TX_1:ABS~AT/TX_2:ABS~AT 85 http://journals.cihanuniversity.edu.iq/index.php/cuesj CUESJ 2020, 4 (1): 85-89 ReseaRch aRticle Effect of Isatis spp. Extraction on the Growth of Aspergillus niger and Candida albicans Zehra Odabaş-Serin1*, Ali H. Salim Agha2, Zhala B. Taha2 1Department of Forest, Kahramanmaraş Sütçü Imam University, Faculty of Forestry, 46040, Kahramanmaraş, Turkey, 2Department of Bioengineering and Science, Kahramanmaraş Sütçü İmam University, Faculty Bioengineering and Science, 46040, Kahramanmaraş, Turkey and Cihan University-Erbil, Department of Biology, Iraq ABSTRACT In this study, the crude extraction of Isatis spp. (Isatis tinctoria, Isatis busichaina, and Isatis lusitanica) was investigated for their antifungal activity. Each of methanol, ethanol, and H2O was used as a solvent. Due to find the most effective part of each species, the plant parts were used separately. The aim of this research was to determine the natural products effect on two common pathogenic fungi Aspergillus niger and Candida albicans. The results show that most of used plants have significant effect on both used fungal species. Extracted each of flower, I. tinctoria was showed the best results comparing to the other used species. Extracted leaf and flower of I. tinctoria by methanol were showed the best result on A. niger and C. albicans. The growth zone was around 90 mm for control and 61 mm at 75% concentration of methanolic and ethanolic extraction. The flower was for followed by the stem. Depend on the results, the methanol was showed highest number, then ethanol and the lowest inhibition zone area was for H2O extraction. Keywords: Antifungal activity, Aspergillus niger and Candida albicans, Isatis spp., pathogenic fungi INTRODUCTION A latest study presented that tertiary care clinics are consuming antimicrobial and antifungal agents improperly. This rising trend is an ever-increasing threat to the health of humans who are currently at risk of dying from previously fixable infections. Unluckily, drug resistance (adaptation of the drug target site, drug modification, or restricted drug penetration) improves at a pace quicker than new drug development.[1] This sensation is also happening in the pathogenic microorganism Candida albicans, an otherwise commensal kinds found in and on the human body.[2] Modern antifungal agents are less active against C. albicans now than when they were first introduced because Candida species have developed resistance to these agents. In addition, research by the major pharmaceutical companies in the development of antifungal agents has been on the decline due to low coming back on investment.[3] MATERIALS AND METHODS Plant Extracts Three methods were used to extract water, ethanolic, and methanolic, according to several studies, with some modification as needed and as follows:[4] Aqueous Extraction Hot water extraction was performed by mixing 40 g of plant form with 160 ml of distilled water twice (i.e., 1:4 weight:volume), heated to 80–90°C, then stirred and left to cool down and mixed together then placed in refrigerator for 24 h, which was then administered through several layers of medical gauze, and again administered by Buchner funnel using filter papers Whatman No.1 to dispose of the non- powdered parts and fibers to obtain the raw liquid extract and then put it in the rotary evaporator device at a temperature not