06/28/2016

What is RexFlavone

 

What is RexFlavone?

Rexflavone is fermented ethanol extraction of the Sophora japonica Linne fruit.

Sophora_japonica _Linne

Sophora japonica Linne

Sophora japonica Linne – also known as Chinese scholar tree (Chinese: “槐,” “zhong guohuai,” or “huai shu” ), Japanese pagoda tree (in English), Hoe-wha-na-moo (in Korean), Sophora du Japon(in French), Japanischer Schnurbaum (in German), and acacia del Japón (in Spanish) – is a shrub species belonging to the subfamily Faboideae of the pea family Fabaceae. It is a deciduous, wide-branching, small to medium-sized tree that grows up to a height of 15~25m.

Every part of this plant, including the flowers, buds, leaves, bark and seeds are used as medicine in Asia, particularly in China, Japan, and Korea. The dried flower (Huaihua or Flos Sophorae) and the flower buds (Huaimi or Flos Sophorae Immaturus) are included in both the Chinese Pharmacopoeia and European Pharmacopeia. The plant is also described in DonguiBogam (UNESCO-registered Korean physician text) and Bencao Gangmu (Compendium of Materia Medica). The dried ripe fruit of S. japonica, also known as Fructus Sophorae or “Huai Jiao” in Chinese, was first listed in the classic Chinese medical text “Shen-Nung′s Pen-Ts′ao” 2000 years ago in the Han Dynasty. It was ranked as the “highest-grade” medicine. Since then, its use has been recorded in generations of classical Chinese medical texts. The dried flowers and buds of S. japonica were first recorded in “Ri Hua Zi Ben Cao (日华子本草).” In the Ming Dynasty, according to “Ben Cao Pin Hui Jing Yao (本草品汇精要),” the unopened flower is preferred, which implies that the bud of S. japonica was commonly used to treat various diseases.

sophora_japonica_linne


Effect of Sophora japonica Linne

The principal components of S. japonica include flavonoids, isoflavonoids, triterpene, glycosides, alkaloids, phospholipids(PLs), amino acids, microelements, and polysaccharides.

Among these compounds, kaempferol, quercetin, rutin, isorhamnetin, genistein, and sophoricoside are the major active constituents of S. japonica. Rutin, in particular, is the most important and abundant constituent of S. japonica and can be extracted easily and inexpensively.

Rutin is a citrus bioflavonoid with strong antioxidant properties. Bioflavonoids have been used in alternative medicine as an aid to enhance the action of vitamin C, to support blood circulation, as an antioxidant, and to treat allergies, viruses, or arthritis and other inflammatory conditions.

(chemical structure of Rutin)

(chemical structure of Rutin)

Another important compound, isoflavonoid glycoside (sophoricoside), exhibits promising biological effects, including anti-inflammatory, estrogenic, osteoblast proliferation stimulatory, antioxidant, and immunosuppressive activities.

(chemical structure of Sophoricoside)

(chemical structure of Sophoricoside)

Modern pharmacological studies have shown that the active components and/or crude extracts of S. japonica exhibit a wide range of pharmacological actions, such as cardiovascular effects as well as anti-inflammatory, anti-osteoporotic, antioxidant, antitumor, antibacterial, antiviral, hemostatic, and anti-atherosclerotic effects. Because of its beneficial biological effects, it was used in traditional Chinese medicine(TCM) to treat conditions such as hemafecia, hemorrhoids, blood flux, dysfunctional uterine bleeding, hematemesis, and diarrhea. The long-term consumption of the fruit has been shown to have no adverse effect; instead, it was presented to alleviate postmenopausal symptoms in postmenopausal women.


Advantages

  • GMO-free, Toxic-free, Pesticide tested, and 100% natural herb extract.
  • Active flavonoids such as kaempferol, rutin, and quercetin.
  • 10%-90% concentration of isoflavonoids such as genistein, daidzein, and Sophoricoside.
  • Excellent physiological activities to maintain bone health, lower cholesterol level, and presents antioxidant effect.
  • Type of phytoestrogen, exerting estrogen-like effect to help alleviate post-menopausal symptoms.

Patent Enrollment

Reg. No. Date Patent Title
0509681 Oct.31. 2003 Method of producing Sophorae japonica L. extract containing isoflavones
0509682 Aug.16.2005 For the prevention and treatment of bone metabolic disorders, a pharmaceutical composition containing the extract of Sophorae japonica as an active ingredient
0510426 Aug.16.2005 Prevention and improvement of bone metabolic diseases food composition containing the extract of Sophorae japonica as an active ingredient
0539457 2004. 03. 04 Prevention and the treatment composition of the hyperlipidemia including Sophorae japonica extract, atherosclerosis and fatty liver

PCT Application

Application No. Date Patent Title
PCT/KR03/02841 2003. 12. 24 METHOD FOR PREPARING SOPHORAE FRUCTOUS EXTRACT CONTAINING ISOFLAVONE
PCT/KR04/000251 2004. 02. 09 COMPOSITION FOR PREVENTING AND TREATING CLIMACTERIC SYMPTOMS COMPRISING THE EXTRACT OF SOPHORAE FRUCTUS

Case Studies

In vivo, hot water extract of Fructus Sophorae, at an oral dosage of 0.556 g/kg/day for 9 weeks, has been shown to increase the trabecular bone area in the tibia and lumbar of ovariectomized (OVX) rats. It is also known to significantly decrease deoxypyridinoline (Dpd: bone resorption marker) and elevate calcium (Ca: bone formation marker) levels in OVX rat serum (Shim et al., 2005).

