Impact Factor 2019 : 1.903 (@Clarivate Analytics)
  • Users Online: 610
  • Print this page
  • Email this page

Table of Contents
Year : 2020  |  Volume : 10  |  Issue : 12  |  Page : 555-562

Potential bioactive phytochemicals, antioxidant properties and anticancer pathways of Nymphaea nouchali

1 Institute of Food Science and Technology, Bangladesh Council of Scientific and Industrial Research, Dhaka 1205, Bangladesh; School of Basic Medicine and Clinical Pharmacy, China Pharmaceutical University, Nanjing, Jiangsu 211198, China
2 Department of Food Technology and Nutritional Science, Mawlana Bhashani Science and Technology University, Santosh, Tangail 1902, Bangladesh
3 Institute of Food Science and Technology, Bangladesh Council of Scientific and Industrial Research, Dhaka 1205, Bangladesh
4 Center for New Drug Safety Evaluation and Research, China Pharmaceutical University, Jiangsu, Nanjing 211198, China
5 School of Pharmacy, Lanzhou University, Lanzhou 730000, China
6 School of Pharmacy, China Pharmaceutical University, Nanjing, Jiangsu 211198, China

Date of Submission25-Dec-2019
Date of Decision20-Jan-2020
Date of Acceptance01-Jun-2020
Date of Web Publication19-Oct-2020

Correspondence Address:
Md. Nazim Uddin
Institute of Food Science and Technology, Bangladesh Council of Scientific and Industrial Research, Dhaka 1205, Bangladesh; School of Basic Medicine and Clinical Pharmacy, China Pharmaceutical University, Nanjing, Jiangsu 211198, China

Login to access the Email id

Source of Support: This work was carried out under the research and development (R and D) project of the Bangladesh Council of Scientific and Industrial Research, Conflict of Interest: None

DOI: 10.4103/2221-1691.297055

Get Permissions


Objective: To investigate bioactive phytochemicals and antioxidant activities of Nymphaea nouchali and to explore its anticancer pathways by a network pharmacology approach.
Methods: Using a spectrophotometer and high-performance liquid chromatography-diode array detector (HPLC-DAD), we quantified bioactive phytochemicals in methanolic extract of Nymphaea nouchali tuber. The extracts were investigated for in vitro antioxidant properties. Targets of these bioactive phytochemicals were predicted and anticancer-associated pathways were analyzed by a network pharmacology approach. Moreover, we identified the predicted genes associated with cancer pathways and the hub genes in the protein-protein interaction network of predicted genes.
Results: Quantitative results indicated the total phenolics, total flavonoids, and total proanthocyanidins in the methanolic extract of Nymphaea nouchali tuber. HPLC-DAD analysis showed rutin (39.44 mg), catechin (39.20 mg), myricetin (30.77 mg), ellagic acid (11.05 mg), gallic acid (3.67 mg), vanillic acid (0.75 mg), rosmarinic acid (4.81 mg), p-coumaric acid (3.35 mg), and quercetin (0.90 mg) in 1 g of dry extract. The extract showed the radical scavenging activities of 2, 2-diphenyl-1-picrylhydrazyl, 2,2’-azino- bis (3-ethylbenzothiazoline-6-sulfonic acid) and N,N-dimethyl-p phenylenediamine. By using network pharmacology, we predicted 130 target genes associated with cancer pathways. The top hub genes (IL6, AKT1, EGFR, JUN, PTGS2, MAPK3, CASP3, and CXCL8) were also identified, which were associated with cancer pathways and interacted with bioactive phytochemicals of the methanolic extract of Nymphaea nouchali tuber.
Conclusions: Our study provides insights into the mechanism of anticancer activities of the methanolic extract of Nymphaea nouchali tuber.

Keywords: Bioactive phytochemicals; Anticancer pathways; Malignancy; Network pharmacology; Nymphaea nouchali

How to cite this article:
Uddin MN, Samad MA, Zubair MA, Haque MZ, Mitra K, Khan TA, Hossain MA, Syed A, Afroze A. Potential bioactive phytochemicals, antioxidant properties and anticancer pathways of Nymphaea nouchali. Asian Pac J Trop Biomed 2020;10:555-62

How to cite this URL:
Uddin MN, Samad MA, Zubair MA, Haque MZ, Mitra K, Khan TA, Hossain MA, Syed A, Afroze A. Potential bioactive phytochemicals, antioxidant properties and anticancer pathways of Nymphaea nouchali. Asian Pac J Trop Biomed [serial online] 2020 [cited 2021 Jan 19];10:555-62. Available from:

