NO inhibitory constituents as potential anti-neuroinflammatory agents for AD from Blumea balsamifera.

Our continuous search for new nitric oxide (NO) inhibitory substances as anti-neuroinflammatory agents for AD resulted in the isolation of one new labdane diterpenoid and three new guaiane sesquiterpenoids, as well as ten known compounds from Blumea balsamifera. Their structures were elucidated by NMR spectroscopic data analysis and the time-dependent density functional theory (TDDFT) electronic circular dichroism (ECD) calculations. The anti-neuroinflammatory effects were examined by inhibiting NO release in LPS-induced murine microglial BV-2 cells. The possible mechanism of NO inhibition of some bioactive compounds was also investigated using molecular docking, which revealed the interactions of bioactive compounds with the iNOS protein.

Bioactive Terpenoids from Salvia plebeia: Structures, NO Inhibitory Activities, and Interactions with iNOS.

A phytochemical investigation to obtain new NO inhibitors resulted in the identification of six new (1-6) and four known (7-10) terpenoids from Salvia plebeia. Compounds 1 and 2 are new diterpenoids, 3-5 are new meroditerpenoids, 6-9 are sesquiterpenoids, and 10 is a known meroditerpenoid. The structures of these isolates were determined by routine NMR experiments and X-ray diffraction, as well as the electronic circular dichroism spectra. Compounds 1-4 are diterpenoids carrying an oxygen bridge, and 6 is a rare copane-type sesquiterpenoid with a bridged tricyclic framework. The isolates inhibited NO generation induced by lipopolysaccharide in BV-2 cells. The possible mechanism of NO inhibition of some bioactive compounds was also investigated using molecular docking, which revealed interactions of bioactive compounds with the iNOS protein.

Di- and Triterpenoids from the Leaves of Casearia balansae and Neurite Outgrowth Promoting Effects of PC12 Cells.

A bioassay-guided phytochemical investigation of the leaves of Casearia balansae led to the isolation of six new cucurbitane-type triterpenoid derivatives (balanterpenes A-F, 1-6) and four new clerdoane-type diterpenoids (balanterpenes G-J, 7-10). The structures of 1-10 were established on the basis of extensive analysis of NMR spectroscopic data, X-ray crystallography, and experimental and calculated electronic circular dichroism spectra. Compound 1 features a ring-expanded triterpenoid skeleton with the C-19 methyl involved in the ring formation, compound 6 possesses a rare hexanortriterpenoid scaffold, and compounds 7-10 may be four new diterpenoid artifacts presumably formed during the extraction and purification processes. Compounds 3 and 7-10 showed promoting effects on neurite outgrowth of PC12 cells with EC50 values in the range 2.9-10.0 µM.

Bioactive Diterpenoids from the Leaves of Callicarpa macrophylla.

A phytochemical investigation of the leaves of Callicarpa macrophylla led to the isolation of five new diterpenoids (1-5), macrophypenes A-E, and nine known analogues (6-14). The structures of 1-5 were established on the basis of extensive analysis of NMR spectroscopic data, X-ray diffraction data, and experimental and calculated electronic circular dichroism spectra. Compound 1 is a spiroditerpenoid with a novel skeleton, and compound 5 is a rare ent-abietane diterpenoid possessing a peroxide bridge. Compounds 1, 5-7, and 11-14 stimulate nerve growth factor mediated neurite outgrowth from PC12 cells.

Isolation and characterization of sesquiterpenes from Celastrus orbiculatus and their antifungal activities against phytopathogenic fungi.

Celastrus orbiculatus is an insecticidal plant belonging to the Celastraceae family. In this survey on the secondary metabolites of plants for obtaining bioactive substances to serve agriculture, the chemical constituents of the fruits of C. orbiculatus were investigated. This phytochemical investigation resulted in the isolation of nine new and one known sesquiterpene. Their structures, especially the complicated stereochemical features, were elucidated on the basis of extensive NMR spectroscopic data analyses, time-dependent density functional theory CD calculations, and the CD exciton chirality method. Biological screenings disclosed that these sesquiterpenes showed antifungal activities against six phytopathogenic fungi. The results of our phytochemical investigation further disclosed the chemical components of C. orbiculatus, and biological screening implied that it may be potentially useful to protect crops against phytopathogenic fungi and the bioactive compounds may be regarded as candidate agents of antifungal agrochemicals for crop protection products.

