Pharmacological aspects of fisetin

Over the past decades, epidemiological studies have concluded that a diet rich in plant-derived products plays a pivotal role in human health. Fisetin (3,3',4',7-tetrahydroxyflavone) is a hydrophobic polyphenolic compound primarily found in edible plants (e.g. strawberry, blueberry, apple, grape, persimmon, kiwi, and cucumber). Various preclinical studies have revealed that fisetin exhibits a wide range of pharmacological effects such as antioxidant, anti-inflammatory, anti-carcinogenic, anti-osteoporotic, antimicrobial, and anti-diabetic properties. Therefore, the pharmacological in vitro and in vivo studies on fisetin are discussed in this review. Additionally, this review would be useful for further study regarding the potential of natural products, notably fisetin, and its therapeutic potential for the prevention and treatment of diseases.

Pharmacological aspects of fisetin

Over the past decades, epidemiological studies have concluded that a diet rich in plant-derived products plays a pivotal role in human health. Fisetin (3,3',4',7-tetrahydroxyflavone) is a hydrophobic polyphenolic compound primarily found in edible plants (e.g. strawberry, blueberry, apple, grape, persimmon, kiwi, and cucumber). Various preclinical studies have revealed that fisetin exhibits a wide range of pharmacological effects such as antioxidant, anti-inflammatory, anti-carcinogenic, anti-osteoporotic, antimicrobial, and anti-diabetic properties. Therefore, the pharmacological in vitro and in vivo studies on fisetin are discussed in this review. Additionally, this review would be useful for further study regarding the potential of natural products, notably fisetin, and its therapeutic potential for the prevention and treatment of diseases.

A Phytopharmacological Review Of Dadim-punica Granatum Linn.

Punica granatum Linn. is a well-known nature power fruit rich in natural bioactive constituents, edible phytoestrogen like substances and other nutritional elements, grown all over the world from Iran to Mediterranean region and Central Asia. It is also described in Ayurveda as Dadim for treating Amlapitta, Raktapitta and used as Hridya and Atisaraghna. It is used for its good nutritive values generally used in the form of Avaleha, Swaras or Juices and Jellies. Several studies conducted previously showed that pomegranate exhibits antibacterial and antifungal activity. Description of pomegranate is being found since Vedic period. Pomegranate is mentioned in Rigveda also. Aacharya sushrut described pomegranate or Dadim (Sanskrit name) as a best fruit i.e. Shrestha under Phalavarga. According to Acharya Vagbhata, Dadim is also included in Shramghna and Hrudya Gana. In various studies in human and rodent models, pomegranate juice has been found to wield antiatherogenic, antioxidant, anti-carcinogenic, and anti-inflammatory, antidiabetic, gastroprotective, hepatoprotective and nephroprotective activities. Several studies on the antioxidant, anti-carcinogenic, and anti-inflammatory and many more potential properties of various parts of pomegranate and its constituents have been already published. Many studies had proved the latent efficacy of pomegranate and its applications including male infertility, Alzheimer’s disease, and obesity. So, the present study aims to discuss the collective information on pomegranate which can provide a summary to study the diverse array of biological actions of pomegranate and thus provide easy accessibility for treating various common diseases.

Plantas utilizadas para el tratamiento del cáncer expendidas en los principales mercados de la provincia de Trujillo, Perú, 2016 ­ 2017 / Plants used for the treatment of cancer expanded in the main markets of the province of Trujillo, Peru, 2016 - 2017

Between 2016 and 2017, we conducted structured interviews with herbalists in market stands in the providence of Trujillo, La Libertad, Peru in order to create a catalog of plants with anticarcinogenic properties. Herbalists shared information about species they use in cancer treatment, including common names, part of the plant used, methods of preparation, plant state, and frequency and method of administration as medicine. We combined this information with the Shannon-Wiener diversity and evenness index to complete a quantitative analysis of the anticarcinogenic species. Our results demonstrate that 46 different species representing 24 genera and 19 families are locally used in cancer treatment, with a Shannon-Wiener index of 3.6 and 0.9 respectively. Our catalog thus represents a great variety of species and source of potentially useful knowledge for fighting cancer.