exceeding 40°C, working on the basis of evaporation under pressure and then put the extracted in the shaker incubator at a temperature of 30–35°C. After the drying of the extract, Corresponding Author: Zehra Odabaş-Serin, Kahramanmaraş Sütçü Imam University, Faculty of Forestry, 46040, Kahramanmaraş, Turkey. Phone: +90 3443001780. Fax: +90 3443001712. E-mail: zehra@ksu.edu.tr Received: Jan 16, 2020 Accepted: Apr 27, 2020 Published: Jun 20, 2020 DOI: 10.24086/cuesj.v4n1y2020.pp85-89 Copyright © 2020 Zehra Odabaş-Serin, Ali H. Salim Agha, Zhala B. Taha. This is an open-access article distributed under the Creative Commons Attribution License. Cihan University-Erbil Scientific Journal (CUESJ) mailto:zehra@ksu.edu.tr https://creativecommons.org/licenses/by-nc-nd/4.0/ Odabaş-Serin, et al.: Antifungal activity of Isatis spp 86 http://journals.cihanuniversity.edu.iq/index.php/cuesj CUESJ 2020, 4 (1): 85-89 it was kept in a sealed containers in the freezer (−4°C) and wrote the information on each until use. Ethanolic Extraction Prepare the ethanol extract by mixing 20 g of plant powder in 200 ml of absolute ethanol with stirring (i.e., 1:10 weight:volume) and then leave the mixture in the refrigerator for 24 h. Then, the extract was filtered through several layers of gauze and then filtered for 2nd time using Whatman No.1 filter papers to remove the non-powdered plant parts and the remaining fibers, then put in the rotary evaporator device at 40°C and after evaporation of the alcohol obtained a thick layer of the extract and then placed in the shaker incubator shaker incubator at 25–30°C. After drying the extract, it was kept in a sealed container in a freezer with writing the information on each until use. Methanolic Extraction Prepare the methanol extract by mixing 20 g of plant powder in 200 ml of absolute methanol with stirring (i.e., 1:10 weight:volume) and then leave the mixture in the refrigerator for 24 h to soak. Then, the extract was filtered through several layers of gauze and then filtered for 2nd time using Whatman No.1 filter papers to remove the non-powdered plant parts and the remaining fibers, then put in the rotary evaporator device at 40°C and after evaporation of the methanol obtained a thick layer of the extract and then placed in the shaker incubator shaker incubator at 25–30°C. After drying the extract, it was kept in a sealed container in a freezer with writing the information on each until use. Media Preparation The above studied media were prepared according to the information on the package by the manufacturer company[5] then sterilized at 121°C and 15 lb/kg2 for 15 min. The medium was distributed in Petri dishes (diameter 9 cm), and the dishes were left under the temperature of the laboratory until the hardening of the medium in sterilizer hood. A quantity of distilled water was also sterilized for use as a substitute for extracts in control transactions (ddH 2 O). Fungi Two types of fungus obtained from the media center in Erbil- Iraq for diagnosing the disease with mention the strain type were used in this study. • Aspergillus niger ATCC 16404 • C. albicans ATCC 10231 Preparation of Petri dishes to Test Extracts against Fungus For this study, concentration method was used by mixing with the medium. The fungal isolates were planted in Petri dishes on the potato dextrose agar media, mixed with three different concentrations of plant extracts that mentioned in previously, then incubated the dishes in the incubator at 25 ± 2°C and 37 ± 2°C. For example, Candida species need a temperature of between 25 ± 2°C and 37 ± 2°C for optimal growth according to the nature of their growth to fungus or semi-yeast. The process of incubation continued for 10 days. The readings were taken every 3 days according to replicates, influenced by concentrations of plant extracts.