Eichhornia crassipes (Mart.) Solms: A Comprehensive Review of Its Chemical Composition, Traditional Use, and Value-Added Products

Eichhornia crassipes (Mart.) Solms, commonly known as water hyacinth, is one of the world’s most invasive aquatic plants of the Pontederiaceae family occurring in tropical and subtropical regions of the world. Although, E. crassipes causes significant ecological and socioeconomic issues such as a high loss in water resources, it has multipurpose applications since it is famous for many industrial applications such as bioenergy, biofertilizer production, wastewater treatment (absorption of heavy metals), and animal feed. Furthermore, E. crassipes is rich in diverse bioactive secondary metabolites including sterols, alkaloids, phenolics, flavonoids, tannins, and saponins. These secondary metabolites are well known for a wide array of therapeutic properties. The findings of this review suggest that extracts and some isolated compounds from E. crassipes possess some pharmacological activities including anticancer, antioxidant, anti-inflammatory, antimicrobial, skin whitening, neuroprotective, and hepatoprotective activities, among other biological activities such as allelopathic, larvicidal, and insecticidal activities. The present review comprehensively summarizes the chemical composition of E. crassipes, reported to date, along with its traditional uses and pharmacological and biological activities.


INTRODUCTION
Eichhornia crassipes (Mart.), commonly known as water hyacinth, is a monocotyledonous freefloating aquatic plant belonging to the family Pontederiaceae. The plant is native to Brazil and the Amazon, but it has been naturalized in tropical and subtropical regions. It has also been reported in several parts of Africa, including Egypt, Sudan, Kenya, Ethiopia, Nigeria, Zimbabwe, Zambia, and South Africa (Dersseh et al., 2019). The plant is characterized by its high growth, rapid and extensive spread, and strong tolerance to pH and nutrient variations as well as temperature conditions. Hence, it has been recognized by the International Union for Conservation of Nature as one of the 100 most aggressive invasive species and identified as one of the 10 severest weed plants in the world (Téllez et al., 2008;Zhang et al., 2010;Patel, 2012). However, E. crassipes possesses many potential benefits but with financial and environmental fallout (Yan et al., 2017;Su et al., 2018). It has been used as phytoremediation agent for wastewater treatments because of its ability to absorb heavy metals and grow in polluted water (Mishra and Maiti, 2017;Mustafa and Hayder, 2021). It has also been considered as a potential source of bioenergy (Carreño Sayago and Rodríguez, 2018) and biofertilizers (Manyuchi et al., 2019). Traditionally, the plant is used to treat gastrointestinal disorders, such as diarrhea, intestinal worms, digestive disorders, and flatulence. In addition, the beans were harnessed for healthy spleen functioning (Sharma et al., 2020). The plant is also rich in various bioactive compounds that exhibit a wide array of pharmacological properties.
The current review comprehensively assesses the state of the art concerning the phytochemical composition, therapeutic uses, and pharmaceutical applications of E. crassipes (Mart.) along with patents reported on the plant.

METHODOLOGY OF RESEARCH
A literature-based search was conducted to provide an overview of the phytochemistry, value-added products, and pharmacological activities of E. crassipes, using accessible online databases such as PubMed, Scopus, Web of Science, and Google Scholar. The literature survey was performed using different keywords including "Eichhornia crassipes" or "water hyacinth" and chemical constituents, or valueadded products, or antioxidant, or anti-inflammatory, or antimicrobial or hepatoprotective or wound healing, which resulted in the gathering of much literature. An extensive number of studies published in research articles, review articles, book chapters, and books were collected. From 2,835 identified studies, a total of 150 studies, which met the inclusion criteria, were preserved in this survey. The outline for literature search and management is presented in Figure 1.

BOTANICAL DESCRIPTION
The Pontederiaceae family possesses nine genera, including Eichhornia. The latter is composed of eight species of aquatic plants, among them is Eichhornia crassipes (Mart.) Solms: synonym of Pontederia crassipes (Mart.). The mature plant has roots, leaves, stolon, inflorescences, and fruit clusters (Parsons and Cuthbertson, 2001) (Figure 2). The root morphology is highly plastic and fibrous, having one single main root with many laterals, forming a huge root system. Because each lateral root has a root tip, E. crassipes may exploit nutrients in a low-nutrient water body, which makes the lateral roots longer and denser at low phosphorus concentrations.
E. crassipes petioles are both erect and horizontal as stolon. There are two types of leaves, thin and round. The thin ones stand erect while the round ones possess a slightly undulating edge. In addition, the two types of leaves are soft, glossy, and glabrous. The leaves possess semi-parallel veins following their curvature (Parsons and Cuthbertson, 2001). The plant possesses beautiful violet flowers with six petals that may be found throughout the year under favorable conditions. However, the intensity of flowering may differ over the four seasons. The fruit contains 300 seeds in a slim threecelled capsule which measures 1-1.5 mm long with many longitudinal ribs. In regions with temperatures around 25°C, the seeds can remain inactive for up to 20 years and then germinate with water. Generally, temperatures between 20 and 35°C enhance germination while temperatures around 35°C enhance rapid growth (Parsons and Cuthbertson, 2001;Malik, 2007).

