Identification of MYB gene family in medicinal tea tree Melaleuca alternifolia (Maiden and Betche) cheel and analysis of members regulating terpene biosynthesis.

BACKGROUND: The tea tree (Melaleuca alternifolia) is renowned for its production of tea tree oil, an essential oil primarily composed of terpenes extracted from its shoot. MYB transcription factors, which are one of the largest TF families, play a crucial role in regulating primary and secondary metabolite synthesis. However, knowledge of the MYB gene family in M. alternifolia is limited. METHODS AND RESULTS: Here, we conducted a comprehensive genome-wide analysis of MYB genes in M. alternifolia, referred to as MaMYBs, including phylogenetic relationships, structures, promoter regions, and GO annotations. Our findings classified 219 MaMYBs into four subfamilies: one 5R-MYB, four 3R-MYBs, sixty-one MYB-related, and the remaining 153 are all 2R-MYBs. Seven genes (MYB189, MYB146, MYB44, MYB29, MYB175, MYB162, and MYB160) were linked to terpenoid synthesis based on GO annotation. Phylogenetic analysis with Arabidopsis homologous MYB genes suggested that MYB193 and MYB163 may also be involved in terpenoid synthesis. Additionally, through correlation analysis of gene expression and metabolite content, we identified 42 MYB genes associated with metabolite content. CONCLUSION: The results provide valuable insights into the importance of MYB transcription factors in essential oil production in M. alternifolia. These findings lay the groundwork for a better understanding of the MYB regulatory network and the development of novel strategies to enhance essential oil synthesis in M. alternifolia.

Marsdenia tenacissima injection induces the apoptosis of prostate cancer by regulating the AKT/GSK3ß/STAT3 signaling axis.

Marsdenia tenacissima injection, a standard Marsdenia tenacissima extract (MTE), has been approved as an adjuvant therapeutic agent for various cancers. Our previous study showed that MTE inhibited the proliferation and metastasis of prostate cancer (PCa) cells. However, the underlying mechanisms and active ingredients of MTE against PCa were not completely understood. This study revealed that MTE induced significant decreases in cell viability and clonal growth in PCa cells. In addition, MTE induced the apoptosis of DU145 cells by reducing the mitochondrial membrane potential and increasing the expression of Cleaved Caspase 3/7, Cyt c, and Bax. In vivo, DU145 xenografted NOD-SCID mice treated with MTE showed significantly decreased tumor size. TUNEL staining and Western blot confirmed the pro-apoptotic effects of MTE. Network pharmacology analysis collected 196 ingredients of MTE linked to 655 potential targets, and 709 PCa-associated targets were retrieved, from which 149 overlapped targets were screened out. Pathway enrichment analysis showed that the HIF-1, PI3K-AKT, and ErbB signaling pathways were closely related to tumor apoptosis. Western blot results confirmed that MTE increased the expression of p-AKTSer473 and p-GSK3ßSer9, and decreased the expression of p-STAT3Tyr705in vitro and in vivo. A total of 13 compounds in MTE were identified by HPLC-CAD-QTOF-MS/MS and UPLC-QTOF-MS/MS. Molecular docking analysis indicated that six compounds may interact with AKT, GSK3ß, and STAT3. In conclusion, MTE induces the endogenous mitochondrial apoptosis of PCa by regulating the AKT/GSK3ß/STAT3 signaling axis, resulting in inhibition of PCa growth in vitro and in vivo.

Lemongrass (Cymbopogon citratus) oil: A promising miticidal and ovicidal agent against Sarcoptes scabiei.

BACKGROUND: Essential oils may represent an alternative strategy for controlling scabies, a neglected tropical disease caused by the infestation of mite from the species Sarcoptes scabiei. Lemongrass (Cymbopogen citratus) oil is reported to possess pharmacological properties including antiparasitc, antioxidant, antimicrobial and anti-inflammatory. The aim of the present study was to assess the potential efficacy of lemongrass oil against the mites and eggs of Sarcoptes scabiei. METHODOLOGY/PRINCIPAL FINDINGS: Mass spectrometry analysis confirmed that the main component presented in lemongrass oil was citral. Lemongrass oil at concentrations of 10% and 5% killed all Sarcoptes mites within 10 and 25 min, respectively. The median lethal concentration value was 1.37%, 1.08%, 0.91%, 0.64%, and 0.48% at 1, 3, 6, 12, and 24 h, respectively. Lemongrass oil at all concentrations (10%, 5%, 1%, 0.5%, 0.1%) was able to significantly decrease the hatching rate of Sarcoptes eggs. CONCLUSIONS/SIGNIFICANCE: Lemongrass oil should be considered as a promising miticidal and ovicidal agent for scabies control.

