Total phenolic content and antioxidant activity of soybeans fermented by mushroom mycelia [10].
Abstract
The medicinal value of mushrooms is long known, but there is increasing awareness of their health benefits and interest in utilizing these in diet as food or nutritional supplement. In this chapter, we discuss the characteristics of 20 wild mushrooms and results from our work on their antioxidant activity, ability to promote nerve growth factor (NGF) synthesis and to convert the glycosylated forms of isoflavones to usable aglycon forms in soybeans fermented with their mycelia. Of the 20 mushroom types, we found that Hericium ramosum (H. ramosum) mycelia had higher antioxidant activity and showed greater capability for increasing the levels of aglycons, such as daidzein, glycitein, and genistein when used for fermentation of soybeans. In general, soybeans fermented with mushrooms increased the levels of aglycons compared to non-fermented ones. Taken together, all these results suggest that mushroom mycelia have a huge potential to be used as food and nutritional supplements for the health benefits they offer and present the prospects for utilizing them in soybean fermentation as natural resources for the large-scale production of aglycons.
Keywords
- H. ramosum mycelia
- antioxidant
- NGF synthesis
- soybean fermentation
- isoflavone
1. Introduction
Mushrooms, their fruiting bodies and mycelia have served as food and food supplements around the world. They are relatively less toxic and are rich in bioactive compounds, such as polysaccharides, proteins, minerals, and other nutrients [1]. Beneficial activities associated with mushroom fruiting bodies and mycelia include antitumor [2], antimutagenic [3], antiviral [4], and antioxidant activities [5]. Some mushrooms alleviate the risk of diseases, such as Parkinson’s and Alzheimer’s disease, and hypertension [6].
Mushroom mycelia contain bioactive compounds as well as mushroom fruiting bodies, which have been investigated for their medicinal value. For example, oral administration of
In this chapter, we first discuss the antioxidant activity of 20 different species of wild mushroom mycelia [9]. These mushrooms are considered edible in the Tohoku area in northern Japan. Second, we present our findings on the ability of the comb tooth cap medicinal mushroom,
2. Characteristics of wild mushroom mycelia
2.1 Collection of mushrooms and separation of mycelia
We investigated the characteristics of 20 species of mushrooms: #1,
Nineteen of these (#2–20) wild mushroom fruiting bodies were collected from the Akita and Iwate prefectures in the Tohoku area in northern Japan.
2.2 Ethanol extract preparation from mushroom mycelia
Mushroom mycelia extraction with ethanol was performed following methods described in previous reports [12, 13] with a few modifications. Lyophilized mushroom mycelia (0.1 g) were extracted with 80% ethanol (10 mL) at 25°C for 24 h and the resulting solutions were concentrated and lyophilized to a powder.
2.3 Antioxidant activity of wild mushroom mycelia
Free radicals exert tissue damage through reactive oxygen species (ROS)-induced oxidative stress, which can be counterbalanced by antioxidants [14, 15]. ROS, such as superoxide anion radicals, hydroxyl radicals, and hydrogen peroxide (H2O2), induce aging and cell damage [16, 17], and have been implicated in several diseases [18]. Recent epidemiological data indicate the association between inactivation of ROS and the disease-prevention benefits resulting from consuming food containing antioxidants, such as fruits, vegetables, and certain cereals [19]. As a result, there is an increasing trend worldwide in the incorporation of antioxidant compounds and foods into regular diet. We measured the antioxidant activity of the 20 wild mushrooms listed above by DPPH radical scavenging activity assay.
2.3.1 Methods
Measurement of 2,2-diphenyl-1-picryhydrazyl (DPPH) radical scavenging activity of mushroom mycelia was performed as previously described [20]. Ethanol extracts of mushroom mycelia (0.3 mL) were mixed with 0.6 mL of 100 mM MES buffer (pH 6.0)/10% ethanol solution, and 0.3 mL of 400 μM DPPH in ethanol. The absorbance of the reaction mixture was quantified at 520 nm after the reaction was set to complete for 20 minutes at RT. The DPPH radical scavenging activity of mushroom mycelia was calculated from assay lines of Trolox (0, 5, 10, 15, 20, and 25 μM) and expressed as μmol Trolox/g dry powder.
