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Phytohaemagglutinin - an overview | ScienceDirect Topics

Lectins and phytohemagglutinins (PHA) are natural toxicants present in many foods, especially in beans and other dietary pulses, which can have toxic effects ...

Abstract

Calorie restriction (CR) is arguably the most potent, broadly acting dietary regimen for suppressing the carcinogenesis process, and many of the key studies in this field have been published in Carcinogenesis . Translation of the knowledge gained from CR research in animal models to cancer prevention strategies in humans is urgently needed given the worldwide obesity epidemic and the established link between obesity and increased risk of many cancers. This review synthesizes the evidence on key biological mechanisms underlying many of the beneficial effects of CR, with particular emphasis on the impact of CR on growth factor signaling pathways and inflammatory processes and on the emerging development of pharmacological mimetics of CR. These approaches will facilitate the translation of CR research into effective strategies for cancer prevention in humans...........

Issue Section: cancer prevention

Indexed for Oxford Academic by Dragonfly Kingdom Library

https://academic.oup.com/carcin/article/31/1/83/2393947?login=false

Daily caloric restriction limits tumor growth more effectively than caloric cycling regardless of dietary composition

Laura C. D. Pomatto-Watson, Monica Bodogai, Oye Bosompra, Jonathan Kato, Sarah Wong, Melissa Carpenter, Eleonora Duregon, Dolly Chowdhury, Priya Krishna, Sandy Ng, Emeline Ragonnaud, Roberto Salgado, Paula Gonzalez Ericsson, Alberto Diaz-Ruiz, Michel Bernier, Nathan L. Price, Arya Biragyn, Valter D. Longo & Rafael de Cabo 

Nature Communications volume 12, Article number: 6201 (2021) 

Abstract

Cancer incidence increases with age and is a leading cause of death. Caloric restriction (CR) confers benefits on health and survival and delays cancer. However, due to CR’s stringency, dietary alternatives offering the same cancer protection have become increasingly attractive. Short cycles of a plant-based diet designed to mimic fasting (FMD) are protective against tumorigenesis without the chronic restriction of calories. Yet, it is unclear whether the fasting time, level of dietary restriction, or nutrient composition is the primary driver behind cancer protection. Using a breast cancer model in mice, we compare the potency of daily CR to that of periodic caloric cycling on FMD or an isocaloric standard laboratory chow against primary tumor growth and metastatic burden. Here, we report that daily CR provides greater protection against tumor growth and metastasis to the lung, which may be in part due to the unique immune signature observed with daily CR.

Introduction

Caloric restriction (CR) is the most effective intervention to reduce the incidence and progression of most spontaneous and induced cancers. Due to the stringency of CR and its associated limitations, including low compliance among study participants and impaired wound healing1, alternative dietary interventions are increasingly being considered as viable strategies to combat cancer. These approaches that include modifications of feeding frequency, diet composition, and or length of fasting often recapitulate CR-mediated benefits by conferring cancer protection2. Much of the improvement from daily CR is attributed to a sustained reduction in overall caloric intake and periods of prolonged fasting2, a frequently overlooked variable that contributes not only to the activation of cellular maintenance and repair pathways, but also to extending health and survival3. Most CR regimens utilize a once-a-day feeding protocol which, depending on the level of restriction, can lead to a fasting period of up to 22 h2,4.

Earlier work has shown that short periods of very low caloric intake, including either periods of short-term fasting (2–4 days) or dietary manipulation of specific macronutrients, can be effective at delaying primary tumor growth4,5. Conversely, excess consumption of animal-derived protein is linked with increased cancer risk and all-cause mortality6,7. Different forms of intermittent fasting (IF) and time-restricted feeding (TRF)2,3 are broadly characterized by cyclical periods of low caloric intake or complete fasting interspersed between periods of ad libitum (AL) feeding. IF and TRF result in a dramatic reduction in tumor growth8,9 and have garnered traction both as an adjuvant to chemotherapy and as a tool for cancer prevention with promising translational applications10,11.

Periods of prolonged fasting result in decreased circulating blood glucose and IGF-1 signaling in target tissues10, thus dampening tumor growth. Under low glucose conditions, normal cells undergo growth arrest, whereas malignant cells no longer respond to these conditions and maintain uncontrolled cell division. Consequently, a striking difference in the response of normal and cancerous cells to chemotherapy under fasting conditions has emerged, whereby normal cells, but not cancer cells, are protected from the cell-killing actions of anticancer drugs12. Therefore, much interest has centered on developing dietary approaches that recapitulate the selective targeting of cancer cells without the burden of CR. A plant-based diet, recently designed to mimic the physiological response to fasting (‘fasting mimicking diet’, FMD), was developed to minimize the burden of fasting while providing adequate micronutrients (vitamins, minerals, etc.), and to elicit beneficial improvements in metabolic parameters13. Periodic cycles (4-day cycle twice a month) of FMD followed by AL feeding promote health span in mice and humans13 and confer protection against primary tumorigenesis, with or without chemotherapy14,15,16,17. This approach was also demonstrated to lower toxicity to chemotherapy in clinical trials18.

Although these findings highlight the important role dietary interventions play in regulating tumor growth, it remains unclear whether the anti-tumorigenic benefits of CR, IF, and FMD are mediated by the salutary effect of diet composition, reduction in caloric intake, duration of fasting, or a combination of all these elements. In one study, Brandhorst et al. showed that 3-day cycles of 50% CR combined with chemotherapy did not delay tumor progression in a 4T1 breast cancer mouse model19. In contrast, severe protein restriction in an otherwise isocaloric diet was shown to slow down the progression of melanoma, but not breast cancer or glioma6,19.

In this work, we assess the relative impact of diet composition vs. low caloric intake in delaying tumor growth in the 4T1 breast cancer mouse model. Tumor-bearing mice are subjected to two 4:10 feeding cycles, with 4 days of severe reduction in caloric intake in animals fed either FMD or standard laboratory chow (AIN-93G), followed by 10 days of AL feeding with AIN-93G. Using this approach, we have been able to evaluate the extent to which diet composition impacts the response to 4:10 feeding cycles and whether this approach is as effective as daily CR at delaying tumorigenesis. Our findings show that compared to daily CR, 4:10 feeding cycles are less effective and fail to protect against lung metastases, regardless of diet composition or treatment initiation period (pre- or post-4T1 injection). Importantly, daily CR elicits a unique signature of immune activation by significantly reducing the number of tumor-promoting immune cells (CD11b+Gr1+), while upregulating tumor-fighting (CD8+ and CD4+) immune cells in peripheral tissues. These findings suggest that the duration and degree of CR are the most critical factors in determining protection against cancer progression in the 4T1 murine breast cancer model.

Results

Low-calorie cycles slow tumor growth independent of diet composition

The impact of diet composition and 4:10 feeding cycles on the growth rate of triple-negative breast cancer (TNBC) was studied in 16-week-old female BALB/cJ mice implanted with syngeneic and highly metastatic murine 4T1 cancer cells in the mammary gland. The responses of 4:10 cycles of FMD vs. an isocaloric standard laboratory chow (AIN-93G), also known as ‘low caloric cycling diet’ (LCC), were compared. During the four days of severe low-calorie intake, FMD and LCC mice were exposed to a 50%:70%:70%:70% reduction in daily calories, followed by 10 days of AL feeding with AIN-93G diet (Fig. 1a, Supplementary Fig. 1a). One week after injection of 4T1 tumor cells, mice that were subjected to two 4:10 cycles of FMD or LCC (Fig. 1b) showed similar declines in tumor growth rate (Fig. 1c) and tumor area (Fig. 1d) compared to AL controls. FMD and LCC mice had identical body weight (Fig. 1e, Supplementary Fig. 1b) and food consumption (Fig. 1g) trajectories during the two cycles, with an overall decrease both in the average body weight (Fig. 1f) and caloric intake (Fig. 1h) across the 28-day period. These results suggest that cycles of very low-calorie intake, rather than diet composition per se, are the main driver behind delayed tumorigenesis....... https://www.nature.com/articles/s41467-021-26431-4

Indexed for Springer Nature/Nature Journal by Dragonfly Kingdom Library 

https://doi.org/10.1016/j.sjbs.2022.03.005

Abstract

From onset to progression, cancer is a ailment that might take years to grow. All common epithelial malignancies, have a long latency period, frequently 20 years or more, different gene may contain uncountable mutations if they are clinically detectable. MicroRNAs (miRNAs) are around 22nt non-coding RNAs that control gene expression sequence-specifically through translational inhibition or messenger degradation of RNA (mRNA). Epigenetic processes of miRNA control genetic variants through genomic DNA methylation, post-translation histone modification, rework of the chromatin, and microRNAs. The field of miRNAs has opened a new era in understanding small non-coding RNAs since discovering their fundamental mechanisms of action. MiRNAs have been found in viruses, plants, and animals through molecular cloning and bioinformatics approaches. Phytochemicals can invert the epigenetic aberrations, a leading cause of the cancers of various organs, and act as an inhibitor of these changes. The advantage of phytochemicals is that they only function on cells that cause cancer without affecting normal cells. Phytochemicals appear to play a significant character in modulating miRNA expression, which is linked to variations in oncogenes, tumor suppressors, and cancer-derived protein production, according to several studies. In addition to standard anti-oxidant or anti-inflammatory properties, the initial epigenetic changes associated with cancer prevention may be modulated by many polyphenols. In correlation with miRNA and epigenetic factors to treat cancer some of the phytochemicals, including polyphenols, curcumin, resveratrol, indole-3-carbinol are studied in this article.