Saponins
Many studies have confirmed the presence of saponins in various extracts of different parts of E. crassipes (Baral and Vaidya, 2011;Jayanthi et al., 2011;Hamid et al., 2013;Anusiya et al., 2020). Saponins were detected in the aqueous extracts from samples collected from the Phewa Lake in Nepal (Baral and Vaidya, 2011). By contrast, aqueous extracts of the plant from Dijla River, Baghdad, showed the absence of saponins (Hamid et al., 2013). Moreover, the phytochemical screening of hexane, chloroform, and ethanol extracts revealed the presence of saponins from samples collected from Nepal (Baral and Vaidya, 2011;Baral et al., 2012;Lalitha and Jayanthi, 2012). For instance, two steroidal saponins, namely spirostane (32) and cholestane (33) were isolated from E. crassipes. The first was found in the acetone extract of the roots and the second in the cyclohexane leaf extract of E. crassipes (Fileto-Pérez et al., 2015) as shown in Supplementary Figure S3. These compounds characterized the plant collected from India and were not detected elsewhere.

Terpenoids
Phytol (34) was identified by GC-MS in the ethanol extract from the whole plant collected from India (Muthunarayanan et al., 2011;Tyagi and Agarwal, 2017a). This compound is considered a major bioactive compound present in the leaves of the plants collected from India (Tyagi and Agarwal, 2017a;Kumar et al., 2018a). Squalene (35), a hypocholesterolemic terpenoid, was identified in the non-polar and polar extracts of the leaves and stems of E. crassipes, from Mexico (Supplementary Figure S4) (Fileto-Pérez et al., 2015). This compound has been only identified in the Mexican plant. GC-MS studies conducted by Lenora et al. (2016) have reported the presence camarolide (36), a pentacyclic triterpenoid, in the methanol extract of the aerial parts of the plant.
Carbohydrates Sucrose (99), fructose (100), glucose (101), xylose (102), arabinose (103), and galactose (104) are the main soluble sugars present in the leaves, along with galactomannan (105) and branched (1→3)-β-D-glucan (Arifkhodzhaev and Shoyakubov, 1995). The chloroform and aqueous extracts of the shoots revealed the presence of cardiac glycosides, however, they were absent in the rhizome (Lata and Dubey, 2010). Sulfated polysaccharides were found in the whole plant, with high amounts in the roots (Dantas-Santos et al., 2012). Furthermore, cellulose xanthate was produced from the chemical treatment of E. crassipes shoot and root biomass with NaOH and CS 2 (Zhou et al., 2009), which is known for its ability to adsorb heavy metals (Deng et al., 2012). Nanocrystalline cellulose was isolated from E. crassipes fibers after chemical and mechanical treatments (Asrofi et al., 2017). Xylitol (106), a pentose polyol, used in food and pharmaceutical industries, was also isolated and identified from the plant (Prakasham et al., 2009). Different studies reported the yield of xylose from E. crassipes biomass. Kalhorinia et al. (2014) reported a yield of 35 g/L of xylitol using simple and efficient acid pretreatment, while 0.25 g/L of xylitol was produced from the hemicellulosic parts of the plant by acid hydrolysis (Shankar et al., 2020). The worldwide market of xylitol is more than 700 million USD/year in the food and pharmaceutical industries and is expected to reach 1.37 USD billion by 2025. The selling price of xylitol is estimated to be 5 USD/kg (Supplementary Figure S10) (Raj and Krishnan, 2020).

