On the Inhibitability of Natural Products Isolated from Tetradium ruticarpum towards Tyrosine Phosphatase 1B (PTP1B) and α-Glucosidase (3W37): An In Vitro and In Silico Study.

Folk experiences suggest natural products in Tetradium ruticarpum can be effective inhibitors towards diabetes-related enzymes. The compounds were experimentally isolated, structurally elucidated, and tested in vitro for their inhibition effects on tyrosine phosphatase 1B (PTP1B) and α-glucosidase (3W37). Density functional theory and molecular docking techniques were utilized as computational methods to predict the stability of the ligands and simulate interaction between the studied inhibitory agents and the targeted proteins. Structural elucidation identifies two natural products: 2-heptyl-1-methylquinolin-4-one (1) and 3-[4-(4-methylhydroxy-2-butenyloxy)-phenyl]-2-propenol (2). In vitro study shows that the compounds (1 and 2) possess high potentiality for the inhibition of PTP1B (IC50 values of 24.3 ± 0.8, and 47.7 ± 1.1 µM) and α-glucosidase (IC50 values of 92.1 ± 0.8, and 167.4 ± 0.4 µM). DS values and the number of interactions obtained from docking simulation highly correlate with the experimental results yielded. Furthermore, in-depth analyses of the structure-activity relationship suggest significant contributions of amino acids Arg254 and Arg676 to the conformational distortion of PTP1B and 3W37 structures overall, thus leading to the deterioration of their enzymatic activity observed in assay-based experiments. This study encourages further investigations either to develop appropriate alternatives for diabetes treatment or to verify the role of amino acids Arg254 and Arg676.

PTP1B and α-glucosidase inhibitors from Selaginella rolandi-principis and their glucose uptake stimulation.

As part of an ongoing search for new protein tyrosine phosphatase 1B inhibitors and glucose uptake stimulators from nature, a new coumarin, selaginolide A (1) and four known isoflavones (2‒5) were isolated from the ethanol extract of a Vietnamese medicinal plant Selaginella rolandi-principis. The chemical structures of the isolates were elucidated by extensive analysis of spectroscopic and physicochemical data. Compounds 3‒5 have been identified from Selaginella genus for the first time. The antidiabetic properties of the isolates (1‒5) were investigated using in vitro assay on 2-NBDG uptake in 3T3-L1 adipocytes and against PTP1B and α-glucosidase enzyme activities as well. Compounds 1 exhibited the most potency with inhibitory IC50 values of 7.40 ± 0.28 and 7.52 ± 0.37 µM against PTP1B and α-glucosidase, respectively. Compounds 3 and 5 possessed potential inhibitions on PTP1B enzyme with IC50 values of 23.02 ± 1.29 and 11.08 ± 0.92 µM and moderate inhibitions on α-glucosidase with IC50 values of 36.47 ± 1.87 and 55.73 ± 2.58 µM, respectively. Compounds 2 and 4 showed weak PTP1B inhibitory activity (IC50 > 30 µM) but displayed remarkable α-glucosidase inhibition with IC50 values of 3.39 ± 0.87 and 9.72 ± 0.62 µM, respectively. Furthermore, ursolic acid as a positive control (IC50 3.42 ± 0.26 µM) and compounds 1 and 5 acted as mixed-competitive inhibitors against PTP1B enzyme with Ki values of 6.46, 10.28, and 15.01 µM, respectively. In addition, compounds 1 and 5 also showed potent stimulatory effects on 2-NBDG uptake at a concentration of 10 µM. The obtained result might suggest the potential of new coumarin (1) as a new type of natural PTP1B and α-glucosidase inhibitor for further research and development of antidiabetic and obese agents.Graphic abstract.

Cytotoxic components from the leaves of Erythrophleum fordii induce human acute leukemia cell apoptosis through caspase 3 activation and PARP cleavage.

