Application of environmental-safe fermentation with Saccharomyces cerevisiae for increasing the cinnamon biological activities
Bioresources and Bioprocessing volume 10, Article number: 12 (2023)
The effect of fermentation by Saccharomyces cerevisiae on biological properties of cinnamon (Cinnamomum cassia) was investigated. The study demonstrated that the extract of S. cerevisiae-fermented cinnamon (S.C.FC) has antioxidants higher than non-fermented one. The optimum results for antioxidant yield were noted with 107 CFU S. cerevisiae/10 g cinnamon and 70 mL of dH2O at pH 6 and incubated for 3 d at 35 °C. Under optimum conditions, ABTS, DPPH, and H2O2 radical-scavenging activity increased by 43.8, 61.5, and 71.9%, respectively. Additionally, the total phenols and flavonoids in S.C.FC were increased by 81.3 and 415% compared by non-fermented one. The fermented cinnamon had antimicrobial activity against L. monocytogenes, S. aureus, E. coli, S. typhi, and C. albicans. Also, the anti-inflammatory properties were increased from 89 to 92% after fermentation. The lyophilized extract of S.C.FC showed positive effect against Huh7 cancer cells which decreased by 31% at the concentration of 700 µg/mL. According to HPLC analysis, p-hydroxybenzoic acid, gentisic acid, catechin, chlorogenic acid, caffeic acid, and syringic acid were increased by 116, 33.2, 59.6, 50.6, 1.6, and 16.9%, respectively. Our findings suggest the applicability of cinnamon fermentation using S. cerevisiae as a useful tool for processing functional foods to increase their antioxidant and anti-inflammatory content.
Cinnamon as a multi-purpose medicinal plant is widely used around the world as a food additive, hot drink, and condiment. It is produced from the inner bark of tropical tree species belonging to the genus Cinnamomum (Lauraceae family). The most well-known species in the genus Cinnamomum are C. cassia, along with C. verum, C. zeylanicum, and C. burmannii (Gutiérrez et al. 2021; Liu et al. 2021; Nunes et al. 2022). Numerous illnesses, including gastrointestinal pain, cancer, infections, and the common cold, can be successfully treated with cinnamon as a supplementary therapy (Hamidpour et al. 2015). According to many reports, cinnamon considered as an antioxidant, analgesic, anti-ulcer, anti-bacterial, anti-allergic, anti-inflammatory, antipyretic, anti-cancer, and anti-diabetic agent (Abdel-Tawwab et al. 2018; Sadeghi et al. 2019).
The antioxidant properties of cinnamon extract are comparable to those of the synthetic antioxidant benchmark butylated hydroxytoluene (BHT). Moreover, it showed protection activity against irradiation-induced lipid peroxidation in liposomes, and managed to quench hydrogen peroxide and hydroxyl radicals (Su et al. 2007; Eweys et al. 2022). Also, it has been reported that cinnamon improves the insulin sensitivity index by enhancing insulin resistance, and thus can reduce diabetic syndrome by normalizing pancreatic function (Li et al. 2013). Cinnamon volatile oils are highly effective as antimicrobials against many multidrug-resistant bacteria and fungi. Its anti-bacterial activity has been reported to be more effective than some common antibiotics (e.g., ampicillin, chloramphenicol, and streptomycin) (El Atki et al. 2019). The nature of food processing has a positive or negative impact on its contents of biologically active compounds (including antioxidants). Some treatments increase the extractability of some compounds or cause structural transformations in others. For example, Ravichandran et al. (2013) reported that microwave, roasting, and boiling provided better extractability. The antioxidant activity of red beets (up to threefold) was significantly increased due to the polyphenol content.
Fermentation converts the conjugated phenolic compounds to more hydroxyl groups which cause changes in antioxidant activity during fermentation (Wang et al. 2018; Eweys et al. 2022). Zhao et al. (2021a) demonstrated how the structural collapse of cereal cell walls, which allowed for the creation and liberation of a variety of bioactive chemicals, allowed microbes to change plant elements. Also, Hur et al. (2014) confirmed that enzymes, such as cellulases, inulinase, tannase, amylase, and glucosidase, could be produced during fermentation, and can breakdown the plant cell wall producing bioactive compounds.
The yeast, Saccharomyces cerevisiae, is a useful tool for most aspects of basic research. Despite efforts to find new microbes, S. cerevisiae continues to be one of the most fermentation bioagent (Klopp et al. 2021). The biotechnological use of S. cerevisiae is based on its unique biological properties, namely its fermentation capacity (Parapouli et al. 2020). In particular, three characteristics are very important for some industrial applications of S. cerevisiae, its capability of withstanding stressful conditions, rapid growth, and fermentation efficiency (Andrietta et al. 2007). Also, there are two important properties of S. cerevisiae that are extremely essential for industrial applications: its tolerance to high sugar concentrations, and the production of fragrant and aromatic chemicals (Parapouli et al. 2020). The improvement of S. cerevisiae to the organoleptic characteristics can be returned to its ability to produce flavor compounds, such as aldehydes, esters, and alcohols (Menezes et al. 2016; Magalhaes et al. 2017). In biological systems, phenolic substances exhibited peroxide decomposition and free radical inhibition (Aryal et al. 2019). Furthermore, numerous studies have shown that flavonoid consumption improves heart performance (Banjarnahor 2014). As a result, recent research emphasizes the functional activity of flavonoids, and phenolics as antioxidants against oxidative stress (Banjarnahor 2014; Aryal et al. 2019). For that, the present work is a scientific contribution to study the effect of S. cerevisiae fermentation on the biological properties of cinnamon. Hopefully, the results of this study are valuable in this field.
Materials and methods
Materials, reagents, and media
Cinnamon (C. cassia) powder was purchased from a local store in Egypt (Kirkland organic ground Saigon cinnamon, Vietnam). Lactobacilli MRS Broth (NEOGEN, NCM0079B), Nutrient broth, and Nutrient agar media were obtained from HiMedia Leading BioSciences Company, India. All chemicals and reagents used were of analytical grade and purchased by lab suppliers from Sigma-Aldrich, VWR chemicals and Merk, India.
Saccharomyces cerevisiae strain
Saccharomyces cerevisiae was isolated and purified from the commercial compressed baker's fresh yeast available in the local markets in Egypt. Briefly, 1 g of compressed baker's fresh yeast were added to 90 mL of sterilized saline water, and various serial dilutions were made (1 mL of previous culture/9 mL water to make new dilution). One mL from different dilutions was inoculated on the surface of nutrient agar plates and then incubated at 35 ± 2 ℃ for 24–48 h. A separated single colony was picked up and re-streaked on new nutrient agar plates for purification. The purified isolate was subjected to microscopic and cultural examination according to the protocol of Kurtzman et al. (2011) and Khattab et al. (2016) to confirm that it is S. cerevisiae. The cultural examinations include the growth pattern on solid and liquid media as well as the ability to use glucose, galactose, maltose, lactose, sucrose, and ethanol individually as the sole carbon source. The purified yeast was maintained on nutrient agar slants at refrigerator (4 °C) for further experiments.