2.3.2 DPPH free radical scavenging activity of mushroom mycelia
Eighty-percent ethanol extracts of mushroom mycelia were used for antioxidant activity measurements using DPPH radical scavenging activity (Figure 1). Among the 20 mushroom mycelia analyzed,
2.4 Total phenolic content of the wild mushroom mycelia
Phenolic compounds are secondary metabolites of plants produced as defensive responses to threatening environments, including pathogen attack and UV radiation [21]. Generally, these polyphenols are classified as phenolic acids, flavonoids, lignans, and stilbenes [22]. These phenolic compounds possess antioxidant, antiglycemic, anticarcinogenic, and anti-inflammatory properties and can protect against bacterial and viral infections [23]. We analyzed the total phenolic content of the mushroom mycelia.
2.4.1 Methods
Folin & Ciocalteu method [24] with catechin as a standard was used for analysis. Ethanol extracts of mushroom mycelia (1 mL) were mixed with 0.5 mL of Folin & Ciocalteu solution and 5 mL of 0.4 M sodium carbonate solution. The absorbance of the reaction mixture was quantified at 660 nm after the reaction was set to complete for 30 minutes at 30°C. Methods are described in detail in Suruga et al. [9].
2.4.2 Measurement of total phenolic content
The phenolic contents of the samples were expressed as mg of catechin equivalent/g dry powder in Figure 2.
2.5 Phenolic compounds enable the DPPH radical scavenging capacity of mushroom mycelia
DPPH radical scavenging activity showed a significant correlation (
3. NGF synthesis of H. ramosum mycelia
Senile dementia, such as AD, is a severe problem, with no effective therapy [25]. Neurotrophic factors, including NGF, brain-derived neurotrophic factor (BDNF), neurotrophin 3, and glial-derived neurotrophic factor (GDNF), have been implicated in the prevention of neuronal death and promotion of neurite outgrowth [26]. Among them, NGF has been associated with AD [27], with decreased NGF levels in the basal forebrain of AD patients. Intracerebroventricular administration of NGF has been reported to eliminate degeneration and resultant cognitive deficits in rats after brain injury [28]. In rats, poor cognitive effects caused by neuronal degeneration have been shown to be eliminated by intracerebroventricular administration of NGF. However, since NGF cannot cross the blood-brain barrier, utilizing it for therapeutic application will be difficult. Several studies have investigated low-molecular-weight compounds, such as catecholamines [29], benzoquinones [30], hericenones [31], and erinacines [32], for their ability to promote NGF synthesis.
3.1 Methods
NGF synthesis was measured as described by Hazekawa et al. [37]. Male ddY mice (25–30 g weight) obtained from Kiwa Laboratory Animals Co., Ltd. (Wakayama, Japan), were housed under a 12-h light/dark cycle at room temperature and 55 ± 5% humidity. The lyophilized mycelia from
3.2 Stimulation of NGF synthesis by H. ramosum and H. erinaceum mycelia
The effects of 14-days of oral administration of 300 mg/kg
Different regions of the mouse brain responded differently to application of varying concentrations of
4. Soybean fermentation using mushroom mycelia
The legume soybean is highly proteinaceous (36% protein in dried beans), rich in major nutrients essential for human nutrition and can potentially be a good replacement for animal-derived proteins [38, 39, 40, 41]. It can be used both in fermented and non-fermented forms [42]. While soybeans are rich in flavonoid groups such as genistein, daidzein, and glycitein isoflavones that have tremendous health benefits [43], they are not easily absorbed and incorporated in their natural glycosylated forms unless hydrolyzed by the microflora of the intestine through their beta-glucosidase production [44]. Isoflavones have health benefits against several diseases and hormone-related issues [45, 46, 47, 48]. The easily absorbable form of flavones is the aglycon form, which is abundant in fermented sources of soybean, such as tempeh, miso, and natto [49].