Cassaine diterpenoids as erythrofordins A-C (1-3), pseudo-erythrosuamin (4), and erythrofordin U (5) isolated from the leaves of Vietnamese Erythrophleum fordii Oliver were tested cytotoxic activity against human leukemia cancer cells. The results showed that these metabolites exhibited dose-dependent cytotoxicity against human leukemia HL-60 and KG cells with IC50 values ranging from 15.2 ± 1.5 to 42.2 ± 3.6 µM. Treatment with erythrofordin B led to the apoptosis of HL-60 and KG cells due to the activation of caspase 3, caspase 9, and poly (ADP-ribose) polymerase (PARP). Erythrofordin B significantly increased Bak protein expression, but downregulated the anti-apoptotic protein Bcl-2, in HL-60 cells. In silico results demonstrated that erythrofordin B can bind to both the procaspase-3 allosteric site and the PARP-1 active site, with binding energies of -7.36 and -10.76 kcal/mol, respectively. These results indicated that the leaves of Vietnamese E. fordii, which contain cassaine diterpenoids, can induce the apoptosis of human leukemia cancer cells.

Antioxidant and Cell Proliferation Properties of the Vietnamese Traditional Medicinal Plant Peltophorum pterocarpum.

Peltophorum pterocarpum is regarded as one of the most important medicinal plants in the traditional medicine system of Vietnam. However, scientific evidence for the antioxidant effects against lipid peroxidation and the potential effects in cancer of this plant are lacking. In our experiments, 70% ethanolic extracts of P. pterocarpum leaves (LPP) and stem bark (SPP) were evaluated for their low-density lipoprotein (LDL) oxidation and cytotoxic activity against cancer cell lines. Both LPP and SPP inhibited Cu2+-mediated LDL by increasing the lag time of conjugated diene formation and inhibiting the generation of thiobarbituric acid reactive substances (TBARS) in a dose-dependent manner. In cancer cells, LPP and SPP triggered the most potent cytotoxic effects against human leukemia cells, CRF-SBA and HL-60, with half-maximal inhibitory concentration (IC50) values ranging from 118.5 to 157.2 µg/mL. SPP exhibited significant cytotoxicity against MIA PACA2, A549, and KG cell lines with IC50 values of 167.5, 244.1 and 255.0 µg/mL, respectively. Meanwhile, LPP showed cytotoxic activity against KG with an IC50 value of 228.1 µg/mL. SPP mediated cytotoxicity in HL-60 and CCRF-SBA cells through the activation of the apoptosis pathway, including the activation of caspases 3, and 9 and poly (ADP-ribose) polymerase (PARP). These results suggested that SPP may prevent the development and progression of atherosclerosis and leukemia in humans.

Cassaine Diterpenoid Amide from Stem Bark of Erythrophleum fordii Suppresses Cytotoxic and Induces Apoptosis of Human Leukemia Cells.

Cassaine diterpenoids amides from the stem bark of Vietnamese Erythrophleum fordii Oliver were screened for their cytotoxic activity against human cancer cells. The cell proliferation assay results showed that, among the active compounds, 3ß-acetyl-nor-erythrophlamide (3AEP) exhibited the most potential cytotoxicity against human leukemia HL-60 and KG cells with IC50 values of 12.0 ± 1.2 and 18.1 ± 2.7 µM, respectively. Treatment of 3AEP resulted in the apoptosis of HL-60 cells via the activation of caspase 3, and poly (ADP-ribose) polymerase (PARP). Molecular docking in silico results showed that the 3AEP can bind to both the procaspase-3 allosteric site and the PARP-1 active site, with binding energies of -7.51 and -9.63 kcal/mol respectively. These results indicated that the stem bark of Vietnamese E. fordii and its cassaine diterpenoid amides may be useful in the apoptosis induction of human leukemia cancer cells.

Inhibitory Effect of Selaginellins from Selaginella tamariscina (Beauv.) Spring against Cytochrome P450 and Uridine 5'-Diphosphoglucuronosyltransferase Isoforms on Human Liver Microsomes.

