Coptidis Rhizoma and its isolated alkaloids are reported to possess a variety of activities, including neuroprotective and antioxidant effects. Thus, the anti-Alzheimer and antioxidant effects of six ...protoberberine alkaloids (berberine, palmatine, jateorrhizine, epiberberine, coptisine, and groenlandicine) and one aporphine alkaloid (magnoflorine) from Coptidis Rhizoma were evaluated via β-site amyloid precursor protein (APP) cleaving enzyme 1 (BACE1), acetylcholinesterase (AChE), and butyrylcholinesterase (BChE) assays, along with peroxynitrite (ONOO−) scavenging and total reactive oxygen species (ROS) inhibitory assays. Six protoberberine alkaloids exhibited predominant cholinesterases (ChEs) inhibitory effects with IC50 values ranging between 0.44—1.07 μM for AChE and 3.32—6.84 μM for BChE; only epiberberine (Ki=10.0) and groenlandicine (Ki=21.2) exerted good, non-competitive BACE1 inhibitory activities with IC50 values of 8.55 and 19.68 μM, respectively. In two antioxidant assays, jateorrhizine and groenlandicine exhibited significant ONOO− scavenging activities with IC50 values of 0.78 and 0.84 μM, respectively; coptisine and groenlandicine exhibited moderate total ROS inhibitory activities with IC50 values of 48.93 and 51.78 μM, respectively. These results indicate that Coptidis Rhizoma alkaloids have a strong potential of inhibition and prevention of Alzheimer's disease (AD) mainly through both ChEs and β-amyloids pathways, and additionally through antioxidant capacities. In particular, groenlandicine may be a promising anti-AD agent due to its potent inhibitory activity of both ChEs and β-amyloids formation, as well as marked ONOO− scavenging and good ROS inhibitory capacities. As a result, Coptidis Rhizoma and the alkaloids contained therein would clearly have beneficial uses in the development of therapeutic and preventive agents for AD and oxidative stress-related disease.
In the present study, we investigated the structure-activity relationship of naturally occurring hesperetin derivatives, as well as the effects of their glycosylation on the inhibition of ...diabetes-related enzyme systems, protein tyrosine phosphatase 1B (PTP1B) and α-glycosidase. Among the tested hesperetin derivatives, hesperetin 5-
-glucoside, a single-glucose-containing flavanone glycoside, significantly inhibited PTP1B with an IC
value of 37.14 ± 0.07 µM. Hesperetin, which lacks a sugar molecule, was the weakest inhibitor compared to the reference compound, ursolic acid (IC
= 9.65 ± 0.01 µM). The most active flavanone hesperetin 5-
-glucoside suggested that the position of a sugar moiety at the C-5-position influences the PTP1B inhibition. It was observed that the ability to inhibit PTP1B is dependent on the nature, position, and number of sugar moieties in the flavonoid structure, as well as conjugation. In the kinetic study of PTP1B enzyme inhibition, hesperetin 5-
-glucoside led to mixed-type inhibition. Molecular docking studies revealed that hesperetin 5-
-glucoside had a higher binding affinity with key amino residues, suggesting that this molecule best fits the PTP1B allosteric site cavity. The data reported here support hesperetin 5-
-glucoside as a hit for the design of more potent and selective inhibitors against PTP1B in the search for a new anti-diabetic treatment.
Most previous studies have been focused on the variation of tea chemical composition by fermentative processes as well as different cultivars and regions. The detailed changes of flavonoid profiles ...were described for the first time by each processing step of green and black tea leaves in this study. A total of 24 flavonoid derivatives including catechins, theaflavins, and flavonols were separated and identified from the tea samples based on UPLC-DAD-QToF/MS data and constructed library. Among these, the fragmentation pathway of theaflavins was proposed specifically in positive ionization mode for structural interpretation. During leaf processing, the individual flavonols were changed as diverse patterns according to their aglycone types and glycosylated forms, but their total content showed a slight difference. EGCG and ECG were increased after roasting approximately twofold higher than that of fresh leaves (EGCG, 2709.5 →6085.6; ECG, 1548.0 →2318.2 mg/100 g dry weight, respectively) in green tea while considerably decreased their contents due to oxidation and conversion to theaflavins after fermentation during black tea processing. Especially, the drying steps also found to be factor to influence positively to increase the flavonoid contents in both tea processing. Therefore, this result indicated that detailed conditions of each processing step played important roles in changing the flavonoid profiles from tea leaves.