Organic Acids
In total, 20 organic acids were identified in different types of extracts from the leaves, stem, and roots of the Mexican plant. These include oxalic acid (107), nonanoic acid (108), malonic acid (109), succinic acid (110), and phthalic acid (111) (Fileto-Pérez et al., 2015). While, propiolic acid (112) was identified from the ethanolic extract of the leaves as a major compound from the plant collected from India (Kumar et al., 2018a).
Furthermore, levulinic acid (113) extracted with microwave heating techniques was isolated from the dried plant with a yield of 9.43% dry weight (Lai et al., 2011). From the aerial parts, shikimic acid (114), an antiviral agent, was isolated with a yield of 0.03-3.25% w/w from 1.0 g of plant material (Bochkov et al., 2012;Cardoso et al., 2014;Lenora et al., 2016). Isoascorbic acid (115), ascorbic acid (116), and dehydroascorbic acid (117) were present in the shoot extracts, however, the latter was detected only in the rhizome (Lata and Dubey. 2010). Humic acids, which play an essential role in retaining water and texture soils were also found to be present in several parts of the plant such as the leaves, stems, and roots (Supplementary Figure S11) (Ghabbour et al., 2004).

Other Compounds
Other metabolites belonging to different classes were detected in different parts of E. crassipes.

VALUE-ADDED PRODUCTS FROM E. CRASSIPES (MART.) SOLMS
The biorefinery of E. crassipes biomass revealed several enzymes and valuable products. Furfural and hydroxymethylfurfural, for instance, were produced using the nonhazardous oxidant (FeCl 3 ) method with the highest yield of 7.9 wt% of the dry mass of the plant (Liu et al., 2018;Poomsawat et al., 2019). Moreover, due to E. crassipes availability, low price, and its high percentage of cellulose, the plant is considered a favorable source to produce fibers, superconductors, and supercapacitors (Sundari and Ramesh, 2012;Asrofi et al., 2017;Sindhu et al., 2017). The liquid tar obtained from the plant (rich in phenolic compounds) yielded 29% of carbon fiber, which makes the plant suitable for fiber production (Soenjaya et al., 2015).
In addition, different biopolymers with diverse applications along with several enzymes such as cellulase, β-glucosidase, and xylanase were obtained from the plant biomass ( Table 1). The enzymes are produced from the plant residue, as carbon source, by submerged fermentation or under solid state fermentation using different microorganisms. The production of these enzymes harnessed on large for cost-effective industrial applications. Table 2 presents the different enzymes produced from E. crassipes residue.
In the same line, biopolymers are produced by various microorganisms, like Cupravidus necatar and Pseudomonas aeruginosa, combined with acid pretreatments using E. crassipes as a substrate. Radhika and Murugesan (2012) revealed that the addition of E. crassipes enzymatic hydrolizate gave 4.3 g/L of PHB.
Meanwhile, the composites are prepared using solution impregnation and hot curving methods (Ramirez et al., 2015). According to several studies, E. crassipes has been used as a raw material to produce high-value chemicals such as furfural, enzymes, biopolymers, and composites as reviewed in Guna et al. (2017), Sindhu et al. (2017), and Ilo et al. (2020).

PHARMACOLOGICAL AND BIOLOGICAL ACTIVITIES
The varied ethnobotanical uses of E. crassipes have led to the ignition of various pharmacological investigations. A diverse range of in vitro and in vivo test systems has been used to evaluate the pharmacological properties of E. crassipes. Table 3 summarizes the reported pharmacological activities of E. crassipes. These include anti-microbial, antioxidant, wound healing, antitumor, and cytotoxic activities encompassing more than 50% of the studies. The activities related to larvicidal, insecticidal, and allelopathic effects accounted for 20% of the studies (Figure 4). The wide range of biological activities of E. crassipes are attributed to the presence of bioactive compounds belonging to different classes of secondary metabolites as reported earlier.

Neuropharmacological Activities
Potential behavioral neuropharmacological activities, as evidenced by the analgesic, anti-epileptic sedative, central nervous system depressant, anti-anxiety, anti-psychosis, antidepressant, and memory-improving properties, were exerted by the ethanol extract of leaves of E. crassipes in combination with ethanol extracts of Nelumbo nucifera leaves in mice models (Farheen et al., 2015). The results showed that the ethanol extract of E. crassipes leaves significantly inhibited motor activity, demonstrated high anti-anxiety property, and decreased the exploratory behavior pattern in evasion tests. The treated mice were able to maintain their posture for over 180 s. Moreover, the same extract prolonged sleep latency and duration, improved latency period, and generated the highest inhibition of writhing test induced by acetic acid. In addition, the histopathological findings confirmed the neuronal protective properties of E. crassipes in combination with N. nucifera, where an important glial reaction was observed in the brain of the treated mice (Farheen et al., 2015). However, there are some shortcomings in the application of E. crassipes extracts as a neuroprotective agent. In this line, further studies are required to confirm the neuropharmacological activity of the plant, to clarify the correlation between the phytochemical composition and the pharmacological activity.