Fermentation technology of cinnamon aqueous solution
Fermentation starter was prepared by cultivation of S. cerevisiae strain loop in 250-mL conical flasks containing 50 mL of Nutrient broth and incubated for 24 h at 35 ℃ on a rotary shaker at 120 rpm. After incubation, cells were harvested by centrifugation (5600 g for 10 min) and then re-suspended in a sufficient volume of sterile distilled water to obtain a cell density of 107 CFU/mL. The immediately obtained S. cerevisiae suspension was used as a fermentation initiator with a specified volume according to the scheme. Fermented cinnamon was prepared according to the method of Eweys et al. (2022) with some minor modifications. In brief, 10 g of sterilized cinnamon powder was mixed with 70 mL of sterilized distilled water, and then, specific volume of S. cerevisiae as inoculum was added. The fermentation mixture was incubated at 35 ℃ on a rotary shaker at 120 rpm. Some important fermentation factors were included to study their effect on antioxidant production, namely inoculum concentration, incubation period, and initial pH. The cell concentration of the S. cerevisiae inoculum used for fermentation was 100, 102, 103, 105, 107, and 109 CFU/ 10 g of cinnamon. While the incubation periods were 1, 2, 3, 4, and 5 days, and the initial pH was adjusted at values of 4, 5, 6, 7, and 8 using 1 N of HCl or NaOH. The unfermented (cinnamon sample without S. cerevisiae inoculation) was used as a control in this experiment. The counts of S. cerevisiae in the fermented samples were enumerated by pour plate technique using nutrient agar medium.
Extraction of fermented cinnamon
The aqueous phase obtained after the centrifugal removal (5600 g for 10 min) of cells and sediment of the cinnamon fermentation mixture was used as the “extract”. For comparison, non-fermented cinnamon was subjected to a similar extraction process using only distilled water. The aqueous extracts of fermented and non-fermented cinnamon were freeze-dried at – 50 ℃ for 48 h (Labconco freeze dryer, Console, USA). Freeze-dried cinnamon extracts were analyzed for their total phenol and flavonoid content, antimicrobial activity, anti-inflammatory activity, and anti-cancer activity. HPLC and TLC analyses also have been conducted for the lyophilized extracts.
Determination of antioxidant activity
The antioxidant samples were prepared by dissolving 0.2 mg of the lyophilized cinnamon extract in 1 mL of distilled water, in which DPPH, ABTS, and hydroxyl radical-scavenging activity (%) were measured.
DPPH radical-scavenging assay
The antioxidant activity of cinnamon was measured using 2, 2-diphenyl-1-picrylhydrazyl (DPPH˙) method described by Darwesh et al. (2022) with some modifications. Briefly, a portion of 0.1 mL sample was added to 3.9 mL of freshly prepared DPPH solution (22 mg of DPPH in 50 mL methanol). The mixture was vortexed for 30 s then kept in a dark place at room temperature for 30 min. The decolorization of DPPH reaction mixture was measured at 515 nm using a UV–Vis spectrophotometer (JASCO serial No. A114761798, Japan). The DPPH free radical-scavenging activity (%) was calculated as the percentage of absorbance decrease.
ABTS radical-scavenging assay
According to Mohdaly et al. (2010) with some modifications, an equal volume of 2.4 mmol/L potassium persulfate was mixed with 7 mM ABTS and then incubated at room temperature for 12–16 h in the dark. The ABTS+ solution was diluted with distilled water to obtain initial absorbance of 0.70 ± 0.02 at 734 nm. A 0.25 mL of 60-fold diluted sample was added to 0.75 mL of distilled water and 1 mL of 2,2′-azino-bis(3-ethylbenzothiazoline-6-sulfonate diammonium) (ABTS+) solution, and then incubated at room temperature for 7 min. The absorbance decrease was recorded at 734 nm and ABTS+ scavenging effect (%) was calculated as the percentage of absorbance decrease.
Hydroxyl radical-scavenging activity assay
Hydroxyl radical-scavenging activity was determined by the method presented by Bhattaram et al. (2002) with some modifications. A volume of 0.3 mL sample was added to 0.9 mL of 50 mM phosphate buffer (pH = 7.4) and 1.8 mL of H2O2 solution (2 mM). The mixture was vortexed and kept at room temperature for 10 min. The absorbance decrease was measured at 230 nm and the scavenging activity (%) was calculated as the percentage of absorbance decrease.
Determination of total phenolic contents
The total phenolic content (TPC) was determined according to Khan et al. (2018) and Eweys et al. (2022) with minor modifications. A 0.5 mL of cinnamon extract solution (2 mg lyophilized extract/mL DW) was mixed with 0.5 mL of 10% Folin–Ciocalteu’s reagent diluted in 13 mL distilled water. After that, 2.5 mL of 7% Na2CO3 solution was added followed by mixing. The reaction mixture was incubated at room temperature for 2 h in the dark. The absorbance was measured at 760 nm. Total phenolic content was calculated by extrapolating a calibration line constructed with gallic acid as standard solution (Additional file 1: Fig. S1). The total phenolic content was expressed as mg gallic acid equivalent per gram dry weight extract (mg GAE/ g lyophilized extract).
Determination of total flavonoid contents
The total flavonoids content was determined according to method described by Khan et al. (2018) with some modifications. In brief, 0.5 mL of cinnamon extract solution (2 mg lyophilized extract/mL DW) was mixed with 2.5 mL of distilled water, 1 mL of potassium acetate (1 M), and 1 mL of 10% aluminum chloride. The total flavonoids’ content was estimated by extrapolating a calibration line constructed with quercetin solution (Additional file 1: Fig. S2). The absorbance of the reaction was measured at 415 nm using UV–Vis spectrophotometer. The total flavonoid content was stated in terms of quercetin equivalent (mg QE/ g of lyophilized extract).
Evaluation of antimicrobial activity
The antimicrobial activity of the lyophilized aqueous cinnamon extract (0.2 g/ mL DW) was determined using the agar well diffusion method reported by Sultan et al. (2016) with some modifications. The tested microorganisms were Gram-negative bacteria (E. coli ATCC-25922 and Salmonella typhi ATCC-15566), Gram-positive bacteria (Listeria monocytogenes ATCC-35152 and Staphylococcus aureus ATCC-47077), and yeast (Candida albicans ATCC-10231). All test strains were obtained from the American Culture Collection (ATCC, Rockville, MD, USA). The tested strains were cultured in nutrient broth medium for 24 h; after that, an adequate volume (100 µL from each) was spread onto the surface of nutrient agar plates. The wells (7 mm diameter) were mined on the inoculated plates and 75 µL of the previous DW–cinnamon mixture was added to the well (Darwesh et al. 2019). The plates were incubated at 35 ± 2 ℃ for 16–24 h, and then, the clear zones have been measured. The antimicrobial activities calculated according to the obtained inhibition zones on agar plates.
