Sulforaphane Inhibits Osteoclastogenesis via Suppression of the Autophagic Pathway

Previous studies have demonstrated that sulforaphane (SFN) is a promising agent against osteoclastic bone destruction. However, the mechanism underlying its anti-osteoclastogenic activity is still unclear. Herein, for the first time, we explored the potential role of autophagy in SFN-mediated anti-osteoclastogenesis in vitro and in vivo. We established an osteoclastogenesis model using receptor activator of nuclear factor kappa-β ligand (RANKL)-induced RAW264.7 cells and bone marrow macrophages (BMMs). Tartrate-resistant acid phosphatase (TRAP) staining showed the formation of osteoclasts. We observed autophagosomes by transmission electron microscopy (TEM). In vitro, we found that SFN inhibited osteoclastogenesis (number of osteoclasts: 22.67 ± 0.88 in the SFN (0) group vs. 20.33 ± 1.45 in the SFN (1 μM) group vs. 13.00 ± 1.00 in the SFN (2.5 μM) group vs. 6.66 ± 1.20 in the SFN (2.5 μM) group), decreased the number of autophagosomes, and suppressed the accumulation of several autophagic proteins in osteoclast precursors. The activation of autophagy by rapamycin (RAP) almost reversed the SFN-elicited anti-osteoclastogenesis (number of osteoclasts: 22.67 ± 0.88 in the control group vs. 13.00 ± 1.00 in the SFN group vs. 17.33 ± 0.33 in the SFN+RAP group). Furthermore, Western blot (WB) analysis revealed that SFN inhibited the phosphorylation of c-Jun N-terminal kinase (JNK). The JNK activator anisomycin significantly promoted autophagy, whereas the inhibitor SP600125 markedly suppressed autophagic activation in pre-osteoclasts. Microcomputed tomography (CT), immunohistochemistry (IHC), and immunofluorescence (IF) were used to analyze the results in vivo. Consistent with the in vitro results, we found that the administration of SFN could decrease the number of osteoclasts and the expression of autophagic light chain 3 (LC3) and protect against lipopolysaccharide (LPS)-induced calvarial erosion. Our findings highlight autophagy as a crucial mechanism of SFN-mediated anti-osteoclastogenesis and show that the JNK signaling pathway participates in this process.     

The Effect of Chrysin-Loaded Phytosomes on Insulin Resistance and Blood Sugar Control in Type 2 Diabetic db/db Mice

Although a variety of beneficial health effects of natural flavonoids, including chrysin, has been suggested, poor solubility and bioavailability limit their practical use. As a promising delivery system, chrysin-loaded phytosomes (CPs) were prepared using egg phospholipid (EPL) at a 1:3 molar ratio and its antidiabetic effects were assessed in db/db diabetic mice. Male C57BLKS/J-db/db mice were fed a normal diet (control), chrysin diet (100 mg chrysin/kg), CP diet (100 mg chrysin equivalent/kg), metformin diet (200 mg/kg) or EPL diet (vehicle, the same amount of EPL used for CP preparation) for 9 weeks. Administration of CP significantly decreased fasting blood glucose and insulin levels in db/db mice compared with the control. An oral glucose tolerance test and homeostatic model assessment for insulin resistance were significantly improved in the CP group (p < 0.05). CP treatment suppressed gluconeogenesis via downregulation of phosphoenolpyruvate carboxykinase while it promoted glucose uptake in the skeletal muscle and liver of db/db mice (p < 0.05). The CP-mediated improved glucose utilization in the muscle was confirmed by upregulation of glucose transporter type 4, hexokinase2 and peroxisome proliferator-activated receptor γ during treatment (p < 0.05). The CP-induced promotion of GLUT4 plasma translocation was confirmed in the skeletal muscle of db/db mice (p < 0.05). Based on the results, CP showed greater antidiabetic performance compared to the control by ameliorating insulin resistance in db/db mice and phytosome can be used as an effective antidiabetic agent.     

