2.1. INTRODUCTION

Herbs and spices are traditionally defined as any part of a plant that is used in the diet for their aromatic properties with no or low nutritional value (Davidson 1999; Hacskaylo 1996; Smith and Winder 1996). However, more recently, herbs and spices have been identified as sources of various phytochemicals, many of which possess powerful antioxidant activity (Larson 1988; Velioglu et al. 1998; Kähkönen et al. 1999; Dragland et al. 2003). Thus, herbs and spices may have a role in antioxidant defense and redox signaling.

In the scientific and public literature, antioxidants and oxidative stress are very often presented in a far too simple manner. First, reactive oxygen species (ROS) are lumped together as one functional entity. However, there are many different ROS that have separate and essential roles in normal physiology and are required for a variety of normal processes. These physiological functions are not overlapping, and the different ROS that exist cannot, in general, replace each other. Different ROS are also strongly implicated in the etiology of diseases such as cancers, atherosclerosis, neurodegenerative diseases, infections, chronic inflammatory diseases, diabetes, and autoimmune diseases (Gutteridge and Halliwell 2000; McCord 2000). Second, the various antioxidants that exist are often viewed as a single functional entity. However, the different endogenous antioxidants that are produced by the body (e.g., glutathione, thioredoxins, glutaredoxin, and different antioxidant enzymes) cannot, in general, replace each other. They have specific chemical and physiological characteristics that ensure all parts of the cells and the organs or tissues are protected against oxidative damage. Dietary antioxidants also exist in various forms, with polyphenols and carotenoids being the largest groups of compounds. These have different functions and are produced by plants to protect plant cells against oxidative damage (Halliwell 1996; Lindsay and Astley 2002).

Based on the complex nature of antioxidants and ROS, it would thus be extremely unlikely that a magic bullet with a high dose of one or a few particular antioxidants such as vitamin C, vitamin E, or β-carotene would protect all parts of the cells, organs, and tissues against oxidative damage and oxidative stress, at the same time without destroying any of the numerous normal and beneficial functions of ROS. Indeed, supplementation with antioxidants has often resulted in no effect or even adverse disease outcomes. Recently, several reviews and meta-analyses have concluded that there is now a strong body of evidence indicating that there is no beneficial effect for supplemental vitamin C, vitamin E, or β-carotene (Vivekananthan et al. 2003; Eidelman et al. 2004; Bjelakovic et al. 2007; Bjelakovic et al. 2008). An alternative and much more likely antioxidant strategy to test protection against oxidative stress and related diseases would be to test the potential beneficial effects of antioxidant-rich foods, since such foods typically contain a large combination of different antioxidants that are selected, through plant evolution, to protect every part of the plant cells against oxidative damage. This is especially relevant for herbs and spices. The aim of this chapter is to discuss the potential role of antioxidants in herbs and spices in normal physiology, oxidative stress, and related diseases. We begin with a brief introduction of ROS and their role in normal physiology and oxidative stress, and then present data that demonstrate herbs and spices are the most antioxidant-dense dietary source of antioxidants that has been described. We end the chapter with a discussion on the potential role of herb and spice antioxidants in oxidative stress.

2.2. REACTIVE OXYGEN SPECIES: COMPLEX ROLES IN NORMAL PHYSIOLOGY

ROS molecules are simply oxygen-containing molecules that are reactive. They can be divided into free-radical ROS and nonradical ROS. Free-radical ROS have unpaired electrons in their outer orbits; examples of such molecules are superoxide and hydroxyl radical. Nonradical ROS do not have unpaired electrons; however, these are chemically reactive and can be converted into free-radical ROS. One example of a nonradical ROS is hydrogen peroxide.

2.3. EXAMPLES OF THE DUAL ROLES OF REACTIVE OXYGEN SPECIES IN PATHOLOGIES

Increased levels of ROS have been implicated in numerous chronic degenerative diseases such as cardiovascular diseases, cancers, type 2 diabetes, neurodegenerative diseases, obesity, and hypertension. However, ROS may have dual roles in many pathologies.

2.4. IS THERE A ROLE OF DIETARY ANTIOXIDANTSIN OXIDATIVE STRESS?

Based on the dual role of ROS described in Section 2.3 and the large variety of ROS and mechanisms involved, it is clear that a beneficial effect of a large intake of one single antioxidant (such as high-dose vitamin C, vitamin E, or β-carotene supplement) would not be expected. An alternative and much more likely strategy would be to test the potential beneficial effects of antioxidant-rich foods, since such foods typically contain a large combination of different antioxidants, which are selected through plant evolution to protect every part of the plant cells against oxidative damage. Moreover, this “package” of antioxidants with different functions is also present in much lower doses than those that are typically used in antioxidant supplements. Thus, we suggest that dietary antioxidants taken in their usual form of food may decrease risk of chronic diseases without compromising the normal functions of ROS (Blomhoff 2005).

