Flavin7 bioflavonoid complex + Artemisinin!
For a description of the active ingredient Artemisinin, the mechanism of action, click here for more information!
What are Flavonoids?
The name flavonoids refers to a group of compounds whose members have a similar chemical backbone and are found mainly in the peel and seeds of fruits and vegetables. Flavonoids are produced by plants for their own protection.
It is important to know about the physiological effects of flavonoids, that they act mainly in the digestive and circulatory systems and are absorbed in the intestinal tract. It neutralizes free radicals, ie they have an antioxidant effect, reduce the risk of atherosclerosis. They inhibit thrombosis, increase the elasticity of blood vessel walls. They have an effect on sootome lesions (mutagenesis) and the process of developing malignancies (carcinogenesis).
They lower LDL (“bad” cholesterol) and blood fat (serum tridlyceride) levels. They have a liver and sunscreen effect. They are anti-inflammatory, prevent long-term complications of diabetes mellitus, and have antiviral, antibacterial effects.
Watch a short introductory video about flavonoids:
How long have we known about Flavonoids?
In 1936, Albert Szent-Györgyi and István Rusznyák were the first to show that two flavonoids (rutin, naringenin) from citrus fruits reduce the fragility and permeability (permeability) of capillaries, which is why rutin was first named vitamin P. Since then, science has isolated thousands of similar compounds.
What are Flavonoids good for?
Flavonoids increase the body’s antioxidant capacity, which can reduce the cell-destroying effects of free radicals. They support the optimal operation of the defense system.
Red grapes can help the vascular system to function optimally, improve circulation. Through its antioxidant properties, it can help protect cells from the destructive effects of free radicals.
Narenda P. Singh¹
Krishna B, Verma²
1. Department of Bioengineering, University of Washington, Seattle, USA
2. Vivekanand Hospital, Pallavpuram, Meerut, UP, India
Case study of squamous cell carcinoma of a larynx treated with artesunate (a semi-synthetic derivative of artemisinin)
The present study describes the treatment of a patient with laryngeal squamous cell carcinoma with a water-soluble artemisinin analog, artesunate. Artesuna is a new type of anti-cancer drug with proven results in killing cancer cells. The patient received artesunate injections and tablets for nine months. After two months of treatment, the tumor contracted significantly (70%). All in all, treatment of the patient with artesunate had a beneficial effect on both prolonging the patient’s life and improving his quality of life. Artemisinin and its analogues are promising in cancer therapy.
Keywords: laryngeal tumors, carcinoma, squamous cell, anti-malarial drugs.
Oncology Archive 2002,10 (4) 279-280 ?? 2002 Institute of Oncology, Sremska Kamenica, Yugoslavia
Approximately one percent of cancers originate in the larynx and laryngeal cancer accounts for 45% of head and neck carcinomas (1). Most laryngeal cancers are squamous cell carcinoma. The majority of laryngeal cancers occur in men over 50 years of age. It is often associated with heavy smoking and alcohol consumption. The most commonly used treatments for laryngeal cancer patients are radiation therapy, surgery, and chemotherapy.
In this case study, we present a new therapy in the treatment of laryngeal cancer in which artesunate, an analogue of the antimalarial drug artemisinin, was used. Artemisinin is a sesquiterpene lactone extracted from a plant called Artemisia annua L. (sweet / annual wormwood). The artemisinin molecule contains an endoperoxide bridge that reacts with the iron atom molecule to form free radicals (2), which cause macromolecular damage and cell death. Because cancer cells have significantly higher iron influx through the transferrin receptor mechanism, they are much more susceptible to the cell-killing effect of artemisinin. Studying the anti-cancer ability of artemisinin analog in vitro has yielded promising results (3, 4).This study is the first in terms of the use of artemisinin as an anticancer therapy in humans.
