Acrostichium aureum Linn: traditional use, phytochemistry and biological activity
Clinical Phytoscience volume 8, Article number: 18 (2022)
Acrostichum aureum L is an edible mangrove plant fern that grows mainly in tropical and subtropical regions of the world. This review was conducted to provide in-depth information regarding the traditional uses, phytochemistry and biological activity of A. aureum.
Scientific literatures were systematically searched using databases including Google scholar, PubMed, Science Direct and ResearchGate for ethnobotany, phytochemistry and pharmacology of the plant. Its potential pharmaceutical and nutritional applications as well as knowledge gap in A. aureum research were also documented.
The outcome revealed that A. aureum is used traditionally across the world to treat several ailments including, non-healing ulcers, boil, wounds, snakebite, bleeding, worm infection, asthma, sore throat, constipation and elephantiasis. Secondary metabolites including, sterols, glycosides, saponins, alkaloids, tannins, flavonoids, phthalates, and terpenoids have been identified in A. aureum. Beneficial phytochemicals including kaempferol, di-(2-methylheptyl) phthalate, β-sitosterol, (2S,3S)-sulfated pterosin C, (+)-pinoresinol-4-O-sulfate, lupeol, α-amyrin and phytol have been detected and/or isolated in the plant. In vitro and in vivo studies also proved that various extracts and phytochemicals in A. aureum have powerful antioxidant, anti-inflammatory, antiulcer, tyrosinase inhibiting, anthelmintic, anti-diarrheal, analgesic, anti-tumor, anti-fertility, anticancer, antibacterial, anti-viral and wound healing properties.
The A.aureum could be harnessed for novel bioactive compounds that can be useful in the treatment of various diseases. Consequently, metabolomic and chemoinformatic analyses could be deployed to fast-track drug discovery and development from the plant. Moreover, safety and activity guided bioassays as well as clinical trials are needed before it could be recommended for clinical use.
The use of herbs as part of the health care delivery system is gradually increasing in many parts of the world especially in developing countries. Many of these plants are used as part of primary health care program especially among rural dwellers, who have limited access to orthodox healthcare facilities. Non-rural dwellers in both developing and developed nations have also turned to the use of herbs for their health care because reliable cure for several diseases including cancer, diabetes and viral diseases remains elusive. Moreover, conventional drugs for many treatable diseases are limited by toxicity and high cost.
Mangrove plants, present a cheap and alternative source of nutraceutical supplements and therapeutic agents that may be beneficial in management and treatment of communicable and non-communicable diseases. The plants are exposed to unfavorable environmental and climatic conditions, which make them develop adaptive defense mechanisms and produce secondary metabolites that protect them against stressful abiotic and biotic factors. Due to the unique nature of their compounds and secondary metabolites, mangrove plants are now being screened for novel compounds that can be used for the treatment of many diseases. One of such plants is Acrostichum aureum Linn (A. aureum) (Fig. 1). A. aureum is a mangrove fern that belongs to the family Pteridaceae and the genus Acrostichum. “Acrostichum” is the only genus of fern that grows in the marine intertidal zone . A. aureum grows worldwide mostly in coastal zones of tropical and subtropical parts of the world. The plant is intrusive and is one of the dominant species in many mangrove ecosystems across the world including Nigeria [2, 3]. The anatomical and molecular features of the plant is adapted to unfavorable conditions including, tidal fluctuations, turbulence, flood, high salinity, and long-term climate change [1, 2]. There is growing interest in the plant probably because of its ethnomedicinal value and ability to produce phytochemicals that could be useful in the management of many diseases such as cancers, diabetes, ulcers and viral diseases [4,5,6,7].
Over the past few decades, many studies have been conducted on traditional uses, phytochemistry and pharmacological effects of the plant. However, an earlier attempt at reviewing literature on the plant was not comprehensive . In the present work, we used systematic approach to give a detailed and updated documentation of scientific studies reported till 30th November 2021 relating to the distribution, morphology, phylogeny, ethnomedicinal uses, phytochemical composition and pharmacological activities of A. aureum. The potential medicinal, pharmaceutical and nutritional applications of the plants as well as knowledge gap in A. aureum research were also highlighted.
Literature search and reporting were done following the Preferred Reporting Items for the Systematic Reviews and Meta-Analyses (PRISMA) protocol  as shown in fig. 2. The data search was carried out using search engines including, Google Scholar, ResearchGate, PubMed and PLOS ONE. The following keywords: “ethnobotany”, “traditional uses”, “medicinal uses”, “phytochemistry”, “phytochemicals”, pharmacological activity”, “biological activity”, “nutritional”, “toxicity,” and safety were combined with A. aureum. Articles were downloaded by two independent authors (YAA and JEU) in Endnote 20  and duplicated articles were removed using the same software. The remaining literatures were scanned based on the relevant titles and abstracts by SMA and MNA. Reference lists of the downloaded papers were also evaluated for other relevant papers. Disagreements between SMA and MNA regarding eligibility of articles were resolved via discussion with the reviewer (EOA) and the lead investigator (KAA). Articles on the morphology, phylogeny, ethnobotany, phytochemical and biological activities of A. aureum that were written in English Language in books, learned journals, dissertations and thesis up to 30th November 2021 were included in the review. In contrast, articles that were not written in English and those containing data that were not relevant to the objectives of the study were excluded. Ethnobotanical data including the country or region where the plant is used, illnesses or diseases that the plant is used to manage and the plant part utilized were recorded. The name of the compounds isolated or identified with their classification, extraction solvent, plant part extracted and analytical method(s) were documented for phytochemistry. In addition, the chemical structures of the compounds were drawn with ACD/ChemSketch software for windows . The data documented for the biological activity are plant part, extraction solvent, and bioassay/model and efficacy outcomes.
