INTRODUCTION:

Mustard seeds are from the mustard plant, which is a cruciferous vegetable related to broccoli, Brussels sprouts and cabbage. While there are approximately forty different varieties of mustard plants, there are three principal types used to make mustard seeds: black mustard (Brassica nigra), white mustard (Brassica alba) and brown mustard (Brassica juncea). Black mustard seeds have the most pungent taste, while white mustard seeds, which are actually yellow in color, are the most mild and are the ones used to make American yellow mustard. Brown mustard, which is actually dark yellow in color, has a pungent acrid taste and is the type used to make Dijon mustard. Mustard seeds are sold either whole or as a ground powder. Mustard seed is a rich source of oil and protein.

The seed has oil as high as 46-48%, and whole seed meal has 43.6% protein. Mustard is used as a food flavouring, for forage, as an emetic, and the medicinal parts were the seeds from which oil is extracted^[1]. It is commonly used as a spice. It is native to tropical regions of North Africa, temperate regions of Europe, and parts of Asia. Among the diversity of medicinal plants, Brassica nigra is one of the medicinal plants used extensively in various non-communicable/chronic, degenerative diseases and also has potential pharmacological effects in cancer.

Brassica nigra is an annual herbaceous plant. It grows up to 2 m (a little over 6 ft), with many branches. The lower leaves are dentate (toothed), pinnatifid (deeply lobed) or lyrate (deeply lobed, but with an enlarged terminal lobe and smaller lateral lobes), and are often hairy, at least on the underside. Upper leaves on flowering stems are narrow and oblong. In contrast to many brassica species, the leaves are little if at all glaucous (waxy). The yellow, four-parted and cross shaped flowers occur in many racemes (spike-like cluster) and produce 4-sided siliques capsular fruit that dehisces (splits open) when mature that may be up to 2.5 cm (1 in) long. Each silique contains 2 to 12 or more reddish brown to black round seeds. A single plant may produce thousands of seeds, which must be harvested by hand or mechanically before they fully ripen, because the siliques spontaneously split and disperse the seeds when they are mature^[2].

Chemical constituents:

Brassica nigra contains the following chemical constituents ^[3]

• Allyl isothicyanate

• Myrosinase

• Sulphoraphane

• Flavonols- flavones, flavan-3-ols, anthocyanidins, flavanones, isoflavones etc.

• Non-flavonoids - phenolic acids, hydroxyl cinnamates, stilbenes etc.

• Flavonoids and hydroxycinnamic acids

• Anthocyanins

• Glucosinolates

Allylisothiocyanate is (AITC) 3-isothiocyanato-1propene or 2-propenyl isothiocyanate. It belongs to a family of naturally occurring isothiocyanates (ITCs) and is a promising cancer preventive agent^[4]. It occurs in many common cruciferous vegetables and is particularly abundant in mustard, horseradish and wasabi. Certainly, it is mainly responsible for the pungent flavour of these vegetables. It is synthesized and stored as sinigrin (a glucosinolate) and is subsequently generated from the latter through myrosinase-catalyzed hydrolysis of sinigrin.

Myrosinase co-exists with sinigrin in vegetables, but glucosinolate hydrolysis does not normally occur until the vegetable is damaged, such as by insect chewing, fungal invasion, chopping and human mastication. Myrosinase activity also exists in the intestinal microflora in both animals and humans, and glucosinolates that escape the action of vegetable myrosinase may be hydrolyzed in vivo. AITC was selectively targets human bladder cancer cells, while sparing normal human bladder epithelial cells, is selectively delivered to bladder cancer tissues through urinary excretion and potently inhibits bladder cancer development. Mustard seed powder (MSP) is a well known rich source of AITC with thousands of years’ history of use in traditional medicine.

Sulphoraphane is 1-isothiocyanat-(4R)-(methylsulfinyl) butane is a natural isothiocyanate found in Brassica vegetables and is among the most potent bioactive components with antioxidant and anti-tumour properties ^[5,6]. According to the National Cancer Institute, one of the most promising more than 40 chemo preventive agents including glucosinolate hydrolysis products, such as phenethyl isothiocyanate and indole-3-carbinol, is also sulphoraphane^[7].