Anti-Inflammatory Activities
The stems and leaves of E. crassipes were used to treat swelling and wounds due to its anti-inflammatory activity associated with the phenolic content in the plant (Rorong et al., 2012). In the sample line, lemon juice plus the juice of E. crassipes leaves have been traditionally used as anti-inflammatory topical agents in the Philippines (Sharma et al., 2020). So far, there are only few articles demonstrating the toxicity of E. crassipes. The hydroalcoholic extract of the leaves at 500 mg/kg showed no death of animals within 14 days of administration of extracts (Ali et al., 2009).
The in vivo anti-inflammatory activity of ethyl acetate, petroleum ether, and aqueous extracts of the leaves and shoot parts of the plant were studied on formaldehyde-induced paw edema. Among the studied extracts, the ethyl acetate extract showed the best anti-inflammatory activity with 67.5% of inhibition of paw edema. This anti-inflammatory activity would be related to the presence of anthocyanins and phenolic compounds (Jayanthi et al., 2011). Moreover, the investigation of the in vitro anti-inflammatory activity of the methanol extract of E. crassipes by the inhibition of albumin denaturation technique demonstrated a maximum inhibition of 79% at a concentration of 500 μg/ml (Sunitha et al., 2018). This activity could be attributed to the presence of sterols, especially stigmasterol, which has a role as an anti-inflammatory compound. Furthermore, the compound could be used as a precursor to produce other bioactive compounds for medical purposes (Paniagua-Pérez et al., 2008).

Hepatoprotective Activities
Different parts of E. crassipes have been used as a traditional herbal remedy for its beneficial effects on human diseases. In Bangladesh, the roots and flowers are used in the treatment of hepatic disorders and abdominal swelling (Rahmatullah et al., 2010).
Furthermore, E. crassipes was shown to have an effective hepatoprotective agent by virtue of its in vivo effect on liver markers and in combating oxidative stress as well, where the coadministration of the leaves aqueous extract with isoniazid in rats exhibited a 46% reduction in malondialdehyde level with concomitant elevation in the total antioxidant value of the plasma (21%). Furthermore, E. crassipes leaf aqueous extract at 400 mg/kg restored the hepatic marker levels in the serum, like alkaline phosphatase (69.22%), SGOT (29%), SGPT (62.31%), creatinine (108.80%), complete bilirubin (48.95%), and hemoglobin (65.69%) (Kumar et al., 2014). Therefore, rat models of liver injury should be investigated more to confirm the effect of E. crassipes as a liver protector agent.
Antitumor/Cytotoxic Activities E. crassipes is known to contain some therapeutic compounds such as alkaloids and terpenoids that display anticancer properties (Aboul-Enein et al., 2014). The antitumor activity of 50% methanolic extract of E. crassipes at different doses showed a good response against melanoma tumor-bearing hybrid mice (Ali et al., 2009). The crude methanolic extract of the whole plant also revealed a notable potency against MCF-7, HeLa cells, EACC, and HepG2 cell lines with IC 50 values of 1.2 ± 0.2, 1.6 ± 0.5, 6.04 ± 0.5, and 7.6 ± 1.5 μg/ml, respectively, compared to doxorubicin, a standard drug that revealed 0.28 μg/ml for HeLa and 0.42 μg/ml for both MCF-7 and HepG2 cell lines (Aboul-Enein et al., 2014). The aqueous leaf extract of E. crassipes displayed 44% inhibition against the NCI-H322 cell line and 20-31% cytotoxic activity against the T47D cell line. However, A549 and PC3 cell lines displayed resistance to E. crassipes extracts (Kumar et al., 2014). Di-amino-di-nitro-methyl dioctyl phthalate (73)  However, no experiments using in vivo cancer models were investigated. Thus, preclinical and clinical studies are required to assess the safety and efficacity of bioactive compounds.

