Lignans of Schisandra chinensis (Turcz.) Baill inhibits Parkinson's disease progression through mediated neuroinflammation-TRPV1 expression in microglia.

BACKGROUND: Schisandra chinensis (Turcz.) Baill (S. chinensis), a member of the Magnoliaceae family, is renowned for its distinctive medicinal attributes and is commonly employed in the treatment of disorders affecting the CNS. PURPOSE: The potential therapeutic effects of a lignan-enriched extract derived from Schisandra chinensis (Turcz.) Baill (LSC) on PD is assessed, which focuses on its mechanisms of action in addressing neuroinflammation. METHODS: The LSC has been obtained by purifying the ethyl alcohol extract of S. chinensis. The Orbitrap-MS method has been employed to analyze the chemical composition of the LSC. In LPS-induced BV2 cells, LSC-induced changes in M1/M2 type inflammatory cytokines have been examined using the Griess reaction, Elisa, JC-1, flow cytometry, IF, and WB methods. A model of PD has been established by treatment of MPTP in C57BL/6 mice. The effect of LSC on behavioral changes, inflammatory factor levels, expression of TH and IBA-1, and production of autophagy in the midbrain has been investigated by TEM, immunohistochemistry, Elisa, and WB. RESULTS: LSC has relieved sports injuries and pathological damage, and targeted the TRPV1-AMPK-NLRP3 signaling pathway, which affected neuroinflammation and autophagy in vivo. Furthermore, in vitro investigations demonstrated that LSC has activated M1/M2 transformation, its related inflammatory factors, and protein expressions of the NLRP3-Caspase1 signaling pathway in LPS-BV2 cells. The research notably demonstrated that the LSC promoted autophagy and suppressed inflammation through targeting TRPV1. CONCLUSION: In the investigation, LSC focused on TRPV1 and controlled neuroinflammation-autophagy by regulating AMPK-NLRP3, which has been proven for the first time. The study has presented molecular data supporting the use of LSC in treating PD and offers references for developing drugs. Remarkably, LSC has the potential to be utilized as a therapeutic or health medication that could significantly decrease PD.

Schisandra chinensis (Turcz.) Baill neutral polysaccharides alleviate Parkinson's disease via effectively activating MCL-1 expression regulation of autophagy signaling.

The purified neutral polysaccharide fraction, namely SBP-1, was isolated and characterized from Schisandra chinensis (Turcz.) Baill crude polysaccharides, which have anti-Parkinson's disease activity were investigated in vivo and in vitro. Experiments have shown that the main chain of SBP-1 was Glcp-(1→, →4)-Glcp-(1→ and →4,6)-Glcp-(1→. We also revealed the effect of SBP-1 on the PD mice model and the potential underlying molecular mechanism. The results showed that SBP-1 administration improved behavioral deficits, increased tyrosine hydroxylase-positive cells, attenuated loss of dopaminergic neurons in MPTP-exposed mice, and reduced cell death induced by MPP+. The MCL-1 was identified as the target of SBP-1 by the combination of docking-SPR-ITC, WB, and IF experiments. Subsequently, the study showed that SBP-1 could target MCL-1 to enhance autophagy with a change in the apoptotic response, which was further demonstrated by a change in LC3/P62, PI3K/AKT/mTOR, and possesses a change in the expression of BCL2/BAX/Caspase3. These results demonstrate that SBP-1 may protect neurons against MPP+ or MPTP-induced damage in vitro and in vivo through enhancing autophagy. In summary, these findings indicate that SBP-1 and S. chinensis show potential as effective candidates for further investigation in the prevention and treatment of PD or associated illnesses, specifically through autophagy apoptotic-based mechanisms.

Protective effect of phenylpropionamides in the seed of Cannabis Sativa L. on Parkinson's disease through autophagy.

Parkinson's disease (PD) is the second most common neurodegenerative disease in the world. As one of the major degradation pathways, autophagy plays a pivotal role in maintaining the effective turnover of proteins and damaged organelles in cells. Lewy bodies composed of α-synuclein (α-syn) abnormally aggregated in the substantia nigra are important pathological features of PD, and autophagy dysfunction is considered to be an important factor leading to abnormal aggregation of α-syn. Phenylpropionamides (PHS) in the seed of Cannabis sativa L. have a protective effect on neuroinflammation and antioxidant activity. However, the therapeutic role of PHS in PD is unclear. In this study, the seeds of Cannabis sativa L. were extracted under reflux with 60% EtOH-H2O, and the 60% EtOH-H2O elution fraction was identified as PHS with the UPLC-QTOF-MS. The 1-methyl-4-phenyl-1,2,3,6-tetrahydro-pyridine (MPTP)-induced PD model in C57BL/6 J mice was used for behavioral and pharmacodynamic experiments. Behavioral symptoms were improved, Nissl-stained and TH-positive neurons in the substantia nigra were significantly increased in PHS-treated MPTP-induced PD model mice. Compared with the model group, PHS treatment reduced the expression level of α-syn, and the expression of TH increased significantly by western blotting, compared with the model group, the PHS group suppressed Caspase 3 and Bax expression and promoted Bcl-2 expression and levels of p62 decreased significantly, the ratio of LC3-II/I and p-mTOR/mTOR in the PHS group had a downward trend, suggesting that the therapeutic effect of PHS on MPTP-induced PD model mice may be triggered by the regulation of autophagy.