Bioactive clerodane diterpenoids from the twigs of Casearia balansae.

Eight new clerodane diterpenes, balanspenes A-H (1-8), along with two known analogues (9 and 10), were isolated from the twigs of Casearia balansae. The structures of 1-8 were elucidated on the basis of extensive 1D and 2D NMR spectroscopic data analysis, and the absolute configurations of compounds 1, 4, and 7 were confirmed by comparing their experimental CD spectra with those calculated by the time-dependent density functional theory method. Compounds 4-7, 9, and 10 were found to possess the property of being able to stimulate NGF-mediated neurite outgrowth from PC12 cells.

Characterization and NO inhibitory activities of chemical constituents from an edible plant Petasites tatewakianus.

Petasites tatewakianus is an edible plant belonging to the family Compositae. In our continuous search for NO inhibitors, which may be useful for the development of anti-inflammatory agents, the chemical constituents of the leaves of the edible plant P. tatewakianus were investigated. This phytochemical investigation led to the isolation of 3 new (1-3) and 10 known (4-13) sesquiterpenes and 2 other types of known compounds (14 and 15). Their structures were elucidated on the basis of extensive 1D and 2D NMR spectroscopic data analyses, and the absolute configurations of compounds 1 and 3 were confirmed by comparing their experimental CD spectra with those calculated by the time-dependent density functional theory (TDDFT) method. The following biological studies disclosed that these isolated compounds showed inhibitory activities on LPS-induced NO production in murine microglial BV-2 cells. The results of our phytochemical investigation, including two new bakkenolide sesquiterpenes (1 and 2), one new sesquiterpene with an unusual carbon skeleton (3), and the first report of compounds 5-7 and 10-15 from this species, further revealed the chemical composition of P. tatewakianus as an edible plant, and the biological studies implied that P. tatewakianus, containing bioactive substances with the inhibitory activities of NO production, was potentially beneficial to human health.

Sesquiterpenes inhibiting the microglial activation from Laurus nobilis.

The inhibitory reagents to inhibit the activation of microglial cells may be potentially useful for the treatment of neurodegenerative diseases. The leaves of the plant Laurus nobilis belonging to the family Lauraceae, namely, bay leaves, have been used as a popular spice, and their extract showed moderate inhibition on microglial activation. A further phytochemical investigation of the leaves led to the isolation of two new (1, 2) and eight known (3-10) sesquiterpenes. Their structures were elucidated on the basis of extensive 1D and 2D NMR (HMQC, HMBC, (1)H-(1)H COSY, and NOESY) spectroscopic data analyses and Chem3D modeling. The following biological studies disclosed that these isolated compounds showed inhibitory activities on LPS-induced microglial activation. The results of our phytochemical investigation, including two new sesquiterpenes (1 and 2) and the first report of two compounds (3 and 4) from this species, further revealed the chemical composition of bay leaves as a popular spice, and the biological studies implied that bay leaves, containing bioactive substances with the inhibition of microglial activation, were potentially beneficial to human health.

Two novel clerodane diterpenenes with NGF-potentiating activities from the twigs of Croton yanhuii.

Nerve growth factor (NGF) and analog reagents to promote the neurite outgrowth of nerve cells against the neuron degeneration are expected to be potentially useful for the medical treatment of Alzheimer's disease. In our focus on the discovery of bioactive diterpenes, we investigated the chemical constituents of the plant Croton yanhuii. This investigation led to the isolation and identification of two novel clerodane diterpenes (1 and 2). Their structures were elucidated on the basis of extensive 1D and 2D NMR (COSY, HMQC, HMBC, and NOESY) and mass (ESIMS and HR-ESIMS) spectroscopic data analyses. Further biological screenings showed that both of the compounds enhanced NGF-mediated neurite outgrowth from PC12 cells.