The concentration of sulphoraphane in broccoli sprouts (1153mg/100g dry weight) is about 10 times greater than mature broccoli (44-171mg 100g dry weight). Therefore, broccoli sprouts are recommended as a rich source of sulphoraphane^[8]. It was isolated from broccoli extracts as the principal inducer of cell-protective phase II enzymes has been shown to inhibit tumour growth. As broccoli and broccoli sprouts are widely consumed, the extracts obtained from them are seen as a suitable tool for giving sulphoraphane to humans^[9].

Phenolic compounds, one of the bioactive compounds that have positive effects on human health. These compounds show antioxidant activity by inhibiting the biological activation of carcinogens and by increasing the detoxification of reactive oxygen species (ROS)^[10]. They are categorized on the basis of the number and arrangement of carbon atoms in flavonoids (flavonols, flavones, flavan-3-ols, anthocyanidins, flavanones, isoflavones and others) and non-flavonoids (phenolic acids, hydroxycinnamates, stilbenes and others). Flavonoids and hydroxycinnamic acids are the most common and heterogeneous group of polyphenols in Brassica species^[11]. Brassica vegetables also contain anthocyanins which cause pigmentation in red cabbage and broccoli sprouts. Glucosinolates are an important phytochemical group found in Brassica vegetables in quantities of 1,500-2,000 μg/g and especially high in Brussels cabbage, cabbage and broccoli^[12,13,14]. Glucosinolate is found in spices such as horseradish and mustard, made from roots and seeds of Brassica vegetables, at concentrations as high as 75,000 μg/g fresh weight^[15].Isothiocyanates are potentially anticarcinogenic phytochemicals that are metabolic product of glucosinolates^[16]. Approximately 100 isothiocyanates have been identified but only a few of them are common in the diet and are found in other selected foods as well as Brassica vegetables.

Cancer Protective Effects:

Cancer is a group of diseases involving abnormal cell growth with the potential to invade or spread to other parts of the body. These contrast with benign tumours , which do not spread.^[17] Possible signs and symptoms include a lump, abnormal bleeding, prolonged cough, unexplained weight loss, and a change in bowel movements .^[18]While these symptoms may indicate cancer, they can also have other causes.^[19] Over 100 types of cancers affect humans.

Tobacco use is the cause of about 22% of cancer deaths. Another 10% are due to obesity, poor diet, lack of physical activity or excessive drinking of alcohol. Other factors include certain infections, exposure to ionizing radiation and environmental pollutants. In the developing world, 15% of cancers are due to infections such as Helicobacter pylori, hepatitis B, hepatitis C, human papillomavirus infection, Epstein–Barr virus and human immunodeficiency virus (HIV). These factors act, at least partly, by changing the genes of a cell. Typically, many genetic changes are required before cancer develops. Approximately 5–10% of cancers are due to inherited genetic defects from a person's parents.^[20] Cancer can be detected by certain signs and symptoms or screening tests. It is then typically further investigated by medical imaging and confirmed by biopsy.

In 2015, about 90.5 million people had cancer. About 14.1 million new cases occur a year (not including skin cancer other than melanoma). It caused about 8.8 million deaths (15.7% of deaths). The most common types of cancer in males are lung cancer, prostate cancer, colorectal cancer and stomach cancer. In females, the most common types are breast cancer, colorectal cancer, lung cancer and cervical cancer. If skin cancer other than melanoma were included in total new cancer cases each year, it would account for around 40% of cases^.[20]In children, acute lymphoblastic leukemia and brain tumours are most common, except in Africa where non-Hodgkin lymphoma occurs more often. In 2012, about 165,000 children under 15 years of age were diagnosed with cancer. The risk of cancer increases significantly with age, and many cancers occur more commonly in developed countries. Rates are increasing as more people live to an old age and as lifestyle changes occur in the developing world.

The World Cancer Research Fund points out that diets being rich in Brassica vegetables protect human body especially from colon, rectum and thyroid cancers. In addition, when consumed in high quantities as part of the diet with other vegetables, Brassica vegetables usually have protective effects against cancer in other regions

[21].

This effect is also attributed to the compounds resulting from the hydrolysis. The ability of Brassica vegetable components to change bio-transformation enzyme expression. Also, its activities play an important role in cancer prevention. Bio-transformation of the components of Brassica nigra can detoxify compounds that can damage DNA by playing an important role in the regulation of the toxic, mutagenic and neoplastic effects of chemical carcinogens^[22]. In addition to their role in metabolizing carcinogens, Biotransformation enzymes can also metabolize endogenous compounds such as steroid hormones. Thus, by altering hormone exposure, it can indirectly affect the promotion and progression of premalignant and malignant tissues.

