Photoinduced [3 + 2] Cycloadditions of Aryl Cyclopropyl Ketones with Alkynes and Alkenes.

The five-membered ring skeleton is one of the most pivotal in the area of pharmaceutical and natural products. [3 + 2] cycloadditions of cyclopropyl and unsaturated compounds are a highly efficient and atom-economical way to build a five-member compound. The previous works about the kind of [3 + 2] cycloadditions usually utilized metal or organic small molecule catalysts. However, an ideal [3 + 2] cycloaddition reaction that smoothly happens without any additives and catalysts under mild conditions is underdeveloped. Hence, we report [3 + 2] cycloadditions of aryl cyclopropyl without any additives and catalysts under purple LED. In this method, a broad scope of cyclopropyl, alkyne, and alkene was very compatible, especially drug derivatives ibuprofen and Ioxoprofen, to obtain the corresponding cycloaddition product with a good yield up to 93%.

Association between enjoyment, physical activity, and physical literacy among college students: a mediation analysis.

Background: Physical literacy and enjoyment are important factors that affect physical activity. Purpose: This work studies whether physical activity enjoyment (PAE) mediates the association between moderate to vigorous physical activity (MVPA) and physical literacy (PL) among college students. Methods: Chinese college students were recruited using the Perceived Physical Literacy Instrument Scale (PPLI-SC), the International Physical Activity Questionnaire Short Form (IPAQ-SF), and the Physical Activity Enjoyment Scale. The SPSS Hayes process macro (model 4) was used to analyze the direct impact and the indirect impact. Pearson correlation, independent sample t-tests, and linear regression were used to analyze the relationship between indicators. Results: The study surveyed 587 boys and 1,393 girls with a total of 1,980 valid questionnaires. MVPA, PAE, and PL of boys were significantly higher than girls (p < 0.01). The correlation analysis showed that MVPA, PL, and PAE were significantly correlated (p < 0.01). The results showed the direct effect of PL on MVPA was still statistically significant (ß = 0.067, p < 0.05) after adding PAE variables; PAE has a positive effect on MVPA after controlling PL (ß = 0.170, p < 0. 01). PL has a positive effect on PAE (ß = 0.750, p < 0.01). PL impacted MVPA as explained by a 65.58% mediating effect of enjoyment. Conclusion: Physical activity enjoyment mediates the relationship between PL and MVPA among college students. This means that even high PL among student may not imply that they are physically active if they do not enjoy physical activity.

Research on the Relationship between Physical Literacy, Physical Activity and Sedentary Behavior.

During the COVID-19 pandemic, college students' health-related physical activity and physical literacy aroused widespread concern. This study evaluated the relationship among physical literacy (PL), sedentary behavior (SB), light physical activity (LPA), and moderate-to-vigorous physical activity (MVPA); we further explored whether LAP and SB mediated the association between PL and MVPA. METHODS: This study was based on a cross-sectional survey of Chinese college students. The Perceived Physical Literacy Instrument Scale (PPLI-SC) and International Physical Activity Questionnaire Short Form (IPAQ-SF) were used to investigate the PL, MVPA, LPA, and SB. RESULTS: There were 2996 valid questionnaires with 829 boys and 2167 girls. The MVPA, LPA, and PL of boys were significantly higher than girls, while the SB values were significantly lower in girls (p < 0.01). The correlation analysis showed that there was a significant correlation between the two indexes except for SB and LPA. Path analysis shows that PL directly, significantly, and positively affects MVPA. PL reduces SB (ß = -0.085, p < 0.001) and increases LPA (ß = 0.097, p < 0.001). The total mediation effect accounted for 14.014%, and the mediation effects of SB and LPA accounted for 4.417% and 9.597%, respectively. CONCLUSIONS: LPA and SB partially mediated the relation between PL and MVPA. SB and LPA partially explain the impact of PL on MVPA. The findings suggest that managing SB and improving LPA could play a significant indirect role in increasing the positive effect of PL on MVPA and that increasing the opportunities for LPA increased the MVPA for Chinese college students.

Correction to Three Novel Alkaloids from Portulaca oleracea L. and Their Anti-inflammatory Effects.