Con el objetivo de registrar las plantas con propiedades anticancerígenas distribuidas en la provincia de Trujillo, La Libertad, durante el 2016 y 2017, realizamos entrevistas estructuradas a hierbateros con puesto de venta en los mercados de abastos, quienes brindaron información sobre las especies usadas para el tratamiento del cáncer, detallando nombres vulgares, parte del vegetal utilizado, formas de preparación, estado de la plantas, frecuencia y forma de administración; así mismo aplicando los índices de diversidad Shannon- Wiener y Equidad se hizo el análisis cuantitativo de los datos encontrados. Se evidenció que para el tratamiento del cáncer se usan 46 especies, representadas 24 géneros y 19 familias; valor que refleja un Índice de Diversidad y de Equidad de 3.6 y 0.9 respectivamente, indicando que existe una gran variedad de especies y un conocimiento potencialmente valioso para combatir esta enfermedad.

Screening of drugs for hepatocellular carcinoma prevention based on drug repositioning and network pharmacology / 第二军医大学学报

ObjectiveTo screen novel drugs for hepatocellular carcinoma (HCC) prevention based on drug repositioning strategy. Methods We collected the gene expression profiles of tissue samples representing the stepwise carcinogenic process covering 4 stages: Cirrhosis, low-grade dysplastic nodule (LGDN), high-grade dysplastic nodule (HGDN) and early HCC, and identified the gene signatures between two consecutive stages. We also collected the gene expression data of human hepatocellular carcinoma cell lines HepG2 treated by 3 927 drugs and small molecules. The similarity between disease expressions and the drug gene expressions was calculated using gene set enrichment analysis (GSEA) algorithm, and drugs negatively correlated with the disease signatures were selected. Finally, we constructed the activated sub-network and performed pathway enrichment analysis to explore the underlying mechanisms of these drugs. Results We screened out the drugs that could prevent HCC during different stages, and found that importazole, picotamide and paclitaxel exhibited preventive potentials at all stages from cirrhosis to early HCC. The genes affected by these 3 drugs showed inverse expression pattern during HCC development, and pathways such as cancer-related pathway, p53 signaling pathway, focal adhesion and retinol metabolism pathway were enriched. Conclusion Preventive drugs for HCC have been screened through drug repositioning strategy, and our results indicated that antiplatelet therapy may play a role in the prevention of HCC, which provides information for further study.

Phenolic composition, antioxidant and anti-proliferative activities of edible and medicinal plants from the Peruvian Amazon

ABSTRACT Among 23 extracts of medicinal and edible plants tested, Mauritia flexuosa L.f., Arecaceae, showed significant antioxidant ability (DPPH and ORAC = 1062.9 and 645.9 ± 51.4 µg TE/mg extract, respectively), while Annona montana Macfad., Annonaceae, demonstrated the most promising anti-proliferative effect (IC50 for Hep-G2 and HT-29 = 2.7 and 9.0 µg/ml, respectively). However, combinatory antioxidant/anti-proliferative effect was only detected in Oenocarpus bataua Mart., Arecaceae (DPPH = 903.8 and ORAC = 1024 µg TE/mg extract; IC50 for Hep-G2 and HT-29 at 102.6 and 38.8 µg/ml, respectively) and Inga edulis Mart., Fabaceae (DPPH = 337.0 and ORAC = 795.7 µg TE/mg extract; IC50 for Hep-G2 and HT-29 at 36.3 and 57.9 µg/ml, respectively). Phenolic content was positively correlated with antioxidant potential, however not with anti-proliferative effect. None of these extracts possessed toxicity towards normal foetal lung cells, suggesting their possible use in development of novel plant-based agents with preventive and/or therapeutic action against oxidative stress-related diseases.

Chlorophyllin in the intra-uterine development of mice exposed or not to cyclophosphamide / Clorofilina no desenvolvimento intra-uterino de camundongos expostos ou não à ciclofosfamida

Chlorophyllin, a sodium-copper salt synthesized from chlorophyll, has already proved to have anticlastogenic, antimutagenic and anticarcinogenic activity, however few are the studies in the teratogenicity area. The present study evaluated the effects of chlorophyllin in intra- uterine development of mice exposed or not to cyclophosphamide. Pregnant females were divided into 8 groups of 15 animals each, G01 - PBS (0.1 mL 10.0-1 g) orally; G02 ­ cyclophosphamide (20.0 mg kg-1) i.p.; G03, G04 and G05 - chlorophyllin at concentrations of (5.0, 10.0 and 15.0 mg kg-1) orally; G06, G07 and G08 (5.0, 10.0 and 15.0 mg kg -1) orally, of chlorophyllin, respectively, and (20.0 mg kg-1) i.p. of cyclophosphamide. In the 18th day the females were submitted to laparotomy and females and fetuses analyzed. The results showed that the chlorophyllin was not effective in protecting the reproductive parameters as well as teratogenicity. Finally, it was observed that the presence of chlorophyllin increased the frequency of some malformations when combined with cyclophosphamide. However, it was not teratogenic and not embryo lethal in this experimental design.

