Huperzia Phlegmaria Research Articles

The traditional food of meiteis from the aspects of medicine, cultural, spiritual and social value

The relationship between plants and human beings has been known since time immemorial. Nowadays, there is scientific study of the relationship that exists between people and plants. This includes plants used as food, phytochemicals, pharmacology, clothing, currency, ritual, medicine, dye, construction, etc. Manipur was a small princely state in North-East India, having a history of about 2000 years. As Manipur is under Indo-Burma Biodiversity Hot Spot of the Northeast region, diverse flora and fauna are available. Meiteis, the dominant community of these states and the other 35 ethnic schedule tribes of Manipur, also have traditional foods like Houttunia chordata, Elsholgia, Polygonum species (phakpai) as condiments, Acorus calamus, Plectranthus, Mimosa pudica (Lam ekaithabi), Vitex negundo (Uriksshibi) as medicinal Plants, Oscimum sanctum (Tulsi), Cedrela toona (Tairen) Eupatorium balmanicum (Langthrei) as spiritual plants, Nicotiana tabacum, Lycopodium phlegmaria (Leishang khekwaiba) as cultural plants, Siroy lily and Dzuco lily as social plants as it indicates the availability in Siroi hilltop, Ukhrul and Dzuco.

PRODUCTION OF HUPERZINE A BY FUNGAL ENDOPHYTES ASSOCIATED WITH HUPERZIACEAE PLANTS

Background: Endophytic fungi are known as a producer of a myriad of bioactive natural products, including those originally produced by the host plants. Huperzine A (Hup A), a lycopodium alkaloid, which was reported as an active acetylcholinesterase inhibitor (AChEI) agent used for the treatment of Alzheimer’s disease, was originally isolated from medicinal Chinese herbs Huperzia serrata. Moreover, various species of endophytic fungi associated with H. serrata and other species within Huperziaceae plants were found capable of producing Hup A, suggesting these microorganisms as promising sources of Hup A. Objective: This review aimed to summarize the evidence of Hup A produced by various endophytic fungi as part of efforts to assess alternative producer of Hup A. Methods: Scientific articles on endophytic fungi producing Hup A published from 2000 until 2022 were screened through scientific databases. Results: Thirty-two endophytic fungal strains belonging to fifteen fungal genera were documented as capable of producing Hup A. These fungal endophytes were isolated from Huperziaceae plants, H. serrata, Phlegmariurus phlegmaria and Phlegmariurus taxifolius. Conclusion: We summarize herein the capability of endophytic fungal strains associated with Huperziaceae plants to produce Hup A, an active AChEI agent, which could be considered as an alternative producer of Hup A on a larger scale.Keywords: Acetylcholinesterase inhibitor (AChEI); Alzheimer’s disease; Fungal endophytes; Huperziaceae; Huperzine A (Hup A).

Lycophlegmarinines A–F, new Lycopodium alkaloids from Phlegmariurus phlegmaria

Six new Lycopodium alkaloids, named lycophlegmarinines A–F (1–6), were isolated from whole plants of Phlegmariurus phlegmaria. Their structures were determined based on spectroscopic data analysis, quantum-chemical NMR calculations, and single-crystal X-ray crystallography. Lycophlegmarinine A (1) possesses a novel C15N skeleton with a 9/5/5 ring system, and its plausible biosynthetic pathway is proposed. Compounds 2 and 3 showed inhibitory activity against acetylcholinesterase, with IC50 values of 6.9 μM and 35.2 μM, respectively.

The Effect of Alkaloid Extracted from Huperzia Phlegmaria on Cognitive Deficits Scopolamine-Induced in Mice

