Neuroprotective and acetylcholinesterase inhibitory activities of alkaloids from Solanum lyratum Thunb.: An in vitro and in silico analyses.

The n-BuOH extract from the herb of Solanum lyratum Thunb. (Solanaceae) was purified by various chromatographic methods, which led to the isolation of seven undescribed alkaloids ((-)-(7'S)-N-feruloyltyramine A, (+)-(7'R)-N-feruloyltyramine A, (+)-(7'S)-N-solanamide A, (-)-(7'R)-N-solanamide A, 7'S-perillascens, solanpyrrole A, and (Z)-asmurratetra A) and 13 known alkaloids, including four pairs of enantiomers. Extensive spectroscopic data and electronic circular dichroism (ECD) calculations were applied to determine the structures of the undescribed compounds. In in vitro biological activity assays, (-)-(7'S)-N-feruloyltyramine A and (+)-(7'R)-N-feruloyltyramine A exhibited pronounced neuroprotective effects against SH-SY5Y cell damage with survival rates of 75.98% and 76.61%, respectively, at 50 µM. Additionally, (-)-(7'S)-N-feruloyltyramine A and N-cis-feruloyl-3'-methoxy-tyramine displayed acetylcholinesterase (AChE) inhibitory effects with IC50 values of 7.41 ± 1.76 µM and 9.21 ± 0.89 µM, respectively. Molecular docking simulations revealed that (-)-(7'S)-N-feruloyltyramine A had a binding site for AChE. These findings reveal the structural diversity of the bioactive compounds in S. lyratum and provides insights into the use of this information for the production of functional components in the pharmaceutical industry.

Insight into Isolation and Characterization of Phenolic Compounds from Hawthorn (Crataegus pinnatifida Bge.) with Antioxidant, Anti-Acetylcholinesterase, and Neuroprotective Activities.

Recent epidemiologic studies have demonstrated a link between the consumption of daily functional fruits rich in phenols and the prevention of disease for neurodegenerative disorders. Hawthorn products are derived from the functional fruit hawthorn, which is rich in phenols and has been used around the world for centuries. In order to explore the phenolic components in hawthorn, the investigation of the ethanol extract led to the separation of five new phenol compounds (1a/1b, 2-4), including one pair of enantiomers (1a/1b), along with seven disclosed analogs (5-11). Their structures were elucidated based on extensive spectroscopic analyses and electronic circular dichroism (ECD). The compounds (1-11) were tested for antioxidant activities by 2,2-diphenyl-1-picrylhydrazyl (DPPH), 2,2'-azino-bis (3-ethylbenzothiazoline-6-sulphonicacid) (ABTS), and ferric reducing antioxidant power (FRAP) methods. Apart from that, monomeric compounds 2, 4, and 6 exhibited more potent protective capabilities against H2O2 (hydrogen peroxide)-induced SH-SY5Y cells. Meanwhile, electronic analyses were performed using the highest occupied molecular orbital (HOMO), and the lowest unoccupied molecular orbital (LUMO) to analyze compounds 2, 4, and 6. Furthermore, compounds (1-11) measured acetylcholinesterase (AChE) inhibitory activities, and 2, 4, and 6 possessed greater AChE inhibitory activity than donepezil. At the same time, molecular docking was used to investigate the possible mechanism of the interaction between active compounds (2, 4, and 6) and AChE.

Chamaejasmenin E from Stellera chamaejasme induces apoptosis of hepatocellular carcinoma cells by targeting c-Met in vitro and in vivo.

Hepatocellular carcinoma (HCC), the most prevalent liver cancer, is considered one of the most lethal malignancies with a dismal outcome. There is an urgent need to find novel therapeutic approaches to treat HCC. At present, natural products have served as a valuable source for drug discovery. Here, we obtained five known biflavones from the root of Stellera chamaejasme and evaluated their activities against HCC Hep3B cells in vitro. Chamaejasmenin E (CE) exhibited the strongest inhibitory effect among these biflavones. Furthermore, we found that CE could suppress the cell proliferation and colony formation, as well as the migration ability of HCC cells, but there was no significant toxicity on normal liver cells. Additionally, CE induced mitochondrial dysfunction and oxidative stress, eventually leading to cellular apoptosis. Mechanistically, the potential target of CE was predicted by database screening, showing that the compound might exert an inhibitory effect by targeting at c-Met. Next, this result was confirmed by molecular docking, cellular thermal shift assay (CETSA), as well as RT-PCR and Western blot analysis. Meanwhile, CE also reduced the downstream proteins of c-Met in HCC cells. In concordance with above results, CE is efficacious and non-toxic in tumor xenograft model. Taken together, our findings revealed an underlying tumor-suppressive mechanism of CE, which provided a foundation for identifying the target of biflavones.

Phosphorus cycling in freshwater lake sediments: Influence of seasonal water level fluctuations.