Results and discussion
Distribution, morphology and phylogeny
The A. auruem is commonly known as golden leather fern, sea fern, swamp fern, mangrove fern and tiger fern (English), Hudo (Bangladesh), Alligator rush (Jamaica). Other local names and general information are shown in Table 1. The plant belongs to the clade: tracheophytes, division: polypodiophyta, class: polypodiopsida, order: polypodiales, family: pteridaceae, subfamily: pantropica, genus: Acrostichum and species: aureum [15, 16]. It occurs all over Southeast Asia America and Africa especially in the tropical and sub-tropical regions of many counties including, Brazil, USA, India, Bangladesh, Vietnam, Sri Lanka China, Costa Rica, Taiwan, Japan, Phillipine, Fiji, Trinidad, Senegal, Guinea, Gambia, Nigeria, Zimbabwe, Sierra Leone, Ghana, Mozambique, Kenya, Ivory Coast, Panama, and Jamaica [3, 17].
The natural habitats of A. aureum are swamps and mangrove areas, riverbanks and salt marshes. It tolerates high salinity levels, but fresh water promotes spore germination. It grows on small elevations in the mangrove swampy regions, but it is occasionally found in freshwater locations. Thus, A. aureum shows strong adaptation to fluctuating environmental conditions and therefore grows in the intertidal zone, especially those that have been altered by human activities . The plant was recently demonstrated to intrinsically express genes related to biotic and abiotic stress conditions including salinity, temperature, and light .
The shrub grows up to 4 m tall  and has adventitious roots that are visible at the bottom of the leaves and knots. The stem is distributed horizontally and grows indefinitely. The fern has broad and glossy frond that is oblong and cuneate at the base, while the apex is mucronate. The venation of the leave is reticulate with uniform elongate areoles diverging from the thickened midrib without free vein endings. The stipes is woody and arises from glabrous woody rhizome . The fronds measure approximately 1 m long and 50 cm wide and are pinnate. The 8–16 alternate pinnae are dark green, leathery and widely spaced [8, 19, 20]. At the basal region, the fronds are greenish-yellow in color and a golden color at the apex. The central fronds are almost straight, but the outer fronds arch over sideways. Some of the fronds produce sporangia located at the apical region along the veins. The sporangia performs the reproductive function by producing spores and are found in the five to eight distal pinna pairs and terminal pinna [19, 21]. The sporangia are brick red and add a felted appearance to the pinnae . The non-indusiate and densely aggregated sori are formed between June and October .
Castrejón-Varela et al.  recently studied the morphogenesis of the sexual part of A. aureum and showed that sporophyte features, germination type and prothallial development are comparable to that of A. danaeifolium. The spore of A. aureum in proximal view is 19(22)25 μm in measurement and is radially symmetrical, trilete and tetrahedral-globose to almost globose. In addition, the spores are homosporous, non-chlorophyllous, hyaline with a faint brownish color and short laesura. The spore of the two species however differs in their exines. Exine of A.aureum is a bit rough with the surface papillate to tuberculate, and rodlets attached to the tubercles in distal and proximal view. In contrast, A. danaeifolium exine is rugose, with strands or rods mainly linked with coarsely papillate structure and papillate surface. Spore germination follows Vittaria-type, while prothallial development corresponds to the Ceratopteris-type. The juvenile prothallus was noticeably lopsided, and the asymmetry persisted until maturity. The meristem was established laterally towards the basal end of the prothallial plate rather than towards the apex. In addition, it was observed that 30 days after sowing, the adult gametophyte of A. aureum was cordiform-spathulate or cordiform-reniform and glabrous with broad wings, a deep notch and a thin cushion. Gametophytes reached maturity in approximately 76–196 days with antheridia and archegonia on the same gametophyte. The sex organs were established to be the common type of leptosporangiate. The young sporophytes are visible on the prothalli at 250 days from spores sowing and were glabrous, dichotomously branched with their first leaves depressed obovate, and with venation. The prothalli produced gemmae, which are visible at 196 days and develop into new prothalli when shed. A. aureum can be also be differentiated from A. danaeifolium by the puberulent lower surfaces of the pinnae in A. danaeifolium, while that of A. aureum is glabrous. The paraphyses are capitate with a dark and circular-lobed apex in A. aureum, but pale and non-capitate in A. danaeifolium . In addition, the leaves of A. aureum are fertile only in the five distal pinna pairs and terminal pinna, whereas the fertile leaves of A. danaeifolium are soriferous throughout their length. Unlike the sporophytes of other acrostichoid species, A. aureum has a unique asymmetrical antheridia.