[6,7] Statistical Analysis GLM-univariate analysis was applied to the arithmetic means obtained in SPSS with 95% confidence interval. If the difference was significant (P ≤ 0.05), the homogeneity groups were determined by Tukey B test. The analytical test was done separately for each solvent type (hot water, ethanol, and methanol) to show the effect of the samples part (flower, leaf, and stem) and extract concentration (25%, 50%, and 75%). RESULTS AND DISCUSSION The antifungal compound is one of the vital substances in pharmaceutical sciences that can find in the natural medicinal plants. This needs to identify the activity of the samples compound by different parameters. In this study, the antifungal activities of extracts obtained with solvents that vary from non- polar to polar were investigated. The results were took after the growth was rich the optimum point of two types of used fungi in optimum incubation condition. The growth of the control Petri dishes was 90 mm for both. The following table is showed the effect of Isatis tinctoria on A. niger ATCC 16404 and C. albicans ATCC 10231 growth. The best results were with flower extraction by methanol with 75% concentration against A. niger ATCC 16404, following by the stem with methanolic extraction 75% against A. niger ATCC 16404 too. In this table, all of the methanolic extraction had significant effect on both fungi A. niger ATCC 16404 and C. albicans ATCC 10231 [Table 1]. The second table is showed the effect of Isatis busichaina on A. niger ATCC 16404 and C. albicans ATCC 10231 growth. The best results were with leaf extraction by methanol with 75% concentration against C. albicans ATCC 10231, following by the flower with methanolic extraction 75% against A. niger ATCC 16404. In this table, all of the methanolic extraction had significant effect on both fungi A. niger ATCC 16404 and C. albicans ATCC 10231 [Table 2]. However, Table 3 shows the effect of Isatis lusitanica on A. niger ATCC 16404 and C. albicans ATCC 10231 growth. The best results were with flower extraction by methanol with 75% concentration against A. niger ATCC 16404, following by the flower with methanolic extraction 75% against C. albicans ATCC 10231. In this table, all of the methanolic extractions had significant effect on both fungi A. niger ATCC 16404 and C. albicans ATCC 10231 [Table 3]. Depend on the results, the significant results were obtained from the extraction of methanol and ethanol for I. tinctoria in all concentrations, plant parts, and both types of used fungi. The aqueous extraction has less effect in correlation with ethanol and methanol [Table 4]. The inhibition effects of the extracts of I. tinctoria obtained from leaf, stem, and flower parts using different solvents on the two different strains of pathogenic fungi. The results were compared with the each to find the correlation. The aqueous leaf extracts were showed significant results on A. niger ATCC 16404, also the flower