Stability of Manganese(II)–Pyrazine, –Quinoxaline or –Phenazine Complexes and Their Potential as Carbonate Sequestration Agents

Carbonate sequestration technology is a complement of CO₂ sequestration technology, which might assure its long-term viability. In this work, in order to explore the interactions between Mn²⁺ ion with several ligands and carbonate ion, we reported a spectrophotometric equilibrium study of complexes of Mn²⁺ with pyrazine, quinoxaline or phenazine and its carbonate species at 298 K. For the complexes of manganese(II)–pyrazine, manganese(II)–quinoxaline and manganese(II)–phenazine, the formation constants obtained were log β₁₁₀ = 4.6 ± 0.1, log β₁₁₀ = 5.9 ± 0.1 and log β₁₁₀ = 6.0 ± 0.1, respectively. The formation constants for the carbonated species manganese(II)–carbonate, manganese(II)–pyrazine–carbonate, manganese(II)–quinoxaline–carbonate and manganese(II)–phenazine–carbonate complexes were log β₁₁₀ = 5.1 ± 0.1, log β₁₁₀ = 9.8 ± 0.1, log β₁₁₀ = 11.7 ± 0.1 and log β₁₁₀ = 12.7 ± 0.1, respectively. Finally, the individual calculated electronic spectra and its distribution diagram of these species are also reported. The use of N-donor ligand with π-electron-attracting activity in a manganese(II) complex might increase its interaction with carbonate ions.     

Tuning Photophysical Properties by p-Functional Groups in Zn(II) and Cd(II) Complexes with Piperonylic Acid

Aggregation between discrete molecules is an essential factor to prevent aggregation-caused quenching (ACQ). Indeed, functional groups capable of generating strong hydrogen bonds are likely to assemble and cause ACQ and photoinduced electron transfer processes. Thus, it is possible to compare absorption and emission properties by incorporating two ligands with a different bias toward intra- and intermolecular interactions that can induce a specific structural arrangement. In parallel, the π electron-donor or electron-withdrawing character of the functional groups could modify the Highest Ocuppied Molecular Orbital (HOMO)–Lowest Unocuppied Molecular Orbital (LUMO) energy gap. Reactions of M(OAc)₂·2H₂O (M = Zn(II) and Cd(II); OAc = acetate) with 1,3-benzodioxole-5-carboxylic acid (Piperonylic acid, HPip) and 4-acetylpyridine (4-Acpy) or isonicotinamide (Isn) resulted in the formation of four complexes. The elucidation of their crystal structure showed the formation of one paddle-wheel [Zn(μ-Pip)₂(4-Acpy)]₂ (1); a mixture of one dimer and two monomers [Zn(µ-Pip)(Pip)(Isn)₂]₂·2[Zn(Pip)₂(HPip)(Isn)]·2MeOH (2); and two dimers [Cd(μ-Pip)(Pip)(4-Acpy)₂]₂ (3) and [Cd(μ-Pip)(Pip)(Isn)₂]₂·MeOH (4). They exhibit bridged (1, µ₂-η¹:η¹), bridged, chelated and monodentated (2, µ₂-η¹:η¹, µ₁-η¹:η¹ and µ₁-η¹), or simultaneously bridged and chelated (3 and 4, µ₂-η²:η¹) coordination modes. Zn(II) centers accommodate coordination numbers 5 and 6, whereas Cd(II) presents coordination number 7. We have related their photophysical properties and fluorescence quantum yields with their geometric variations and interactions supported by TD-DFT calculations.     

β-Boswellic Acid Inhibits RANKL-Induced Osteoclast Differentiation and Function by Attenuating NF-κB and Btk-PLCγ2 Signaling Pathways