Clorofilina é um sal de cobre e sódio sintetizado a partir da clorofila. Provou-se ter atividade anticlastogênica, antimutagênica e anticarcinogênica. No entanto, poucos são os estudos sobre esta substância na área de teratologia. Dessa forma, o presente trabalho avaliou os efeitos da clorofilina no desenvolvimento intrauterino de camundongos expostos ou não à ciclofosfamida. Para tal, fêmeas prenhez foram divididas em oito grupos experimentais contendo 15 animais cada: G01 - PBS (0,1 mL 10.0-1 g) via oral; G02 - ciclofosfamida (20,0 mg kg-1), intraperitoneal; G03, G04 e G05 - clorofilina em concentrações de (5,0; 10,0 e 15,0 mg kg-1) via oral; G06, G07 e G08 (5,0, 10,0 e 15,0 mg kg-1) via oral, de clorofilina, respectivamente, e 20,0 mg kg-1, via intraperitoneal, de ciclofosfamida. No 18º dia de gestação, os animais foram submetidos à laparotomia e os fetos, analisados para parâmetros teratogênicos. Os resultados mostraram que a clorofilina não foi eficaz para proteger os parâmetros reprodutivos, bem como a teratogenicidade. Finalmente, foi observado que a clorofilina quando combinada com a ciclofosfamida aumentou a frequência de algumas malformações. No entanto, a clorofilina não se apresentou teratogênica e nem letal para este desenho experimental.

Extracto acuoso de uchuva (Physalis peruviana): actividades antiproliferativa, apoptótica y antioxidante / Aqueous extract of golden berry (Physalis peruviana): antiproliferative, apoptotic and antioxidant activities

Antecedentes: extractos etanólicos de P. peruviana han mostrado actividad citotóxica contra diferentes células cancerosas. Objetivo: estudiar la actividad anticancerígena de un extracto acuoso del fruto uchuva en células de cáncer de colon SW480 y SW620. Materiales y métodos: se analizaron citotoxicidad e índice de selectividad (SI) (MTT), antiproliferación (sulforodamina-B), apoptosis (ciclo celular, anexina-V, receptores TRAIL-DR4/-DR5 y caspasa-3), actividad antioxidante (contenido de flavonoides y carotenoides totales). Resultados: el extracto acuoso de uchuva mostró efecto citotóxico y antiproliferativo en células SW480 (IC50=44,2 mg/mL, SI=11,6) y SW620 (IC50=85,1mg/mL, SI=6,0). Las células hipodiploides SW480 y SW620 aumentaron 13% y 12%, respectivamente. Las células apoptóticas incrementaron 19% y 21% en SW480 y SW620, respectivamente, con incremento en la expresión de receptores TRAIL-DR4/-DR5 en SW480 (+59%/+53%) y SW620 (+67%/+65%), y activación de caspasa-3 en ambas líneas celulares. El extracto neutralizó radicales OH-, presentó baja capacidad reductora y atrapadora de especies reactivas del oxígeno y nitrógeno. El contenido de flavonoides y carotenoides fue 487,1 mg catequina y 0,9 mg β-caroteno por 100 g de liofilizado, respectivamente. Conclusiones: estos hallazgos sugieren que la uchuva puede ser una fuente prometedora de compuestos bioactivos con actividad quimiopreventiva en cáncer de colon humano.