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Keywords

Natural productsmiRNACancerEpigenetic factor

1. Introduction

Despite advances in medicine, cancer is now the world's leading death cause. Now need a more safe and effective strategy for cancer prevention. Treatment through dietary phytochemicals is preferable due to its safety, easy access, and less toxicity (Pratheeshkumar, Son, Korangath, Manu, & Siveen, 2015). Many epidemiological studies and research based on diet intervention in human beings using experimental animals have provided us much evidence to recommend the progression of the huge variety of neoplasms due to the lifestyle of humans and many environmental factors. The etiology of human cancer is focused on organic carcinogens, toxins in the atmosphere, physical carcinogens, and dietary impurity (LISOUZA, 2021).

On the other hand, some lifestyle factors can also enhance the progression and development of cancer like smoking, enhanced consumption of fat, exposure to sunlight, consumption of an increased amount of alcohol, and chronic stress. It has also been proposed that mother-nutrition imbalances or metabolic abnormalities during embryo development adversely affect the health of offspring and may be inherited. The adverse effect of genetic and epigenetic events may consider as Carcinogenic (Shankar, Kumar, & Srivastava, 2013).

Micro RNAs are minor, non-coding RNAs and almost 20–24 nucleotides involved in genetic material and cell signaling regulation. About 2469 miRNAs are detected in an individual, and many researchers have considered that miRNA dysregulation performs a substantial part in the growth of cancer (Acunzo, Romano, Wernicke, & Croce, 2015). Many plant chemicals can regulate the manifestation of many non-coding RNAs, which are cancer-associated (Debnath, Nath, Kim, & Lee, 2017). Currently, the expression of non-coding RNAs has conclusively related to cancer growth, and the profile of miRNA can be applied to categorize human cancers (Jansson & Lund, 2012). RNA polymerase II miRNAs are generally transcribed and encoded in our genome (Chuang & Jones, 2007). The role of human microRNAs within various kinds of cancer can be described by their transcriptional targets and level of expression in that way up-regulated micro RNAs are under oncogenic classification in comparison to down-regulated undergo classification of tumor suppressors (Hargraves, He, & Firestone, 2016).

The carcinogenic side effects are hereditary and epigenetic. Linear changes are created in epigenetics, but not in gene expression due to fluctuations in the DNA structure. In cell life, epigenetic mechanisms have always existed. This comprises DNA methylation, microRNA expression, histone modifications, chromatin remodeling, and multi-gene expression non-coding RNA silencing. Many studies revealed that epigenetic events are the leading cause of cancer (S. Sharma, Kelly, & Jones, 2010) and involve the inactivation of retrotransposons through genomic instability (Kanwal and Gupta, 2010, Shukla et al., 2014). The vital epigenetic processes for gene expression regulation are methylation of DNA, chromatin alteration by histone and non-histone proteins post-translational modifications, and micro RNA (non-coding RNA), which can degrade messenger RNA, or their process of translation undergo modulation. In regulating the proper functioning of cells at all stages, these epigenetic changes include development and differentiation. However, modification in targets of epigenetic events may also lead to many life-threatening diseases, including cancer (Thakur, Deb, Babcook, & Gupta, 2014). miRNAs correlated with epigenetic events that might also show a substantial part in the control of methylation of DNA and histone modifications (Chuang and Jones, 2007, Schröder et al., 2021, Sun et al., 2021).

There are a wide range of methods of treating cancer, including chemotherapy and synthetic medicines. Plant extract for disease treatment is as early as civilization and traditional medicines before forming an enormous part of the routine treatment of various diseases (Gavamukulya, Abou-Elella, Wamunyokoli, & AEl-Shemy, 2014). Rendering to the suggestion of the world health organization (WHO), almost all developed countries are moving back toward the conventional medicinal system. Approximately 65% of the world's overall population has integrated the value of herbs used as an herbal medicine for health care. It is estimated that almost 25% of total drugs authorized nowadays are derived from plants (Mukhopadhyay, Banerjee, & Nath, 2012).

Plant extracted chemicals have various valuable properties, and they can use against inflammation and have anti-cancerous properties (Gavamukulya et al., 2014). The source of these phytochemicals are vegetables, herbs, fruits, many dietary supplements, and beverages. Therefore, consuming food that is rich in vegetables and fruit can minimize the cancer risk. Almost 47% of drugs against cancer are plant-based, which is affiliated with the FDA (Debnath et al., 2017). Nearby not before a decade, researches show that plant extracted chemicals could target the functioning of many epigenetic events, like DNMTs and HDACs it might be effective to stop and remedy many ailments involving cancer (Mortoglou et al., 2021, W. Watson et al., 2013). In correlation with miRNA and epigenetic factors to treat cancer some of the phytochemicals including tea polyphenols, curcumin, resveratrol, indole-3-carbinol (Shukla et al., 2014)........... 

Indexed for Saudi Journal of Biological Sciences via Science Direct by Dragonfly Kingdom Library

https://www.sciencedirect.com/science/article/pii/S1319562X22001498

Published online 2021 Apr 7. doi: 10.3390/nu13041212

PMCID: PMC8067583

PMID: 33916931

The Anticancer Effects of Flavonoids through miRNAs Modulations in Triple-Negative Breast Cancer

Getinet M. Adinew, Equar Taka, Patricia Mendonca, Samia S. Messeha, and Karam F. A. Soliman*

Raffaella Canali, Academic Editor and Fausta Natella, Academic Editor

Abstract

Triple- negative breast cancer (TNBC) incidence rate has regularly risen over the last decades and is expected to increase in the future. Finding novel treatment options with minimum or no toxicity is of great importance in treating or preventing TNBC. Flavonoids are new attractive molecules that might fulfill this promising therapeutic option. Flavonoids have shown many biological activities, including antioxidant, anti-inflammatory, and anticancer effects. In addition to their anticancer effects by arresting the cell cycle, inducing apoptosis, and suppressing cancer cell proliferation, flavonoids can modulate non-coding microRNAs (miRNAs) function. Several preclinical and epidemiological studies indicate the possible therapeutic potential of these compounds. Flavonoids display a unique ability to change miRNAs’ levels via different mechanisms, either by suppressing oncogenic miRNAs or activating oncosuppressor miRNAs or affecting transcriptional, epigenetic miRNA processing in TNBC. Flavonoids are not only involved in the regulation of miRNA-mediated cancer initiation, growth, proliferation, differentiation, invasion, metastasis, and epithelial-to-mesenchymal transition (EMT), but also control miRNAs-mediated biological processes that significantly impact TNBC, such as cell cycle, immune system, mitochondrial dysregulation, modulating signaling pathways, inflammation, and angiogenesis. In this review, we highlighted the role of miRNAs in TNBC cancer progression and the effect of flavonoids on miRNA regulation, emphasizing their anticipated role in the prevention and treatment of TNBC.

Keywords: cancer, flavonoid, microRNA, triple-negative breast cancer

1. Introduction

Globally, breast cancer (BC) is the major and most common repeatedly diagnosed cancer in women, which accounts for 30% of new female cancer cases [1], and also the second cause of death in women worldwide [2]. Approximately 1 million breast cancer cases are diagnosed annually worldwide [3]. In the United States, more than 276,000 new breast cancer cases were estimated by the end of 2020, and 12.9% of all women will be diagnosed with breast cancer over their lifetime [4,5,6,7]. Approximately 15% of breast cancers are categorized as triple- negative breast cancer (TNBC), characterized by a poor prognosis, early relapse, distant recurrence, unresponsiveness to conventional treatment, aggressive tumor growth, aggressive clinical demonstration, and lowest survival rate [8]. Compared with other BC subtypes, TNBC is more often associated with hereditary conditions. Evidence showed that among newly diagnosed BC patients, around 35% of BC suppressor protein1 (BRCA1) and 8% of BC suppressor protein2 (BRCA2) mutations in this population were TNBC [9]. Lack of progesterone (PR), estrogen (ER), and human epidermal growth factor receptor 2 (HER2) receptors are the major features of TNBC [10]. Recently, according to intrinsic gene signature, TNBC can be classified into six main types: basal-like 1 and 2, mesenchymal stem-like, immunomodulatory, mesenchymal, and luminal androgen receptor [11]. Of the TNBC cases, an estimated 75% are basal-like [12]. The prevalence of TNBC in African American women is higher than non-African American women. Indeed, 39% of African American premenopausal women diagnosed with BC are TNBC [13]. Previously reported studies revealed the continuous increase in BC incidence rate over the last decades and in the future [14].