Steroidal saponins from the roots of Paris verticillata and their anti-proliferative and anti-inflammatory activities.

Thirteen previously undescribed steroidal saponins, named parisverticilloside A-M (1-13) and twenty known steroidal saponins (14-33) were isolated from ethanol extract of the roots of Paris verticillata. Their structures were identified by a series of spectroscopic methods, including 1D and 2D NMR, HR-ESI-MS, optical rotatory dispersion and chemical processes. The anti-proliferative activities of all compounds against LN229, HepG2, MDA-MB-231 and 4T1 cell lines were evaluated using the CCK8 assay with cisplatin or capecitabine as the positive control. The anti-inflammatory activities of all compounds were measured by inhibition of LPS-induced NO release from BV2 cell lines, with dexamethasone as the positive control.

Terpenoid compounds from the fruits of Solanum virginianum.

Eleven compounds were isolated and identified from ethanolic extracts of Solanum virginianum fruits, including two new compounds (1-2) and nine known compounds (3-11). Their structures were determined to be melongenaterpene C15-O-ß-D-glucopyranoside (1), (9Z)-3,7,11,15-tetramethyl -hexadeca-1,6,10-triene-3,5,14,15-tetraol-5-O-ß-D-glucopyranoside (2), actini-dioionoside A (3), byzantionoside B (4), citroside A (5), 7Z-roseoside (6), matenoside A (7), megastigmane (8), dihydrophaseic acid 3'-O-ß-D-glucopyranoside (9), taraxerol (10), and huzhangoside C (11). In this paper, NMR spectroscopy was used to study the structures of the compounds, comparing their data with those in the literature. In addition, the potential anti-inflammatory activity of the compounds was also evaluated using the RAW264.7 cell inflammation model induced by lipopolysaccharide (LPS). The terpenoids showed no significant anti-inflammatory activity.

New chromones from the roots of Saposhnikovia divaricata (Turcz.) Schischk with anti-inflammatory activity.

Fifteen new chromones, sadivamones A-E (1-5), cimifugin monoacetate (6), sadivamones F-N (7-15), together with fifteen known chromones (16-30), were isolated from the ethyl acetate portions of 70% ethanol extract of Saposhnikovia divaricata (Turcz.) Schischk roots. The structures of the isolates were determined using 1D/2D NMR data and electron circular dichroism (ECD) calculations. Meanwhile, LPS induced RAW264.7 inflammatory cell model was used to determine the potential anti-inflammatory activity of all the isolated compounds in vitro. The results showed that compounds 2, 8, 12-13, 18, 20-22, 24, and 27 significantly inhibited the production of lipopolysaccharide (LPS)-induced NO in macrophages. To determine the signaling pathways involved in the suppression of NO production by compounds 8, 12 and 13, we investigated ERK and c-Jun N-terminal protein kinase (JNK) expression by western blot analysis. Further mechanistic studies demonstrated that compounds 12 and 13 inhibited the phosphorylation of ERK and the activation of ERK and JNK signaling in RAW264.7 cells via MAPK signaling pathways. Taken together, compounds 12 and 13 may be valuable candidates for the treatment of inflammatory diseases.

Inositol Derivatives with Anti-Inflammatory Activity from Leaves of Solanum capsicoides Allioni

Eight new inositol derivatives, solsurinositols A-H (1-8), were isolated from the 70% EtOH extract of the leaves of Solanum capsicoides Allioni. Careful isolation by silica gel column chromatography followed by preparative high-performance liquid chromatography (HPLC) allowed us to obtain analytically pure compounds 1-8. They shared the same relative stereochemistry on the ring but have different acyl groups attached to various hydroxyl groups. This was the first time that inositol derivatives have been isolated from this plant. The chemical structures of compounds 1-8 were characterized by extensive 1D nuclear magnetic resonance (NMR) and 2D NMR and mass analyses. Meanwhile, the in vitro anti-inflammatory activity of all compounds was determined using lipopolysaccharide (LPS)-induced BV2 microglia, and among the isolates, compounds 5 (IC50 = 11.21 ± 0.14 µM) and 7 (IC50 = 14.5 ± 1.22 µM) were shown to have potential anti-inflammatory activity.