was showed the significant results by ethanol extraction for C. albicans ATCC 10231, although the flower extracts by methanol were showed the significant results for A. niger ATCC 16404. Other differences are shown in Table 4. Odabaş-Serin, et al.: Antifungal activity of Isatis spp 87 http://journals.cihanuniversity.edu.iq/index.php/cuesj CUESJ 2020, 4 (1): 85-89 Table 1: Fungi test results of I. tinctoria. (Control=90 mm) Plant Plant part Strains Growth of fungi (mm) Water concentration Ethanol concentration Methanol concentration 25% 50% 75% 25% 50% 75% 25% 50% 75% I. tinctoria Flower C. albicans 85.75 (0.96) 82.75 (0.50) 80.25 (0.96) 81.00 (0.82) 79.00 (0.82) 72.50 (1.29) 73.00 (1.15) 71.75 (0.50) 62.00 (1.41) A. niger 84.00 (0.82) 82.50 (1.29) 79.00 (0.82) 81.25 (0.96) 80.00 (0.82) 78.00 (1.41) 69.75 (0.50) 68.00 (0.82) 61.25 (0.50) Leaf C. albicans 84.50 (2.38) 80.75 (0.96) 79.50 (1.29) 79.75 (1.26) 78.75 (0.96) 77.75 (0.96) 70.5 (0.58) 69.25 (0.50) 62.00 (1.41) A. niger 84.00 (0.82) 81.00 (0.82) 79.25 (0.96) 80.25 (1.71) 78.75 (0.96) 77.50 (0.58) 70.25 (0.50) 68.50 (1.00) 62.75 (0.50) Stem C. albicans 84.75 (0.96) 82.25 (2.06) 80.50 (0.58) 82.00 (0.82) 80.50 (0.58) 73.00 (1.83) 73.50 (1.29) 70.25 (0.50) 63.25 (1.50) A. niger 84.50 (1.29) 82.75 (0.96) 80.00 (0.82) 81.25 (0.50) 79.25 (0.96) 78.50 (0.58) 70.75 (0.96) 69.50 (1.29) 61.75 (0.50) I. tinctoria: Isatis tinctoria, C. albicans: Candida albicans, A. niger: Aspergillus niger Table 2: Fungi test results of I. busichaina. (Control=90 mm) Plant Plant part Strains Growth of fungi (mm) Water concentration Ethanol concentration Methanol concentration 25% 50% 75% 25% 50% 75% 25% 50% 75% I. busichaina Flower C. albicans 84.75 (0.96) 80.25 (1.26) 79.50 (1.29) 80.00 (0.82) 78.50 (0.58) 76.00 (1.41) 71.00 (0.82) 70.00 (1.63) 63.00 (1.83) A. niger 83.50 (1.29) 79.75 (0.96) 77.75 (2.22) 80.00 (0.82) 78.25 (0.50) 76.00 (0.82) 70.75 (0.96) 68.00 (0.82) 61.5 (1.29) Leaf C. albicans 83.25 (0.96) 79.50 (1.29) 77.00 (1.83) 80.00 (0.82) 79.00 (0.82) 75.50 (1.29) 71.00 (1.15) 66.75 (2.06) 61.00 (0.82) A. niger 83.25 (0.96) 80.50 (0.58) 77.25 (1.71) 80.75 (0.96) 78.50 (0.58) 74.25 (0.50) 70.75 (0.50) 66.25 (0.50) 63.00 (1.83) Stem C. albicans 84.00 (0.82) 80.75 (1.50) 77.25 (1.50) 81.75 (0.96) 80.00 (0.82) 78.25 (0.96) 72.5 (2.38) 70.50 (0.58) 68.50 (0.58) A. niger 84.75 (1.50) 82.25 (1.26) 79.25 (0.96) 81.75 (0.96) 80.50 (0.58) 79.25 (0.96) 71.75 (0.96) 70.00 (0.82) 69.00 (1.41) I. busichaina: Isatis busichaina, C. albicans: Candida albicans, A. niger: Aspergillus niger Table 3: Fungi test results of I. lusitanica. (Control=90 mm) Plant Plant part Strains Growth of fungi (mm) Water concentration Ethanol concentration Methanol concentration 25% 50% 75% 25% 50% 75% 25% 50% 75% I. lusitanica Flower C. albicans 83.25 (0.96) 81.50 (1.29) 79.00 (0.82) 80.50 (0.58) 79.50 (1.29) 78.00 (0.82) 70.00 (0.82) 67.75 (0.50) 64.50 (1.29) A. niger 83.25 (0.96) 80.75 (0.96) 79.00 (0.82) 80.50 (0.58) 78.25 (1.71) 76.75 (0.96) 68.50 (1.29) 66.50 (1.00) 63.75 (1.71) Leaf C. albicans 82.25 (1.71) 81.75 (1.71) 79.50 (1.29) 80.00 (0.82) 79.00 (0.82) 76.75 (0.96) 69.75 (0.96) 67.50 (0.58) 66.50 (1.00) A. niger 82.00 (0.82) 80.25 (0.96) 79.50 (0.58) 80.25 (0.50) 78.25 (1.71) 77.50 (1.29) 68.25 (0.96) 65.75 (0.96) 65.25 (0.50) Stem C. albicans 84.50 (0.58) 82.25 (0.50) 80.50 (1.29) 81.50 (1.29) 80.75 (0.96) 79.00 (0.82) 72.00 (0.82) 