  1. Introduction Top

Nymphaea nouchali (N. nouchali) (Burm. f) is a flowering plant belonging to the family Nymphaeceae. It is a national flower of Bangladesh and Srilanka, commonly known as “Shapla” in Bangladesh. N. nouchali grows abundantly as a mixed population in nearly all shoals and natural water bodies [1]. This plant has various bioactivities including anti-inflammatory and diuretic activities [2]. In the Ayurveda and Siddha systems of medicines, it is used for the treatment of diabetes, inflammation, liver disorders, urinary disorders, menorrhagia, blennorrhagia, menstruation problem, and used as an aphrodisiac, and a bitter tonic [3],[4]. Rhizomes and flowers have been widely used for the treatment of kidney problems [3]. Flower extract can attenuate melanogenesis by regulation of cAMP/ CREB/MAPKs/MITF pathway and proteasomal degradation of tyrosinase [1]. Alam et al. revealed that N. nouchali flower extracts had DNA-protecting activities by phosphorylating mitogen- activated protein kinase (MAP kinase) followed by enhancing the nuclear translocation of the nuclear factor erythroid 2-related factor 2 (Nrf2). These cellular signaling activities attenuate cellular ROS generation and are associated with the protection from cell death [5]. The presences of gallic acid, catechin, epicatechin, epigallocatechin, epicatechin gallate, caffeic acid, quercetin, and apigenin were identified in the flower of this plant [5]. N. nouchali flower also has antimicrobial activity on human and plant pathogenic bacteria and endophytic fungi [6]. Seed extract promotes adipocyte differentiation and glucose consumption by inducing the PPARγ activation, which in turn increases mRNA GLUT-4 expression [7]. These previous studies proved the medicinal value of N. nouchali at molecular levels. Plant-derived natural dietary bioactive phytochemicals have potent antioxidants and cancer chemopreventive agents [8]. Dietary phytochemicals are often used as anticancer agents against breast cancer, skin cancer, diverse types of thyroid cancers, prostate cancer, and gastroenterological cancer, as well as play a role in modulating coding and non-coding genes in cancers [9]. N. nouchali tubers are eaten usually boiled or roasted. A novel Ca2+-dependent lectin was isolated from the N. nouchali tuber and exhibited antiproliferative properties [10]. Additionally, the tuber and root of N. nouchali were used by the folk medicine practitioners in three districts of Bangladesh for the prevention and management of malignancy in cancer [11]. However, to the best of our knowledge, there have been no investigations to date that identify the subset of anticancer pathways associated with the bioactive phytochemicals of N. nouchali tuber extract. Therefore, we designed the present study to identify the potential bioactive phytochemicals, to evaluate in vitro antioxidant properties, and to investigate the predicted genes interacting with bioactive phytochemicals and the association of these predicted genes with cancer pathways. In addition, we investigated the hub genes, which are regulated by the bioactive phytochemicals of N. nouchali.

  2. Materials and methods Top

2.1. Collection and preparation of methanolic crude extract of N. nouchali

The N. nouchali tubers were collected from different canals and ponds in Bangladesh. Collected tubers were thoroughly washed with fresh water, dried under shade at room temperature for 2 d. Then the skin of the tubers was removed and the tubers were cut into thin pieces. The pieces were sun-dried and powdered in a mechanical blender. About 100 g of dry powders were macerated in 500 mL methanol for 3 d in a flat bottomed container with occasional shaking, stirring, homogenization, and sonication [12]. Then it was filtered through a filter paper and the supernatant was collected. The extraction was repeated three times. The methanol was evaporated under reduced pressure below 50 °C through the rotatory evaporator (RE 200 Sterling, UK). The concentrated N. nouchali tuber extract was stored at 4 °C until further use.

2.2. Quantification of bioactive phytochemicals in methanolic extract of N. nouchali tuber

The amount of total phenolic and total tannin content was determined following the established method with some modifications by using Folin-Ciocalteu reagent [13]. The content of total flavonoids and proanthocyanidins was determined spectrophotometrically using a standard curve of catechin [14]. Ascorbic acid was assessed based on the established procedure [15]. Methanolic extract of N. nouchali tuber was then subjected to the high-performance liquid chromatography-diode array detector (HPLC-DAD) analysis. The composition of bioactive phytochemicals was determined by HPLC [14],[16]. Chromatographic analyses were carried out on a Thermo Scientific Dionex ultimate 3000 rapid separation LC (RSLC) systems (Thermo Fisher Scientific Inc., MA, USA), coupled to a quaternary rapid separation pump (LPG-3400RS), Ultimate 3000RS autosampler (WPS-3000) and rapid separation diode array detector (DAD-3000RS). Bioactive phytochemicals were separated on an Acclaim® C18 (4.6 mm χ 250 mm × 5 μm) column (Dionix, USA), which was controlled at 30 °C using a temperature-controlled column compartment (TCC-3000). For the preparation of calibration curve, a standard stock solution was prepared in methanol containing all bioactive phytochemicals. Data acquisition, peak integration, and calibrations were performed with Dionix Chromeleon software (Version 6.80 RS 10). At least three determinations were conducted for every analysis.

