Phytochemical therapy - Polysulfides

Polysulfides are phytochemicals in a class of chemical compounds containing chains of sulfur atoms, belonging to the group of Organosulfides found abundantly in ioxidized product, including beer, wine, whiskey, garlic oil, etc.
1. Phytochemical Polysulfides and colon cancer
Bowel cancer also known as colorectal cancer, is defined as a condition of the abnormal proliferation of cells in the colon, rectum, or vermiform appendix. Bowl is divided in 2 parts, the first part of the bowel, the small bowl, is involved with the digestion and absorption of food. The 2nd part, the large bowel which consist the the colon and rectum, is involved in absorption of water from the small bowel contents and broken down of certain materials in the feces into substances of which some of them to be re absorbed and reused by the body. Bowel cancer is relatively very common and slowly growing and progress cancer and in predictable way.
Bowel cancer is the third most commonly diagnosed cancer in developed countries, including U>S and Canada.
According to the study of the University of the Saarland, coumarin polysulfides showed to inhibit cell growth and induce apoptosis in HCT116 colon cancer cells, through regulated the phosphatase activity of the cell cycle regulating cdc25(Cell division cycle 25, family of dual-specificity phosphatases) family members(1). Diallylsulfides, another family member of Garlic-derived organo sulphur compounds, also inhibited HCT116 human colon cancer cells, through reduced cell viability, cell cycle arrest and apoptosis(2) and colo 205 human colon cancer cells through affected resistant gene expression(3)

Reference
(1) Coumarin polysulfides inhibit cell growth and induce apoptosis in HCT116 colon cancer cells by Saidu NE¹, Valente S, Bana E, Kirsch G, Bagrel D, Montenarh M.(PubMed)
(2) Diallylpolysulfides induce growth arrest and apoptosis by Busch C¹, Jacob C, Anwar A, Burkholz T, Aicha Ba L, Cerella C, Diederich M, Brandt W, Wessjohann L, Montenarh M.(PubMed)
(3). Diallyl sulfide, diallyl disulfide and diallyl trisulfide affect drug resistant gene expression in colo 205 human colon cancer cells in vitro and in vivo by Lai KC¹, Kuo CL, Ho HC, Yang JS, Ma CY, Lu HF, Huang HY, Chueh FS, Yu CC, Chung JG.(PubMed)

2. . Phytochemical Polysulfides and breast cancer
Breast cancer (malignant breast neoplasm) is a cancer started in the tissues of the breast either from the inner lining of milk ducts (Ductal carcinoma) or the lobules (Lobular carcinoma) that supply the ducts with milk. there is also rare cases that breast cancer starts in other areas of the breast. In 2010, over 250,000 new cases of breast cancer were expected to be diagnosed in women in the U.S. alone and the risk of getting invasive breast cancer during life time of a women is 1/8.
Eating garlic daily and regularly is associated to reduced risk of cancer due to its properties in stimulated cells arrest at G2/M phase, the cells with a sub-G1 DNA content, and the cells with caspase-3 activity(1). In sensitive (MCF-7) and resistant (Vcr-R) human breast carcinoma cells , Diallyl- and dipropyltetrasulfides showed to inhibit growth of both cancer cell lines, through cell cycle arrest associated to antiproliferative effect(2). The Alexandria University study also supported the role of diallyl trisulfide in inhibition of MCF-7 breast cancer but throught enhanced the expression levels of FAS and cyclin D1, but in contrast, downregulated the expression levels of Akt and Bcl-2(3).

References
(1) Anticancer effects of diallyl trisulfide derived from garlic by Seki T¹, Hosono T, Hosono-Fukao T, Inada K, Tanaka R, Ogihara J, Ariga T.(PubMed)
(1) Antiproliferative effect of natural tetrasulfides in human breast cancer cells is mediated through the inhibition of the cell division cycle 25 phosphatases by Viry E¹, Anwar A, Kirsch G, Jacob C, Diederich M, Bagrel D.(PubMed)
(2) Garlic constituent diallyl trisulfide induced apoptosis in MCF7 human breast cancer cells by Malki A¹, El-Saadani M, Sultan AS.(PubMed)

3. Polysulfides and skin cancer
Skin cancer is a medical condition of uncontrolled growth of abnormal skin cells and often detected at an early stage.
In skin cancer progression, diallyl trisulfide (DATS) is more potent than mono- and disulfides against skin cancer, through inhibited cell growth of human melanoma A375 cells and basal cell carcinoma (BCC) cells by increasing the levels of intracellular reactive oxygen species (ROS) and DNA damage and by inducing G2/M arrest, endoplasmic reticulum (ER) stress, and mitochondria-mediated apoptosis(1). The study by the National Taiwan University, also showed that Diallyl sulfide (DAS), diallyl disulfide (DADS), and diallyl trisulfide (DATS), extracted from crushed garlic, inhibited skin cancer cell growth through involved in G(2)/M arrest and apoptosis via activation of p53 pathway in response to the oxidative DNA damage(2). The Chung Shan Medical University Hospital, study also insisted that DAS protect against ultraviolet B (UVB)-induced skin tumor formation through anti photocarcinogenesis effect accompanied by the down-regulation of cell-proliferative controls, involving thymine dimer, PCNA, apoptosis, transcription factors NF-κB, and of inflammatory responses involving COX-2, PGE2, and NO, and up-regulation of p53, p21/Cip1 to prevent DNA damage and facilitate DNA repair in hairless mice(3).

References

(1) Molecular mechanisms of garlic-derived allyl sulfides in the inhibition of skin cancer progression by Wang HC¹, Pao J, Lin SY, Sheen LY.(PubMed)
(2) Allyl sulfides inhibit cell growth of skin cancer cells through induction of DNA damage mediated G2/M arrest and apoptosis By Wang HC¹, Yang JH, Hsieh SC, Sheen LY.(PubMed)
(3) Diallyl sulfide protects against ultraviolet B-induced skin cancers in SKH-1 hairless mouse: analysis of early molecular events in carcinogenesis by Cherng JM¹, Tsai KD, Perng DS, Wang JS, Wei CC, Lin JC.(PubMed)

4. Phytochemical Polysulfides and cardiovascular diseases
There are many causes of heart diseases. Most of heart diseases are caused by high blood pressure contributes to hardening of the arteries. High levels of bad cholesterol (LDL) build up in the arteries as a result of uncontrolled diet with high levels of saturated fat and trans fat. Beside cancer, heart disease kills more than 2,000 Americans everyday. Approximately 60 million Americans have heart disease.
Epidemiologic studies link intake of garlic in association to reduce risk as well as progression of cardiovascular disease(1).
According to the Institute of Preventive and Clinical Medicine, polysulfides from garlic are converted into hydrogen sulfide which has the unique property for relaxing vascular smooth muscle, inducing vasodilation of blood vessels, and significant reducing blood pressure(2), probably through its anti-apoptotic, anti-inflammatory and antioxidant effects(3). The ¹Semmelweis University Institute of Human Physiology and Clinical Experimental Research, suggested that H2S as a novel gasotransmitter in the central nervous and cardiovascular systems, similarly to nitric oxide (NO) and carbon monoxide (CO), may be of value in cytoprotection during the evolution of myocardial infarction(4).


References
(1) Garlic and cardiovascular disease: a critical review by Rahman K¹, Lowe GM.(PubMed)
(2) Garlic (Allium sativum L.) and cardiovascular diseases by Ginter E¹, Simko V.(PubMed)
(3) Hydrogen sulfide-mediated cardioprotection: mechanisms and therapeutic potential by Lavu M¹, Bhushan S, Lefer DJ.(PubMed)(4) The cardioprotective potential of hydrogen sulfide in myocardial ischemia/reperfusion injury (review) by Dongó E¹, Hornyák I, Benko Z, Kiss L.(PubMed)


5. Polysulfides and antifungal activity
A range of sulfur-containing natural products showed to inhibit their antioxidant, antibacterial, antimicrobial, antifungal and anticancer properties, through specific chemical properties which converge in chemotypes, including polysulfides(1).
Garlic extracts and individual components, i.e., allicin, ajoen, polysulfides, essential oil, showed  a significant antifungal activity, according to ¹Katedra farmaceutické botaniky a ekologie Farmaceutické fakulty Univerzity Karlovy(2). Polysulfides, through its biological activity, showed effectively against candidosis in mice, according to the ¹Pharmaceutical Research Laboratories III, Takeda Chemical Industries, Japan(3).