Chemotherapy and radiotherapy are the two most common treatment strategies for TNBC patients in the early or advanced stages [15]. Compared to hormone receptor-positive patients, TNBC patients initially respond to conventional chemotherapy. However, the frequent disease relapse results in the worst outcome and low survival rate due to high metastasis rates and lack of effective treatment after relapse [16,17]. Although chemoresistance is a challenge that accounts for a significant share of drug failures [18], chemotherapy remains the primary cancer treatment approach. It is the only agent approved by the Food and Drug Administration (FDA) in treating nonmetastatic TNBC [19]. Even though the mechanism of resistance depends on the chemotherapeutic agent and patient; drug inactivation, drug target alteration, DNA damage repair, cell death inhibition, cancer cell heterogeneity, epigenetic alteration, and epithelial–mesenchymal transition or combination of these are the major direct or indirect contributing factor for developing resistance against cancer chemotherapeutic agents [18]. In TNBC cells, epigenetic mechanisms are implicated in chemotherapy resistance. For instance, an inherent defect in drug uptake and a lack of reduced folate carrier expression is the main cause of methotrexate resistance in MDA-MB-231 cells. However, treating MDA-MB-231 cells with DNA methylation inhibitor or reduced folate carrier cDNA was previously reported to restore methotrexate uptake and enhance sensitivity to methotrexate [20].

MicroRNAs were identified to be correlated with chemoresistance in TNBC. For instance, resistance to neoadjuvant chemotherapy was strongly linked to upregulated miR-181a [21]. Similarly, in the MDA-MB-231 cell line, upregulation of miR-21-3p, miR-155-5p, miR-181a-5p, miR-181b-5p, 183-5p and downregulation of miR-10b-5p, miR-31-5p, miR-125b-5p, miR-195-5p, and miR-451a were associated with doxorubicin resistance [22,23]. Moreover, downregulation of miR-200c was associated with doxorubicin resistance, poor response to radiotherapy, and increased multidrug resistance mediated gene expression [24]. Taken all together, chemoresistance is still a challenge in preventing and treating TNBC, and finding the best options is needed to manage the disease by developing drugs that combat the resistance gene or any target molecules of TNBC, miRNAs.

This review focuses on the anticancer properties of flavonoids in TNBC through miRNA regulation, utilizing compounds that target various pathways involved in cancer initiation, growth, proliferation, differentiation, survival, migration, invasiveness metastasis, and epithelial-to-mesenchymal transition (EMT). Additionally, the miRNA mechanism of action on cancer proliferation, cell cycle, immune system, mitochondrial dysregulation, modulating signaling pathways, inflammation, angiogenesis, invasion and metastasis, and apoptosis will be examined.......... 

Indexed for MDPI Nutrients/NIH by Dragonfly Kingdom Library

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8067583/

Abstract

Cancer is traditionally considered a genetic disease. It starts with a gene mutation, often caused by environmental carcinogens that are enzymatically activated to metabolites that covalently bind to DNA. If these now-damaged carcinogen-DNA adducts are not repaired before the cell replicates, they result in a mutation, which is inherited by daughter cells and their subsequent progeny. Still more mutations are added that are thought to advance cellular independence, metastasis, and drug resistance, among other characteristics typically observed for advanced cancer. The stages of initiation, promotion and progression of cancer by mutations infer irreversibility because back mutations are exceedingly rare. Thus, treatment protocols typically are designed to remove or kill cancer cells by surgery, chemotherapy, immunotherapy and/or radiotherapy. However, empirical evidence has existed to show a fundamentally different treatment option. For example, the promotion of cancer growth and development in laboratory animals initiated by a powerful mutagen/carcinogen can be repetitively turned on and off by non-mutagenic mechanisms, even completely, by modifying the consumption of protein at relevant levels of intake. Similar but less substantiated evidence also exists for other nutrients and other cancer types. This suggests that ultimate cancer development is primarily a nutrition-responsive disease rather than a genetic disease, with the understanding that nutrition is a comprehensive, wholistic biological effect that reflects the natural contents of nutrients and related substances in whole, intact food. This perspective sharply contrasts with the contemporary inference that nutrition is the summation of individual nutrients acting independently. The spelling of ‘holism’ with the ‘w’ is meant to emphasize the empirical basis for this function. The proposition that wholistic nutrition controls and even reverses disease development suggests that cancer may be treated by nutritional intervention.

Keywords: cancer treatment, cancer mutations, cancer etiology, cancer prevention

Introduction

A new perspective is needed on the failed War on Cancer begun 46 years ago by President Nixon because there is little or no convincing evidence that this project has specifically decreased the all-important rates of cancer. There certainly has been progress, however, in understanding this exceptionally complex disease. Newer methods for research and possible treatment protocols have been developed. For example, much has been learned about the fascinating but especially complex genetic basis for cancer and clever proposals have been made to re-engineer components of the immune system to treat cancer(1). But these advances have not yet changed overall cancer rates or have identified a ‘cure’ for cancer.

Cytotoxic chemotherapy, radiotherapy and surgery are still the traditional treatments of cancer, hopefully leading to the selective killing of cancer cells while minimizing damage to the neighboring normal cells. Except for the promises offered by novel versions of immunotherapy and a better understanding of the underlying genetics, cancer is still on the public’s mind as the same costly, dreaded disease that it has always been. Consider, for example, an ominous 2004 report showing that cytotoxic chemotherapy (for 22 types of cancer) increases 5-year survival only by 2.1%(2) while the cost of developing a new cancer drug approximates $2 billion. This cannot sustain public support, especially when a placebo effect might be as high or higher than the 2.1%.

Having been in the cancer research community for more than 60 years, I am well aware that progress in controlling this extraordinarily complex disease has been difficult. I contend that it will stay difficult, however, because of an inadequate understanding of its basic biochemistry as well as the basic biochemistry of nutrition, which is a major effector of cancer development. I suggest that this concept of complexity for both disciplines is seriously underestimated or, at best, is seriously oversimplified, thus the association of diet with cancer cannot be fully understood. For example, consider the landmark 1981 report on diet and cancer submitted to the Office of Technology Assessment of the U.S. Congress which concluded that 35% of total cancer was attributed to diet(3), with estimates by some authorities surveyed for that report being as high as 70%. The 35% estimate of diet-attributable cancer has been widely cited by many authorities and institutions ever since 1981, often as the dietary causation of one-third of all cancers. But this evidence mostly referred to associations of specific nutrients with specific cancers. Is it possible that this is an over-simplification of this obviously complex diet-cancer relationship? Also, does the well-established belief that cancer is a genetic disease moot the nutritional contribution to cancer? The objective of this paper therefore is to encourage discussion of the fundamental relationship of nutrition with cancer, mainly centered on the unusual complexity of the underlying biology of each process.

Most conventional wisdom holds that research interest in the effect of diet on cancer began in earnest during the 1940s to 1960s (summarized by the National Academy of Sciences in 1982)(4). Laboratory animal studies were showing that experimental tumor formation, initiated by chemical carcinogens, was increased by consumption of nutrients like fat, animal protein and/or calories,(4) which generally represented the effects of diets rich in animal-based foods.(4, 5) The emphasis was on the cancer modifying (not initiating) effects of nutrients, which were mostly investigated as single agents in laboratory animal experiments.

Later, in the 1960s and 1970s, diet and cancer research turned toward human population studies that correlated cancer rates with foods, generally explained by their nutrient contents(6– The most cited correlations were those of dietary fat with breast(7, 9–14) and colon cancers(15, 16) and dietary fiber with large bowel cancer(17, 18) The consumption of nutrients of animal-based foods were associated with increased cancer risk while nutrients of plant-based food were associated with decreasing risk.

However, instead of nutrients explaining the association of food with cancer, another school of thought suggested that certain non-nutrient (environmental) chemicals in food were more responsible, especially those that caused genetic mutations. This concern with environmental chemicals was highlighted with the so-called cranberry scare during the late 1950s when evidence suggested that a herbicide sprayed on cranberries, aminotriazole, caused thyroid cancer in laboratory animals, a highly publicized report that almost wiped out the cranberry season that year.(19) The cancer properties of environmental chemicals became highly publicized and politicized, resulting in a 1958 amendment to the Food and Drug Act, famously called the Delaney Clause, which demanded zero tolerance of chemical carcinogens in food (reviewed elsewhere(20, 21)). Also, at about this same time, the publication of the popular book “Silent Spring” by Rachel Carson generated widespread public attention on the possible health hazards of environmental chemicals for human health and, in the views of many, led to the founding in the early 1970s of the U.S. Environmental Protection Agency.(22)

Somewhat before this time (1950s), in a related development, the Watson and Crick model for DNA structure and function was elucidated, cementing the idea that all biological events arise from genes and, for cancer, probably from genes that were mutated. This convergence of events (mutation of cancer by environmental chemicals and associations of diet with cancer), therefore, required a technology to search for and test environmental chemicals (mostly in food) that might cause cancer in humans. Because no simple lab-based method was available for this purpose, an animal bioassay program(23–25) was developed, the results of which were used to estimate human cancer risk contributed by these environmental chemicals.(25)