Transcriptomic data for A. aureum, A. speciosum and a related species, Ceratopteris thalictroides made available by Zhang et al.  showed 47,517, 36,420 and 60,823 unigenes for the three ferns respectively. Phylogeny of chloroplast gene and transcriptomic data showed that A. danaeifolium, A. aureum and A. speciosum formed a monophyletic clade. A. danaeifolium however, diverge first since 88.1 Mya, while A. aureum and A. speciosum are sister species that diverge much later at about 2.2 Mya. In addition, the two species differ by 16,183 amino acid, out of which 15,181 were caused by changes in elementary amino acid. Moreover, analyses of the genomic and transcriptomic data suggest that Ceratopteris and Acrostichum previously shared the same ancestor about 88.1 million years ago during the late Cretaceous. Their divergence time was found to be approximately 93.8 Mya. In addition, positively selected genes including SKIP and NPH3 family protein were detected and may contribute to differential adaptations of Acrostichum species to different intertidal habitats.
In another study conducted more recently by Zhong et al. , the entire chloroplast genome of A. aureum was sequenced using an Illumina platform and compared with the chloroplast genomes of ten other species in the fern Pteridacea family. The A. aureum chloroplast genome was found to be154,805 bp in length with 38.38% GC content. The large single copy region was found to be 82,826 bp, while the small single copy region was 21,617 bp. Both regions were separated by a pair of inverted repeat region of 25,181 bp each. Additionally, the chloroplast genome contain one hundred and fifteen genes out of which eighty-four codes for protein, twenty-seven tRNA genes and four rRNA genes. Phylogenetic analysis revealed that A. aureum is closest to Ceratopteris cornuta in the subfamily Parkerioideae .
Different parts of A. aureum are widely used traditionally to cure various ailments and diseases in different countries across the world (Table 2). The A. aureum is used to treat skin diseases including abscess that could lead to boils and deep red coloration of the affected area. The leaves are used in manufacturing lotions, creams and ointments for treatment of skin infections. The natives of Malaysia, Sri Lanka and Vietnam use the powdered or ground rhizomes in treating wounds, non-healing ulcers, boils and stopping bleeding [14, 24, 31]. The leaves are also used in the treatment of hemorrhoids, gastritis, dysentery and inguinal hernia in Sri Lanka .
The Indians apply the frond as antidote for venomous snakebites , while the fertile fronds and roots are used in treating syphilitic ulcers, pharyngitis and diabetes [24, 25]. The natives of Fiji use different parts of A. aureum to treat chest pains, fever, elephantiasis, asthma, sore throat and constipation [12, 25, 28]. It is also believed to be efficient in increasing the chances of a healthy pregnancy in Fiji. In addition, it is useful in treating respiratory ailments including throat infection and sinusitis. The plant is used as styptic, anthelmintic and also as an astringent in bleeding by the Keralans [24, 29]. Furthermore, the leaves of A. aureum are used to cure women with cloudy urine in Bangladesh and Costa Rica [24, 29]. The Cunas of Panama and Colombia extract fish bones from the throat using the young fiddleheads and as a medicinal bath for infants [17, 25]. In China, the rhizome is used to treat worm infections, inveterate ulcers and bladder ailments [17, 25]. It is a common remedy for treating hemorrhage, myelitis wound, rheumatism and boil in many parts of Asia [26, 27, 30, 37,38,39]. Young fronds of A. aureum are sold as vegetables that are eaten fresh and as well-cooked or blanched in Sri Lanka, Malaysia and Indonesia [40,41,42]. In Western Kalimantan of Indonesia, the plant is used to stop bleeding and relieve pain . The rhizome is made into paste and used for treating snakebite, boils and wounds, while the leaves are used to stop bleeding in Malaysia . In addition, Malaysians use the young fronds of the plants that are under 14 days old in treating hypotension, worms and digestive problems . The Ahanev people of Badagry, South-West Nigeria, use concoctions from the roots of A. aureum as newborn baby ointment, while the plant is used for the treatment of severe stomachache and skin infection . Inhabitants of the South-south Nigeria, use the plants for treating migraine and internal heat. In Suriname, it is used as abortifacient [32, 33]. Other traditional non-medicinal uses of the plant include its use as plant support [43, 44], thatching material , parks for catching shrimps , and fodder and beddings for livestock animals .
Phytochemicals are bioactive compounds that are present in various plants that perform vital functions in plants including protection from severe environmental conditions and predators. In addition, these phytochemicals have significant medicinal and pharmaceutical properties as they possess several beneficial biological activities including anti-inflammatory, antioxidant, and antimicrobial. Different parts of A. aureum are rich in secondary metabolites such as flavonoids, gum, sterols, glycosides, saponins, alkaloids, gums, tannins terpenoids and triterpenoids [6, 7, 14, 15, 47, 48]. Quantitative analysis of ethanol extracts of the fronds revealed that it contained alkaloids (160 μg/ml), flavonoids (81.5 μg/ml), tannins (12.1 μg/ml) and phenol (64.0 μg/ml) . Another quantitative study showed that the whole plant has 0.11, 28.29, 19.90, 3.02, 0.83, 1.11 g/100 g dry weight of proline, phenol, alkaloid, saponin, tannins and cardiac glycosides respectively . Tannin concentrations of 0.52, 1.39, 9.45, 10.90 and 28.8 TAE/g extract were reported for n-hexane, ethyl acetate, methanol, ethanol and 70% acetone extract respectively . The phytosterol and triterpenoids content of the leaves of A. aureum were recorded as 34.1 and 40.5% respectively, while the concentration of phytosterol and triterpenoids in the roots of the plant was 38.8 and 57.9% respectively . Basyuni et al  quantified the amount of polyisoprenoids, polyprenyl acetones, polyprenols and dolichols content of 14 mangrove plants including A. aureum. The result showed that the root contained 4.1, 2.4, 1.7 mg/g DW of polyisoprenoids, polyprenols and dolichols respectively, while the polyisoprenoids, polyprenols and dolichols content of the matured leaves were found to be 4.6, 2.6 and 2.0 mg/g DW respectively. The values obtained for the young leaves of the plant were 7, 0.7, 7.0 mg/g DW of polyisoprenoids, polyprenols and dolichols respectively.