Compound Discovery and Structure-Activity Relationship Study of Neoantimycins Against Drug-Resistant Cancer Cells.

Four neoantimycins H-K (1-4) with C1-keto, including the new ones (1-2), were isolated from the culture of Streptomyces conglobatus RJ8. After enzymatically converting into their respective reduced type derivatives (5-8) in vitro, the absolute structures of 1-8 were established/reconfirmed by analyzing hydrolyzed components. The obtained NATs (4, 7, and 8) exhibited excellent cytotoxicity against drug-resistant colon and gastric cancer cells but low toxicity in the noncancerous cell. Further SAR investigation suggested that C1-hydroxyl, C9-isobutyl, and N-formyl contribute to the antiproliferation remarkably.

Effect of Y6, an epigallocatechin gallate derivative, on reversing doxorubicin drug resistance in human hepatocellular carcinoma cells.

Cancer cells can acquire resistance to a wide variety of diverse and unrelated drugs, this phenomenon is termed multidrug resistance (MDR). Multidrug resistance has been an obstacle to the success of cancer chemotherapy. The present study investigated the reversal effect of Y6, a new compound obtained by chemically modifying the structure of epigallocatechin-3-gallate (EGCG) extracted from green tea. Y6 was proven to be effective in inhibiting cell proliferation and reversing drug resistance in doxorubicin (DOX) resistant human hepatocellular carcinoma cells (BEL-7404/DOX). BEL-7404/DOX cells were treated with either doxorubicin combination regimen (doxorubicin plus Y6 or epigallocatechin-3-gallate or verapamil separately) or doxorubicin alone. The results showed that cell proliferation was inhibited and late cell apoptosis increased in the combination treatment group, especially in the group treated with doxorubicin plus Y6. Further analysis revealed that the expressions of hypoxia-inducible factor-1α and multidrug resistance 1/P-glycoprotein decreased at both messenger RNA and protein levels by treatments with combined drugs compared to doxorubicin alone. Our results indicated that Y6, as a drug resistance reversal agent, increased the sensitivity of drug resistant cells to doxorubicin. The mechanisms of actions of Y6 in reversal effect were associated with the decreased expression of hypoxia-inducible factor-1α and multidrug resistance 1/P-glycoprotein.

Benzofuran glycosides and coumarins from the bark of Streblus indicus (Bur.) Corner.

Two pairs of rare benzofuran glucoside epimers, indicuses A and B and indicuses C and D, three biogenetically related compounds indicuses E-G, and one coumarin indicus H, as well as 11 known compounds, were isolated from the bark of Streblus indicus (Bur.) Corner. The structures of indicuses A-H were elucidated by NMR and MS data, as well as by CD. (S)-Marmesinin exhibited moderate antimicrobial activity in vitro against Bacillus subtilis and Saccharomyces cerevisiae. 7,8-Dihydroxy-3-(3-methyl-2-butenyl) coumarin, umbelliferone, and scopoletin displayed strong cytotoxic activity in vitro against human bladder carcinoma cell line EJ. The structure-activity relationships indicate that hydroxylation at C-7 in the cytotoxic compounds is crucial to their activities.

Two new coumarins from the bark of Streblus indicus (Bur.) Corner.

Two new coumarins 7-O-(6-O-(5-O-3,4,5-tri-methoxycinnamate-ß-d-apiofuranosyl-ß-d-glucopyranosyl)-6-methoxy coumarin (1) and 7-O-(6-O-(4-(2-hydroxy-1-hydroxymethyl-ethoxy)-3-methoxy-cinnamyl)-ß-d-glucopyranosyl)-6-methoxy coumarin (2), along with 10 known metabolites, were isolated from the bark of Streblus indicus, their structures were identified by comparison of experimental and published spectroscopic data. (S)-marmesinin (6) and scoparone (7) exhibited moderate antimicrobial activity in vitro against Staphylococcus aureus strain with the MIC values of 62.5 and 125.0 µg/mL, respectively. Betulinic acid showed inhibitory activity in vitro against MCF-7 cell with IC50 value of 9.5 ± 0.1 µM.