Osteoporosis is a systemic metabolic bone disorder that is caused by an imbalance in the functions of osteoclasts and osteoblasts and is characterized by excessive bone resorption by osteoclasts. Targeting osteoclast differentiation and bone resorption is considered a good fundamental solution for overcoming bone diseases. β-boswellic acid (βBA) is a natural compound found in Boswellia serrata, which is an active ingredient with anti-inflammatory, anti-rheumatic, and anti-cancer effects. Here, we explored the anti-resorptive effect of βBA on osteoclastogenesis. βBA significantly inhibited the formation of tartrate-resistant acid phosphatase-positive osteoclasts induced by receptor activator of nuclear factor-B ligand (RANKL) and suppressed bone resorption without any cytotoxicity. Interestingly, βBA significantly inhibited the phosphorylation of IκB, Btk, and PLCγ2 and the degradation of IκB. Additionally, βBA strongly inhibited the mRNA and protein expression of c-Fos and NFATc1 induced by RANKL and subsequently attenuated the expression of osteoclast marker genes, such as OC-STAMP, DC-STAMP, β3-integrin, MMP9, ATP6v0d2, and CtsK. These results suggest that βBA is a potential therapeutic candidate for the treatment of excessive osteoclast-induced bone diseases such as osteoporosis.     

Equilibrium Studies of Iron (III) Complexes with Either Pyrazine,Quinoxaline, or Phenazine and Their Catecholase Activity in Methanol

Currently, catalysts with oxidative activity are required to create valuable chemical, agrochemical, and pharmaceutical products. The catechol oxidase activity is a model reaction that can reveal new oxidative catalysts. The use of complexes as catalysts using iron (III) and structurally simple ligands such as pyrazine (pz), quinoxaline (qx), and phenazine (fz) has not been fully explored. To characterize the composition of the solution and identify the abundant species which were used to catalyze the catechol oxidation, the distribution diagrams of these species were obtained by an equilibrium study using a modified Job method in the HypSpec software. This allows to obtain also the UV-vis spectra calculated and the formation constants for the mononuclear and binuclear complexes with Fe³⁺ including: [Fe(pz)]³⁺, [Fe₂(pz)]⁶⁺, [Fe(qx)]³⁺, [Fe₂(qx)]⁶⁺, [Fe(fz)]³⁺, and [Fe₂(fz)]⁶⁺. The formation constants obtained were log β₁₁₀ = 3.2 ± 0.1, log β₂₁₀ = 6.9 ± 0.1, log β₁₁₀ = 4.4 ± 0.1, log β₂₁₀ = 8.3 ± 0.1, log β₁₁₀ = 6.4 ± 0.2, and log β₂₁₀ = 9.9 ± 0.2, respectively. The determination of the catechol oxidase activity for these complexes did not follow a traditional Michaelis–Menten behavior.     

Screening of Carbonic Anhydrase,Acetylcholinesterase, Butyrylcholinesterase,and α-Glycosidase Enzyme Inhibition Effects and Antioxidant Activity of Coumestrol

Coumestrol (3,9-dihydroxy-6-benzofuran [3,2-c] chromenone) as a phytoestrogen and polyphenolic compound is a member of the Coumestans family and is quite common in plants. In this study, antiglaucoma, antidiabetic, anticholinergic, and antioxidant effects of Coumestrol were evaluated and compared with standards. To determine the antioxidant activity of coumestrol, several methods—namely N,N-dimethyl-p-phenylenediamine dihydrochloride radical (DMPD^•+)-scavenging activity, 2,2′-azinobis-(3-ethylbenzothiazoline-6-sulphonate) radical (ABTS^•+)-scavenging activity, 1,1-diphenyl-2-picrylhydrazyl radical (DPPH^•)-scavenging activity, potassium ferric cyanide reduction ability, and cupric ion (Cu²⁺)-reducing activity—were performed. Butylated hydroxyanisole (BHA), Trolox, α-Tocopherol, and butylated hydroxytoluene (BHT) were used as the reference antioxidants for comparison. Coumestrol scavenged the DPPH radical with an IC₅₀ value of 25.95 μg/mL (r²: 0.9005) while BHA, BHT, Trolox, and α-Tocopherol demonstrated IC₅₀ values of 10.10, 25.95, 7.059, and 11.31 μg/mL, respectively. When these results evaluated, Coumestrol had similar DPPH^•-scavenging effect to BHT and lower better than Trolox, BHA and α-tocopherol. In addition, the inhibition effects of Coumestrol were tested against the metabolic enzymes acetylcholinesterase (AChE), butyrylcholinesterase (BChE), carbonic anhydrase II (CA II), and α-glycosidase, which are associated with some global diseases such as Alzheimer’s disease (AD), glaucoma, and diabetes. Coumestrol exhibited K_i values of 10.25 ± 1.94, 5.99 ± 1.79, 25.41 ± 1.10, and 30.56 ± 3.36 nM towards these enzymes, respectively.     

