Lycopodiastrum Research Articles

Lycocasine A, a Lycopodium Alkaloid from Lycopodiastrum casuarinoides and Its Acid-Sensing Ion Channel 1a Inhibitory Activity.

A novel Lycopodium alkaloid, lycocasine A (1), and seven known Lycopodium alkaloids (2-8), were isolated from Lycopodiastrum casuarinoides. Their structures were determined through NMR, HRESIMS, and X-ray diffraction analysis. Compound 1 features an unprecedented 5/6/6 tricyclic skeleton, highlighted by a 5-aza-tricyclic[6,3,1,02,6]dodecane motif. In bioactivity assays, compound 1 demonstrated weak inhibitory activity against acid-sensing ion channel 1a.

Casuattimines A–N, fourteen new Lycopodium alkaloids from Lycopodiastrum casuarinoides with Cav3.1 channel inhibitory activity

Two new dimeric Lycopodium alkaloids, casuattimines A and B (1 and 2), along with twelve previously undescribed Lycopodium alkaloids, casuattimines C–N (3–14), and eight known Lycopodium alkaloids, were isolated from Lycopodiastrum casuarinoides. Casuattimines A and B (1 and 2) are the first two ether-linked Lycopodium alkaloid dimers. Casuattimines C and D (3 and 4) are unique Lycopodium alkaloids characterized by a long fatty acid chain. Structural elucidation was achieved through HRESIMS, NMR, and electronic circular dichroism (ECD) calculations. In addition, the absolute configurations of compounds 7, 13, and 14 were determined by single crystal X-ray diffraction. Compounds 1, 2, and 4 demonstrated notable Cav3.1 channel inhibitory activities presenting IC50 values of 10.75 ± 1.02 μM, 9.33 ± 0.79 μM, and 7.14 ± 0.86 μM, respectively. The dynamics of compound 4 against the Cav3.1 channel and preliminary structure–activity relationships of these active Lycopodium alkaloids were also discussed.

Anti-inflammatory activity via NO production inhibition of compounds from Vietnamese Lycopodium casuarinoides Spring

In our investigation of the methanol extract derived from the aerial parts of Vietnamese Lycopodium casuarinoides Spring, we successfully isolated two novel secondary metabolites: 3β,21α,24-trihydroxyserrat-14-en-29-yl-E-4′-hydroxy-3′-methoxycinnamate (1) and lycocasuarinol A (2), and eight known compounds, namely α-onocerin (3), salcolin A (4), salcolin B (5), (2 R,3 R)-dihydrokaempferol (6), apigenin (7), huperzinine (8), 4-methoxycinnamic acid (9), and (E)-p-coumaric acid (10). The structural elucidation of these compounds was accomplished through high-resolution electrospray ionization mass spectrometry (HR-ESI-MS) and one-dimensional (1D) and two-dimensional (2D) nuclear magnetic resonance (NMR) spectroscopy techniques. All isolates were tested for their potential to inhibit nitric oxide (NO) production in lipopolysaccharide (LPS)-induced RAW264.7 cells. Notably, the flavonoids (2 R,3 R)-dihydrokaempferol (6) and apigenin (7) exhibited significant inhibitory activity against NO production, with IC50 values of 3.4 µM and 3.0 µM, respectively. These values surpassed the inhibition observed with the positive control, celastrol. Furthermore, a comparison of the guaiacyl glyceryls salcolin A (4) and salcolin B (5), differing in their threo-β- and erythro-guaiacyl glyceryl moieties, revealed potential structure-activity relationships. These findings suggest that the extract from Lycopodium casuarinoides and its phytochemical constituents hold promise as potential anti-inflammatory agents

Entropy analysis and grey cluster analysis of multiple indexes of 5 kinds of genuine medicinal materials