Antioxidant Activities
E. crassipes induces substantial antioxidant activities, and it is confirmed to be a great source of natural antioxidants . The plant is a source of many compounds with radical scavenging activity, such as phenolic acids, sterols, terpenoids, and other metabolites with high antioxidant activity (Tyagi and Agarwal, 2017a). Ethanol extracts from the leaves exerted robust Fe 2+ chelating activity. Meanwhile, the ethanolic extract of the flowers with a high content of phenolic compounds exhibited a substantial reducing power and radical scavenging activity (Surendraraj et al., 2013). In addition, the antioxidant properties of the methanolic crude extract of the whole plant and its isolated compounds, the alkaloids and terpenoids derivatives, were studied using the 2,2-diphenyl-1picrylhydrazyl radical (DPPH) scavenging activity. As results the crude extract showed a good antioxidant activity while some compounds such as 1,2-benzene dicarboxylic acid, dioctyl ester (131), 1,2-benzene dicarboxylic acid, diisooctyl ester (132), 3-methyl-phenyl)-phenylmethanol (133) ). E. crassipes extracts have shown encouraging antiaging effects, as determined through DNA damage inhibition and DPPH radical scavenging assays. There was a pronounced increase in the DNA damage inhibition and DPPH radical scavenging ability with an increase in the concentration of ethyl acetate extracts of the plant (Lalitha and Jayanthi, 2014). Moreover, the highest radical scavenging activity was observed in the petiole with an IC 50 value = 6.411 ± 0.46 mg/ml as compared with IC 50 = 0.516 ± 0.22 mg/ml obtained by the reference compound-the gallic acid (Tyagi and Agarwal, 2017b).
The methanolic extract of E. crassipes showed good DPPH radical scavenging activity with a maximum inhibition of 78% at 250 μg/ml, while in hydrogen peroxide scavenging activity, the maximum inhibition was 80% observed at 250 μg/ml; ascorbic acid, a standard antioxidant drug demonstrated a maximum inhibition of 69% and 68% in both tests at 100 μg/ml, respectively (Sunitha et al., 2018). In the same line, methanol, n-hexane, and carbon tetrachloride extracts of the leaves demonstrated free radical scavenging activity with IC 50 of 0.018, 0.387, and 1.03 μg/ml, respectively (Islam, 2018). Recently, the antioxidant properties of the leaf protein hydrolysates indicated excellent antioxidant activities, especially the two peptides that have shown high radical scavenging activities with 86.37% of superoxide anion radical scavenging activity at 1 mg/ml and 56.51% of ABTS cation radical scavenging activity at 100 μg/ml (Zhang et al., 2018). However, quercetin 7-methyl ether (30) isolated from the whole plant exhibited weak antioxidant activities using DPPH method, with an IC 50 = 254.66 μg/ml compared with quercetin (IC 50 = 23.24 mg/ml) (Elvira et al., 2018). Thus, additional in vivo studies are required to confirm the important effect demonstrated by in vitro studies, to determine the molecular mechanisms of the extracts and the bioactive compounds found in E. crassipes.

Antimicrobial Activities
Many extracts of E. crassipes demonstrated antibacterial and antifungal activities ( Table 4).
In Ethiopia, it has been used for the preparation of crude medicine for treating numerous kinds of virulent diseases related to bacterial infections (Kiristos et al., 2018). In fact, the presence of saponins in the leaves makes them a good candidate, with notable biopotency, as an antimicrobial agent. Gutiérrez E. crassipes displayed antibacterial activities against S. faecalis, E. coli, and S. aureus. Meanwhile, developments of A. niger, A. flavus, and C. albicans were repressed by the plant through crude extract or its fractions (Shanab et al., 2010). The water extract of the leaves demonstrated antimicrobial activity as well (zone of inhibition, 8-22 mm) against Bordetella bronchiseptica, Proteus vulgaris, and Salmonella typhi (Kumar et al., 2014).