Background: Huperzia phlegmaria has been used for the treatment of neurological disorder. Alkaloids are main bioactive compounds found in Huperzia phlegmaria. We aimed to investigate the acetylcholinesterase (AChE) inhibitory activity in vitro of Huperzia phlegmaria alkaloid extract (HpAE) and protective effects on mice which were induced cognitive deficits by scopolamine. Methods: AChE inhibitory activity and kinetic inhibition mechanism was investigated by Ellman's assay. Mice were administrated orally HpAE (30 mg/kg and 60 mg/kg) for fourteen days, and injected scopolamine at a dose of 1 mg/kg intraperitoneally for four days to induce cognitive impairment. The Y-maze and the Morris water maze were used for evaluating the memory behaviors. Acetylcholine (ACh) levels and AChE activity were measured in brain tissue. Glutathione peroxidase (GPx), superoxide dismutase (SOD) activities, and malondialdehyde (MDA) groups were also evaluated in the mouse brain tissues. Results: Our data showed that HpAE had a strong AChE inhibitory activity with an IC50 value of 5.12 ± 0.48 μg/mL in a concentration-dependent manner. Kinetic inhibition analysis demonstrated that HpAE inhibited AChE followed the mixed inhibition type with Ki (representing the affinity of the enzyme and inhibitor) was 4.37 ± 0.35 μg/mL. Scopolamine induced the cognitive impairment in the Morris Water Maze and Y-maze test along with reduced brain levels of ACh and antioxidant enzyme and increased AChE activity in mouse brain tissues. Treatment with HpAE at both doses (30 mg/kg and 60 mg/kg) decreased the SCP-induced cognitive impairment in both behavioral tests along with decreased acetylcholinesterase activity and MDA level, and increased ACh level and antioxidant enzyme in mouse brain tissues. Conclusion: Our results suggested that the HpAE at both dose (30 mg/kg and 60 mg/kg) may be used for prevent and treatment of Alzheimer’s disease.

The complete chloroplast genome of Phlegmariurus phlegmaria, one representative species of genus Phlegmariurus

Phlegmariurus (Herter) Holub is the largest genus of Lycopodiaceae, with about 250 species distributed in the tropics and subtropics of the world. Phlegmariurus phlegmaria is the representative species of Phlegmariurus. In this study, we reported the complete chloroplast genome of P. phlegmaria. This complete chloroplast genome is 1,49,711 bp in size. In total, 134 genes were identified, including 84 protein-coding genes, 42 tRNA genes, and eight rRNA genes. In phylogenetic analysis, a close relationship with genus Huperzia was supported by maximum-likelihood (ML) tree. The complete plastome of P. phlegmaria will provide potential genetic resources to understand the evolution of lycophytes.

The use of Huperzia species for the treatment of Alzheimer's disease.

Alzheimer's disease (AD), which relates to nervous degeneration, is the most popular form of memory loss. The pathogenesis of AD is not fully understood, and there are no therapies for this disorder. Some drugs have been used in clinical applications for preventing and treating AD, but they have significant adverse reactions. Therefore, there is a need to develop treatment for AD. Traditional medicine has used many medicinal plants to alleviate the symptoms of AD. Medicinal plants may reduce neurodegenerative disorders with fewer side effects than chemical drugs, and they are promising drug candidates for AD therapy. This review is the summary of the pathogenesis and treatments of AD and includes information about the chemistry and bioactivities of some medicinal plants from the Huperzia species, such as Huperzia saururus, Huperzia selago, Huperzia phlegmaria, Huperzia fargesii, Huperzia serrata, Huperzia reflexa and Huperzia quadrifariata, that are used for the treatment of AD. We searched literature, including Medline, Embase, Google Scholar and PubMed database, and did a bibliographic review of relevant articles. Key words included Huperzia species, huperzine, huperin, Huperzia and Alzheimer's disease. We found that the main bioactive compounds of the Huperzia species are alkaloids, which have shown significant effects on preventing the development of AD. They are new promising compounds against AD due to their antioxidant, anti-inflammatory and acetylcholinesterase inhibitory activities in the neural system. Our conclusion from this review is that the Huperzia species are potential source containing various pharmaceutical compounds for the treatment of AD.

Phlegmadines B and C, two Lycopodium alkaloids with 6/5/5/5/7 pentacyclic skeleton from Phlegmariurus phlegmaria

Two Lycopodium alkaloids named phlegmadines B (1) and C (2), along with biogenetically related known compounds 3–6, were obtained from Phlegmariurus phlegmaria. Their structures were elucidated based on NMR spectroscopic analysis, and the absolute configuration of 1 was determined by single-crystal X-ray diffraction. Compounds 1 and 2 represent the first pentacyclic (6/5/5/5/7) C16N2Lycopodium alkaloid skeleton. In addition, a possible biosynthetic pathway for 1 and 2 was proposed. Moreover, compound 1 exhibited moderate neurotrophic effects on PC12 cells.

Phlegmadine A: A Lycopodium Alkaloid with a Unique Cyclobutane Ring from Phlegmariurus phlegmaria.

Phlegmadine A (1), a Lycopodium alkaloid with a unique cyclobutane ring and featuring a complex tetracyclo[4.2.2.03,8.03,10]decane-bridged system, together with three biogenetically related known compounds, was isolated from the Phlegmariurus phlegmaria. The structures and absolute configurations of 1 and 2 were determined by NMR and single-crystal X-ray analysis. Among them, compound 2 exhibited noticeable protective effects for long-term potentiation impairment by corticosterone induced in mice. Moreover, we succeeded in the efficient synthesis of 1 from 3 by a biomimetic synthesis method.

