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Lygodium japonicum (Thunb.) Sw (Courtesy of Jianguo Cao)

Lygodium japonicum (Thunb.) Sw (Courtesy of Jianguo Cao)

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Ferns are an important phytogenetic bridge between lower and higher plants. Historically they have been used in many ways by humans, including as ornamental plants, domestic utensils, foods, and in handicrafts. In addition, they have found uses as medicinal herbs. Ferns produce a wide array of secondary metabolites endowed with different bioactivit...

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... Throughout their extensive evolutionary history, tree ferns have adapted to changes in paleogeographic environments, developing mechanisms to cope with environmental stresses, thereby contributing to further adaptive evolution. In addition to their evolutionary significance, tree ferns exhibit high ornamental values and serve as a source of natural products with pharmaceutical applications (Cao et al., 2017). Traditional medicine utilizes tree ferns to treat various health conditions, including bacterial skin infections, kidney diseases, hemorrhoids, varicose veins, and diabetes (Chaparro-Hernández et al., 2022). ...
... Tree ferns serve as a crucial evolutionary link between lower and higher plant species (Cao et al., 2017). They are widely utilized globally for ornamental, medicinal, and occasionally culinary purposes, but face challenges such as overexploitation, climate change, harsh living conditions, and insect pests (Dadang et al.,FIGURE 4 The interaction network between DEGs and DAMs associated with R genes. ...
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As ancient organisms, tree ferns play a crucial role as an evolutionary bridge between lower and higher plant species, providing various utilitarian benefits. However, they face challenges such as overexploitation, climate change, adverse environmental conditions, and insect pests, resulting in conservation concerns. In this study, we provide an overview of metabolic and transcriptomic resources of leaves in two typical tree ferns, A. spinulosa and A. metteniana, and explore the resistance genes for the first time. The landscape of metabolome showed that the compound skimmin may hold medicinal significance. A total of 111 differentially accumulated metabolites (DAMs) were detected, with pathway enrichment analysis highlighting 14 significantly enriched pathways, including 2-oxocarboxylic acid metabolism possibly associated with environmental adaptations. A total of 14,639 differentially expressed genes (DEGs) were found, among which 606 were resistance (R) genes. We identified BAM1 as a significantly differentially expressed R gene, which is one of the core genes within the R gene interaction network. Both the maximum-likelihood phylogenetic tree and the PPI network revealed a close relationship between BAM1, FLS2, and TMK. Moreover, BAM1 showed a significant positive correlation with neochlorogenic acid and kaempferol-7-O-glucoside. These metabolites, known for their antioxidant and anti-inflammatory properties, likely play a crucial role in the defense response of tree ferns. This research provides valuable insights into the metabolic and transcriptomic differences between A. spinulosa and A. metteniana, enhancing our understanding of resistance genes in tree ferns.
... The mass spectrum of the analyzed sample revealed three prominent peaks corresponding to the major compounds and thirteen peaks below 6%, with these three peaks representing 74.572% of the total sample ( Figure 4). The main compounds identified in Hsf6 were pregn-16-en-20-one, 3-hydroxy-, [3β,5β]-; bis (2ethylhexyl) phthalate; and 3-(1,5-dimethyl-hexyl)-3a,10,10,12b-tetramethyl-1,2,3,3a,4,6,8,9,10,10a,11,12,12a,12b-tetradecahydro-benzo [4,5]cyclohepta[1,2-E]indene, with percentages of 44.93%, 17.97%, and 11.66%, respectively (Table 4). These identified compounds can be grouped into three main categories: alkanes such as hexadecane; alkenes such as eicosane (which do not show relevant biological activity reports); and finally, the group of terpenoids which encompasses most of the molecules identified in this analysis. ...