2.3. In vitro antioxidant activity

Total antioxidant activity was determined by using the phosphomolybdenum blue and FRAP reagent [14]. 2, 2-diphenyl- 1-picrylhydrazyl (DPPH), 2,2’-azino-bis (3-ethylbenzothiazoline- 6-sulfonic acid) (ABTS), and N, N-dimethyl-p-phenylenediamine (DMPD) were used to evaluate the in vitro radical scavenging activity [14]. Standard ascorbic acid was used in DPPH scavenging assay and gallic acid was used as a standard in ABTS and DMPD scavenging assays. The reducing power was determined by using ascorbic acid as a standard. The chelation of ferrous ions and superoxide radical scavenging capacity were also assessed according to our previous work [14],[17]. Based on the screening results of the triplicate measurement of the extract, the inhibition concentration (IC50) value was determined from extrapolating the graph of scavenging activity versus the concentration of extract (using linear regression analysis), which is defined as the amount of antioxidant necessary to reduce the initial radical concentration by 50%. EC50 value was determined from extrapolating the graph of the concentration of extract or standard versus absorbance at a specific nanometer (nm) using linear regression analysis. EC50 is the concentration of extract or standard to obtain absorbance=0.50[14].

2.4. Bioinformatics analysis

2.4.1. Target gene prediction for bioactive phytochemicals

On the basis of network pharmacology-based prediction, STITCH 5 ( was used to identify target genes related to bioactive phytochemicals [18]. It calculates a score for each pair of protein-chemical interactions. Chemical names of bioactive compounds (rutin, catechin, myricetin, ellagic acid, gallic acid, vanillic acid, rosmarinic acid, p-coumaric acid, quercetin, and ascorbic acid) were input into STITCH 5 singly to match their potential targets, with the organism selected as “Homo sapiens” and minimum required interaction score being ≥ 0.4. We predicted 20 genes with top confidence score for each bioactive compound by chromatographic and spectrophotometric analysis. The compound targets without a relationship with the compound-proteins interactions were not considered for further analysis. According to the results, only rosmarinic acid was not detected for any target genes. Usually, interactions with score ≥ 0.4 are considered as medium confidence.

2.4.2. Identification of Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway by enrichment analyses of the predicted genes

We performed a gene-set enrichment analysis of the predicted genes [19]. The KEGG [20] pathways significantly associated with the predicted genes were identified. The false discovery rate (FDR) < 0.05, calculated by the Benjamini and Hochberg method [21], was considered as significant.

2.4.3. Construction of protein-protein interaction (PPI) network of the predicted genes

We constructed a PPI network of the predicted genes by search tool for the retrieval of interacting genes (STRING) database (; STRING-DB v11.0)[22]. The hub genes (with no less than ten edges connected to other nodes) in the PPI network were identified using the node explorer module of NetworkAnalyst software [23].

  3. Results Top

3.1. Bioactive phytochemicals in the methanolic extract of N. nouchali tuber

The yield of methanolic extract of N. nouchali tuber was 5.49% (w/w). The content of total phenolics [(353.66±2.98) mg/g of the extract] was higher than total flavonoids [(102.86±14.13) mg/g of the extract], total tannins [(78.14±21.28) mg/g of the extract], and total proanthocyanidins [(4.42±2.67) mg/g of the extract]. The extract contained a moderate amount of ascorbic acid [(27.57±0.12) mg/100 g sun-dried tuber powder]. Furthermore, we identified bioactive phytochemicals using a HPLC system [Figure 1] and the results showed the presence of rutin (39.44 mg), catechin (39.20 mg), myricetin (30.77 mg), ellagic acid (11.05 mg), gallic acid (3.67 mg), vanillic acid (0.75 mg), rosmarinic acid (4.81 mg), p-coumaric acid (3.35 mg), and quercetin (0.90 mg) in 1 g of dry methanolic extract of N. nouchali tuber.
Figure 1: HPLC-DAD chromatogram of the methanolic extract of Nymphaea nouchali tuber. 1: gallic acid, 2: (+)-catechin, 3: vanillic acid, 4: p-coumaric acid, 5: ellagic acid, 6: rutin, 7: rosmarinic acid, 8: myricetin, and 9: quercetin.

Click here to view

3.2. In-vitro antioxidant activities of methanolic extract of N. nouchali tuber

By using phosphomolybdenum blue, the total antioxidant capacity in the methanolic extract of N. nouchali tuber was determined using the following linear regression equation: y=0.010x-0.090, R2=0.975, where y is absorbance and x is the ascorbic acid concentration in microgram. The total antioxidant capacity was (159.78±23.11) mg ascorbic acid equivalent in 1 g of the methanolic extract. By using FRAP reagents, the total antioxidant capacity was (763.58±36.88) mg ascorbic acid equivalent in 1 g of the methanolic extract (Linear regression equation of standard ascorbic acid: y=0.041x-0.072, R2=0.998).

We used DPPH, ABTS, and DMPD assays to screen free radical scavenging capacity of the extract. The IC50 value of standard ascorbic acid and the N. nouchali tuber extract was 13.77 μg/mL and 26.44 μg/mL, respectively in DPPH assay. For the extract and the standard gallic acid in ABTS assay, the IC50 value was 25.14 μg/mL and 8.86 μg/mL, respectively. In DMPD assay, the value was 49.32 μg/mL and 22.86 μg/mL, respectively.