References
(1) A scent of therapy: pharmacological implications of natural products containing redox-active sulfur atoms by Jacob C.(PubMed)
(1) [Pharmaceutical significance of Allium sativum L. 4. Antifungal effects].[Article in Czech]by Sovová M¹, Sova P.(PubMed)
(2) Optically active antifungal azoles. II. Synthesis and antifungal activity of polysulfide derivatives of (2R,3R)-2-(2,4-difluorophenyl)-3-mercapto-1-(1H- 1,2,4-triazol-1-yl)-2-butanol by Tasaka A¹, Tamura N, Matsushita Y, Hayashi R, Okonogi K, Itoh K.(PubMed)

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Weight loss in Vitamin D Points of view

 Kyle J. Norton (Draft article)

The prevalence of extreme overweight and obesity has caused concerns of scientific community in the South East Asian population, due unhealthy diet and life style change over 2 decades of economic prosperity. Overweight and obesity have reached epidemic proportions in many Asian countries, affecting even younger age than in Western populations with economic burden in the development of  obesity-related disorders such as diabetes, hypertension, and cardiovascular diseases(1).  One of six Malaysian are either extreme overweight or obese, according to Datin Paduka Santha Kumari, chairman of the Selangor branch of the Malaysian Diabetes Association and  according to global health observatory, at least 2.8 million people die each year as a result of being overweight or obese, and an estimated 35.8 million (2.3%) of global DALYs are caused by overweight or obesity, worldwide(2).
Epidemiological studies, linking herbal medicine, foods and vitamins in preventing and treating these diseases have been inconclusive(a)
Some researchers suggested that intake of certain herbal medicine may enhance appetite suppression. According to the Georgetown University Medical Center, average daily food intake was decreased only with the herbal formulation, not the phenylpropanolamine (PPA) at the low and high doses, in comparison of the effectiveness among herbal formulation and a commonly available(3). Other researchers insisted that using herbs and supplements to induce weight loss should be taken with care, as a  considerable number of reports have been published on hepatotoxicity associated with herbal products attributed with weight-reducing properties(4)(5)(6)(7). The College of Medicine, The Ohio State University insisted that various dietary, lifestyle, and psychologic factors are involved in the etiology of Prameha, particularly in relation to disturbances in fat and carbohydrate metabolism(8), without effective management, obtaining a workable weight loss plan may be extremely difficult.
Vitamin D is a fat-soluble secosteroids found in small amount in few foods, including salmon, mackerel, sardines and tuna. The vitamin plays an important role in modulation of cellular proliferation, apoptosis induction, tumor growth suppression and promotion in absorption of minerals, including calcium, iron, magnesium, phosphate and zinc.
The serum level of vitamin D
Low levels of micronutrients, including vitamin D are most common among overweight and obese children. According to the study, low serum 25-hydroxyvitamin D3 (25(OH)D) levels not only is associated to insulin resistance and cardiovascular diseases risks(9) but also  incidence of obesity(10).
The study of Suspected Nonalcoholic Fatty Liver Disease in Chinese American Children also supported the link of obesity and metabolic syndrome among Chinese American  childrenand suggested that testing for metabolic disorders and low vitamin D levels would be necessary to identify the early indication of NAFLD in childhood will allow for intervention with lifestyle modification, providing a means to reduce the prevalence of NAFLD in children and adults(11).
DR, Peterson CA,  and Dr. Belenchia AM. told PubMed "There is a well-established inverse relationship between vitamin D status and obesity; however, it is unknown as to whether vitamin D deficiency contributes to, or is a consequence of obesity"(12). Some researchers suggested that correction of poor vitamin D status through dietary supplementation may be an effective addition to the standard treatment of obesity and its associated insulin resistance(13) as vitamin D deficiency is accounted for the secular trends in the prevalence of obesity and for individual differences in its onset and severity(14).

Vitamin D and adiponectin
A suggestion of association of low levels of Vitamin D and adiponectin is associated to obesity instead of vitamin D itself(15).
Adiponectin is a  protein involved in regulating glucose levels as well as fatty acid breakdown.
According to the study by the Università del Piemonte Orientale, in the confirmation Adiponectin tight association with obesity and diabetes mellitus, suggested that multimeric adiponectin may be a key plasma protein that links vitamin D deficiency to pediatric obesity(16).
In support the link between Vitamin D and adiponectin and obesity, the Ramathibodi Hospital, Mahidol University study showed that circulating adiponectin appears to be inversely related to beta cell dysfunction in addition to insulin resistance only in obese women(17). Other in the study insisted that since low serum levels of 1α,25-dihydroxycholecalciferol (DHCC) attenuates (monocyte chemotactic protein-1)MCP-1 and adiponectin production in human adipocytes, thereby reducing the expression of both pro- and anti-inflammatory factors may explain the difficulties so far in determining the role of DHCC in insulin sensitivity and obesity in human(18).

Taken altogether, low serum levels of vitamin D and vitamin D deficiency are associated to increase risk of obesity and obese complications through involvement of vary mechanisms. Over doses of vitamin D supplement may cause excessive calcium absorption, calcification, Urinary stones etc. please make sure to follow the guideline of  the Institute of Medicine of the National Academies.

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References
(1) Rising Burden of Obesity in Asia by Ambady Ramachandran and Chamukuttan Snehalatha(Journey of Obesity)
(2) Obesity - Situation and trends(WHO)
(3) Influence of a combination of herbs on appetite suppression and weight loss in rats by Talpur NA¹, Echard BW, Manohar V, Preuss HG.(PubMed)
(4) [Hepatotoxicity induced by herbs and medicines used to induce weight loss].[Article in Spanish]by Herrera S¹, Bruguera M.(PubMed)
(5) A case report of adult lead toxicity following use of Ayurvedic herbal medication by Breeher L¹, Gerr F, Fuortes L.(PubMed)
(6) [Chronic lead intoxication associated with Ayurvedic medication].[Article in Dutch] by Kanen BL¹, Perenboom RM.(PubMed)
(7) Potential toxicity of caffeine when used as a dietary supplement for weight loss by Pendleton M¹, Brown S, Thomas C, Odle B.(PubMed)
(8) Multinutrient supplement containing ephedra and caffeine causes weight loss and improves metabolic risk factors in obese women: a randomized controlled trial by Hackman RM¹, Havel PJ, Schwartz HJ, Rutledge JC, Watnik MR, Noceti EM, Stohs SJ, Stern JS, Keen CL.(PubMed)
(9) The association of vitamin D status with cardiometabolic risk factors, obesity and puberty in children by Aypak C¹, Türedi O, Yüce A.(PubMed)
(10) Serum 25-hydroxyvitamin D (25-OH-D) in obese adolescents by Garanty-Bogacka B¹, Syrenicz M, Goral J, Krupa B, Syrenicz J, Walczak M, Syrenicz A.(PubMed)
(11) Prevalence and Correlates of Suspected Nonalcoholic Fatty Liver Disease in Chinese American Children by Malespin M¹, Sleesman B, Lau A, Wong SS, Cotler SJ.(PubMed)
(12) Vitamin D deficiency & childhood obesity: a tale of two epidemics by Peterson CA, Belenchia AM.(PubMed)
(13) Correcting vitamin D insufficiency improves insulin sensitivity in obese adolescents: a randomized controlled trial by Belenchia AM¹, Tosh AK, Hillman LS, Peterson CA.(PubMed)
(14) Vitamin D deficiency is the cause of common obesity by Foss YJ.(PubMed)
(15) Cardiometabolic risk factors related to vitamin d and adiponectin in obese children and adolescents by Kardas F¹, Kendirci M, Kurtoglu S.(PubMed)
(16) Pediatric obesity and vitamin D deficiency: a proteomic approach identifies multimeric adiponectin as a key link between these conditions by Walker GE¹, Ricotti R², Roccio M¹, Moia S¹, Bellone S², Prodam F², Bona G².(PubMed)
(17) Differences in insulin sensitivity, pancreatic beta cell function and circulating adiponectin across glucose tolerance status in Thai obese and non-obese women by Chailurkit LO¹, Chanprasertyothin S, Jongjaroenprasert W, Ongphiphadhanakul B.(PubMed)
(18) Differential effects of 1α,25-dihydroxycholecalciferol on MCP-1 and adiponectin production in human white adipocytes by Lorente-Cebrián S¹, Eriksson A, Dunlop T, Mejhert N, Dahlman I, Aström G, Sjölin E, Wåhlén K, Carlberg C, Laurencikiene J, Hedén P, Arner P, Rydén M.(PubMed)

The Science of Soy - The East Viewpoints: Part A4 Soy and Obeisty in Japanese

 By Kyle J. Norton (Draft Article)

Soy foods, including tofu have been in traditional Chinese diet over thousands of year, according to Chinese literature. The reduced risk of chronic disease, including metabolic syndrome such as cardiovascular diseases, obesity and diabetes and lesser menopause symptoms in advanced age, may be aided by eating a lot of soy food accompanied with large portion of vegetables and fruits. Indeed, according to the study, only 10% of women in the East are experience symptoms of menopause in advanced age compared to over 70% of their Western counterparts.
According to Dr. Mark Messina, Ph.D., Soy foods contributed from 6.5%8  to 12.8%7  of total protein intake in older adult in Japan.(b)

The approval of cardiovascular benefit of soy by FDA in 1999 accompanied with the discovery of health benefits in clinical studies over past decade, prompted the promotion and advertisement of soy's health benefits in every aspect in Western society. Evidences could be seen by walking through the supermarkets and drug  stores.  Soy supplements and products such as tofu, soy milk, soy-based infant formula, and meatless “texturized vegetable protein” burgers were widely available. According to the United Soybean Board’s 2004–2005, 25% of Americans consume soy foods or beverages at least once per week, and 74% view soy products as healthy.

Today, the promotion of soy are no longer existed, it may be results of discovery of adverse effect in single ingredient and animal studies, as intake of soy is associated to induce risk certain mammary cancers and infertility. The publication of the result have drawn many criticisms. According to Thomas Badger, director and senior investigator at the Arkansas Children’s Nutrition Center in Little Rock, these effects are seen only under certain experimental conditions that are not likely to occur in humans—and therein lies the crux of the debate(a). Equol (4',7-isoflavandiol), an isoflavandiol metabolized from daidzein may be the causes, as 90% of Eastern population are equol producers but only 30% in the West.
The explanation of the positive effect of soy isoflavones in reduced risk of mammary cancers by  University of Goettingen may be interesting, as researchers said" Most importantly, there is dispute as to whether isoflavones derived from soy or red clover have negative, positive or any effect at all on the mammary gland or endometrium. It is beyond any doubt that soy products may have cancer preventing properties in a variety of organs including the mammary gland. However, these properties may only be exerted if the developing organ was under the influence of isoflavones during childhood and puberty.