There are numerous antioxidants in dietary plants. Carotenoids are ubiquitous in the plant kingdom, and as many as 1000 naturally occurring variants have been identified. At least 60 carotenoids occur in the fruits and vegetables commonly consumed by humans (Lindsay and Astley 2002). Besides the pro-vitamin A carotenoids, α- and β-carotene, and β-cryptoxanthin, lycopene and the hydroxy carotenoids (xanthophylls) lutein and zeaxanthin are the main carotenoids present in the diet. Their major role in plants is related to light harvesting as auxiliary components and quenching of excited molecules, such as singlet oxygen, that might be formed during photosynthesis. Phenolic compounds are also ubiquitous in dietary plants (Lindsay and Astley 2002). They are synthesized in large varieties, and belong to several molecular families, such as benzoic acid derivatives, flavonoids, proanthocyanidins, stilbenes, coumarins, lignans, and lignins. Over 8000 plant phenols have been isolated. Plant phenols are antioxidants by virtue of the hydrogen-donating properties of the phenolic hydroxyl groups.

We hypothesize that antioxidant-rich foods may be beneficial and provide a balanced combination of a variety of antioxidants in appropriate doses that would protect against excessive oxidative stress and oxidative damage without disturbing the normal role of ROS. In order to test this hypothesis, we first need to identify antioxidant-rich foods, that is, foods that contain relatively large amounts of total antioxidants. Therefore, we perform a systematic screening of the total antioxidant content (Benzie and Strain 1996) of more than 3500 foods (Halvorsen et al. 2002; Halvorsen et al. 2006; Carlsen et al. 2010). This novel and unique antioxidant food table enables us to calculate the total antioxidant content of complex diets, identify and rank potentially good sources of antioxidants, and provide the research community with data on the relative antioxidant capacity of a wide range of foods.

There is not necessarily a direct relationship between the antioxidant content of a food sample consumed and the subsequent antioxidant activity in the target cell. Factors influencing the bioavailability of phytochemical antioxidants include the food matrix and food preparation methods, as well as absorption, metabolism, and catabolism. With the present study, food samples with high antioxidant content are identified, but further investigation into each individual food is needed to identify those samples that may have biological relevance and the mechanisms involved in antioxidant activity. Such studies, including mechanistic cell-culture and experimental animal research, preclinical studies on bioavailability and bioefficacy, as well as clinical trials, are in progress.

2.5. TOTAL ANTIOXIDANT CONTENT OF FOODS AND DRINKS: LARGEST DENSITY OF ANTIOXIDANTS CONTAINED IN SPICES AND HERBS

The results of our study show large variations both between different food categories and within each category; all the food categories contain products almost devoid of antioxidants (Table 2.1). Please refer to the antioxidant food table published as an electronic supplement to the paper by Carlsen et al. (2010) for the antioxidant results on all products analyzed. The updated database is available online at http://www.blomhoff.no (link to “Scientific Online Material”).

TABLE 2.1

Characteristics of the Antioxidant Food Table.

Interestingly, the categories “spices and herbs” and “herbal/traditional plant medicine” include the most antioxidant-rich products analyzed in the study. The categories “berries and berry products,” “fruit and fruit juices,” “nuts and seeds,” “breakfast cereals,” “chocolate and sweets,” “beverages,” and “vegetables and vegetable products” include most of the common foods and beverages, which have medium to high antioxidant values. We find that plant-based foods are generally higher in antioxidant content than animal-based and mixed food products, with median antioxidant values of 0.88, 0.10, and 0.31 mmol/100 g, respectively. Furthermore, the 75th percentile of antioxidant-content threshold for plant-based foods is 4.11 mmol/100 g, compared to that of 0.21 and 0.68 mmol/100 g for animal-based and mixed foods, respectively. The high mean value of plant-based foods is due to a minority of products with very high antioxidant values, found among plant medicines, spices, and herbs. Table 2.1 summarize results from the 24 food categories tested.

2.6. TOTAL AMOUNTS OF ANTIOXIDANTS IN HERBS AND SPICES

Herbal/traditional plant medicine is the most antioxidant-rich category in the present study and also the category with the largest variation between products (Table 2.2). Half of the products have antioxidant values above the 90th percentile of the complete food table and the mean and median values are 91.7 and 14.2 mmol/100 g, respectively. The 59 products included originate from India, Japan, Mexico, and Peru. Sangre de grado (“dragon’s blood”) from Peru has the highest antioxidant content of all the products in the database (2897.1 mmol/100 g). Other antioxidant-rich products are triphala, amalaki, and arjuna from India and goshuyu-tou, a traditional kampo medicine from Japan, with antioxidant values in the range 132.6–706.3 mmol/100 g. Only four products in this category have values less than 2.0 mmol/100 g.