(2700) Proposal to conserve the name Lycopodium mirabile (Phlegmariurus mirabilis) (Lycopodiaceae) with a conserved type

[Excerpt] Lycopodium mirabilewas described by Willdenow (Sp. Pl. 5(1):11. 1810) from Ceylon [Sri Lanka] and Cochinchina [southern Vietnam] citing two synonyms from five earlier works (“Lycopodium phleg-mariaβ.Lam. encycl.3.p. 618.Loureiro cochin.2.p.837”and“Selagoindica orientalis sive Plegmaria admirabilis zeylanica. Breyn. cent. 180. t. 92. Raj. hist. 1582 [sic = t. 1852]. suppl. 655. Dill. musc. t. 61.f.D.E.F.”) and giving the distribution, etc. as “Habitat in Zeylona,Cochinchina. H. (v. s.)”. All the synonym references refer to a species similar to Lycopodium phlegmaria (≡Phlegmariurus phlegmaria(L.)Holub). Willdenow indicated that he had seen dried material, but specimen details were not cited. The only material labelled L. mirabile in the Willdenow Herbarium at B is barcode B -W 19340 -01 0 (!), which was considered to be the holotype by Ollgaard (in Biol. Skr. 34: 57. 1989). This is technically an inadvertent lectotypification, as additional original elements are known.

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A personal selection of 32 recent papers is presented covering various aspects of current developments in bioorganic chemistry and novel natural products such as phlegmadine A from Phlegmariurus phlegmaria.

Two Lycopodium alkaloids from the aerial parts of Huperzia phlegmaria

Background: Huperzia phlegmaria has been used to enhancing memory and alleviate brain disorders. It contains high amount of alkaloids, which are potent acetylcholinesterase (AChE) inhibitor. Materials and Methods: Lycopodium alkaloids from aerial parts of H. phlegmaria were isolated by chromatographic methods. Their structures were elucidated by spectroscopic methods, including mass spectrometry and nuclear magnetic resonance. AChE inhibitory effect of isolated compounds in vitro was evaluated using Ellman's assay. Results: These compounds were identified as fawcettidine and 12-epilycodoline N-oxide. Two compounds showed moderately AChE inhibitory effects with IC50values of 33.11 μg/mL and 64.56 μg/mL, respectively. Conclusion:These isolated compounds could be promising drugs for the treatment of Alzheimer's disease.

Three Lycopodium alkaloids from Thai club mosses

Phytochemical constituents in alkaloid extracts from three Thai club mosses Huperzia squarrosa, Huperzia phlegmaria and Phlegmariurus nummularifolius were investigated. Squarrosinoxide was an undescribed Lycopodium alkaloid from H. squarrosa possessing an unprecedented 6/5/7 tricyclic spiro system. Acetyllycophlegmarianol was an undescribed N-oxide lycopodine-type alkaloid isolated from H. phlegmaria. 4-Epilycopodine, an undescribed epimer of lycopodine, was first isolated from P. nummularifolius. The structural assignments were established through comprehensive spectroscopic techniques and chemical correlations. All compounds were assayed for their anti-acetylcholinesterase activity in vitro.

Huperphlegmines A and B, two novel Lycopodium alkaloids with an unprecedented skeleton from Huperzia phlegmaria, and their acetylcholinesterase inhibitory activities

Two novel Lycopodium alkaloids, huperphlegmines A and B (1 and 2), were isolated from the aerial parts of Huperzia phlegmaria collected in Vietnam, together with the five known compounds lycophlegmariol A (3), phlegmariurine B (4), 5-hydroxymethyl-2-furaldehyde (5), rhemanone C (6), and loliolide (7). The chemical structures of the present compounds were elucidated by means of 1D and 2D NMR and HRESIMS spectroscopy, and by comparisons to the reported data in the literature. Compounds 1 and 2 showed moderate acetylcholinesterase inhibitory activities, with IC50 values of 25.95 ± 0.67 and 29.14 ± 0.77 μg/mL, respectively.