Mushroom mycelia can be used as a source of beta glucosidase to convert isoflavone glycosides to their aglycon form. For example,
Studies from our laboratory investigated the health effects of fermentation using mushrooms, such as
Soybean fermentation was carried out as described in Suruga et al. [10]. We found that
4.1 Antioxidant activity of fermented soybean
4.1.1 Methods
The DPPH radical scavenging activity and total phenolic content of fermented soybeans were analyzed using the methods described in Subsections 2.3.1 and 2.4.1. Oxygen radical absorbance capacity (ORAC) was determined using the OxiSelect™ ORAC Activity Assay Kit (Cell Biolabs Inc., San Diego, CA, USA) [51]. The assay was performed as described in Suruga et al. [10]. Briefly, fluorescence activity of the reaction mixture with antioxidant and fluorescein solution was measured after adding the free radical initiator. Increasing Trolox concentrations were used for the standard curve, and extracts were quantified and expressed as μmol Trolox equivalents/g of dry fermented soybean powder.
4.1.2 Total phenolic content and antioxidant activity of fermented soybean by mushroom mycelia
Total phenolic content was higher in all the fermented extracts compared to non-fermented control soybeans. Both DPPH radical scavenging activity and antioxidant activity were higher in fermented soybeans than in non-fermented ones (Table 1).
Control | ||||
---|---|---|---|---|
Total phenolic content (mg/g dry powder) | 1.547 ± 0.068 | 2.304 ± 0.035 | 2.074 ± 0.066 | 2.160 ± 0.014 |
DPPH radical scavenging activity (μmol Trolox/g dry powder) | 1.847 ± 0.073 | 4.246 ± 0.010 | 2.246 ± 0.061 | 2.367 ± 0.173 |
ORAC (μmol Trolox/g dry powder) | 49.763 ± 2.856 | 60.090 ± 1.506 | 66.147 ± 1.898 | 72.897 ± 2.113 |
4.2 Alpha-glucosidase inhibitory activity of soybeans fermented with mushroom mycelia
4.2.1 Methods
Yeast alpha-glucosidase inhibitory activity was measured using methods reported before [52] with modifications as described in Suruga et al. [10]. Briefly, yeast alpha-glucosidase was incubated with fermented soybean extract solutions and then p-nitrophenyl α-D-glucopyranoside (pNP-glucoside) was added and absorbance was determined at 400 nm. For the mammalian reaction, alpha glucosidase from rat intestinal acetone powder [53] was incubated with fermented soybean extract and the amount of glucose released was measured. We also used maltose as the substrate and calculated the % inhibition rate of alpha glucosidase [54].
4.2.2 Fermented soybean showed higher inhibition of alpha-glucosidase activity compared to non-fermented ones
Comparison of control (non-fermented soybeans) to soybeans fermented with mushroom mycelia showed that significant alpha-glucosidase inhibition could be achieved in the fermented soybeans using both pNP-glucoside and maltose (Figure 7A and B). Yeast alpha-glucosidase inhibition was the highest with
4.3 Comparison of isoflavone concentrations in soybeans fermented with mycelia versus non-fermented soybeans
4.3.1 Methods: high-performance liquid chromatography (HPLC) analysis
We followed the methods described in Kudou et al. [55] for measuring isoflavone concentrations in fermented and non-fermented soybeans. An LC-6A system (Shimadzu, Kyoto, Japan) equipped with a PEGASIL-ODS (4.6 mm i.d. × 250 mm) HPLC column (Senshu Scientific, Tokyo, Japan) was used for analysis. HPLC parameters used for the measurement of different isoflavones, such as genistein, daidzein, glycitein, daidzin, and glycitin, both in the glycosylated and in aglycone forms, are detailed in Suruga et al. [10].