Oleracimine and oleracimine A were isolated from Portulaca oleracea L. and described in the J. Agric. Food Chem, but the alternative structures of the two compounds are proposed on the basis of NMR analyses.

Cytotoxicity of hydroxydihydrobovolide and its pharmacokinetic studies in Portulaca oleracea L. extract

ABSTRACT Hydroxydihydrobovolide (HDB) was for the first time isolated from Portulaca oleracea L. and then its cytotoxicity against SH-SYTY cells was studied. Moreover, a rapid and sensitive ultra-high performance liquid chromatographic (UHPLC) method with bergapten as internal standard (IS) was developed and validated to investigate the pharmacokinetics of HDB in rats after intravenous and oral administrations of extract (POE). The UHPLC analysis was performed on a Diamonsil C18 analytical column, using acetonitrile-water (35:65, v/v) as the mobile phase with UV detection at 220 nm. The calibration curve was linear over the range of 0.2-25 µg/mL in rat plasma. The average extraction recovery was from 90.1 to 98.9%, and the relative standard deviations (RSDs) of the intra- and inter-day precisions were less than 4.7 and 4.1%, respectively. The results showed that 50 µM HDB had significant cytotoxicity on the SH-SY5Y cells, which was rapidly distributed with a Tmax of 11 min after oral administration and presented a low absolute bioavailability, 4.12%.

Three Novel Alkaloids from Portulaca oleracea L. and Their Anti-inflammatory Effects.

Three novel carbon skeleton alkaloids, named oleracimine (1), oleracimine A (2), and oleracone A (3), with one novel azulene carbon skeleton compound, oleracone B (4), and one known compound, ß-carboline (5), were first isolated from Portulaca oleracea L. The structures were determined using spectroscopic methods, including one- and two-dimensional nuclear magnetic resonance and high-resolution electrospray ionization time-of-flight mass spectrometry techniques. In addition, oleracimine (1) was used to investigate the anti-inflammatory effects on lipopolysaccharide-stimulated macrophages. The results of enzyme-linked immunosorbent assay, western blot, and real-time polymerase chain reaction showed that oleracimine (1) remarkably inhibited nitric oxide production and could dose-dependently decrease the secretions of interleukin 6, tumor necrosis factor α, nitric oxide, and prostaglandin E2 in cell culture supernatants as well as the mRNA of cyclooxygenase-2 and inducible nitric oxide synthase.

The anti-inflammation and pharmacokinetics of a novel alkaloid from Portulaca oleracea L.

OBJECTIVES: This study was to elucidate the pharmacokinetics of a novel alkaloid, 6-acetyl-2,2,5-trimethyl-2,3-dihydrocyclohepta[b]pyrrol-8(1H)-one, named oleracone isolated from Portulaca oleracea L., and to examine the anti-inflammatory ability with lipopolysaccharide (LPS) stimulated macrophages. METHODS: The novel alkaloid, oleracone, was isolated from Portulaca oleracea L., and its structure was determined by spectroscopic analysis including HRESIMS, 2D NMR spectroscopic data and single-crystal X-ray diffraction. The activity of anti-inflammation was assayed via the test with RAW 264.7 activated by LPS, and the pharmacokinetics of oleracone in rat plasma after intravenous and oral administration at dose of 2.5 mg/kg was, respectively, investigated by a rapid and sensitive ultra high-performance liquid chromatography (UHPLC) method with bergapten as internal standard. KEY FINDINGS: Oleracone was a novel alkaloid first isolated from Portulaca oleracea L. and possessed unique structure in natural products, whose anti-inflammatory effecting on nitrite oxide production and several pivotal pro-inflammatory cytokines was found at the concentration of 50 µm, and the pharmacokinetic results indicated that oleracone was rapidly distributed with Tmax of 15.7 min after oral administration and presented a higher oral absolute bioavailability to be 74.91 ± 10.7%. CONCLUSIONS: Oleracone as novel alkaloid presented remarkably anti-inflammatory effect, which was rapid distributed in rat with high bioavailability of 74.91 ± 10.7%.