Freshwater lakes experience drastic water level fluctuations because of climate change and human activities. However, the influence of such fluctuations on phosphorus cycling in sediments has rarely been investigated. We conducted a geochemical investigation on the phosphorus cycle in a shallow freshwater lake, Dongting Lake; under the influence of human activities and climate change, its water regime undergoes drastic changes. Irrespective of the permanent inundation zone (PIZ) or seasonal inundation zone (SIZ), the phosphorus cycle in sediments was found to be dominated by the reductive dissolution of iron (Fe) (oxyhydr)oxides, degradation of organic matters, and conversion between authigenic phosphorus (Ca-P) and detrital phosphorus in individual seasons. From winter to summer, with increasing water level, the content of Fe-bound phosphorus and organic phosphorus increase due to the deposition of suspended matter, thus increasing total phosphorus in PIZ. Moreover, the rising water level also reduces the dissolved oxygen content and promotes the reductive dissolution of Fe (oxyhydr)oxides. The mineralization of increased organic matter can release CO2 and reduce pH in the vicinity, which can further result in the acidic dissolution of detrital apatite. In turn, most of the released phosphorus can be adsorbed or co-precipitated with calcium minerals, resulting in the significant increase of Ca-P. The mechanisms of phosphorus transformation in SIZ are similar to those in PIZ, but most of the increased organic matter and total P in a core from SIZ are attributable to the decomposition of plant matter. Therefore, the water level rise not only changes the conservative speciation of phosphorus in sediments to active speciation, but also triggers the release of phosphorus adsorbed to oxides and further increases the risk of phosphorus release from sediments to overlying water. Thus, our findings have major implications for freshwater shallow lakes and their P-driven productivity.

Effects of Transcutaneous Electrical Acupoint Stimulation (TEAS) on Postoperative Recovery in Patients with Gastric Cancer: A Randomized Controlled Trial.

PURPOSE: Transcutaneous electrical acupoint stimulation (TEAS) is an innovative choice for postoperative pain management. However, the safety and effectiveness of this traditional Chinese medicine (TCM) therapy for patients who underwent gastrectomy is largely unknown. So, the purpose of this study is to evaluate the safety and effectiveness of TEAS for patients who underwent gastrectomy. PATIENTS AND METHODS: We recruited 96 patients with gastric cancer from May 2019 to November 2019; 82 patients were enrolled, and 81 patients completed. Patients were randomly assigned to TEAS group (TG) received TEAS on postoperative day (POD) 1-3 or control group (CG) at a 1:1 ratio. The primary outcomes were pain score and consumption of analgesics. The secondary were the time of first postoperative flatus and defecation, frequency of postoperative nausea, vomiting, distention, diarrhea, comfort of semi-fluid diet, Clavien-Dindo grade (C-D grade) and length of postoperative day. We performed hematological analysis to explore the possible mechanisms. RESULTS: Overall, 81 patients were enrolled included in the analysis. Compared with CG, pain scores in TG were lower on POD 1-5 (average: 2.55±0.21 vs 3.10±0.42, P<0.001), and the use rate of opioids was lower (43.9 vs 75.0, P=0.004); time of first postoperative flatus (55.63±16.74 vs 72.60±20.92, P<0.001) and defecation (72.20±16.24 vs 95.78±17.75, P<0.001) were shorter; the frequency of nausea were fewer (1.88±1.09 vs 2.58±0.77, P=0.029) and patients were more comfortable with semi-fluid diet (7.63±0.63 vs 6.93±0.69, P<0.001); among the hematologic results, ß-endorphin (ß-End), interleukin-2 (IL-2), motilin (MTL) on POD 3, POD 5 were lower, 5-hydroxytryptamine (5-HT), interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α) were higher. And no adverse event was reported. CONCLUSION: TEAS can relieve postoperative pain and promote the recovery of gastrointestinal function. Consequently, it can be an adjunctive therapy to enhance postoperative recovery for patients after gastrectomy.

Evaluation of a tumor electric field treatment system in a rat model of glioma.

OBJECTIVE: Glioma is a devastating disease lacking effective treatment. Tumor electric field therapy is emerging as a novel non-invasive therapy. The current study evaluates the efficacy and safety of a self-designed tumor electric field therapy system (TEFTS ASCLU-300) in a rat orthotopic transplantation model of glioma. METHODS: A model of intracranial orthotopic transplantation was established in rats using glioma C6 cells. For electric field therapy, glioma-bearing rats were exposed to alternating electric fields generated by a self-developed TEFTS starting on either 1st (Group 2) or 3rd (Group 3) day after transplantation, while other conditions were maintained the same as non-treated rats (Group 1). Glioma size, body weight, and overall survival (OS) were compared between groups. Immunohistochemical staining was applied to access tumor cell death and microvessel density within the tumor. In addition, the systemic effects of TEFTS on blood cells, vital organs, and hepatorenal functions were evaluated. RESULTS: TEFTS treatment significantly elongated the OS of tumor-bearing rats compared with non-treated rats (non-treated vs treated: 24.77 ± 7.08 days vs 40.31 ± 19.11 days, P = .0031). Continuous TEFTS treatment starting on 1st or 3rd day significantly reduced glioma size at 2 and 3 weeks after tumor cell inoculation (Week 2: Group 1:289.95 ± 101.69 mm3 ; Group 2:70.45 ± 17.79 mm3 ; Group 3:73.88 ± 33.21 mm3 , P < .0001. Week 3: Group 1:544.096 ± 78.53 mm3 ; Group 2:187.58 ± 78.44 mm3 ; Group 3:167.14 ± 109.96 mm3 , P = .0005). Continuous treatment for more than 4 weeks inhibited tumor growth. The TEFTS treatment promoted tumor cell death, as demonstrated by increased number of Caspase 3+ cells within the tumor (non-treated vs treated: 38.06 ± 10.04 vs 68.57 ± 8.09 cells/field, P = .0007), but had minimal effect on microvessel density, as shown by CD31 expression (non-treated vs treated: 1.63 ± 0.09 vs 1.57 ± 0.13% of positively stained areas, P > .05). No remarkable differences were observed in hepatorenal function, blood cell counts, or other vital organs between non-treated and treated groups. CONCLUSION: The TEFTS developed by our research team was proved to be effective and safe to inhibit tumor growth and improve general outcomes in a rat model of brain glioma.