4.3.2 Methods: liquid chromatography/mass spectrometry (LC/MS) analysis
An ACQUITY UPLC apparatus (Waters MS Technologies, Manchester, UK) equipped with a reversed-phase Acquity UPLC CHS C18 column with a particle size of 2.1 mm × 100 mm × 1.7 μm (Waters MS Technologies) was used for LC/MS analysis. Parameters of analysis are documented in detail in Suruga et al. [10].
4.3.3 Fermentation with mushrooms decreased the concentrations of glycosylated forms of isoflavones and increased the concentrations of aglycon forms
LC/MS profile was shown in Figure 8. The concentration of glycosylated forms of isoflavones, such as daidzin, glycitin, and genistin was about 95.6% in non-fermented soybeans, while it was reduced to 52.5, 15.8, and 17.6% in soybeans fermented by the
5. Discussion
5.1 Characteristics of H. ramosum mycelia and other mushroom mycelia
While the beneficial effects of mushrooms in human health and nutrition have long been known and their pharmacological use has been studied in several types of mushrooms, including
DPPH radical scavenging activity is a good indicator of antioxidant properties. Our study indicated that several mushrooms (
From our analyses, we have found that
Several compounds responsible for DPPH and antioxidant activity have been isolated from mushrooms and studied in detail. However, little information has been published regarding the DPPH scavenging activity of active compounds from mycelia of
The present findings indicate that the DPPH radical scavenging activity of the Hericiaceae group, including
NGF plays a crucial role in nerve growth and neuronal cell function, and protection of neurons. NGF has been implicated in various diseases, including in Alzheimer’s disease, the most common type of dementia that affects language, memory, processing of visual cues, judgment, and mood [69]. Reduced levels of NGF or increased accumulation of β-amyloid peptide and tau protein have been suggested as causes of AD [70]. Given its importance, there has been a demand for finding natural inducers of NGF synthesis. Natural compounds such as hericenones and erinacines isolated from
5.2 Soybean fermentation of mushroom mycelia
Mushrooms are effective in combating issues caused by obesity, diabetes, and other health issues [74]. The medicinal value of mushrooms has been known for thousands of years [75, 76] and they have been incorporated in nutrition supplements [74] and in the production of fermented foods, such as soybean-based foods, bread and cheese, and in alcoholic beverages [77]. However, detailed analysis of soybeans fermented by mushroom mycelia has not been conducted, insofar as their oxidative properties or alpha-glucosidase inhibitory activity are concerned. Our study analyzed all these properties and the LC/MS profiles of the bioactive products to glean more insights into the medicinal value of fermented soybeans.
We found that soybeans fermented with mushroom mycelia had stronger DPPH radical scavenging activity and ORAC than the non-fermented control ones. We also found that
The compound 8-hydroxydaidzein (peak #3 in Figure 8b) and one unidentified compound (peak #6) were identified by LC/MS analysis in soybeans fermented using
Alpha-glucosidases are the primary enzymes responsible for hydrolyzing carbohydrates into glucose. Inhibition of alpha-glucosidase activity, therefore, is a strategy for controlling increase in blood glucose levels in diabetic conditions. We have shown that soybeans fermented with mushroom mycelia have significantly higher alpha-glucosidase activity than the non-fermented control groups. When pNP-glucoside was used as a substrate, the yeast alpha-glucosidase activity was inhibited in soybeans fermented with
The beta-glucosidase enzyme (EC 3.2.1.21) produced by microbes facilitates the breakdown of glycosylated isoflavones to their aglycon form, which is more easily absorbable [85]. Several microbes, including
Our mass spectrometry analysis data revealed that the aglycon form of isoflavones obtained in soybeans fermented with
Acknowledgments
We are grateful to the Chairman and CEO Masahito Hoashi, Kibun Foods Inc., for his support of this study.
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