Moreover, reducing power, superoxide radical scavenging capacity, and chelation of ferrous ions of the methanolic extract were determined. Ascorbic acid and the extract showed the EC50 of 44.42 μg/mL and 164.50 μg/mL, respectively in reducing power assay, indicating that bioactive phytochemicals of the extract are election donors and can reduce the oxidized intermediates. Superoxide was generated by alkaline DMSO method and the IC50 value of standard gallic acid and the methanol extract of the tuber was 75.90 μg/mL and 677.50 μg/mL, respectively. The assay for chelation capability of ferrous ion showed the IC50 value of standard ethylene diamine tetraacetic acid and the extract was 30.65 μg/mL and 1 949.69 μg/ mL, respectively, which indicates that the extract has extremely poor chelation capacity of ferrous ion. These results clearly indicated that the bioactive phytochemicals responsible for the antioxidant potentials might be present in the methanolic extract of N. nouchali tuber.

3.3. Network-based target prediction for bioactive phytochemicals

A drug-target network was constructed to further examine the potential mechanisms of action of the bioactive phytochemicals. The freely available STITCH software ( was used to construct the drug-target network and to provide genetic identification in humans. We selected 20 genes/protein for each bioactive phytochemical identified by chromatographic analysis. Altogether, 130 unique target genes were predicted by all the compounds (ascorbic acid, catechin, myricetin, ellagic acid, gallic acid, vanillic acid, p-coumaric acid, quercetin, and rutin). The network-based target predicted genes are summarised in [Supplementary Table 1] [Additional file 1].

3.4. Enrichment of cancer pathways of the predicted genes

Enriched KEGG pathways of the predicted 130 unique genes were analyzed. These pathways were mainly involved in cellular development, immune regulation, metabolism, and cancer (Supplementary Table 2] [Additional file 2]. -Log10(FDR) values of some significantly (FDR<0.05) enriched cancer-associated pathways are shown in [Figure 2]. Some of significant cancer-associated pathways (FDR<0.05) were as follows: pathways in cancer (MAPK3, PIK3CG, AKT1, PRKCA, JUN, CHUK, CXCL8, IL6, CASP3, PTGS2, SLC2A1, ARNT, EGFR, BMP2, MMP2, MMP9, NOS2, and FGF2), renal cell carcinoma (MAPK3, PIK3CG, AKT1, JUN, SLC2A1, and ARNT), bladder cancer (MAPK3, MMP2, EGFR, MMP9, and CXCL8), non-small cell lung cancer (MAPK3, PIK3CG, AKT1, PRKCA, and EGFR), acute myeloid leukemia (MAPK3, PIK3CG, AKT1, CHUK, and PIM1), colorectal cancer (MAPK3, PIK3CG, AKT1, CASP3, and JUN), glioma (MAPK3, PIK3CG, AKT1, PRKCA, and EGFR), pancreatic cancer (MAPK3, PIK3CG, AKT1, CHUK, and EGFR), melanoma (MAPK3, PIK3CG, AKT1, FGF2, and EGFR), small cell lung cancer (PIK3CG, AKT1, NOS2, CHUK, and PTGS2), prostate cancer (MAPK3, PIK3CG, AKT1, CHUK, and EGFR), endometrial cancer (MAPK3, PIK3CG, AKT1, and EGFR), and chronic myeloid leukemia (MAPK3, PIK3CG, AKT1, and CHUK).
Figure 2: Some of significantly enriched cancer-associated KEGG pathways in human. FDR: false discovery rate.

Click here to view

3.5. Identification of hub genes associated with pathways in cancer

Using STRING database and NetworkAnalyst software, a total of 130 predicted genes were mapped into the PPI network, including 128 nodes and 841 edges with the PPI enrichment P-value less than 1.0×1016. Interestingly, we found that 117 genes were involved in the PPI network and 65 genes (hub genes) had PPI connectivity degree not less than 10 [Figure 3] and [Supplementary Table 3] [Additional file 3]. In addition, we identified top ten hub genes (IL6, AKT1, EGFR, CAT, JUN, PTGS2, MAPK3, CASP3, CXCL8, and NOS3) with a higher degree of connectivity, which are associated with pathways in cancer in this study, and eight of them interacted with bioactive phytochemicals of the methanolic extract of N. nouchali tuber [Figure 4] and [Table 1]. These hub genes interacted with one or more bioactive phytochemicals. For example, AKT1 interacted with gallic acid, myricetin, and quercetin; CASP3 with gallic acid, rutin, quercetin, and myricetin. Based on the hub genes and the bioactive phytochemicals, we established a gene-bioactive phytochemicals regulatory network that may contribute to the treatment of cancer. This network included the interactions of IL6-catechin, AKT1-gallic acid/myricetin/quercetin, EGFR/MAPK3/CXCL8-rutin, JUN-gallic acid, PTGS2-catechin/p-coumaric acid/quercetin, and CASP3-gallic acid/rutin/quercetin/myricetin.
Figure 3: Protein-protein interaction network of the 130 predicted genes. 117 genes were involved in the protein-protein interaction network.

Click here to view
Figure 4: Hub genes (CXCL8, EGFR, MAPK3, JUN, CASP3, AKT1, PTGS2, and IL6) interacted with bioactive phytochemicals of Nymphaea nouchali tuber extract (NNTE) and associated with cancer pathways.