The mechanism also involves the induction of apoptosis which causes the deletion of genetically damaged cells and stopping the progression of the cell cycle. Isothiocyanates which induce apoptosis, inhibit cell cycle progression, inhibit angiogenesis, and shows anticarcinogenic properties.

Numerous mechanisms of action are proposed for potential cancer chemo-protective activity of organic isothiocyanates. The cytotoxicity of mustard derivatives on neuroblastoma cells has been investigated. The effects of organic isothiocyanates on P-glycoprotein and multidrug, resistance-associated, protein (MRP1) mediated transport in multidrug resistant (MDR) human cancer cell lines. Both P-glycoprotein and MRP1 are involved in the bioavailability, distribution, and elimination of many drugs. Dietary organic isothiocyanates inhibited the P-glycoprotein– and MRP1–mediated efflux of daunomycin and vinblastine in MDR human cancer cells, enhancing the efficacy of cancer chemotherapy.

Colorectal Cancer:

Colon cancer is the third most common cause of cancer related deaths. It is also known as bowel cancer and colon cancer, is the development of cancer from the colon or rectum (parts of the large intestine).^[23] A cancer is the abnormal growth of cells that have the ability to invade or spread to other parts of the body.^[24]Gupta US and Kim MK et al., was reported thata reduction in cancer risk is observed when high Brassica vegetable intake and low intake are compared. In clinical study, consumption of 250 g/day of broccoli and 250 g/day of Brussels sprouts was found to significantly increase excretion of a potentially carcinogenic 2-amino-1methyl-6-phenylimidazo [4,5-b] pyridine (PhIP) presented in well cooked meat. It was shown that high consumption of Brassica vegetables can reduce the risk of colorectal cancer by increasing the elimination of PhIP and diet-related heterocyclic amine carcinogens^[25]. In a multi-centre study, the risk of colorectal cancer was found to be less in the group with the highest consumption of broccoli according to the food frequency [26].

Lung cancer:

Lung cancer arises as a result of genetic lesions caused by exposure to smoking, bacterial, viral infections, oestrogens, and is the leading cause of death worldwide ^[27]. In many patients with lung cancer, the diseased area cannot be removed because of distant metastases or advanced lesions. Therefore, to reduce the incidence of lung cancer, protective dietary habits are an alternative approach^[28].

Abdull Razis A.F, et al., was reported the effects of various phytochemical agents on lung cells, GSTP1 and NQO1 inducers of phase II enzymes were investigated in humans. GSTP1 mRNA levels slightly increased after bronchial epithelial cells were exposed to NQO1 mRNA levels were found to be higher in sulphoraphane. NQO1 protein expression increased by 11.8 fold in sulphoraphane -treated bronchial epithelial cells^[29]. In this study investigating the effects of glucocinolates on cytochrome P450 and phase II enzyme activities in lung cells, glucosinolates at a concentration of 1 μM isolated from Brassica vegetables were incubated for 24 hours with cut rat liver slices. It was found that glucosinolates can modulate basic enzymes (cytochrome P450 and phase II enzymes) in pulmonary carcinogen metabolism, and thus Brassica vegetables was showed chemo preventive activity in the lung cell^[30].

Pawlik A, et al., was reported, the relationship between urinary isothiocyanate levels and lung cancer risk was investigated in non-smokers. Isothiocyanate levels in urine were not associated with lung cancer risk among non-smokers. However, in the secondary analyses, isothiocyanate levels in the urine were found to be an interaction between the GSTM1 genotype and lung cancer risk^[31]. In another study, isothiocyanates were found to exhibit cytotoxicity as dose-dependent in different lung adenocarcinomas (A549) and large cell lung carcinoma (H1299) cells (non-small cell lung cancer cell lines) in p53 status. While the effect of Brassica vegetable consumption on the risk of lung cancer is evaluated, it should be remembered that the benefits of consuming increasing amounts of Brassica vegetables are probably small compared to the benefit of giving up smoking^[32].