Determination the effect of fermentation technology on the anti-inflammatory activity of cinnamon
The human red blood cell (HRBC) membrane stabilization method was applied to test the in vitro anti-inflammatory activity of cinnamon sample (Vana and Botting 1995). Blood was collected from one healthy volunteer. The collected blood was mixed with equal volume of sterilized Alsever′s Solution (2% dextrose, 0.8% sodium citrate, 0.05% citric acid, and 0.42% sodium chloride in water). The blood was centrifuged at 2016 g for 20 min and packed cells were separated. The packed cells were washed with isosaline (0.85%, pH 7.2) and a 10% v/v suspension was made with isosaline. The HRBC suspension was used for the estimation of anti-inflammatory activity. One milliliter of sample and Diclofenac sodium (as positive control) were separately mixed with 1 mL of phosphate buffer (0.15 M, pH 7.4), 2 mL of hyposaline (0.36%) and 0.5 mL of HRBC suspension. Instead of sample, 2 mL distilled water was used as the negative control. All the assay mixture was incubated at 37 °C for 30 min and centrifuged at 2016 g for 20 min. The supernatant liquid was decanted and the hemoglobin content in the supernatant solution was estimated using spectrophotometer at 560 nm. Percentage of hemolysis was estimated by assuming the hemolysis produced in the control as 100%. The percentage hemolysis was calculated using the following formula:
The percentage of HRBC membrane stabilization or protection was calculated by the following formula:
Anticancer activity evaluation and cytotoxicity determination of cinnamon
Huh7 (liver cancer cell line) and Wi38 cells (human lung fibroblast cell line) were purchased from VACSERA (the Holding Company for Biological Products and Vaccines) at Giza governorate, Egypt and the procedures were done in Cairo University Research Park (CURP). The test was done according to neutral red uptake assay (Repetto et al. 2018; Hussein et al. 2019). Trypsinized cells were sub-cultured into 25cm2 tissue culture flasks. A 5 × 105 cells were cultured in each flask containing 7 mL of complete Dulbecco’s modified eagle medium (DMEM) supplemented with 1% antibiotic solution (100 U/mL penicillin and 100 μg/mL streptomycin) and 10% of fetal bovine serum and incubated at 37 ± 1 °C. All culture reagents were purchased from Lonza supplier in Egypt. Huh7 cells as cancer cells were divided as follows: Group 1 served as untreated control without any treatment, Group 2 cells inoculated with freeze-dried fermented cinnamon extract at 100, 300, 500, and 700 µg/mL, and Group 3 cells inoculated with freeze-dried non-fermented cinnamon extract at 100, 300, 500, and 700 µg/mL. Also, Wi38 cells as normal cells were divided as mentioned with Huh7 cells. The cells were exposed to neutral red dye (4 mg/mL) in serum free DMEM after treatment periods for 3 h. The cells were washed with phosphate-buffered saline (PBS) and then de-stained using de-staining solution (50% EtOH and 5% glacial acetic acid in distilled water). The absorbance of residues neutral red dye was measured at 540 nm using spectrophotometer. Each treatment was done in triplicates after 24 h of incubation.
Thin-layer chromatography for characterization of cinnamon extracts
Active components of lyophilized fermented and non-fermented cinnamon extracts were characterized by thin-layer chromatography (TLC). TLC silica gel 60 F254 plates (Merck KGaA, Darmstadt, Germany) were prepared in system of ethyl acetate: hexane at a ratio of 1:1 v/v using TLC paper covered with silica gel as stationary phase (Utchariyakiat et al. 2016). They were emerged in the working solvent system as mobile phase. The TLC plate was visualized under UV light (254 and 366 nm).
HPLC analysis for characterization of cinnamon extracts
High-performance liquid chromatography (HPLC) analysis was carried out according to Kim et al. (2006) using Agilent Technologies 1100 series liquid chromatograph equipped with an autosampler and a diode-array detector. The analytical column was an Eclipse XDB-C18 (150 × 4.6 µm; 5 µm) with a C18 guard column (Phenomenex, Torrance, CA). The mobile phase consisted of acetonitrile (solvent A) and 2% acetic acid in water (v/v) (solvent B). The flow rate was kept at 1 mL/min for a total run time of 60 min and the gradient program was as follows: 100 to 85% B in 30 min, 85 to 50% B in 20 min, 50 to 0% B in 5 min, and 0 to 100% B in 5 min. The injection volume was 20 µL and peaks were monitored simultaneously at 280 and 320 nm for the benzoic acid and cinnamic acid derivatives, respectively, as well as 360 nm for flavonoids. All samples were filtered through a 0.45 µm acrodisc syringe filter (Gelman Laboratory, MI) before injection. Peaks were identified by congruent retention times and UV spectra and compared with those of the standards.
All analyses were performed in triplicate and data reported as the mean ± standard deviation (SD). Results were processed by One-Way ANOVA: analysis of variance using the statistical software of Statistix 8.1 (Analytical Software, Tallahassee, FL, USA) using LSD’s test for pairwise comparison.
Results and discussion
S. cerevisiae strain, isolation, purification, and identification
Choosing the right microbial strain contributes significantly to the success of fermentation process, types, and quantities of emerging products. In this context, S. cerevisiae is one of the most industrially known yeast strains for large-scale fermentation in a long time (Walker and Stewart 2016). As that, S. cerevisiae was selected as the bioagent for cinnamon powder fermentation and the potential to influence its yield of antioxidants and other vital compounds. The isolate, S. cerevisiae, was obtained by purification of the commercial compressed baker’s fresh yeast available in the local markets in Egypt. The purified yeast underwent characterization and morphological identification to confirm its identity as S. cerevisiae.
The developed single colony on the surface of nutrient agar plate (after being incubated at 35 ± 2 ℃ for 24–48 h) appeared as smooth and raised with a creamy color. The color of the precipitated cells after similar incubation period in the nutrient broth medium was white. Microscopically, the cells were ovoidal and globose with multilateral budding (Fig. 1). On the other hand, the isolate showed well assimilation to glucose, maltose, and sucrose but not lactose, and glycerol. The results of the biochemical tests and the morphological characteristics of the isolated yeast confirm that it is S. cerevisiae according to Khattab et al. (2016).
Influence of S. cerevisiae fermentation on the antioxidant activity of cinnamon
The present study aimed mainly to improve the antioxidant activity of cinnamon by fermentation with the edible probiotic yeast, S. cerevisiae. Fermentation products are expected to be affected by the number of microorganisms involved in the fermentation, the fermentation time, and initial pH of the fermentation mixture. Hence, for such investigations, S. cerevisiae was applied to cinnamon solution to determine their ability to enhance antioxidant substances production.
The optimum yeast concentration must be used to provide the optimum fermentation properties. Fermentation is an enzymatic process; hence, the low concentration of yeast will cause slow fermentation (Gunawan et al. 2018). Using a high yeast concentration can cause yeast competition and fighting each other, leading to growth inhibition (Hibbing et al. 2010). Therefore, it is very important to use the optimum yeast concentration as an inoculum for the fermentation process. In this context, the antioxidant productivity of cinnamon based on fermentation with different concentrations of S. cerevisiae was investigated. Five cell concentrations of yeast were applied for cinnamon fermentation; 102, 103, 105, 107, and 109 CFU/10 g of cinnamon. A 100 CFU/ 10 g of cinnamon was used as a control.
