Diterpenoids with α-glucosidase inhibitory activities from the fruits of Vitex trifolia Linn.

Viticis Fructus, known as "Man-jing-zi", are the fruits of the traditional Chinese medicine Vitex trifolia Linn. and its variant Vitex trifolia Linn. var. simplicifolia. These fruits are used as folk medicines to treat various diseases. Although V. trifolia is useful for treating diabetes, the antidiabetic effect of its purified constituents is still under investigation. The phytochemical investigation on the ethanol extract of the fruits of V. trifolia yielded four new labdane diterpenoids vitetrolins A-D (1-4), together with seven (5-11) known analogs. The structures of these compounds were elucidated by spectroscopy techniques and the absolute configuration of 4 was determined by electronic circular dichroism (ECD) calculations. The isolated diterpenoids were evaluated for their α-glucosidase inhibitory activities. Compounds 5, 6, 8, and 9 exhibited moderate inhibitory activities against α-glucosidase with IC50 values ranging from 44.9 ± 6.1 to 70.5 ± 5.5 µM.

Diterpenoids and C13 Nor-Isoprenoid Identified From the Leaves and Twigs of Croton yanhuii Activating Apoptosis and Pyroptosis.

Croton yanhuii (Family Euphorbiaceae) is an annual aromatic plant endemic to Yunnan Province, China, which yields an aromatic, spicy oil used as a flavoring and fragrance. The aim of the present study was to acquire secondary metabolites from the leaves and twigs of C. yanhuii and to evaluate their cytotoxic activity. Five new diterpenoids, croyanhuins A-E (1-5), and one new C13 nor-isoprenoid, croyanhuin F (6), were isolated from the leaves and twigs of C. yanhuii. Their structures and absolute configurations were determined by extensive spectroscopic methods (1D and 2D NMR, IR, and HRESIMS) and confirmed by electronic circular dichroism (ECD) spectra or single-crystal X-ray diffraction analysis. Among the new terpenoids, compounds 1 and 3 inhibited cell proliferation and viability in a dose- and time-dependent manner, whereas both induced cleavage of either caspase-3 or PARP-1 in the SW480 cell line. Additionally, we observed that Z-YVAD-FMK and Z-VAD-FMK, two caspase inhibitors, inhibited the compound-dependent cell viability loss, suggesting that either of them can induce pyroptosis and caspase-dependent apoptosis. These biological assay results revealed that compounds 1 and 3 induce different kinds of programmed cell death in SW480 cells.

A new highly oxygenated germacranolide from Carpesium nepalense var. lanatum (C.B.Clarke) Kitam.

A new highly oxygenated germacranolide, carcerlane A (1), together with four known highly oxygenated germacranolides (2-5), was isolated from an ethanol extract of the whole plant of Carpesium nepalense var. lanatum (C.B.Clarke) Kitam. The structures were determined by HRESIMS and extensive analysis of their spectroscopic data including IR, 1 D and 2 D NMR spectra. To our best knowledge, it was the first time to report the phytochemical investigation on this plant. The anti-Alzheimer's disease (AD) activities of 1-5 were evaluated using Caenorhabditis elegans AD pathological model. All the tested compounds showed that they have the anti-AD bioactivities of delaying worms paralysis.

Two new aromatic derivatives from Codonopsis pilosula and their α-glucosidase inhibitory activities.

The ethanol extract of the roots of Codonopsis pilosula was subjected to chromatographic fractionation, which result in the isolation and characterization of two new aromatic derivatives 2,3-dihydroxypropyl 2,4-dihydroxy-3,6-dimethylbenzoate (1) and 2-oxopropyl 3-hydroxy-4-methoxybenzoate (2), along with three known compounds pilosulinene A (3), pollenfuran B (4) and (+)-pinoresinol (5). Their structures were demonstrated by HRESIMS and spectroscopic methods including NMR and IR. It is worth noting that compound 4 was isolated for the first time from the genus Codonopsis. The potential hypoglycemic properties of compounds 2-5 were evaluated by measuring their α-glucosidase inhibitory effects. As a result, compounds 2 and 3 showed weak α-glucosidase inhibitory activities with IC50 values of 154.8 ± 11.0 µM and 24.0 ± 2.2 µM, respectively.[Formula: see text].

Albumin Fusion at the N-Terminus or C-Terminus of HM-3 Leads to Improved Pharmacokinetics and Bioactivities.