This bioassay program gradually evolved over 2–3 decades, involving the participation of three government agencies (two US, one WHO). Experimentally, this bioassay program required 1) the testing of candidate chemicals in both sexes of two species of animals (mostly rats and mice but sometimes dogs and/or monkeys in earlier years), 2) four experimental groups (dietary control group, a group fed 100 times the amount of suspect chemical anticipated for human food, a group fed the maximum tolerated dose of this chemical, and an intermediate dose group), 3) two-year lifetime studies, and 4) a histological search for tumors at the end of the study.(26) Although the cost of testing one candidate chemical in 1961 was $10,000 to $15,000, it eventually rose to $2–4 million in 2009, based on the testing for carcinogenicity in two species.(26)

As time passed, this bioassay program also became more comprehensive in order to include other toxicological responses. Certain pharmaceutical products, like oral contraceptives, require longer test periods up to ten years and the use of species (dogs, monkeys) that were deemed more appropriate for human comparison. In recent years, efforts have been made to refine dose selection, number of dose groups, control group characteristics, choice of animal species/strain and duration of study, among other experimental parameters.(26, 27)

Estimates of human risk from the results of this bioassay program requires both high dose to low dose interpolation and species to species extrapolation, which have been highly debatable exercises.(28, 29) For much of the earlier history of this program, it also was assumed that candidate chemicals for testing were those that cause mutations to initiate cancer. This program continues until the present day(27) although more recently, chemicals capable of promoting cancer without being mutagenic also may be called carcinogens.(30, 31) This program is now more than a half-century old but it is still beset with concerns about its purpose and its relevance, as was first questioned more than three decades ago.(20, 32, 33) A decade later, in 1995, it was refered to as “archaic cancer research” but it still survives, having created a profound belief in the idea that it is our exposure to environmental chemicals that chiefly cause human cancer}.(33)

Explaining how food associates with cancer during the past half-century, therefore, fundamentally depended on two hypotheses, one focused on environmental chemicals that are mutagenic and carcinogenic, the other on nutrients that are not mutagenic. There is no doubt that most public interest in the food and cancer connection was and still is focused on carcinogens that cause mutations. Aside for the testing of single chemicals in the animal bioassay program, this led many years ago to the development of non-animal, short-term, lab-based assays, the most popular being the Ames assay.(34, 35) It tested the in vitro ability of suspect chemicals to cause mutations in bacterial and other cell cultures, perhaps as a surrogate or as a replacement for the animal bioassay.

Because nutrients are not mutagenic and are not investigated by this bioassay program, other mechanisms for their cancer enhancing effects were sought during the 1970s and 1980s. A private research organization, the American Health Foundation, became particularly active in seeking mechanistic explanations, investigating, for example, how circulating estrogens(36, 37) might explain dietary fat and fiber effects on breast cancer,(38, 39) and how bile acid activities(40) might explain large bowel cancer. Findings from other researchers concerned the effect of calorie consumption and energy metabolism on various cancers(41, 42)and the antioxidant activity of vitamin A,(43) especially β-carotene,(44) on lung cancer. In laboratory rodent studies, animal-based protein increased mammary cancer, perhaps related to its effect on estrogenic hormone activities,(45–47) while its effect on neoplastic(48) and pre-neoplastic liver cancer development(49–51) was unusually impressive. Dietary animal-based protein at a level of 20% (of total calories) dramatically increased while 5% dietary protein decreased cancer development through the participation of multiple mechanisms acting simultaneously.(21, 52–55) None of these nutrient-based effects was attributed to mutations because increased activities were readily reversible, both ways.

In 1975, a seminal conference sponsored by the American Health Foundation(8) featured migration patterns (56, 57) and time-dependent trends(58, 59) on cancer risk, both implicating dietary and environmental causation. A few years later, the U.S. National Academy of Sciences provided funding through the U.S. National Cancer Institute (of NIH), for a committee to undertake a three-year project to review these emerging findings, resulting in a seminal 1982 report,(4) Diet, Nutrition and Cancer along with a 1983 report(60) on suggestions for research. This coincided with the previously cited report on diet and cancer(3) which concluded that diet was responsible for a higher proportion of avoidable cancer deaths than even smoking, with estimates that a dietary contribution could be as high as 70%. This same report concluded that genetic predisposition accounted for only 2–4% of avoidable cancer deaths. Thereafter, several institutionally funded summaries of studies on diet and cancer were published over the next quarter century mostly referring to the same conclusion that diet was responsible for about one-third of all cancers.(5, 61–64) This meant diets high in animal-based meat, dairy and eggs and low in plant-based vegetables, fruits, whole grains and legumes. Coupled with the laboratory animal-based evidence on the effects of dietary fat and animal based protein on experimental cancer, the human-based evidence suggested that nutrition contributes far more to the cause of cancer than genetics, whether these were genes acquired from previous generations or were created by environmental mutagens.

But, still today, considerable debate and uncertainty exists as to how food affects cancer prevention and treatment, leaving many unanswered questions. Is it the nutrients or is it the ‘environmental’ chemical carcinogens in food that mostly contribute to human cancer? Are the effects of nutrients consumed in isolation (i.e., supplements) the same as when consumed in food? Because chemical carcinogens mutate genes and nutrients don’t, is there any evidence in human studies that genes are more important causes of cancer than nutrition? Is the oft-cited dietary fat association with cancer mortality rates the same for all cancers and is it linear throughout the full range of dietary fat? Does this association depend on type of fat? How does the cancer modifying effect of anti-inflammatory omega-3 fat compare with pro-inflammatory omega-6 fat and are these effects of fat type dependent on total dietary fat? Should nutritional modification of cancer be considered causal? These are only a small sample of such questions that often have a tendency to add more confusion than clarity.

There is reason to believe that there may be more awareness and understanding of the association of diet with heart disease and diabetes during the past couple of centuries than there has been for cancer. But when people transition from simple diets of rural cultures to complex diets of urban cultures, that is, from diets low in fat and protein to diets high in fat and protein, rates of heart disease, diabetes and cancer, as a group, generally increase.(64, 65) Is there something to be learned from the causation of these other diseases that might be helpful to an understanding of the causation of cancer, especially something concerning common biochemical mechanisms?

Although nothing much can be specifically attributed to the War on Cancer, it should be noted that, according to the American Cancer Society, recent trends in cancer mortality rates do show some favorable trends since the onset of that program, although it is unclear what role, if any, diet or other aspects of that program has affected these trends.(66) Lung cancer is declining in women since about 2000 and in men since about 1990, probably attributed to smoking cessation begun with the Surgeon General’s report on smoking in 1964(67). Breast cancer has been steadily declining about 2–3% per year in whites and 1–2% per year in blacks, depending on menopausal status. Uterine cancer death rates have been steadily decreasing since about 1930. Stomach cancer started receding several years before 1930, probably in response to the decreasing use of salt preservation of meats in favor of increasing use of food refrigeration. Colorectal cancers began declining in women about 1945 and in men about 1985. Yet, total cancer mortality still is the second leading cause of death in the U.S. Almost one-half of men and somewhat more than one-third of women will be diagnosed with cancer during their lifetimes.(66)

Although it is often said that the association of nutrition with cancer is not yet understood, thus diminishing its possible significance, I suggest that existing evidence is more promising than generally known. Consider, for example, the highly variable cancer rates for different countries as a function of diet and other lifestyle practices. If we assume that the lowest observable cancer rate is that which is theoretically achievable and if we were to know the factors causing the higher rates, then all rates above the lowest rate are avoidable. This was suggested by the former director of the UN Agency for Research on Cancer about four decades ago, who stated that 80–90% of total cancer was caused by dietary and environmental factors.(6) Based on a similar analysis, a survey of total cancer rates for 65 counties in China showed that 88.5% of male cancers and 80.3% of female cancers are avoidable.(68) These estimates of avoidable cancers may be even greater because countries/counties with the lowest rates are likely experiencing the same causal factors observed in the high rate region but at much lower levels of exposure.

Although it is not possible to know what proportion of these avoidable cancers is due to improper nutrition and what proportion is due to environmental chemicals, the evidence strongly suggests that improper nutrition predominates. Among Western type diseases (cancer, heart disease, etc.) in a 65-county, 130 village cohort in rural China, county average serum cholesterol (range of 90–162 mg/dL and mean of 127.6 mg/dL) was the most highly correlated lifestyle factor (r=0.48, p<0.001) for these diseases (including most cancers(69, 70)

Serum cholesterol, substantially influenced by nutritional practices, is correlated with diets having more animal based foods and less plant based foods,(68)}an observation that is consistent with experimental animal studies over a century ago.(71–73) The popular impression that environmental chemicals are the main dietary cause of cancer—for which there is almost no reliable evidence, diverts attention away from a role for nutrition in cancer.

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Diet, Nutrition and Cancer Initiation.........