Background: Ethanolic extracts from P. peruviana showed cytotoxic activity against different cancer cell lines. Objective: To evaluate the antiproliferative activity of aqueous extract of the fruit golden berryin colon cancer cells. Materials and Methods: We analyzed cytotoxicity and selectivity index (SI) (MTT), antiproliferation (sulforhodamine-B), apoptosis (cell cycle, Annexin-V, receptors TRAIL-DR4/-DR5 and caspase-3), and antioxidant activity (content of total carotenoids and flavonoids). Results: The aqueous extract showed cytotoxic and antiproliferative effect on SW480 (IC50 = 44.2 mg/ml, SI = 11.6) and SW620 (IC50 = 85.1 mg/ml, SI = 6.0). The hypodiploid SW480 and SW620 cells increased 13% and 12% respectively as well as apoptotic SW480 and SW620 cells (19% and 21 %, respectively), expression of receptors TRAIL-DR4 /-DR5 (SW480: +59% / +53%; SW620: +67% / +65%) and activation of caspase-3. The aqueous extract scavenged OH- radicals, showed low oxygen radical capacity and low scavenging capacity for reactive oxygen and nitrogen species. The total flavonoids and carotenoids contente was 487.1 mg catechin y 0.9 mg β-carotene by 100 g powder, respectively. Conclusions: These findings suggest that golden berry may be a promising source of bioactive compounds with chemopreventive activity against human colon cancer.

El benzo(a)pireno en los alimentos y su relación con el cáncer / Benzo[a]pyrene from food and cancer

Antecedentes: el benzo(a)pireno es un hidrocarburo aromático policíclico con efectos adversos para la salud, una de las fuentes es la ingestión de alimentos, formados durante procesamiento industrial o en el hogar. Objetivo: indagar sobre la formación de benzo(a)pireno en los alimentos, su activación biológica, relación con el cáncer, contenido en los alimentos y la normativa que regula la cantidad en alimentos para humanos. Materiales y métodos: se realizó una búsqueda bibliográfica de artículos publicados en las bases de datos nacionales e internacionales. Resultados: el benzo(a)pireno ingerido con los alimentos se absorbe por el intestino, se metaboliza predominantemente en el hígado, allí se activa y puede inducir cáncer de diversa localización, como esófago, estómago, intestino, piel, vejiga, pulmón e hígado, evidenciado en estudios experimentales en animales. El benzo(a)pireno atraviesa la placenta y es potencialmente tóxico para el feto. Las cantidades en algunos alimentos exceden las máximas permitidas por la Comisión Europea entidad que periódicamente actualiza las normas sobre el tema. En Colombia no se encontró reglamentación. Conclusión: el benzo(a)pireno procedente de alimentos genera compuestos capaces de desarrollar cáncer principalmente del tracto gastrointestinal. La Comisión Europea actualiza periódicamente la normativa que regula el contenido de benzo(a)pireno en alimentos, Colombia carece de normas sobre el tema.

Background: Benzo[a]pyrene is a polycyclic aromatic hydrocarbon which has been related with adverse health outcomes. Food is a source of benzo[a]pyrene; which is produced during industrial processing or cooking. Objective: To review information about benzo(a)pyrene formation in food, biological activation, association with cancer, food content and regulation of benzo(a)pyrene content in human food. Methods: A literature search from national and international scientific databases was developed. Results: benzo[a]pyrene ingested is absorbed by the intestine metabolized and activated, predominantly, by the liver. Animal studies have associated benzo[a]pyrene with esophagus, stomach, intestine, skin, bladder, lung, and liver cancer. Benzo[a]pyrene is potentially toxic to the fetus, due to it passes trough placenta. Benzo[a]pyrene amounts in some foods exceed the maximum level allowed by the European Commission; which periodically updates legislation on this topic. In Colombia there is not regulation about benzo[a]pyrene. Conclusion: benzo[a]pyrene in food generates compounds that may be associated with cancer, mainly gastrointestinal cancer. The European Commission regularly updates regulation about benzo[a] pyrene content in foods. Colombia does not have regulation on this topic.

Chemotherapeutic potential of Boerhaavia diffusa Linn: A review.

Boerhaavia diffusa Linn. has been shown to exhibit a wide range of medicinal properties for the treatment of diabetes, inflammation, stress, hepatotoxicity, jaundice and heart failure. The extraordinary antioxidant, hepatoprotective, antibiotic, antidiabetic and anticarcinogenic properties of B. diffusa have attracted pioneers in the field of science and medicine. Moreover, the therapeutic importance of this plant, which is due to presence of polyphenols and flavanoids, makes this plant medically more important to be exploited by clinicians and scientists to gain more insight into its biological and medicinal properties. The present review on B. diffusa focuses over the chemical compositions and its ethno-medicinal uses, linked from ancient times to the present with a scope of development in future. Furthermore, a recent update on mechanistic approaches of B. diffusa has also been discussed, which could be helpful for the researchers working in this field. Eventually, based on its antioxidant and antidiabetic characteristics, it is hypothesized that B. diffusa might exhibit antiglycating properties as well.