5 kinds of genuine medicinal materials, including Diding (Latin name: Corydalis bungeana Turcz), Purslane (Latin name: Portulaca oleracea L.), straw sandal board (Latin name: Hoya carnosa (L.f.) R. Br), June snow (Latin name: Serissa japonica (Thunb.) Thunb.), pine vine rattan (Latin name: Lycopodiastrum casuarinoides (Spring) Holub. [Lycopodium casuarinoides Spring]), were selected as the research objects. The combustion heat, thermo gravimetric parameters, and fat content, calcium content, trace element content, ash content of 5 kinds of genuine medicinal materials were measured. The combustion heat, differential thermal gravimetric analysis, fat content, calcium content, trace elements content, and ash content of 5 kinds of genuine medicinal materials were used to build a systematic multi-index evaluation system by gray pattern recognition and grey correlation coefficient cluster analysis, which can make up for the gaps in this area and provide scientific basis and research significance for the study of genuine medicinal materials quality. The results showed that the order of combustion heat of 5 kinds of genuine medicinal materials, including Diding, Purslane, straw sandal board, June snow, pine vine rattan, was Diding > June snow > straw sandal board > Purslane > pine vine rattan, the order of fat content (%) of 5 kinds of genuine medicinal materials was straw sandal board > Diding > pine vine rattan > June snow > Purslane, the order of calcium content (%) was pine vine rattan > June snow > Purslane > straw sandal board > Diding, the order of ash content was June snow > Purslane > straw sandal board > pine vine rattan > Diding. From the analysis of thermogravimetric analysis results and thermogravimetric combustion stability, the order of combustion stability of 5 kinds of genuine medicinal materials was June snow > pine Vine rattan > straw sandal board > Diding > Portulaca oleracea. The order of the content of 12 trace elements in 5 kinds of genuine medicinal materials, in terms of trace element content, June snow contains the highest trace elements in all samples. According to combustion heat, combustibility (combustion stability of genuine medicinal materials), fat, calcium, ash, trace element content, the comprehensive evaluation results of multi-index analysis constructed by gray correlation degree, gray correlation coefficient factor analysis, and gray hierarchical cluster analysis showed that the comprehensive evaluation multi-index order of 5 genuine medicinal materials, including Diding, Purslane, straw sandal board, June snow and pine vine rattan, was June snow > straw sandal board > Diding > Purslane > pine vine rattan. Therefore, the comprehensive evaluation results of the quality of genuine medicinal materials selected in this study were June snow the best, followed by straw sandal board. This research has important theoretical and practical significance for the multi-index measurement and comprehensive evaluation of genuine medicinal materials, and can provide scientific basis and research significance for the research of multi-index quality control of genuine medicinal material.

New unsaturated fatty acids from the aerial parts of Lycopodiastrum casuarinoides

Abstract Two new unsaturated fatty acid esters (1 and 2) and five new unsaturated fatty acids (4–8), together with two known analogs (3 and 9) were isolated from the aerial parts of Lycopodiastrum casuarinoides. Their structures were unambiguously elucidated by obtaining extensive spectroscopic data and comparing them with data in the literature. The absolute configurations of 1 and 2 were established by a modified Mosher's method. All compounds were evaluated in vitro for their inhibitory activities against acetylcholinesterase (AChE) and butyrylcholinesterase (BChE). Compound 8 exhibited the most potent inhibitory activity against AChE with an IC50 value of 1.16 ± 0.13 μM.

Lycodine-type alkaloids from Lycopodiastrum casuarinoides and their acetylcholinesterase inhibitory activity

Five previously undescribed lycodine-type alkaloids, named huperzine Y (1), 8,15-epoxy-N-demethylhuperzinine (2), 7-hydroxyl-huperzinine (3), huperzine Z (4), and huperzine D N-oxide (5), were isolated from the aerial parts and roots of Lycopodiastrum casuarinoides (Lycopodiaceae), along with ten known analogues. The structures of the new compounds were elucidated by means of spectroscopic technique (IR, UV, MS and NMR). The absolute configurations of the new compounds were established on the basis of comparison of their experimental and TD-DFT (time-dependent density functional theory) calculated ECD spectra. Moreover, all the isolates were evaluated for acetylcholinesterase (AChE) inhibitory activity. Only huperzine C showed moderate activity, with an IC50 value of 0.525 ± 0.140 μM, which was comparable with the positive control, huperzine A (IC50 = 0.143 ± 0.029 μM).