Soybean is the genus Glycine, belonging to the family Fabaceae, one of the legumes that contains twice as much protein per acre as any other major vegetable or grain crop, native to Southeast Asia. Now, it is grown worldwide with suitable climate for commercial profits.
Nutrients
1. Carbohydrates
2. Dietary fiber
3. Fat
4. Protein
5. Essential amino acid
6. Vitamin A
7. Vitamin B6
8. Vitamin B12
9. Vitamin C
10. Vitamin K
11. Calcium
12. Iron
13. Magnesium
14. Phosphorus
15. Potassium
16. Sodium
17. Zinc
18. Etc.
Phytochemicals
1. Isoflavones
2. Genistein
3. Saponins
4. Beta-sitosterol
5. Daidzein

I. Soy in Eastern population
A. The Japanese population
Japan, an island nation in the Pacific Ocean, lies to the east of the Sea of Japan, China, North Korea, South Korea and Russia, stretching from the Sea of Okhotsk in the north to the East China Sea and Taiwan in the south(1). According to Moriyama, Japanese women and men live longer and healthier than everyone else on Earth, it may be result of  healthier Japanese diet and lifestyle. According to the World Health Organization, the Japanese have an average of 75 years healthy living with disability-free, it may be due to average soy intake 10 to 70 times higher than in Western people(1a)(1b).

A4. Soy and Obesity in Japanese 
Soy foods intake is well known for it estrogenic effects because it binds the estrogen receptor with relatively high affinity, but effects induced risk of obesity are inconclusive in the West(1)(2)(3).
It may be results of most Westerner are non equol producers(4)(5). Some researchers suggested that the prevalence of obesity in the West may be result of typical American diet with high in saturated and trans-fat and less in fruits and vegetables. Other blamed the epidemic obesity is a result of economic environment which make healthy foods more expensive than junk and suggested of taxes on foods with low nutritional value could nudge behavior toward healthier diets, as could subsidies/discounts for healthier(8).  According to a report on NBC by Melissa Dhal, just 10.8 percent of Asians in America are considered obese, a slim percentage when compared with the 33 percent of whites, 42 percent of Hispanics and 48 percent of blacks with a BMI of 30 or higher(7).
In fact, the traditional Japanese diet with high amount of soy products are associated to a lower BMI in adulthood(9).

According to the Dr. Ma J and the research team,  the early exposure to a high-fat diet diminished the abundance of non-pathogenic Campylobacter in the juvenile gut of that may enhance the risk of obesity(10). In fact, DR. Sakata T. said that a very-low-calorie conventional Japanese diet of 370 kcal/day has been shown to be useful for weight reduction and its long-term maintenance(11). and dietary content and food patterns used in management among Japanese patients with type 2 diabetes are quite close to those reported as suitable for prevention of obesity, type 2 diabetes, cardiovascular disease, and total mortality in Europe and America, according to the study of 1,516 patients with type 2 diabetes aged 40-70 years from outpatient clinics in 59 university and general hospitals(12).

In fact, comparison of diet habit of the West and  Japanese working women, the proportion of eating problems is low in comparison with Western adult populations(15).

Study of Occupational Class Differences in Body Mass Index and Weight Gain in Japan and Finland may provide us with interesting result "BMI was higher at baseline and BMI gain was more rapid in Finland than in Japan, it may be results of clear socioeconomic gradients in obesity in Finland compared to Japanese environment is less obesogenic than the Finnish environment, or factors such as easy access to fast-food restaurants and limited possibilities for physical exercise are suggested characteristics of an obesogenic environment or due to the Japanese diet has traditionally been very healthy, with high consumption of vegetables, soy protein, and fish, with the general nutritional status of the Japanese population is still healthier than that in many Western countries" (13).

Unfortunately, Due to influence of the West, many Japanese have abandoned the traditional Japanese diet but opted for quick, high fat diet with a lots of junk foods. According to the Kagawa Nutrition University, Japanese traditional and Western, were all independently and significantly related to the risk of obesity even among a relatively lean young Japanese female population(14).
Other study suggested that adapting maternal Western-style diet consumption  may lead to increased susceptibility to type 2 diabetes in the offspring(16), and Western diet increased risk for atherosclerosis and promoted the progression of preclinical atherosclerosis, in correspondence with the extent of westernization(17). As undergoing rapid "Westernization," , change in Japanese dietary patterns continued, with high intake of butter & margarine, cheese, bread and ham & sausage, etc.(18), the Westernized chronic illness may rise to a level currently found in the "Western" countries in the coming few decades, including diverticular disease, mammary cancers(19)(20).

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For over 100 healthy recipes, http://diseases-researches.blogspot.ca/p/blog-page_17.html
 
References
(1) Genistein exposure during the early postnatal period favors the development of obesity in female, but not male rats by Strakovsky RS¹, Lezmi S, Flaws JA, Schantz SL, Pan YX, Helferich WG.(PubMed)
(2) Arginine, soy isoflavone and hydroxypropylmethylcellulose have protective effects against obesity in broiler breeder hens fed on high-energy diets by Khalaji S¹, Zaghari M, Ganjkhanloo M, Ghaziani F.(PubMed)
(3) Effects of voluntary running and soy supplementation on diet-induced metabolic disturbance and inflammation in mice by Yan L¹, Graef GL, Claycombe KJ, Johnson LK.(PubMed)
(4) Effects of natural S-equol supplements on overweight or obesity and metabolic syndrome in the Japanese, based on sex and equol status by Usui T¹, Tochiya M, Sasaki Y, Muranaka K, Yamakage H, Himeno A, Shimatsu A, Inaguma A, Ueno T, Uchiyama S, Satoh-Asahara N.(PubMed)
(5) Obesity prevalence in relation to gut microbial environments capable of producing equol or O-desmethylangolensin from the isoflavone daidzein by Frankenfeld CL¹, Atkinson C², Wähälä K³, Lampe JW⁴.(PubMed)
(6) Family-focused physical activity, diet and obesity interventions in African-American girls: a systematic review by Barr-Anderson DJ¹, Adams-Wynn AW, DiSantis KI, Kumanyika S.(PubMed)
(7). What's actually behind the low Asian-American obesity rate? by Melissa Dahl
(8) Obesity and economic environments by Sturm R¹, An R.(PubMed)
(9) Soy intake is related to a lower body mass index in adult women by Maskarinec G¹, Aylward AG, Erber E, Takata Y, Kolonel LN.(PubMed)
(10) High-fat maternal diet during pregnancy persistently alters the offspring microbiome in a primate model by Ma J¹, Prince AL², Bader D³, Hu M⁴, Ganu R⁴, Baquero K⁵, Blundell P⁵, Alan Harris R⁶, Frias AE⁵, Grove KL⁵, Aagaard KM(PubMed)
(11) A very-low-calorie conventional Japanese diet: its implications for prevention of obesity by Sakata T.(PubMed)
(12) Dietary intake in Japanese patients with type 2 diabetes: Analysis from Japan Diabetes Complications Study by Horikawa C¹, Yoshimura Y², Kamada C², Tanaka S³, Tanaka S⁴, Takahashi A⁵, Hanyu O⁶, Araki A⁷, Ito H⁷, Tanaka A⁸, Ohashi Y⁵, Akanuma Y⁹, Yamada N¹⁰, Sone H⁶.(PubMed)
(13) ccupational Class Differences in Body Mass Index and Weight Gain in Japan and Finland

Karri Silventoinen,¹ Takashi Tatsuse,² Pekka Martikainen,¹ Ossi Rahkonen,³ Eero Lahelma,³ Michikazu Sekine,² and Tea Lallukka^3,4by PubMed)

(14) Three major dietary patterns are all independently related to the risk of obesity among 3760 Japanese women aged 18-20 years by Okubo H¹, Sasaki S, Murakami K, Kim MK, Takahashi Y, Hosoi Y, Itabashi M; Freshmen in Dietetic Courses Study II group.(PubMed)

(15) Eating problems and related weight control behaviour in adult Japanese women by Nakamura K¹, Hoshino Y, Watanabe A, Honda K, Niwa S, Yamamoto M.(PubMed)

(16) Consumption of a Western-style diet during pregnancy impairs offspring islet vascularization in a Japanese Macaque model by Pound LD¹, Comstock SM², Grove KL².(PubMed)

(17) Influence of the extent of westernization of lifestyle on the progression of preclinical atherosclerosis in Japanese subjects by Egusa G¹, Watanabe H, Ohshita K, Fujikawa R, Yamane K, Okubo M, Kohno N.(PubMed)
(18) Dietary factors related to higher plasma fibrinogen levels of Japanese-americans in hawaii compared with Japanese in Japan by Miura K¹, Nakagawa H, Ueshima H, Okayama A, Saitoh S, Curb JD, Rodriguez BL, Sakata K, Okuda N, Yoshita K, Stamler J; INTERMAP Research Group; INTERLIPID Research Group.(PubMed)

(19) Changes in dietary fiber intake among Japanese in the 20th century: a relationship to the prevalence of diverticular disease by Ohi G, Minowa K, Oyama T, Nagahashi M, Yamazaki N, Yamamoto S, Nagasako K, Hayakawa K, Kimura K, Mori B.(PubMed).
(20) Relationship between westernization of dietary habits and mortality from breast and ovarian cancers in Japan. Kato I, Tominaga S, Kuroishi T.(PubMed)

Weight loss in Vitamin C Points of view

The prevalence of extreme overweight and obesity has caused concerns of scientific community in the South East Asian population, due unhealthy diet and life style change over 2 decades of economic prosperity. Overweight and obesity have reached epidemic proportions in many Asian countries, affecting even younger age than in Western populations with economic burden in the development of  Obesity-related disorders such as diabetes, hypertension, and cardiovascular diseases(1).  One of six Malaysian are either extreme overweight or obese, according to Datin Paduka Santha Kumari, chairman of the Selangor branch of the Malaysian Diabetes Association and  according to global health observatory, at least 2.8 million people die each year as a result of being overweight or obese, and an estimated 35.8 million (2.3%) of global DALYs are caused by overweight or obesity, worldwide(2).
Epidemiological studies, linking herbal medicine, foods and vitamins in preventing and treating these diseases have been inconclusive(a)
Some researchers insisted that using herbs and supplements to induce weight loss should be taken with care, as a  considerable number of reports have been published on hepatotoxicity associated with herbal products attributed with weight-reducing properties(4)(5)(6)(7). The College of Medicine, The Ohio State University insisted that various dietary, lifestyle, and psychologic factors are involved in the etiology of Prameha, particularly in relation to disturbances in fat and carbohydrate metabolism(8), without effective management, obtaining a workable weight loss plan may be extremely difficult.