... The mass spectrum of the analyzed sample revealed three prominent peaks corresponding to the major compounds and thirteen peaks below 6%, with these three peaks representing 74.572% of the total sample ( Figure 4). The main compounds identified in Hsf6 were pregn-16-en-20-one, 3-hydroxy-, [3β,5β]-; bis(2-ethylhexyl) phthalate; and 3-(1,5-dimethyl-hexyl)-3a,10,10,12b-tetramethyl-1,2,3,3a,4,6,8,9,10,10a,11,12,12a,12btetradecahydro-benzo [4,5]cyclohepta [1,2-E]indene, with percentages of 44.93%, 17.97%, and 11.66%, respectively (Table 4). These identified compounds can be grouped into three main categories: alkanes such as hexadecane; alkenes such as eicosane (which do not show relevant biological activity reports); and finally, the group of terpenoids which encompasses most of the molecules identified in this analysis. ...
... This validates its traditional use as an antimicrobial agent. (D) β-sitosterol acetate; (E) 7-dehydrodiosgenin; (F) 3-(1,5-dimethyl-hexyl)-3a,10,10,12b-tetramethyl-1,2,3,3a, 4,6,8,9,10,10a,11,12,12a,12b-tetradecahydro-benzo [4,5]cyclohepta [1,2-E]indene; (G) stigmasta-3,5-dien-7-one; (H) pregn-16-en-20-one, 3-hydroxy-, [3β,5β]. Structures of alkanes and alkenes without reported biological activity were excluded. ...
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Pleopeltis crassinervata is a fern documented in ethnobotanical records for its use in Mexican traditional medicine to treat gastric disorders and mouth ulcers. Consequently, conducting biological and pharmacological assays is crucial to validate the therapeutic efficacy of this plant within the context of traditional medicine. In the present study, we investigated the biological activity of extracts and fractions obtained from P. crassinervata organs against bacteria (Salmonella typhimurium, Salmonella typhi, Staphylococcus aureus, Proteus mirabilis, Shigella flexneri, Bacillus subtilis, Escherichia coli) and Trichomonas vaginalis using in vitro models. The precipitate fraction obtained from the frond methanolic extract showed significant antibacterial activity (minimal inhibitory concentration [MIC] 120 µg/mL) against the Staphylococcus aureus strain and was effective against both Gram-positive and Gram-negative bacteria. The hexane fraction also obtained from frond methanolic extract, showed a trichomonacidal effect with an IC50 of 82.8 μg/mL and a low cytotoxic effect. Hsf6 exhibited the highest activity against T. vaginalis, and the GC-MS analysis revealed that the predominant compound was 16-pregnenolone. The remaining identified compounds were primarily terpene-type compounds.
... Ferns are seedless vascular plants, representing a group of underutilized food and medicinal sources (Tan et al. 2018). Phytochemical studies of ferns had found a dozen of natural products with important medicinal and pharmacological applications, including anti-viral, anti-inflammatory, and anticancer activity (Cao et al. 2017;Sridhar 2022). The genus Aleuritopteris Fée consists of around 30 medium-sized plants mainly distributed in Asia and Africa (Wang et al. 2023a). ...
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A new pimarane-type diterpene, ent-8(14),15-pimaradiene-2β,19-diol (JXE-23), was isolated from the fern plant Aleuritopteris albofusca by our previous work; however, the biological activity of this diterpene remains unclear. In the present study, the anti-cancer potential of JXE-23 in various cancer cells was investigated. Among MCF-7 breast cancer cells, A549 lung cancer cells, and HepG2 liver cancer cells, JXE-23 displayed significant cytotoxicity to HepG2 cells with an IC50 value of 17.20 ± 1.73 µM, while showing no obvious toxicity in normal hepatocytes HL7702. JXE-23 inhibited cell growth and colony formation in HepG2 cells. A cell cycle distribution analysis showed that JXE-23 caused G2/M cell cycle arrest. Besides, JXE-23 also suppressed the migration of HepG2 cells. Interestingly, an increase of light chain 3 II (LC3II) and Beclin 1 and a decrease of P62 have occurred in JXE-23-treated cells, as well as the formation of GFP-LC3 dots, indicative of autophagy induction by JXE-23. When combined with autophagy inhibitor 3-methyladenine and chloroquine, the cell viability was significantly reduced, suggesting that JXE-23 triggered protective autophagy in hepatoma cells. Further study showed that JXE-23 inactivated the CIP2A/p-AKT/c-Myc signaling axis in HepG2 cells. Our data provided evidence that JXE-23 inhibited cell growth, arrested cells at the G2/M phase, and induced protective autophagy in HepG2 hepatocellular carcinoma cells. JXE-23 may be a potential lead compound for anti-cancer drug development, and autophagy inhibitor treatment may provide an effective strategy for improving its anti-cancer effect.