The bioactive compounds in A. aureum have only been reported to a limited extent. Till date, relatively few bioactive compounds have so far been isolated or detected from the plant. An early study in Japan isolated ponasterone (I) and quercetin-3-O-β-D-glucoside (II) from the plant , while quercetin-3-O-β-D-glucosyl-(6 → 1)-α-L-rhamnoside (III), quercetin-3-O-α-L-rhamnoside (IV) and quercetin-3-O-α-L-rhamnosyl-7-O-β-D-glucoside (V) were isolated from the fern collected in Bangladesh . The presence of pterosterone (VI), kaempferol (VII), quercetin (VIII), 2-butanone (IX) and ponasterone (I) was confirmed in ethanol extract of the fern growing in Chin . A novel phthalic acid ester, 2″-(methoxycarbonyl)-5″-methylpentyl 2′-methylhexyl phthalate (X) was isolated from the aerial parts of the plant by Uddin et al . In addition, patriscabratine (XI), tetracosane sesquiterpene (XII), (2S,3S)-Pterosin C (XIII), (2R)-Pterosin P (XIV), (2S,3S)-Sulphated pterosin C (XV) and (2R, 3S)-sulfated pterosin C (XVI) were isolated from the methanol extract of the whole plant . Sterols including cycloartanol (XVII), 24-methylene cycloartanol (XVIII), stigmasterol (XIX), γ-sitosterol (XX) and campesterol (XXI) were recently isolated from the mangrove fern . Similarly, Basyuni et al  using GCMS detected cycloartanol (XVII), campesterol (XXI), stigmasterol (XIX) and β-sitosterol (XXII) from roots and leaves of the plant. In addition, triterpenoids including taraxerol (xxiii), β-amyrin (XXIV), germanicol (XXV), lupenone (XXVI), betulin (XXVII), lupeol (XXVIII), α-amyrin (XXIX), cholesterol (XXX), phytol (XXXI) and squalene (XXXII) were identified in both parts of the plant . While studying nicotinamide metabolism in ferns, Ashihara et al.  found a large amount of nicotinic acid glucoside (XXXIII) in leaves of A. aureum. Moreover, in matured leaves of A. aureum, slight stimulation of nicotinic acid glucoside formation by 250 mM NaCl was observed. Similarly, accumulation of glucose (XXXIV), sucrose (XXXV), myo-inositol (XXXVI), D-chiro-inositol (XXXVII), D-ononitol (XXXVIII), D-1-O-methyl-muco-inositol (XXXIX) and D-pinitol (Xl) were observed in gametophytes and sporophyte of A. aureum grown under saline conditions . A recent study isolated three new compounds including, 4-(3′-O-sulfate-4′-hydroxyphenyl)-2-(R)-butanol (XLI), dihydrodehydrodiconiferyl alcohol 9-O-sulfate (XLII) and 4-(3′-O-sulfate-4′-hydroxyphenyl)-2-butanone (XLIII) with known phenolic compounds namely; (+)-pinoresinol-4-O-glucoside (XLIV), dihydrodehydrodiconiferyl alcohol-4-O-glucoside (XLV), (+)-isolarisiresinol-9-O-sulfate (XLVI), (+)-pinoresinol-4-O-sulfate (XLVII), and isotachioside (XLVIII) from methanol extract of A. aureum . The compounds isolated or detected in A. aureum are summarized in Table 3 and their chemical structures are displayed in Fig. 3.
In addition to the ethnobotanical uses of A. aureum, many pharmacological activities have been reported for different parts and extracts of the plant. As depicted in Fig. 4, the plant has been found to exhibit analgesic, antioxidant, contraceptive, cytotoxic, anti-inflammatory, antibacterial and wound healing activities. Studies on the biological activity of A. aureum are presented below and summarized in Table 4.
