Sleep Anti-stress material VENETRON® (Rafuma extract)

  • Features / Abundant Functions
  • About Rafuma
  • A journey of Rafuma production areas(available in Japanese only)

Rafuma, a natural herb material.

It contains more than 4% Hyperoside (H) + Isoquercitrin (I)

Rafuma (Apocynum venetum L.) is a wild perennial plant which is native to Central Asia and warm regions in Europe. Its main production regions are Tarim Basin, Sinkiang Uighur an Autonomous Region and it’s also distributed in Qinghai Province and Sichuan Province in China. It is a herbal medicine that is recorded in Chinese Pharmacopeia as “a mind stabilizer and calms the liver. It is used for insomnia, high blood pressure and nervous breakdown treatments.” In China, Rafuma has been used in various way e.g. clothes fabrics, fishing nets and as tea leaves. Yanlong tea is a roasted Rafuma leave to fit Japanese taste. It’s identified as a Food for Specified Health Uses (FOSHU) as it promotes improvement of high blood pressure.

Tokiwa Phytochamical’s VENETRON® is a powder extracted from Rafuma dry leaves in aqueous ethanol and purified with resin. It contains more than 4% “Hyperoside” and “Isoquercitrin” that are active components of St. John’s wort (SJW), a representative of western herb for anti-stress and anti-depressant.

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Based on clinical data, its effectiveness is verified.

Sleep quality improvement

The improvement of sleep quality related to deep sleep feeling and sleep initiation

A double-blind, and placebo-controlled crossover study on healthy adults with subjective dissatisfaction of sleep quality was conducted. The subjects continued to ingest orally either VENETRON® (50 mg/day) or placebo for 8 days. As the result of the Oguri-Shirakawa-Azumi Sleep Inventory MA version (OSA-MA) (※1), the significantly increase of factor II, initiation and maintenance of sleep, in OSA-MA was confirmed in VENETRON® group compared with placebo group. Therefore, the result suggested the improvement of sleep quality related to deep sleep feeling and sleep initiation (Source:Jpn Pharmacol Ther, 2018, 46(1), 117-125).

(※1) Oguri-Shirakawa-Azumi Sleep Inventory MA version (OSA-MA)
: The OSA-MA examination was performed to assess the sleep quality. The examination included 16 questions, and the results were consolidated into 5 items which were as follows: sleepiness on rising, initiation and maintenance of sleep, frequent dreaming, refreshing on rising, sleep length. A higher number indicated the improvement of sleeping quality.

The change of factor II in the OSA-MA (Initiation and maintenance of sleep) (n=11)

Effect of increasing deep sleep

A placebo-controlled trial on healthy adults with slight sleep disorder were conducted. The subjects continued to take either VENETRON® (50 mg/day) or placebo for 7 days. The sleep state was evaluated by electroencephalogram (EEG) measurement. As the result, it was confirmed that the ratio of non-rapid eye movement (REM) sleep (a state of deep sleep) was significantly increased in VENETRON® group compared with placebo group. Therefore, it suggested that the ingestion of VENETRON® was effective for increasing deep sleep (Source : J Nutr Sci Vitaminol., 2015, 61, 182-187).

The change of ratio non-REM sleep (n=7)

Relieving psychological stress

Improvement of rate of resting effect

A double-blind, and placebo-controlled crossover study on healthy adults with subjective dissatisfaction of sleep quality was conducted. The subjects continued to ingest orally either VENETRON® (50 mg/day) or placebo for 7 days. Then, before the Uchida Kraepelin performance test (UK) (※2) was performed, either VENETRON® (50 mg/day) or placebo was also ingested on each examination days. As the result of the UK, the item “Rate of resting effect” (※3) was significantly increased in VENETRON® group compared with placebo group. It suggested the improvement of resting effect by VENETRON® ingestion (Source:Jpn Pharmacol Ther, 2018, 46(1), 117-125).

(※2) The Uchida Kraepelin performance test (UK)
: The UK was performed by adding two neighboring figures and writing in the last digit number, to assess work performance by evaluating accuracy and amount of work. The subjects were asked to perform UK for 30 min, 15 min of the first half and another 15 min of the second half, with 5 min rest in between.