Selaginella tamariscina (Beauv.) has been used for traditional herbal medicine for treatment of cancer, hepatitis, and diabetes in the Orient. Numerous bioactive compounds including alkaloids, flavonoids, lignans, and selaginellins have been identified in this medicinal plant. Among them, selaginellins having a quinone methide unit and an alkylphenol moiety have been known to possess anticancer, antidiabetic, and neuroprotective activity. Although there have been studies on the biological activities of selaginellins, their modulatory potential of cytochrome P450 (P450) and uridine 5'-diphosphoglucuronosyltransferase (UGT) activities have not been previously evaluated. In this study, we investigated the drug interaction potential of two selaginellins on ten P450 isoforms (CYP1A2, 2A6, 2B6, 2C8, 2C9, 2C19, 2D6, 2E1, 2J2 and 3A) and six UGT isoforms (UGT1A1, 1A3, 1A4, 1A6, 1A9 and 2B7) using human liver microsomes and liquid chromatography-tandem mass spectrometry. Selaginellin and selaginellin M had high inhibitory potential for CYP2C8-mediated amodiaquine O-demethylation with IC50 values of 0.5 and 0.9 µM, respectively. Selaginellin and selaginellin M also showed medium inhibitory potential against CYP2C9, CYP2J2, UGT1A1, and UGT1A3 (1 µM < IC50 < 5 µM). These two selaginellins had low inhibitory potential against CYP1A2, CYP2A6, CYP2E1, and UGT1A6 (IC50 > 25 µM). This information might be helpful to predict possible drug interaction potential of between selaginellins and co-administered drugs.

Anthraquinones from Morinda longissima and their insulin mimetic activities via AMP-activated protein kinase (AMPK) activation.

AMP-activated protein kinase (AMPK) activators are known to increase energy metabolism and to reduce body weight, as well as to improve glucose uptake. During for searching AMPK activators, a new anthraquinone, modasima A (10), along with eighteen known analogues (1-9 and 11-19) were isolated from an ethanol extract of the roots of Morinda longissima Y. Z. Ruan (Rubiaceae). Using the fluorescent tagged glucose analogues, 2-(N-(7-nitrobenz-2-oxa-1,3-diazol-4-yl)amino)-2-deoxy-D-glucose (2-NBDG), insulin mimetics were screened with compounds 1-19 in 3T3-L1 adipocytes. Among them, compounds 2, 8 and 10 enhanced significantly glucose uptake into adipocytes and up-regulated the phosphorylated AMPK (Thr172) whereas the glucose uptake enhancing activities of compounds 2, 8 and 10 were abrogated by treatment of compound C, an AMPK inhibitor. Taken together, these anthraquinones showed the potential action as insulin mimetic to improve glucose uptake via activation of AMPK.

Anti-inflammatory terpenylated coumarins from the leaves of Zanthoxylum schinifolium with α-glucosidase inhibitory activity.

Nine terpenylated coumarins, namely 7-[(E)-3',7'-dimethyl-6'-oxo-2',7'-octadienyl]oxy-coumarin (1), schinilenol (2), schinindiol (3), collinin (4), 7-[(E)-7'-hydroxy-3',7'-dimethy-locta-2',5'-dienyloxy]-coumarin (5), 8-methoxyanisocoumarin (6), 7-(6'R-hydroxy-3',7'-dimethyl-2'E,7'-octadienyloxy)coumarin (7), (E)-4-methyl-6-(coumarin-7'-yloxy)hex-4-enal (8), and aurapten (9), along with a 4-quinolone alkaloid (10) and integrifoliodiol (11), were isolated from the leaves of Zanthoxylum schinifolium. Of the isolates, compounds 4 and 7 potentially inhibited NO production in lipopolysaccharide (LPS)-stimulated macrophage RAW264.7 cells, with IC50 values of 5.9 ± 0.8 and 18.2 ± 1.8 µM, respectively. Furthermore, compounds 4 and 7 dose-dependently reduced the LPS-induced iNOS expression. Moreover, pre-incubation of cells with 4 and 7 significantly suppressed LPS-induced COX-2 protein expression. In addition, compounds 4, 7, 8, and 10 showed strong α-glucosidase inhibitory effects, with IC50 values of 92.1 ± 0.7, 90.6 ± 0.9, 78.2 ± 0.2, and 82.4 ± 0.8 µM, respectively. Compounds 1, 5, and 11 displayed moderate effects with IC50 values of 161.6 ± 0.3, 164.4 ± 1.1, and 155.4 ± 0.9 µM, while acarbose, a positive control, possessed an IC50 value of 121.5 ± 1.0 µM. This is the first investigation on the α-glucosidase inhibitory effect of components from Zanthoxylum schinifolium. Further studies should be made on active compounds.