The antioxidant activity was recorded (and calculated) as a percentage of ABTS radical-scavenging activity, DPPH radical-scavenging activity, and H2O2 scavenging activity. The results of antioxidant activities after aqueous extraction were measured for fermented and non-fermented cinnamon and are illustrated in Table (1). The obtained results revealed that the concentration of S. cerevisiae cells in fermentation mixture for cinnamon influences its antioxidant yield. Regarding DPPH scavenging activity, the results of antioxidant yield due to initial inoculum yeast concentration of 109 CFU/ 10 g of cinnamon were significantly the highest compared to lower other initial inoculant concentrations and the control. However, the inoculum concentration of 107 CFU/ 10 g of cinnamon showed significantly higher antioxidant activity than all other lower concentrations, but without significance compared to the control group. The antioxidant activity expressed with ABTS was highest when the initial inoculum was 107 CFU/10 g of cinnamon; although it was not significant with those of 105 and 109 CFU/10 g of cinnamon. In addition, there were no significant differences between the ABTS results for non-fermented cinnamon and the fermented with initial yeast concentrations of 102 and 105 CFU/10 g cinnamon. On the contrary, the antioxidant activity of cinnamon expressed as H2O2 scavenging activity scored the lower value when the applied yeast inoculant was 109 CFU/10 g cinnamon. The results showed that the concentration of yeast inoculum at 107 CFU/10 g cinnamon was the most suitable in terms of high antioxidant production during the fermentation of cinnamon by S. cerevisiae. The low cell concentration gave lower value as compare to without fermentation, it may due to the microbial culture is not enough to ferment the cinnamon (decomposition of polyphenols or complex compounds to phenols or simple one) and the microbial cells uses the simple compounds like phenols for growth, followed decreasing in antioxidant activity.
For the fermentation process, the length of time that microorganisms are in contact with the substrate is crucial. Therefore, it is crucial to provide the fermentation process enough time to produce the targeted components (Gunawan et al. 2018; Aung 2022). Hence, the effect of different yeast fermentation periods on the production of antioxidants from cinnamon was studied to determine the sufficient time to obtain the highest yield. Five different incubation periods, 1, 2, 3, 4, and 5 days, were used for cinnamon fermentation. Following various incubation times, the antioxidant activities of aqueous extract samples of S. cerevisiae-fermented cinnamon were examined and the results of scavenging activities expressed by ABTS, DPPH, and H2O2 radicals are shown in Table (2). In general, the antioxidant yield of fermented cinnamon increased until the third incubation day and then decreased on the fourth and fifth days. The increase in fermentation-induced antioxidants during the first 3 days can be attributed to the activity of S. cerevisiae in converting the complex compounds in cinnamon into simple, easy-to-extract forms. Whereas the decrease in antioxidant activity after a relatively long incubation period can be attributed to microbial competition, or microbial decomposition of some bioactive compounds (Hibbing et al. 2010). Based on the high antioxidant yield of cinnamon by fermentation during 3 days with yeast, this period was used as an incubation period for the following experiments.
The microbe's enzymatic system is directly impacted by the pH of the fermentation medium, which has an impact on how will the microbe can grow and create different byproducts (Namasivayam et al. 2011; Zhao et al. 2021b). Furthermore, changing the pH below or above the optimum value may result in the formation of different (sometimes undesirable) fermentation products. In addition, it may affect the bio-transformation processes of materials either negatively or positively (Lee et al. 2021). The effect of the difference in initial pH of S. cerevisiae–cinnamon mixture on the antioxidant yield after 3 days of fermentation was studied. The initial pH values under study ranged from 4 to 8, and the values of the antioxidants produced in the aqueous extract of fermented cinnamon are represented in Table 3. The cinnamon fermented by S. cerevisiae had the maximum antioxidant activity measured by ABTS, DPPH, and H2O2 when the initial pH was 7. Although cinnamon initially fermented at pH 7 had the highest levels of antioxidants, its antioxidant activity was not significantly different from that fermented at pH 6. It is noted that the original pH of the cinnamon–yeast mixture was close to 6 (at 10 g of cinnamon and 70 mL of distilled water). Therefore, the economic cost of adjusting the pH to 7 at the industrial or semi-industrial level should be taken into account, since there are no significant differences between it and the results of the pH 6 regarding the yield of antioxidants from fermented cinnamon.
Optimized cinnamon fermentation conditions with S. cerevisiae
The current study focuses on the effect of fermentation by S. cerevisiae on increasing the antioxidant productivity from cinnamon. According to earlier findings, adjusting the fermentation conditions can increase the amount of antioxidants produced by cinnamon. Optimal conditions include a 3-day incubation period at 35 °C, an initial pH of 6, and an initial yeast density of 107 CFU/10 g cinnamon. Aqueous extracts of fermented cinnamon (under ideal conditions) and non-fermented cinnamon that had been freeze-dried were evaluated. The characteristic covers antioxidant activities, total phenols and flavonoids, antimicrobial activity, anti-inflammatory, anti-cancer and cytotoxic activities, TLC, and HPLC were analyzed.
Antioxidant activities, total phenols, and flavonoids
Indicators of DPPH, ABTS, and H2O2 were used to assess the antioxidant activity of lyophilized cinnamon extracts. The results showed that the lyophilized extract of fermented cinnamon scavenged ABTS, DPPH, and hydroxyl radicals considerably better than non-fermented cinnamon (Table 4). According to the ABTS radical-scavenging activity, cinnamon fermented with S. cerevisiae was 43.8% better than non-fermented cinnamon. Based on the DPPH test for radical-scavenging activity, fermented cinnamon had 61.5% more antioxidants than unfermented. While the percentage of increase when taking into account the measure of H2O2 radical-scavenging activity for antioxidants was about 71.9% in fermented cinnamon than in non-fermented cinnamon. On the other hand, fermentation was found to enhance the content of phenols and total flavonoids of cinnamon extract. The obtained result (Table 4) confirms the increase of total extracted phenols and flavonoids in S. cerevisiae-fermented cinnamon more than non-fermented one by 81.3 and 415%, respectively. Natural flavonoid and phenolic compounds are plant secondary metabolites which hold an aromatic ring bearing at least one hydroxyl group (Tungmunnithum et al. 2018). It is well clear that fermentation of cinnamon causes an increase in the contents of total flavonoid and phenolic contents in its lyophilized extract. This incensement could be attributed to the bio-transformation of some cinnamon’s components or the breakdown of cell walls, which helps produce a variety of antioxidant chemicals (Hur et al. 2014).