In addition, the antibacterial activities of silver nanoparticles, synthesized biologically from the extract of E. crassipes, were checked against selected gram-positive and gram-negative bacteria, and significant zones of inhibition were observed (ZOI ranged between 13 and 18 mm) (Kiruba Daniel et al., 2012;Thombre et al., 2014). Joshi and Kaur (2013) investigated the antimicrobial activity of hydroalcoholic and ethanolic extracts on E. coli, S. epidermidis, P. aeruginosa, and B. subtilis ( Table 4). The antifungal effects of the shoots and leaves of the ethanol extracts were evaluated against two fungi, A. fumigates and M. ruber, employing the disk diffusion method. They revealed notable activity (ZOI = 11 and 12 mm, respectively) toward all the tested organisms comparable to the standard cotrimaxozole (ZOI = 16 and 18 mm) (Thamaraiselvi and Jayanthi, 2012). Furthermore, the antifungal and antibacterial effects of different  extracts of the plant against seven phytopathogenic fungi and 11 clinical bacteria showed that the most susceptible organisms were K. pneumoniae, S. typhi, S. rolfsii, and F. moniliforme. The methanolic fraction was more effective (54.45%) against the bacterial strains as compared to the cold aqueous extract (Baral and Vaidya, 2011). It has been noted that aqueous extracts of the leaves contained active compounds such as chlorogenic acid, alkaloids, flavonoids, sterols, anthocyanins, and quinones, which significantly improved resistance against pathogen Lactococcus garvieae in prawn (Jayanthi et al., 2011;Chang and Cheng, 2016). The ethyl acetate extracts prepared from the stems showed significant antimicrobial activity at 2 mg against S. aureus and S. typhi (activity index = 0.21 and 0.23, respectively). While the ethyl acetate extracts of the leaves, at the same concentration, were only active against S. typhi with an activity index of 0.24 (Hossain et al., 2018). The n-butyl alcohol extract exhibited antimicrobial activities against some bacteria including E. coli, B. cereus, L. casei, and B. subtilis (MIC = 16 μg/ml) and antifungal activity against six pathogenic fungi: A. flavus, A. niger, A. alternata, C. gloeosporioides, C. albicans, and F. solani (minimum inhibitory concentration ranged between 8 and 32 μg/ml) (Haggag et al., 2017). Concerning staphylococcal contaminations, E. crassipes showed a high potency against MRSA found in cows, oxacillin-sensitive S. aureus (SOSA), and coagulase-negative S. epidermidis (CoNS) present in bunnies (Gutiérrez-Morales et al., 2017). The in silico antibacterial activity of stigmasterol, 1-monolinoleoylglycerol trimethylsilyl ether, 17-pentatriacontene, and octasiloxane phytocompounds from E. crassipes leaves was assessed by the inhibition of AprX enzyme through molecular docking. The results showed that the phytocompounds are strong inhibitors of AprX enzyme with better degrees of docking and interaction analysis (Kumar et al., 2018b). Moreover, the antibacterial activity of iron oxide nanoparticles (FeNPs) synthesized using the leaf extract of the plant was determined using well diffusion method. The FeNPs showed good antibacterial activity with the highest zone of inhibition at 100 μg/ml against Staphylococcus aureus (23.3 mm) and Pseudomonas fluorescens (22.6 mm) (Jagathesan and Rajiv, 2018). E. crassipes water leaf extract showed totally bacteriostatic and bactericidal activities at concentrations of 6.25-100%, against Aggregatibacter actinomycetemcomitans, a gram-negative bacterium and the major cause of aggressive periodontitis, at a minimal concentration of 1.56% (Afidati et al., 2019). From all studies, it can be concluded that the process of extractions and the type of solvent used could affect the microbial activity of E. crassipes.