Protein tyrosine phosphatase 1B (PTP1B) inhibitory activity and glucosidase inhibitory activity of compounds isolated from Agrimonia pilosa.

CONTEXT: Despite phytochemical studies of Agrimonia pilosa Ledeb. (Rosaceae), the antidiabetic effects of this plant are unknown. OBJECTIVE: This study characterizes the isolated compounds from the aerial parts of A. pilosa and evaluates their PTP1B and α-glucosidase inhibitory properties. MATERIALS AND METHODS: Ethanol extract of A. pilosa was found to inhibit 64% PTP1B activity at 30 µg/mL. The ethanol extract was partitioned with methylene chloride, ethyl acetate, n-butanol, and water fractions. Among these, the ethyl acetate fraction displayed the most potent PTP1B activity. The ethyl acetate extract was separated by chromatographic methods to obtain flavonoids and triterpenoids (1-11); which were evaluated for their inhibitory effects on PTP1B activity with p-nitrophenyl phosphate (p-NPP) as a substrate, and also α-glucosidase enzyme. RESULTS: Compounds 1-11 were identified as apigenin-7-O-ß-d-glucuronide-6″-methyl ester, triliroside, quercetin-7-O-ß-d-glycoside, quercetin-3-O-ß-d-glycoside, kaempferol, kaempferol-3-O-α-l-rhamnoside, ß-sitosterol, ursolic acid, tormentic acid, methyl 2-hydroxyl tricosanoate, and palmitic acid. Compounds 8, 9, and 11 displayed inhibitory effects on PTP1B activity with IC50 values of 3.47 ± 0.02, 0.50 ± 0.06, and 0.10 ± 0.03 µM, respectively. Compounds 3, 4, 6, and 9 exhibited inhibition of the α-glucosidase activity with IC50 values of 11.2 ± 0.2, 29.6 ± 0.9, 28.5 ± 0.1, and 23.8 ± 0.4 µM, respectively. DISCUSSION AND CONCLUSION: As major ingredients of A. pilosa, compounds 1, 6, 8, and 9 showed the greatest inhibitory potency on PTP1B activity. Compounds 3, 6, 8, and 9 also showed potent inhibitory effects on α-glucosidase enzyme. This result suggested the potential of these compounds for developing antidiabetic agents.

Chemical Constituents of Euonymus alatus (Thunb.) Sieb. and Their PTP1B and α-Glucosidase Inhibitory Activities.

Phytochemical study on the corks of Euonymus alatus resulted in the isolation of a novel 3-hydroxycoumarinflavanol (23), along with ten triterpenoids (1-10), ten phenolic derivatives (11-20), and two flavonoid glycosides (21 and 22). Their structures were determined by extensive 1D and 2D-nuclear magnetic resonance spectroscopic and mass spectrometry data analysis. Furthermore, their inhibitory effects against the protein tyrosine phosphatases 1B (PTP1B) and α-glucosidase enzyme activity were evaluated. Compounds 6, 7, 9, 15, 19, and 23 were non-competitive inhibitors, exhibiting most potency with IC50 values ranging from 5.6 ± 0.9 to 18.4 ± 0.3 µm, against PTP1B. Compound 3 (competitive), compounds 5 and 15 (mixed-competitive) displayed potent inhibition with IC50 values of 15.1 ± 0.7, 23.6 ± 0.6 and 14.8 ± 0.9 µm, respectively. Moreover, compounds 15, 20, and 23 exhibited potent inhibition on α-glucosidase with IC50 values of 10.5 ± 0.8, 9.5 ± 0.6, and 9.1 ± 0.5 µm, respectively. Thus, these active ingredients may have value as new lead compounds for the development of new antidiabetic agents.

