Actinodaphnine

Pharmacological properties and their medicinal uses of Cinnamomum: a review.[Pubmed:31646653]

J Pharm Pharmacol. 2019 Dec;71(12):1735-1761.

OBJECTIVES: Cinnamomum (Family Lauraceae) is traditionally used for flavouring food and in pharmaceutical preparations against various ailments. Detailed literature on the ethnobotanical and pharmacological properties of Cinnamomum is segregated and not present in well-documented form. In the present review, we have been trying to gather its detailed medicinal as well as pharmacological properties. The ethnobotanical and pharmacological properties of Cinnamomum were collected by searching several scientific databases, that is PubMed, Elsevier, Google Scholar, Science Direct and Scopus. KEY FINDINGS: The plant extracts have been reported to possess astringent, warming stimulant, carminative, blood purifier, digestive, antiseptic, antifungal, antiviral, antibacterial, antioxidant, anti-inflammatory and immunomodulatory properties and also help to reduce cholesterol and blood sugar levels. A wide range of phytochemical compounds including aldehydes, acetate, alcohol, terpinenes, flavonoids, alkaloids, anthraquinones, coumarins, phenols, saponins, tannins, carboxylic acid, hydrocarbons, camphene, spathulenol, fatty acids, Actinodaphnine, butanolides, lignans, steroids, propenoids and kaempferol glycosides are found in various parts of plant. SUMMARY: This review provides detailed information about history, traditional uses, phytochemistry and clinical impacts of cinnamon as a spice and medicine. So we recommend further study on the clinical, medicinal, purification and identification of the most effective antibacterial activity of cinnamon to cure various infectious diseases.

Improving the acetylcholinesterase inhibitory effect of Illigera aromatica by fermentation with Clonostachys rogersoniana.[Pubmed:31178168]

J Biosci Bioeng. 2019 Nov;128(5):525-528.

Illigera aromatica was fermented by Clonostachys rogersoniana. The acetylcholinesterase (AChE) inhibitory effects of unfermented and fermented I. aromatica revealed that C. rogersoniana-fermented I. aromatica (CFIA) induced significantly more AChE inhibitory activity (IC50: 35.4 +/- 2.1 mug/mL). The biotransformation of Actinodaphnine (1) into (4R,6aS)-4-hydroxyActinodaphnine (2) was found during the fermentation, which played an important role in the improvement of the AChE inhibitory activity of I. aromatica. Subsequently, the fermentation conditions-including the solid-liquid ratio, fermentation temperature, and fermentation time-were optimized. I. aromatica immersed in 100-200% water and fermented with C. rogersoniana at ambient temperature for 30 days was conducive to the biotransformation of Actinodaphnine (1) and improved the AChE inhibitory activity of I. aromatica. The present study provides a novel approach for improving the pharmacological effect of I. aromatica and suggests that CFIA may be used as an alternative AChE inhibitor.

Anti-inflammatory monoterpene esters from the stems of Illigera aromatica.[Pubmed:31135220]

Nat Prod Res. 2019 May 28:1-7.

Two new monoterpene esters illigerates F and G (1 and 2) together with 5 know compounds illigerate A (3), illigerate C (4), Actinodaphnine (5), N-methylActinodaphnine(6) and N-methyllaurotetanine(7) were isolated from Illigera aromatica S. Z. Huang et S. L. Mo. Their structures were identified by extensive NMR data and by comparing with the known compounds. The anti-inflammatory activity of four monoterpenes (1 - 4) was evaluated by inhibiting nitric oxide (NO) production in lipopolysaccharide-activated murine macrophage RAW 264.7 cells and four monoterpenoids exhibited inhibitory effect with IC50 values of 71.5 +/- 7.3, 74.7 +/- 5.6, 48.0 +/- 7.4 and 65.1 +/- 3.7 muM, respectively.

(-)-Grandiflorimine, a new dibenzopyrrocoline alkaloid with cholinesterase inhibitory activity from Illigera grandiflora.[Pubmed:31079474]

Nat Prod Res. 2019 May 10:1-7.

A new dibenzopyrrocoline alkaloid, (-)-grandifloramine (1), together with five known ones, Actinodaphnine (2), N-methyllaurotetanine (3), boldine (4), lindcarpine (5), and (+)-norboldine (6), were isolated from Illigera grandiflora W. W. Sm. et J. F. Jeff. The structure of 1 was identified by HRESIMS, 1D/2D NMR, and electronic circular dichroism (ECD) spectra. Compound 1 and 2 exhibited the moderate inhibitory activity against acetylcholinesterase and 3 showed moderate butyrylcholinesterase inhibitory activity. This is the first report of the chemical constituents of I. grandiflora.