Wound Healing Activity
E. crassipes could be used in cosmeceutical preparations because of its wound healing efficiency.
In Nigeria, the plant is used for skin care applications (Abd El-Ghani, 2016). Moreover, the leaf extract of the plant combined with turmeric and rice flour were used to treat eczema. This activity is due to the significant levels of vitamin C reported in the plant (Sharma et al., 2020).
The methanol extract of E. crassipes leaves was formulated as an ointment using 10 and 15% of leaf extracts and had significantly improved wound contraction potential compared to the control due to the presence of phenolic compounds (Ali et al., 2010). In the same line, the plant extracts demonstrated encouraging antiaging effects through DNA damage inhibition. The ethyl acetate extract of the E. crassipes plant, in combination with musk and lemon, was formulated as a cream and revealed 8-11% tyrosinase inhibition with skin whitening effects. Furthermore, the inhibition of DNA damage was correlated with the increase in concentration of the ethyl acetate extracts (Lalitha and Jayanthi, 2014). More attention and effort should be given to the investigation of the wound healing effect and the underlining molecular mechanisms for promising cosmeceutical industry prospects.

OTHER BIOLOGICAL ACTIVITIES
Larvicidal Activity E. crassipes displayed effective larvicidal activity in which the crude root extract showed effects on Chironomus ramosus eggs and larvae in addition to the toxic potential of the acetone extract toward the two pests Achaea janata (LD 50 > 100 mg/21 m 2 /larva) and Spodoptera litura (Fab.) (LD 50 = 93 mg/21 m 2 /larva) (Devanand and Rani, 2008). The ethanol extract of E. crassipes leaves and shoot showed higher larvicidal activity against C. quinquefasciatus (LC 50 = 71.43,94.68,120.42,and 152.15 ppm) compared to other solvent extracts. This activity might be due to the presence of metabolites like anthraquinones, alkaloids, and flavonoids . Sterols, sitosterol, have been reported to possess larvicidal activity (Rahuman et al., 2008). The crude ethyl acetate, hexane, methanol, and aqueous leaf extracts were tested for larvicidal effects against the early fourth instar larvae of C. quinquefasciatus. The results showed that hexane and methanol extracts were the most effective at doses of 62.5 and 500 mg/L with an LC 50 value of 80.54 and 137.50 mg/L, respectively (Annie et al., 2015). Furthermore, the effect of the plant infusions on mosquito attractiveness and stimulation of oviposition was investigated, and the results suggested that the plant emits volatile chemicals, such as terpenoids and fatty acid derivatives that attract A. aegypti and A. quadrimaculatus, and stimulates the egg rafts position of C. quinquefasciatus (Turnipseed et al., 2018).
Linoleic acid (44), glycerol-1,9-12(ZZ)-octadecadienoic ester (125), and N-phenyl-2-naphthylamine (126) isolated from the acetone extract of the roots showed a stronger anti-algal effect than the common algaecide CuSO 4 (Shanyuan et al., 1992). The crude extract of E. crassipes and its fractions exhibited some antialgal activity against the green microalgae: Dictyochloropsis splendida and Chlorella vulgaris. This activity was high against Chlorella vulgaris (ZOI = 18-33 mm) and could be attributed to the presence of phthalate derivatives and alkaloids (Shanab et al., 2010). Wu et al. (2012) investigated the allelopathic effect of the plant against Microcystis aeruginosa using coexistence assay. As a result, the growth of the blue-green algae root system was significantly inhibited by the hydroalcoholic extract of the plant. By contrast, no allelopathic effect of the plant on spinach growth was noticed (Barman et al., 2006).
Moreover, the phytotoxic effect of the leaves extract of the plant was assessed against Mimosa pigra (an invasive weed) and Vigna radiata (a crop species). The results of the biochemical parameters demonstrated the allelopathy activity of the plant extract against the speed germination of M. pigra and V. radiata. The H 2 O 2 content of the root tissues of M. pigra and V. radiata seeds increased 4.3 and 3.8 folds, respectively, with 5% of the extract. Furthermore, the 5% extract reduced the MDA content of the non-pregerminated and pregerminated seedlings by 18% and 44%, respectively, and resulted in the inhibition of 66% and 59% in the soluble POD activities (Chai et al., 2013). However, it could be interesting to investigate the effect of natural compounds isolated from E. crassipes as herbicides, since few research have been conducted. Moreover, further research is required on the physiological and ecological mechanisms of allelopathy for its worldwide application in agricultural production.

Insecticidal Activity
Few studies have demonstrated the insecticidal potential of E. crassipes extracts against household insects (Hassan, 2013;Lenora and Senthilkumar, 2017). The antifeedant potential of plant extracts at 2% varied against Tobacco caterpillar, with 57.8% in hexane extract and 35.9% in methanol extract (Lenora and Senthilkumar, 2017). This activity could be related to the presence of terpenoids. These results confirm the strong insecticidal activity of the plant. Future research will further explore the in-depth mechanistic effect of the plant and its bioactive compounds, to highlight its potential as natural, plant-derived pesticide for the management of plant pests.

Immunostimulant Effect
E. crassipes has been utilized as an immunostimulant for protection against viral, bacterial, and fungal diseases related to aquaculture. Chang et al. (2013) stated that the extract of the plant, at 2 and 3 g/kg, enhanced immune responses and resistance of prawn Macrobrachium rosenbergii against Lactococcus gravieae by 39.1% and 52.2%, respectively. Moreover, different strategies using the water extracts of E. crassipes leaves were incorporated into the diet of the prawn Macrobrachium rosenbergii as an immunostimulant against Lactococcus gravieae. As a result, the long-term administration of the infusion of the plant (2-20 g/kg) had increased innate immunity by 88.4% and resistance against the pathogen by 68.5% (Chang and Cheng, 2016). The dietary administration of E. crassipes water extract improved immunity (higher immune parameters such as LYZ, Ig, ACH50, and RBA with more than 1000 U/mL) and enhanced the resistance of rainbow trout Oncorhychus mykiss against Streptococcus iniae by 49.6% (Rufchaei et al., 2020).

Animal Feed Formulation
E. crassipes is rich in protein, vitamins, and minerals and is used as duck feed. In Indonesia, China, Philippines, and Thailand, the plant serves as a high-quality feedstock for some nonruminant animals and poultry, and in fishery. The plant biomass is also commonly used as forage for cattle, as basal feed resource or supplement to a diet consisting of sugarcane, molasses, and cereal The method takes E. crassipes as a raw material to optimize the process of triterpenoid extraction. As a result, Box-Behnken response surface method improves the yield of triterpenoid which improves the anti-inflammatory activity and the antioxidant capacity of the extract, with high industrialization value CN111184801A 2020-05-22 Preparation method of E. crassipes leaf total flavonoids The invention relates to the extraction of total flavonoids from the leaves of the plant by adopting a homogenization-ultrasonic method. The invention has the advantages of rapidness and high efficiency, using small amounts of the solvent with good reproducibility Frontiers in Pharmacology | www.frontiersin.org March 2022 | Volume 13 | Article 842511 straw, as it contains adequate minerals that are sufficient for maintenance and production requirements (Hossain et al., 2015;Tham, 2016).