A seventy-two-year-old vegetarian man with a long tobacco chewing and smoking background was admitted to Vivekanand Hospital (Meerut, India) on December 15, 2000. The patient has complained of increasing hoarseness, loss of appetite, and weight loss over the past eight months. Over the past six months, he has experienced recurring difficulties in swallowing solid food, which has increased over time. Four months before visiting the clinic, the patient noticed pain in his right ear. The pain was stinging in nature, moderate and intermittent, with no radiation. Two months before admission, she noticed pain on the right side of her neck under her jaw. The pain was mild in intensity, intermittent and without radiation. Fifteen days prior to admission, the patient was unable to swallow food. As soon as you took solid food with you,accompanied by a cough reflex, he vomited immediately. There were blood marks in the vomit. On the day of admission, the patient showed the following symptoms: 1) significant difficulty in swallowing solid food; 2) hoarse voice; and 3) a complaint of pain on the right side of the neck under the jaw. Physical examination revealed enlarged cervical lymph nodes on the right side of the neck. Laryngoscopic examination showed swelling of the right side of the larynx. The growth extended to the right vocal cords, the right pear-shaped cavity, the frontal view of the laryngeal head and the adjacent pharyngeal wall lateral area.and 3) a complaint of pain on the right side of the neck under the jaw. Physical examination revealed enlarged cervical lymph nodes on the right side of the neck. Laryngoscopic examination showed swelling of the right side of the larynx. The growth extended to the right vocal cords, the right pear-shaped cavity, the frontal view of the laryngeal head and the adjacent pharyngeal wall area.and 3) a complaint of pain on the right side of the neck under the jaw. Physical examination revealed enlarged cervical lymph nodes on the right side of the neck. Laryngoscopic examination showed swelling of the right side of the larynx. The growth extended to the right vocal cords, the right pear-shaped cavity, the frontal view of the laryngeal head and the adjacent pharyngeal wall area.
The surface of the swelling was irregular, lumpy, ulcerated, and bleeding on touch. Its size is approximately 3 cm x 2.5 cm x 3 cm = 22.5 cm³. The diagnosis II. stage laryngeal cancer (T2 N1 M0). After histopathological examination of the biopsy from the swelling, a diagnosis of differentiated squamous cell carcinoma was made. Following the patient’s consent, artesunate treatment was started on 22.01.2001. On the first day of treatment, a capsule containing 150 mg of ferrous sulphate and 0.5 mg of folic acid was administered orally at 2.00 pm after a meal. Artesunate injections (Cadila Healthcare Ltd, Ahmedabad, India, 60 mg intramuscularly, daily) were administered daily from the first day of treatment (January 22, 2001) to day 15 (February 5, 2001) at 10:00 am. One tablet of artesunate (50 mg, Cadila Healthcare Ltd., Ahmedabad, India) was taken in the evening 10.00:00 every day after the evening meal from the 16th day of treatment (February 6, 2001). The patient has been doing weight lifting exercises since starting treatment.
You can get more information about the treatment by contacting the first author.
The patient had a fever (37.7–38.3 º C) from the fourth to the seventh day of treatment. After the start of treatment, the hoarseness of his voice continuously decreased. After two weeks of treatment, her voice became clear. The patient was able to take in solid food quite easily. He regained his good appetite. Clinical trials have revealed a reduction in the size of swollen cervical lymph nodes. Laryngoscopic examinations performed on March 25, 2001 showed an increase, including the right vocal cord, the right pear-shaped cavity, the larynx, and a frontal view of the adjacent pharyngeal wall area. The size of the increase is approximately 2.25 cm x 2 cm x 1.5 cm = 6.75 cm³, which is a significant decrease of 70% compared to the original size (22.5 cm x 6.75 cm = 15.75 cm³).
The growth was non-nodular and non-ulcerative. The patient gained two kilograms in the two months since starting treatment and felt physically and mentally strong.
It does not belong directly here, but we note that the patient had extensive pigmented skin patches around his mouth, on the fingers of both hands, which responded well to artesunate treatment during the nine months of observation.
This is the first report on the use of a daily dose of artesunate in cancer treatment.
We have previously reported that artemisinin selectively killed lymph node tumor cells (belonging to the human leukemia cell line) after incubation with holotransfermin (3), whereas this treatment had a significantly smaller effect on normal human lymphocytes. A similar effect was observed for human breast cancer cells (4). Furthermore, we found that oral administration of artemisinin analog and iron sulfate delayed the growth of ingested fibrosarcoma cancer in rats (5).