Anti-cholinesterase activities of constituents isolated from Lycopodiastrum casuarinoides

Phytochemical investigation of the ethyl acetate extract of Lycopodiastrum casuarinoides (Spring) Holub (Lycopodiaceae) led to the isolation of nine compounds, including two new serratene triterpenoids, serrat-14-en-3α,21α-diol (1), 26-nor-8-oxo-21-one-α-onocerin (6), one new abietane diterpenoid, lycocasuarinone A (7), one new sesquiterpene acid, 7, 9-diene-1,4-epoxy-2-hydroxy-10-carboxylic acid (8) and one new chromone derivative, 5,7-dihydroxy-2-methyl esterchromone (9), together with four known serratene triterpenoids (2–5). Abietane diterpenoid (7) and sesquiterpene acid (8) from Lycopodiastrum casuarinoides are reported for the first time. Their structures and stereochemistry were unambiguously elucidated by spectroscopic analysis and comparison with known ones. All the compounds were tested for acetylcholinesterase (AChE) and butyrocholinesterase (BuChE) inhibitory activities. Bioactivity assays revealed that compound 6 exhibited the most potent AChE inhibitory effect.

Lycocasuarines I–Q, new Lycopodium alkaloids isolated from Lycopodiastrum casuarinoides

Lycocasuarines I–Q (1–9), nine new lycodine-type Lycopodium alkaloids were isolated from the aerial parts of Lycopodiastrum casuarinoides (Spring) Holub ex R.D.Dixit. Their structures were unambiguously determined via extensive spectroscopic analyses, including HRESIMS, NMR, and electronic circular dichroism (ECD). The new alkaloids were evaluated for their in vitro inhibitory activity against acetylcholinesterase (AChE). Compounds 3, 5–8 exhibited marginal or weak activities with IC50 values ranging from 97.2 to 171.9 μM.

Cytotoxic lycodine alkaloids from the aerial parts of Lycopodiastrum casuarinoides

A phytochemical investigation on the 75% EtOH extract of the aerial parts of Lycopodiastrum casuarinoides resulted in the isolation of three new lycodine alkaloids, 16-hydroxy-9-oxo-lycocasuarinine D (1), 6α-hydroxy-16-dehydroxy-lycocasuarinine A (2), and 6α,16-dihydroxy-lycocasuarinine B (3). Structural elucidation of all the compounds was performed by spectral methods such as 1D- and 2D-NMR, infrared, ultraviolet, and HR-ESI-MS. The isolated alkaloids were tested in vitro for cytotoxic potential against six lung cancer cell lines. Consequently, alkaloid 1 exhibited cytotoxicity against all the tested tumor cell lines with IC50 values less than 20 μM.

Lycodine type alkaloids from Lycopodiastrum casuarinoides with cytotoxic and cholinesterase inhibitory activities

A chemical investigation on the 70% EtOH extract of the aerial parts of Lycopodiastrum casuarinoides led to the isolation of six novel lycodine type alkaloids, lycocasuarines A-F (1–6). The structures of the isolated compounds were established based on 1D and 2D (1H1H COSY, HMQC, and HMBC) NMR spectroscopy, in addition to high resolution mass spectrometry. The isolated alkaloids were tested in vitro for cytotoxic potentials against seven malignant melanoma cell lines as well as acetylcholinesterase (AChE) and butyrocholinesterase (BuChE) inhibitory activities. As a result, alkaloids 1 and 3 exhibited significant cytotoxic activities against all the tested tumor cell lines with IC50 values <10 μM and the inhibitory activities for AchE (0.94 ± 0.15 and 0.24 ± 0.03 μM, respectively) and BuchE (1.82 ± 0.12 and 7.31 ± 0.42 μM, respectively).

Lycodine-type alkaloids from Lycopodiastrum casuarinoides and their cholinesterase inhibitory activities

Four new trace alkaloids with lycodine-related structures, Lycocasuarinines A–D (1–4), together with seven known analogues (5–11), were isolated from the chloroform extract of Lycopodiastrum casuarinoides. The structures and stereochemistry of 1–4 were elucidated by spectroscopic analysis (IR, UV, MS, NMR, HRESIMS and CD) and comparison with known ones. The acetylcholinesterase (AChE) and butyrocholinesterase (BuChE) inhibitory activities of nine isolates were evaluated. Lycocasuarinine D (4) showed the most potent AChE inhibitory effect. In addition, a plausible biogenetic pathway of compound 4 was proposed.