Structural Characterization and Assessment of the Cytotoxicity of 2,3-Dihydro-1H-indene Derivatives and Coumarin Glucosides from the Bark of Streblus indicus.

A pair of enantiomers and a pair of 2,3-dihydro-1H-indene epimers, rac-indidene A (rac-1), indidenes B and C (2, 3); four new coumarin glucosides (4-7); and four known coumarin glucosides (8-11) were isolated from the bark of Streblus indicus (Bur.) Corner. The structures of 1-11 were defined by physical data analyses, including MS, NMR, and single-crystal X-ray diffraction. The absolute configurations of the 2,3-dihydro-1H-indene derivatives were defined via experimental and calculated ECD data. rac-Indidene A and indidenes B and C showed inhibitory activity against A549 and MCF-7 tumor cells with IC50 values in the range of 2.2 ± 0.1 to 7.2 ± 0.9 µM.

Effect of Phyllanthus amarus Extract on 5-Fluorouracil-Induced Perturbations in Ribonucleotide and Deoxyribonucleotide Pools in HepG2 Cell Line.

The aim of this study was to investigate the antitumor activities of Phyllanthus amarus (PHA) and its potential of herb-drug interactions with 5-Fluorouracil (5-FU). Cell viability, ribonucleotides (RNs) and deoxyribonucleotides (dRNs) levels, cell cycle distribution, and expression of thymidylate synthase (TS) and ribonucleotide reductase (RR) proteins were measured with 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, high performance liquid chromatography tandem mass spectrometry (HPLC/MS/MS) method, flow cytometry and Western blot analysis, respectively. Our standardized PHA extract showed toxicity to HepG2 cells at high concentrations after 72 h exposure and induced G2/M cell cycle arrest. Combined use of 5-FU with PHA resulted in significant decreases in ATP, CTP, GTP, UTP and dTTP levels, while AMP, CMP, GMP and dUMP levels increased significantly compared with use of 5-FU alone. Further, PHA could increase the role of cell cycle arrest at S phase induced by 5-FU. Although PHA alone had no direct impact on TS and RR, PHA could change the levels of RNs and dRNs when combined with 5-FU. This may be due to cell cycle arrest or regulation of key enzyme steps in intracellular RNs and dRNs metabolism.

Synthesis and hypoglycemic activity of esterified-derivatives of mangiferin.

AIM: To synthesize three novel esterified-derivatives of mangiferin and evaluate their hypoglycemic activities. METHODS: Acetic, propionic, and butyric anhydride were reacted with mangiferin, respectively. The hypoglycemic activity of the derivatives was evaluated using a hyperglycemic mouse model induced by streptozotocin (STZ), and the islet cells were checked by biopsy inspection. RESULTS: 7, 2', 3', 4', 6'-penta-acetyl-mangiferin (PAM), 3, 6, 7, 2', 3', 4', 6'-hepta-propionyl-mangiferin (HPM) and 3, 6, 7, 2', 3', 4'-hexa-butyryl-mangiferin (HBM) were synthesized and their structures were identified by MS,(1)H, (13)C NMR, and 2D NMR. These three compounds were reported for the first time. PAM group (0.5, 0.25 mmol·kg(-1)), HPM group (0.5, 0.25 mmol·kg(-1)), and HBM group (0.5, 0.25, 0.125 mmol·kg(-1)) mice showed strong hypoglycemic activity (P < 0.01); mangiferin group (1, 0.5 mmol·kg(-1)), PAM group (0.125 mmol·kg(-1)) and HPM group (0.125 mmol·kg(-1)) showed marginal hypoglycemic activity (P < 0.05); mangiferin group (0.25 mmol·kg(-1)) had the potential for a hypoglycemic effect, although it did not demonstrate that statistically. In histological examination, the islet cells of the PAM, HPM, and HBM groups could recover from the STZ damage; islet cells of the mangiferin group could recover also, but less than the esterified-derivative groups. CONCLUSION: Derivatives could repair the damaged islet cells, and had higher lipid-solubility and stronger hypoglycemic activity than mangiferin itself. There existed a structure activity effect, and a solubility effect relationship: the larger esterification moieties, or the higher lipid-solubility, the stronger the hypoglycemic activity (no ester → acetyl → propionyl → butyryl). Esterified derivatives of mangiferin are potential compounds for new anti-diabetes drugs.