 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5646698/

Indexed for NIH/HHS/National Library of Medicine by Dragonfly Kingdom Library 

Abstract

Cancer is uncontrolled growth of abnormal cells in the body. Nowadays, cancer is considered as a human tragedy and one of the most prevalent diseases in the wide, and its mortality resulting from cancer is being increased. It seems necessary to identify new strategies to prevent and treat such a deadly disease. Control survival and death of cancerous cell are important strategies in the management and therapy of cancer. Anticancer agents should kill the cancerous cell with the minimal side effect on normal cells that is possible through the induction of apoptosis. Apoptosis is known as programmed cell death in both normal and damaged tissues. This process includes some morphologically changes in cells such as rapid condensation and budding of the cell, formation of membrane-enclosed apoptotic bodies with well-preserved organelles. Induction of apoptosis is one of the most important markers of cytotoxic antitumor agents. Some natural compounds including plants induce apoptotic pathways that are blocked in cancer cells through various mechanisms in cancer cells. Multiple surveys reported that people with cancer commonly use herbs or herbal products. Vinca Alkaloids, Texans, podo phyllotoxin, Camptothecins have been clinically used as Plant derived anticancer agents. The present review summarizes the literature published so far regarding herbal medicine used as inducers of apoptosis in cancer.......

Indexed for NIH/Advanced Pharmaceutical Bulletin by Dragonfly Kingdom Library

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4213780/

Abstract

Background: Artemisia annua L. has gained increasing attention for its anticancer activity. However, beside artemisinin, less is known about the possible bioactive ingredients of Artemisia annua and respective herbal preparations. We hypothesized that, in addition to artemisinin, Artemisia annua preparations might contain multiple ingredients with potential anticancer activity.

Methods: MDA-MB-231 triple negative human breast cancer (TNBC) cells along with other treatment resistant, metastatic cancer cell lines were used to investigate in vitro and in vivo the anticancer efficacy of an Artemisia annua extract marketed as a herbal preparation, which contained no detectable artemisinin (limit of detection = 0.2 ng/mg). The extract was characterized by HPLC-DAD and the most abundant compounds were identified by 1H- and 13C NMR spectroscopy and quantified by UHPLC-MS/MS. Cell viability and various apoptotic parameters were quantified by flow cytometry. In vitro data were validated in two in vivo cancer models, the chick chorioallantoic membrane (CAM) assay and in orthotopic breast cancer xenografts in nude mice.

Results: The Artemisia annua extract, the activity of which could be enhanced by acetonitrile maceration, inhibited the viability of breast (MDA-MB-231 and MCF-7), pancreas (MIA PaCa-2), prostate (PC-3), non-small cell lung cancer (A459) cells, whereas normal mammary epithelial cells, lymphocytes, and PBMC were relatively resistant to extract treatment. Likewise, the extract's most abundant ingredients, chrysosplenol D, arteannuin B, and casticin, but not arteannuic acid or 6,7-dimethoxycoumarin, inhibited the viability of MDA-MB-231 breast cancer cells. The extract induced accumulation of multinucleated cancer cells within 24 h of treatment, increased the number of cells in the S and G2/M phases of the cell cycle, followed by loss of mitochondrial membrane potential, caspase 3 activation, and formation of an apoptotic hypodiploid cell population. Further, the extract inhibited cancer cell proliferation, decreased tumor growth, and induced apoptosis in vivo in TNBC MDA-MB-231 xenografts grown on CAM as well as in nude mice.

Conclusion: An extract of an artemisinin-deficient Artemisia annua herbal preparation exhibits potent anticancer activity against triple negative human breast cancer. New active ingredients of Artemisia annua extract with potential anticancer activity have been identified.......

Indexed for NIH/National Library of Medicine by Dragonfly Kingdom Library

https://pubmed.ncbi.nlm.nih.gov/31132755/

Abstract

G-quadruplex (G4) structures are considered a promising therapeutic target in cancer. Since Ayurveda, Piperine has been known for its medicinal properties. Piperine shows anticancer properties by stabilizing the G4 motif present upstream of the c-myc gene. This gene belongs to a group of proto-oncogenes, and its aberrant transcription drives tumorigenesis. The transcriptional regulation of the c-myc gene is an interesting approach for anticancer drug design. The present study employed a chemical similarity approach to identify Piperine similar compounds and analyzed their interaction with cancer-associated G-quadruplex motifs. Among all Piperine analogs, PIP-2 exhibited strong selectivity, specificity, and affinity towards c-myc G4 DNA as elaborated through biophysical studies such as fluorescence emission, isothermal calorimetry, and circular dichroism. Moreover, our biophysical observations are supported by molecular dynamics analysis and cellular-based studies. Our study showed that PIP-2 showed higher toxicity against the A549 lung cancer cell line but lower toxicity towards normal HEK 293 cells, indicating increased efficacy of the drug at the cellular level. Biological evaluation assays such as TFP reporter assay, quantitative real-time PCR (qRT- PCR), and western blotting suggest that the Piperine analog-2 (PIP-2) stabilizes the G-quadruplex motif located at the promoter site of c-myc oncogene and downregulates its expression. In conclusion, Piperine analog PIP-2 may be used as anticancer therapeutics as it affects the c-myc oncogene expression via G-quadruplex mediated mechanism.......

Indexed for Nature Journal/Springer Nature Scientific Reports 

https://www.nature.com/articles/s41598-021-01529-3

Abstract

Abstract

Objective

Chondrocyte apoptosis plays a vital role in osteoarthritis (OA) progression. Angelica sinensis polysaccharide (ASP), a traditional Chinese medicine, possesses anti-inflammatory and anti-apoptotic properties in chondrocytes. This study aimed to determine the protective role of ASP on sodium nitroprusside (SNP)-induced chondrocyte apoptosis, and explore the underlying mechanism.

Method

Human primary chondrocytes isolated from the articular cartilage of OA patients were treated with SNP alone or in combination with different doses of ASP. Cell viability and apoptosis were assessed, and apoptosis-related proteins including Bcl-2 and Bax were detected. Autophagy levels were evaluated by light chain 3 (LC3) II immunofluorescence staining, mRFP-GFP-LC3 fluorescence localization, and western blot (LC3II, p62, Beclin-1, Atg5). Meanwhile, activation of the ERK 1/2 pathway was determined by western blot. The autophagy inhibitors, 3-methyladenine (3-MA), chloroquine (CQ), and a specific inhibitor of ERK1/2, SCH772984, were used to confirm the autophagic effect of ASP.

Results

The results showed that SNP-induced chondrocyte apoptosis was significantly rescued by ASP, whereas ASP alone promoted chondrocyte proliferation. The anti-apoptotic effect of ASP was related to the enhanced autophagy and depended on the activation of the ERK1/2 pathway.

Conclusion

ASP markedly rescued SNP-induced apoptosis by activating ERK1/2-dependent autophagy in chondrocytes, and it made ASP as a potential therapeutic supplementation for OA treatment.........

Indexed for Biomed Central by Dragonfly Kingdom Library

https://arthritis-research.biomedcentral.com/articles/10.1186/s13075-020-02409-3

Abstract

The effect of ingestion of microwaved foods on serum antioxidant enzymes and vitamins in albino rats was investigated. In the study, thirty two (32) male wistar albino rats were obtained and grouped into four groups (A, B, C and D) of eight animals each. The animals were acclimatized for 7 days on commercial rat feed. The animals in groups B, C and D were all fed ad libitum with porridge yam, porridge beans and jellof rice with meat/fish reheated for 2 min, 4 min and 6 min for groups B, C and D respectively for 42 days. Group A was fed with un-microwaved food and water for the duration of the study (42 days) and served as control. Antioxidant enzymes superoxide dismutase (SOD), Catalase (CAT) activities, vitamins A and E concentrations were determined using standard methods. Result obtained from the study showed that microwaved food consumption resulted in a significant (P < 0.05) decrease in SOD and CAT activity in rats fed with the microwaved food. Furthermore, antioxidant enzyme activity were more significantly (P < 0.05) reduced in rats exposed to food microwaved for 6 min compared to the control group (A). Also, serum vitamins A and E concentrations were significantly (P < 0.05) decreased in rats fed with food exposed to microwaves for 6 min as compared to the control group. Microwaves and increased microwaving time resulted to a significant reduction in SOD, CAT, vitamin A and E in fed rats. Therefore our study demonstrated that consumption of microwaved foods resulted in a significant decrease in antioxidant protection and may be implicated in the pathogenesis of oxidative stress and degenerative diseases....

Indexed for Science Direct by Dragonfly Kingdom Libraryhttps://www.sciencedirect.com/science/article/pii/S1687850717300481

Environment International

Volume 163, May 2022, 107199

Discovery and quantification of plastic particle pollution in human blood

https://doi.org/10.1016/j.envint.2022.107199

Highlights

•

A method was validated for polymer mass concentrations in human whole blood.

•

Polymers from plastics were detected and quantified in human blood.

•

Polymers in human blood represent several high production volume plastics.

•

Blood donors were from general public.

•

Quality control of background plastic throughout sampling and analysis is key.