Vitamin C, also known as L-ascorbic acid, is a water-soluble vitamin, found in fresh fruits, berries and green vegetables. It is best known for its free radical scavengers activity and regenerating oxidized vitamin E for immune support.

Vitamin C deficiency and incidence of obesity
Vitamin C  and other nutrient deficiency not only is associated to the risk of Obesity(15) but also enhances the risk of lipids, inflammation and insulin resistance(16).
According to the research team at Universidad Autónoma de Querétaro, there is an associated link between Obesity and  Zinc and vitamins A and C concentration in in women from rural Mexico, in a fasting blood sample analysis (11).
Although genetic susceptibility to obesity is associated with gene polymorphisms affecting biochemical pathways which also impacted by specific foods and nutrients. According to Dr. Johnston CS., vitamin C depletion is associated to positively related to body mass, individuals with adequate vitamin C status oxidize 30% more fat during a moderate exercise bout than individuals with low vitamin C status(10)

Vitamin C, the protective effect against obesity
Endothelial dysfunction has found to be associated to the incidence of obesity(12). The study of 76 healthy subjects (50 men and 26 women aged 21-45 years) obese subject, showed a positive effect of vitamin C and indomethacin in reduced oxidative stress contributed to endothelial dysfunction in human obesity(13).
In the evaluation of the potential inhibitory activity on α-glucosidase and pancreatic lipase by Citrus spp. fruits of Spanish origin, grapefruit, contained higher contents of phytochemicals such as vitamin C, is found to have a great value for nutrition and treatment of diet-related diseases(14).
L-Ascorbic acid in the study, whether  would facilitate the anti-obesity effects of chitosan and psyllium husk in vivo, showed addition of vitamin C in diet  influenced the reduction in body weight gain and food efficiency ratio, and the increase in total fecal weight and fecal fat excretion in guinea pigs fed a high-fat diet(16).

Taken altogether, deficiency of vitamin C and other nutrient is associated to increased risk obese incidence. Vitamin C may be effective in induced weight loss for obese subjects due tom its positive interaction in inhibiting oxidative stress causes of endothelial dysfunction. Daily ingestion of high-dose vitamin C may be considered safe, but in rare incidence, overdoses in a prolonged period of time, may cause intra-renal oxalate crystal deposition, a fatal nephrotoxicity(18)(19).

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References
(1) Rising Burden of Obesity in Asia by Ambady Ramachandran and Chamukuttan Snehalatha(Journey of Obesity)
(2) Obesity - Situation and trends(WHO)
(3) Influence of a combination of herbs on appetite suppression and weight loss in rats by Talpur NA¹, Echard BW, Manohar V, Preuss HG.(PubMed)
(4) [Hepatotoxicity induced by herbs and medicines used to induce weight loss].[Article in Spanish]by Herrera S¹, Bruguera M.(PubMed)
(5) A case report of adult lead toxicity following use of Ayurvedic herbal medication by Breeher L¹, Gerr F, Fuortes L.(PubMed)
(6) [Chronic lead intoxication associated with Ayurvedic medication].[Article in Dutch] by Kanen BL¹, Perenboom RM.(PubMed)
(7) Potential toxicity of caffeine when used as a dietary supplement for weight loss by Pendleton M¹, Brown S, Thomas C, Odle B.(PubMed)
(8) Multinutrient supplement containing ephedra and caffeine causes weight loss and improves metabolic risk factors in obese women: a randomized controlled trial by Hackman RM¹, Havel PJ, Schwartz HJ, Rutledge JC, Watnik MR, Noceti EM, Stohs SJ, Stern JS, Keen CL.(PubMed)
(9) Associations between body mass index and the prevalence of low micronutrient levels among US adults by Kimmons JE¹, Blanck HM, Tohill BC, Zhang J, Khan LK.(PubMed)
(10) Strategies for healthy weight loss: from vitamin C to the glycemic response by Johnston CS.(PubMed)
(11) Zinc, vitamin A, and vitamin C status are associated with leptin concentrations and obesity in Mexican women: results from a cross-sectional study by García OP¹, Ronquillo D, Caamaño Mdel C, Camacho M, Long KZ, Rosado JL.(PubMed)
(12) Mechanisms of endothelial dysfunction in obesity(Science direct)
(13) Obesity and body fat distribution induce endothelial dysfunction by oxidative stress: protective effect of vitamin C. by Perticone F¹, Ceravolo R, Candigliota M, Ventura G, Iacopino S, Sinopoli F, Mattioli PL.(PubMed)
(14) Phytochemistry and biological activity of Spanish Citrus fruits by Gironés-Vilaplana A¹, Moreno DA, García-Viguera C.(PubMed)
(15) High-fat feeding increases hepatic vitamin C synthesis and its circulatory mobilization in mice by Tranberg B¹, Hansen AK, Lykkesfeldt J.(PubMed)
(16) Zinc, iron and vitamins A, C and e are associated with obesity, inflammation, lipid profile and insulin resistance in mexican school-aged children by García OP¹, Ronquillo D, del Carmen Caamaño M, Martínez G, Camacho M, López V, Rosado JL.(PubMed)
(17) Anti-obesity effects of chitosan and psyllium husk with L-ascorbic acid in guinea pigs by Jun SC¹, Jung EY, Hong YH, Park Y, Kang Dh, Chang UJ, Suh HJ.(PubMed)
(18) Fatal vitamin C-associated acute renal failure by McHugh GJ, Graber ML, Freebairn RC.(PubMed)

(19) Ascorbic acid overdosing: a risk factor for calcium oxalate nephrolithiasis by Urivetzky M, Kessaris D, Smith AD.(PubMed)

The Science of Soy - The East Viewpoints: Soy and Prostate Cancer in Japanese Men

Soy foods, including tofu have been in traditional Chinese diet over thousands of year, according to Chinese literature. The reduced risk of chronic disease, including metabolic syndrome such as cardiovascular diseases, obesity and diabetes and lesser menopause symptoms in advanced age, may be aided by eating a lot of soy food accompanied with large portion of vegetables and fruits. Indeed, according to the study, only 10% of women in the East are experience symptoms of menopause in advanced age compared to over 70% of their Western counterparts.
According to Dr. Mark Messina, Ph.D., Soy foods contributed from 6.5%8  to 12.8%7  of total protein intake in older adult in Japan.(b)

The approval of cardiovascular benefit of soy by FDA in 1999 accompanied with the discovery of health benefits in clinical studies over past decade, prompted the promotion and advertisement of soy's health benefits in every aspect in Western society. Evidences can be seen by walking through the supermarkets and drug  stores.  Soy supplements and products such as tofu, soy milk, soy-based infant formula, and meatless “texturized vegetable protein” burgers are widely available. According to the United Soybean Board’s 2004–2005, 25% of Americans consume soy foods or beverages at least once per week, and 74% view soy products as healthy.

Today, the promotion of soy are no longer existed, it may be results of discovery of adverse effect in single ingredient and animal studies, as intake of soy is associated to induce risk certain mammary cancers and infertility. The publication of the result have drawn many criticisms. According to Thomas Badger, director and senior investigator at the Arkansas Children’s Nutrition Center in Little Rock, these effects are seen only under certain experimental conditions that are not likely to occur in humans—and therein lies the crux of the debate(a). Equol (4',7-isoflavandiol), an isoflavandiol metabolized from daidzein may be the causes, as 90% of Eastern population are equol producers but only 30% in the West.
The explanation of the positive effect of soy isoflavones in reduced risk of mammary cancers by  University of Goettingen may be interesting, as researchers said" Most importantly, there is dispute as to whether isoflavones derived from soy or red clover have negative, positive or any effect at all on the mammary gland or endometrium. It is beyond any doubt that soy products may have cancer preventing properties in a variety of organs including the mammary gland. However, these properties may only be exerted if the developing organ was under the influence of isoflavones during childhood and puberty.

Soybean is genus Glycine, the family Fabaceae, one of the legumes that contains twice as much protein per acre as any other major vegetable or grain crop, native to Southeast Asia. Now, it is grown worldwide with suitable climate for commercial profits.
Nutrients
1. Carbohydrates
2. Dietary fiber
3. Fat
4. Protein
5. Essential amino acid
6. Vitamin A
7. Vitamin B6
8. Vitamin B12
9. Vitamin C
10. Vitamin K
11. Calcium
12. Iron
13. Magnesium
14. Phosphorus
15. Potassium
16. Sodium
17. Zinc
18. Etc.
Phytochemicals
1. Isoflavones
2. Genistein
3. Saponins
4. Beta-sitosterol
5. Daidzein

I. Soy in Eastern population
A. The Japanese population
Japan, an island nation in the Pacific Ocean, lies to the east of the Sea of Japan, China, North Korea, South Korea and Russia, stretching from the Sea of Okhotsk in the north to the East China Sea and Taiwan in the south(1). According to Moriyama, Japanese women and men live longer and healthier than everyone else on Earth, it may be result of  healthier Japanese diet and lifestyle. According to the World Health Organization, the Japanese have an average of 75 years healthy living with disability-free, it may be due to average soy intake 10 to 70 times higher than in Western people(1a)(1b).

A3. Soy and Prostate cancer in Japanese Men
Prostate cancer is defined as a condition in which the cells of prostate has become cancerous, causing abnormal cell growth with possibility of spreading to the distant parts of the body. Most prostate cancers are slow growing and enlarged prostate and prostate cancer may be detected during physical (rectum) exams.

The widespread of prostate cancer, once considered a disease of aging male, now have become major concerns of governments and scientific community in South East Asian with tendency to effect even younger age population. Suggestions emerged of over consuming bad fats in any time in history accompanied with unhealthy diet and life style may be the possible causes of the disease, linking to the economic prosperity over 2 decades.