Graphical abstract
(L.) Areschoug (
) is a species of littoral brown algae of the class Phaeophyceae. Only a few studies on the apoptotic, antiviral, and antioxidant properties of
have been reported, and its inhibitory ...effect on melanin synthesis has not been studied. The aim of this study was to investigate the anti-melanogenic effect of
extract on α-melanocyte-stimulating hormone (α-MSH)-induced B16F10 melanocytes and its mechanism of action.
was extracted using 80% ethanol (LDE) and then fractioned between ethyl acetate (LDE-EA) and water (LDE-A). Our data demonstrated that LDE-EA significantly inhibited melanin level and cellular tyrosinase activity in α-MSH-stimulated B16 cells. In addition, the expression of genes associated with melanin synthesis, such as microphthalmia-associated transcription factor (
), tyrosinase (
), tyrosinase-related protein-1 (
), dopachrome tautomerase (
), and melanocortin 1 receptor (
) was down-regulated by LDE-EA treatment. Moreover, LDE-EA decreased p-CREB levels, which suggests that the inhibition of the cAMP/PKA/CREB pathways may be involved in the anti-melanogenic effect of LDE-EA. Thus, this study revealed that LDE-EA is an effective inhibitor of hyperpigmentation through inhibition of CREB pathways and may be considered as a potential therapeutic agent for hyperpigmentation disorders.
A new β-cyclogeraniol diglycoside (5), along with four known components, cycloartenol (1), p-hydroxybenzoic acid (2), vanilloloside (3), and 5′-O-methyladenosine (4), were first isolated from the ...n-BuOH fraction of Nelumbo nucifera stamens. The chemical structure of 5 was elucidated as 1-hydroxymethyl-2,6,6-trimethyl-1-cyclohexene 9-O-β-D-glucopyranosyl-(1→6)-β-D-glucopyranoside (nuciferoside) on the basis of chemical and spectroscopic evidence, including 1D, 2D NMR, and MS. The anti-Alzheimer effects of 1—5 were evaluated via the acetylcholinesterase (AChE), butyrylcholinesterase (BChE), and β-site amyloid precursor protein (APP) cleaving enzyme 1 (BACE1) inhibition assays. Compounds 1—3 and 5 showed good and noncompetitive inhibition against AChE with IC50 values of 11.89, 20.07, 4.55, and 3.20 μM and Kivalues of 15.71, 25.44, 7.76, and 5.76 μM, respectively. Compounds 1, 2, and 5 also possessed BChE inhibitory activities with IC50 values of 13.93, 62.29, 205.78, and 83.06 μM, respectively. The selectivity index (SI) values of 1, 2, 3, and 5, calculated from IC50 values of BChE and AChE, were 1.2, 3.1, 45.7, and 26.0. However, all isolated compounds lacked BACE1 inhibition up to 100 μM. Therefore, N. nucifera stamens-derived compounds could potentially exert their primary anti-Alzheimer effects as AChE inhibitors rather than BACE1 inhibitors.
The addition of ovarian function suppression (OFS) for 5 years to tamoxifen (TAM) for treatment of premenopausal patients with breast cancer after completion of chemotherapy has beneficial effects on ...disease-free survival (DFS). This study evaluated the efficacy of adding 2 years of OFS to TAM in patients with hormone receptor-positive breast cancer who remain in a premenopausal state or resume ovarian function after chemotherapy.
