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.

Smoking Behavior and its Effect on Psychiatric Symptoms of Patients with Stable Schizophrenia.

Context: Schizophrenia is a common and clinically disabling mental disorder. Many patients with schizophrenia smoke. Research on the effects of smoking on schizophrenia's symptoms are inconsistent. Objective: The study intended to investigate the smoking status of patients with stable schizophrenia to determine the effects of smoking on schizophrenia-related symptoms. Design: The research team performed an case-control study. Setting: The study took place at Beijing Huilongguan Hospital in Beijing, Changping District, China. Participants: Participants were 160 patients at the hospital who had been diagnosed with stable schizophrenia between April 2018 and March 2020. Groups: The research team divided participants into two groups based on their current smoking status: (1) a smoking group with 72 participants and (2) a nonsmoking group with 88 participants. Outcome Measures: The research team: (1) examined the types of antipsychotic drugs that participants received; (2) used a schizophrenia-related scale, the Positive and Negative Syndrome Scale (PANSS), to examine participants' status; (3) examined the smoking habits of the smoking group; and (4) analyzed the correlation between the PANSS score and the smoking group's smoking index. Results: No significant difference existed between the groups in the type of medicine used (P > .05). The smoking group's PANSS total (P = .014), positive symptom (P = .039), and negative symptom (P = .003) scores were significantly lower than those of the nonsmoking group (P < .05). No significant difference existed between the groups in the general psychopathological symptom score (P > .05). The smoking group started smoking between 13 and 24 years of age, with an mean age of 19.11 ± 4.10 years. The group smoked 10-30 cigarettes/d, with a mean smoking amount of 18.4 ± 3.1 cigarettes/d, and the smoking index was 344.7 ± 48.0. The smoking group's smoking index was significantly negatively correlated with the positive symptom, negative symptom, and total PANSS scores (all P = .000). No correlation existed between the smoking index and the general psychopathological symptom score (P > .05). Conclusions: Smoking patients with stable schizophrenia generally exhibit fewer symptoms than nonsmoking patients, which relate to the alleviation of mental tension that smoking can provide.

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.

Chemical Profiling, Quantitation, and Bioactivities of Ginseng Residue.

Ginseng residue is a by-product stemming from the commercial extraction of ginsenosides. To assess the disparities between ginseng residue and ginseng tablet, we employed the ultra-high-performance liquid chromatography-quadrupole time-of-flight/mass spectrometry (UPLC-Q-TOF/MS) technique for sample analysis. The analyses revealed the presence of 39 compounds in both ginseng residue and ginseng tablets. Subsequently, the contents of total ginsenosides and total ginseng polysaccharides in the ginseng residue and ginseng tablet were determined. The results indicate that while only a small fraction of ginsenosides remained in the ginseng residue, a significant amount of polysaccharides was retained. Furthermore, our evaluation encompassed the antioxidant activities of both ginseng residue and ginseng tablets. Notably, ginseng residue exhibited robust antioxidant effects, thereby showcasing its potential for recycling as a functional food raw material.

Selenium nanoparticles coupling with Astragalus Polysaccharides exert their cytotoxicities in MCF-7 cells by inhibiting autophagy and promoting apoptosis.

BACKGROUND: Astragalus Polysaccharides (APS) had been reported to exhibit antitumor activities. Given that nanoparticles possessed unique advantages in cancer treatment, APS was used as the modifier to prepare gold, silver and selenium nanoparticles (APS-Au, APS-Ag and APS-Se NPs) in the present study. METHODS: The three nanoparticles were synthesized via a green approach and characterized by DLS, TEM, XRD, FT-IR and UV-Vis. The inhibitory effects of these nanoparticles on various tumor cells proliferation were examined by MTT assay in vitro. Reactive oxygen species (ROS), mitochondrial membrane potential (MMP) and the expression of apoptosis and autophagy-related proteins were also detected. RESULTS: Among these, APS-Se NPs displayed the most potent antitumor activities against MCF-7 cells in vitro. Flow cytometric analysis suggested that after cells were exposed to elevated concentrations of APS-Se NPs (10, 20 and 40 µmol/L), the rate of apoptosis was increasing (16.63 ± 0.89, 38.60 ± 3.46 and 44.38 ± 2.62%, respectively). Further analysis by immunofluorescence revealed an increase in intracellular ROS and a loss of MMP. This was accompanied by increased LC3-I to LC3-II conversion. Also, western blot analysis demonstrated that the ratios of Bax/Bcl-2 and cleaved caspase9/caspase 9 rose, and LC3-II and p62 protein levels increased. The addition of chloroquine, an inhibitor of autophagy, further enhanced protein expression of p62 and LC3-II. CONCLUSION: APS-Se NPs exerted their cytotoxic activity in MCF-7 cells by blocking autophagy and facilitating mitochondrial pathway-mediated apoptosis.

Microemulsions containing long-chain oil ethyl oleate improve the oral bioavailability of piroxicam by increasing drug solubility and lymphatic transportation simultaneously.

Drug solubility and lymphatic transport enhancements are two main pathways to improve drug oral bioavailability for microemulsions. However, it is not easy to have both achieved simultaneously because excipients used for improving lymphatic transport were usually insufficient in forming microemulsions and solubilizing drugs. Our research is to explore whether ethyl oleate, an oil effective in developing microemulsions with desired solubilizing capability, could increase bioavailability to a higher extent by enhancing lymphatic transport. As a long-chain oil, ethyl oleate won larger microemulsion area than short-chain tributyrin and medium-chain GTCC. In contrast, long-chain soybean oil failed to prepare microemulsions. The solubility of piroxicam in ethyl oleate microemulsions (ME-C) increased by about 30 times than in water. ME-C also won significantly higher AUC0-t compared with tributyrin microemulsions (ME-A) and GTCC microemulsions (ME-B). Oral bioavailability in ME-C decreased by 38% after lymphatic transport was blocked by cycloheximide, severer than those in ME-A and ME-B (8% and 34%). These results suggest that improving lymphatic transport and solubility simultaneously might be a novel strategy to increase drug oral bioavailability to a higher extent than increasing solubility only. Ethyl oleate is a preferred oil candidate due to its integrated advantages of high solubilizing capability, large microemulsion area and effective lymphatic transport.