In fact, the incidence of prostate cancer is still lower if compared to their Western counterparts.
The  study of the Research Center for Cancer Prevention and Screening, National Cancer Center. suggested that isoflavones and soy food are associated with a dose-dependent decrease in the risk of localized cancer, in a population-based prospective study in 43,509 Japanese men ages 45 to 74 years with  participants responded to a validated questionnaire, which included 147 food items. During follow-up from 1995 through 2004, 307 men were newly diagnosed with prostate cancer, of which 74 cases were advanced, 220 cases were organ localized, and 13 cases were of an undetermined stage(5).

Environment, Diet,  intestinal microbiota and Geography
The testing of North American Japanese and Japanese in Japan showed the environment factor may be involved in the development of prostate cancer regardless to genetic similar(7). The incidence of the disease increased vary both from country to country and according to the ethnic group, with the highest incidence reported for Afro-Americans and the lowest for Asian men(2).

 The study of  the associations between nutritional and other lifestyle factors and the prevalence of prostate cancer in a case-control study of Japanese men, showed that soy isoflavone significantly decreased the risk of prostate cancer regardless to the intake of other nutrients such as  PUFA, (n-6) fatty acids or magnesium from other food sources(9).

Other suggested that legumes (not limited to soy products) and certain categories of vegetables may protect against prostate cancer(10).

DR. Akaza H. said "not having equol converting bacteria in the intestine (non-equol producers) can be a risk factor for prostate cancer and that one direction for future research will be to examine the possibility of improving the intestinal environment to enable equol production"(13).

Genes differentiation
1n gene differentiation, estrogen related genes may be the culprits for the development of prostate cancer. In an one hundred and eighty cases and 177 controls selected from three geographic areas of Japan study,  though analysis by the multifactor dimensionality reduction method, soy isoflavones, showed to exhibit its anti prostate cancer, depending to differ between the genotypes of estrogen related genes(3).
According to Dr. Kimura T., the incidence of prostate cancer  in Asia is much lower than that in African Americans and European Caucasians and soy food consumption, more popular in Asian populations, is associated with a 25% to 30% reduced risk of prostate cancer, it may be as a result of  genetic mutation of approximately 30 genetic polymorphisms in populations of countries in the West.(1).

Serum of isoflavones
In a case-control study within the Japan Public Health Center-based Prospective of a total of 14,203 men aged 40 to 69 years who had returned the baseline questionnaire and provided blood samples observed from 1990 to 2005, showed that plazma genistein level is associated inversely to the risk of prostate cancer(4).

Other in the study of four isoflavonoids in plasma of 14 Japanese and 14 Finnish men, also showed  that the mean plasma  of total individual isoflavonoid levels of Japnaese are 7 to 110 times higher Japanese than in the Finnish men. Genistein, a tyrosine kinase inhibitor, occurred in the highest concentration(11).

In the experiment of  Urinary excretion of lignans and isoflavonoid phytoestrogens in Japanese men and women consuming a traditional Japanese diet showed that the excretion of isoflavonoids correlated with soybean-product intake is associated to reduced  mortality in breast and prostate cancer of Japanese women and men(12).

In view of above, the Loma Linda University, insisted that  soy isoflavones should be tested against different populations of prostate cancer patients for its efficacy(6). Other suggested that the lower incidence of prostate cancer in Japanese men may be a result of traditional Japanese diet with a lot of soy foods and fishes(8) and promotes the production of Soy-derived food products and the metabolization of the isoflavones to enhance equol production to those of non producers of Asian and European/North American populations(13).

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References
(1) East meets West: ethnic differences in prostate cancer epidemiology between East Asians and Caucasians by Kimura T.(PubMed)
(2) Hereditary prostate cancer and other genetic predispositions to prostate cancer by Cussenot O¹, Valeri A, Berthon P, Fournier G, Mangin P.(PubMed)
(3) Polymorphisms in estrogen related genes may modify the protective effect of isoflavones against prostate cancer risk in Japanese men by Sonoda T¹, Suzuki H, Mori M, Tsukamoto T, Yokomizo A, Naito S, Fujimoto K, Hirao Y, Miyanaga N, Akaza H.(PubMed)
(4) Plasma isoflavones and subsequent risk of prostate cancer in a nested case-control study: the Japan Public Health Center by Kurahashi N¹, Iwasaki M, Inoue M, Sasazuki S, Tsugane S.(PubMed)
(5) Soy product and isoflavone consumption in relation to prostate cancer in Japanese men by Kurahashi N¹, Iwasaki M, Sasazuki S, Otani T, Inoue M, Tsugane S; Japan Public Health Center-Based Prospective Study Group.(PubMed)
(6) An overview of the health effects of isoflavones with an emphasis on prostate cancer risk and prostate-specific antigen levels by Messina M¹, Kucuk O, Lampe JW.(PubMed)
(7) Prostate cancer in native Japanese and Japanese-American men: effects of dietary differences on prostatic tissue by Marks LS¹, Kojima M, Demarzo A, Heber D, Bostwick DG, Qian J, Dorey FJ, Veltri RW, Mohler JL, Partin AW.(PubMed)
(8) A case-control study of diet and prostate cancer in Japan: possible protective effect of traditional Japanese diet by Sonoda T¹, Nagata Y, Mori M, Miyanaga N, Takashima N, Okumura K, Goto K, Naito S, Fujimoto K, Hirao Y, Takahashi A, Tsukamoto T, Fujioka T, Akaza H.(PubMed)
(9) Nagata Y¹, Sonoda T, Mori M, Miyanaga N, Okumura K, Goto K, Naito S, Fujimoto K, Hirao Y, Takahashi A, Tsukamoto T, Akaza H.(PubMed)
(10) Vegetables, fruits, legumes and prostate cancer: a multiethnic case-control study by Kolonel LN¹, Hankin JH, Whittemore AS, Wu AH, Gallagher RP, Wilkens LR, John EM, Howe GR, Dreon DM, West DW, Paffenbarger RS Jr.(PubMed)
(11) Plasma concentrations of phyto-oestrogens in Japanese men by Adlercreutz H¹, Markkanen H, Watanabe S.(PubMed) (12) Urinary excretion of lignans and isoflavonoid phytoestrogens in Japanese men and women consuming a traditional Japanese diet by Adlercreutz H¹, Honjo H, Higashi A, Fotsis T, Hämäläinen E, Hasegawa T, Okada H.(PubMed)
(13) Prostate cancer chemoprevention by soy isoflavones: role of intestinal bacteria as the "second human genome" by Akaza H.(PubMed)

Food therapy - Eggplant (Solanum Melongena)

Eggplant is a species of S. melongena, belonging to the family Solanaceae and native to India. The plant has been cultivated in southern and eastern Asia since prehistory. It is famous with its deeply purple and the best eggplant can be found from August through October when it is in season.

Nutritional Supplements
1. Carbohydrates
2. Sugars
3. Fiber
4. Fat
5. Protein
6. Thiamine (Vitamin B1)
7. Riboflavin (Vitamin B2)
8. Niacin (Vitamin B3)
9. Pantothenic acid (B5)
10. Vitamin B6
11. Folate (Vitamin B9)
12. Vitamin C
13. Tryptophan
14. Manganese
15. Calcium
16. Copper
17. Iron
18. Magnesium
19. Phosphorus
20. Potassium
21. Zinc
22. Etc.

Chemical constituents
The vegetable chemical compounds containing include sterols (i.e. typical plant sterols, androstane, pregnane and cholestane derivatives, steroidal alkaloids and sapogenins), phytosterols, triterpenes, δ-amyrin, Chlorogenic acid, Nasunin and other Polyphenolic compounds.

1. Eggplant and cancer
Cancer is a class of diseases in which a group of cells growing and multiplying disordered and uncontrollable way in our body, have become progressively worse and damaged other healthy tissues, sometimes spreads to other organs in the body via lymph or blood and results may be in death.
The study of antiproliferative activities against human colon (HT29) and liver (HepG2) cancer cells conducted by Yeungnam University, the eggplant glycoalkaloids solamargine showed to inhibit both cancer cell lines but greater in colon cancer cell line(1). In human fibrosarcoma HT-1080 cell, delphinidin, a flavonoid pigment contained in the peel of eggplant, slightly inhibited tumor cell invasiveness probably through slight inhibition of the activity of MMPs(secretes matrix metalloproteinase)(2). According to Dr. Shimada A. in an one year (continuous 2 days for 12 months) food surveys held at 5 areas in Japan, the frequency of intake eggplant may associate to increase risk of gastric cancer and gastric cancer mortality rate(3), but may account partly for the geographic variation in gastric cancer mortality in Japan(4).

References
(1) Glycoalkaloids and metabolites inhibit the growth of human colon (HT29) and liver (HepG2) cancer cells by Lee KR¹, Kozukue N, Han JS, Park JH, Chang EY, Baek EJ, Chang JS, Friedman M.(PubMed)
(2) Inhibitory effect of delphinidin from Solanum melongena on human fibrosarcoma HT-1080 invasiveness in vitro by Nagase H¹, Sasaki K, Kito H, Haga A, Sato T.(PubMed)
(3) [Regional differences in gastric cancer mortality and eating habits of people].[Article in Japanese] by Shimada A.(PubMed)
(4) Food consumption and gastric cancer mortality in five regions of Japan by Tsubono Y¹, Kobayashi M, Tsugane S.(PubMed)

2. Eggplant and cholesterol
Cholesterol is needed for our body to build cell walls, make hormones and vitamin D, and create bile salts that help you digest fat. However too much of it can be dangerous because cholesterol cannot dissolve in your blood. The special particle called lipoprotein moves this waxy, soft substance from place to place. If you have too much low density lipoprotein LDL that is known as bad cholesterol, overtime cholesterol can build up in your arterial walls causing blockage and leading to heart attack and stroke.
Eggplant (Solanum melongena) has been used as hypocholesterolemic agent in many countries, including Brazil. its phenolic may has the potential to reduce hyperglycemia-induced pathogenesis linked to cellular oxidation stress(1). In a study of 38 hypercholesterolemic human volunteers ingesting S. melongena infusion for five weeks, researchers found no differences when compared to control, but in Intraindividual analysis  S. melongena infusion significantly reduced the blood levels of total and LDL cholesterol and of apolipoprotein B(1).
 But in a  double-blind placebo-controlled study of the effectiveness of oral Solanum melongena (SM) against hyperlipidemia, showed the potential result in decreased serum total cholesterol, LDL-c and LDL-c/HDL-c, but no change in serum triglycerides, HDL-c, VLDL-c, AST, ALT, gGT, glucose and body mass index, after 3 months(2) and  according to Universidade Federal de Minas Gerais, eggplant did not alter the total cholesterol and atherogenic lipoproteins after 12 week of intake in its study (3).