Phytochemistry, traditional uses and cancer chemopreventive activity of Amla (Phyllanthus emblica): The Sustainer.

Ayurveda, which is the oldest health system in the world, appreciates and uses amla to treat a host of diseases and promote positive health. Amla [Emblica officinalis, or emblic myrobalan], is called amalaki in Sanskrit. It is extensively used as a rejuvenator in ayurveda. It is also used widely in combination with other two [chebulic and belleric] myrobalans [fruit-bearing plant species] as triphala. Amla is indeed, the key ingredient in the popular ayurvedic recipe, Chyavanaprasha. More than anything, it may be called as "King of Rasayana" [rejuvenation], owing to its multiple health benefits. Phyllanthus emblica or Indian gooseberry (Amla) possesses a vastethnomedical history and represents a phytochemical reservoir of heuristic medicinal value. It is one of the oldest oriental medicines mentioned in Ayurveda as potential remedy for various ailments. The fruit is rich in quercetin, phyllaemblic compounds, gallic acid, tannins, flavonoids, pectin and vitamin C and also contains various polyphenolic compounds. A wide range of phytochemical components including terpenoids, alkaloids, flavonoids, and tannins have been shown to posses’ useful biological activities. Many pharmacological studies have demonstrated the ability of the fruit shows antioxidant, anticarcinogenic, antitumour, antigenotoxic, antiinflammatory activities, supporting its traditional uses. In this review, we have focused our interest on phytochemistry, traditional uses, cancer chemopreventive activity of Phyllanthus emblica both in vivo and in vitro. In view of its reported pharmacological properties and relative safety, P. emblica could be a source of therapeutically useful products.

Selenium: More than just a micronutrient mineral

Selenium is a micronutrient mineral found mainly in soils. Studies on selenium have increased rapidly worldwide especially after it has been shown to reduce the risk of certain types of cancer in humans and animals. The exact mechanism of action on how selenium inhibits diseases, in particular cancer, is still unknown. To date, the use of selenium in preventing or treating diseases is limited. However, many aspects about the biochemistry of selenium have been identified. This article reviews a number of key clinical, experimental and epidemiological studies on selenium as an anti-carcinogenic agent for some types of cancers. Some nutritional information on selenium and its recommended intake are also included. More clinical and experimental studies are needed to confirm previous findings on the role of selenium as an anticarcinogenic agent.

Biomedical Issues of Dietary fiber beta-Glucan

beta-Glucan is a polysaccharide in the form of fiber and the main element of fiber in grains such as barley, oats, yeast and mushrooms. Many studies have examined the efficacy of beta-Glucan in terms of the lipid lowering effects, blood sugar reduction, weight reduction, immune modulator, and anticarcinogenic effect. However, there is no comprehensive review article on the biomedical issues regarding beta-Glucan. The authors searched for systematic reviews and clinical experiments for each relevant topic and reviewed the biomedical effects of beta-Glucan, for the purpose of developing research strategies for the future.

A PRELIMINARY APPROACH TO BIOLOGICAL FUNCTION OF SOYBEAN SELENOPROTEIN / 营养学报

Objective: To investigate the biological function of soybean selenoprotein by the study of anti-oxidation,immunological and anticarcinogenic efficacy. Method: The soybean selenoprotein at different doses of Se were fed intra-gastrically in Kunming mice. A low Se feedstuff was used as basic diet. Result: (1) when dose is below 202.5 ?g/kg bw Se, the number of white cell and red cell was increased remarkably, and the activity of GSH-Px and SOD in liver and serum was increased at dose dependent manner, but LPO in serum and liver was decreased noticeably. At level of 607.5?g/kg, all the indices were reversed; (2) A dose-dependent cancer protective effect was expressed in range of 22.5-202.5?g/kg Se of soybean selemoprotein in the diet. Feeding soybean selenoprotein can postpone the death of mice with carcinoma . Total tumour yield was consistently reduced by 78% with 202.5?g/kg supplementation; (3) Any abnormal response was never noticed during all trial by supplementing 202.5?g/kg selenoprotein. Conclusion: The increased effect of anti-oxidation and immunological modulation might be the mechanism of tumour suppression by soybean selenoprotein, and Kunming mice tolerated the soybean selenoprotein very well without any side effects.