Application of a proton quantitative nuclear magnetic resonance spectroscopy method for the determination of actinodaphnine in Illigera aromatica and Illigera henryi.[Pubmed:30414014]

J Nat Med. 2019 Jan;73(1):312-317.

Illigera aromatica S. Z. Huang et S. L. Mo and Illigera henryi W. W. Sm., belonging to the genus Illigera (Hernandiaceae), are used as herbal medicines for promoting blood circulation and treating tuberculosis. Actinodaphnine, the major bioactive alkaloid, plays an important role in the quality controls of the herbs. In the present study, a rapid, simple, accurate, and precise proton quantitative nuclear magnetic resonance ((1)H-qNMR) method was developed to determine the content of Actinodaphnine in I. aromatica and I. henryi. DMSO-d6 enabled satisfactory separation of the signals to be integrated in (1)H NMR spectrum. 1,4-Dinitrobenzene was selected as an internal standard. The limits of determination and quantitation were 0.005 and 0.038 mg/mL, respectively. This work implied that (1)H-qNMR represents a feasible alternative to HPLC-based methods for quantitation of Actinodaphnine in I. aromatica and I. henryi and is suitable for the quality control of I. aromatica and I. henryi.

Hypoglycemic Efficacy of Docking Selected Natural Compounds against alpha-Glucosidase and alpha-Amylase.[Pubmed:30189596]

Molecules. 2018 Sep 5;23(9). pii: molecules23092260.

The inhibition of alpha-glucosidase and alpha-amylase is a clinical strategy for the treatment of type II diabetes, and herbal medicines have been reported to credibly alleviate hyperglycemia. Our previous study has reported some constituents from plant or herbal sources targeted to alpha-glucosidase and alpha-amylase via molecular docking and enzymatic measurement, but the hypoglycemic potencies in cell system and mice have not been validated yet. This study was aimed to elucidate the hypoglycemic efficacy of docking selected compounds in cell assay and oral glucose and starch tolerance tests of mice. All test compounds showed the inhibition of alpha-glucosidase activity in Caco-2 cells. The decrease of blood sugar levels of test compounds in 30 min and 60 min of mice after OGTT and OSTT, respectively and the decreased glucose levels of test compounds were significantly varied in acarbose. Taken altogether, in vitro and in vivo experiments suggest that selected natural compounds (curcumin, antroquinonol, HCD, docosanol, tetracosanol, rutin, and Actinodaphnine) via molecular docking were confirmed as potential candidates of alpha-glucosidase and alpha-amylase inhibitors for treating diabetes.

Improving the acetylcholinesterase inhibitory effect of Illigera henryi by solid-state fermentation with Clonostachys rogersoniana.[Pubmed:28619612]

J Biosci Bioeng. 2017 Nov;124(5):493-497.

Illigera henryi, an endemic traditional Chinese medicine, contains abundant aporphine alkaloids that possess various bioactivities. In the present study, tubers of I. henryi were fermented by several fungi, and the acetylcholinesterase (AChE) inhibitory activities of non-fermented and fermented I. henryi were measured. The results showed that the fermentation of I. henryi with Clonostachys rogersoniana 828H2 is effective for improving the AChE inhibitory activity. A key biotransformation was found during the C. rogersoniana fermentation for clarifying the improvement of the AChE inhibitory activity of I. henryi: (S)-Actinodaphnine (1) was converted to a new 4-hydroxyaporphine alkaloid (4R,6aS)-4-hydroxyActinodaphnine (2) that possessed a stronger AChE inhibitory activity, with an IC50 value of 17.66+/-0.06 muM. This paper is the first to report that the pure strain fermentation processing of I. henryi and indicated C. rogersoniana fermentation might be a potential processing method for I. henryi.

Monoterpene esters and aporphine alkaloids from Illigera aromatica with inhibitory effects against cholinesterase and NO production in LPS-stimulated RAW264.7 macrophages.[Pubmed:27848145]

Arch Pharm Res. 2017 Dec;40(12):1394-1402.