The Effect of Growth Parameters on Electrophysical and Memristive Properties of Vanadium Oxide Thin Films

We have experimentally studied the influence of pulsed laser deposition parameters on the morphological and electrophysical parameters of vanadium oxide films. It is shown that an increase in the number of laser pulses from 10,000 to 60,000 and an oxygen pressure from 3 × 10⁻⁴ Torr to 3 × 10⁻² Torr makes it possible to form vanadium oxide films with a thickness from 22.3 ± 4.4 nm to 131.7 ± 14.4 nm, a surface roughness from 7.8 ± 1.1 nm to 37.1 ± 11.2 nm, electron concentration from (0.32 ± 0.07) × 10¹⁷ cm⁻³ to (42.64 ± 4.46) × 10¹⁷ cm⁻³, electron mobility from 0.25 ± 0.03 cm²/(V·s) to 7.12 ± 1.32 cm²/(V·s), and resistivity from 6.32 ± 2.21 Ω·cm to 723.74 ± 89.21 Ω·cm. The regimes at which vanadium oxide films with a thickness of 22.3 ± 4.4 nm, a roughness of 7.8 ± 1.1 nm, and a resistivity of 6.32 ± 2.21 Ω·cm are obtained for their potential use in the fabrication of ReRAM neuromorphic systems. It is shown that a 22.3 ± 4.4 nm thick vanadium oxide film has the bipolar effect of resistive switching. The resistance in the high state was (89.42 ± 32.37) × 10⁶ Ω, the resistance in the low state was equal to (6.34 ± 2.34) × 10³ Ω, and the ratio R_HRS/R_LRS was about 14,104. The results can be used in the manufacture of a new generation of micro- and nanoelectronics elements to create ReRAM of neuromorphic systems based on vanadium oxide thin films.     

Chemical Indices and Kinetic Evaluation of β-Sitosteryl Oleate Oxidation in a Model System of Bulk Oil

Concerns have been raised about the safety and tolerability of phytosterol esters due to their vulnerability to oxidation. Herein, oxidation of the unsaturated fatty acid-phytosterol ester, namely β-sitosteryl oleate, was observed in comparison to native β-sitosterol after accelerated storage at 65 °C for 35 days in a bulk oil model system. Depending on the sterol structure, various chemical indices of lipid oxidation, including hydroperoxide value (HPV), thiobarbituric acid reactive substances (TBARS), p-anisidine value (AnV), and 7-keto derivatives, changed at varying rates in both samples. Such indicators for β-sitosteryl oleate appeared to be obtained at higher concentrations than those for β-sitosterol. The first order kinetic was used to describe the losses of β-sitosteryl oleate and β-sitosterol in bulk oil. It was discovered that the β-sitosteryl oleate (k = 0.0202 day⁻¹) underwent oxidative alteration more rapidly than β-sitosterol (k = 0.0099 day⁻¹). Results indicated that physical structure was the principal factor in the determination of storage stability of phytosterol and its ester. Research on antioxidants and storage techniques can be expanded in order to reduce the oxidative loss of phytosterol esters during storage and improve the safety and tolerability of phytosterol esters.     

Comparative Study of Bioactivity and Safety Evaluation of Ethanolic Extracts of Zanthoxylum schinifolium Fruit and Pericarp