Lycodine-type alkaloids and their glycosides from Lycopodiastrum casuarinoides

Thirteen previously undescribed lycodine-type Lycopodium alkaloids, namely, five alkaloids (lycocasuarines D–H) each possessing an uncommon five-membered C ring and eight Lycopodium alkaloid glycosides (casuarinosides A–H), together with a known analog, were isolated from the aerial parts of Lycopodiastrum casuarinoides (Spring) Holub ex R.D.Dixit (Lycopodiaceae). The structures of the compounds were elucidated by extensive spectroscopic analysis, single-crystal X-ray diffraction, and chemical methods. In addition, the acetylcholinesterase inhibitory activity of the isolated compounds was evaluated.

Leveraging plant exine capsules as pH-responsive delivery vehicles for hydrophobic nutraceutical encapsulation.

Plant exine capsules are natural microscale capsules that are highly physically robust and chemically resilient. They are extracted from pollen grains and plant spores, and can be used as renewable and safe microcapsules for encapsulation applications. Herein, we report the successful evacuation of natural sunflower pollen grains (SPGs) and Lycopodiastrum casuarinoides spore exine capsules (SECs) and investigated the effects of different loading methods on the encapsulation and release of nobiletin, a model hydrophobic nutraceutical. The compositional and morphological characterizations of SPGs and SECs obtained by the developed extraction protocol confirmed that the inside contents had been removed and hollow pollen cavities were obtained successfully. In addition, coumarin-6, a hydrophobic fluorescent probe, was encapsulated into SPGs and SECs, which proved the possibility of using them to encapsulate hydrophobic nutraceuticals. Furthermore, controlled release in simulated digestive fluids (SDF) was achieved by coating calcium alginate onto the outside of the SPGs and SECs. Looking forward, this may provide an effective and potential delivery model to protect loads from degradation in the stomach and achieve pH-responsive delivery of hydrophobic nutraceuticals after oral administration.

Lycocasuarines A–C, Lycopodium alkaloids from Lycopodiastrum casuarinoides

Three lycodine-type Lycopodium alkaloids (1–3) were isolated from Lycopodiastrum casuarinoides. Their structures were elucidated by spectroscopic analysis, single-crystal X-ray crystallography, and computational methods. Compound 1 possesses a rearranged five-membered ring D resulting from C-8/C-15 cleavage and a new C-7/C-15 linkage. Compound 2 is the first Lycopodium alkaloid found to bear an additional carbon (C-17) directly bonded to C-8, which is particularly unusual from a biogenetic point of view. Compounds 1–3 were evaluated for acetylcholinesterase inhibitory activities.

Rapid screening and identification of lycodine‐type alkaloids in Lycopodiaceae and Huperziaceae plants by ultra‐performance liquid chromatography coupled with quadrupole time‐of‐flight mass spectrometry

Lycodine-type alkaloids have gained significant interest owing to their unique skeletal characteristics and acetylcholinesterase activity. This study established a rapid and reliable method using ultra-performance liquid chromatography coupled with electrospray ionization quadrupole time-of-flight tandem mass spectrometry (UPLC-ESI-Q/TOF-MS/MS) for comprehensive characterization of lycodine-type alkaloids for the first time. The lycodine-type alkaloids were detected successfully from Lycopodiastrum casuarinoides, Huperzia serrata and Phlegmarirus carinatus in seven plants of the Lycopodiaceae and Huperziaceae families, based on the established characteristic MS fragmentation of five known alkaloids. Furthermore, a total of 13 lycodine-type alkaloids were identified, of which three pairs of isomers were structurally characterized and differentiated. This study further improves mass analysis of lycodine-type alkaloids and demonstrates the superiority of UPLC with a high-resolution mass spectrometer for the rapid and sensitive structural elucidation of other trace active compounds. Copyright © 2016 John Wiley & Sons, Ltd.

Two New Lycodine Alkaloids from Lycopodiastrum casuarinoides

AbstractTwo new lycodine alkaloids, 11β‐methoxyhuperzine B (1) and 16‐oxohuperzinine (2), together with seven known ones, huperzinine N‐oxide, huperzine D, casuarinine A, huperzine B, casuarinine B, huperzinine, and N‐methyllycodine, were isolated from whole plants of Lycopodiastrum casuarinoides. Their structures were elucidated by spectroscopic methods, including NMR and MS experiments.