Epidemiological Study on Cancer Prevention by Ginseng: Are All Kinds of Cancers Preventable by Ginseng?

In the light of experimental results, two case-control studies and one cohort study in a population of ginseng cultivation area were conducted to confirm whether ginseng has any anticarcinogenic effect on human cancers. All participants were interviewed using a standardised questionnaire to obtain the information on demographics, cigarette smoking, alcohol consumption and ginseng intake. In 905 pairs case-control study, 62% had a history of ginseng intake compared to 75% of the controls, a statistically significant difference (p<0.01). The odds ratio (OR) for cancer in relation to ginseng intake was 0.56. In extended case-control study with 1987 pairs, the ORs for cancer were 0.37 in fresh ginseng extract users, 0.57 in white ginseng extract users, 0.30 in white ginseng extract users, 0.30 in white ginseng powder users, and 0.20 in red ginseng users. Those who took fresh ginseng slices, fresh ginseng juice, and white ginseng tea, however, did not show decrease in the risk. Overall, the risk decreased as the frequency and duration of ginseng intake increased. With respect to the site of cancer, the ORs for cancers of the lip, oral cavity, pharynx, esophagus, stomach, colorectum, liver, pancreas, larynx, lung and ovary were significantly reduced by ginseng intake. Smokers with ginseng intake showed lower ORs for cancers of lung, lip, oral cavity and pharynx and liver than those without ginseng intake. In 5 yr follow- up cohort study conducted in the ginseng cultivation area, Kangwha-eup, ginseng intakers had significantly lower risk than non-intakers. As for the type of ginseng, cancer risk significantly decreased among intakers of fresh ginseng extract, alone or together with other ginseng preparations. Among 24 red ginseng intakers, no cancer death occurred during the follow-up period. The risk for stomach and lung cancers was significantly reduced by ginseng intake, showing a statistically significant dose-response relationship in each follow-up year. In conclusion, Panax ginseng C.A. Meyer has been established as non-organ specific cancer preventive, having dose response relationship. These results warrant that ginseng extracts and its synthetic derivatives should be examined for their preventive effect on various types of human cancers.

Molecular Mechanisms Underlying Anti-Tumor Promoting Activities of Heat-Processed Panax ginseng C.A. Meyer

Recently, there have been considerable efforts to search for naturally occurring substances that can inhibit, reverse, or retard the multi-stage carcinogenesis. A wide array of phenolic substances derived from edible and medicinal plants have been reported to possess anticarcinogenic and antimutagenic activities and in many cases, the chemopreventive activities of phytochemicals are associated with their anti-inflammatory and/or antioxidative properties. Panax ginseng C.A. Meyer cultivated in Korea has been widely used in traditional herbal medicine for the treatment of various diseases. Certain fractions or purified ingredients of ginseng have been shown to exert anticarcinogenic and antimutagenic activities. Our previous studies have revealed that the methanol extract of heat-processed Panax ginseng C.A. Meyer attenuates the lipid peroxidation in rat brain homogenates and is also capable of scavenging superoxide generated by xanthine- xanthine oxidase or by 12-O-tetradecanoylphorbol-13-acetate (TPA) in differentiated human promyelocytic leukemia (HL-60) cells. Topical application of the same extract onto shaven backs of female ICR mice also suppressed TPA-induced skin tumor promotion. Likewise, topical application of ginsenoside Rg3, one of the constituents of heat-treated ginseng, significantly inhibited TPA-induced mouse epidermal ornithine decarboxylase activity and skin tumor promotion. Expression of cyclooxygenase-2 (COX-2) in TPA-stimulated mouse skin was markedly suppressed by Rg3 pretreatment. In addition, Rg3 inhibited TPA-stimulated activation of NF-kB and extracellular-regulated protein kinase (ERK), one of the mitogen-activated protein (MAP) kinase in mouse skin and also in cultured human breast epithelial cells (MCF-10A).