Antimicrobial and anti-inflammatory activity evaluation
Many herbs and spices have antimicrobial properties that offer them therapeutic value in medicine. They can also be used as food ingredients to extend the shelf life of food and protect it against food poisoning bacteria. The therapeutic use of cinnamon includes its natural anti-bacterial activity against many pathogens such as Moraxella catarrhalis that can cause respiratory system infections (Rasheed and Thajuddin 2011; Nabavi et al. 2015). Fermentation is expected to positively or negatively affect cinnamon's antimicrobial activity. It was therefore important to study the antimicrobial efficacy of lyophilized cinnamon extract and the effect of this activity in the case of S. cerevisiae-fermented cinnamon. Gram-positive bacteria L. monocytogenes and S. aureus, Gram-negative bacteria E. coli and S. typhi, and the yeast C. albicans were used in the evaluation. The applied concentration, that is, 200 mg/mL of lyophilized fermented and non-fermented cinnamon extract, showed a positive effect against all studied pathogens. However, fermented cinnamon extract showed lower inhibition than non-fermented cinnamon (measured by diameter of inhibition) against all tested bacteria (Table 5 and Fig. 2). The fermentation cause around 10.5 to 26.6% decrease in the antimicrobial activity of cinnamon extract. The reduced antimicrobial activity of fermented cinnamon extract may be attributed to the hydrolysis of some antimicrobial components of cinnamon, such as cinnamaldehyde and eugenol to their derivatives (Tadasa 1977; Nabavi et al. 2015). It should be noted that cinnamaldehyde degrades to cinnamic acid, which has higher free radical-scavenging properties than cinnamaldehyde besides its anti-tuberculosis and anti-inflammatory properties (Suryanti et al. 2018). In addition, vanillin and ferulic acid are produced during the breakdown of eugenol (Tadasa 1977). This vanillin product has been previously shown to have stronger antioxidant activity than ascorbic acid, trueox in ABTS( +)-scavenging, and oxygen radical absorption capacity (ORAC) assays (Tai et al. 2011).
In case of anti-inflammatory properties of C. cassia extract after fermentation by S. cerevisiae, the cinnamon powder was fermented and evaluated its anti-inflammatory properties comparing with non-fermented one and diclofenac as a non-steroidal anti-inflammatory and phenylacetic acid derivative drug (standard at concentration of 2000 μg/mL). The obtained results (Fig. 3) indicated that increasing the anti-inflammatory properties of cinnamon after fermentation by S. cerevisiae from 89 to 92% of human red blood cells’ protection from agglomeration. This may be returned to available of some compounds like cinnamic acid (Godoy et al. 2000; Suryanti et al. 2018), vanillin (Kim et al. 2019), or ferulic acid (Liu et al. 2022).
Anticancer activity and cytotoxicity evaluation
Cinnamon has been shown to have anti-cancer properties (Hamidpour et al. 2015), and it could inhibit cancer cell proliferation and increases apoptosis in human oral cancer (Wu et al. 2018). On the other hand, liver cancer is a serious health problem, the fourth-largest cause of cancer-related deaths globally, and the sixth most prevalent cancer (Leone et al. 2021). The most frequent type of liver cancer, hepatocellular carcinoma (HCC), is ranked as the fourth-leading cause of cancer-related death worldwide (Huang et al. 2020). Therefore, it is crucial to understand if fermentation with the yeast S. cerevisiae could increase or decrease this activity based on liver cancer cells (Huh7). The obtained results showed that at all concentrations tested, extracts of fermented cinnamon clearly decreased the metastasis of cancer cells compared to the extracts of non-fermented cinnamon (Fig. 4). The fermented cinnamon decreased the cancer cell viability by 31% at the concentration of 700 µg/mL. However, the obtained results was limited to the concentration of 700 µg/mL, and higher concentrations of lyophilized fermented cinnamon extracts may increase the death of cancer cells. Consequently, the fermentation of cinnamon powder with the yeast S. cerevisiae successfully increases the anti-cancer activity of cinnamon (Additional file 1: Fig. S3).
Characterization and identification the products of fermentation processes
Some biologically active chemicals may be created or removed from the fermentation media as a result of fermentation. Therefore, to examine the primary components of cinnamon before and after fermentation of cinnamon with S. cerevisiae, thin-layer chromatography was employed. Analysis at Additional file 1: Fig. S4 revealed that one of the components from the fermented cinnamon had vanished. Cinnamaldehyde, an aromatic aldehyde chemical found in cinnamon, may be this substance (Utchariyakiat et al. 2016). Cinnamaldehyde separated on silica gel more quickly than cinnamic acids. Additionally, the oxidation of aldehydes produced carboxylic acids like cinnamic acid. As a result, cinnamaldehyde may oxidize to cinnamic acid during fermentation (Poole and Poole 1994; Dvorackova et al. 2015). Caffeic acid and p-coumaric acid were discovered in both fermented and unfermented cinnamon using thin-layer chromatography. Both of those substances have been identified as natural antioxidants (Kiliç and Yeşiloğlu 2013; Espíndola et al. 2019). TLC analysis is regarded as the first stage of characterization and must be followed by a more advanced analysis, such as HPLC. Therefore, utilizing a number of common antioxidant chemicals, the fermented samples were analyzed using HPLC.
The extracts of both fermented and non-fermented cinnamon were subjected to HPLC analysis to identify and measure certain bioactive components (Table 6). Gallic acid, p-hydroxybenzoic acid, catechin chlorogenic acid, and protocatechuic acid were all put into HPLC as standards (Fig. 5). Some bioactive compounds have been increased in the lyophilized extract of S. cerevisiae-fermented cinnamon. According to HPLC analysis (Table 6), p-hydroxybenzoic acid, gentisic acid, catechin, chlorogenic acid, caffeic acid, and syringic acid increases by 116, 33.2, 59.6, 50.6, 1.6, and 16.9%, respectively. The content of antioxidant p-hydroxybenzoic acid and gentisic acid may be enhanced because of hydrolysis of benzoic acid during fermentation (Dvorackova et al. 2015; Adhikari et al. 2021). p-Hydroxybenzoic acid has antioxidant, and anti-inflammatory characteristics by increasing the expression of antioxidants leading to better plasma lipid profiles (Juurlink et al. 2014). Also, gentisic acid has anti-inflammatory, antigenotoxic, and antimicrobial activities (Abedi et al. 2020). In addition, epicatechin may be converted to the antioxidant catechin during fermentation of cinnamon (Rao and Gan 2014; Fathima and Rao 2016). Additionally, caffeic acid may connect to quinic acid to form chlorogenic acid which has antioxidant activity (Bhattaram et al. 2002; Xu et al. 2012). Moreover, hydrolysis of hydroxycinnamic acid by fermentation may form caffeic acid which is antioxidant and neuroprotective (Sakai and Tsukuba 2015). Furthermore, Janel and Noll (2014) mentioned that lignin can be hydrolyzed to the antioxidant compound syringic acid (Srinivasulu et al. 2018). Fortunately, the decreased compounds, such as gallic acid, may be hydrolyzed to the antioxidant compound catechin (Ahmed and Steppy 2013). Also, protocatechuic acid content was lowered; it may be esterified, and the esterification of hydrophilic phenolic antioxidants increased their antioxidant activity (Reis et al. 2010). According to these results, S. cerevisiae fermentation increased the free radical-scavenging activity of cinnamon.