Datinolides E-I, five new withanolides with anti-inflammatory activity from the leaves of Datura inoxia Mill.

Five new withanolides, datinolides E-I (1-5), and three known withanolides (6-8) were separated from Datura inoxia Mill. leaves, and datinolide E (1) was the first withanolide with C-27 connected to a nitrogen-containing group. Their structures were clarified by comprehensive spectroscopic analysis and comparison with literature. The anti-inflammatory of isolated compounds against RAW264.7 cells was investigated by the CCK8 assay.

Four new withanolides with anti-inflammatory activity from Datura inoxia Mill. leaves.

Four previously undescribed withanolides, datinolides A-D (1-4) and eight known withanolides (5-12), were separated from the 70% ethyl alcohol extract of Datura inoxia Mill. leaves. All structures were clarified by comprehensive spectroscopic analysis. Furthermore, all withanolides were assessed for their anti-inflammatory activity and results showed that 1 exhibited a fairly good suppression against nitric oxide generation in lipopolysaccharide-stimulated RAW 264.7 cells (IC50 = 10.33 ± 1.53 µM).

Chemical Constituents of the Roots of Schisandra chinensis.

One new phenylpropanoid schineolignin D (1), one new sesquiterpene (-)-(7S,10S)-3,11,12,13-tetrahydroxycalamenene (2), one new quinic acid 4-(E)-O-coumaroylquinic acid ethyl ester (3), and seven known compounds 4-10 were separated from the roots of Schisandra chinensis. The chemical structures of all compounds were characterized by NMR spectroscopic experiments. All compounds were assessed for their neuroprotective effects on PC12 cell lines induced by H2 O2 . Compounds 1, 3-4, and 7 showed statistically significant neuroprotective activities with the negative control group at 12.5 µM.

Bioactive lipids from the fruits of Solanum xanthocarpum and their anti-inflammatory activities.

Bioactive lipids widely found in daily consumed plants and animals are essential or beneficial to health and some of them are important physiological regulators in the human body. In our current investigation, 18 bioactive lipids (1-18), including 8 sphingolipids (1-8), 7 oxylipins (9-15), 3 phenolic lipids (16-18) were isolated from the fruits of Solanum xanthocarpum. And compounds 1, 9, 15, 16, and 18 were new lipids. In this study, homologues (4-8, 16, and 17) and configuration isomers (2 and 3) of bioactive lipids were separated, and NMR combined with MS/MS2 was an effective method to identify these compounds. These findings provided the reference for the separation and structural identification of bioactive lipids. The anti-inflammatory activities of all isolated lipids were evaluated by their inhibition of the NO release of LPS-induced RAW 264.7 cells. Aglycone components of sphingolipids, oxylipids with free carboxylic acid groups, phenylpropionic acid-fatty acid glyceride polymer exhibited significant anti-inflammatory activities. Further analysis by molecular docking revealed the interactions of bioactive compounds with the iNOS protein.

Prevalence of Delirium and Coma In Mechanically Ventilated Patients Sedated With Dexmedetomidine or Propofol.

OBJECTIVE: To assess the prevalence of delirium and coma in mechanically ventilated patients sedated with dexmedetomidine or propofol alone; to evaluate the hospital length of stay for both treatment groups; and to evaluate the level of sedation, adverse effects, and hospital outcomes. METHODS: Medical records were reviewed retrospectively for patients who were admitted to the medical or surgical intensive care units (ICUs) in a 591-bed teaching hospital and who received either dexmedetomidine or propofol alone for 24 hours or more for sedation. RESULTS: A total of 111 patients were included in the study, with 56 patients in the dexmedetomidine group and 55 patients in the propofol group. Results of the analysis showed that the propofol group had a higher prevalence of coma (43.6% versus 12.5%; P < 0.001). Dexmedetomidine patients had a longer median hospital length of stay of 23.5 days (interquartile range [IQR], 11.5-39.5 days) versus 15.0 days (IQR, 7.0-24.0 days; P = 0.01). The rates of delirium were similar in both groups, with 16% in dexmedetomidine-treated patients versus 20% in propofol-treated patients (P = 0.63). CONCLUSION: No difference in the prevalence of delirium was found when comparing the dexmedetomidine- and propofol-treated groups. Propofol was associated with more coma and oversedation; dexmedetomidine was associated with longer time to extubation, longer length of stay in the ICU, and longer hospital length of stay.