In vitro, the dichloromethane fractionated extracts from the mature fruit of S. japonica stimulates alkaline phosphatase (ALP) activity and matrix mineralization of C3H10T1/2 clone 8 cells in a dose-dependent manner. These extracts also induce the expression of osteoblast markers such as ALP, osterix, and osteocalcin in C3H10T1/2 and primary bone marrow cells in a dose-dependent manner. In addition, the dichloromethane fractions also induce ALP expression in freshly isolated mouse embryonic fibroblasts. Further studies show that genistein is the most abundant compound (8.070.08 g/kg) in the dichloromethane fractions, which points to genistein as the key phytoestrogen and critical pro-osteogenic compound in dichloromethane extracts (Yoon et al., 2013).

In 2014, Abdallah et al. showed that sophoricoside isolated from S. japonica seeds exhibited the potential anti-osteoporotic effect. In OVX rats, oral administration of 15 and 30 mg/kg for 45 days increased the level of ALP and osteocalcin, decreased the level of serum acid phosphatase, and ameliorated ovariectomy-induced osteoporosis in a dose-dependent manner. Furthermore, with sophoricoside treatment at a dose of 30 mg/kg, the original mechanical bone hardness was regained in osteoporotic rats compared with normal non-osteoporotic rats (Abdallah et al., 2014).

A cerebral infarction is a type of ischemic stroke due to a blockage in the blood vessels supplying blood to the brain. The aqueous extract of S. japonica shows a positive effect against myocardial infarction. Pretreatment with 100 or 200mg/kg of S. japonica and post treatment with 200mg/kg of S. japonica lead to a significant reduction in the area of cerebral infarction and the grade of neurological deficit. Pretreatment with 200mg/kg of S. japonica also significantly reduces microglial activation, ED1and IL-1β release, and the number of apoptotic cells in rats with ischemia–reperfusion cerebral infarction(Lao et al.,2005).

Kaempferol, genistein, and sophoricoside isolated from fruits of S. japonica show antifertility effects in laboratory animals(Ho et al.,1982,1984). Further study indicates that sophoricoside could impair embryo implantation by modulating the expression levels of estrogen receptor alpha(ERα) and progesterone receptor(PR) in the uterus, affecting the formation of pinopods and reducing mouse endometrial receptivity(Qu et al.,2014).

Genistein, sophoricoside, and genistin, isolated from fruits of S. japonica at 100 mg/mL, show positive antitumor activity with inhibitory rates of 82.01%, 38.87%, and 32.97% for A549, and 91.25%, 23.26%, and 13.98% for BGC-823, respectively (Ma and Lou,2006).

In vitro, the isoflavonoids genistein, orobol, sophoricoside, and genistein, isolated from Fructus Sophorae, have been shown to have the most potent activity against interleukin (IL)-5 (main pro-inflammatory mediators). In particular, sophoricoside exhibits a significant and dose-dependent inhibitory effect in the IL-5 bioassay.

To observe the protective effect of orally administrated Rexflavone (Sophorae fructus extract) for the postmenopausal symptoms, a randomized double-blind placebo controlled clinical trial was designed. Rexflavone significantly improved 11 menopausal symptoms including hot flash, which was evaluated by the modified Kupperman Index (KI), while hormone level and lipid profile were little changed by consumption. Rexflavone group significantly decreased KI score (-14.91 ± 8.79) compared to placebo group (-11.45 ± 6.62) as a representative index for improvement of menopausal symptoms (p < 0.05). (Lee et al., 2010)


Animal Preclinical Study

(Arch. Pharm. Res., 2005, 28, 566-572)

Preclinical_study

Oral injection RexFlavone into ovariectomized rat, total cholesterol, LDL-cholesterol were reduced at 4 weeks and HDL-cholesterol was increased. RexFlavone almost suppressed no and iNOS to control level in BV-2 cell stimulated by LPS.


Human Clinical Study

(Arch. Pharm. Res., 2005, 28, 566-572)

human_clinical_study_1

Clinical studies has shown that change of total Kupperman Index (KI) was significantly decreased at 8 weeks (p<0.05), 12 weeks (p<0.01) compared to control group. KI covers menopausal symptoms vasomotor (hot flashes), paresthesia, insomnia, melancholia, vertigo weakness, nervousness, arthralgia, headaches, formication, and palpitations.

human_clinical_study_2

Significant improvement for hot flash (p=0.0315). Other statistic showed significant improvement in insomnia (p=0.0416), fatigue (p=0.0023), and headache (p=0.0383).