Abstract

Plastic particles are ubiquitous pollutants in the living environment and food chain but no study to date has reported on the internal exposure of plastic particles in human blood. This study’s goal was to develop a robust and sensitive sampling and analytical method with double shot pyrolysis - gas chromatography/mass spectrometry and apply it to measure plastic particles ≥700 nm in human whole blood from 22 healthy volunteers. Four high production volume polymers applied in plastic were identified and quantified for the first time in blood. Polyethylene terephthalate, polyethylene and polymers of styrene (a sum parameter of polystyrene, expanded polystyrene, acetonitrile butadiene styrene etc.) were the most widely encountered, followed by poly(methyl methacrylate). Polypropylene was analysed but values were under the limits of quantification. In this study of a small set of donors, the mean of the sum quantifiable concentration of plastic particles in blood was 1.6 µg/ml, showing a first measurement of the mass concentration of the polymeric component of plastic in human blood. This pioneering human biomonitoring study demonstrated that plastic particles are bioavailable for uptake into the human bloodstream. An understanding of the exposure of these substances in humans and the associated hazard of such exposure is needed to determine whether or not plastic particle exposure is a public health risk.......

Indexed for Science Direct by Dragonfly Kingdom Library

https://www.sciencedirect.com/science/article/pii/S0160412022001258

Spices in the Apiaceae Family Represent the Healthiest Fatty Acid Profile: A Systematic Comparison of 34 Widely Used Spices and Herbs

Ramesh Kumar Saini, Awraris Derbie Assefa, and Young-Soo Keum

Abstract

Spices and herbs are well-known for being rich in healthy bioactive metabolites. In recent years, interest in the fatty acid composition of different foods has greatly increased. Thus, the present study was designed to characterize the fatty acid composition of 34 widely used spices and herbs. Utilizing gas chromatography (GC) flame ionization detection (FID) and GC mass spectrometry (MS), we identified and quantified 18 fatty acids. This showed a significant variation among the studied spices and herbs. In general, oleic and linoleic acid dominate in seed spices, whereas palmitic, stearic, oleic, linoleic, and α-linolenic acids are the major constituents of herbs. Among the studied spices and herbs, the ratio of n−6/n−3 polyunsaturated fatty acids (PUFAs) was recorded to be in the range of 0.36 (oregano) to 85.99 (cumin), whereas the ratio of PUFAs/saturated fatty acids (SFAs) ranged from 0.17 (nutmeg) to 4.90 (cumin). Cumin, coriander, fennel, and dill seeds represent the healthiest fatty acid profile, based upon fat quality indices such as the ratio of hypocholesterolemic/hypercholesterolemic (h/H) fatty acids, the atherogenic index (AI), and the thrombogenic index (TI). All these seed spices belong to the Apiaceae family of plants, which are an exceptionally rich source of monounsaturated fatty acids (MUFAs) in the form of petroselinic acid (C18:1n12), with a very small amount of SFAs.

Keywords: polyunsaturated fatty acids (PUFAs), erucic acid, petroselinic acid, fat quality indices, hypocholesterolemic fatty acids, atherogenic index (AI)

1. Introduction

Spices and herbs are a vital part of human nutrition around the world, especially in India, China, and southeastern Asian countries [1]. Spices and herbs are food adjuncts, traditionally used as flavoring, seasoning, coloring, and as a food preservative agent [1,2]. Moreover, spices and herbs are an exceptionally rich source of nutritionally important phenolic compounds [3]. These phenolic compounds are primarily responsible for the potent antioxidative, digestive stimulative, hypolipidemic, antibacterial, anti-inflammatory, antiviral, and anticancer properties of spices and herbs [4,5,6].

In general, the terms herbs and spices have more than one meaning. However, the most widely used are those that consider herbs to be derived from the green parts of a plant, such as a stem and leaves used in small amounts to impart flavor, whereas spices are obtained from seeds, buds, fruits, roots, or even the bark of the plants [2].

Fatty acids are the primary nutritional components found in edible seed oils [7]. Seed oils provide essential polyunsaturated fatty acids, linoleic acid (ω−6 or n−6), and α-linolenic acid (n−3) to humans and other higher animals. In the human body, linoleic acid give rise to n−6 very long-chain (VLC)-PUFA arachidonic acid, and α-linolenic acid converts to n−3 VLC-PUFA eicosapentaenoic acid (EPA), and docosahexaenoic acid (DHA, n−3). These n−6 and n−3 VLC-PUFAs plays key distinct roles in regulating body homeostasis. In general, n−6 VLC-PUFAs gives rise to proinflammatory mediators (eicosanoids) whereas n−3 VLC-PUFAs give rise to anti-inflammatory mediators. Thus, a higher amount of n−3 VLC-PUFAs in the body may protect from chronic diseases, including cancer, inflammatory, or cardiovascular diseases (CVD) [8]. Moreover, a diet with a high proportion of n−6 PUFAs (high ratio of n−6/n−3 PUFAs) cannot be considered beneficial to health, as n−3 PUFAs to n−3 VLC-PUFAs conversion occurs at a very low rate (e.g., 8% for EPA and less than 1% for DHA), and conversion is largely dependent upon the ratio of ingested n−6 (linoleic acid) and n−3 (α-linolenic) PUFAs [9]. In human hepatoma cells, this conversion is highest when these n−6 and n−3 acids are provided at a 1:1 ratio. Thus, the consumption of an appropriate amount of fats with a 1:1 n−6/n−3 PUFAs ratio, which was probably followed by our ancestors [10], may be considered beneficial.

Similar to the consumption of fats with a balanced ratio of n−6/n−3 PUFAs, growing evidence suggests that replacing saturated fatty acids (SFAs) with monounsaturated fatty acids (MUFAs) from plant sources may decrease the risk of CVD [11]. And with the health benefits associated with consumption of n−3 PUFAs and MUFAs, consumer interest is shifting towards foods with a low proportion of SFAs, a high proportion of MUFAs, and balanced n−6/n−3 PUFAs. Given this, it is necessary to characterize all the major and minor components of the diet to acquire a better estimate of the fatty acid composition of our food.

Spices and herbs are not a significant source of fatty acids, as they form a small part of the diet. However, a detailed and comparative study of the fatty acid composition of various spices and herbs may be useful to identify those with health-beneficial fatty acids. Considering these facts, this study aims to investigate the fatty acid composition of commercially available major spices and herbs utilizing gas chromatography-flame ionization detection and GC-mass spectrometry analysis. We used fatty acid composition data to study spices and herbs to determine their fat quality indices. We anticipate the results contained herein will contribute significantly to the identification of spices with a healthy fatty acid profile.

2. Materials and Methods

2.1. Plant Material, Reagents, and Standards

A total of 34 commercially packed spices and herbs (Table 1; 200–500 g each spice and herb from at least three different brands) were obtained from retail outlets in Seoul, Korea. The spice and herb samples of different brands were mixed in equal proportions (200–300 g total) to make a representative sample, ground into a fine powder using a 7010HG laboratory blender (Waring Commercial, Torrington, CT, USA), placed into an air-tight container, and stored at room temperature. The fatty acid standard mix (37 Component FAME Mix, CRM47885) was obtained from Merck Ltd., Seoul, Korea. The organic solvents used for the extraction of lipids were of high-pressure liquid chromatography (HPLC) grade, obtained from Samchun Chemical Co., Ltd., Seoul, Korea.

List of spices and herbs used in the present investigation (arranged according to botanical name).

2.2. Extraction of Crude Lipid Compounds

The crude lipids were extracted by using the previous method [12,13] with minor modification. Briefly, 0.6 g dehydrated and powdered spices and herb samples were precisely weighed and transferred to a 50 mL glass tube. In each tube, 150 mg sodium ascorbate and 22 mL (isopropyl alcohol/cyclohexane, 10:12, v/v) containing 0.075% butylated hydroxytoluene (BHT: w/v; antioxidant) were added, and the contents were subjected to bath sonication (JAC-2010; 300 w, 60 Hz, for 12 min) for efficient disintegration and complete extraction, followed by 15 h shaking (200 RPM at 22 °C) in a rotary shaker. Contents were centrifuged at 7000× g (12 min at 4 °C). The supernatant was collected, and pellets were extracted again with 30 mL cyclohexane. Supernatants from both extractions were pooled (total volume of ~50 mL) and partitioned with an equal volume of 1 M of sodium chloride (NaCl). The upper cyclohexane phase containing crude lipids were collected, filtered over anhydrous sodium sulfate, transferred to a 250-mL round-bottom flask, and vacuum-dried in a rotary evaporator at 30 °C. The crude lipids were recovered into 3 mL methanol/dichloromethane (DCM) (1:3, v/v) containing 0.1% BHT, transferred to a 5 mL glass vial fitted with a Teflon-lined screw cap, and stored at −20 °C. One milliliter of sample was used to prepare fatty acid methyl esters (FAMEs).

