Tuliposides H-J and Bioactive Components from the Bulb of Amana edulis.

Three new tuliposides H-J (1-3) and 11 known compounds were obtained from the methanolic extracts of the bulbs of Amana edulis for the first time. Their structures were elucidated by NMR, MS, and IR spectroscopic data, optical rotation, and Mosher's method. The melanogenesis properties of all the isolates were evaluated in B16 melanoma cells. Consequently, tributyl citrate (9) had anti-melanogenesis activity but was cytotoxic toward B16. (+)-Pyroglutamic acid (4), (+)-butyl 5-oxopyrrolidine-2-carboxylate (6), (-)-3-hydroxy-2-methylbutyrolactone (10), and 5-(hydroxymethyl)furfural (12) had increased melanin productions and tyrosinase activities. Those active components could be further studied as the candidates against melanoma and vitiligo for skin diseases or whitening/hypopigmentation for hair.

Characterization Of Secondary Metabolites From The Rhizome Of Cynara Scolymus And Their Antioxidant Properties.

The aerial portions of Cynara scolymus commonly have been eaten as vegetables or functional foods by the people lived in Mediterranean region. In preliminary antioxidant screening, the rhizome portions (CSR) of this species showed better potential than leaves ones. However, neither phytochemical nor pharmacology studies of CSR have been reported to date. The purpose of this research was to identify the active components from CSR through bioassay-guided fractionation. The antioxidant properties of secondary metabolites 1-9 were evaluated in this investigation. Compounds 4-6, 8, and 9 showed antioxidant activities based on DPPH free radical scavenging activity with IC50 values of 22.91-147.21 µM. Besides, compound 8 significantly and dose-dependently reduced H2O2-induced ROS levels in keratinocyte HaCaT cells without cytotoxicity toward HaCaT. Overall, our studies demonstrated the rhizome of C. scolymus could be used as a new natural antioxidant like the edible aerial portions and phenolic compounds are the active components.

Anti-Proliferative Activity of Triterpenoids and Sterols Isolated from Alstonia scholaris against Non-Small-Cell Lung Carcinoma Cells.

(1) Background: In China and South Asia, Alstonia scholaris (Apocynaceae) is an important medicinal plant that has been historically used in traditional ethnopharmacy to treat infectious diseases. Although various pharmacological activities have been reported, the anti-lung cancer components of A. scholaris have not yet been identified. The objective of this study is to evaluate the active components of the leaf extract of A. scholaris, and assess the anti-proliferation effects of isolated compounds against non-small-cell lung carcinoma cells; (2) Methods: NMR was used to identify the chemical constitutes isolated from the leaf extract of A. scholaris. The anti-proliferative activity of compounds against non-small-cell lung carcinoma cells was assessed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay; (3) Results: Eight triterpenoids and five sterols were isolated from the hexane portion of A. scholaris, and structurally identified as: (1) ursolic acid, (2) oleanolic acid, (3) betulinic acid, (4) betulin, (5) 2ß,3ß,28-lup-20(29)-ene-triol, (6) lupeol, (7) ß-amyrin, (8) α-amyrin, (9) poriferasterol, (10) epicampesterol, (11) ß-sitosterol, (12) 6ß-hydroxy-4-stigmasten-3-one, and (13) ergosta-7,22-diene-3ß,5α,6ß-triol. Compound 5 was isolated from a plant source for the first time. In addition, compounds 9, 10, 12, and 13 were also isolated from A. scholaris for the first time. Ursolic acid, betulinic acid, betulin, and 2ß,3ß,28-lup-20(29)-ene-triol showed anti-proliferative activity against NSCLC, with IC50 of 39.8, 40.1, 240.5 and 172.6 µM, respectively.; (4) Conclusion: These findings reflect that pentacyclic triterpenoids are the anti-lung cancer chemicals in A. scholaris. The ability of ursolic acid, betulinic acid, betulin, and 2ß,3ß,28-lup-20(29)-ene-triol to inhibit the proliferative activity of NSCLC can constitute a valuable group of therapeutic agents in the future.

Antibacterial and Synergistic Activity of Pentacyclic Triterpenoids Isolated from Alstonia scholaris.

(1) BACKGROUND: Alstonia scholaris (Apocynaceae) is an important medicinal plant that has been historically used in "Dai" ethnopharmacy to treat infectious diseases in China. Although various pharmacological activities have been reported, the antimicrobial constitutes of A. scholaris have not yet been identified. The objective of this study is to evaluate the antibacterial constitutes from the leaf extract of A. scholaris and to assess the synergistic effects of isolated compounds with antibiotics against bacterial pathogens.; (2) METHODS: The chemical constitutes isolated from the leaf extract of A. scholaris were structurally identified by NMR. The antibacterial and synergistic effect of compounds was assessed by calculating the minimal inhibitory concentration (MIC), checkerboard dilution test, and time-kill assay.; (3) RESULTS: Six pentacyclic triterpenoids were structurally identified as (1) lupeol, (2) betulin, (3) 3-hydroxy-11-ursen-28,13-olide, (4) betulinic acid, (5) oleanolic acid and (6) ursolic acid. Both oleanolic and ursolic acid showed antibacterial activity but were limited to Gram-positive bacteria. Ursolic acid showed a synergistic effect with ampicillin and tetracycline against both Bacillus cereus and S. aureus.; (4) CONCLUSION: These findings reflect that pentacyclic triterpenoids are the antibacterial chemicals in A. scholaris. The ability of ursolic acid to enhance the activity of antibiotics can constitute a valuable group of therapeutic agents in the future.