Three new monoterpene phenylpropionic acid esters, illigerates A-C (1-3), and one new aporphine alkaloid, illigeranine (4), as well as four known ones, Actinodaphnine (5), nordicentrine (6), 8-hydroxy carvacrol (7), and 3-hydroxy-alpha,4-dimethyl styrene (8), were isolated from the tubers of Illigera aromatica. The structures of 1-4 were identified by HRESIMS, 1D and 2D NMR, and electronic circular dichroism spectra. Compound 1 potently inhibited NO production in LPS-stimulated RAW264.7 cells with an IC50 value of 18.71 +/- 0.85 muM; compound 1, 3, and 4 showed moderate butyrylcholinesterase inhibitory activities with the IC50 values of 46.86 +/- 0.65, 53.51 +/- 0.71, and 31.62 +/- 1.15 muM, respectively. Compound 4 showed weak AChE inhibitory activity with an IC50 value of 81.69 +/- 2.07 muM, and compounds 5 and 6 possessed moderate AChE inhibitory activities with the IC50 values of 47.74 +/- 1.66 and 40.28 +/- 2.73 muM, respectively. This paper provides a chemical structure and bioactive foundation for using I. aromatica as an herbal medicine.

Anti-Acetylcholinesterase Alkaloids from Annona glabra Leaf.[Pubmed:26197510]

Nat Prod Commun. 2015 Jun;10(6):891-3.

Bioassay guided fractionation and separation of the EtOH extract of Annona glabra leaf against acetylcholinesterse led to the characterization of 15 alkaloids. Among them, (-)-Actinodaphnine (2) and (-)-(6aS,7R)-7-hydroxyActinodaphnine (9) are new aporphines, although (+)-2 and (+/-)-2 have been found in several plants. Their structures were established by spectroscopic analysis. (-)-Anolobine (5) and (-)-roemeroline (8) showed moderate inhibitory activity against eel acetylcholinesterase with IC50 values of 22.4 and 26.3 muM, respectively.

Screening alpha-glucosidase and alpha-amylase inhibitors from natural compounds by molecular docking in silico.[Pubmed:26154585]

Biofactors. 2015 Jul-Aug;41(4):242-51.

The alpha-glucosidase inhibitor is a common oral anti-diabetic drug used for controlling carbohydrates normally converted into simple sugars and absorbed by the intestines. However, some adverse clinical effects have been observed. The present study seeks an alternative drug that can regulate the hyperglycemia by down-regulating alpha-glucosidase and alpha-amylase activity by molecular docking approach to screen the hyperglycemia antagonist against alpha-glucosidase and alpha-amylase activities from the 47 natural compounds. The docking data showed that Curcumin, 16-hydroxy-cleroda-3,13-dine-16,15-olide (16-H), Docosanol, Tetracosanol, Antroquinonol, Berberine, Catechin, Quercetin, Actinodaphnine, and Rutin from 47 natural compounds had binding ability towards alpha-amylase and alpha-glucosidase as well. Curcumin had a better biding ability of alpha-amylase than the other natural compounds. Analyzed alpha-glucosidase activity reveals natural compound inhibitors (below 0.5 mM) are Curcumin, Actinodaphnine, 16-H, Quercetin, Berberine, and Catechin when compared to the commercial drug Acarbose (3 mM). A natural compound with alpha-amylase inhibitors (below 0.5 mM) includes Curcumin, Berberine, Docosanol, 16-H, Actinodaphnine/Tetracosanol, Catechin, and Quercetin when compared to Acarbose (1 mM). When taken together, the implication is that molecular docking is a fast and effective way to screen alpha-glucosidase and alpha-amylase inhibitors as lead compounds of natural sources isolated from medicinal plants.

Lancifoliaine, a new bisbenzylisoquinoline from the bark of Litsea lancifolia.[Pubmed:21490559]

Molecules. 2011 Apr 13;16(4):3119-27.

A new bisbenzylisoquinoline, lancifoliaine (1), together with seven known alkaloids--N-allyllaurolitsine (2), reticuline (3), Actinodaphnine, norboldine, pallidine, cassythicine and boldine--were isolated from the stem bark of Litsea lancifolia (Lauraceae). In addition to that of lancifoliaine, complete (1)(3)C-NMR data of N-allyl-laurolitsine (2) was also reported. The alkaloidal structures were elucidated by means of high field 1D- and 2D-NMR IR, UV, and LCMS-IT-TOF spectral data. N-Allyllaurolitsine (2) showed a moderate vasorelaxant activity on isolated rat aorta.

Actinodaphnine induces apoptosis through increased nitric oxide, reactive oxygen species and down-regulation of NF-kappaB signaling in human hepatoma Mahlavu cells.[Pubmed:16168547]

Food Chem Toxicol. 2006 Mar;44(3):344-54.

