Picrachinentins A-F, 14-Membered Cyclopeptide Alkaloid-Type Burpitides with Uncommon N-Terminal Modifications from Picrasma chinensis and Their Neuroprotective Activity.

Picrachinentins A-F (1-6, respectively), six novel cyclopeptide alkaloid-type burpitides (CPABs), were isolated and fully elucidated from the EtOH extract of the stems and leaves of Picrasma chinensis. Structurally, compounds 1-6 have a 14-membered paracyclophane ring system that was closed through an ether bond between the ß-hydroxy amino acid and tyrosine and modified with a 4,5-methylenedioxybenzoyloxy (MDBz, 3 and 5) or hexanoyl (Hexa, 1, 2, 4, and 6) group at the N-terminus. Interestingly, this is the first report on the isolation and characterization of CPABs from plants of the Simaroubaceae family. In addition, all compounds showed a neuroprotective effect against H2O2-damaged SH-SY5Y cells. Compound 1 was further investigated for its neuroprotective activities using a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced Parkinson's disease animal model, and it dramatically improved MPTP-impaired motor behavioral performance. Biochemical analysis revealed compound 1 restored the tyrosine hydroxylase expression in the striatum of the MPTP-damaged mouse brain, which demonstrates its protective effect on dopaminergic neurons.

New sesquiterpenoids with neuroprotective effects in vitro and in vivo from the Picrasma chinensis.

Three undescribed sesquiterpenes, designed as pichinenoid A-C (1-3), along with nine known ones (4-12) were isolated from the stems and leaves of Picrasma chinensis. The new isolates including their absolute configurations were elucidated based on extensive spectroscopic methods, single crystal X-ray diffraction, and electronic circular dichroism (ECD) experiments, as well as comparison with literature data. Structurally, compounds 1 and 2 are descending sesquiterpenes, while pichinenoid C (3) is a rare sesquiterpene bearing a 2-methylenebut-3-enoic acid moiety at the C-6 side chain. All the isolated compounds were tested for their neuroprotective effects against the H2O2-induced damage on human neuroblastoma SH-SY5Y cells, and most of them showed moderate neuroprotective activity. Especially, compounds 1, 3-5, and 7 showed a potent neuroprotective effect at 25 or 50 µM. Moreover, the neuroprotective effects of compounds 1 and 4 were tested on a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced Parkinson's disease (PD) mouse model. Results of western blot and immunofluorescence indicated that compound 4 significantly counteract the toxicity of MPTP, and reversed the expression of tyrosine hydroxylase (TH) in substantia nigra (SN) and striatum (ST) of the mouse brain. Interestingly, western blot data suggested compound 4 also enhanced B-cell lymphoma-2 (Bcl-2) and heme oxygenase 1 (HO-1) expressions in the brain tissues from MPTP damaged mouse.

Clerodane diterpenoids with in-vitro anti-neuroinflammatory activity from the tuberous root of Tinospora sagittata (Menispermaceae).

Twenty-six clerodane diterpenoids have been isolated from T. sagittata, a plant species of traditional Chinese medicine Radix Tinosporae, also named as "Jin Guo Lan". Among them, there are eight previously undescribed clerodane diterpenoids (tinotanoids A-H: 1-8), and 18 known diterpenoids (9-26). The absolute configurations of compounds 1, 2, 5, 8, 13, 17 and 20 were determined by single-crystal X-ray diffraction. Compound 1 is the first example of rotameric clerodane diterpenoid with a γ-lactone ring which is constructed between C-11 and C-17; meanwhile, compounds 3 and 4 are two pairs of inseparable epimers. Compounds 2, 12 and 17 demonstrated excellent inhibitory activity on NO production against LPS-stimulated BV-2 cells with IC50 values of 9.56 ± 0.69, 9.11 ± 0.53 and 11.12 ± 0.70 µM, respectively. These activities were significantly higher than that of the positive control minocycline (IC50 = 23.57 ± 0.92 µM). Moreover, compounds 2, 12 and 17 dramatically reduced the LPS-induced upregulation of iNOS and COX-2 expression. Compounds 2 and 12 significantly inhibited the levels of pro-inflammatory cytokines TNF-α, IL-1ß and IL-6 that were increased by LPS stimulation.

New polychlorinated bibenzyls from Rhododendron minutiflorum.

Five new polychlorinated bibenzyls (1-5) along with 3 known compounds (6-8) were isolated from the stems and leaves of Rhododendron minutiflorum. The chemical structures of all the isolates were determined by spectroscopic methods, and compounds 1 and 2 were further verified by single-crystal X-ray diffraction analyses. Compounds 1-5 were halogenated compounds which bear three to five chlorine atoms in their chemical structures. Biologically, compounds 2, 5 and 6 showed varying degrees of toxicity toward the Asian citrus psyllid (Diaphorina citri) with LD50 values 27.15, 17.02 and 16.20 mg/L, respectively. These values were comparable to the positive control matrine (LD50 = 11.86 mg/L), which were calculated using observations on day 6. Meanwhile, compound 4 had α-glucosidase inhibitory activity with IC50 value of 17.87 ± 0.74 µM.

Terpenoids with α-glucosidase inhibitory activity from Rhododendron minutiflorum Hu.

Five undescribed triterpenoids, two unusual omphalane-type sesquiterpenoids together with twenty-five known compounds were isolated from the leaves and stems of Rhododendron minutiflorum Hu. The absolute configurations of 1-3 and 6 were established by single-crystal X-ray diffraction analysis and electronic circular dichroism (ECD). Compounds 6-7 feature the rare omphalane-type sesquiterpene skeleton and are verified by single-crystal X-ray diffraction analysis for the first time. In the biological activity assay, most of the triterpenoids have different degrees of inhibitory effects on α-glucosidase, with IC50 values ranging from 6.97 to 229.3 µM (the positive control drug acarbose has an IC50 value of 3.07 × 10-3 µM). Structure and activity relationship (SAR) study reveals that the oxidation degrees of C-3, C-8, or C-11 to C-13 of the ursane-type triterpenoid influence the inhibitory activity dramatically.