Inventarisasi Tumbuhan Paku di Jalur Ciwalen Taman Nasional Gunung Gede Pangrango Jawa Barat

After being observed as a whole, Gunung Gede Pangrango National Park has a high diversity of Ferns. This research aims to describe Ferns in the Ciwalen Gunung Gede Pangrango National Park, so it is hopefully could describe the diversity of ferns in that path. The Inventory of ferns is done by using exploration method with random sampling technique which then identified with General Key to Malayan Fern referral. The results of this research showed that there are ten types of ferns that have been founded in the Ciwalen Gunung Gede Panggrango National Park, such as Sphaerostephanos sp., Asplenium truncata, Nephrolepis davallioides, Botrychium daucifolium, Selaginella opaca, Huperzia phlegmaria, Equisetum ramosissimum, Didymochlaena truncatula, Hymenophyllum sp., and Diplazium poliferum. Features any distinctive Ferns can be seen from the form such as rhizome, type of frond, an accessory, the sorus, habitats that were found, and others.

Two new abietane diterpenes huperphlegmarins A and B from Huperzia phlegmaria

Two new abietane diterpenes, huperphlegmarin A–B (1–2), were isolated from the aerial parts of Huperzia phlegmaria (L.) Rothm. (Lycopodiaceae), in addition to five known compounds including lycoxanthol (3), 21β-hydroxyserrat-14-en-3β-yl acetate (4), 21α-hydroxyserrat-14-en-3β-yl acetate (5), 21α-hydroxyserrat-14-en-3β-ol (6), and fawcettidine (7). Their structures were determined by the combination analyses of spectroscopy, including 1D-, 2D-NMR, HRESIMS, CD and comparison with the reported data in the literature. Huperphlegmarin B (2) presented the rare 1,11-epoxy group in the molecule. Compounds 3, 4, 5 and 6 were performed for AChE inhibitory activity and compound 3 showed the inhibitory activity against AChE with IC50 of 465.6 μg/mL.

First insights on the biogeographical history of Phlegmariurus (Lycopodiaceae), with a focus on Madagascar

We explored the biogeographical history of a group of spore-bearing plants focusing on Phlegmariurus (Lycopodiaceae), a genus of lycophytes comprising ca. 250 species. Given its wide distribution in the Southern Hemisphere, Phlegmariurus provides a good model to address questions about the biogeographical processes underlying southern distributions, notably in Madagascar and surrounding islands, also called the Western Indian Ocean (WIO). Our aims were (i) to discuss the systematics of the Malagasy species in the light of molecular phylogenetic results, (ii) to provide the first dating analysis focused on Phlegmariurus and (iii) to understand the relative role of vicariance, dispersal and diversification in the origin of the Malagasy Phlegmariurus species.The phylogenetic relationships were inferred based on three plastid DNA regions (rbcL, trnH-psbA and trnL+trnL-trnF) and on a dataset comprising 93 species, including 16 Malagasy species (80% of the total Malagasy diversity for the genus). Our results highlighted the need to combine Malagasy Huperzia species in Phlegmariurus, as well as the polyphyly of widely distributed species: Phlegmariurus phlegmaria, P. squarrosus and P. verticillatus with the Malagasy species not belonging with the types of P. phlegmaria or P. squarrosus. This led us to propose new circumscriptions of Phlegmariurus species, especially in the WIO.Our dating analysis, relying on fossil calibrations, showed that Phlegmariurus would have originated in the Late Cretaceous and diversified in the Early Eocene. The biogeographical analysis highlighted uncertainties about the biogeographical origins of Phlegmariurus: the genus would have started to diversify in an ancestral range covering at least the Neotropics and Australasia. Hypotheses on the biogeographical history of Phlegmariurus were discussed, especially the roles of long distance dispersal, migration via Antarctica and via the Boreotropics. Six long distance dispersal events over the last 40 Ma would explain the Malagasy species diversity of Phlegmariurus, in combination with an important in situ diversification starting in the Miocene.

Edible ferns and fern–allies of North East India: a study on potential wild vegetables

The North East India houses around 130 ethnic tribal communities which exhibits unique tradition, dialect and culture. These communities collect edible plants from wild forming a common practice for livelihood and subsistence even today. Of the varieties of plant consumed, ferns and fern–allies also constitute an important food supplement. An inventory survey was conducted in order to assess the wild edible ferns and fern–allies which are used as vegetables by various ethnic communities of North East India. Altogether, twenty-three (23) ferns and fern–allies are found to be edible, and used in preparing various cuisines. Four species viz. Diplazium esculentum (Retz.) Sw., Huperzia phlegmaria (L.) Rothm., Huperzia squarrosa (G. Forst.) Trevis. and Nephrolepis cordifolia (L.) C. Presl were cultivated in small scale for consumption and horticultural purposes, while the rest of the species were directly harvested from wild habitat. Role of these ferns in local cuisines, other reported uses and bioactive components were discussed. The study also emphasises on future development of ferns and its allies as potential vegetables in North East India.