Antioxidants are compounds that prevent oxidation in living and non-living organisms. They can donate hydrogen and thereby reduce reactive oxygen species, reactive nitrogen species or metals in their oxidized forms. Antioxidants also can prevent free radical chain reactions that occur in living organisms. Due to their antiradical and reducing properties, they play a major role in preparation of pharmaceutical formulations against various diseases. The antioxidant capacities of different extracts of A. aureum have been reported by many authors using different antioxidant assays. The methanol twig extract of the plant showed a 2, 2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging activity with an EC50 of 103.0 μg/ml, while the IC50 for inhibition of lipid peroxidant was reported to be 28.99 μg/ml . The IC50 for the induction of quinone reductase was found to be greater than 20 μg/ml. The ethanol extract of A. aureum was also reported to possess a robust 42 μg/ml in vitro antioxidant activity against DPPH radicals , while that of ascorbic acid used as standard in the study was 16 μg/mL . In addition, out of 15 species of ferns that were screened for total phenolic contents and antioxidant activities, A. aureum exhibited strong antioxidant capacity and ranked eighth amongst the ferns investigated . The antioxidant activity of A. aureum was attributed to high TPC (524 GAE) and anti-lipid peroxidation activity (51%). It can also be inferred from the study that the phenolics in A. aureum are strong metal chelators as the plant had the highest metal chelating potential amongst the investigated ferns. In another study, comprehensive in vitro antioxidant evaluation of the plant by Badhsheeba and Vadivel  demonstrated a dose dependent antioxidant activity for different extracts of the plant using DPPH, ABTS, hydroxyl and superoxide scavenging assays as well as reducing power assay. The petroleum ether showed IC50 values of 31.56, 25.16, 26.12 and 26.18 μg/ml for DPPH, hydroxyl, ABTS and superoxide respectively, while the benzene extract had IC50 values of 34.13, 30.18, 22.46 and 24.16 μg/ml respectively for scavenging DPPH, hydroxyl, ABTS and superoxide ions. The IC50 values for scavenging DPPH, hydroxyl, ABTS and superoxide by the ethyl acetate fraction were found to be 30.36, 31.48, 27.16 and 28.16 μg/ml respectively, whereas the IC50 values of 36.54, 32.16, 30.11 and 30.96 μg/ml for DPPH, hydroxyl, ABTS and superoxide respectively were obtained in the methanol extract. The ethanol extract of A. aureum showed IC50 values of 32.16, 30.84, 28.36 and 34.84 μg/ml for scavenging DPPH, hydroxyl, ABTS* and superoxide ions respectively. The increasing order of the reducing power of the plant was petroleum ether < benzene < ethyl acetate < ethanol < methanol. Generally, the values obtained were similar to that of the standard used in the study, ascorbic acid . Furthermore, in a recent study, Nurhasnawati et al  reported that the ethanol leaf extract of A. aureum grown in East Kalimantan region of Indonesia, exhibited the strongest DPPH scavenging activity (IC50 = 29.53 ppm), when compared to four other ferns investigated in the study. The total phenolic content (366.44 ± 2.21 mg GAE g− 1) and flavonoid content (228 ± 2.2548 mg QE g− 1) were also found to be the highest among the ferns. Therefore, the strong antioxidant capacity of A. aureum could be attributed to its high phenolic and flavonoid content. The strong antioxidant activity displayed by A. aureum suggests that the plant could serve as an important source of antioxidants with varying pharmaceutical and nutraceutical applications.
Anti-ulcer and anti-inflammatory activity
The gastroprotective activity of water extract of A. aureum in ethanol-induced gastric injury was evaluated by Wu et al. . Pretreatment with A. aureum dose dependently reduced gastric ulcer and attenuated the pathological damage in the gastric tissue induced by alcohol. The extract also dose-dependently reduced ROS generated by ethanol, but it enhanced the levels of glutathione, catalase and superoxide dismutase in the stomach of rats co-exposed to ethanol and aqueous extract of A. aureum in a dose dependent manner. Furthermore, the secretion of proinflammatory cytokines including, tumor necrosis factor-α (TNF-α), interleukin-1 β (IL-1 β) and interleukin-6 (IL-6) were also decreased by the extract. Moreover, the expressions of phosphorylation of IkBa and p65 were decreased by the water extract. The therapeutic effectiveness of the extract against gastric ulcer was therefore linked to suppression of inflammatory response and oxidative stress . In an earlier study, the anti-inflammatory activity of ethanol rhizome extract of A. aureum was evaluated in a rat model of carrageenan-induced oedema . The extract at 400 mg/kg exhibited a 66.95% decrease in paw volume after 24 h, which was comparable to 67.66% inhibition obtained for indomethacin, a known inhibitor of cycloxygenase that was used as standard. It can therefore be inferred that the anti-inflammatory effect of the extract may be due to inhibition of cycloxygenase pathway.
The analgesic activity of the ethanol leaf extract of A. aureum against acetic-induced writhing was assessed in mice . The results showed that A. aureum at 250 and 500 mg/kg body weight respectively showed 28.86 and 46.77% writhing inhibition. The analgesic effect was lower, but comparable to the 69.15% obtained for 25 mg/kg body weight diclofenac sodium that was used as the standard drug .