... D. esculentum, colloquially known as paku sayur in Indonesia, serves both dietary and medicinal purposes. Historically, this plant has been used in traditional medicine to treat a variety of ailments ranging from respiratory disorders like asthma and coughs to metabolic and inflammatory conditions, like diabetes and rheumatism (Cao et al., 2017). Recent pharmacological studies have given its traditional applications a scientific twist. ...
... Notably, it contains a large number of secondary metabolites, including steroids, saponins, flavonoids, and phenolics. Cao et al. (2017) found in their study that the D. esculentum plant contains a variety of secondary metabolites, including alkaloids, flavonoids, phenols, saponins, steroids, and tannins. ...
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Background: Hyperglycemia arises from excessive blood glucose due to starch hydrolysis by α-amylase and α-glucosidase. Drugs like acarbose inhibit these enzymes to manage hyperglycemia, but long-term use poses risks. Fern species Diplazium esculentum metabolites show promise as acarbose alternatives. Methods: Sequential extraction of secondary metabolites from D. esculentum involved solvents in successive stages: hexane, ethyl acetate, and water. Subsequently, an assessment of phenolic and flavonoid concentrations within the ethyl acetate and aqueous extracts was conducted. Furthermore, the investigation encompassed the evaluation of % inhibition and IC50 values pertaining to the activities of α-amylase and α-glucosidase. Results: The findings indicated that the flavonoid concentrations in the ethyl acetate and aqueous extracts were 146.90 ± 27.20 µg quercetin equivalent per gram of fresh weight (eq./g FW) and 101.95 ± 40.62 µg quercetin eq./g FW, respectively. In terms of total phenolic content, the ethyl acetate extract contained 121.25 ± 8.29 µg of gallic acid eq./g FW, whereas the aqueous extract had 109.90 ± 7.22 µg gallic acid eq./g FW. The IC50 values demonstrated that the aqueous extract had moderate inhibitory effects on α-amylase with a value of 108.05 µg/mL, while acarbose exhibited very strong inhibition with a value of 3.12. Conclusion: Ferns are relatively ineffective in treating hyperglycemia.
... Plant secondary metabolites are the chemicals that are not required for the immediate survival of the plant, but which are synthesized to increase the fitness of the plant to survive by allowing it to interact with its environment, including pathogens, herbivores and insects (Kennedy et al. 2011). Ferns produce a wide array of secondary metabolites endowed with different bioactivities that could potentially be useful in the treatment of many diseases (Cao et al. 2017). Liquid Chromatography-Mass Spectrometry (LC-MS) or High-Resolution Liquid Chromatography -Mass Spectrometry (HR-LC/MS) is an analytical technique that combines high resolution chromatographic separation with sensitive and specific mass spectrum detection (Kumar and Vijayan 2014). ...
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Doryopteris concolor (Langsd. & Fisch.) Kuhn was collected from Nelliyampathy hills in Palakkad, Kerala, India and its methanol extract was subjected to HR-LC/MS analysis, which confirmed the presence of 43 bioactive chemicals. Betulin was determined to be the most efficient chemical against breast cancer proteins, with an LD50 value of 2000 mg/kg, whereas cynaroside demonstrated greater anti-diabetic action than others, with an LD50 value of 5000 mg/kg. D. concolor (Langsd. & Fisch.) Kuhn has a lot of potential for future phytochemical and pharmacological research, especially in the treatment of diabetes and cancer.