Click here to view
Table 1: The top ten hub genes with a higher degree of connectivity which are targeted by bioactive phytochemicals from the methanolic extract of Nymphaea nouchali tuber.

Click here to view

  4. Discussion Top

Phenolics have remarkable bioactivities including anticancer, anti-inflammatory, antibacterial, anti-diabetes, anti-cardiovascular, anti-neurodegenerative, anti-analgesic, anti-allergic, and anti- Alzheimer’s properties [24]. Phenolics also stimulate the expression of tumor-suppressing proteins such as p53, phosphatase and tensin homolog (PTEN), p21, and p27[25]. The biological and pharmacological effects of flavonoids include antioxidant, anti- inflammatory, cardioprotective, hepatoprotective, antimicrobial, and anticancer activities [26]. Proanthocyanidins and tannins have various pharmacological effects, including antioxidant and free radical scavenging activity, antimicrobial, anti-cancer, anti-nutritional, and cardioprotective properties [27]. Our study showed the presence of bioactive phytochemicals in methanolic extract of N. nouchali tuber. Natural antioxidants exhibit a wide range of biological effects, such as anti-inflammatory, antibacterial, antiviral, anti-aging, and anticancer [28]. Therefore, our results suggested that the extract of N. nouchali tuber might be used as an effective and safe source of natural antioxidants against various diseases, including cancer.

Network medicine offers a platform to systematically explore the molecular complexity of a particular disease, which helps identify modules and pathways of diseases as well as the molecular relationships among apparently distinct phenotypes [29]. Integrating network biology and pharmacology is a paradigm for drug discovery [30]. Phytochemicals activate pathways and thereby enhance the ability of cells to resist injury and disease [31]. Dietary phytochemicals demonstrate strong anticancer effects and affect several cancer-related pathways [32]. Dietary bioactive phytochemicals have gained tremendous attention because of their ability to inhibit multiple signaling pathways as a promising approach to prevent and treat cancers [33]. Our findings indicate that bioactive phytochemicals in the methanolic extract of N. nouchali tuber are associated with anticancer pathways, and these bioactive phytochemicals may be better therapeutic agents for treating cancers. PPI network plays an important role in molecular processes, and abnormal PPI is the basis of many pathological conditions, including tumors [34]. The IL-6/JAK/STAT3 pathway is aberrantly hyperactivated in many types of cancer [35]. Another hub gene PTGS2 is upregulated during both inflammation and cancer [36]. IL6 and PTGS2 both interact with catechin, and it was stated that catechin intake may ensure a protective epigenetic status against the adverse effects through the interaction with IL6[37]. An important antioxidant enzyme catalase (CAT) is another hub gene with 46 connectivity degree and is associated with genetic, epigenetic, and posttranscriptional processes. Abnormal expression levels of CAT have been reported in cancer tissues [38]. Gallic acid significantly increased the activity of CAT in rat model. A recent study demonstrated the link between aberrant cell cycle progression and AKT hyperactivation in cancer [39]. Gallic acid inhibited the activities of AKT as well as migration and invasion in human osteosarcoma [40]. Quercetin facilitates cell death and chemosensitivity through RAGE/PI3K/AKT/mTOR axis in human pancreatic cancer cells [41]. A proto-oncogene JUN is a molecular target for improving cancer therapy [42]. CASP3 is used as a marker for efficacy of cancer therapy and this gene may not only increase the sensitivity of cancer cells to chemotherapy and radiotherapy, but also inhibit cancer cell invasion and metastases [43]. Gallic acid, rutin, tannic acid, and quercetin significantly inhibited cell proliferation of human prostate cancer by increasing the caspase-3 activity [44]. Gallic acid also upregulated the expression of CASP3 that induced apoptosis [45]. Aberrant expression of MAPK3 is associated with invasion, metastasis, and drug resistance of multiple tumor cells [46].

EGFR is involved in the pathogenesis and progression of different carcinoma types [47]. CXCL8 is the most studied chemokine in human malignancies and displays multifaceted pro-tumorigenic effects, including tumor cell growth, metastatization, and angiogenesis, contributing to the progression of several cancers [48]. Polyphenols downregulated gene expression of pro-inflammatory cytokines/ enzymes and differentially modulated the inflammatory response of human keratinocytes through distinct signal transduction pathways, including EGFR-MAPK pathways [49]. Our results reveal that three hub genes (MAPK3, EGFR, and CXCL8) interacted with rutin. The above findings suggested that these hub genes might play a crucial role in various types of cancers and interact with bioactive compounds of the N. nouchali tuber extract.

  5. Conclusion Top

The discovery of bioactive phytochemicals and their predicted target genes will be of great importance in various treatments against chronic diseases including various cancers. The results strongly indicate that this medicinal plant can serve as a very useful source of antioxidant and anticancer components. The network pharmacology contributes to understanding the complex interactions between bioactive phytochemicals and anticancer pathways from a network perspective. Consequently, network pharmacology provides a novel approach to promote drug discovery in a precise manner from this plant. Furthermore, clinical experiments are required to characterize the potent molecule from the pharmaceutical point of view in future studies.