Cytotoxic and anticancer activity
Compounds isolated from the methanol extract of A. aureum were screened for in vitro cytotoxicity against Hep-G2, SKLU-1, and MCF-7cells by Minh et al.  using sulforhodamine B assay. Out of the 8 compounds screened, only (+)-pinoresinol-4-O-sulfate showed weak cytotoxic activity against the tested cell lines with IC50 values of 64.73 ± 5.33, 65.54 ± 6.47 and 73.78 ± 5.86 respectively for Hep-G2, SKLU-1 and MCF-7 cells. The ethyl acetate extract of A. aureum showed strong cytotoxicity with an IC50 value of 6.3 μg/mL among medicinal plants from Hainan in China that were screened for cytotoxic activity against HeLa human cervical cancer cells . The aqueous extract however had no cytotoxicity against the same cell line. The A. aureum showed the most potent selective cytotoxicity amongst sixteen Bangladeshi plants that were screened against human colon, gastric, and breast cancer cell lines . In addition, the cytotoxicity of flavonoids including quercetin-3-O-α-lrhamnosyl-7-O-β-D-glucoside, quercetin3-O-β-D-glucosyl-(6 → 1)-α-l-rhamnoside, quercetin-3-O-β-D-glucoside, quercetin-3-O-α-l-rhamnopyranoside, kaempferol, patriscabratine and tetracosane isolated from methanol extract of the whole part of the plant were evaluated in NIH 3 T3, MDA-MB-231, AGS and MCF-7 cells . Patriscabratine exhibited moderate cytotoxic activity against MDA-MB-231, AGS and MCF-7 cells with IC50 values between 69.8 and 197.3 μM, while tetracosane exhibited some level of toxicities against MDA-MB-231, HT-29, NIH 3 T3 and AGS cells with IC50 values that ranged from 128.7 to > 250 μM . Both compounds showed apoptotic effect on AGS cells that was either comparable or greater than cycloheximide, which was used as the positive control. The authors therefore concluded that patriscabratine was active against gastric cancer cells and could contribute to the ethnomedicinal use of the plant in the treatment of peptic ulcer, which is a risk factor for gastric cancer. Similarly, anticancer properties of two novel sesquiterpenes, (2R,3S)-sulfated pterosin C and (2S,3S)-sulfated pterosin C, as well as their derivatives, (2S,3S)-pterosin C and (2R)-pterosin P isolated from the methanol extract of the aerial part of A. aureum were evaluated against AGS, HT29, MDA-MB-231, and MCF-7 human cancer cell lines using MTT assay . Only (2S,3S)-sulfated pterosin C displayed selective cytotoxicity with IC50 values that ranged between 23.9 and 68.8 μM. Additionally, AGS gastric adenocarcinoma cell, which was the most sensitive to the compound showed a time dependent cell death when treated with 15 μg/ml (2S,3S)-sulfated pterosin C for 48 hours. The observed proapoptotic effect was greater than that of 150 μg/ml cycloheximide that was used as standard drug. The cytotoxicity of the compound was attributed in part to the presence of sulphate group at C-14 and trans configuration at C-2. Furthermore, in silico studies indicated the phytosterols namely campesterol, cycloartanol, 24-methylene cycloartanol, stigmasterol and γ-sitosterol detected in A. aureum possess the ability to suppress carcinoma, adenocarcinoma and mesothelioma . The selective cytotoxic effects of some compounds found in A. aureum against cancer lines suggest the compounds may have huge potential as anticancer agents. However, this needs to be corroborated in vivo and their detailed mechanisms of actions elucidated.
Animal studies have revealed that acetone and ethanol extracts of A. aureum have potent anti-implantation activity in rats. Praskash et al.  evaluated the anti-fertility properties of 158 medicinal plant extracts and found that the acetone and ethanol extracts of A. aureum exhibited between 60 and 70% anti-implantation activity in rats. Additionally, during administration on day 1–7 postcoitus, the water-soluble fraction of the ethanol (95%) extract of A. aureum was found to have prevented pregnancy in female rats . The fraction has neither oestrogenic nor anti-oestrogenic activities, which suggest a unique mechanism for the observed antifertility effect. Therefore, the fraction could be a source of novel contraceptive(s) with better efficacy than the existing ones that are limited by side effects including induction of hormonal imbalance.
Lai et al  investigated the antibacterial activity of the leaves of A. aureum and reported that methanol extract of A. aureum leaves exhibited no antibacterial activity when tested against Pseudomonas aeruginosa, Salmonella choleraesuis, Enterobacter aerogenes Micrococcus luteus, Bacillus cereus, Staphylococcus aureus, Escherichia coli, and Klebsiella pneumoniae. Similarly, the aqueous extracts and petroleum ether extracts of the leaves of A. aureum exhibited no antibacterial activity when tested against S. marcescens, S. aureus, E. coli, P. aeruginosa and M. luteus . However, the acetone extract inhibited all the bacterial species tested except for M. luteus. The methanol extract inhibited S. marcescens and E. coli only. Furthermore, when antibacterial potential of the fronds was evaluated with various solvent extracts, the methanol extract exhibited minimum inhibitory and bactericidal concentrations of 50 and 25 mg/ml respectively against Pseudomonas aeruginosa . These values were better than those obtained for chloramphenicol and amoxicillin in the same study. Pseudomonas aeruginosa is commonly found in the lungs, kidney and urinary tract of patients suffering from cystic fibrosis and those being managed for burns and related painful dermal damage conditions. Therefore, the inhibition of the organism by A. aureum may justify the ethnobotanical uses of the plant in the treatment of burns, skin disorders and respiratory diseases. In addition, Numbere and Maduike  examined the antibacterial properties of dimethyl sulfoxide (DMSO) extract of A. aureum at concentrations between 32.25 and 500 mg/ml on the bacterial species namely Escherichia coli, Salmonella paratyphi, Staphylococcus aureus and Pseudomonas aeruginosa. They reported that E. coli and S. aureus were more sensitive to the extract, while S. paratyphi was the least sensitive. In addition, 250 and 500 mg/ml showed the greatest inhibitory effect on all bacterial growth. In another study, Shamsuddin et al  reported that A. aureum had narrow spectrum antibacterial activity against Vibrio species. Out of six isolates of Vibrio species investigated, only the methanol extract of A. aureum inhibited Vibrio parahaemolyticus isolated from Scylla serrata. The mechanism of the antibiotic action of A. aureum is yet to be investigated. However, the plant is rich in secondary metabolites such as phenols and flavonoids that may inhibit bacteria by acting as cell wall, protein and nucleic acid synthesis inhibitors. Therefore, novel and safe antibacterial agents could be sourced from A. aureum against multidrug resistance bacteria especially those that have been identified to be sensitive to the extracts of the plant such as E. coli, P. aeruginosa and S. paratyphi. However, animal and clinical studies are needed to give credence to the observed in vitro antibiotic properties of A. aureum.
