[Two new benzyl-benzoate glucosides from Plumeria rubra].

The components with hypoglycemic activity in Plumeria rubra were isolated and purified by various column chromatography techniques and activity tracing methods. The physical and chemical properties of all the purified monomer compounds were characterized and analyzed, and a total of six compounds were isolated and identified, including 6″-acetyl-6-hydroxy-benzyl-benzoate-2-O-ß-D-glucoside(1), 6-acetyl-6-hydroxy-benzyl-benzoate-2-O-ß-D-glucoside-(1→6″)-ß-D-glucoside(2), 2-hydroxy-6-methoxy-benzyl-benzoate-2-O-ß-D-glucoside(3), 6-hydroxy-benzyl-benzoate-2-O-ß-D-glucoside(4), 6-hydroxy-benzyl-benzoate-2-O-ß-D-glucoside-(1→6″)-ß-D-glucoside(5), and 6-hydroxy-benzyl-benzoate-2-O-ß-D-glucoside-(1→6″)-ß-D-xyloside(6). Compounds 1 and 2 were new compounds, and compounds 3-6 were isolated from Plumeria for the first time. The α-glucosidase inhibitory activity of six identified compounds was tested. The results show that compounds 1-6 show certain inhibitory activity with an IC_(50) value ranging from 8.2 to 33.5 µmol·L~(-1).

Plumeriapropionics A-E, Carboxyl-Substituted Phenylpropionic Acid Derivatives with Anti-Inflammatory Activity from Plumeria rubra L.

Five rare carboxyl-substituted phenylpropionic acid derivatives, plumeriapropionics A-E (1-5), together with one known analog, cerberic acid B (6), were isolated from flowers of Plumeria rubra L. Their structures were elucidated using comprehensive spectroscopic methods. To date, only one compound of this structural type has been reported. The inhibitory activities of compounds 1-6 against nitric oxide (NO) production induced by lipopolysaccharide (LPS) were evaluated in vitro using mouse macrophage RAW264.7 cells. Compounds 1-6 showed remarkable inhibitory activities on NO production, with IC50 values in the range of 6.52 ± 0.23 to 35.68 ± 0.17 µM. These results indicate that the discovery of carboxyl-substituted phenylpropionic acid derivatives from the flowers of P. rubra, which show significant anti-inflammatory properties, could be of great importance for the research and development of novel natural anti-inflammatory agents.

The Antioxidant and Xanthine Oxidase Inhibitory Activity of Plumeria rubra Flowers.

Plumeria rubra Linn of the family Apocynaceae is locally known in Malaysia as "Kemboja". It has been used by local traditional medicine practitioners for the treatment of arthritis-related disease. The LCMS/MS analysis of the methanol extract of flowers (PR-ME) showed that it contains 3-O-caffeyolquinic acid, 5-caffeoquinic acid, 1,3-dicaffeoquinic acid, chlorogenic acid, citric acid, 3,3-di-O-methylellagic acid, kaempferol-3-O-glucoside, kaempferol-3-rutinoside, kaempferol, quercetin 3-O-α-l-arabinopyranoside, quercetin, quinic acid and rutin. The flower PR-ME contained high amounts of phenol and flavonoid at 184.632 mg GAE/g and 203.2.2 mg QE/g, respectively. It also exhibited the highest DPPH, FRAP, metal chelating, hydrogen peroxide, nitric oxide superoxide radical scavenging activity. Similarly, the XO inhibitory activity in vitro assay possesses the highest inhibition effects at an IC50 = 23.91 µg/mL. There was no mortality or signs of toxicity in rats at a dose of 4 g/kg body weight. The administration of the flower PR-ME at doses of 400 mg/kg to the rats significantly reduced serum uric acid 43.77%. Similarly, the XO activity in the liver was significantly inhibited by flower PR-ME at doses of 400 mg/kg. These results confirm that the flower PR-ME of P. rubra contains active phytochemical compounds as detected in LCMS/MS that contribute to the inhibition of XO activity in vitro and in vivo in reducing acid uric level in serum and simultaneously scavenging the free radical to reduce the oxidative stress.

Integration of the metabolome and transcriptome reveals the molecular mechanism of drought tolerance in Plumeria rubra.