Selaginellin and biflavonoids as protein tyrosine phosphatase 1B inhibitors from Selaginella tamariscina and their glucose uptake stimulatory effects.

As part of an ongoing search for new antidiabetic agents from medicinal plants, the methanol extract of the aerial parts of Selaginella tamariscina was found to possess stimulatory effect on glucose uptake in 3T3-L1 adipocyte cells. Thus, bioassay-guided isolation of this active extract yielded two new compounds (1 and 2) along with five known biflavonoids (3-7). Their structures were elucidated by extensive analysis of spectroscopic and physicochemical data. The absolute configuration of compound 2 was determined by specific rotation and CD data analysis. All isolates exhibited potent inhibitory effects on PTP1B enzyme with IC50 values ranging from 4.5±0.1 to 13.2±0.8µM. Furthermore, the isolates (1-7) showed significant stimulatory effects on 2-NBDG uptake in 3T3-L1 adipocyte cells. Of these, compounds (1, 6, and 7) which exhibited mixed-competitive inhibition modes against PTP1B, showed potent stimulatory effects on 2-NBDG uptake. This result indicated the potential of these biflavonoids as lead molecules for development of antidiabetic agents and the beneficial use of S. tamariscina against hyperglycemia.

Protein tyrosine phosphatase 1B (PTP1B) inhibitory constituents from the aerial parts of Tradescantia spathacea Sw.

Inhibitors of protein tyrosine phosphatase 1B (PTP1B) are promising agents for the treatment of type 2 diabetes and obesity. The bioactivity-guided isolation led to the separation of two new compounds, (±)-tradescantin (13) and tradescantoside (16), along with fourteen known compounds (1-12, 14, and 15) from the aerial parts of Tradescantia spathacea Sw. (Commelinaceae). Their chemical structures were elucidated by spectroscopic methods as well as by comparing with those reported in the literature. The isolated compounds (1-16) were then examined for their inhibitory activity toward PTP1B. The results indicated that compounds 2, 6, 8, and 12 possessed potent inhibition with IC50 values of 7.82±0.79, 6.80±0.89, 4.55±0.92, and 6.38±0.14 µM, respectively. Kinetic study of compounds 2, 6, 8, 12, 13, and 16 was conducted and the structure-activity relationships of the isolated compounds (1-16) were also discussed herein. To the best of our knowledge, all the isolates were separated for the first time from this plant.

Insulin-mimetic selaginellins from Selaginella tamariscina with protein tyrosine phosphatase 1B (PTP1B) inhibitory activity.

As part of an ongoing search for new antidiabetic agents from medicinal plants, three new (2, 4, and 5) and two known selaginellin derivatives (1 and 3) were isolated from a methanol extract of Selaginella tamariscina. The structures of the new compounds were determined by spectroscopic data analysis. All isolates showed strong glucose uptake stimulatory effects in 3T3-L1 adipocyte cells at a concentration of 5 µM. Furthermore, these compounds were found to possess inhibitory effects on PTP1B enzyme activity with IC50 values ranging from 4.6 ± 0.1 to 21.6 ± 1.5 µM. Compound 2 showed the greatest potency, with an IC50 value of 4.6 ± 0.1 µM, when compared with the positive control (ursolic acid, IC50 = 3.5 ± 0.1 µM). Therefore, these selaginellin derivatives may have value as new lead compounds for the development of agents against type 2 diabetes.