Conflict of interest statement

The authors declare that they have no conflicts of interest.


This work was carried out under the research and development (R and D) project of the Bangladesh Council of Scientific and Industrial Research.

Authors’ contributions

MNU performed data analyses, conceived the research, designed analysis strategies, and wrote the manuscript. MZH and MAZ conceived the research and designed analysis strategies. MAS and TAK performed data analyses. MAH, AS, and AA drew the figures and helped write the manuscript. KM helped to revise the manuscript. All the authors read and approved the final manuscript.

  References Top

Alam MB, Ahmed A, Motin MA, Kim S, Lee SH. Attenuation of melanogenesis by Nymphaea nouchali (Burm. f) flower extract through the regulation of cAMP/CREB/MAPKs/MITF and proteasomal degradation of tyrosinase. Sci Rep 2018; 8 (1): 13928. Doi: 10.1038/s41598-018- 32303-7.  Back to cited text no. 1
Siddhanta AK, Mody KH, Ramavat BK, Chauhan VD, Garg HS, Goel AK, et al. Bioactivity of marine organisms: Part ffl-Screening of some marine flora of western coast of India. Indian J Exp Biol 1997; 35 (6): 638-643.  Back to cited text no. 2
Bhandarkar MR, Khan A. Antihepatotoxic effect of Nymphaea stellata willd., against carbon tetrachloride-induced hepatic damage in albino rats. J Ethnopharmacol 2004; 91 (1): 61-64.  Back to cited text no. 3
Raja MKMM, Sethiya NK, Mishra SH. A comprehensive review on Nymphaea stellata: A traditionally used bitter. J Adv Pharm Technol Res 2010; 1 (3): 311-319.  Back to cited text no. 4
Alam MB, Ju MK, Lee SH. DNA protecting activities of Nymphaea nouchali (Burm. f) flower extract attenuate t-BHP-induced oxidative stress cell death through Nrf2-mediated induction of heme oxygenase-1 expression by activating MAP-kinases. Int J Mol Sci 2017; 18 (10). Doi: 10.3390/ijms18102069.  Back to cited text no. 5
Dissanayake RK, Ratnaweera PB, Williams DE, Wijayarathne CD, Wijesundera RLC, Andersen RJ, et al. Antimicrobial activities of endophytic fungi of the Sri Lankan aquatic plant Nymphaea nouchali and chaetoglobosin A and C, produced by the endophytic fungus Chaetomium globosum. Mycology 2016; 7 (1): 1-8.  Back to cited text no. 6
Parimala M, Debjani M, Vasanthi HR, Shoba FG. Nymphaea nouchali Burm. f. hydroalcoholic seed extract increases glucose consumption in 3T3-L1 adipocytes through activation of peroxisome proliferator-activated receptor gamma and insulin sensitization. J Adv Pharm Technol Res 2015; 6 (4): 183-189.  Back to cited text no. 7
Shankar E, Kanwal R, Candamo M, Gupta S. Dietary phytochemicals as epigenetic modifiers in cancer: Promise and challenges. Semin Cancer Biol 2016; 40-41: 82-99.  Back to cited text no. 8
Budisan L, Gulei D, Zanoaga OM, Irimie AI, Chira S, Braicu C, et al. Dietary intervention by phytochemicals and their role in modulating coding and non-coding genes in cancer. Int J Mol Sci 2017; 18 (6). Doi: 10.3390/ijms18061178.  Back to cited text no. 9
KabirSR, Zubair MA, Nurujjaman M, Haque MA, Hasan I, Islam MF, et al. Purification and characterization of a Ca(2+)-dependent novel lectin from Nymphaea nouchali tuber with antiproliferative activities. Biosci Rep 2011; 31 (6): 465-475.  Back to cited text no. 10
KabidulAzam MdN, Rahman MdM, Biswas S, Ahmed MdN. Appraisals of Bangladeshi medicinal plants used by folk medicine practitioners in the prevention and management of malignant neoplastic diseases. Int Sch Res Not 2016; 2016: 7832120. Doi: 10.1155/2016/7832120.  Back to cited text no. 11
PisoschiAM, Pop A, Cimpeanu C, Predoi G. Antioxidant capacity determination in plants and plant-derived products: A review. Oxid Med Cell Longev 2016; 2016: 9130976. Doi: 10.1155/2016/9130976.  Back to cited text no. 12
AinsworthEA, Gillespie KM. Estimation of total phenolic content and other oxidation substrates in plant tissues using Folin-Ciocalteu reagent. Nat Protoc 2007; 2 (4): 875-877.  Back to cited text no. 13
UddinMN, Mitra K, Haque MZ. Comparative bio-active compounds determination and in vitro antioxidant properties of newly developed soy mixed wheat flour and traditional wheat flour. Int J Food Prop 2016; 19 (9): 2113-2126.  Back to cited text no. 14