Fermenting cinnamon with S. cerevisiae can increase its antioxidant and anti-carcinogenic properties without releasing harmful chemicals. The presence of more phenolic components and flavonoids in fermented cinnamon aqueous extracts may be the cause of their improved radical-scavenging capacity. Fermentation process increased p-hydroxybenzoic acid, gentisic acid, catechin, and chlorogenic acid which resulted in increasing the antioxidant, anti-inflammatory, antigenotoxic, and neuroprotective activities of cinnamon. Moreover, lyophilized extract of S. cerevisiae-fermented cinnamon causes decreasing of human cancer cell viability by 31% at the concentration of 700 µg/mL. The results obtained highlight the significance of the fermenting approach in enhancing the antioxidant and anti-cancer properties of numerous medical plants and herbs.
Availability of data and materials
Data will be made available on request.
- C . cassia :
Cinnamon (Cinnamomum Cassia)
- S. cerevisiae :
- H2O2 :
Gallic acid equivalent
High-performance liquid chromatography
Dulbecco’s modified eagle medium
Abdel-Tawwab M, Samir F, Abd El-Naby AS, Monier MN (2018) Antioxidative and immunostimulatory effect of dietary cinnamon nanoparticles on the performance of Nile tilapia, Oreochromis niloticus (L.) and its susceptibility to hypoxia stress and Aeromonas hydrophila infection. Fish Shellfish Immunol 74:19–25. https://doi.org/10.1016/j.fsi.2017.12.033
Abedi F, Razavi BM, Hosseinzadeh H (2020) A review on gentisic acid as a plant derived phenolic acid and metabolite of aspirin: comprehensive pharmacology, toxicology, and some pharmaceutical aspects. Phytother Res 34(4):729–741. https://doi.org/10.1002/ptr.6573
Adhikari M, Joshi NK, Joshi HC, Mehata MS, Mishra H, Pant S (2021) Revisiting the photochemistry 2, 5-dihydroxy benzoic acid (gentisic acid): solvent and pH effect. J Phys Organic Chem 34(4):e4168. https://doi.org/10.1002/poc.4168
Ahmed S, Steppy JR (2013) c0005 Pu-erh Tea: Botany, Production, and Chemistry, Tea in Health and Disease Prevention. Elsevier .https://doi.org/10.1016/B978-0-12-384937-3 00005-7.
Andrietta MGS, Andrietta SR, Steckelberg C, Stupiello ENA (2007) Bioethanol—30 years of Proálcool. Int Sugar J 109:195–200
Aryal S, Baniya MK, Danekhu K, Kunwar P, Gurung R, Koirala N (2019) Total phenolic content, flavonoid content and antioxidant potential of wild vegetables from Western Nepal. Plants 8(4):96. https://doi.org/10.3390/plants8040096
Aung T, Eun JB (2022) Impact of time and temperature on the physicochemical, microbiological, and nutraceutical properties of laver kombucha (Porphyra dentata) during fermentation. LWT 154:112643. https://doi.org/10.1016/j.lwt.2021.112643
Banjarnahor SD, Artanti N (2014) Antioxidant properties of flavonoids. Med J Indonesia 23(4):239–244. https://doi.org/10.13181/mji.v23i4.1015
Bhattaram VA, Graefe U, Kohlert C, Veit M, Derendorf H (2002) Pharmacokinetics and bioavailability of herbal medicinal products. Phytomedicine 9:1–33. https://doi.org/10.1078/1433-187X-00210
da Magalhães VMI, de Figueiredo VL, da Cruz Pedroso MMG, Santos C, Lima N, Freitas SR (2017) Impact of a microbial cocktail used as a starter culture on cocoa fermentation and chocolate flavor. Molecules 22(5):766. https://doi.org/10.3390/molecules22050766
Darwesh OM, Barakat KM, Mattar MZ, Sabae SZ, Hassan SH (2019) Production of antimicrobial blue green pigment Pyocyanin by marine Pseudomonas aeruginosa. Biointerface Res Appl Chem 9:4334–4339
Darwesh OM, Mahmoud RH, Abdo SM, Marrez DA (2022) Isolation of Haematococcus lacustris as source of novel anti-multi-antibiotic resistant microbes agents; fractionation and identification of bioactive compounds. Biotechnol Reports 35:e00753. https://doi.org/10.1016/j.btre.2022.e00753
Dvorackova E, Snoblova M, Chromcova L, Hrdlicka P (2015) Effects of extraction methods on the phenolic compounds contents and antioxidant capacities of cinnamon extracts. Food Sci Biotechnol 24(4):1201–1207. https://doi.org/10.1007/s10068-015-0154-4
El Atki Y, Aouam I, El Kamari F, Taroq A, Nayme K, Timinouni M, Lyoussi B, Abdellaoui A (2019) Antibacterial activity of cinnamon essential oils and their synergistic potential with antibiotics. J Adv Pharm Technol Res 10(2):63–67. https://doi.org/10.4103/japtr.JAPTR_366_18
Espíndola KMM, Ferreira RG, Narvaez LEM, Silva Rosari ACR, Da Silva AHM, Silva AGB, Monteiro MC (2019) Chemical and pharmacological aspects of caffeic acid and its activity in hepatocarcinoma. Front Oncol. https://doi.org/10.3389/fonc.2019.00541
Eweys AS, Zhao YS, Darwesh OM (2022) Improving the antioxidant and anticancer potential of Cinnamomum cassia via fermentation with Lactobacillus plantarum. Biotechnol Reports 36:e00768. https://doi.org/10.1016/j.btre.2022.e00768
Fathima A, Rao JR (2016) Selective toxicity of Catechin—a natural flavonoid towards bacteria. Appl Microbiol Biotechnol 100(14):6395–6402. https://doi.org/10.1007/s00253-016-7492-x
Godoy ME, Rotelli A, Pelzer L, Tonn CE (2000) Antiinflammatory activity of cinnamic acid esters. Molecules 5(3):547–548. https://doi.org/10.3390/50300547
Gunawan S, Aparamarta HW, Zarkasie IM, Prihandini WW (2018) Effect of initial bacterial cells number and fermentation time on increasing nutritive value of sago flour. Malays J Fundament Appl Sci 14(2):246–250
Gutiérrez RMP, Jerónimo FFM, Soto JGC, Ramírez AM, Mendoza MFE (2021) Optimization of ultrasonic-assisted extraction of polyphenols from the polyherbal formulation of Cinnamomum verum, Origanum majorana, and Origanum vulgare and their anti-diabetic capacity in zebrafish (Danio rerio). Heliyon. https://doi.org/10.1016/j.heliyon.2021.e08682
Hamidpour R, Hamidpour M, Hamidpour S, Shahlari M (2015) Cinnamon from the selection of traditional applications to its novel effects on the inhibition of angiogenesis in cancer cells and prevention of Alzheimer’s disease, and a series of functions such as antioxidant, anticholesterol, antidiabetes, antibacterial, antifungal, nematicidal, acaracidal, and rpellent activities. J Tradit Complement Med 5(2):66–70