Wound healing property
In order to provide the scientific rationale for the use of Acrostichum species in many Asian countries, ethanol extract of the plant was evaluated in a rabbit’s excision wound model by . Topical application of 10% A. aureum rhizome resulted in improved wound contraction and epithelization period when compared to the control. The authors attributed the wound healing capacity of A. aureum to its antibacterial activity and its phytochemical composition. Similarly, in a thesis submitted to the International Islamic University of Malaysia, Herman  demonstrated that aqueous extract of A. aureum rhizomes and leaves showed exciting wound healing activities among four different extracts evaluated at doses of 5 and 10% in rabbits inflicted with back injury. The treated animals displayed enhanced collagen and fibroblasts proliferation in addition to complete epithelized cells. In a similar work, in vitro wound healing ability of several fractions and extracts of A. aureum evaluated using scratch wound assay on NIH/3 T3 cell line revealed that eight extracts and fractions of the plant showed promising mean migration rate . Taken together, these results may justify the traditional uses of the plant in the treatment of wounds and ulcers. The plant may therefore hold potential as a cheap source of principle(s) that can be further developed to manage human wounds.
Hossain et al  investigated the anti-diarrhea property of ethanol root extract of A. aureum in a castor oil model of diarrhea induction in mice. It was found that the ethanol extract of A. aureum root exerted anti-diarrheal effect in treated mice by reducing the rate of defecation and faeces inconsistency. The extract at 400 mg/kg decreased diarrhea by 55% compared to the standard drug, loperamide that exerted a 66% decrease in diarrhea. Thus, justifying the ethnobotanical use of the plant in the treatment of diarrhea. The anti-diarrhea effect of the root was partly linked to its high tannin content (251.41 mg/g of TAE), which probably provoked intestinal mucosa resistance and reduction in secretion. In addition, other secondary metabolites present in the plant such as flavonoids could also reduce intestinal motility and secretion by inhibiting prostaglandins and autacoids release. However, further research efforts are required to ascertain the actual mechanism(s) for the anti-diarrhea effect of A. aureum root and to characterize the compound (s) that are responsible for the antidiarrhea property.
Both the rhizome and starch extracts of A. aureum were evaluated for nutritional and phytochemical characteristics by Lobo and Gulimane . The rhizome was found to be a rich source of starch (53.3%) and essential nutrients such as protein (4.87%), fiber (10.3%), ash (4.32%), tannins (0.52%), and oxalate (0.44%). The total lipid and moisture content were found to be 0.7 and 68.8% respectively . The rhizome is also rich in minerals including, potassium (3.2 mg/g), phosphorous (0.8 mg/g), calcium (1.5 mg/g), sodium (1.93 mg/g), magnesium (1.33 mg/g), iron (0.086 mg/g), zinc (0.017 mg/g) and copper (0.038 mg/g). The starch is a bit acidic and has an amylose content of 24.42% . The solubility, swelling power and paste clarity recorded for the starch are 35.2, 12.3 and 10.3% respectively . Thus, indicating that the starch has potential pharmaceutical application in the formulation of capsules and tablets. The moisture and ash of the leaves harvested from Kanyakumari District, India were found to be 9.25 and 7.10% respectively , while the total lipid and non-saponifiable lipid of the leaves obtained from North Sumatra Indonesia were found to be 7.58 and 0.22 mg/g respectively . The total lipid and non-saponifiable lipid for the root were recorded as 1.54 and 0.12 mg/g respectively . More research efforts should be intensified on the nutrient composition of other parts, especially the leaf that is widely consumed as vegetable in Asia. This could open new opportunities for further exploitation of the plant in food and pharmaceutical industry.
A novel antiviral secondary metabolite isolated from the methanol extract of aerial parts of A. aureum, 2″-(methoxycarbonyl)-5″- methylpentyl 2′-methylhexyl phthalate exhibited only post infection antiviral activity against human parainfluenza virus, dengue virus and chikungunya . The highest antiviral activity was against human parainfluenza virus type 3 (EC50 = 29.4 μM) and it was better than the EC50 of 44 μM obtained for BCX 2798 that was used as control. However, the compound was not cytotoxic in both Vero and LLC-MK2 cells when tested at 100 and 500 μM. The fact that the compound exhibited only post infection activity made the authors to reach a conclusion that the compound was an inhibitor of viral replication rather than the viral entry process.
The potential of A. aureum spore as causative allergen was investigated in two hundred and twenty-six allergic rhinitis patients using intracutaneous test and 61.5% of the patients reacted positively . Similarly, 70.8% of twenty-four patients suffering from allergic rhinitis gave positive test with nasal provocation test . In addition, the ability of spores and fractions of A. aureum in eliciting dermal contact allergy was also reported by Yasmeen et al. . The allergenic material was found in both the sporangial matter and spore. The protoplasm and exine of the spores were found to be active with the solvent extraction, suggesting that more than one active material is present. Furthermore, the protein and lipid content of the cell wall as well as intracellular content were all involved in allergenic skin reaction. However, the actual allergenic principles in the A. aureum are still unknown. Thus, research efforts should be directed at identification and characterization of aeroallergens that are present in A. aureum.