2.3. Preparation of Fatty Acid Methyl Esters (FAMEs)

The crude lipids extracted from the spices and herb samples were used to prepare the FAMEs, following the previously optimized method [14] with minor modification. Briefly, 1 mL of a crude lipids sample was transferred into a 5 mL glass vial fitted with a Teflon-lined screw cap. Contents were evaporated to dryness using a rotary evaporator at 30 °C. After evaporation, 3 mL of anhydrous methanolic-HCl (methanol/acetyl chloride, 95:5, v/v) was added and incubated for 2 h at 55 °C in a heat block. Samples were cooled in ice, and FAMEs were sequentially washed with 1M NaCl and 2% sodium bicarbonate (NaHCO3) and recovered in 4 mL hexane. A pinch of anhydrous sodium sulfate (Na2SO4) was added to the recovered sample (hexane) to absorb the traces of water. One milliliter of sample was filtered through a 0.45 μm PTFE syringe filter and transferred to a 1.5 mL autosampler vial for GC-FID and GC-MS analysis.

2.4. GC-FID and GC-MS Analysis of FAMEs

FAMEs were quantitatively analyzed with GC (Agilent 7890B, Agilent Technologies Canada, Inc., Mississauga, ON, Canada) equipped with an autoinjector, an FID, and an SP-2560 capillary column (100 m, 0.20 μm film thickness, 0.25 mm ID; Merck KGaA, Darmstadt, Germany). The injector and the detectors were maintained at 250 °C and 260 °C, respectively. The inlet flow was 2 mL/min with a constant pressure of 54 psi. The FID parameters of hydrogen (H2) fuel flow, airflow, and make flow (nitrogen, N2) were set to 30, 400, and 25 mL/min, respectively. The column oven temperature was kept at 140 °C for 5 min, then progressively increased to 240 °C for 25 min (linear temperature program 4 °C/min and held at 240 °C for 15 min [15]. The FAMEs were precisely identified by comparing them with the retention time with authentic standards. For a more accurate qualitative analysis, the mass spectra were also recorded using a GC-MS system (QP2010 SE; Shimadzu, Kyoto, Japan), following the optimized GC-FID analysis thermal program. The identity of FAMEs was confirmed by comparing their fragmentation pattern with authentic standards, and also by using the National Institute of Standards and Technology (NIST; U.S. Department of Commerce, Gaithersburg, MD, USA) mass spectrum database (NIST08 and NIST08s).

2.5. Calculation of Fat Quality Indices

We used the spice and herbs fatty acid profile to determine several nutritional parameters of lipids, including the ratios of PUFAs/monounsaturated fatty acids (MUFAs), PUFAs/saturated fatty acids (SFAs), the ratio of hypocholesterolemic/hypercholesterolemic (h/H) fatty acids, atherogenic index (AI), and thrombogenic index (TI) [16]. The ratio of h/H fatty acids, AI, and TI was calculated with the following equations [16]:

2.6. Statistical Analysis and Quality Control

We performed a total of six replicate extractions and analyses from each representative sample. The data were analyzed by one-way analysis of variance (ANOVA), and homogenous subsets (mean separation) were determined using Turkey HSD with a significance level of p < 0.05, utilizing the IBM statistical 25.0 software.

The method used for GC-FID quantification of FAMEs was validated recently [15].

3. Results and Discussion

3.1. Fatty Acids Composition

In the present study, 18 fatty acids were identified and quantified, utilizing GC-FID and GC-MS analyses (Table 2). The results, given in Table 2, show that oleic (C18:1n9) and linoleic acid (C18:2n6) are dominated in seed spices, and palmitic (C16:0), stearic, oleic, linoleic, and α-linolenic acid (C18:3n3) are the major constituents of herbs. An exception was myristic (C14:0) acid, which was 60.8% of total fatty acids in Myristica fragrans (nutmeg) seeds (Figure 1A,B). Surprisingly, myristic acid was just 1.59% of the total fatty acids in the M. fragrans (mace; Figure 1C) seed arils. The highest proportions of oleic acid (41.64–41.85%) were recorded in cardamon pods/capsules (Figure S1) and white pepper seeds (Table 2). The data of the fatty acid composition of cardamom pods and white pepper seeds are scarce. However, 40.6–49.2% of oleic acid has been reportedly extracted from cold-pressed cardamom seeds [17,18], which agrees with data obtained in the present study from whole cardamon pods.

(A) The gas chromatography (GC)-flame ionization detection (FID) profiles of fatty acid methyl esters (FAMEs) of nutmeg. (B) The GC-mass spectrum of dominating fatty acid (myristic acid) from nutmeg. (C) The GC-FID profiles of FAMEs of mace. The numbers, ...

Fatty acid composition of spices and herbs.

In the present study, a substantial amount of erucic (C22:1n9; 17.3%) and eicosenoic (20:1n9; gondoic acid; 8%) acids were exclusively recorded in white mustard (Sinapis alba; syn Brassica alba) seeds. Similarly, a significant amount of petroselinic acid (C18:1n12c; an isomer of oleic acid) was recorded only in Apiaceae family seeds.

Among the studied 34 spices and herbs, total fatty acids were recorded to be in the range of 2.3 (galangal root) to 130.32 mg/g (mace). The odd chain fatty acid, pentadecanoic (C15:0) acid, was recorded as being a minor constituent (1.18%) in the galangal root. Similarly, heptadecanoic (C17:0) was recorded at only 0.13–0.14% in cayenne pepper, allspice, and mace. In nutmeg (Myristica fragrans) seed hexane extract, Anaduaka et al. [19] reported a significant amount of (27%) heptadecanoic (C17:0; margaric) acid. However, in the present study, heptadecanoic acid is not detected in nutmeg seeds.

3.2. Black Pepper and White Pepper

Black pepper and white pepper are prepared from the fruits of Piper nigrum L., according to the harvesting time and inclusion of the outer skin. Black pepper is the dried immature but fully developed fruit, whereas white pepper consists of the mature fruit lacking the outer skin [20]. The fatty acid composition data of black and white pepper is scarce. In the present study, 28.57%, 14.95%, 26.61%, and 9.32% of palmitic, oleic, linoleic, and α-linolenic acid were recorded being in black pepper. In contrast, 22.55%, 41.64%, 17.19%, and 1.49% of palmitic, oleic, linoleic, and α-linolenic was reported as being in white pepper (Table 2). These observations show that oleic acid increases significantly, whereas the palmitic, linoleic, and α-linolenic acids decrease significantly during the maturation of pepper fruits.

3.3. Nutmeg and Mace

Nutmeg and mace spices are obtained from different parts of the same fruit of the nutmeg (Myristica fragrans; Myristicaceae) tree. Nutmeg is the dried kernel of the seed, whereas mace is the dried aril surrounding the seed [21]. Myristic acid’s name is derived from Myristica fragrans, from which it was first isolated [22]. In the present study, myristic acid was 60.8% of total fatty acids in nutmeg, followed by oleic (C18:1n9c; 13.4%), linoleic (C18:2n6c; 11.9%), and palmitic (C16:0; 8.94%) (Figure 1A). Surprisingly, in mace, linoleic acid was 33.7% of total fatty acids, followed by palmitic (30.6%) and oleic (28.0%). Myristic acid was only 1.59% of the total fatty acids (Figure 1C, Table 2). In the investigations of Al-Khatib et al. [23], myristic acid was recorded as being 79.7% of the total fatty acids in nutmeg. Kozłowska et al. [24] analyzed the fatty acids composition of plant seeds, including anise, coriander, caraway, white mustard, and nutmeg. They reported dominance of oleic (56.5%), palmitic (18.29%), and linoleic (13.6%) acids in nutmeg. These contrasting observations probably arose as these authors reported only above C16 fatty acids. Myristic acid is widely used in the food industry as a flavor ingredient. It is approved as a pharmaceutical excipient by the Food and Drug Administration (FDA) and declared generally recognized as safe (GRAS) by various regulators [25].

3.4. Erucic Acid in White Mustard

Mustard (Sinapis alba; syn Brassica alba) seeds are well known for the occurrence of a substantial amount of erucic and eicosenoic acid [24]. In the present study, white mustard seeds were found containing 17.3% and 8.0% of erucic and eicosenoic acid, respectively (Figure 2A, Table 2). High intake of erucic acid is considered harmful for cardiac health [26]. The panel on contaminants in the food chain established a tolerable daily intake (TDI) of 7 mg/kg body weight (BW) for erucic acid based on a no-observed adverse effect level (NOAEL) for myocardial lipidosis in rats and pigs [26]. Considering the 43 mg of total fatty acids/g of white mustard seeds, consumption of 100 g of seeds may provide 7.31 mg of erucic acid. The intake of erucic acid from white mustard used as food condiments in daily food preparations is far below the TDI and is safe for consumption.

(A) The gas chromatography (GC)-flame ionization detection (FID) profiles of fatty acid methyl esters (FAMEs) of white mustard seeds. (B,C) The GC-mass spectrum of eicosenoic acid and erucic acid from white mustard seeds. (D) The GC-FID profiles of FAMEs ...