References
(1) In vitro studies of eggplant (Solanum melongena) phenolics as inhibitors of key enzymes relevant for type 2 diabetes and hypertension by Kwon YI¹, Apostolidis E, Shetty K.(PubMed)(2) Eggplant (Solanum melongena) infusion has a modest and transitory effect on hypercholesterolemic subjects by Guimarães PR¹, Galvão AM, Batista CM, Azevedo GS, Oliveira RD, Lamounier RP, Freire N, Barros AM, Sakurai E, Oliveira JP, Vieira EC, Alvarez-Leite JI.(PubMed)(3) [Absence of hypolipidemic effect of Solanum melongena L. (eggplant) on hyperlipidemic patients].[Article in Portuguese] by Silva GE¹, Takahashi MH, Eik Filho W, Albino CC, Tasim GE, Serri Lde A, Assef AH, Cortez DA, Bazotte RB.(PubMed)
(4) Effects of eggplant (Solanum melongena) on the atherogenesis and oxidative stress in LDL receptor knock out mice (LDLR(-/-)) by Botelho FV¹, Enéas LR, Cesar GC, Bizzotto CS, Tavares E, Oliveira FA, Gloria MB, Silvestre MP, Arantes RM, Alvarez-Leite JI.(PubMed)

3. Eggplant as antioxidant
Free radicals are atoms, molecules, or ions with unpaired electrons through chemical bonds with other atoms or molecules during a chemical reaction. They may have positive, negative or zero charge. The unpaired electrons cause radicals to be highly chemically reactive in the human body, leading to aging and cancers.
Eggplant fruit contains a rich source of polyphenol compounds endowed with antioxidant properties. According to Università degli Studi di Catania, dry peeled skin combined with 50% aqueous ethanol, irradiated with microwave contained showed a high quantity of flavonoids with good antioxidant activity expressed through its capacity to scavenge superoxide anion and to inhibit lipid peroxidation(1).  Solanum anguivi fruit (SAG)  exhibited potent and concentration dependent free radical-scavenging activity as well as protected against Ca(2+) (110 μmol/L)-induced mitochondrial swelling and maintained the mitochondrial membrane potential, in the evaluation of the antioxidant and radical scavenging activities of Solanum anguivi fruit (SAG) and its possible effect on mitochondrial permeability transition pore(2).
The City University of New York, in the study of the antioxidant-caffeoylquinic acid isomers in fruits of wild eggplant relatives, 3-O-malonyl-5-O-(E)-caffeoylquinic acid (isomer 1) and 4-O-(E)-caffeoyl-5-O-malonylquinic acid (isomer 2) exhibited free radical scavenging activity, albeit about 4-fold lower than that of the flavonol quercetin dehydrate(3).

References
(1) Antioxidant activity and phenolic content of microwave-assisted Solanum melongena extracts by Salerno L, Modica MN, Pittalà V, Romeo G, Siracusa MA, Di Giacomo C, Sorrenti V, Acquaviva R.(PubMed)
(2) African eggplant (Solanum anguivi Lam.) fruit with bioactive polyphenolic compounds exerts in vitro antioxidant properties and inhibits Ca(2+)-induced mitochondrial swelling by Elekofehinti OO¹, Kamdem JP, Bolingon AA, Athayde ML, Lopes SR, Waczuk EP, Kade IJ, Adanlawo IG, Rocha JB.(PubMed)
(3) Two new antioxidant malonated caffeoylquinic acid isomers in fruits of wild eggplant relatives by Ma C¹, Dastmalchi K, Whitaker BD, Kennelly EJ.(PubMed)

4. Eggplant and cardiovascular diseases
Beside cancer, heart disease kills more than 2,000 Americans everyday. Approximately 60 million Americans have heart disease. Most of heart diseases are caused by high blood pressure contributes to hardening of the arteries. High levels of bad cholesterol (LDL) build up in the arteries as a result of uncontrolled diet with high levels of saturated fat and trans fat.

 Animals fed freeze-dried products of either raw or grilled eggplants for 30 days study showed a positive effect of raw and cooked eggplant (Solanum melongena L) in increase left ventricular function, and reduce myocardial infarct size and cardiomyocyte apoptosis with high potency in grilled eggplants(1). According to Tuskegee University,  eggplant containing high sources of phenolic compounds, which might provide anti-oxidative protection against free radicals in the human body and might reduce the risk of chronic diseases(2)

References
(1) Cardioprotective properties of raw and cooked eggplant (Solanum melongena L) by Das S¹, Raychaudhuri U, Falchi M, Bertelli A, Braga PC, Das DK.(PubMed)
(2) Total phenolics and antioxidant capacity of indigenous vegetables in the southeast United States: Alabama Collaboration for Cardiovascular Equality Project by Huang Z¹, Wang B, Eaves DH, Shikany JM, Pace RD.(PubMed)

5.  Eggplant and Type II diabetes
Diabetes is defined as a condition caused by insufficient insulin entering the bloodstream to regulate the glucose. It is either caused by cells in pancreas dying off or receptor sites clogged up by fat and cholesterol. In some cases, diabetes is also caused by allergic reactions of cells in the immune system.

According to University of Massachusetts, phenolic-enriched extracts of eggplant with moderate free radical scavenging-linked antioxidant activity had high alpha-glucosidase inhibitory activity, through inhibition of key enzymes relevant for type 2 diabetes and hypertension(1). Chlorogenic acids (CGAs (71 compounds), being esters of derivatives of cinnamic acids with quinic acid  found in many foods, including eggplant may be associated to reduce risk of the risk of human chronic diseases such as inflammation, diabetes(2).

References
(1) In vitro studies of eggplant (Solanum melongena) phenolics as inhibitors of key enzymes relevant for type 2 diabetes and hypertension by Kwon YI¹, Apostolidis E, Shetty K.(PubMed)
(2) n outlook on chlorogenic acids-occurrence, chemistry, technology, and biological activities by Upadhyay R¹, Mohan Rao LJ.(PubMed)







 

Phytochemicals Dithiolthiones (isothiocyanates)

Dithiolthiones are phytochemicals in the class of Organosulfides, found abundantly in cruciferous vegetables, garden sorrel, horseradish, etc.

The study of the hepatoprotective drug anisyldithiolthione was showed to be effective  in acting as hepoprotective agent in inhibited lipid peroxidation induced in rat liver microsomes either chemically by FeSO4 and reducing agents (cysteine or ascorbate) or enzymatically, probably through the presence of its dithiolthione function(1) Other medication such as Anethol dithiolthione (ADT), usually prescribed as a choleretic drug, also exhibited an hepatoprotective potency at doses as low as 10 mg/kg relative to serum aminotransferase activities and hepatic glutathione related enzyme system in in Swiss female mice(2)

References
(1) A new potent inhibitor of lipid peroxidation in vitro and in vivo, the hepatoprotective drug anisyldithiolthione by Mansuy D, Sassi A, Dansette PM, Plat M.(PubMed)
(2) Protective effect of anethol dithiolthione against acetaminophen hepatotoxicity in mice by Warnet JM¹, Christen MO, Thevenin M, Biard D, Jacqueson A, Claude JR.(PubMed).

2. Isothiocyanates and cancers
Cancer is a class of diseases in which a group of cells growing and multiplying disordered and uncontrollable way in our body, have become progressively worse and damaged other healthy tissues, sometimes spreads to other organs in the body via lymph or blood and results may be in death.
In a case-control study conducted in urban Shanghai. The cases (from December 2006 to December 2008, ITC consumption from cruciferous vegetables intake showed a positive effect in reduce risk of pancreatic cancer after adjusting for possible confounding factors such as age, sex, history of diabetes and pancreatitis(1). Thiazolo, the synthesis of a novel class of quinazoline, produced by the reaction of 4,6-dichloro-5-aminopyrimidine with isothiocyanates in presence of 20 mol% KF/alumina, showed to exhibit antiproliferative activity in lung (NCI-H322 and A549), epidermal (A431) and glioblastoma (T98G), HL-60 cell lines at 20 μM. The effect of compound 4a on mitochondrial potential loss in HL-60 cells probably through cleavage of PARP-1 and procaspase-3 inhibition(2).
The study by Campus Morro do Cruzeiro suggested that the phytochemical  inhibited the cell viability of human cervical cancer cells, human pancreatic cancer cells, human hepatocellular carcinoma cells, human ovarian cancer cells, and have antiinflammatory properties in the treatment of human T-cell leukemia cells(3).