TABLE 2.2

Antioxidants in Herbal/Traditional Plant Medicine.

A summary of the 425 spices and herbs analyzed in our study is presented in Table 2.3. The study includes spices and herbs from 59 different manufacturers or countries. Although 27 single products have a total antioxidant content in the range 100–465 mmol/100 g, the variation is from 0.08 mmol/100 g in raw garlic paste procured in Japan to 465 mmol/100 g in dried and ground clove purchased from Norway. When sorted by antioxidant content, clove has the highest mean antioxidant value, followed by peppermint, allspice, cinnamon, oregano, thyme, sage, rosemary, saffron, and estragon, all dried and ground, with mean values ranging from 44 to 277 mmol/100 g. When analyzed in fresh samples compared to the dried herbs, oregano, rosemary, and thyme have lower values, in the range 2.2–5.6 mmol/100 g. This is also true for basil, chives, dill, and parsley. In addition to common spices and culinary herbs, we also analyzed other herbs, such as birch leaves, wild marjoram, and wood cranesbill, among others. Most of the spices and herbs analyzed have very high antioxidant content. Although spices and herbs contribute little weight to the dinner plate, they may still be important contributors to antioxidant intake, especially in dietary cultures where spices and herbs are used regularly. We interpret the elevated concentration of antioxidants observed in several dried herbs compared to fresh samples as a normal consequence of the drying process leaving most of the antioxidants intact in the dried end product.

TABLE 2.3

Antioxidants in Herbs and Spices.

2.7. RESEARCH NEEDS: POTENTIAL HEALTH EFFECTS OF DIETARY ANTIOXIDANTS

Only a few spices have been relatively extensively studied in terms of possible health effects (those include turmeric and ginger, both of which are described in more detail elsewhere in this book). Clove, oregano, and thyme are all among the commercially available spices with the highest total antioxidant capacity (Table 2.3). Several phytochemicals found in these spices, such as rosmarinic acid (Lee et al. 2006) in thyme and oregano (Shan et al. 2005), eugenol in clove and allspice (Chainy et al. 2000) and gallic acid in clove, have all been identified as inhibitors of NF-κB, a transcription factor which is crucial in the orchestration of immune and inflammatory responses. Thyme and oregano essential oils in combination decreased the levels of IL-1β and IL-6, as well as inflammation related tissue damage in a model of colitis (Bukovska et al. 2007), both of which may also be related to NF-κB. We found an extract of clove, oregano, thyme, together with walnuts and coffee to inhibit NF-κB activation in a synergistic manner in vitro, and also in vivo in transgenic mice (Paur et al. 2010). Furthermore, thyme has been found to induce or maintain levels of endogenous cytoprotective proteins in the liver (Sasaki et al. 2005). This is in consonance with a study by Kluth et al. (2007), in which extracts of thyme, allspice, or clove induced phase I- and/or phase II-related transcription in vitro (through the CYP3A4 promoter, and pregnane X receptor [PXR] and electrophile response element [EpRE]-dependent transcription).

Further underlining the potency of phytochemicals, we (Paur, Austenaa, and Blomhoff 2008) and others (Takada et al. 2004) have found several phytochemicals to be equally or even more efficient inhibitors of NF-κB as compared to classical anti-inflammatory drugs, such as ibuprofen and dexamethasone.

Even though there is limited literature on the health effects of whole herbs or spices or extracts of whole herbs or spices, the number of studies investigating the possible health effects of single phytochemicals originating from herbs or spices is much higher. Resveratrol, curcumin, genistein, capsaicin, epigallocatechin gallate (EGCG), quercetin, β-carotene, and lycopene are among the most widely studied phytochemicals. Phytochemicals can alter the activity of several cell signaling pathways, which can lead to modulation of inflammatory processes, regulation of cytoprotective mechanism and regulation of cell growth and differentiation (extensively reviewed by Surh (2003) and Aggarwal and Shishodia (2006)). Most of the products categorized as herbal and traditional plant medicines are also based on antioxidant-rich dietary plants or isolated phytochemicals.