Cinnamtannin D1 from Rhododendron formosanum Induces Autophagy via the Inhibition of Akt/mTOR and Activation of ERK1/2 in Non-Small-Cell Lung Carcinoma Cells.

In our previous study, ursolic acid present in the leaves of Rhododendron formosanum was found to possess antineoplastic activity. We further isolated and unveiled a natural product, cinnamtannin D1 (CNT D1), an A-type procyanidin trimer in R. formosanum also exhibiting anticancer efficacy that induced G1 arrest (83.26 ± 3.11% for 175 µM CNT D1 vs 69.28 ± 1.15% for control, p < 0.01) and autophagy in non-small-cell lung carcinoma (NSCLC) cells. We found that CNT D1-mediated autophagy was via the noncanonical pathway, being beclin-1-independent but Atg5 (autophagy-related genes 5)-dependent. Inhibition of autophagy with a specific inhibitor enhanced cell death, suggesting a cytoprotective function for autophagy in CNT D1-treated NSCLC cells. Moreover, CNT D1 inhibited the Akt/mammalian target of the rapamycin (mTOR) pathway and activated the extracellular signal-regulated kinases 1/2 (ERK1/2) pathway, resulting in induction of autophagy.

Structure Elucidation of Procyanidins Isolated from Rhododendron formosanum and Their Anti-Oxidative and Anti-Bacterial Activities.

Rhododendron formosanum is an endemic species distributed in the central mountains of Taiwan. In this study, the biological activities of major procyanidins isolated from the leaf extract of R. formosanum were investigated. Four compounds, including two procyanidin dimers, procyanidin A1 (1) and B3 (2), and two procyanidin trimmers, procyanidin C4 (4) and cinnamtannin D1 (5), were isolated and identified on the basis of spectroscopic data. The structure of a new procyanidin dimer, rhodonidin A (3), was elucidated by 2D-NMR, CD spectrum and MS. The procyanidin trimmers and rhodonidin A are reported for the first time in Ericaceae. The biological activities of these procyanidins were evaluated using anti-bacterial and anti-oxidative assays. Only the new compound 3 demonstrated strong anti-bacterial activity against Staphylococcus aureus at an MIC value of 4 µg/mL. All compounds showed pronounced antioxidant activities and the activities are enhanced as the amount of OH groups in procyanidins increased. In conclusion, the pleiotropic effects of procyanidins isolated from the leaves of R. formosanum can be a source of promising compounds for the development of future pharmacological applications.

New bioactive chromanes from Litchi chinensis.

Seven new δ-tocotrienols, designated litchtocotrienols A-G (1-7), together with one glorious macrocyclic analogue, macrolitchtocotrienol A (8), and one new meroditerpene chromane, cyclolitchtocotrienol A (9), were isolated from the leaves of Litchi chinensis. Their structures were mainly determined by extensive spectroscopic analysis, and their biological activities were evaluated by cytotoxicity against human gastric adenocarcinoma cell lines (AGS, ATCC CRL-1739) and hepatoma carcinoma cell line (HepG2 2.2.1.5). The structure-activity relationship of the isolated compounds was also discussed.

The impact of microbial biotransformation of catechin in enhancing the allelopathic effects of Rhododendron formosanum.

Rhododendron formosanum is distributed widely in the central mountains in Taiwan and the major allelopathic compound in the leaves has been identified as (-)-catechin, which is also a major allelochemical of an invasive spotted knapweed in North America. Soil microorganisms play key roles in ecosystems and influence various important processes, including allelopathy. However, no microorganism has been identified as an allelochemical mediator. This study focused on the role of microorganisms in the allelopathic effects of R. formosanum. The microorganism population in the rhizosphere of R. formosanum was investigated and genetic analysis revealed that the predominant genera of microorganisms in the rhizosphere of R. formosanum were Pseudomonas, Herbaspirillum, and Burkholderia. The dominant genera Pseudomonas utilized (-)-catechin as the carbon source and catalyzed the conversion of (-)-catechin into protocatechuic acid in vitro. The concentrations of allelochemicals in the soil were quantified by liquid chromatography-electrospray ionization/tandem mass spectrometry. The concentration of (-)-catechin in the soil increased significantly during the extreme rainfall in the summer season and suppressed total bacterial populations. Protocatechuic acid accumulation was observed while total bacterial populations increased abundantly in both laboratory and field studies. Allelopathic interactions were tested by evaluating the effects of different allelochemicals on the seed germination, radicle growth, and photosynthesis system II of lettuce. Protocatechuic acid exhibited higher phytotoxicity than (-)-catechin did and the effect of (-)-catechin on the inhibition of seed germination was enhanced by combining it with protocatechuic acid at a low concentration. This study revealed the significance of the allelopathic interactions between R. formosanum and microorganisms in the rhizosphere. These findings demonstrate that knowledge regarding the precise biotransformation process of (-)-catechin by microorganisms in the environment is necessary to increase our understanding of allelopathy.