Another study also showed that artesunate was effective in inhibiting the growth of various types of human cancer cells in vitro (6). Without treatment, laryngeal cancer patients die in an average of 12 months (1). The patient lived for almost a year and eight months (until his death from pneumonia on November 1, 2002) after the onset of symptoms, despite discontinuation of treatment after nine months. Considering the complication factors in this case, including treatment discontinuation and treatment at a late stage, we feel that artemisinin has been successful in both prolonging the patient’s life and improving their quality of life.
The observations that the patient regained voice, appetite, and weight after a short treatment with artesunate, and the fact that the tumor size was significantly reduced (by 70%), while no visible side effects were observed, indicate that this could be an effective and economical alternative treatment for cancer, especially in the case of late detection when available treatment procedures are limited. Following this incident, treatment of several different cancer patients with artemisinin and its analogs began with promising results. We feel that this new emerging therapy is promising in the prevention and treatment of different cancers because it exerts its effect through a simple mechanism that is common to all cancer cells (i.e., by increasing iron intake).
Dihydroartemisinin increases the efficacy of chemotherapy for lung cancer in vivo and inhibits the growth of the rat Lewis lung cancer cell line In vitro
Zhou HJ, Zhang Jl, Wang Z, Lou XE, Author’s Information
Dihydroartemisinin (DHA), a semi-synthetic derivative of artemisinin, showed the strongest antimalarial activity among artemisinin derivatives. There is growing evidence that DHA has antitumor effects. Our aim was to evaluate the antitumor properties of DHA in rats in the Lewis Lung Carcinoma (LLC) cell line in vitro.
However, the therapeutic effect of DHA in combination with cyclophosphamide (cytoxan – CTX) in combination with Lewis lung cancer (LLC) and cisplatin (CDDP) in xenotransplantation of human non-small cell lung cancer (A549) was investigated in vivo.
Cytotoxicity was measured by 3- (4,5-dymethylthiazol-2-yl) -2,5-diphenyltetrazolium bromide, programmed cell death by AO / EB [(acridine orange / ethidium bromide) acridine orange / ethidium bromide] double staining and measured by flow cytometry. Expression of the vascular endothelial growth factor (VEGF) receptor (KDR / flk-1) was measured by Western blot and RT-PCR (reverse transcription polymerase chain reaction). The in vivo activity of the combination of DHA with CTX or CD-DP was assessed based on tumor growth and metastasis.
Dihydroartemisinin showed high anticancer activity in the LLC cell line. DHA also promoted programmed necrosis of LLC cells and influenced VEGF (KDR / flk-1) receptor expression. Furthermore, greater growth inhibition was achieved in xenografts of both cancers when DHA and chemotherapy were used in combination. The effect of DHA combined with CTX on LLC cancer metastases was significant.
In vitro, dihydroartemisinin (DHA) is an active compound against the LLC cell line. In vivo, a combined strategy of DHA and chemotherapy is promising in the treatment of relatively large and rapidly growing lung cancers.
Dyhydroartemisinin (DHA) promotes caspase-3-dependent directed cell death in human lung adenocarcinoma ASTC-a-1 cells
Lu YY, Chen TS, Qu JL, Sun L, Wei XB
Dihydroartemisinin (DHA) is a semi-synthetic derivative of artemisinin extracted from the traditional Chinese herb, Artemisia annua (annual wormwood), and is recommended primarily as a low-toxicity antimalarial agent.
DHA has shown properties with promising anti-cancer activity and promoted the death of cancer cells by programmed cell death, although its molecular mechanisms are not yet fully understood.
In this study, a cell counting kit (CCK-8) was used to evaluate the survival of DHA-treated ASTC-a-1 cells. Detection of apoptosis induction was performed by HOechst 33258 and P1 staining as well as flow cytometric analysis.
Mitochondrial transmembrane potential (DeltaPsim) collapse was measured by dynamic detection under a laser scanning confocal microscope and by flow cytometric analysis using Rhodamine 123. Caspase-3 activity was measured with or without pretreatment with Z-VAD-fmk (a broad-spectrum caspase inhibitor), FRET (Fluorescence Resonance Energy Transfer), caspase-3 activity measurement and Western blot analysis. .
Our results showed that DHA induced dose- and duration-dependent programmed cell death with mitochondrial morphological changes, DeltaPsim loss, and caspase-3 activation.