Isolation and characterzation of endophytic Huperzine A-producing fungi from Phlegmariurus phlegmaria

Based on special colony morphology, 340 endophytic fungi were isolated from the stems, leaves, and roots of Phlegmariurus phlegmaria. Among the 340 strains, eight, representative species (MY298, MJ216, MY237, MJ422, MY311, MY183, MJ484, and MY252) could produce HupA analyzed by UPLC-MS/MS (Ultra performance liquid chromatography), which compared with standard HupA under the same chromatographic conditions. And through the standard curve generated, among these HupA-producing fungi, the MY311 had highest content which was 40.53 µg/L. The extract of eight strains was examined by AChE inhibition activity assay in vitro and ELISA (enzyme-linked immunosorbent assay). These eight strains were found to have positive results for HupA production and MY311 extract obviously exhibited the highest inhibition activity. Furthermore, the genera of the eight fungi were identified based on the internal transcribed spacer sequence analysis. All eight distinctive genotypes were grouped into four fungal genera and six fungal species, however, MY311 and MY183 were Ceriporia lacerata and Hypoxylon investiens, which had never been reported as HupA-producing endophytic fungi.

Two new Lycopodium alkaloids from Phlegmariurus phlegmaria (L.) Holub

Two new Lycopodium alkaloids, 4β-hydroxynankakurine B (1) and Δ13,N,Nα-methylphlegmarine-Nβ-oxide (2), together with three known analogues, lycoposerramine E (3), nankakurine B (4) and lobscurinol (5), were isolated from Phlegmariurus phlegmaria. Their structures were established by mass spectrometry and 1D and 2D NMR techniques.

Morfología y anatomía de ejes caulinares, licofilos y esporangios de Phlegmariurus phylicifolius: un aporte a la sistemática de las Lycopodiaceae neotropicales

Phlegmariurus is the only genus of Lycopodiaceae with the species grouped in 22 informal groups. Species level relationships within Phlegmariurus are poorly understood and their circumscriptions require a thorough molecular and morphological review. A detailed study of morphology and anatomy of caulinar axes, lycophylls and sporangia of Phlegmariurus phylicifolius was carried out in order to contribute to the elucidation of species circumscription in the informal group Phlegmariurus phlegmaria. Small pieces of caulinar axes bearing trophophylls, sporophylls and sporangia were fixed, dehydrated, Histowax (paraffin) embedded, sectioned in a rotatory microtome, and stained using the common Safranin O-Fast Green technique; handmade cross sections were also made and stained with the same technique. P. phylicifolius includes slender, pendulous plants up to 40cm long. Shoots heterophyllous, in the basal divisions ca. 10-20(-25) mm in diameter including the trophophylls, then abruptly constricted to (1-) 1.5-2(-2.5) mm in diameter including the imbricate, reduced sporophylls. Trophophylls are borne in alternating whorls of three, or decussate, subdecussate, or alternate, widely spaced in alternate leaved caulinar axes portions, perpendicular to the caulinar axes to falcately ascending, lanceolate to linear-lanceolate, with flat to slightly revolute margins. Each lycophyll is supplied by a single central vascular bundle, connected to a protoxylem pole in the stele. At the site of leaf-trace departure, no leaf (lycophyll) gap is present. Caulinar axes excluding leaves 0.7-1.2 mm thick at the base, upward tapering to ca. 0.5 mm. Caulinar axes present unistratified epidermis and endodermis, the cortex is characterized by the presence of a trabecular structure of lisigenous origin formed in the parenchimatous tissue next to the endodermis. The vascular tissue occupies the central part of the caulinar axes, forming a plectostele ofsubradiate organization, with five poles ofprotoxylem. The epidermal cells present sinuous anticlinal walls; invaginations in the inner side of external periclinal wall of the epidermal cells could be probably adaptive morphological feature of a water deficient environment. Leaves of constricted terminal divi- sions are decussate, or subdecussate, continuously or discontinuously sporangiate, appressed, abaxially rounded to carinate, widely lanceolate to widely ovate or subcordate, acute to mucronate or cuspidate, shorter than the sporangia. Each sporangium originates from a group of epidermal cells, axilar to the sporophylls. The cell walls of epidermal cell of the sporangia are Huperzioideae type. The morphological studies of trophophylls contribute to confirm the differences between P. phylicifolius and P. subulatus.