin derived from Ipomoea batatas cultivar Ayamurasaki can be achieved through the alpha glucosidase inhibitory action
J Agr Food Chem
(2002)
Effect of Astragalus complanatus flavonoid on liver fibrosis induced by DMN in rats.
CPB
Effect of Astragalus complanatus flavonoid on liver fibrosis induced by CCl4 and serum levels of IFN-γ and TGF-β1 in rats
J Chin PHA SCI
Protective effect of Astragalus complanatus flavonoid on liver fibrosis induced by CCl4 and CalN in mice and hhepatocellular primary culture
Chin Tradit Herb Drugs
Effect of flavonoids of Astragalus complanatus on SMMC7721 human liver caner subcutaneous transplanting tumor in nude mice
CPB
Screening of antineoplasmic active component of flavonoids of Astragalus complanatus in vivo and vitro
Chin Tradit Herb Drugs
Tumorous depressant effect and effect on immune function of Astragalus complanatus flavonoid in H22 tumor-bearing mice
Chin Tradit Patent Medicine
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