(※3) Rate of resting effect
: Proportion of the amount of work after and before the rest

The change of rate of resting effect (n=11)

The subjective mental stress improvement

In the same clinical trial, the subjective symptoms of the subjects following psychological stress were evaluated by the questionnaire after the UK. The items “Nervous”, “Restless” and “Irritated” in the questionnaire showed significant decrease after ingestion in the VENETRON® group, compared with placebo group. It suggested that the ingestion of VENETRON® relieved psychological stress induced by desk work (Source:Jpn Pharmacol Ther, 2018, 46(1), 117-125).

The change of the subjective symptoms (n=17)

Synergistic Effect of VENETRON® and GABA

A double blind, placebo-controlled crossover clinical trial was conducted among healthy males, who were divided into 4 groups: placebo, GABA (25 mg/day), VENETRON® (25 mg/day) and GABA (25 mg/day)+VENETRON® (25 mg/day). The subjects continued to ingest orally each sample for 4 days. The chromogranin A (CgA) (※4) concentration in salivary was quantified before and after the UK. As the results, single-ingestion of VENETRON® or GABA was confirmed a less increase in CgA concentration compared with placebo group. Also, co-ingestion of VENETRON® and GABA exhibited a significant less increase in CgA concentration compared with placebo group. Synergistic effect of VENETRON® and GABA was suggested, and co-ingestion of VENETRON® and GABA may be more potent for stress (Japanese Journal of Physiological Anthropology, 2009, 14(3), 151-155).

(※4) Chromogranin A (CgA)
: A sensitive and promising index for psychosomatic stress. A higher concentration of CgA indicated the high stress.

The change of CgA concentration before and after the ingestion under the psychosomatic stress (n=11)

Improvement of focusing ability maintenance

Focusing ability maintenance

A double-blind, and placebo-controlled crossover study on healthy adults with subjective dissatisfaction of sleep quality was conducted. The subjects continued to ingest orally either VENETRON® (50 mg/day) or placebo for 7 days. Then, before the UK was performed, either VENETRON® (50 mg/day) or placebo was also ingested on each examination days. As the result of UK, the item “Fluctuation rates of performance” showed significant decrease after VENETRON® ingestion compared with placebo group. It suggested that the ingestion of VENETRON® improved the maintenance of focusing ability (Source:Jpn Pharmacol Ther, 2018, 46(1), 117-125).

(※5) Fluctuation rates of performance
: The value which is the average work performance divided by the subtraction of minimum work performance and maximum work performance during the UK. It indicated the unevenness of work performance during the UK. The lower number indicated improvement of unevenness of work performance and maintenance of focusing ability.

The change of fluctuation rates of performance (n=15)

Depression improvement

Improvement of Hamilton Rating Scale for Depression (HAM-D score)

In America, a double-blind, and placebo-controlled study on individuals with mild depression was conducted. The subjects continued to ingest orally either VENETRON® (50 mg/day) or placebo for 8 weeks. The HAM-D score (※6) was evaluated before VENETRON® ingestion, after 4 and 8 weeks of VENETRON® ingestion. As the result, continuous decrease in the HAM-D score was observed from baseline to week 8 in VENETRON® group. It indicated that the ingestion of VENETRON® could help to reduce symptoms of mild to moderate depression. Also, the score related to insomnia in HAM-D score showed decrease in 60% in VENETRON® group.

(※6) Hamilton Rating Scale for Depression (HAM-D score)
: One of the most commonly used scales for rating depression with questionnaire, included a 17-item scale that evaluates depressed mood, vegetative and cognitive symptoms of depression, insomnia and comorbid anxiety symptoms. A higher HAM-D score indicated the worsening of the symptoms.

The changes of HAM-D score and the score related to insomnia (n=20)

Improvement of blood marker regarding depression

In the same clinical trial, the plasma MHPG concentration (※7) was evaluated before and after 8 weeks of VENETRON® ingestion. As the result, 50% of VENETRON® group showed an increase in serotonin levels, and 65% of VENETRON® group showed a decrease in MHPG levels. It indicated that the ingestion of VENETRON® could help to improve symptoms of mild to moderate depression, which is consistent with the above results.