... However, in this study, kaempferol and rosmarinic acid were only detected in D. esculentum because phytochemical profiles can be affected by agro-climatic conditions, growth locations or even plant parts [26,27]. Ferns are rich in flavonoids and also contain various types of alkaloids such as lycodine, fawcettimine, diterpenoids, terpene glycosides, β-sitosterols, and bioflavonoids [28]. Further elucidation would assist in the identification of additional bioactive chemicals in D. esculentum with the potential to treat AD. ...
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Alzheimer’s disease (AD) is the most common type of dementia and a significant concern to global public health due to the prevalence of aging populations. Donepezil is one of only a few medications approved for use as an anti-AD agent but all have adverse side effects. Reducing the dosage of AD drugs with plant extracts (phytotherapy) while maintaining efficacy is one strategy to minimize adverse side effects. We previously reported the anti-AD properties of an edible fern, Diplazium esculentum (Retz.) Sw. (DE), which inhibited key enzymes involved in AD pathogenesis including acetylcholinesterase (AChE), butyrylcholinesterase (BChE), and β-secretase 1 (BACE-1). This study aimed to determine whether DE exhibited a synergistic effect with donepezil. The enzyme inhibitory assay showed that DE extract and its bioactive compounds, kaempferol, and quercetin, slightly impeded AChE inhibition with donepezil, while DE extract and quercetin showed synergistic or additive effects with donepezil against BChE and BACE-1, respectively. DE extract combined with donepezil also improved eye phenotypes in a Drosophila model of AD by preventing ommatidia atrophia and bristle breakages. Furthermore, the DE extract exhibited no genotoxic activities, as determined by the Ames test. Our data revealed that DE extract showed promise when combined with donepezil during AD treatment by targeting BChE and BACE-1.
... Flavonoids are phenolic phytochemicals with potential to have strong pharmacological effects as modulators of numerous signal transduction pathways (Castellano et al., 2012;Yu et al., 2021). Thousands of phytochemicals have been extracted and identified from plants, making phytochemicals a huge and varied category of compounds (Cao et al., 2017;Singh & Chaudhuri, 2018). Phenolic compounds are reducing agents, and they all operate as potent antioxidants, playing essential roles through many mechanisms such as the control of antioxidant enzyme activity, chelation of metal ions (Fe, Cu, and others), and anti-inflammatory effects Nicod et al., 2014). ...
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Vitiligo is a common skin disorder resulting from the breakdown of functional epidermal melanocytes. The global prevalence of vitiligo ranges from 0.5% to 2%, with higher rates reported in certain populations. Melanocytes, responsible for skin color, are destroyed in vitiligo condition leading to the appearance of smooth, white patches on the skin. The progression of vitiligo is influenced by various factors, including genetics, autoimmunity, psychosis, melanocyte self-destruction, trace element deficiency, oxidative stress, and other biochemical and environmental variables. Recent research has identified herbal plant extractions as potential agents for re-pigmentation and regeneration of normal skin color. Specific components of these herbal plants, such as furocoumarin, thymoquinone, flavonoids, curcuminoids, and glycyrrhizin, play crucial roles in promoting re-pigmentation. Combination therapies involving these herbal compounds have shown promise in increasing tyrosinase activity and reducing oxidative stress, which are two important aspects of vitiligo treatment. The review aims to comprehensively evaluate the efficacy of herbal plant therapies for melanocyte re-pigmentation in vitiligo patients. By analyzing the effectiveness of various herbal extracts and their active components, this study seeks to advance the understanding and potential application of herbal treatments for vitiligo. The findings from this review may contribute to the current knowledge on therapeutic options available for vitiligo patients.
... Ferns contain secondary metabolites such as phenolic, flavonoids, terpenoids, and alkaloid substances which are responsible for their pharmaceutical activities. The pharmacological studies reported that ferns exhibited antioxidant, antibacterial, anticancer, and antiprotozoal [9]. However, the literature about the phytochemicals present in ferns and their biological activities is still little information. ...