HM-3, an integrin antagonist, exhibits anti-tumor biological responses and therefore has potential as a therapeutic polypeptide. However, the clinical applications of HM-3 are limited by its short half-life. In this study, we genetically fused human serum albumin (HSA) to the N or C-terminus of HM-3 to improve HM-3 pharmacokinetics. HM-3/HSA proteins were successfully expressed in Pichia pastoris and displayed improved pharmacokinetic properties and stability. Among them, the half-life of HM-3-HSA was longer than HSA-HM-3. In vitro, the IC50 values of HSA-HM-3 and HM-3-HSA were 0.38 ± 0.14 µM and 0.25 ± 0.08 µM in B16F10 cells, respectively. In vivo, the inhibition rates of B16F10 tumor growth were 36% (HSA-HM-3) and 56% (HM-3-HSA), respectively, indicating antitumor activity of HM-3-HSA was higher than HSA-HM-3. In conclusion, these results suggested that the HM-3/HSA fusion protein might be potential candidate HM-3 agent for treatment of melanoma and when HSA was fused at the C-terminus of HM-3, the fusion protein had a higher stability and activity.

[Changes in microglia number and Iba1 expression level in the prefrontal cortex of type 1 diabetic mice].

The aim of the present study was to observe the activation of microglia in the prefrontal cortex of type 1 diabetes mellitus (T1DM) mice, and the expression of the marker genes of the disease-associated microglia (DAM) associated with neurodegenerative diseases. Sixty healthy adult male C57BL/6J mice were randomly divided into two groups, normal control (CON) group and T1DM group. Streptozocin (STZ) was injected intraperitoneally to induce T1DM mice. The spatial learning and memory function of mice was detected by Morris water maze at the 8th week after the successful model establishment. The number and activation of microglia in the prefrontal cortex of mice were detected by immunofluorescence staining and Western blot. Changes in the mRNA level of several DAM molecular markers were detected by RT-FQ-PCR. The results showed that, compared with CON mice, the fasting blood glucose of T1DM mice increased significantly, while the body weight of T1DM mice decreased remarkably (P < 0.05). The escape latency of water maze in T1DM mice was longer than that in CON mice (P < 0.05). Compared with CON group, the Iba1 protein expression and the number of microglia in prefrontal cortex of T1DM group increased significantly (P < 0.05). In addition, the mRNA levels of several DAM markers in prefrontal cortex of T1DM group were increased significantly (P < 0.05). These results suggest that the microglia are activated and transformed to DAM type in the prefrontal cortex of T1DM mice.

Polyoxygenated sesquiterpenoids from Salvia castanea and their potential anti-Alzheime's disease bioactivities.

Salvia castanea (Family Labiatae), a perennial fragrant herb with castaneous flowers, is mainly distributed in areas with an altitude of 2500-3750 m. The roots of this plant were used as a tea drink by local residents to strengthen physical health. The aim of present study was to acquire secondary metabolites of the ethanol extract obtained from the whole plant of S. castanea and to evaluate their potential anti-Alzheimer's disease. Six new sesquiterpene lactones, salcastanins A-F (1-6), together with three known guaiane-type sesquiterpenoids nubiol (7), nubdienolide (8), and nubenolide (9), were separated from the whole plant of S. castanea. The structures of these compounds were determined by HRESIMS and NMR experiments. The absolute configurations of 1-6 were ascertained by electronic circular dichroism (ECD) experiments. The humanized Caenorhabditis elegans AD pathological model was used to evaluate anti-Alzheimer's disease (AD) activities of 1-9. The results showed the compounds 1-3 and 7 significantly delayed AD-like symptoms of worm paralysis phenotype, which could be used as novel anti-AD candidates.

Eupulcherol A, a triterpenoid with a new carbon skeleton from Euphorbia pulcherrima, and its anti-Alzheimer's disease bioactivity.

Eupulcherol A (1), a novel triterpenoid with an unprecedented carbon skeleton, was isolated from Euphorbia pulcherrima. Its structure was determined by comprehensive analysis of spectroscopic data, including HRESIMS and 1D and 2D NMR, and the absolute configuration was defined by single crystal X-ray diffraction analysis. Biological studies showed that compound 1 possessed anti-Alzheimer's disease (AD) bioactivity, which could delay paralysis of transgenic AD Caenorhabditis elegans. A plausible biogenetic pathway for eupulcherol A (1) was also proposed.

[PSA derivative indicators in the diagnosis of prostate cancer: Advances in studies].

Serum PSA is a most widely used biomarker for prostate cancer, which can help effectively screen out the high-risk population of prostate cancer and monitor the changes of the disease. However, the specificity of serum total PSA (tPSA) is poor and can easily lead to misdiagnosis. In recent years, a series of PSA derivative indicators have been developed, which can be used in combination with other diagnostic methods, such as MRI, ultrasonography, digital rectal examination, and other tumor markers, to improve the accuracy of early diagnosis, assess the malignancy, invasiveness and biochemical recurrence of prostate cancer, and make prostatic biopsy decisions. This review summarizes the advances in the application of PSA derivative indicators on the diagnosis of prostate cancer.