(※7) Plasma MHPG concentration
: 3-methoxy-4-hydroxyphenylethyleneglycol. A marker of which people with strong anxiety and/or frustration marked high scores.

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It complies with the system of “Food with Function Claims”

About the system of “food with function Claims”

As a part of the whole nation’s initiative for disease prevention and health care aiming at realizing a society that “extends the healthy life expectancy of the Japanese people”, the system of “Food with Function Claims” was established in April 2015.
This system allows manufacturers to show consumers an easy-to-understand way about the health functions of food.
To be authorized as a functional food that conforms to the system of “Food with Function Claims”, it is required to submit to the Consumer Affairs Agency (CAA) a “scientific base mandated to describe functions of the foods on its label”. This means any company that wants to apply to the system, needs to review literature on the functionality of necessary ingredients as well as verify that its product contains an effective dose of the identified ingredients.
Tokiwa phytochemical Co., Ltd. offers materials corresponding to the system of “Food with Function Claims”: VENETRON®(Sleep quality improvement), BILBERON®(Focus accommodative function, eye fatigue), GINKGOLON(Cognitive function improvement), SIRTMAX®(Anti-hyperglycemia, anti-aging, in preparation).

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Safety is secured through animal and human trials

A safety review of VENETRON® was published as an scientific paper (Source:Jpn Pharmacol Ther, 2018, 46(1), 127-135).

The safety of VENETRON® in human clinical trial

A human monitor test was conducted for 12 weeks on 30 healthy males. The subjects had been continuously taken VENETRON® 50 mg/day for 8 weeks and then 150 mg/day, a three-times more than recommended dosage for 4 weeks. After the continuous intake, they went through hematology tests, blood chemistry tests, urine tests, as well as weight, blood pressure and pulse evaluation. As a result, there was no abnormality finding on all evaluation item.

Self-affirmed GRAS certification

VENETRON® has acquired self-affirmed GRAS certification. We will challenge to acquire GRAS certification of VENETRON® recognized from FDA.

A safety of VENETRON® in animal studies

Another aspect of VENETRON® which has excellent clinical results is that it has no effect on drug metabolic enzymes and it does not induce p-glycoprotein (chart below).It draws people’s attention as an anti-depressant and anti-stress herb. In comparison with SJW, safety of VENETRON® has been clearly verified (Source:Biol Pharm Bull, 2004, 27, 1649-1652).

Acute single-dose toxicity in mouse
: LD50 ≧ 2000 mg/kg
Subchronic toxicity in rat
:NOAEL ≧ 250 mg/kg/day (Equivalent to 150 mg/day human)

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Patent intellectual property

US patent
Apocynum venetum extract for use as antidepressant (US 6,737,085 B2)
VENETRON® was applied for US patent about usage for sleep improvement (15/938 618)
[Title of the Invention] COMPOSITION FOR IMPROVING SLEEP ONSET AND SLEEP MAINTENANCE, COMPOSITION FOR REDUCING STRESS AND IMPROVING RELAXATION, COMPOSITION FOR IMPROVING PERFORMANCE AND CONCENTRATION, AND COMPOSITION FOR IMPROVING RESTING EFFECT AND PROMOTING RECOVERY FROM FATIGUE

Japan patent
Antidepressant (JP 4629933)
VENETRON® was applied for Japan patent about usage for sleep improvement (JP 2017-193127)

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JIHFS GMP for health food raw materials certification

Tokiwa Phytochemical’s main factory in Chiba is the production base of VENETRON® JIHFS GMP authorized factory. It has obtained JIHFS GMP for health food raw materials certification and is taking all possible measures for production management of VENETRON®. GMP is an abbreviation for Good Manufacturing Practice. Aiming at using domestic raw material only for VENETRON® , Tokiwa has been conducting various arrangements and coordination in all lines of business.

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Development of water-soluble type of VENETRON®

We have developed the water-soluble type of VENETRON® for use in various type of product.

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Studies on VENETRON®

  • Research results
  • Medical Herb Dictionary(available in Japanese only)

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Product PDF
For more Information, call +81-3-5200-1251