Antiplatelet and Anticoagulant Effects of Two New Phenylpropanoid Sucrose Esters and Other Secondary Metabolites from the Aerial Part of Canna edulis.

This study isolated pure compounds from Canna edulis aerial parts and assessed their antiplatelet and anticoagulant potential. Structural elucidation resulted in the identification of two new compounds: caneduloside A (1) and caneduloside B (2), and eleven known compounds: 6'-acetyl-3,6,2'-tri-p-coumaroyl sucrose (3), 6'-acetyl-3,6,2'-triferuloyl sucrose (4), tiliroside (5), afzelin (6), quercitrin (7), 2-hydroxycinnamaldehyde (8), cinnamic acid (9), 3,4-dimethoxycinnamic acid (10), dehydrovomifoliol (11), 4-hydroxy-3,5-dimethoxybenzaldehyde (12), and (S)-(-)-rosmarinic acid (13). Compounds 3, 4, 6-9, 13 were previously reported for antithrombotic properties. Hence, antithrombotic tests were conducted for 1, 2, 5, 10-12. All tested compounds demonstrated a dose-dependent antiaggregatory effect, and 10 and 12 were the most potent for both ADP and collagen activators. Additionally, 10 and 12 showed anticoagulant effects, with prolonged prothrombin time and activated partial thromboplastin time. The new compound 1 displayed antiplatelet and anticoagulant activity, while 2 mildly inhibited platelet aggregation. C. edulis is a potential source for developing antithrombotic agents.

Potential antithrombotic effect of two new phenylpropanoid sucrose esters and other secondary metabolites of Canna indica L. rhizome.

Canna indica L. has been traditionally used to treat various diseases. Based on previously reported antithrombotic effect for this plant, two new phenylpropanoid sucrose esters (canindicoside A (1) and canindicoside B (2)) and seven known compounds: nepetoidin B (3), caffeic acid (4), ferulic acid (5), (R)-(+)-rosmarinic acid (6), isorinic acid (7), (S)-(-)-rosmarinic acid (8) and (S)-(-)-rosmarinic acid methyl ester (9) were isolated from the ethyl acetate extract. Compounds were elucidated by NMR and MS spectroscopic methods. The antiplatelet effect was evaluated using turbidimetric method. Anticoagulant activity was examined by measuring activated partial thromboplastine time (APTT), prothrombin time, and thrombine time (TT). It was shown for the first time that both new phenylpropanoid sucrose esters 1 and 2, 7 and 9 displayed dose-dependent antiplatelet effects. 2 and 9 had the highest inhibitory activity on both adenosine diphosphate (ADP)- and collagen-induced platelet aggregation. Moreover, 1, 7 and 9 also exhibited anticoagulant activity. At 0.4 mg/mL, both 1 and 7 prolonged APTT compared to the negative control (p < 0.05), suggesting the possible inhibitory impact on the intrinsic coagulation pathway. Moreover, 9 at 0.4 mg/mL exerted higher TT values than the negative control (p < 0.05). C. indica and its bioactive phytochemicals are potential candidates for development of anti-thrombosis therapy.

Data on antiplatelet aggregation, anticoagulation and antioxidant activities of Canna edulis Ker rhizome and its secondary metabolites.

Canna edulis Ker rhizome has been used in Traditional Vietnamese Medicine to prevent and treat heart diseases without thorough scientific evidence. The data presented in this article characterize the antiplatelet aggregation, anticoagulant and antioxidant activity of C. edulis rhizome extracts and the bio-guided isolation of bioactive compounds from the active fraction. The data on tested bioactivities of isolated compounds were also provided. The inhibitory effect on adenosine diphosphate- and collagen-induced human platelet aggregation was evaluated through three parameters: percentage inhibition of platelet aggregation, aggregation velocity and area under the platelet aggregation curve. Prothrombin time, activated partial thromboplastine time and thrombine time were measured to examine the anticoagulant activity. The free radical scavenging ability was assessed with DPPH and ABTS assays. The structures of compounds were elucidated by NMR and MS spectroscopic methods. The data showed that the ethyl acetate fraction showed the most potent antiplatelet aggregation, anticoagulant and antioxidant activity. Seven known compounds: 5-hydroxy-6-methyl-2H-pyran-2-one (1), epimedokoreanone A (2), nepetoidin B (3), ferulic acid (4), caffeic acid (5), hydroxytyrosol (6), and 1H-indole-3-carboxaldehyde (7) were isolated from this active fraction. Moreover, this article provided experimental data on antiplatelet effect of epimedokoreanone A (2) and nepetoidine B (3), anticoagulant and antioxidant activity of epimedokoreanone A (2) and also antiplatelet and antioxidant activity of 5-hydroxy-6-methyl-2H-pyran-2-one (1).