Actinodaphnine, extracted from Cinnamomum insularimontanum (Lauraceae), possesses cytotoxicity in some cancers, but the mechanism by which Actinodaphnine induces apoptosis in human hepatoma cells remains poorly understood. In this study, we investigated the mechanisms of apoptosis induced by Actinodaphnine in human hepatoma Mahlavu cells. Treatment with Actinodaphnine dose-dependently induced apoptosis in Mahlavu cells that correlated with increased intracellular nitric oxide (NO) and reactive oxygen species (ROS), disruptive mitochondrial transmembrane potential (DeltaPsi(m)), and activation of caspase 3/7. Our data also demonstrated that Actinodaphnine down-regulated activity of nuclear factor kappaB (NF-kappaB). The apoptotic response to Actinodaphnine was markedly decreased in Mahlavu cells pretreated with dexsamethasone, a NO inhibitor, N-acetylcysteine (NAC), an antioxidant, and Boc-Asp(OMe)-fmk, a broad caspases inhibitor. These results suggested that Actinodaphnine-induced apoptosis is initially mediated through the NO and/or ROS increase and caspases-dependent pathway. In conclusion, our results indicate that an increase of ROS and/or NO is the initial essential event that results in the decrease of DeltaPsi(m) and the activation of caspases that commits the cells to the apoptotic pathway in Actinodaphnine-treated hepatoma Mahlavu cells.

Alkaloids from Cassytha filiformis and related aporphines: antitrypanosomal activity, cytotoxicity, and interaction with DNA and topoisomerases.[Pubmed:15124084]

Planta Med. 2004 May;70(5):407-13.

Cassytha filiformis (Lauraceae), a widely distributed parasitic plant, contains several aporphine alkaloids and is often used in African folk medicine to treat cancer, African trypanosomiasis and other diseases. In a previous investigation, we showed that the alkaloid plant extract and the isolated aporphines possessed in vitro cytotoxic properties. In this paper, we evaluated the in vitro activity of the alkaloid extract (IC50 = 2.2 microg/mL) and its three major aporphine alkaloids (Actinodaphnine, cassythine, and dicentrine) on Trypanosoma brucei brucei as well as four related commercially available aporphines (bulbocapnine, glaucine, isocorydine, boldine). Only the three alkaloids from Cassytha filiformis were active on the trypanosomes in vitro (IC50 = 3-15 microM). Additionally, we compared the cytotoxicity of these seven compounds on HeLa cells. Glaucine was the most cytotoxic compound on HeLa cells (IC50 = 8.2 microM) in the series. In order to elucidate their mechanism of action, the binding mode of these molecules to DNA was studied by UV absorption, circular and linear dichroism spectroscopy. The results of the optical measurements indicated that all seven aporphines effectively bind to DNA and behave as typical intercalating agents. Biochemical experiments showed that Actinodaphnine, cassythine and dicentrine also interfere with the catalytic activity of topoisomerases in contrast to the four other aporphines. These interactions with DNA may explain, at least in part, the effects observed on cancer cells and on trypanosomes.

Cytotoxic aporphine alkaloids from Cassytha filiformis.[Pubmed:12451500]

Planta Med. 2002 Nov;68(11):1042-4.

Purification of a cytotoxic crude alkaloid extract of Cassytha filiformis led to the isolation of four known aporphine alkaloids: neolitsine, dicentrine, cassythine (= cassyfiline) and Actinodaphnine. Their structures were determined by analysis of spectroscopic data. All isolated alkaloids were tested for their cytotoxic activities on cancer and non-cancer cell lines in vitro. Neolitsine was the most active against HeLa and 3T3 cells (IC 50 :21.6 microM, and 21.4 microM, respectively). Cassythine and Actinodaphnine showed the highest activity against Mel-5 (IC 50 : 24.3 microM and 25.7 microM, respectively) and HL-60 (IC 50 : 19.9 microM and 15.4 microM, respectively). This is the first report on the cytotoxic activity of C. filiformis extract and of neolitsine and cassythine. Furthermore, the complete NMR data of cassythine and Actinodaphnine are given here for the first time.

Chemical constituents from Cassytha filiformis II.[Pubmed:9677264]

J Nat Prod. 1998 Jul;61(7):863-6.

Using a bioassay-directed fractionation method, three new compounds, including an aporphine alkaloid, cassyformine (4); an oxoaporphine alkaloid, filiformine (8), and a lignan, (+)-diasyringaresinol (10), along with 14 known compounds, were further isolated and characterized from the MeOH extract of the fresh herbs of Cassytha filiformis. Among the isolates of this plant, cathafiline (1), cathaformine (2), Actinodaphnine (3), N-methylActinodaphnine (5), predicentrine (6), and ocoteine (7) exhibited significant antiplatelet aggregation activity.