Breast Cancer:

Breast cancer is cancer that develops from breast tissue.^[33]Risk factors for developing breast cancer include being female, obesity, lack of physical exercise, drinking alcohol, hormone replacement therapy during menopause, ionizing radiation, early age at first menstruation, having children late or not at all, older age, prior history of breast cancer, and family history.^[34] About 5–10% of cases are due to genes inherited from a person's parents, Worldwide, breast cancer is the leading type of cancer in women, accounting for 25% of all cases. In 2018 it resulted in 2 million new cases and 627,000 deaths. It is more common in developed countries and is more than 100 times more common in women than in men.^[35]

Kim and Park, et al., reported that the consumption of some Brassica vegetables reduces the breast cancer risk. The endogenous oestrogen 17[beta]-oestradiol, 16ahydroxyestrona (16aOHE1) or 2-hydroxystreone (2OHE1) can be metabolized. In contrast to 2OHE1, 16aOHE1 is more estrogenic and oestrogen in culture has been found to increase sensitive breast cancer cells. Shifting 17β-oestradiol metabolism to 2OHE1 and staying away from 16aOHE1 can reduce the risk of oestrogen sensitive cancer, such as breast cancer^[36]. In another study, 2832 breast cancer women aged 50-74 years and 2650 healthy women’s diets were compared. It was reported that daily consumption of 1-2 portions of Brassica vegetable reduces the risk of breast cancer by 20-40%, possibly by altering the pathway of oestrogen metabolism^[37].

In this study measuring Brassica vegetable consumption with urinary isothiocyanate biomarker, excess consumption of Brassica vegetables was found to be associated with a significantly reduced risk of breast cancer in womens^[38]. In a case-control study of Caucasian women suffering from breast cancer, Brassica vegetable consumption, especially broccoli consumption, was negatively associated with breast cancer risk in premenopausal women^[39]. These findings suggest that Brassica vegetables may play a role in reducing the risk of breast cancer in pre menopausal women^[40].

Prostate cancer:

Prostate cancer is the most common solid tumour. Nutritional habits are associated with prostate cancer risk. The most reported finding about diet and prostate cancer is associated with increased risk of fat and high fat foods. However, developments of the understanding of cellular events leading to cancer and regulation of metabolic and genetic changes leading to cancer suggest that vegetable products may indeed play a role in prostate cancer^[41].

Steinbrecher A and Higdon JV et al.,^[42]was reported that an induction of Brassica vegetables and GST-π in cell culture models is particularly concerned with prostate cancer. GST-π is the predominant GST active in prostate tissue and expression of this gene disappears in the prostate cancer, prostate cancer precursor lesion and prostate intra epithelial neoplasm. Loss of GST-π appears to be an important step in the early development of prostate cancer, and it is thought that upregulation of this gene may provide protection against prostate cancer growth^[43].

A population-based case-control study in which consumption of 28 or more portions of vegetables per week was compared with 14 or fewer portions of vegetables per week, it was found that a high level of consumption of vegetables, especially Brassica vegetables, reduces the risk of prostate cancer in prostate cancer patients under the age of 65^[44]. Similarly, in another case-control study, Brassica vegetable consumption was found to reduce the risk of prostate cancer^[45]. Taking high amounts of Brassica vegetables, including broccoli and cauliflower, can reduce the risk of advanced prostate cancer and especially metastatic prostate cancer. Although glucosinolate hydrolysis products were found to inhibit the growth of cultured prostate cancer cells and induce apoptosis, the results of epidemiological studies of Brassica vegetable intake and prostate cancer risk are inconsistent.

Pancreatic Cancer:

In worldwide pancreatic cancer is the fifth and fourth cause of cancer-related deaths, respectively. This type of cancer is usually diagnosed at an advanced stage and for this reason its prognosis is very poor^[46].

Ohara M and Larsson SC, et al.,^[47]was report, that among specific subgroups of fruits and vegetables, a non-significant inverse correlation was observed between Brassica vegetable consumption of three or more servings per week and consuming one serving of Brassica vegetable per week. There was a statistically significant lower risk of pancreatic cancer, when people consuming one or more portions of Brassica nigra^[48]. Investigating the effects of benzyl isothiocyanate (BITC), one of the isothiocyanate family, on radiation sensitivity of human pancreatic cancer cells, two human pancreatic cancer cell lines were treated with BITC and then exposed to X-rays, resulting in an increase in the number of apoptotic cells. It was concluded that BITC has the potential to be a supplement to the existing radiation therapy for pancreatic carcinoma^[49].