KhalilI, Moniruzzaman M, Boukraâ L, Benhanifia M, Islam A, Islam N, et al. Physicochemical and antioxidant properties of Algerian honey. Mol Basel Switz 2012; 17 (9): 11199-11215.  Back to cited text no. 15
ChuanphongpanichS, Phanichphant S. Method development and determination of phenolic compounds in broccoli seeds samples. J Sci 2006; 33 (1): 103-107.  Back to cited text no. 16
UddinMN, Rahman MA, Hossain H, Khan TA, Akter R. High- performance liquid chromatographic analysis explores the potential antioxidative agents of Argyreia argentea ARN. EX CHOISY extract. J Pharm Bioallied Sci 2019; 11 (1): 16.  Back to cited text no. 17
SzklarczykD, Santos A, von Mering C, Jensen LJ, Bork P, Kuhn M. STITCH 5: Augmenting protein-chemical interaction networks with tissue and affinity data. Nucleic Acids Res 2016; 44 (D1): D380-D384.  Back to cited text no. 18
Subramanian A, Tamayo P, Mootha VK, Mukherjee S, Ebert BL, Gillette MA, et al. Gene set enrichment analysis: A knowledge-based approach for interpreting genome-wide expression profiles. Proc Natl Acad Sci U S A 2005; 102 (43): 15545-15550.  Back to cited text no. 19
KanehisaM, Furumichi M, Tanabe M, Sato Y, Morishima K. KEGG: New perspectives on genomes, pathways, diseases and drugs. Nucleic Acids Res 2017; 45 (D1): D353-D361.  Back to cited text no. 20
BenjaminiY, Hochberg Y. Controlling the false discovery rate: A practical and powerful approach to multiple testing. J R Stat Soc Ser B Methodol 1995; 57 (1): 289-300.  Back to cited text no. 21
SzklarczykD, Gable AL, Lyon D, Junge A, Wyder S, Huerta-Cepas J, et al. STRING v11: Protein-protein association networks with increased coverage, supporting functional discovery in genome-wide experimental datasets. Nucleic Acids Res 2019; 47 (Database issue): D607-D613.  Back to cited text no. 22
XiaJ, Benner MJ, Hancock REW. NetworkAnalyst - integrative approaches for protein-protein interaction network analysis and visual exploration. Nucleic Acids Res 2014; 42 (Web Server issue): W167-W174.  Back to cited text no. 23
ShahidiF, Yeo J. Bioactivities of phenolics by focusing on suppression of chronic diseases: A review. Int J Mol Sci 2018; 19 (6). Doi: 10.3390/ ijms19061573.  Back to cited text no. 24
AnantharajuPG, Gowda PC, Vimalambike MG, Madhunapantula SV. An overview on the role of dietary phenolics for the treatment of cancers. Nutr J 2016; 15 (1): 99.  Back to cited text no. 25
GontijoVS, Dos Santos MH, Viegas C. Biological and chemical aspects of natural biflavonoids from plants: A brief review. Mini Rev Med Chem 2017; 17 (10): 834-862.  Back to cited text no. 26
SmeriglioA, Barreca D, Bellocco E, Trombetta D. Proanthocyanidins and hydrolysable tannins: Occurrence, dietary intake and pharmacological effects. Br J Pharmacol 2017; 174 (11): 1244-1262.  Back to cited text no. 27
ZhengJ, Zhou Y, Li Y, Xu DP, Li S, Li HB. Spices for prevention and treatment of cancers. Nutrients 2016; 8 (8): 495. Doi: 10.3390/nu8080495.  Back to cited text no. 28
BarabásiAL, Gulbahce N, Loscalzo J. Network medicine: A network- based approach to human disease. Nat Rev Genet 2011; 12 (1): 56-68.  Back to cited text no. 29
HopkinsAL. Network pharmacology: The next paradigm in drug discovery. Nat Chem Biol 2008; 4 (11): 682-690.  Back to cited text no. 30
LeeJ, Jo DG, Park D, Chung HY, Mattson MP. Adaptive cellular stress pathways as therapeutic targets of dietary phytochemicals: Focus on the nervous system. Pharmacol Rev 2014; 66 (3): 815-868.  Back to cited text no. 31
KapinovaA, Kubatka P, Golubnitschaja O, Kello M, Zubor P, Solar P, et al. Dietary phytochemicals in breast cancer research: Anticancer effects and potential utility for effective chemoprevention. Environ Health Prev Med 2018; 23 (1): 36. Doi: 10.1186/s12199-018-0724-1.  Back to cited text no. 32
DandawatePR, Subramaniam D, Jensen RA, Anant S. Targeting cancer stem cells and signaling pathways by phytochemicals: Novel approach for breast cancer therapy. Semin Cancer Biol 2016; 40-41: 192-208.  Back to cited text no. 33
WongFH, Huang CYF, Su LJ, Wu YC, Lin YS, Hsia JY, et al. Combination of microarray profiling and protein-protein interaction databases delineates the minimal discriminators as a metastasis network for esophageal squamous cell carcinoma. Int J Oncol 2009; 34 (1): 117128.  Back to cited text no. 34