These results showed for the first time that DHA can inhibit cell proliferation and cause programmed cell death through caspase-3-dependent mitochondrial death in ASTC-a-1 cells. Our work may provide further evidence for further study of DHA as a potential anticancer agent in the clinical treatment of lung adenocarcinoma.
The anti-malarial artesunate is also effective against cancer
Efferth T, Dunstan H. Sauerbrey A. Miyachi H. Chitambar CR.
Artesunate (ART) is a semi-synthetic derivative of artemisinin, the active ingredient in the Chinese herb Artemisia annua (annual wormwood). ART shows significant activity against the otherwise multidrug-resistant pathogens Plasmodium falciparum and Plasmodium vivax. ART was tested for anti-cancer activity against 55 cell lines by the National Cancer Institute Developmental Therapeutics Program (USA).
ART was most active against leukemia and colon cancer cell lines [representing the following GI50 values: 1.11 +/- 0.56 microM and 2.13 +/- 0.74 microM, respectively]. Non-small cell cancer cell lines showed the highest mean GI50 (25.62 +/- 14.95 microM) and showed the lowest susceptibility to ART in this test panel. Intermediate GI50 values were obtained for melanomas, breast, ovarian, prostate, central nervous system, and renal cell lines. It is important to note that a comparison of the cytotoxicity of ART with the cytotoxicity of other standard cytostatic drugs showed that ART showed activity in the molar ranges in which already introduced anticancer agents are used. Furthermore, we tested CEM leukemia sublines that were resistant to doxorubicin,vincdistine, methoterxate, or hydroxyurea and that were not on the screening panel of the NCI (National Cancer Institute). None of these drug-resistant cell lines showed cross-resistance to ART. In order to gain insight into the molecular mechanisms of ART cytotoxicity, isogenic strains of Saccharomyces cerevisiae carrying specific mutations in the DNA repair system, DNA checkpoints, and cell proliferation genes were used.to gain insight into the molecular mechanisms of ART cytotoxicity, isogenic strains of Saccharomyces cerevisiae carrying specific mutations in the DNA repair system, DNA checkpoints, and cell proliferation genes were used.to gain insight into the molecular mechanisms of ART cytotoxicity, isogenic strains of Saccharomyces cerevisiae carrying specific mutations in the DNA repair system, DNA checkpoints, and cell proliferation genes were used.
None of these drug-resistant cell lines showed cross-resistance to ART. In order to gain insight into the molecular mechanisms of ART cytotoxicity, isogenic strains of Saccharomyces cerevisiae carrying specific mutations in the DNA repair system, DNA checkpoints, and cell proliferation genes were used. One yeast strain with a defective mitosis-regulating BUB3 gene showed increased ART sensitivity, and another strain with a defective cell proliferation-regulating CLN2 gene showed increased ART resistance compared to the wild-type strain wt644. No other isogenic strain with other defective DNA repair or DNA checkpoints showed a difference from the wild type. Because of these results and the known low toxicity of ART, ART may be a promising new candidate for cancer chemotherapy.
Artesunate induces programmed cell death by BAK-mediated caspase-independent intrinsic mechanism in human lung cancer cells
Zhou C, Pan W. Wang XP, Chen Ts.
The aim of this study was to study the precise molecular mechanisms by which artesunate (ART), a plant-derived antimalarial drug, a semi-synthetic derivative of artemisin, induces programmed cell death in human lung cancer (ASTC-a-1 and A549). cell lines. ART treatment induces ROS (reactive oxygen species) -mediated programmed cell death in a concentration- and time-dependent manner, associated with decreased mitochondrial potential and Smac and AIF (apoptosis inducing factor) release, leading to intrinsic program blockade of caspase-8 and -9 showed no inhibitory effect on ART-induced cell death, but in contrast, silencing of AIF inhibited it.Most importantly, ART treatment induced activation of BAK – but not BAX (bcl2 associated X protein) and silencing of BAK but not BAX significantly inhibited ART-induced programmed cell death and AIF release.
Furthermore, although ART treatment did not significantly induce downregulation of voltage-dependent anion channel 2 (VDAC2) expression and upregulation of BIM (bcl2 interacting mediator) expression, silencing of VDAC2 strongly increased ART induced BAK activation and programmed cell death, which in turn was significantly hindered by BIM silencing. In summary, our data showed for the first time that ART Capricorn-mediated intrinsic programmed cell death induces in which BIM and VDAC2 as well as AIF play an important role in both ASTC-a-1 and A549 cell lines, indicating a potential cure for ART. effect in lung cancer.