Plumeria rubra L. cv. Acutifolia is an ornamental tree that displays a good drought-tolerance level. However, the molecular mechanisms of P. rubra adaptation to drought stress remains unclear. Here, drought-simulating pot experiments were conducted to explore drought stress response mechanism of P. rubra. Transcriptome analysis revealed 10,967 differentially expressed genes (DEGs), 6,498 of which were increased and 4,469 decreased. Gene Ontology (GO) analysis revealed that the DEGs were enriched in binding category, in metabolic process category, and in catalytic activities category. The Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis showed that 9 pathways were significantly enriched, including biosynthesis of secondary metabolites (ko01110), plant hormone signal transduction (ko04075) and so on. In addition, the transcription factor families of AP2/ERFs, bZIP, and C2H2 were significantly upregulated while the families of bHLH, MYB-related, and NAC were significantly downregulated. Moreover, the results of metabolomics analysis indicated that some compounds were accumulated under drought stress, especially flavonoids. Overall, it was speculated that under drought stress, P. rubra first activates the plant hormone signal transduction pathway to regulate hormone contents. Then osmotic regulating substances such as organic acids and amino acids are accumulated to maintain osmotic balance. Finally, flavonoid levels are increased to scavenge reactive oxygen species. These results preliminarily revealed the molecular mechanisms adopted by P. rubra in response to drought stress.

Identification and screening of potential inhibitors obtained from Plumeria rubra L. compounds against type 2 diabetes mellitus.

Type 2 diabetes mellitus (T2DM) is the inability of the body's cells to retaliate to insulin, which can periodically culminate into absolute insulin deficiency. Hyperinsulinemia can be alleviated by administering oral medications or insulin. Prevailing medicaments engender repercussions with prolonged use, as they transmute to an inefficacious form. Hence, it will be advantageous to design plant-derived antihyperglycemic drugs with remarkable efficacy and safety quotients to address T2DM and associated comorbidities. Based on prior research, we have identified 7 novel phytocompounds from Plumeria rubra L. and 5 co-crystals that serve as an important residence for T2DM. The compounds are assessed for their inhibitory activity and dynamic stability against five major receptors which are responsible for T2DM. Additionally, in silico ADMET assessment followed by GPU-enabled GROMACS was performed on the selected compounds. The results demonstrated that ß-d-Hexaglucoside had the highest binding affinity, hydrophobicity and bond length in contrast to all the targeted receptors. ß-d-Hexaglucoside was subjected to dynamic simulation to analyze the root mean square deviation and root mean square fluctuation graph rates using the GROMOS force field in GROMACS software. Furthermore, ß-d-Hexaglucoside exhibited inhibitory activity against diabetic receptors with a docking score of -9.5 kcal/mol. The current study proposes ß-d-Hexaglucoside as a potential candidate for in-vitro or pre-clinical investigations to ameliorate T2DM management.Communicated by Ramaswamy H. Sarma.

Potential anti-diabetic isoprenoids and a long-chain δ-lactone from frangipani (Plumeria rubra).

A decoction of Plumeria rubra flowers has been used traditionally for the treatment of diabetes in China and Mexico. Chemical investigations on the bioactive constituents of these flowers led to the isolation of 30 compounds, including the four new compounds, one iridoiod (1), two triterpenoids (4, 5), and a long-chain δ-lactone (16). In addition, 26 known compounds (2, 3, 6-15, 17-30) are also reported. All of these compounds were identified on the basis of spectroscopic data interpretation and the absolute configurations of compound 4, 5, 16 were determined by Mosher's method. Compounds 1-4, 7, 8 and 16 showed moderate to significant inhibitory activities against α-glucosidase and protein tyrosine phosphatase 1B, with 4 having IC50 values of 19.45 µM and 0.21 µM, respectively.

Insights into milk-clotting activity of latex peptidases from Calotropis procera and Cryptostegia grandiflora.

Latex fractions from Calotropis procera, Cryptostegia grandiflora, Plumeria rubra, and Himatanthus drasticus were assayed in order to prospect for new plant peptidases with milk-clotting activities, for use as rennet alternatives. Only C. procera and C. grandiflora latex fractions exhibited proteolytic and milk-clotting activities, which were not affected by high concentrations of NaCl and CaCl2. However, pre-incubation of both samples at 75°C for 10min eliminated completely their activities. Both proteolytic fractions were able to hydrolyze k-casein and to produce peptides of 16kDa, a similar SDS-PAGE profile to commercial chymosin. RP-HPLC and mass spectrometry analyses of the k-casein peptides showed that the peptidases from C. procera or C. grandiflora hydrolyzed k-casein similar to commercial chymosin. The cheeses made with both latex peptidases exhibited yields, dry masses, and soluble proteins similar to cheeses prepared with commercial chymosin. In conclusion, C. procera and C. grandiflora latex peptidases with the ability to coagulate milk can be used as alternatives to commercial animal chymosin in the cheese manufacturing process.