References
(1) [A case-control study on the association between urinary levels of isothiocyanates and the risk of pancreatic cancer].[Article in Chinese] by Wang J¹, Han L, Zhang W, Wang J, Ni Q, Shen M, Gao Y².(PubMed)
(2) Synthesis, antiproliferative and apoptosis-inducing activity of thiazolo[5,4-d]pyrimidines by Singh B¹, Guru SK, Kour S, Jain SK, Sharma R, Sharma PR, Singh SK, Bhushan S, Bharate SB, Vishwakarma RA.(PubMed) 
(3) The anti-oxidant properties of isothiocyanates: a review by de Figueiredo SM¹, Filho SA, Nogueira-Machado JA, Caligiorne RB.(PubMed)

3. Isothiocyanates as Antioxidants
Free radicals are atoms, molecules, or ions with unpaired electrons through chemical bonds with other atoms or molecules during a chemical reaction. They may have positive, negative or zero charge. The unpaired electrons cause radicals to be highly chemically reactive in the human body, leading to aging and cancers.
In Fuchs endothelial corneal dystrophy (FECD), an oxidative stress disorder, treatment with Sulforaphane, a molecule within the isothiocyanate group, decreased CEC apoptosis by 55% in unstressed group and by 43% in tBHP-treated specimens, through inhibition of oxidative stress(1).
The Universidade Federal de Ouro Preto study also indicated the similar result of sulforaphane in improvement of antioxidant status in the testing of number of cancer cell lines(2). Other study suggested that isothiocyanates (ITCs), found abundantly in cruciferous vegetables, may be effective as a cancer chemopreventive agent through modulation of phase II detoxifying/antioxidant enzyme activities(3).

Reference
(1) Sulforaphane decreases endothelial cell apoptosis in fuchs endothelial corneal dystrophy: a novel treatment by Ziaei A¹, Schmedt T, Chen Y, Jurkunas UV.(PubMed)
(2) The anti-oxidant properties of isothiocyanates: a review by de Figueiredo SM¹, Filho SA, Nogueira-Machado JA, Caligiorne RB.(PubMed)
(3) Structural influence of isothiocyanates on the antioxidant response element (ARE)-mediated heme oxygenase-1 (HO-1) expression by Prawan A¹, Keum YS, Khor TO, Yu S, Nair S, Li W, Hu L, Kong AN.(PubMed)

4. Isothiocyanates and heart diseases
Beside cancer, heart disease kills more than 2,000 Americans everyday. Approximately 60 million Americans have heart disease.
There are many causes of heart diseases. Most of heart diseases are caused by high blood pressure contributes to hardening of the arteries. High levels of bad cholesterol (LDL) build up in the arteries as a result of uncontrolled diet with high levels of saturated fat and trans fat.
In human immunodeficiency virus (HIV) patients, showed to improve AIDS-related heart dysfunction through inhibition of apoptosis by decreasing iNOS and Bax expression through suppression of NF-κB.(1). In ischemic injury of hearts patients, showed to inhibit reactive oxygen species mediators in exerting a toxic effect during ischemia-reperfusion through mitochondrial K(ATP) channels and antioxidant pathway(2). On ischaemia-reperfusion-induced cardiac injury. steamed broccoli  showed a superior cardioprotective properties over cooked broccoli, probably through through the redox signalling of sulphoraphane(3). the phytochemical also found to trduce risk of vascular disease due to aging by inhibiting oxidative stress (4).

References
(1) Isothiocyanates ameliorate the symptom of heart dysfunction and mortality in a murine AIDS model by inhibiting apoptosis in the left ventricle. by Ho JN¹, Yoon HG, Park CS, Kim S, Jun W, Choue R, Lee J.(PubMed)
(2) Sulforaphane protects ischemic injury of hearts through antioxidant pathway and mitochondrial K(ATP) channels.by Piao CS¹, Gao S, Lee GH, Kim do S, Park BH, Chae SW, Chae HJ, Kim SH.(PubMed)
(3) Comparison of the protective effects of steamed and cooked broccolis on ischaemia-reperfusion-induced cardiac injury. by Mukherjee S¹, Lekli I, Ray D, Gangopadhyay H, Raychaudhuri U, Das DK.(PubMed)
(4) Crosstalk between Nrf2 and the proteasome: therapeutic potential of Nrf2 inducers in vascular disease and aging by Chapple SJ¹, Siow RC, Mann GE.(PubMed)

5. Isothiocyanates and neuroprotective effect
Sulforaphane, a naturally organosulfur compound found in broccoli, showed to exert its neuroprotective effects through significantly attenuated the scopolamine-induced memory impairment and improved cholinergic system reactivity, as indicated by an increased ACh level, decreased AChE activity, and increased choline acetyltransferase (ChAT) expression in the hippocampus and frontal cortex(1). in a variety of acute and chronic neurodegenerative diseases, phytochemicals, isothiocyanate sulforaphane, derived from the hydrolysis of the glucosinolate glucoraphanin mainly present in Brassica vegetables, demonstrated its neuroprotective effects in several in vitro and in vivo studies, may be mainly ascribed to its peculiar ability to activate the Nrf2/ARE pathway(2). In dopaminergic neurotoxicity in mice induced by 6-hydroxydopamine (6-OHDA), the phytochemical showed the neuroprotective effect through its ability to enhance glutathione levels and its dependent enzymes (glutathione-S-transferase and glutathione reductase) and to modulate neuronal survival pathways(3).

References
(1) Sulforaphane alleviates scopolamine-induced memory impairment in mice by Lee S¹, Kim J¹, Seo SG², Choi BR³, Han JS³, Lee KW⁴, Kim J⁵.(PubMed)
(2) Sulforaphane as a potential protective phytochemical against neurodegenerative diseases byTarozzi A¹, Angeloni C, Malaguti M, Morroni F, Hrelia S, Hrelia P.(PubMed)
(3) Neuroprotective effect of sulforaphane in 6-hydroxydopamine-lesioned mouse model of Parkinson's disease byMorroni F¹, Tarozzi A, Sita G, Bolondi C, Zolezzi Moraga JM, Cantelli-Forti G, Hrelia P.(PubMed)

6. Sulforaphane and Obesity
Obesity is defined as a medical condition of excess body fat has accumulated overtime, while overweight is a condition of excess body weight relatively to the height. According to the Body Mass Index(BMI), a BMI between 25 to 29.9 is considered over weight, while a BMI of over 30 is an indication of obesity. According to the statistic, 68% of American population are either overweight or obese.
Taking foods containing sulforaphane may be effective in managing weight loss for obese patients accompanied with change of lifestyle with more vegetables and fruits into diet. Sulforaphane,  a molecule within the isothiocyanate group, according to Chungbuk National University, showed to prevent high-fat diet (HFD)-induced obesity in C57BL/6N mice. through inhibiting adipogenesis( the cells differentiation for a vital role in energy homeostasis and process the largest energy reserve  in the body of animals). via down-regulation of PPARγ(regulation of metabolism) and C/EBPα (inflammatory process) and by suppressing lipogenesis( protein as an intermediate stage in metabolism of simple sugars) through activation of the AMPK(in cellular energy homeostasis) pathway(1). Chronic oral administration of sulforaphane, on obesity and insulin resistance induced by a highly palatable (HP) diet in male Wistar rats, at the specific dose was able to accentuate glucose intolerance and may affect GLUT3 expression involed neuronal glucose transport in the cerebral cortex and hypothalamus(2). The  Chonbuk National University also suggested that Sulforaphane suppressed AMPK phosphorylation(cellular energy homeostasis) at Thr-172 in a dose-dependent manner(3).

References
(1) Sulforaphane attenuates obesity by inhibiting adipogenesis and activating the AMPK pathway in obese mice by Choi KM¹, Lee YS¹, Kim W¹, Kim SJ², Shin KO¹, Yu JY³, Lee MK¹, Lee YM¹, Hong JT¹, Yun YP¹, Yoo HS⁴.(PubMed)(2) Chronic sulforaphane oral treatment accentuates blood glucose impairment and may affect GLUT3 expression in the cerebral cortex and hypothalamus of rats fed with a highly palatable diet by Souza CG¹, Riboldi BP, Hansen F, Moreira JD, Souza DG, de Assis AM, Brum LM, Perry ML, Souza DO.(PubMed)
(3) Sulforaphane induced adipolysis via hormone sensitive lipase activation, regulated by AMPK signaling pathway by Lee JH¹, Moon MH, Jeong JK, Park YG, Lee YJ, Seol JW, Park SY.(PubMed)

7. Sulforaphane and Lung diseases
Lung diseases is defined as a condition, affecting  the upper respiratory tract, trachea, bronchi, bronchioles, alveoli, pleura and pleural cavity, and the nerves and muscles of breathing.
Sulforaphane may be used as a preventive chemical constituent of  pulmonary damage for patient who exposure to arsenic. According to China Medical University, arsenic-containing dust resulted in ; all of which were blocked by sulforaphane (SF) blocked pathological alterations, oxidative DNA damage, and mild apoptotic cell death in the lung caused by 2 weeks of exposure to arsenic through activation of Nrf2(master regulator of the total antioxidant system)(1). In wildtype neonatal mice exposed to hyperoxia. SF also found to activated Nrf2 activation through induced expression of anti-oxidant genes,(2). In the lungs of the arrhythmic Clock(Δ19) mice, SF also activated  it anti ovidative damage effect through activation of NRF2/glutathione defense pathway in combating oxidative/fibrotic lung damage(3).