Protein tyrosine phosphatase 1B (PTP1B) inhibitors from Morinda citrifolia (Noni) and their insulin mimetic activity.

As part of our ongoing search for new antidiabetic agents from medicinal plants, we found that a methanol extract of Morinda citrifolia showed potential stimulatory effects on glucose uptake in 3T3-L1 adipocyte cells. Bioassay-guided fractionation of this active extract yielded two new lignans (1 and 2) and three new neolignans (9, 10, and 14), as well as 10 known compounds (3-8, 11-13, and 15). The absolute configurations of compounds 9, 10, and 14 were determined by ECD spectra analysis. Compounds 3, 6, 7, and 15 showed inhibitory effects on PTP1B enzyme with IC50 values of 21.86 ± 0.48, 15.01 ± 0.20, 16.82 ± 0.42, and 4.12 ± 0.09 µM, respectively. Furthermore, compounds 3, 6, 7, and 15 showed strong stimulatory effects on 2-NBDG uptake in 3T3-L1 adipocyte cells. This study indicated the potential of compounds 3, 6, 7, and 15 as lead molecules for antidiabetic agents.

New prenylated isoflavonoids as protein tyrosine phosphatase 1B (PTP1B) inhibitors from Erythrina addisoniae.

Bioassay-guided fractionation of the EtOAc extract of the root of Erythrina addisoniae (Leguminosae) resulted in the isolation of four new (1-4), along with 2 known prenylated isoflavonoids (5-6). The structures of the isolates were assigned on the basis of spectroscopic data analysis, focusing on interpretation of 1D and 2D NMR, and MS data. All the isolates were evaluated for their inhibitory effects on protein tyrosine phosphatase 1B (PTP1B), as well as their growth inhibition on MCF7, adriamycin-resistant MCF7 (MCF7/ADR), and MDA-MB-231 breast cancer cell lines. Compounds which exhibited PTP1B inhibitory activity (IC(50) values ranging from 4.6 ± 0.3 to 24.2 ± 2.1 µM) showed potential cytotoxic activity (IC(50) values ranging from 3.97 ± 0.17 to 11.4 ± 1.9 µM). Taken together, our data suggest that prenylated isoflavonoids, especially the isoflavone-type skeleton could be considered as new lead compounds against breast cancer via PTP1B inhibition.

Nectandrin B activates endothelial nitric-oxide synthase phosphorylation in endothelial cells: role of the AMP-activated protein kinase/estrogen receptor α/phosphatidylinositol 3-kinase/Akt pathway.

We revealed previously that nectandrin B isolated from Myristica fragrans (nutmeg, Myristicaceae) functions as a potent AMP-activated protein kinase (AMPK) activator and showed its antiobesity effect. In this study, we investigated whether nectandrin B affects phosphorylation of endothelial nitric-oxide synthase (eNOS) in human endothelial cells. Nectandrin B increased the phosphorylation of eNOS and nitric oxide (NO) production in a concentration-dependent manner and maximal effect was found at 10 µg/ml. Nectandrin B activates AMPK, presumably via Ca(2+)/calmodulin kinase II activation and nectandrin B-stimulated eNOS phosphorylation was reversed by AMPK inhibition. Both the enzyme activity of phosphatidylinositol 3-kinase (PI3K) and the estrogen receptor (ER)-dependent reporter gene transcription were enhanced by nectandrin B. ERα inhibition by specific antagonist or small interfering siRNA (siRNA) suppressed nectandrin B-mediated eNOS phosphorylation. Moreover, AMPK inhibition significantly reversed the activation of ER-dependent transcription and PI3K activation in response to nectandrin B. Nectandrin B evoked endothelium-dependent relaxation in rat aortic rings, and this was blocked by inhibition of AMPK, ER, or PI3K. These results suggest that potent AMPK activator nectandrin B enhances NO production via eNOS phosphorylation in endothelial cells and ERα-dependent PI3K activity is required.