[Analysis of compositions of the essential oil from Curcuma aromatica by gas chromatography-mass spectrometry].

OBJECTIVE: To analyze the compositions of the essential oil from the rhizome of Curcuma aromatica in Guangxi. METHODS: The essential oil from the rhizome of Curcuma aromatica was extrated by steam distillation and analysed by GC-MS. RESULTS: 50 chemical constituents accounting for 93.11% of total content were identified. CONCLUSION: The main components are eucalyptol (53.86%), neocurdione (9.89%), linalool (4.24%), camphor (3.14%), alpha-terpineol (2.94%) and germacrone (2.89%).

Synthesis, characterization and in vitro anti-tumor activities of matrine derivatives.

Nineteen previously unreported matrine derivatives were synthesized and characterized using elemental analysis, infrared spectroscopy, proton nuclear magnetic resonance spectroscopy, and mass spectrometry. Target compounds 6a-6l and 7a-7c showed stronger inhibitory activities than matrine in the in vitro antitumor tests and inhibited the growth of the Hep7402, B16-F10, A549, and TW03 cell lines. In addition, compound 6i exhibited a potent antitumor activity similar to that of colchicine.

[Analysis of essential oil from Mahonia duclouxiana].

OBJECTIVE: To analyze the compositions of essential oil from Mahonia duclouxiana. METHODS: The essential oil was extracted by steam distillation, its chemical components were analyzed by GC-MS, and principal component was confirmed by GC. RESULTS: 80 peaks were detected and 41 components have been identified, which made up more than 90% of total essential oil. The major component was 4-Terpineol (43.73%), the other high content components were alpha-Terpineol (5.23%), (Z)-3-Hexen-1-ol (4.78%), Linalool (4.04%), etc. CONCLUSION: The chemical components of essential oil of from Mahonia duclouxiana by GC-MS for the first time. This study provided science basis for further research development of Mahonia duclouxiana.

[Study on the volatile oil of Murraya exotica].

OBJECTIVE: To study the volatile oil of Murraya exotica. METHODS: The volatile oil of Murraya exotica was extracted by steam-stilling and was identified by GC-MS-DS. RESULTS: More than 90 compounds were separated, and 59 compounds were identified, accounting for 93.9% of the total essential oil of Murraya exotica. The major constituents of volatile oil were bicyclogermacrene (26.0%), beta-caryophyllene (20.8%), alpha-caryophyllene (5.8%), delta-cadinene (4.7%), spathulenol (4.3%), trans-alpha-bergamotene (4.1%), germacrene D (3.7%), beta-bisabolene (3.0%), ar-Curcumene (2.5%). CONCLUSION: The major components of Murraya exotica are the terpenoids, including 80.6% of sesquiterpenoids and 11.9% of monoterpenoids. Bicyclogermacrene is identified in Murraya genus for the first time.

[Study on quality analysis of essential oil from twig and leaf of Baeckea frutescens].

OBJECTIVE: To provide scientific methods for quality criterion by studying the chemical components of essential oil from Baeckea frutescens. METHOD: The chemical components of essential oil from B. frutescens were identified by GC-MS-DS, TLC and capillary GC. The relative contents of main components were determined by area normalization. RESULT: More than 50 peaks were separated, and 38 components were identified, which accounted for over 94% of the total GC peaks areas of the essential oil. The methods for quality evaluation of essential oil from B. frutescens by TLC and capillary GC were established. CONCLUSION: The chemical components of essential oil from B. frutescens collected from different habitats and collecting periods have common characteristics as well as differences. Some components, such as linalool, can be used as a standard and chromatography fingerprint to analyze the quality of essential oil from B. frutescens.