Petroselinic acid (C18:1n12c; an isomer of oleic acid) is the major component of the lipid constituent of Apiaceae family seeds [27,28]. In a previous study [27] of dill (Anethum graveolens) seeds, 87.2% of total fatty acids were composed of petroselinic acid. Similarly, in celery (Apium graveolens), coriander seeds (Coriandrum sativum), and fennel seeds (Foeniculum vulgare), petroselinic acid was recorded as being 56.1%, 72.8%, and 31.32% of total fatty acids. In agreement with the present study, we have also recorded the 50.4%, 49.4%, 62.1%, and 63.3% of petroselinic acid in dill, coriander celery, and fennel seeds, respectively (Table 2). And a similar high amount of petroselinic acid was reported to be in the seeds of other Apiaceae family plants, such as caraway (Carum carvi, 34.1%) and cumin (Cuminum cyminum; 49.9%). In seeds of different varieties of caraway, Reiter et al. [28] recorded 33.5–42.5% of petroselinic acid, which is in agreement with the present study. Petroselinic acid possesses potent anti-inflammatory and antiaging properties by reducing the metabolites of arachidonic acid [29]. And owing to its anti-aging properties, petroselinic acid is widely used in cosmetics or dermatological compositions [29]. Surprisingly, petroselinic acid was not detected in herbs (leaves) of the Apiaceae family member parsley (Petroselinum crispum). In the parsley herb, hexadecatrienoic (C16:3n3) was reported to be 17.7% of the total fatty acids (Figure 2D), whereas no other spices were found to contain this fatty acid. Parsley has been previously classified as a “16:3” plant owing to the presence of a significant amount of hexadecatrienoic acid in photosynthetic tissues, which is part of primitive lipid metabolism [30].

3.5. Fat Quality Indices

The present study is based on the fatty acid composition of 34 spices and herbs. We evaluated them for fat quality indices, including the n–6/n–3 ratio, AI, TI, and h/H fatty acid ratios (Table 3). Among the studied spices and food condiments, the ratio of n–6/n–3 PUFAs was found to be in the range of 0.36 (oregano) to 85.99 (cumin). In view of health benefits associated with the consumption of n−6/n−3 PUFAs ratio of 0.5–2.0 (nearest to 1:1), lipids obtained from leaf spices, including tarragon (0.76), bay leaf (1.33), basil (0.55), marjoram (0.75), parsley (0.48), white mustard (0.95), sage (0.86), and thyme (0.52) can be considered to be beneficial. In general, the high occurrence of α-linolenic acids compared to linoleic acid is responsible for the low n−6/n−3 ratio in leaves (photosynthetic tissue).

The fat quality indices of lipids of spices and herbs.

In view of the high risk of CVD and other chronic diseases that are associated with the dietary intake of SFAs [11], fats with a PUFAs/SFAs ratio lower than 0.45 are not advised for diet [31]. In the present study, PUFAs/SFAs ratios ranged from 0.17 (nutmeg) to 4.90 (cumin). Low PUFAs/SFAs ratios of 0.17 in nutmeg lipids are the result of the dominance of myristic acid (an SFA; Figure 1A), whereas in the case of cumin, linoleic acid is dominant over SFAs. In addition to the nutmeg, low PUFAs/SFAs ratios (<0.44) were recorded from galangal root (0.29), lemongrass (0.24), rosemary (0.28), and sage (0.38) because of the occurrence of a substantial amount of palmitic acid (Figure S2).

Fats with lower AI and TI and higher ratios of h/H fatty acids are recommended for minimizing the risk of CVD [32]. In the present study, a significant difference was recorded for AI, TI values as well as h/H fatty acids among the studied spices and herbs. The lowest significant values of the AI (0.06) and the highest ratios of h/H fatty acids (17.0) were obtained from cumin seeds (Table 3, Figure 3), because of the presence of a low amount of atherogenic lauric, myristic, and palmitic fatty acids, and high amounts of hypocholesterolemic C18:1 MUFAs and PUFAs. Whereas the lowest significant values of TI (white mustard, due to the low contents SFAs and high content of PUFAs.

(A) Illustrations showing the high content of healthy monounsaturated (MUFAs) and polyunsaturated fatty acids (PUFAs) in cumin, compared to low contents of MUFAs and PUFAs, and high contents of saturated fatty acids (SFAs) in nutmeg. (B) Arrangements ...

Overall, based on a higher ratio of h/H fatty acids and their lower AI and TI values, cumin, coriander, fennel, and dill spices have the healthiest fatty acid profiles (Figure 3). These spices belong to the Apiaceae family. White mustard also represents a higher ratio of h/H fatty acids and lower values of AI and TI. However, it contains a substantial amount of erucic acid.

In Figure 3, cumin, coriander, fennel, and dill spices top the fat quality indices, the ratio of h/H fatty acids, AI, and TI. However, the occurrence of a very low proportion of α-linolenic acid (a n−3 PUFA; 0.35–0.85%) and a fairly good amount of linoleic acid (a n–6 PUFA; 19.60–33.34%) in these spices, give rise to the high ratio of n–6/n–3 PUFAs (24.02–85.99), which is substantially higher than the recommended ratio of 1:1. Considering this, the culinary use of these spices can be recommended with n–3 PUFA rich components to obtain the overall n–6/n–3 PUFAs ratio of 1:1.

Previously, we had analyzed the total phenolic contents (TPC) and antioxidant activities of 39 spices and herbs (including the 34 spices and herbs investigated in the present study) and found that cloves possess the highest antioxidant activities, followed by allspice, cinnamon, oregano, and marjoram [33]. The high antioxidant activities of these spices and herbs were probably the results of the richness of phenolic compounds, as the antioxidant activities showed a good correlation (0.835–0.966) with TPC. In contrast, in the present study, cumin, coriander, fennel, and dill spices showed the healthiest fatty acid profile among the 34 spices and herbs. These observations show that the selection of healthy spices and herbs may vary with nutrient requirements. Thus, in the present study, cumin, coriander, fennel, and dill spices are the recommendations based on the fatty acid profile. However, other spices and herbs might be richer in other health-beneficial dietary components.

4. Conclusions

Spices belonging to Apiaceae family plants (cumin, coriander, fennel, and dill) are an exceptionally rich source of monounsaturated fatty acids (MUFAs) in the form of petroselinic acid, a good amount of polyunsaturated fatty acids (PUFAs; linoleic acid), and a small amount of saturated fatty acids. And, with high proportions of MUFAs and PUFAs, the Apiaceae family spices top the fat quality indices, particularly in terms of a higher ratio of hypocholesterolemic/hypercholesterolemic fatty acids, and lower values of the atherogenic index and the thrombogenic index (Figure 3).

Acknowledgments

This paper was supported by the KU Research Professor Program of Konkuk University, Seoul, Korea.

Supplementary Materials

The following are available online at https://www.mdpi.com/article/10.3390/foods10040854/s1, Figure S1: (A) The gas chromatography (GC)-flame ionization detection (FID) profiles of fatty acid methyl esters (FAMEs) of cardamom. (B) The GC-mass spectrum of dominating fatty acid (Palmitic acid); Figure S2. (A–C) The gas chromatography (GC)-flame ionization detection (FID) profiles of fatty acid methyl esters (FAMEs) of lemongrass, rosemary, and Sage. The GC-mass spectrum of dominating fatty acid (Palmitic acid). The numbers, 4, 7, 9, 11, and 14 correspond to peak numbers illustrated in Table 1. BHT: Butylated hydroxytoluene (A synthetic antioxidant used during lipid extraction).

Author Contributions

Conceptualization, R.K.S. and A.D.A.; methodology, R.K.S. and A.D.A.; software, R.K.S. and A.D.A.; validation, R.K.S. and A.D.A. and Y.-S.K.; formal analysis, R.K.S.; investigation, R.K.S.; resources, Y.-S.K.; data curation, R.K.S. and A.D.A.; writing—original draft preparation, R.K.S.; writing—review and editing, A.D.A. and Y.-S.K.; visualization, Y.-S.K.; supervision, Y.-S.K.; project administration, R.K.S.; funding acquisition, R.K.S. All authors have read and agreed to the published version of the manuscript.

Funding

This paper was supported by the KU Research Professor Program of Konkuk University, Seoul, Republic of Korea and “The APC was supported by Konkuk University research fund (2021A0190061)”.

Conflicts of Interest

The authors declare no conflict of interest.

Footnotes

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Article information

Foods. 2021 Apr; 10(4): 854.

Published online 2021 Apr 14. doi: 10.3390/foods10040854

PMCID: PMC8071036

PMID: 33920058

Ramesh Kumar Saini,1 Awraris Derbie Assefa,2 and Young-Soo Keum1,*

Andreas Eisenreich, Academic Editor and Bernd Schaefer, Academic Editor

1Department of Crop Science, Konkuk University, Seoul 05029, Korea; rk.ca.kuknok@7991inias

2National Agrobiodiversity Center, National Institute of Agricultural Sciences, Rural Development Administration, Jeonju 54874, Korea; rk.aerok@sirarwa

*Correspondence: rk.ca.kuknok@lanoitar

Received 2021 Mar 8; Accepted 2021 Apr 12.

Copyright © 2021 by the authors.

Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).

This article has been cited by other articles in PMC.

Articles from Foods are provided here courtesy of Multidisciplinary Digital Publishing Institute (MDPI)

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