SIRT1 inhibitory diterpenoids from the Vietnamese medicinal plant Croton tonkinensis.

Silent information regulator two ortholog 1 (SIRT1) is a member of the sirtuin deacetylase family of enzymes that removes acetyl groups from the lysine residues in histones and other proteins. It has been suggested that SIRT1 inhibitors might be beneficial in the treatment of cancer and neurodegenerative diseases. Bioassay-guided fractionation of the MeOH extract of the leaves of CROTON TONKINENSIS resulted in the isolation of a new ENT-kaurane diterpenoid (1) along with 11 known compounds (2- 12). The structure of the new compound 1 was determined to be ENT-11 alpha-acetoxy-7 beta-hydroxykaur-16-en-15-one based on spectroscopic analyses. Compounds 3, 4, 6- 9, 11, and 12 exhibited SIRT1 inhibitory activity in an IN VITRO assay, with IC (50) values ranging from 16.08 +/- 0.11 to 44.34 +/- 2.32 microM. This is the first report showing the potential of ENT-kaurane diterpenoids as a new class of natural SIRT1 inhibitors.

New prenylated flavanones from Erythrina abyssinica with protein tyrosine phosphatase 1B (PTP1B) inhibitory activity.

As the insulin and leptin signaling pathway can be regulated by PTP1B, it has been suggested that compounds that reduce PTP1B activity or expression levels can be used for treating type 2 diabetes and obesity. In the course of our screening efforts on new PTP1B inhibitors, six new flavanones ( 1- 6) with dihydrofuran moiety and two known flavanones ( 7 and 8) were isolated from the stem bark of Erythrina abyssinica (Leguminosae). Their structures were elucidated on the basis of spectroscopic (including UV, CD, MS, 1D, and 2D NMR) and physicochemical analyses. With the exception of 3 and 5, the compounds inhibited PTP1B activity in an IN VITRO assay with IC (50) values ranging from 15.2 +/- 1.2 to 19.6 +/- 2.3 microM, whereas RK-682 as a positive control displayed an IC (50) value of 4.7 +/- 0.5 microM.

Crotonkinensins A and B, diterpenoids from the Vietnamese medicinal plant Croton tonkinensis.

Two new diterpenoids, crotonkinensins A (1) and B (2), were isolated from the leaves of the Vietnamese endemic medicinal plant Croton tonkinensis. Their structures were determined to be 7alpha,10alpha-epoxy-14beta-hydroxygrayanane-1(5),16(17)-dien-2,15-dione (1) and 7alpha,10alpha-epoxy-14beta-hydroxygrayanane-1(2),16(17)-dien-15-one (2) by spectroscopic analysis. Compounds 1 and 2 showed strong anti-inflammatory effects on the LPS-induced COX-2 promoter activity and COX-2 expression in Raw 264.7 cells.

Pterocarpans with inhibitory effects on protein tyrosine phosphatase 1B from Erythrina lysistemon Hutch.

Bioassay-guided fractionation of the MeOH extract of the stem bark of Erythrina lysistemon Hutch. resulted in isolation of pterocarpans (1-3), named erylysins A-C, along with nine known pterocarpans (4-12). Their structures were determined to be 3''-hydroxy-2',2'-dimethylpyrano[6',5':3,4]-2'',2''-dimethyldihydropyrano[6'',5'':9,10]pterocarpan (1), furano[5',4':3,4]-9-hydroxy-10-prenylpterocarpan (2), and 8-formyl-3,9-dihydroxy-4,10-diprenylpterocarpan (3), based on spectroscopic analyses. All the isolates, with the exception of 3, 6, and 11, strongly inhibited protein tyrosine phosphatase 1B (PTP1B) activity in an in vitro assay, with IC(50) values ranging from 1.01+/-0.3 to 18.1+/-0.9 microg/mL. This is the first report showing the potential of prenylated pterocarpans as a class of natural PTP1B inhibitors.