The fruit and pericarp of Zanthoxylum schinifolium (ZS) have been used in traditional medicine; however, few studies have characterized ZS fruit and pericarp. Therefore, in the present study, we evaluated the safety of ZS fruit (ZSF) and pericarp (ZSP) extracts and compared their bioactivity. To evaluate the safety of ZSF and ZSP, mutagenicity, cytotoxicity, and oxidative stress assays were performed and nontoxic concentration ranges were obtained. ZSP was found to be superior to ZSF in terms of its antimutagenic, antioxidant, and anti-inflammatory activities. In the S9 mix, the mutation inhibition rate of ZSP was close to 100% at concentrations exceeding 625 µg·plate⁻¹ for both the TA98 and TA100 strains. ZSP exhibited efficient DPPH (IC₅₀ = 75.6 ± 6.1 µg·mL⁻¹) and ABTS (IC₅₀ = 57.4 ± 6 µg·mL⁻¹) scavenging activities. ZSP inhibited the release of cytokines, involved in IL-1β (IC₅₀ = 134.4 ± 7.8), IL-6 (IC₅₀ = 262.8 ± 11.2), and TNF-α (IC₅₀ = 223.8 ± 5.8). These results indicate that ZSP contains a higher amount of biochemicals than ZSF, or that ZSP contains unique biochemicals. In conclusion, for certain physiological activities, the use of ZSP alone may be more beneficial than the combined use of ZSF and ZSP.     

Ferro- and Antiferromagnetic Interactions in Oxalato-Centered Inverse Hexanuclear and Chain Copper(II) Complexes with Pyrazole Derivatives

Two novel copper(II) complexes of formulas {[Cu(4-Hmpz)₄][Cu(4-Hmpz)₂(µ₃-ox-κ²O¹,O²:κO^2′:κO^1′)(ClO₄)₂]}_n (1) and {[Cu(3,4,5-Htmpz)₄]₂[Cu(3,4,5-Htmpz)₂(µ₃-ox-κ²O¹,O²:κO^2′:κO^1′)(H₂O)(ClO₄)]₂[Cu₂(3,4,5-Htmpz)₄(µ-ox-κ²O¹,O²:κ²O^2′,O^1′)]}(ClO₄)₄·6H₂O (2) have been obtained by using 4-methyl-1H-pyrazole (4-Hmpz) and 3,4,5-trimethyl-1H-pyrazole (3,4,5-Htmpz) as terminal ligands and oxalate (ox) as the polyatomic inverse coordination center. The crystal structure of 1 consists of perchlorate counteranions and cationic copper(II) chains with alternating bis(pyrazole)(µ₃-κ²O¹,O²:κO^2′:κO^1′-oxalato)copper(II) and tetrakis(pyrazole)copper(II) fragments. The crystal structure of 2 is made up of perchlorate counteranions and cationic centrosymmetric hexanuclear complexes where an inner tetrakis(pyrazole)(µ-κ²O¹,O²:κ²O^2′,O^1′-oxalato)dicopper(II) entity and two outer mononuclear tetrakis(pyrazole)copper(II) units are linked through two mononuclear aquabis(pyrazole)(µ₃-κ²O¹,O²:κO^2′:κO^1′-oxalato)copper(II) units. The magnetic properties of 1 and 2 were investigated in the temperature range 2.0–300 K. Very weak intrachain antiferromagnetic interactions between the copper(II) ions through the µ₃-ox-κ²O¹,O²:κO^2′:κO^1′ center occur in 1 [J = −0.42(1) cm⁻¹, the spin Hamiltonian being defined as H = −J∑S_1,i · S_2,i+1], whereas very weak intramolecular ferromagnetic [J = +0.28(2) cm⁻¹] and strong antiferromagnetic [J’ = −348(2) cm⁻¹] couplings coexist in 2 which are mediated by the µ₃-ox-κ²O¹,O²:κO^2′:κO^1′ and µ-ox-κ²O¹,O²:κ²O^2′,O^1′ centers, respectively. The variation in the nature and magnitude of the magnetic coupling for this pair of oxalato-centered inverse copper(II) complexes is discussed in the light of their different structural features, and a comparison with related oxalato-centered inverse copper(II)-pyrazole systems from the literature is carried out.     