We enrolled 1,483 premenopausal women (age ≤ 45 years) with estrogen receptor-positive breast cancer treated with definitive surgery after completing adjuvant or neoadjuvant chemotherapy. Ovarian function was assessed every 6 months for 2 years since enrollment on the basis of follicular-stimulating hormone levels and vaginal bleeding history. If ovarian function was confirmed to be premenopausal at each visit, the patient was randomly assigned to complete 5 years of TAM alone (TAM-only) group or 5 years of TAM with OFS for 2 years that involved monthly goserelin administration (TAM + OFS) group. DFS was defined from the time of enrollment to the time of the first event.
A total of 1,293 patients were randomly assigned, and 1,282 patients were eligible for analysis. The estimated 5-year DFS rate was 91.1% in the TAM + OFS group and 87.5% in the TAM-only group (hazard ratio, 0.69; 95% CI, 0.48 to 0.97;
= .033). The estimated 5-year overall survival rate was 99.4% in the TAM + OFS group and 97.8% in the TAM-only group (hazard ratio, 0.31; 95% CI, 0.10 to 0.94;
= .029).
The addition of 2 years of OFS to TAM significantly improved DFS compared with TAM alone in patients who remained premenopausal or resumed ovarian function after chemotherapy.
The COVID-19 pandemic has increased the prevalence of depressive disorders worldwide, requiring alternative treatments beyond medication and psychotherapy. Exercise has positive effects on the brain; ...therefore, it has emerged as a promising therapeutic option for individuals with depression. Considerable research involving humans and animals offers compelling evidence to support the mental health benefits of physical activity or exercise mediated by the regulation of complex theoretical paradigms. However, challenges such as conducting long-term follow-up assessments and considering individual characteristics remain in human studies despite extensive efforts. While animal studies provide valuable insights into the potential benefits of exercise and its impact on outcomes related to depression and anxiety in rodents exposed to different stress paradigms, translating the findings to humans requires careful evaluation. More research is needed to establish precise exercise prescription guidelines and to better understand the complex relationship between exercise and depressive disorders. Therefore, this concise review explores the evidence supporting exercise intervention as an antidepressant treatment and its underlying mechanisms.
To improve the ionic conductivity and thermal stability of a polyethylene oxide (PEO)-ethylene carbonate (EC)-LiClO4-based solid polymer electrolyte for lithium-ion batteries, polymethyl methacrylate ...(PMMA) and silica aerogel were incorporated into the PEO matrix. The effects of the PEO:PMMA molar ratio and the amount of silica aerogel on the structure of the PEO-PMMA-LiClO4 solid polymer electrolyte were studied by X-ray diffraction, Fourier-transform infrared spectroscopy and alternating current (AC) impedance measurements. The solid polymer electrolyte with PEO:PMMA = 8:1 and 8 wt% silica aerogel exhibited the highest lithium-ion conductivity (1.35 × 10−4 S∙cm−1 at 30 °C) and good mechanical stability. The enhanced amorphous character and high degree of dissociation of the LiClO4 salt were responsible for the high lithium-ion conductivity observed. Silica aerogels with a high specific surface area and mesoporosity could thus play an important role in the development of solid polymer electrolytes with improved structure and stability.
Non-targeted metabolomic analysis of hot pepper (Capsicum annuum “CM334”) was performed at six development stages 16, 25, 36, 38, 43, and 48 days post-anthesis (DPA) to analyze biochemical changes. ...Distinct distribution patterns were observed in the changes of metabolites, gene expressions, and antioxidant activities by early (16–25 DPA), breaker (36–38 DPA), and later (43–48 DPA) stages. In the early stages, glycosides of luteolin, apigenin, and quercetin, shikimic acid, γ-aminobutyric acid (GABA), and putrescine were highly distributed but gradually decreased over the breaker stage. At later stages, leucine, isoleucine, proline, phenylalanine, capsaicin, dihydrocapsaicin, and kaempferol glycosides were significantly increased. Pathway analysis revealed metabolite–gene interactions in the biosynthesis of amino acids, capsaicinoids, fatty acid chains, and flavonoids. The changes in antioxidant activity were highly reflective of alterations in metabolites. The present study could provide useful information about nutrient content at each stage of pepper cultivation.
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