Artesunate increases the sensitivity of human non-small cell A549 lung cancer cells to radiation through increased NO production, which increases cell cycle disruption in the G2 / M phase
Zhao Y, Jiang W, Li B, Yao Q, Dong J. Ian X. Li J, Zheng J, Pang X, Zhou H,
Radiation resistance in non-small cell lung cancer (NSCLC) is the main reason why radiotherapy fails in this type of cancer.
There is currently no effective radiation sensitizer in clinical use. Artemisinin and its derivatives increase the radiotherapeutic effect in some cancers; however, whether artemisinin and its derivatives can increase the sensitivity of NSCLC to radioactivity is not yet known.
Therefore, in the present experiments, artemisinin and its derivatives were first investigated for radiosensitization of NSCLC A549 (A549) cells and then the potential mechanisms were investigated. Our results showed that in vitro, of artemisinin and its derivatives, artesunate increased the radiation sensitivity of A549 cells and that artesunate in combination with topical radiotherapy inhibited tumor growth in xenografts; the inhibition rate for artesunate 30 mg / kg was 74.6%. In terms of possible mechanisms, the results showed that artesunate increased NO levels in irradiated A549 cells. Artesunate did not induce programmed cell death of irradiated cells, but induced G (2) / M arrest. The induced G (2) / M arrest was associated with downregulation of cyclin B1 mRNA expression.Overall, artesunate induced effective radiation sensitivity in human A549 cells in vitro and in vivo, presumably by inducing cell cycle inhibition in the G (2) / M phase through the NO signal transduction mechanism.
Therefore, artesunate should be further investigated as a radiation sensitiser in clinical use.
Oral artemisinin prevents and inhibits 7,12-dimethylbenz [a] anthracene (DMBA) -induced breast cancer in rats.
Lai H1, Singh NP.
Artemisinin, an active substance isolated from the annual wormwood (Artemisia annua L.), has previously been shown to be selectively toxic to cancer cells in vitro. In the present experiment, we investigated the ability of artemisinin to prevent the development of breast cancer in rats induced by a single oral dose of 50 mg / kg 7,12-dimethylbenz [a] anthracene (DMBA), a substance known to cause multiple its effect on breast tumors. Immediately after the day after DMBA treatment, one group of rats received a powdered rat diet containing 0.02% artemisinin, while the control group received a simple powdered rat diet.
Breast tumors were observed in both groups for 40 weeks. Oral artemisinin significantly delayed (P <.002) the development of breast cancer and prevented the development of tumors in some animals (57% in the artemisinin-fed group compared to 96% in the control group, P <.01). during the observation period.
In addition, artemisinin-fed rats had significantly fewer breast cancers (P <.002) and were smaller in size (P <.05) than in the control group. Because artemisinin is a relatively safe compound that does not cause known side effects, even at very high oral doses, current data indicate that artemisinin is a potentially effective cancer-preventing compound.
Effects of artemisinin dimers on rat breast cancer in vitro and in vivo.
Singh NP1, Lai HC, Park JS, Gerhardt TE,
Kim BJ, Wang S, Sasaki T.
Artemisinin has already been shown to be an effective anti-malarial and anti-cancer compound. Dimers of artemisinin have been synthesized and shown to have potent antimalarial activity relative to monomers. In the present experiment, we investigated how dimers of artemisinin (dimer alcohol and dimer hydrazone) affect rat adenocarcinoma cells (MTLn3) in vitro and in vivo compared to artemisinin monomeric dihydroartemisinin (DHA). We have found that dimers are much more effective in killing MTLn3 cells in vitro and suppressing the growth of MTLn3 breast tumors in vivo than DHA.
Involvement of mitochondrial mechanism and Bim / Bcl-2 balance in human breast cancer with dihydroartemisinin-induced apoptosis in vitro.
Mao H1, Gu H, Qu X, Sun J, Song B,
Gao W, Liu J, Shao Q.