Hepatic, gastric and intestinal first-pass effects of vitexin-2''-O-rhamnoside in rats by ultra-high-performance liquid chromatography.

Previous research in our laboratory found that the absolute bioavailability of vitexin-2''-O-rhamnoside (VR) was quite low at 4.89%. A rapid and sensitive UHPLC method using hesperidin as an internal standard was therefore developed and validated to investigate the reasons for this by determining VR in rat plasma after administering intravenously, intraportally (5 mg/kg), intraduodenally and intragastrically (40 mg/kg) to the rat model of the hepatic, gastric and intestinal first-pass effects. As only a high intestinal first-pass effect of VR was found, that is, there existed a low bioavailability of VR (2.40%), inhibitors of P-glycoprotein (P-gp) and cytochrome P450 3A (CYP3A), including verapamil, cyclosporin A and midazolam, and absorption enhancers, including bile salts and borneol, combined with VR, were instilled into duodenum to evaluate the effects on bioavailability of VR. The results demonstrated that area under the concentration-time curve (AUC) values of VR slightly increased after administration of verapamil, cyclosporin A and midazolam, indicating that CYP3A and P-gp do not play an important role in the first-pass effect in the intestine. AUC values of VR significantly increased after administering bile salts or borneol, indicating that the low bioavailability of VR was mainly related to its poor absorption in the intestine.

Tissue distribution and excretion of the five components of Portulaca oleracea L. extract in rat assessed by UHPLC

The aim of the present study was to investigate the tissue distribution and excretion of five components of Portulaca oleracea L. extract (POE) in rat following oral administration. A rapid, sensitive and specific ultra-high performance liquid chromatography (UHPLC) method with puerarin as the internal standard was used for the quantitative analysis of five components of POE, including caffeic acid (CA), p-coumaric acid (p-CA), ferulic acid (FA), quercitrin (QUER) and hesperidin (HP) in rat tissues including the liver, intestine, stomach, muscle, heart, lung, brain, kidney and spleen, urine and feces. The results show that onlyp-CA and FA were found in nearly all tissues with low cumulative ratios, and CA was higher in the intestine and stomach with a slightly higher cumulative ratio in the urine and feces after 24 h. HP and QUER were found at low levels in the tissues with low cumulative ratios.

O objetivo do presente estudo foi investigar a distribuição tecidual e excreção de cinco componentes de extrato Portulaca oleracea L. (POE) em ratos após administração oral. Um método analítico rápido, sensível e específico para quantificação de cinco componentes de POE (ácido cafeico (CA), ácidop-cumárico (p-CA), ácido ferúlico (FA), quercitrina (QUER) e hesperidina (HP)) por cromatografia líquida de ultra eficiência (UHPLC), empregando puerarina como padrão interno de referência. Os compostos foram quantificados em diferentes tecidos dos animais, sendo eles fígado, intestino, estômago, músculo, coração, pulmão, cérebro, rim e baço, urina e fezes. Os resultados mostraram que apenas p-CA e FA foram encontradas em todos os tecidos com baixas taxas cumulativas e CA apresentou níveis mais altos no intestino e estômago com a taxa cumulativa um pouco mais elevada na urina e nas fezes após 24 h. HP e QUER apresentaram baixas concentrações nos tecidos com baixas taxas cumulativas.

Hepatic, gastric, and intestinal first-pass effects of vitexin in rats.