Inhibitory effect on human platelet aggregation and coagulation and antioxidant activity of C. edulis Ker Gawl rhizome and its secondary metabolites.

ETHNOPHARMACOLOGICAL RELEVANCE: Although Canna edulis Ker Gawl rhizome has been used in Traditional Vietnamese Medicine to prevent and treat heart diseases without thorough scientific evidence, limited intensive search for the bioactivities and useful substances has been done. AIM OF THE STUDY: This study aims to investigate the antiplatelet aggregation, anticoagulant and antioxidant activity of extracts from C. edulis rhizome, separate and purify its compounds from the most active fraction and evaluate the antiplatelet aggregation, anticoagulant and antioxidant activity of isolated compounds. MATERIALS AND METHODS: C. edulis rhizome was extracted with ethanol, then fractionated with n-hexane, ethyl acetate and water. The inhibitory effect on adenosine diphosphate- and collagen-induced human platelet aggregation was evaluated. Prothrombin time, activated partial thromboplastine time and thrombine time were measured to examine the anticoagulant activity. The free radical scavenging ability was assessed with DPPH and ABTS assays. The fraction that showed the most active was used to separate and purify compounds. The structures of compounds were elucidated by NMR and MS spectroscopic methods. Isolated compounds were also tested for antiplatelet, anticoagulant and antioxidant activity. RESULTS: The ethyl acetate fraction showed the most potent antiplatelet aggregation, anticoagulant and antioxidant activity. Subsequent fractionation of this active fraction resulted in the isolation of seven known compounds: 5-hydroxy-6-methyl-2H-pyran-2-one (1), epimedokoreanone A (2), nepetoidin B (3), ferulic acid (4), caffeic acid (5), hydroxytyrosol (6), and 1H-indole-3-carboxaldehyde (7). Previous studies reported the antiplatelet, anticoagulant and antioxidant activity of ferulic acid (4), caffeic acid (5) and hydroxytyrosol (6) and the antioxidant activity of nepetoidin B (3). This study demonstrated that both epimedokoreanone A (2) and nepetoidine B (3) also exhibited good antiplatelet effect and epimedokoreanone A (2) also had effective anticoagulant and antioxidant activity, while 5-hydroxy-6-methyl-2H-pyran-2-one (1) showed weaker antiplatelet and antioxidant activity but no anticoagulant effect. CONCLUSIONS: This is the first experimental study to demonstrate the potent dose-dependent antiplatelet aggregation, anticoagulant and antioxidant activity of C. edulis rhizome and its pure compounds, supporting the traditional use of this plant for the treatment of heart diseases. The C. edulis rhizome is a potential source of bioactive compounds or functional food for treatment and/or prevention of heart- and oxidative stress-related diseases and its bioactive compounds are good candidates for drug development of anti-thrombosis and antioxidant agents.

Synthesis and biological evaluation of oseltamivir analogues from shikimic acid.

New oseltamivir analogues were designed and synthesized, starting from shikimic acid. Biological evaluation against three human cancer cell lines (KB, MCF7 and Lu-1) showed that many of them exhibited cytotoxic activity. Azides 5 are more active than the corresponding amines 6. Thus, the reduction of the azide group into amine led to the loss of cytotoxicity. The compounds with a cyclohexanemethyloxy group at C-3 were more active than the other investigated compounds belonging to the same series. This cyclohexanemethyloxy group seems to be critical for the cytotoxic activity of this class of compounds. The synthetic oseltamivir analogues 6a-e had no inhibition activity, even at the concentration of 50 microM when they were evaluated for their in vitro influenza A neuraminidase inhibitory activity by an enzymatic assay.