Haemonchus contortus is an economically important parasite of ruminant animals that causes huge loss to farmers throughout the world especially in the tropics. It causes helminthiasis and it is well known to exert resistance against common anthelmintic drugs including ivermectin, benzimidazole and imidazothiazole. The potential of A. aureum as an anthelmintic agent was investigated with Haemonchus contortus in vitro and in sheep by Kalpana Devi et al . The result of in vitro study showed that ethanol extract of A. aureum was more effective in causing death and paralysis to Haemonchus contortus than water and petroleum ether extracts. Additionally, a 56 % reduction in faecal egg count was also observed in sheep infected with Haemonchus contortus before treatment with 100 mg/ml body weight of the ethanol leaf extract. Moreover, treated animals did not show any signs of toxicity. Thus, suggesting that the plant may provide new anthelmintic compounds for effective control of helminthiasis that is devoid of potential to enter food chain, toxicity and therapeutic resistance, which are the limitation of currently used drugs.
Tyrosinase inhibiting activity
The tyrosinase inhibiting activity of methanol extract of A. aureum was investigated by Lai et al  using Dopachrome assays. The extract displayed a tyrosinase inhibitory activity of 33% (equivalent to 91.3 mg of quercetin/g of extract and 9.8 mg of kojic acid/g of extract). The strong tyrosinase inhibitory activity displayed by A.aureum suggests that the plant could find application in the treatment of dermal hyperpigmentation. It could also be useful in the cosmetic industry as a source of whitening agent (s) and for prevention of browning in the food industry.
Phytoremediation of contaminated soil and water
The A. aureum exhibits promising potential in removing environmental toxicants from soil, waste water and effluents. Hoang et al.  investigated the ability of A. aureum in remediating ciprofloxacin and norfloxacin in sediment soil of shrimp farmland. The result showed that the antibiotics were absorbed mainly in the root and the half-lives for reduction of both drugs were about 10 days. In addition, drugs accumulate more in the root and translocation time from the roots to other parts of the plant was slow. Similarly in a recent study, pollution parameters of shrimp farm effluent including nitrate, biochemical and chemical oxygen demands were drastically reduced after 30 days of treatment with A. aureum . Thus, suggesting that A. aureum promote biodegradation of pollutants and appropriate for phytoremediation of effluents produced from shrimp farm, although enzymic and non- enzymic antioxidants were raised in the plant.
A. aureum holds strong potential in remediating heavy metal pollution especially in marine wetlands. The plant exhibited high degree of tolerance against arsenate toxicity . Additionally, the leaf biomass of A. aureum served as suitable bio-sorbent for the removal of Pb2+, Cu2+ and Zn2+ from aqueous solution . Furthermore, the plant showed strong capacity to bioaccumulate Zn, Cr, Cu, Ni and Pb from contaminated sediments in West Coast of Kamataka in India . Moreover, Nyugen et al  used systems made from activated carbon and different parts of A. aureum to treat pseudo-waste water containing Zn2+, Fe2+ and Cu2+. The result showed that the systems were very effective in removing and phyto-accumulating the metals even though the root was more efficient.
Safety of A. aureum
Our literature search on the safety of A. aureum returned no information on its in vitro and in vivo toxicity. Therefore, toxicological studies are urgently needed to know the potential toxicity of the plant and to determine the dosage that can be safely consumed by humans and veterinary animals.
Conclusion and future perspective
The A. aureum is a potential health-promoting food and medicinal plant. However, there is lack of human trials assessing the wide range of documented pharmacological effects of A. aureum. Most of the mechanisms of action for the pharmacological activities reported for A. aureum and its compounds are also still unknown. In vitro and in vivo mechanistic studies are therefore urgently needed to fill this void. In addition, the active compounds that are responsible for most of the biological activities of A. aureum are yet to be identified. In order to bridge this gap, activity guided biological assays are necessary to know pharmacologically active compounds that are responsible for the reported biological actions of A. aureum. Furthermore, chemoinformatics can be deployed to hasten drug discovery and development from the plant. Moreover, metabolomic tools and analysis could be employed to fast track the process of identification and characterization of more compounds in A. aureum. The lack of safety or toxicity studies on A. aureum would limit its translational application. Therefore safety/toxicity studies are urgently needed to lay the foundation for clinical trials and the possible clinical use of the plant.
Nonetheless, the information in this review would be useful in making a monograph for the plant, and it will certainly benefit natural product researchers, who are interested in developing novel nutraceutics and therapeutics from the plant. Moreover, it has highlighted knowledge gaps that are needed to be filled before A. aureum can be fully integrated into clinical use.
Availability of data and materials
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Akinwumi, K.A., Abam, E.O., Oloyede, S.T. et al. Acrostichium aureum Linn: traditional use, phytochemistry and biological activity. Clin Phytosci 8, 18 (2022). https://doi.org/10.1186/s40816-022-00349-w
- Acrostichum aureum L
- Secondary metabolites