Hibbing ME, Fuqua C, Parsek MR, Peterson SB (2010) Bacterial competition: surviving and thriving in the microbial jungle. Nat Rev Microbiol 8(1):15–25. https://doi.org/10.1038/nrmicro2259
Huang TE, Deng YN, Hsu JL, Leu WJ, Marchesi E, Capobianco ML, Marchetti P, Navacchia ML, Guh JH, Perrone D, Hsu LC (2020) Evaluation of the anticancer activity of a bile acid-dihydroartemisinin hybrid ursodeoxycholic-dihydroartemisinin in hepatocellular carcinoma cells. Frontiers in Pharmacology. 1776
Hur SJ, Lee SY, Kim YC, Choi I, Kim GB (2014) Effect of fermentation on the antioxidant activity in plant-based foods. Food Chem 160:46–356. https://doi.org/10.1016/j.foodchem.2014.03.112
Hussein HA, Darwesh OM, Mekki BB, El-Hallouty SM (2019) Evaluation of cytotoxicity, biochemical profile and yield components of groundnut plants treated with nano-selenium. Biotechnol Reports 24:e00377. https://doi.org/10.1016/j.btre.2019.e00377
Janel N, Noll C (2014) Protection and reversal of hepatic fibrosis by polyphenols. Polyphenols in human health and disease. Academic Press, Cambridge, pp 665–679
Juurlink BH, Azouz HJ, Aldalati AM, AlTinawi BM, Ganguly P (2014) Hydroxybenzoic acid isomers and the cardiovascular system. Nutr J 13(1):63. https://doi.org/10.1186/1475-2891-13-63
Khan MS, Yusufzai SK, Rafatullah M, Sarjadi MS, Razlan M (2018) Determination of total phenolic content, total flavonoid content and antioxidant activity of various organic crude extracts of Licuala spinosa leaves from sabah, Malaysia. ASM Science Journal 11:53–58
Khattab SMR, Abdel-Hadi AM, Abo-Dahab NF, Atta OM (2016) Isolation, characterization, and identification of yeasts Associated with foods from Assiut City. Egypt British Microbiol Res J 13(1):1–10
Kiliç I, Yeşiloğlu Y (2013) Spectroscopic studies on the antioxidant activity of p-coumaric acid. Spectrochim Acta Part A Mol Biomol Spectrosc 115:719–724
Kim KH, Tsao R, Yang R, Cui SW (2006) Phenolic acid profiles and antioxidant activities of wheat bran extracts and the effect of hydrolysis conditions. Food Chem 95:466–473. https://doi.org/10.1016/j.foodchem.2005.01.032
Kim ME, Na JY, Park YD, Lee JS (2019) Anti-neuroinflammatory effects of vanillin through the regulation of inflammatory factors and NF-κB signaling in LPS-stimulated microglia. Appl Biochem Biotechnol 187:884–893. https://doi.org/10.1007/s12010-018-2857-5
Klopp RN, Yoon I, Eicher S, Boerman JP (2021) Effects of feeding Saccharomyces cerevisiae fermentation products on the health of Holstein dairy calves following a lipopolysaccharide challenge. J Dairy Sci 105(2):1469–1479. https://doi.org/10.3168/jds.2021-20341
Kurtzman CP, Fell JW, Boekhout T, Robert V (2011) Methods for isolation phenotypic characterization and maintenance of yeasts. In: Kurtzman CP, Fell JW, Boekhout T (eds) The Yeasts a Taxonomic Study, 5th edn. Elsevier, Amsterdam, pp 87–110
Lee JW, Wang S, Seefeldt T, Donkor A, Logue BA, Kim HS, Woyengo TA (2021) Porcine in vitro fermentation characteristics of canola co-products in neutral and acidic fermentation medium pH. Animal Feed Sci Technol. https://doi.org/10.1016/j.anifeedsci.2021.115188
Leone V, Ali A, Weber A, Tschaharganeh DF, Heikenwalder M (2021) Liver inflammation and hepatobiliary cancers. Trends in Cancer 7(7):606–623. https://doi.org/10.1016/j.trecan.2021.01.012
Li R, Liang T, Xu L, Li Y, Zhang S, Duan X (2013) Protective effect of cinnamon polyphenols against STZ-diabetic mice fed high-sugar, high-fat diet and its underlying mechanism. Food Chem Toxicol 51:419–425. https://doi.org/10.1016/j.fct.2012.10.024
Liu Z, Li H, Cui G, Wei M, Zou Z, Ni H (2021) Efficient extraction of essential oil from Cinnamomum burmannii leaves using enzymolysis pretreatment and followed by microwave-assisted method. LWT 147:111497. https://doi.org/10.1016/j.lwt.2021.111497
Liu Y, Shi L, Qiu W, Shi Y (2022) Ferulic acid exhibits anti-inflammatory effects by inducing autophagy and blocking NLRP3 inflammasome activation. Mol Cell Toxicol 18:509–519. https://doi.org/10.1007/s13273-021-00219-5
Menezes AGT, Batista NN, Ramos CL, Silva ARA, Efraim P, Pinheiro ACM, Schwan RF (2016) Investigation of chocolate produced from four different Brazilian varieties of cocoa (Theobroma cacao L.) inoculated with Saccharomyces cerevisiae. Food Res Int 81:83–90. https://doi.org/10.1016/j.foodres.2015.12.036
Mohdaly AA, Sarhan MA, Smetanska I, Mahmoud A (2010) Antioxidant properties of various solvent extracts of potato peel, sugar beet pulp and sesame cake. J Sci Food Agric 90(2):218–226. https://doi.org/10.1002/jsfa.3796
Nabavi SF, Di Lorenzo A, Izadi M, Sobarzo-Sánchez E, Daglia M, Nabavi SM (2015) Antibacterial effects of cinnamon: from farm to food, cosmetic and pharmaceutical industries. Nutrients 7(9):7729–7748. https://doi.org/10.3390/nu7095359
Namasivayam E, Ravindar JD, Mariappan K, Akhil J, Mukesh K, Jayaraj R (2011) Production of extracellular pectinase by Bacillus cereus isolated from market solid waste. J Bioanaly Biomed 3(3):70–75
Nunes C, Raposo MFDJ, Petronilho S, Machado F, Fulgêncio R, Gomes MH, Coimbra MA (2022) Cinnamomum burmannii decoction: a thickening and flavouring ingredient. LWT 153:112428. https://doi.org/10.1016/j.lwt.2021.112428
Parapouli M, Vasileiadis A, Afendra AS, Hatziloukas E (2020) Saccharomyces cerevisiae and its industrial applications. AIMS Microbiol 6(1):1–31. https://doi.org/10.3934/microbiol.2020001
Poole SK, Poole CF (1994) Thin-layer chromatographic method for the determination of the principal polar aromatic flavour compounds of the cinnamons of commerce. Analyst 119(1):113–120
Rao PV, Gan SH (2014) Cinnamon: a multifaceted medicinal plant. Evidence-Based Complementary and Alternative Medicine. 2014