Chemoprevention of Mammary, Cervix and Nervous system Carcinogenesis in Animals using Cultured Panax ginseng Drugs and Preliminary Clinical Trials in Patients with Precancerous Lesions of the Esophagus and Endometrium

The anticarcinogenic effects and mechanisms of the biotechnological drugs of Panax ginseng C.A. Meyer cultivated in Russia, bioginseng, panaxel and panaxel- 5, were studied. Bioginseng was produced from a tissue culture of ginseng root cultured on standard medium, whereas panaxel and panaxel-5 were produced from ginseng tissue root cultures using standard mediums enriched with 2-carboxyethylgermanium sesquioxide and 1-hydroxygermatran-monohydrate respectively. All three ginseng drugs inhibited the development of mammary tumors induced by intramammary injections of N-methyl-N-nitrosourea (MNU) in rats, the development of the brain and spinal cord tumors induced by transplacental administration of N-ethyl-N-nitrosourea (ENU) in rats, and the development of uterine, cervical and vaginal tumors induced by intravaginal applications of 7,12-dimethylbenz(a)anthracene (DMBA) in mice. The ginseng drugs induced the cytotoxic activity of macrophages in mice, enhanced T-lymphocyte rosette formation in guinea pigs exposed to cyclophosphamide, and stimulated the production of thyroid hormones in rats. These mechanisms may contribute to the anticarcinogenic action of the ginseng drugs. The organic germanium compounds present in panaxel and panaxel-5 did not potentiate the anticarcinogenic or immuno- stimulatory effects as much as biogeinseng. Preliminary clinical trials with panaxel and bioginseng were carried out in patients with precancerous lesions of the esophagus and endometrium. Panaxel was found to have a strong therapeutic effect in patients suffering from chronic erosive esophagitis. Bioginseng induced the regression of adenomatous-cystic hyperplasia of the endometrium in some patients. Thus, we conclude that the drugs of ginseng appear to hold considerable promise for future cancer chemoprevention.

Anticarcinogenic Effect of Red Ginseng on the Development of Liver Cancer Induced by Diethylnitrosamine in Rats

Anticarcinogenic effect of red ginseng (Panax ginseng C.A. Meyer cultivated in JiLin, China) on the development of liver cancer induced by diethylnitrosamine (DEN) in rats was studied, especially in preventive and curative groups. In the preventive group, the rats were given with DEN concomitantly with red ginseng fluid, and in the curative group, the rats were administered with red ginseng fluid after they developed liver cancer nodules induced by DEN. The result of the preventive group revealed that the developmental rate of liver cancer in the experimental group was 14.3%, while 100% in the control group, with the difference being statistically significant. DNA, RNA, glycogen, gamma-GT, SDH, and 5'-NT were maintained at relatively normal level in experimental group, and decreased or increased in the control group. The result of curative group showed that hepatoma nodules of the DEN-red ginseng group I were smaller than those of control group I, the structure of hepatic tissue was well preserved, the area with gamma-GT positive was smaller, and the ultrastructure of hepatocytes was normal. The average life span the DEN-red ginseng group II and the DEN control group II were 72.8 and 42.3 days, respectively. To sum up, all findings on preventive and curative groups had clearly proved that the red ginseng had the anticarcinogenic effect on the development of liver cancer induced by DEN in rats.

Effects of (-)-Epigallocatechin Gallate (EGCG) on DNA Strand Breaks as Evaluated by Single-cell Gel Electrophoresis (SCG) in Human Lymphocytes

(-)-Epigallocatechin gallate (EGCG), a catechin polyphenol component, is the main ingredient of green tea extract. Although the anti-carcinogenic and cancer inhibitory effects of EGCG have been widely reported, its genotoxicity is not clear and seldom reported. In this study, we examined the effects of EGCG on DNA strand breaks in the isolated lymphocytes and whole blood lymphocytes obtained from two smoking subjects and a nonsmoking healthy subject using a single-cell gel electrophoresis (SCG) assay. The results showed that after 2 hrs of treating the isolated lymphocytes from the smokers, EGCG induced a significant increase in DNA strand breaks at concentrations from 2.5 × 10-5 M to 2.0 × 10-4 M, while after 2 hrs of treating the whole blood obtained from the same smokers, EGCG suppressed the DNA strand breaks in the lymphocytes at concentrations of 1.0 × 10-4 M and 2.0 × 10-4 M. A similar suppressive result was also shown in the whole blood lymphocytes from the nonsmoker at nearly the same concentrations, while at concentrations of 1.0 × 10-3 M or 2.0 × 10-3 M, EGCG induced a significant increase in DNA strand breaks in the whole blood lymphocytes from the nonsmoker. This result suggests that EGCG is not only inhibitory against DNA strand breaks in whole blood, but also genotoxic to the isolated or whole blood lymphocytes at high concentrations. Thus, more research is needed to comprehensively assess the effects of EGCG on genetic materials.