References
(1) Sulforaphane prevents pulmonary damage in response to inhaled arsenic by activating the Nrf2-defense response. by Zheng Y¹, Tao S, Lian F, Chau BT, Chen J, Sun G, Fang D, Lantz RC, Zhang DD.(PubMed)
(2) Transcriptional responses of neonatal mouse lung to hyperoxia by Nrf2 status by McGrath-Morrow SA¹, Lauer T, Collaco JM, Lopez A, Malhotra D, Alekseyev YO, Neptune E, Wise R, Biswal S.(PubMed)
(3) The circadian clock regulates rhythmic activation of the NRF2/glutathione-mediated antioxidant defense pathway to modulate pulmonary fibrosis by Pekovic-Vaughan V¹, Gibbs J, Yoshitane H, Yang N, Pathiranage D, Guo B, Sagami A, Taguchi K, Bechtold D, Loudon A, Yamamoto M, Chan J, van der Horst GT, Fukada Y, Meng QJ.(PubMed)


8. Sulforaphane and Liver disease
Liver disease in most cases are linked to alcohol or drugs. In fact, it can be caused by a variety of factors and affecting everyone from infants to older adults.
In CYP2E1-dependent binge alcohol-induced liver steatosis, oral treatment of sulforphane sulforaphane showed to  activated Nrf2, increased levels of the Nrf2 target heme oxygenase-1 and subsequently lowered oxidant stress as shown by the decline in lipid peroxidation and 3-nitrotyrosine protein adducts and an increase in GSH levels(1). In  the comparison of the effectiveness of Sulforaphane and glucoraphanin in modulating carcinogen-metabolising enzymes in Hep G2 cells, Dr Abdull Razis AF¹, and Noor NM found that sulforphane is superior to glucoraphanin in modulators of various phase I and phase II enzymes involved in carcinogen-metabolising enzyme systems in vitro(2). The University of Rhode Island, Kingston study also insisted that SF activate  Nrf2 activation in inhibited lipid accumulation in white adipose tissue, suppressed adipogenesis, induced insulin resistance and glucose intolerance, and increased hepatic steatosis in Lep(ob/ob) mice(3)..

References
(1) Sulforaphane induces Nrf2 and protects against CYP2E1-dependent binge alcohol-induced liver steatosis by Zhou R¹, Lin J, Wu D.(PubMed)
(2) Sulforaphane is superior to glucoraphanin in modulating carcinogen-metabolising enzymes in Hep G2 cells by Abdull Razis AF¹, Noor NM.(PubMed)
(3) Enhanced Nrf2 activity worsens insulin resistance, impairs lipid accumulation in adipose tissue, and increases hepatic steatosis in leptin-deficient mice by Xu J¹, Kulkarni SR, Donepudi AC, More VR, Slitt AL.(PubMed)


9. Sulforaphane and Breast cancer
Breast cancer (malignant breast neoplasm) is a cancer that starts in the tissues of the breast either from the inner lining of milk ducts (Ductal carcinoma) or the lobules (Lobular carcinoma) that supply the ducts with milk. there is also rare cases that breast cancer starts in other areas of the breast. In 2010, over 250,000 new cases of breast cancer were expected to be diagnosed in women in the U.S. alone and the risk of getting invasive breast cancer during life time of a women is 1/8.
The University of Michigan, also insisted that ingestion of sulforaphane at a dose of 50 mg/kg  for 2 weeks inhibited breast cancer stem cells(1). According to Manipal University, Sulforaphane inhibited growth of human breast cancer cell line MCF-7 cells, through induces apoptosis and anti-inflammatory effects on MCF-7 cells via downregulation of Bcl-2 (anti-apoptotic protein) and COX-2 (inlvoved inflammatory process) respectively(2). Also in testing of MCF-7 breast cancer cells, researchers at the The Catholic University of Korea, showed that sulforaphane induced the inhibition of 12-O-tetradecanoyl phorbol-13-acetate (TPA)-induced MMP-9 expression(involved in keratinocyte migration and granulation tissue remodeling during wound healing) and cell invasion by via the suppression of the NF-κB (nvolved in cellular responses)pathway in MCF-7 cells(3).

References
(1) Sulforaphane, a dietary component of broccoli/broccoli sprouts, inhibits breast cancer stem cells by Li Y¹, Zhang T, Korkaya H, Liu S, Lee HF, Newman B, Yu Y, Clouthier SG, Schwartz SJ, Wicha MS, Sun D.(PubMed)
(2) Sulforaphane inhibits growth of human breast cancer cells and augments the therapeutic index of the chemotherapeutic drug, gemcitabine by Hussain A¹, Mohsin J, Prabhu SA, Begum S, Nusri Qel-A, Harish G, Javed E, Khan MA, Sharma C.(PubMed)
(3) Sulforaphane controls TPA-induced MMP-9 expression through the NF-κB signaling pathway, but not AP-1, in MCF-7 breast cancer cells by Lee YR¹, Noh EM, Han JH, Kim JM, Hwang BM, Kim BS, Lee SH, Jung SH, Youn HJ, Chung EY, Kim JS.(PubMed)

10. Sulforaphane and Prostate cancer
Prostate cancer is defined as a condition in which the cells of prostate has become cancerous, causing abnormal cell growth which spread to the distant parts of the body. Most prostate cancers are slow growing and enlarged prostate and prostate cancer may be detected during the Physical (rectum) exams.
Oral administration of d,l-sulforaphane (SFN) can decrease the incidence or burden of early-stage prostate cancer [prostatic intraepithelial neoplasia (PIN)] and well-differentiated cancer (WDC) but not late-stage poorly differentiated cancer (PDC)., according to the University of Pittsburgh Cancer Institute and  University of Pittsburgh School of Medicine(1)
In advanced prostate cancer stem-like cells, sulforaphane showed to inhibit tumor engraftment and tumor growth, without the induction of liver necrosis or other obvious side effects, In vivo(2).
In the comparison of the effect of sulforaphane(SFN) and 3,3'-diindolylmethane(DIM) in normal prostate epithelial cells and prostate cancer cells, researchers at the Oregon State University found that SFN and DIM reversed many of the cancer-associated methylation alterations, including aberrantly methylated genes that are dysregulated or are highly involved in cancer progression(3).


References
(1) Chemoprevention of prostate cancer by d,l-sulforaphane is augmented by pharmacological inhibition of autophagy by Vyas AR¹, Hahm ER, Arlotti JA, Watkins S, Stolz DB, Desai D, Amin S, Singh SV.(PubMed)
(2) Sulforaphane and TRAIL induce a synergistic elimination of advanced prostate cancer stem-like cells by Labsch S, Liu L, Bauer N, Zhang Y, Aleksandrowicz E, Gladkich J, Schönsiegel F, Herr I.(PubMed)
(3) Effects of sulforaphane and 3,3'-diindolylmethane on genome-wide promoter methylation in normal prostate epithelial cells and prostate cancer cells by Wong CP¹, Hsu A¹, Buchanan A², Palomera-Sanchez Z¹, Beaver LM¹, Houseman EA², Williams DE³, Dashwood RH³, Ho E⁴.(PubMed)


11. Sulforaphane and colon cancer
Bowel cancer is relatively very common and slowly growing and progress cancer and in predictable way. Bowel cancer is the third most commonly diagnosed cancer in developed countries, including US and Canada.
According to ¹INRA, Laboratoire des Xénobiotiques, sulforaphane inhibited colon cancer cell line (HT29) through cell cycle arrest via an apoptotic process(1). GE132+Natural, a novel supplement consisting  Resveratrol, Ganoderma lucidum, Sulforaphane, Lycopene and Royal jelly, in the testing of tested cancer cell lines (PC3, MCF7 and SW480), is found to be effective in inhibiting all tested cancer cell proliferation, the University of Belgrade insisted(2). Other study also showed the effective of sulforaphane and related dietary isothiocyanates in treating colon cancer cells via included cell growth arrest, autophagy and apoptosis depending to Depending on the isothiocyanates (ITCs)  and treatment conditions(3).

References
(1) Sulforaphane, a naturally occurring isothiocyanate, induces cell cycle arrest and apoptosis in HT29 human colon cancer cells by Gamet-Payrastre L¹, Li P, Lumeau S, Cassar G, Dupont MA, Chevolleau S, Gasc N, Tulliez J, Tercé F.(PubMed)
(2) GE132+Natural: Novel promising dietetic supplement with antiproliferative influence on prostate, colon, and breast cancer cells by Okic-Djordjevic I¹, Trivanovic D, Krstic J, Jaukovic A, Mojsilovic S, Santibanez JF, Terzic M, Vesovic D, Bugarski D.(PubMed)
(3) HDAC turnover, CtIP acetylation and dysregulated DNA damage signaling in colon cancer cells treated with sulforaphane and related dietary isothiocyanates by Rajendran P¹, Kidane AI, Yu TW, Dashwood WM, Bisson WH, Löhr CV, Ho E, Williams DE, Dashwood RH.(PubMed)


12. Sulforaphane and cervical cancer
Cervix is the lower part of uterus that opens at the top of the vagina. Cervix acts an transition area for vaginal lining (squamous epithelium) change to uterus type (columnar epithelium) through the transitional area (squamous columnar epithelium) to host the development of the fetus. Cervical cancer is malignant neoplasm of the cervix uteri or cervical area caused by abnormal cells growth with alternation of cells DNA.
According to the Manipal University in the study of the effect of sulforaphane and eugenol effects on human cervical cancer cells, found that combined treatment with variable dose combinations resulted in differential effects with an antagonistic effect at lower and synergistic at higher sub-lethal doses as reflected in cell cytotoxicity and apoptosis induction(1). The Manipal University  also showed that application of SFN inhibited human cervical cancer cell lines through  apoptosis induction and anti-inflammatory properties(2). In human cervical carcinoma HeLa, treatment with SFN  inhibit the cancer cell through down-regulation of anti-apoptotic Bcl-2 and Bcl-XL, and the up-regulation of pro-apoptotic Bax expression(3).

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References
(1) Concurrent sulforaphane and eugenol induces differential effects on human cervical cancer cells by Hussain A¹, Priyani A, Sadrieh L, Brahmbhatt K, Ahmed M, Sharma C.(PubMed)
(2) Anti-carcinogenic effects of sulforaphane in association with its apoptosis-inducing and anti-inflammatory properties in human cervical cancer cells by Sharma C¹, Sadrieh L, Priyani A, Ahmed M, Hassan AH, Hussain A.(PubNed)
(3) Induction of apoptosis by isothiocyanate sulforaphane in human cervical carcinoma HeLa and hepatocarcinoma HepG2 cells through activation of caspase-3 by Park SY¹, Kim GY, Bae SJ, Yoo YH, Choi YH.(PubMed)