Dihydroartemisinin (DHA), a semi-synthetic derivative and active metabolite of artemisinin, has been shown to have potent anti-cancer activity in addition to its potent anti-malarial effect. The aim of the current experiment was to thoroughly investigate the antitumor effects of DHA and to understand the molecular basis of the use of DHA in the treatment of breast cancer. Our results showed that DHA was able to significantly inhibit cell proliferation in a dose- and time-dependent manner associated with induced apoptosis and cell arrest in the G0 / G1 phase. The half-maximal inhibitory concentrations (IC50) of DHA treatment were 60.03, 33.86, and 17.18 μM at 24, 48, and 72 hours, respectively. DHA treatment also dramatically increased the expression of caspase-8 protein as well as cleaved caspase-9 and activated Bid,and induced cytochrome c release from mitochondria to the cytosol. In addition, the apoptotic effect of DHA was associated with increased expression of the Bim pro-apoptotic gene as well as decreased expression of the anti-apoptotic gene Bcl-2.
Therefore, the mitochondrial mechanism is involved in DHA-induced apoptosis of breast cancer cells, and an imbalance in the Bim / Bcl-2 interaction may promote a beneficial effect against cancer cells. All in all, our experiment provides scientific arguments for the clinical use of DHA in breast cancer cases.
Selective cancer cell cytotoxicity due to exposure to dihydroartemisinin and holotransferrin.
Lai H1, Singh NP.
Rapid cell death was observed, as evidenced by the decreasing cell number when molt-4-lymphoblastoid cells (a human leukemia cell type) were treated with holotransferrin (12microM) and dihydroartemisinin (1-200 microM). Incubation with both compounds alone was much less effective. Significantly fewer cell deaths were observed when normal human lymphocytes were exposed to a combination of these two drugs. Dose-response probit analysis shows that the drug combination is approximately one hundred times more effective on molt-4 cells than on lymphocytes (LD50 for molt-4 was 2.59 microM, for lymphocytes was 230 microM).
This drug combination may provide a whole new approach to cancer treatment.
Effect of artemisinin and artemisinin dimer transferrin conjugates on breast cancer cell lines.
Gong Y1, Gallis BM, Goodlett DR, Yang Y, Lu H, Lacoste E, Lai H, Sasaki T.
Monomeric artemisinin (ART) and artemisinin dimer transferrin (Tf) conjugates were synthesized.
The two conjugates, ART-Tf and dimer-Tf, retained their original protein structure and formed stable aggregates in aqueous buffer. ART-Tf induced a decrease in the amount of proteins involved in apoptosis (survivin), cell cycle (cyclin D1), oncogenesis (c-myelocytomatosis oncogenic product (c-MYC)) and dysregulated WNT signaling (beta-catenin), in both human prostate cancer cells (DU145) and breast cancer cells (MCF7).
Both ARTTf and dimer-Tf decreased the expression of survinin, c-MYC, and mutant human epidermal growth factor receptor-2 (ERBB2 or HER2) in BT474 breast cancer. To the best of our knowledge, for the first time, an ART derivative has been shown to reduce ERBB2 expression in human breast cancer cells. The possible mechanisms of the effects observed in the paper are presented. Both transferrin conjugates strongly inhibited the growth of BT474 cells at the same concentration as they reduced the levels of ERBB2, survivin, and c-MYC, but showed essentially no toxicity to normal MCF10A mammalian cells.
65 g (100 x 650 mg).
Artemisinin absinthium sprout extract, Flavin7 bioflavonoid complex (red grape seed-husk drying, sorghum seed-husk drying, blackberry seed husk drying, black cherry husk drying, blackcurrant seed husk drying, redcurrant husk drying, redcurrant husk) apple peel dried), capsule shell: gelatin, titanium dioxide.
Each capsule can be pulled apart and the active ingredient in it can be consumed without it!
Active ingredient in the recommended daily intake:
|1 capsule||2 capsules|
|Artemisinin||294 mg||588 mg|
|Total polyphenols:||16.6 mg + – 10%||33.2 mg + – 10%|
|of which: -flavonoid||11.6 mg||23.2 mg|
|of which: -resveratrol||0.008 mg||0.016 mg|
– 2 capsules / day.
The preparation is recommended for min. Apply continuously for 3 months.
– 30 capsules, 100 capsules.
It is recommended to use iron for the product!
Flavitamin Iron (60pcs)
E-lit Vitamin – Iron + Vitamin C capsules (60pcs)