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The increasing incidence of neurodegenerative diseases (NDDs) has stressed the need to develop new treatments. In this regard, alkaloids from medicinal plants are being identified and developed as inhibitors of acetylcholinesterase, other enzymes, and receptors associated with the onset of NDDs. Nardostachys jatamansi, a medicinal herb native to the Himalayan region and belonging to the Caprifoliaceae family, has long been used in Indian traditional medicine to treat neurobiological symptoms. In this study, we have isolated and identified the major alkaloids from N. jatamansi using LC–MS/MS analysis. The dried root extract of N. jatamansi contained actinidine and glaziovine as its major alkaloids. These compounds were identified using LC–MS/MS fragmentation pattern and purified by semi-preparative HPLC. The molecular docking analysis was performed for the purified alkaloids with 15 target proteins associated with NDDs pathology. Notably, actinidine and glaziovine showed better interaction energy with the acetylcholine esterase, VGF nerve growth factor, cyclin-dependent kinase, and glycogen synthase kinase when compared to the clinically used drugs memantine and tacrine. Glaziovine also showed better interaction energy when docking was performed with GluN1/GluN2B NMDA receptor, β-secretase, tyrosine phosphorylation regulation kinase, necrosis factor-kappa, adenosine A2A receptor, alpha-synuclein, beta-site amyloid precursor protein cleaving enzyme 1, c-Jun N terminal kinase, monoamine oxidase B, compared to tacrine, galantamine, and memantine. Furthermore, actinidine and glaziovine showed borderline cytotoxicity on PC12 and SH-SY 5Y cells with IC50 values ranging from 85.32 ± 0.87 μM, and 92.12 ± 0.56 μM, respectively, indicating that these alkaloids can be further developed as promising drug leads. [ABSTRACT FROM AUTHOR]

ABSTRACT Introduction The Unonopsis genus is a promising source of aporphinoid alkaloids, substances with great biological potential. These alkaloids have a well-defined mass spectrometry fragmentation pattern that, together with previous phytochemical knowledge, can guide the isolation of alkaloids not yet described for the genus. Objective Isolate substances not yet described in the Unonopsis genus, guided by alkaloidal profile analyses of stem barks, twigs and leaves of Unonopsis duckei using electrospray ionisation ion-trap tandem mass spectrometry (ESI-IT/MS n). Methods Methanolic extracts from stem barks, twigs and leaves were submitted to a liquid-liquid, acid-base partitioning treatment to obtain the alkaloidal fractions. These fractions were analysed by direct infusion into an ESI-IT/MS n system. The major alkaloids observed for each fraction were submitted to fragmentation analysis. Results The MS fragmentation patterns revealed the presence of alkaloids previously reported for Annonaceae, including nornuciferine, anonaine, asimilobine, liriodenine and lysicamine, known for the Unonopsis genus, as well as others that were not yet described for this genus. In this way, the proaporphine alkaloid glaziovine was isolated, as well as a mixture of the aporphine alkaloids glaucine and norglaucine, all described for the first time in the Unonopsis genus. Conclusion Mass spectrometry monitoring was fundamental to prioritise the isolation of substances not yet identified for the Unonopsis genus, dismissing known compounds and simplifying the phytochemical study. Copyright © 2013 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

The main alkaloids in leaves, stems and rhizomes of Antizoma angustifolia, a traditional medicinal plant of the family Menispermaceae, were isolated and identified. The main compound in leaves is almost invariably crotsparine, while stems and rhizomes have several other alkaloids (glaziovine, pronuciferine, bulbocapnine, salutaridine, cissacapine, insularine) in lower yields. These results do not agree with a previous study, where salutaridine was identified as the main alkaloid. Salutaridine was detected as a minor constituent of the rhizomes of only one of the samples. Alkaloids appear to be quite variable within different plant parts and different provenances of A. angustifolia, a fact that may explain the apparent absence of salutaridine in our samples. [Copyright &y& Elsevier]

The phytochemical study of Nectandra cuspidata led to the isolation and characterization of the new megastigmane 7-megastigmen-3β,6β,9ξ-triol ( 1 ), the aporphinoid alkaloids (−)-glaziovine ( 2 ) and (+)-apoglaziovine ( 3 ), the sesquiterpene costic acid ( 4 ), polyprenols ( 5 , 6 and 8 ), α-tocopherol ( 7 ) and the steroid β-sitosterol ( 9 ). The structures of the compounds were elucidated based on spectroscopic data. This is the first description of the presence of megastigmanes in Nectandra genus. All compounds ( 1-9 ) were isolated for the first time from this species. The chemotaxonomic significance of these compounds was also summarized. [ABSTRACT FROM AUTHOR]

The pharmacokinetic parameters of Glaziovine, a pro-aporphine alkaloid with neuropharmacological properties, were investigated in healthy human volunteers. Glaziovine-C 20 mg was administered in capsules (oral route) and in vials (i.v. route). Total radioactivity was measured in plasma, urine and faeces. When administered orally, peak plasma levels were encountered at 2 h. The cumulative urinary excretion of total radioactivity over a 24 h period was 38% after oral and 50% after i.v. administration. Investigation of metabolites in urine revealed Glaziovine glucuronide as the sole metabolite of the drug. By comparing the percentage of urinary excretion or the area under the plasma level-time curve (AUC) obtained in the first 24 hours after i.v. and oral administration, enteral absorption was found to range from 78 to 84%. Thus, glaziovine appears to show very high enteral absorption. [ABSTRACT FROM AUTHOR]

Introduction: The Unonopsis genus is a promising source of aporphinoid alkaloids, substances with great biological potential. These alkaloids have a well-defined mass spectrometry fragmentation pattern that, together with previous phytochemical knowledge, can guide the isolation of alkaloids not yet described for the genus., Objective: Isolate substances not yet described in the Unonopsis genus, guided by alkaloidal profile analyses of stem barks, twigs and leaves of Unonopsis duckei using electrospray ionisation ion-trap tandem mass spectrometry (ESI-IT/MS(n) )., Methods: Methanolic extracts from stem barks, twigs and leaves were submitted to a liquid-liquid, acid-base partitioning treatment to obtain the alkaloidal fractions. These fractions were analysed by direct infusion into an ESI-IT/MS(n) system. The major alkaloids observed for each fraction were submitted to fragmentation analysis., Results: The MS fragmentation patterns revealed the presence of alkaloids previously reported for Annonaceae, including nornuciferine, anonaine, asimilobine, liriodenine and lysicamine, known for the Unonopsis genus, as well as others that were not yet described for this genus. In this way, the proaporphine alkaloid glaziovine was isolated, as well as a mixture of the aporphine alkaloids glaucine and norglaucine, all described for the first time in the Unonopsis genus., Conclusion: Mass spectrometry monitoring was fundamental to prioritise the isolation of substances not yet identified for the Unonopsis genus, dismissing known compounds and simplifying the phytochemical study., (Copyright © 2013 John Wiley & Sons, Ltd.)