Light Intensity and Photoperiod Affect Growth and Nutritional Quality of Brassica Microgreens

We explored the effects of different light intensities and photoperiods on the growth, nutritional quality and antioxidant properties of two Brassicaceae microgreens (cabbage Brassica oleracea L. and Chinese kale Brassica alboglabra Bailey). There were two experiments: (1) four photosynthetic photon flux densities (PPFD) of 30, 50, 70 or 90 μmoL·m⁻²·s⁻¹ with red:blue:green = 1:1:1 light-emitting diodes (LEDs); (2) five photoperiods of 12, 14, 16, 18 or 20 h·d⁻¹. With the increase of light intensity, the hypocotyl length of cabbage and Chinese kale microgreens shortened. PPFD of 90 μmol·m⁻²·s⁻¹ was beneficial to improve the nutritional quality of cabbage microgreens, which had higher contents of chlorophyll, carotenoids, soluble sugar, soluble protein and vitamin C, as well as increased antioxidant capacity. The optimal PPFD for Chinese kale microgreens was 70 μmol·m⁻²·s⁻¹. Increasing light intensity could increase the antioxidant capacity of cabbage and Chinese kale microgreens, while not significantly affecting glucosinolate (GS) content. The dry and fresh weight of cabbage and Chinese kale microgreens were maximized with a 14-h·d⁻¹ photoperiod. The chlorophyll, carotenoid and soluble protein content in cabbage and Chinese kale microgreens were highest for a 16-h·d⁻¹ photoperiod. The lowest total GS content was found in cabbage microgreens under a 12-h·d⁻¹ photoperiod and in Chinese kale microgreens under 16-h·d⁻¹ photoperiod. In conclusion, the photoperiod of 14~16 h·d⁻¹, and 90 μmol·m⁻²·s⁻¹ and 70 μmol·m⁻²·s⁻¹ PPFD for cabbage and Chinese kale microgreens, respectively, were optimal for cultivation.     

Preservation of Contractile Reserve and Diastolic Function by Inhibiting the NLRP3 Inflammasome with OLT1177® (Dapansutrile) in a Mouse Model of Severe Ischemic Cardiomyopathy Due to Non-Reperfused Anterior Wall Myocardial Infarction

Interleukin-1β (IL-1β), a product of the NLRP3 inflammasome, modulates cardiac contractility and diastolic function. We proposed that OLT1177^® (dapansutrile), a novel NLRP3 inhibitor, could preserve contractile reserve and diastolic function after myocardial infarction (MI). We used an experimental murine model of severe ischemic cardiomyopathy through the ligation of the left coronary artery without reperfusion, and after 7 days randomly assigned mice showing large anterior MI (>4 akinetic segments), increased left ventricular (LV) dimensions ([LVEDD] > 4.4 mm), and reduced function (LV ejection fraction < 40%) to a diet that was enriched with OLT1177^® admixed with the chow in the diet at 3.75 g/kg (Group 1 [n = 10]) or 7.5 g/kg (Group 2 [n = 9]), or a standard diet as the no-treatment control group (Group 3 [n = 10]) for 9 weeks. We measured the cardiac function and contractile reserve with an isoproterenol challenge, and the diastolic function with cardiac catheterization at 10 weeks following the MI surgery. When compared with the control (Group 3), the mice treated with OLT1177 (Group 1 and 2) showed significantly greater preservation of their contractile reserve (the percent increase in the left ventricular ejection fraction [LVEF] after the isoproterenol challenge was +33 ± 11% and +40 ± 6% vs. +9 ± 7% in the standard diet; p < 0.05 and p < 0.005 for Group 1 and 2, respectively) and of diastolic function measured as the lower left ventricular end-diastolic pressure (3.2 ± 0.5 mmHg or 4.5 ± 0.5 mmHg vs. 10.0 ± 1.6 mmHg; p < 0.005 and p < 0.009 respectively). No differences were noted between the resting LVEF of the MI groups. These effects were independent of the effects on the ventricular remodeling after MI. NLRP3 inflammasome inhibition with OLT1177^® can preserve β-adrenergic responsiveness and prevent left ventricular diastolic dysfunction in a large non-reperfused anterior MI mouse model. OLT1177^® could therefore be used to prevent the development of heart failure in patients with ischemic cardiomyopathy.     