Suppressive effects of total alkaloids of Lycopodiastrum casuarinoides on adjuvant-induced arthritis in rats

Ethnopharmacological relevanceLycopodiastrum casuarinoides is a folk medicine used to treat inflammation-associated diseases including rheumatoid arthritis in South China. Since the major secondary metabolites in Lycopodiastrum casuarinoides are alkaloids, the present study aims to investigate the suppressive effects of total alkaloids of Lycopodiastrum casuarinoides (ALC) on adjuvant-induced arthritis (AA) in rats. Materials and methodsAA was induced (day 0) in male Sprague–Dawley rats by intradermal injection of complete Freund׳s adjuvant (CFA) in right hind footpad. Diclofenac sodium (SD) was chosen as the positive drug. SD (10mg/kg) and ALC (20 and 40mg/kg) administration started from day 1 and continued for 28 days. Paw swelling, arthritis scores, and histopathological changes were evaluated. In addition, the serum levels of tumor necrosis factor alpha (TNF-α), interleukin-6 (IL-6), and prostaglandin E2 (PGE2), as well as cyclooxygenase-2 (COX-2) and nuclear factor (NF)-κB expressions in joint synovial tissues were detected. ResultsALC administration significantly suppressed the inflammatory responses in the joints of AA rats. It also decreased the serum levels of TNF-α, IL-6 and PGE2. Moreover, Western blot analysis showed that COX-2 and NF-κB expressions in synovial tissues of AA rats were significantly reduced. ConclusionThese results indicated that ALC prevented the pathological development of AA in rats. ALC may be a potential candidate for the treatment of inflammation and arthritis.

Lycodine-type alkaloids from Lycopodiastrum casuarinoides and their acetylcholinesterase inhibitory activity.

Four new lycodine-type alkaloids, namely 16-hydroxyhuperzine B (1), N-methyl-11-acetoxyhuperzine B (2), 8,15-dihydrolycoparin A (3) and (7S, 12S, 13R)-huperzine D-16-O-β-d-glucopyranoside (4), along with ten known analogues 5−14, were isolated from the whole plant of Lycopodiastrum casuarinoides. The structures of the new compounds were elucidated by means of spectroscopic techniques (IR, MS, NMR, and CD) and chemical methods. Compounds 1 and 2 possessed four connected six-membered rings, while compounds 3 and 4 were piperidine ring cleavage products. In particular, compound 4 was a lycopodium alkaloidal glycoside which is reported for the first time. Among the isolated compounds N-demethylhuperzinine (7), huperzine C (8), huperzine B (9) and lycoparin C (13) possessed significant inhibitory activity against acetylcholinesterase, and the new compound 1 showed moderate inhibitory activity. The structure activity relationships were discussed.

ChemInform Abstract: Casuarines A and B, Lycopodium Alkaloids from Lycopodium casuarinoides.

AbstractA phytochemical study on Lycopodium casuarinoides leads to the isolation of two new C16N2‐type Lycopodium alkaloids, casuarine A (I), a cage‐like structure featured with a fused 6/6/6/6/6 pentacyclic ring system, and casuarine B (II).

Casuarinines A–J, Lycodine-Type Alkaloids from Lycopodiastrum casuarinoides

Ten new lycodine-type alkaloids, named casuarinines A-J (1-10), along with eight known analogues (11-18), were isolated from the whole plant of Lycopodiastrum casuarinoides . The new structures were established by spectroscopic methods and chemical transformations. Casuarinines A-D (1-4) and J (10) are common lycodine alkaloids possessing four connected six-membered rings, while tricyclic casuarinines E-H (5-8) are the piperidine ring cleavage products. In particular, casuarinine I (9) has an unprecedented five-membered tetrahydropyrrole ring instead of the piperidine ring. A plausible biosynthetic pathway to 9 is proposed. Among the compounds reported, casuarinine H (8) exhibited significant neuroprotective effect against hydrogen peroxide (H₂O₂)-induced neuronal cell damage in human neuroblastoma SH-SY5Y cells, while casuarinines C (3) and I (9) showed moderate inhibitory activity against acetylcholinesterase (AChE).