70.50 (0.58) 69.00 (0.82) A. niger 83.50 (1.29) 80.75 (0.96) 80.25 (1.26) 81.50 (0.58) 80.00 (0.82) 79.00 (0.82) 72.00 (0.82) 70.25 (0.96) 69.50 (0.58) I. lusitanica: Isatis lusitanica, C. albicans: Candida albicans, A. niger: Aspergillus niger The inhibition effects of extracts of I. busichaina obtained from leaf, stem, and flower parts using different solvents on the two different strains of pathogenic fungi. The results were compared with the each to find the correlation. For C. albicans Odabaş-Serin, et al.: Antifungal activity of Isatis spp 88 http://journals.cihanuniversity.edu.iq/index.php/cuesj CUESJ 2020, 4 (1): 85-89 ATCC 10231, each of aqueous leaf extraction, ethanol extraction of flower and leaf, and leaf extraction by methanol was showed the significant result correlations. For A. niger ATCC 16404, the aqueous extraction of flower and leaf, the ethanol extraction of flower and leaf, and methanol extraction of flower and leaf too was showed the significant results. The total result statistics shown in Table 5. The inhibition effects of the extracts of I. lusitanica obtained from leaf, stem, and flower parts using different solvents on the two different strains of pathogenic fungi. The results were compared with the each to find the correlation. For C. albicans ATCC 10231, each of flower and leaf of aqueous, ethanol, and methanol extraction was showed the significant results. For A. niger ATCC 16404, the ethanol and methanol extraction of flower and leaf was showed the significant results. The total result statistics is shown in Table 6. Some factors have to be measured to select a solvent for extracting herbal medicine. About 65–75% methanol extraction at room temperature for 15 h is practical for routine analytical study. Although, it is not fully active to extract other plants with same procedure because of dissimilarities in the biological compositions. This method is appropriate for controlling a large number of fixed samples and needs no special equipment.[8] The present study proved that methanol and ethanol showed best results than water extracts. Our study was in accordance with several studies.[9] Tryptanthrin, indole-3- acetonitrile, and p-coumaric acid methylester were identified by physical and spectral data (MS, NMR) and by comparison with authentic synthesized samples of these compounds. Tryptanthrin has already been isolated from I. tinctoria and characterized as an antidermatophytic.[10] Phenylpropanoids mainly comprised flavonoid and lignan metabolites, have been considered as the primary antiviral constituents, which Table 4: Fungi arithmetic values and Tukey B statistical analysis results of I. tinctoria C. albicans concentration A. niger concentration Tukey B Plant part 25% 50% 75% Tukey B 25% 50% 75% Water Flower 85.75 (0.96) 82.75 (0.50) 80.25 (0.96) A 84.00 (0.82) 82.50 (1.29) 79.00 (0.82) AB Leaf 84.50 (2.38) 80.75 (0.96) 79.50 (1.29) A 84.00 (0.82) 81.00 (0.82) 79.25 (0.96) B Stem 84.75 (0.96) 82.25 (2.06) 80.50 (0.58) A 84.50 (1.29) 82.75 (0.96) 80.00 (0.82) A Tukey B A B C A B C Ethanol Flower 81.00 (0.82) 79.00 (0.82) 72.50 (1.29) B 81.25 (0.96) 80.00 (0.82) 78.00 (1.41) A Leaf 79.75 (1.26) 78.75 (0.96) 77.75 (0.96) A 80.25 (1.71) 78.75 (0.96) 77.50 (0.58) A Stem 82.00 (0.82) 80.50 (0.58) 73.00 (1.83) AB 81.25 (0.50) 79.25 (0.96) 78.50 (0.58) A Tukey B A B C A B C Methanol Flower 73.00 (1.15) 71.75 (0.50) 62.00 (1.41) B 69.75 (0.50) 68.00 (0.82) 61.25 (0.50) B Leaf 70.50 (0.58) 69.25 (0.50) 62.00 (1.41) C 70.25 (0.50) 68.50 (1.00) 62.75 (0.50) A Stem 73.50 (1.29) 70.25 (0.50) 63.25 (1.50) A 70.75 (0.96) 69.50 (1.29) 61.75 (0.50) A Tukey B A B C A B C I. tinctoria: Isatis tinctoria, C. albicans: Candida albicans, A. niger: Aspergillus niger Table 5: Fungi arithmetic values and Tukey B statistical analysis results of I. busichaina Plant part C. albicans concentration Tukey B A. niger concentration Tukey B 25% 50% 75% 25% 50% 75% Water Flower 84.75 (0.96) 80.25 (1.26) 79.50 (1.29) A 83.50 (1.29) 79.75 (0.96) 77.75 (2.22) B Leaf 83.25 (0.96) 79.50 (1.29) 77.00 (1.83) B 83.25 (0.96) 80.50 (0.58) 77.25 (1.71) B Stem 84.00 (0.82) 80.75 (1.50) 77.25 (1.50) AB 84.75 (1.50) 82.25 (1.26) 79.25 (0.96) A Tukey B A B C A B C Ethanol Flower 80.00 (0.82) 78.50 (0.58) 76.00 (1.41) B 80.00 (0.82) 78.25 (0.50) 76.00 (0.82) B Leaf 80.00 (0.82) 79.00 (0.82) 75.50 (1.29) B 80.75 (0.96) 78.50 (0.58) 74.25 (0.50) B Stem 81.75 (0.96) 80.00 (0.82) 78.25 (0.96) A 81.75 (0.96) 80.50 (0.58) 79.25 (0.96) A Tukey B A B C A B C Methanol Flower 71.00 (0.82) 70.00 (1.63) 63.00 (1.83) B 70.75 (0.96) 68.00 (0.82) 61.5 (1.29) B Leaf 71.00 (1.15) 66.75 (2.06) 61.00 (0.82) C 70.75 (0.50) 66.25 (0.50) 63.00 (1.83) B Stem 72.5 (2.38) 70.50 (0.58) 68.50 (0.58) A 71.75 (0.96) 70.00 (0.82) 69.00 (1.41) A Tukey B A B C A B C I. busichaina: Isatis busichaina, C. albicans: Candida albicans, A. niger: Aspergillus niger Odabaş-Serin, et al.: Antifungal activity of Isatis spp 89 http://journals.cihanuniversity.edu.iq/index.php/cuesj CUESJ 2020, 4 (1): 85-89 Table 6: Fungi arithmetic values and Tukey B statistical analysis results of I. lusitanica Plant part C. albicans concentration Tukey B A. niger concentration Tukey B 25% 50% 75% 25% 50% 75% Water Flower 83.25 (0.96) 81.50 (1.29) 79.00 (0.82) B 83.25 (0.96) 80.75 (0.96) 79.00 (0.82) A Leaf 82.25 (1.71) 81.75 (1.71) 79.50 (1.29) B 82.00 (0.82) 80.25 (0.96) 79.50 (0.58) A Stem 84.50 (0.58) 82.25 (0.50) 80.50 (1.29) A 83.50 (1.29) 80.75 (0.96) 80.25 (1.26) A Tukey B A B C A B C Ethanol Flower 80.50 (0.58) 79.50 (1.29) 78.00 (0.82) B 80.50 (0.58) 78.25 (1.71) 76.75 (0.96) B Leaf 80.00 (0.82) 79.00 (0.82) 76.75 (0.96) B 80.25 (0.50) 78.25 (1.71) 77.50 (1.29) B Stem 81.50 (1.29) 80.75 (0.96) 79.00 (0.82) A 81.50 (0.58) 80.00 (0.82) 79.00 (0.82) A Tukey B A B C A B C Methanol Flower 70.00 (0.82) 67.75 (0.50) 64.50 (1.29) B 68.50 (1.29) 66.50 (1.00) 63.75 (1.71) B Leaf 69.75 (0.96) 67.50 (0.58) 66.50 (1.00) B 68.25 (0.96) 65.75 (0.96) 65.25 (0.50) B Stem 72.00 (0.82) 70.50 (0.58) 69.00 (0.82) A 72.00 (0.82) 70.25 (0.96) 69.50 (0.58) A Tukey B A B C A B C I. lusitanica: Isatis lusitanica, C. albicans: Candida albicans, A. niger: Aspergillus niger probably contribute to the outstanding pharmacological activity of Radix isatidis.[11,12] It is distinguished that a solvent system for extraction is selected according to the purpose of extraction such as preparation or analysis, the nature of interested components, the physicochemical properties of the matrix, the availability of reagents and equipment, cost, and safety concerns.[13] The solvent systems included complete ethanol at 25°C by different methods, 95% ethanol, ethanol–water for 10 min,[14] methanol–water, methanol–HCl (1.0 N, 85:15, v/v), and H 2 O. 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