Bladder Cancer:

Increased risk of urothelial bladder cancer in humans is associated with GST or NQO1 deficiency^[50]. The main place of bladder cancer development is the bladder epithelium. Isothiocyanates present in Brassica vegetables are delivered to the bladder epithelium by urinary excretion, where they protect the cells against cancer^[51].

It was reported by Bhattacharya A, et al.,^[52^]that isothiocyanate extract obtained from broccoli sprouts significantly induces both GST and quinone oxido reductase in bladder tissues and cells of mice^[53]. It evaluating the specific role of Brassica vegetables or isothiocyanates in the diet against bladder cancer, a Brassica nigra extract showed that human bladder carcinoma cells inhibit growth and almost all of this inhibition results from due to isothiocyanates^[54].

The Health Professionals Follow-up Study also reported a non-significant inverse association between total fruit and vegetable intake and the risk of bladder cancer. However, it was found that consumption Brassica nigra was significantly associated with the risk of bladder cancer. These observations suggest that high Brassica consumption may reduce the risk of bladder cancer^[55,56].

In a study of 697 newly diagnosed bladder carcinoma patients and a control group, it was shown that isothiocyanates from Brassica vegetable consumption are protective against bladder cancer was reported by Zhao H, et al.,^[^57]Isothiocyanate intake was negatively correlated with the risk of bladder cancer and this effect was shown to be stronger in non-smokers than in heavy smokers^[58].

In another study was reported by Munday. R, et al.,^[59^] an application of freeze-dried Brassica nigra extracts to rats was found to inhibit the development of N-butyl-N- (4hydroxybutyl) nitrosamine-induced bladder cancer in a significant and dose-dependent manner without causing histological alteration in the bladder^[60]. Isothiocyanate extract in Brassica vegetables is a potent stimulant of GST and quinone oxido reductase 1 in the bladder, and is a promising agent to prevent bladder cancer. Furthermore, the major isothiocyanate, sulphoraphane found in Brassica nigra extracts not only induces enzymes that detoxify carcinogens, but also activates apoptosis and blocks cell cycle progression^[61].

Liver cancer:

Liver cancer is one of the leading causes of cancer death worldwide. A very high incidence of new liver cancer cases is diagnosed every year, and metastasis has been found to correlate to poor prognoses in humans. Better treatments for liver cancer are thus clearly needed.

Chen YJ, et al.,^[62]was reported that sinigrin is one of the major ingredients present in Brassica nigra, which has been used in combination with other herbs for treatment of various diseases. The anti-proliferative activities of sinigrin were studied in a model of carcinogen-induced hepatotoxicity in rats. It was found to significantly inhibit the proliferation of liver tumour cells; the number of surface tumour in the rat liver was dramatically reduced. Sinigrin induced apoptosis of liver cancer cells through up-regulation of p53 and downregulation of Bcl-2 family members and caspases. Cell cycle analysis indicated that sinigrin caused cell cycle arrest in G0/G1 phase. The results suggest that sinigrin exerts important anti-proliferative activities in carcinogen-induced hepato-carcinogenesis and highlight the potential of sinigrin as an anti-cancer agent for liver cancer^[62].

CONCLUSION:

Brassica nigra is easily available in worldwide and plantation also easy. In all spicy foods we are adding this mustard seed and is possible to eat from child age to older age people it doesn’t produce any side effects.

Brassica vegetables contain compounds that are rich in sulphur known as glucosinolates. Bioactive hydrolysis products of glucosinolate such as isothiocyanates and indole-3-carbinol. Glucosinolates is involved in relatively high concentrations in these vegetables; and the presence of sinigrin, sulpharphane, allyl isothiocyanates are mainly involved in apoptosis, inhibit cell cycle progression, inhibit angiogenesis, and shows anti-carcinogenic properties. From the available data reveal that the consumption of vegetables belonging to only Brassica nigra reduces risk of diseases and might narrow the metastasis of tumours. Based on the above studies our future study mainly concentrate consumption of this Brassica nigra may also reduce the risk of cervical cancer.

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Received on 22.01.2020 Modified on 01.03.2020

Research J. Pharm. and Tech. 2021; 14(2):1115-1121.

DOI: 10.5958/0974-360X.2021.00201.8