Rasheed MU, Thajuddin N (2011) Effect of medicinal plants on Moraxella cattarhalis. Asian Pac J Trop Med 4:133–136. https://doi.org/10.1016/S1995-7645(11)60053-9
Ravichandran K, Saw TM, Mohdaly AAA, Gabr MA, Kastell A, Riedel H, Cai Z, Knorr D, Smetanska I (2013) Impact of processing of red beet on betalain content and antioxidant activity. Food Res Int 50:670–675. https://doi.org/10.1016/j.foodres.2011.07.002
Reis B, Martins M, Barreto B, Milhazes N, Garrido EM, Silva P, Borges F (2010) Structure− property− activity relationship of phenolic acids and derivatives. protocatechuic acid alkyl esters. J Agric and Food Chem 58(11):6986–6993. https://doi.org/10.1021/jf100569j
Repetto G, Del Peso A, Zurita JL (2008) Neutral red uptake assay for the estimation of cell viability/cytotoxicity. Nat Protoc 3(7):1125–1131. https://doi.org/10.1038/nprot.2008.75
Sadeghi S, Davoodvandi A, Pourhanifeh MH, Sharifi N, ArefNezhad R, Sahebnasagh R, Mirzaei H (2019) Anti-cancer effects of cinnamon: insights into its apoptosis effects. Eur J Med Chem 178:131–140. https://doi.org/10.1016/j.ejmech.2019.05.067
Sakai E, Tsukuba T (2015) Coffee and bone metabolism: Kahweol and osteoclastogenesis. Coffee in Health and Disease Prevention. Academic Press, Cambridge, pp 869–875
Srinivasulu C, Ramgopal M, Ramanjaneyulu G, Anuradha CM, Kumar CS (2018) Syringic acid (SA)-a review of its occurrence, biosynthesis, pharmacological and industrial importance. Biomed Pharmacother 108:547–557. https://doi.org/10.1016/j.biopha.2018.09.069
Su L, Yin JJ, Charles D, Zhou K, Moore J, Yu LL (2007) Total phenolic contents, chelating capacities, and radical-scavenging properties of black peppercorn, nutmeg, rosehip, cinnamon and oregano leaf. Food Chem 100(3):990–997. https://doi.org/10.1016/j.foodchem.2005.10.058
Sultan YY, Ali MA, Darwesh OM, Embaby MA, Marrez DA (2016) Influence of nitrogen source in culture media on antimicrobial activity of Microcoleus lacustris and Oscillatoria rubescens. Res J Pharm, Biol Chem Sci 7(2):1444–1452
Suryanti V, Wibowo FR, Khotijah S, Andalucki N (2018) Antioxidant activities of cinnamaldehyde derivatives. In IOP Conference Series Mater Sci Eng 333:012077
Tadasa K (1977) Degradation of eugenol by a microorganism. Agric Biol Chem 41(6):925–929. https://doi.org/10.1080/00021369.1977.10862621
Tai A, Sawano T, Yazama F, Ito H (2011) Evaluation of antioxidant activity of vanillin by using multiple antioxidant assays. Biochem Biophys Acta. https://doi.org/10.1016/j.bbagen.2010.11.004
Tungmunnithum D, Thongboonyou A, Pholboon A, Yangsabai A (2018) Flavonoids and other phenolic compounds from medicinal plants for pharmaceutical and medical aspects: An overview. Medicines 5(3):93. https://doi.org/10.3390/medicines5030093
Utchariyakiat I, Surassmo S, Jaturanpinyo M, Khuntayaporn P, Chomnawang MT (2016) Efficacy of cinnamon bark oil and cinnamaldehyde on anti-multidrug resistant Pseudomonas aeruginosa and the synergistic effects in combination with other antimicrobial agents. BMC Complement Altern Med 16(1):158. https://doi.org/10.1186/s12906-016-1134-9
Vana JR, Botting RM (1995) New insight into the mode of action of anti-inflammatory drugs. Inflammatory Res 44:1–10. https://doi.org/10.1007/BF01630479
Walker GM, Stewart GG (2016) Saccharomyces cerevisiae in the production of fermented beverages. Beverages 2(4):30. https://doi.org/10.3390/beverages2040030
Wang L, Liu Y, Luo Y, Huang K, Wu Z (2018) Quickly screening for potential αGlucosidase Inhibitors from guava leaves tea by bioaffinity ultrafiltration coupled with HPLC-ESI-TOF/MS method. J Agric Food Chem 66(6):1576–1582. https://doi.org/10.1021/acs.jafc.7b05280
Wu HC, Horng CT, Lee YL, Chen PN, Lin CY, Liao CY, Chu SC (2018) Cinnamomum cassia extracts suppress human lung cancer cells invasion by reducing u-PA/MMP expression through the FAK to ERK pathways. Int J Med Sci 15(2):115. https://doi.org/10.7150/ijms.22293
Xu JG, Hu QP, Liu Y (2012) Antioxidant and DNA-protective activities of chlorogenic acid isomers. J Agric Food Chem 60(46):11625–11630. https://doi.org/10.1021/jf303771s
Zhao YS, Eweys AS, Zhang JY, Zhu Y, Bai J, Darwesh OM, Xiao X (2021a) Fermentation affects the antioxidant activity of plant-based food material through the release and production of bioactive components. Antioxidants 10(12):2004. https://doi.org/10.3390/antiox10122004
Zhao Y, Wu C, Zhu Y, Zhou C, Xiong Z, Eweys AS, Xiao X (2021b) Metabolomics strategy for revealing the components in fermented barley extracts with Lactobacillus plantarum dy-1. Food Res Int 139:109808. https://doi.org/10.1016/j.foodres.2020.109808
The authors would like to express their gratitude for the fruitful cooperation between the National Research Centre (NRC), Egypt, Cairo University, Egypt, and Jiangsu University, China followed by providing necessary facilities to carry out the research work.
Open access funding provided by The Science, Technology & Innovation Funding Authority (STDF) in cooperation with The Egyptian Knowledge Bank (EKB). This work was not received any external funding.
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Figure S1. The standard curve of Gallic acid for determination of total phenolic content. Figure S2. The standard curve of quercetin for determination of total flavonoids content. Figure S3. Microscopic photo for cancer cells without treatment, treated with fermented cinnamon extract, treated with non-fermented cinnamon extract. Figure S4. TLC chromatogram of lyophilized fermented (1) and non-fermented cinnamon (2) extracts compared with caffeic acid (3) and P-coumaric acid (4).
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Darwesh, O.M., Eweys, A.S., Zhao, YS. et al. Application of environmental-safe fermentation with Saccharomyces cerevisiae for increasing the cinnamon biological activities. Bioresour. Bioprocess. 10, 12 (2023). https://doi.org/10.1186/s40643-023-00632-9