PATENTS INCLUDING E. CRASSIPES (MART.) SOLMS
Several inventions have focused on exploring some potential ways to produce high value-added products from E. crassipes (Mart.). Cumulative increases in the number of patents published in the last few years clearly justifies the importance of the weed in the treatment of various disorders and as a source for new therapeutic agents. As shown in Table 5, these patents have highlighted the use of the different plant parts in various applications such as antiaging, antioxidant, anti-microbial, anti-inflammatory, among others. In general, several patents found in the literature have disclosed the use of E. crassipes in the cosmetic industries, combining a traditional formula and using modern techniques of extractions to guarantee strong effects. The invention by Wang (2015) and Cui (2015) provided methods of formulation of hand and herb creams, respectively. The hand cream prepared from the plant can accelerate skin healing from secondary infection during the treatment period. The cream cooperates with the immune system to eliminate inflammation, relieve itches, and remove edema. While the herb cream is prepared by using E. crassipes with other herbal medicines through a modern technology, Cui (2015) has reported that the cream is suitable for preventing skin infections caused by fungi and bacteria. In addition, the invention by Leconte and Rossignol-Castera (2014) has described a method to prepare a novel cosmetic composition using the lipophilic extract of water hyacinth for moisturizing the skin, and to maintain and restore the hydration of the skin. Other inventions are related to the utilization of E. crassipes in medicine and pharmacology. The invention by Yu et al. (2020) introduced a pharmaceutical composition for use in the treatment of inflammation. They reported that triterpenoid improves antiinflammatory activity and antioxidant capacity, with high industrialization value.

CONCLUSION AND PERSPECTIVES
This comprehensive review on the phytochemical composition and pharmacological/biological activities of the plant was done to assess the chemical composition and value-added applications of E. crassipes aiming to highlight the plant's potential to enhance its limited pharmaceutical applications in Africa, especially in Ethiopia. In this review, various constituents of the plant have been identified for a multitude of applications. The results of multiple phytochemical studies rely on the isolation and identification of various phytocompounds such as polyphenols, flavonoids, sterols, alkaloids, among other secondary metabolites. Phytosterols and terpenoids, considered as major compounds, could be used to provide valueadded compounds for the food and pharmaceutical industries. Moreover, the physicochemical processes have been used to produce other value-added products from E. crassipes biomass, such as furfural, xylitol, enzymes, polymers, and composites and have been applied in distinct fields of applications. In this line, it will be interesting to study various strategies using combined processes for by-products production at the industrial scale. In addition, pharmacological and biological properties of E. crassipes have been discussed in detail. Different extracts and bioactive compounds isolated from the plant showed anticancer ability against various cancer cell lines. In addition, different studies witnessed the antiinflammatory, antioxidant, antibacterial, and antifungal activities of E. crassipes extracts. Furthermore, several patents have described the pharmacological effect of the plant, but clinical applications are still rare and should be further evaluated. Since most of the studies those reported the potential effect of E. crassipes on health are animal-based studies, pharmacological findings need to be supported by the mechanisms. Other studies showed the use of E. crassipes extracts in wound healing. The plant has demonstrated potential effects in antiaging. Recent innovations targeted the development of new formulations in related fields for the standardization and validation of the plant as an antiaging agent. However, the plant requires further attention for the isolation of bioactive compounds responsible for biological activities. Accordingly, it is important to further clarify the effectiveness of compounds and elucidate their toxicity for future studies.
Undoubtedly, the limitations could not be avoided in this study in terms of quality and the limited number of included studies. Concurrently, new findings could increase the present therapeutic importance of E. crassipes and promote its future uses in modern medicine. Furthermore, it is necessary to investigate the pharmacological and toxicological mechanisms of the plant and establish an effective evaluation system which could promote the development and application of this valuable resource in pharmaceutical industries.

AUTHOR CONTRIBUTIONS
All authors listed have made a substantial, direct, and intellectual contribution to the work and approved it for publication. WBB collected the appropriate literature, analyzed the data, and drafted the manuscript. AE and FK provided helpful comments. MS revised the manuscript and provided helpful comments. MK, MH, LK and AY critically revised the manuscript. All authors approved the final version of the manuscript.

FUNDING
The authors are thankful to OCP and OCP Ethiopia for their assistance and financial support of this research, which is a part of the project entitled "Integrated sustainable management of the water hyacinth in Lake Tana, Ethiopia."