Herbal and traditional plant medicines emerged as many of the highest antioxidant-containing products in our study of various foods. We speculate that a highly inherent antioxidant property is an important contributor to an herb’s medicinal qualities. In our study, we identified sangre de grado, the sap from the tree trunk of the species Croton lechleri sampled in Peru, to have exceptionally high antioxidant content. This tree sap has a long history of indigenous use in South America for healing wounds and as an antifungal, antiseptic, antiviral, and antihemorrhagic medicine. Proanthocyanidins are major constituents of this sap (Cai et al. 1991), and studies have shown that sangre de grado limits the transcription of a wide range of proinflammatory cytokines and mediators, accelerates the healing of stomach ulcers (Miller et al. 2000, 2001), and promotes apoptosis in cancer cells (Sandoval et al. 2002). Other herbal medicines that are extremely rich in antioxidants include triphala, an Indian Ayurvedic herbal formulation, that was shown to have anti-inflammatory activity (Rasool and Sabina 2007), antibacterial and wound-healing properties (Srikumar et al. 2007; Kumar et al. 2008), and cancer chemopreventive potential (Deep et al. 2005). Arjuna, another Ayurvedic formula, has been shown to have health benefits (Devi et al. 2007; Manna, Sinha, and Sil 2007), whereas goshuyu-tou, a traditional kampo medicine, has been shown to significantly lower the extracellular concentration of NO in lipopolysaccharide (LPS)-stimulated RAW 264.7 cells (Okayasu et al. 2003).

The herbs Cinnamomi cortex and Scutellariae radix both contain very high levels of antioxidants (75 mmol/100 g). The herbal medicines saiko-keishi-to, juzaen-taiho-to, and hocyu-ekki-to, which are used for various kinds of inflammatory and infectious diseases, are all taken in a daily dose of 7.5 g, corresponding to 1.6, 1.1, and 0.7 mmol antioxidants per day, respectively. The antioxidant activity of the Japanese herbal medicine sho-saiko-to, which is composed of herbs tested in this study, was calculated to be about 1.3 mmol/7.5 g (the recommended daily dose of the medicine). This drug, which is commonly used to treat chronic hepatitis in Japan, may also inhibit the development of hepatocellular carcinoma (Oka et al. 1995) and decrease lipid peroxidation and hepatic fibrosis in experimental animals (Sakaida et al. 1998; Shimizu et al. 1999). The herbal medicine stronger neo-minophagen C, a glycyrrhizin preparation, has also been used extensively with considerable success in Japan for the treatment of chronic hepatitis in intravenous doses up to 100 mL/day (Kumada 2002). Our analyses reveal that this injection volume equals about 1 mmol antioxidants. Thus, such injections will boost the total antioxidant content within the body. It is tempting to speculate that several of the effects observed with these herbal medicines are mediated by their antioxidant activity.

It is not likely that all antioxidant-rich foods are good bioactive sources, or that all antioxidants provided in the diet are bioactive. Bioavailability differs greatly from one phytochemical to another, so the most antioxidant-rich foods in our diet are not necessarily those leading to the highest concentrations of active metabolites in target tissues. The antioxidants obtained from foods include many different molecular compounds and families with different chemical and biological properties including differences in absorption, transport and excretion, cellular uptake and metabolism, and eventually their effects on oxidative stress in various cellular compartments. Biochemically active phytochemicals found in plant-based foods also have many powerful biological properties that are not correlated with their antioxidant capacity. Thus, a food low in antioxidants may have beneficial health effects due to other food components or phytochemicals executing bioactivity through other mechanisms.

Understanding the complex role of diet in chronic diseases is challenging since a typical diet provides more than 25,000 bioactive food constituents, many of which may modify a multitude of processes that are related to these diseases. Because of the complexity of this relationship, it is likely that a comprehensive understanding of the role of these bioactive food components is needed to assess the role of dietary plants in human health and disease development. We suggest that both their numerous individual functions and their combined additive or synergistic effects are crucial to their beneficial effects on human health, and thus a food-based research approach is likely to elucidate more health effects than the effects derived from each individual nutrient. The antioxidant food table is a valuable research contribution for plant-based nutritional research and may be utilized in epidemiological studies where reported food intakes can be assigned antioxidant values. It can also be used to test antioxidant effects and synergy in experimental animals, cell studies, or in human clinical trials. The ultimate goal of this research is to combine these strategies in order to understand the role of dietary phytochemical antioxidants in the prevention of chronic diseases related to oxidative stress.

2.8. CONCLUSIONS

The concepts discussed in this chapter can be summarized as follows:

• The total content of antioxidants has been assessed in more than 3500 foods; this provides a large database to support research into dietary antioxidants, health, and disease.
• The results show large variations both between food categories and within each category.
• Herbs and spices and composite herbal medicines are among the categories that contain the most antioxidants.
• Further research is needed to study the biological effects of antioxidant-rich herbs and spices on oxidative-stress-related diseases.

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