JohnsonDE, O’Keefe RA, Grandis JR. Targeting the IL-6/JAK/STAT3 signalling axis in cancer. Nat Rev Clin Oncol 2018; 15 (4): 234-248.  Back to cited text no. 35
DesaiSJ, Prickril B, Rasooly A. Mechanisms of phytonutrient modulation of cyclooxygenase-2 (COX-2) and inflammation related to cancer. Nutr Cancer 2018; 70 (3): 350-375.  Back to cited text no. 36
ZhongJ, Colicino E, Lin X, Mehta A, Kloog I, Zanobetti A, et al. Cardiac autonomic dysfunction: Particulate air pollution effects are modulated by epigenetic immunoregulation of toll-like receptor 2 and dietary flavonoid intake. J Am Heart Assoc 2015; 4 (1): e001423. Doi: 10.1161/ JAHA.114.001423.  Back to cited text no. 37
GlorieuxC, Zamocky M, Sandoval JM, Verrax J, Calderon PB. Regulation of catalase expression in healthy and cancerous cells. Free Radic Biol Med 2015; 87: 84-97.  Back to cited text no. 38
LiuP, Begley M, Michowski W, Inuzuka H, Ginzberg M, Gao D, et al. Cell-cycle-regulated activation of Akt kinase by phosphorylation at its carboxyl terminus. Nature 2014; 508 (7497): 541-545.  Back to cited text no. 39
LiaoCL, Lai KC, Huang AC, Yang JS, Lin JJ, Wu SH, et al. Gallic acid inhibits migration and invasion in human osteosarcoma U-2 OS cells through suppressing the matrix metalloproteinase-2/-9, protein kinase B (PKB) and PKC signaling pathways. Food Chem Toxicol Int J Publ Br Ind Biol Res Assoc 2012; 50 (5): 1734-1740.  Back to cited text no. 40
LanCY, Chen SY, Kuo CW, Lu CC, Yen GC. Quercetin facilitates cell death and chemosensitivity through RAGE/PI3K/AKT/mTOR axis in human pancreatic cancer cells. J Food Drug Anal 2019; 27 (4): 887-896. Doi: 10.1016/j.jfda.2019.07.001.  Back to cited text no. 41
XiaY, Yang W, Bu W, Ji H, Zhao X, Zheng Y, et al. Differential regulation of c-Jun protein plays an instrumental role in chemoresistance of cancer cells. J Biol Chem 2013; 288 (27): 19321-19329.  Back to cited text no. 42
ZhouM, Liu X, Li Z, Huang Q, Li F, Li CY. Caspase-3 regulates the migration, invasion, and metastasis of colon cancer cells. Int J Cancer 2018; 143 (4): 921-930.  Back to cited text no. 43
FerrueloA, Romero I, Cabrera PM, Arance I, Andrés G, Angulo JC. Effects of resveratrol and other wine polyphenols on the proliferation, apoptosis and androgen receptor expression in LNCaP cells. Actas Urol Esp 2014; 38 (6): 397-404.  Back to cited text no. 44
ChandramohanReddy T, Bharat Reddy D, Aparna A, Arunasree KM, Gupta G, Achari C, et al. Anti-leukemic effects of gallic acid on human leukemia K562 cells: Downregulation of COX-2, inhibition of BCR/ ABL kinase and NF-KB inactivation. Toxicol Vitro Int J Publ Assoc BIBRA 2012; 26 (3): 396-405.  Back to cited text no. 45
CaoHY, Xiao CH, Lu HJ, Yu HZ, Hong H, Guo CY, et al. MiR-129 reduces CDDP resistance in gastric cancer cells by inhibiting MAPK3. Eur Rev Med Pharmacol Sci 2019; 23 (15): 6478-6485.  Back to cited text no. 46
NormannoN, De Luca A, Bianco C, Strizzi L, Mancino M, Maiello MR, et al. Epidermal growth factor receptor (EGFR) signaling in cancer. Gene 2006; 366 (1): 2-16.  Back to cited text no. 47
RotondiM, Coperchini F, Latrofa F, Chiovato L. Role of chemokines in thyroid cancer microenvironment: Is CXCL8 the main player? Front Endocrinol 2018; 9: 314. Doi:10.3389/fendo.2018.00314.  Back to cited text no. 48
PotapovichAI, Lulli D, Fidanza P, Kostyuk VA, De Luca C, Pastore S, et al. Plant polyphenols differentially modulate inflammatory responses of human keratinocytes by interfering with activation of transcription factors NFKB and AhR and EGFR-ERK pathway. Toxicol Appl Pharmacol 2011; 255 (2): 138-149.  Back to cited text no. 49


  [Figure 1], [Figure 2], [Figure 3], [Figure 4]

  [Table 1]


    Similar in PUBMED
   Search Pubmed for
   Search in Google Scholar for
 Related articles
    Access Statistics
    Email Alert *
    Add to My List *
* Registration required (free)  

  In this article
1. Introduction
2. Materials and...
3. Results
4. Discussion
5. Conclusion
Article Figures
Article Tables

 Article Access Statistics
    PDF Downloaded285    
    Comments [Add]    

Recommend this journal