CONTEXT: Recent research has demonstrated that vitexin exhibits a prominent first-pass effect. In this light, it is necessary to investigate the causes of this distinct first-pass effect. OBJECTIVE: The aim of this study was to evaluate hepatic, gastric, and intestinal first-pass effects of vitexin in rats and, furthermore, to investigate the role of P-glycoprotein (P-gp) and cytochrome P450 3A (CYP3A) in the absorption and secretion of vitexin in the duodenum. MATERIALS AND METHODS: Vitexin was infused into rats intravenously, intraportally, intraduodenally, and intragastrically (30 mg/kg). In addition, verapamil (50 mg/kg), a common substrate/inhibitor of P-gp and CYP3A, was also instilled with vitexin into the duodenum to investigate the regulatory action of P-gp and CYP3A. The plasma concentrations of vitexin were measured by the HPLC method using hesperidin as an internal standard. RESULTS: The hepatic, gastric, and intestinal first-pass effects of vitexin in rats were 5.2%, 31.3%, and 94.1%, respectively. In addition, the total area under the plasma concentration-time curve from zero to infinity (AUC) of the vitexin plus verapamil group and of the normal saline group was 44.9 and 39.8 µgc min/mL, respectively. DISCUSSION AND CONCLUSION: The intestinal first-pass effect of vitexin was considerable, and gastric and hepatic first-pass effects also contribute to the low absolute oral bioavailability of vitexin. The AUC of the vitexin plus verapamil group was slightly higher than that of the vitexin plus normal saline group (by approximately 1.13-fold), suggesting that verapamil does not play an important role in the absorption and secretion of vitexin.

Hepatic and gastrointestinal first-pass effects of vitexin-4″-O-glucoside in rats.

OBJECTIVES: This paper was to clarify the reasons of low bioavailability of vitexin-4″-O-glucoside (VOG) in rats via hepatic combined with gastrointestinal first-pass effect. METHODS: Observed the hepatic first-pass effect through the comparison of area under the plasma concentration-time curve from zero to infinity (AUC0→∞ ) of VOG in arterial plasma after femoral and portal vein administration (10 mg/kg), similarly, evaluated the gastrointestinal first-pass effect after portal vein (10 mg/kg) and gastrointestinal administration (20 mg/kg). For the study on regulatory mechanisms of cytochrome P450 3A (CYP3A) and P-glycoprotein (P-gp) on the bioavailability of VOG, the solution of verapamil hydrochloride (60 mg/kg) was instilled into intestine at 10 min before the infusion of VOG. KEY FINDINGS: The bioavailability of VOG after intraportal, intestinal as well as gastric administration was 45.1%, 8.1% and 9.8%, respectively. The value of AUC0→∞ for verapamil group was approximately 1.4-fold higher than that for normal saline group, meaning that perhaps CYP3A participated in the metabolism of VOG or P-gp transported VOG outside. CONCLUSIONS: The hepatic and intestinal first-pass effect were considered to mostly contribute to the low bioavailability of VOG in rats, and the gastric first-pass effect should be neglected. Also, the contribution of CYP3A to metabolism and P-gp mediated efflux have played a significant role in low bioavailability of VOG.

Pharmacokinetic study of isoquercitrin in rat plasma after intravenous administration at three different doses

The aim of this study is to develop a simple and specific HPLC method using vitexin as the internal standard to investigate the pharmacokinetics of isoquercitrin (ISOQ) after three different doses administrated intravenously to rats. The pharmacokinetic parameters were calculated by both compartmental and non-compartmental approaches. The results showed that ISOQ fitted a three-compartment open model. The values of AUC increased proportionally within the range of 5-10 mg·kg-1. Moreover, a half-life, b half-life, ªCL, MRT0-t and MRT0→∞ of ISOQ in rats showed significant differences between 20 mg·kg-1 and other doses, indicating that ISOQ presented dose-dependent pharmacokinetics in the range of 5-10 mg·kg-1 and non-linear pharmacokinetics at higher doses.

O objetivo deste estudo é desenvolver um método simples e específico de HPLC usando vitexina como padrão interno para investigar a farmacocinética do isoquercitrina (ISOQ) após três doses diferentes administradas por via intravenosa a ratos. Os parâmetros farmacocinéticos foram calculados pelas abordagens compartimental e não compartimental. Os resultados mostraram que ISOQ se encaixa no modelo de três compartimentos. Os valores de AUC aumentaram proporcionalmente na faixa de 5-10 mg·kg-1. Além disso, a meia-vida, b meia-vida, ªCL, MRT0-t and MRT0→∞ de ISOQ em ratos mostraram diferenças significativas entre 20 mg·kg-1 e outras doses, o que significa que ISOQ apresenta farmacocinética dose-dependente no intervalo de 5-10 mg·kg-1 e farmacocinética não linear em doses mais elevadas.