... All the 1 H and 13 C resonances belonging to the glucosyl substituent were assigned using the combined information gained from the 1D selective TOCSY spectrum ( Figure S2), the 2D 1 H-13 C HSQC spectrum ( Figure S5), the 2D 1 H-13 C H2BC spectrum ( Figure S6 Tables 1 and 2). Furthermore, the 1D 1 H NMR spectrum and the 1D 13 C NMR spectrum of 14 showed the presence of a glucosyl substituent and a malonyl substituent, respectively (Figure S1 and 1 13 3.50 s 3 Table 2. 13 C chemical shift values (ppm) of Pteroside D (12), Pteroside X (13), 3-malonyl-pteroside D (14), and Pterosin D (15) dissolved in DMSO-D 6 at 298K. ...
... Pterosin D and Pteroside D were first isolated by Yoshihira et al. [12] from P. aquilunum and have later been found in other fern varieties, such as P. aqullinum subsp. wightianum (Wall) Shich, H. punctata (Thunb) Mett, J. scammanae Tryon, M. speluncae (L.) Moore, M. strigosa (Thunb) Presl, and D. wilfordii (Moore) Christ [13]. ...
... Flavonoids are important natural products of ferns. A multitude of these compounds has hitherto been reported from ferns belonging to Dryopteridaceae, Thelypteridaceae, Selaginellaceae, Equisetaceae, Helminthostachyaceae, Ophioglossaceae, Lygodiaceae, Athyriaceae, and Aspleniaceae species [13]. In the genus Pteridaceae, the flavonoids of the Pteris species have been extensively investigated. ...
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Parsley fern, Cryptogramma crispa, is a common fern in arctic–alpine regions, and even though this species has been known since ancient times and has been presumed to cause the poisoning of horses, its natural products have not previously been investigated. Here, we characterise 15 natural products isolated from the aerial parts of Cryptogramma crispa, including the previously undescribed compound 3-malonyl pteroside D. The structure determinations were based on several advanced 1D and 2D NMR spectroscopic techniques, Circular Dichroism spectroscopy and high-resolution mass spectrometry. The pteroside derivatives exhibited selective moderate cytotoxic activity against the acute myeloid leukaemia MOLM13 cell line and no cytotoxicity against the normal heart and kidney cell lines, suggesting that their potential anticancer effect should be further investigated
... In the kingdom plantae, ferns represent an important phylogenetic bridge between lower and higher plants because they have an ability to produce very unique types of secondary metabolites, many of which are not produce in other vascular plants ] 1 ...
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Ferns are considered as important medical herbs. They produce a wide range of secondary metabolites that could be useful in treating different diseases. However, they still remain underexplored in medical aspects in Iraq. Hence, the purpose of this study was to identify alkaloids components in the methanol extracts of four fern species (Asplenium ceterach L., A. scolopendrium L., Cheilanthes pteridioides (Richard) C. Chr. from Malakan region in Erbil Governorate and Equisetum ramosissimum Desf. from Chemi Rezan in Sulaimaniyah Governorate, of northen Iraq during March-June 2018. The research was conducted by using High performance liquid chromatography (HPLC) technique to identify the alkaloid compounds. Seven types of alkaloids (martensine, almazoline, caulerpin, hordenine, corilagin, colocynthis and isoquinoline) were detected in four fern methanolic extracts. The results showed that the alkaloids varied in concentrations between the studied localities as well as in variance of the alkaloid content between these species. The results revealed that caulerpin was recorded as the highest concentration (563.3 µg/ ml), while isoquinoline was recorded as the lowest (23.7 µg/ ml) in both A. scolopendrium and C. pteridioides. In this study the highest total alkaloid content was recorded 1460.1 µg/ ml in E. ramosissimum extract and the lowest content (603.8 µg/ ml) was recorded in C. pteridioides extract during the study period.