Synthesis,Structure and Biological Evaluations of Zn(II) Pincer Complexes Based on S-Triazine Type Chelator

2,4-bis (3,5-dimethyl-1H-pyrazol-1-yl)-6-methoxy-1,3,5-triazine (BPMT) pincer ligand was used to synthesize the new [Zn(BPMT)(NCS)₂] (1) and [Zn(BPMT)(Br)₂] (2) complexes by a reaction with Zn(NO₃)₂·6H₂O in the presence of either KSCN or KBr, respectively. The structure of complex 1 has been exclusively confirmed using single crystal X-ray diffraction. In this neutral heteroleptic complex, the BPMT is a pincer chelate coordinating the Zn(II) ion via three interactions with the two pyrazole moieties and the s-triazine core. Hence, BPMT is a tridentate NNN-chelate. The coordination environment of Zn(II) is completed by two strong interactions with two terminal SCN⁻ ions via the N-atom. Hence, the Zn(II) is penta-coordinated with a distorted square pyramidal coordination geometry. Hirshfeld analysis indicated the predominance of H…H, H…C and N…H intermolecular interactions. Additionally, the S…H, S…C and S…N contacts are the most significant. The free ligand has no or weak antimicrobial, antioxidant and anticancer activities while the studied Zn(II) complexes showed interesting biological activity. Complex 1 has excellent antibacterial activity against B. subtilis (2.4 μg/mL) and P. vulgaris (4.8 μg/mL) compared to Gentamycin (4.8 μg/mL). Additionally, complex 1 (78.09 ± 4.23 µg/mL) has better antioxidant activity than 2 (365.60 ± 20.89 µg/mL). In addition, complex 1 (43.86 ± 3.12 µg/mL) and 2 (30.23 ± 1.26 µg/mL) have 8 and 12 times the anticancer activity of the free BPMT ligand (372.79 ± 13.64 µg/mL).     

Optimising the Polyphenolic Content and Antioxidant Activity of Green Rooibos (Aspalathus linearis) Using Beta-Cyclodextrin Assisted Extraction

Antioxidant activity associated with green rooibos infusions is attributed to the activity of polyphenols, particularly aspalathin and nothofagin. This study aimed to optimise β-cyclodextrin (β-CD)-assisted extraction of crude green rooibos (CGRE) via total polyphenolic content (TPC) and antioxidant activity assays. Response surface methodology (RSM) permitted optimisation of β-CD concentration (0–15 mM), temperature (40–90 °C) and time (15–60 min). Optimal extraction conditions were: 15 mM β-CD: 40 °C: 60 min with a desirability of 0.985 yielding TPC of 398.25 mg GAE·g⁻¹, metal chelation (MTC) of 93%, 2,2′-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) radical scavenging of 1689.7 µmol TE·g⁻¹, ferric reducing antioxidant power (FRAP) of 2097.53 µmol AAE·g⁻¹ and oxygen radical absorbance capacity (ORAC) of 11,162.82 TE·g⁻¹. Aspalathin, hyperoside and orientin were the major flavonoids, with quercetin, luteolin and chrysoeriol detected in trace quantities. Differences (p < 0.05) between aqueous and β-CD assisted CGRE was only observed for aspalathin reporting the highest content of 172.25 mg·g⁻¹ of dry matter for extracts produced at optimal extraction conditions. Positive, strong correlations between TPC and antioxidant assays were observed and exhibited regression coefficient (R²) between 0.929–0.978 at p < 0.001. These results demonstrated the capacity of β-CD in increasing polyphenol content of green rooibos.     

Synthesis,Characterization, DFT and Photocatalytic Studies of a New Pyrazine Cadmium(II) Tetrakis(4-methoxy-phenyl)-porphyrin Compound

This study describes the synthesis, theoretical investigations, and photocatalytic degradational properties of a new (pyrazine)(meso-tetrakis(4-tert-methoxyphenyl)-porphyrinato)-cadmium (II) ([Cd(TMPP)-Pyz]) complex (1). The new penta-coordinated Cd^II porphyrin complex (1) was characterized by various spectroscopic techniques, including FT-IR, NMR, UV-visible absorption, fluorescence emission, and singlet oxygen, while its molecular structure was studied using single crystal X-ray diffraction. The UV–Vis spectroscopic study highlighted the redshift of the absorption bands after the insertion of the Cd(II) metal ion into the TMPP ring. The co-coordination of the pyrazine axial ligand enhanced this effect. A fluorescence emission spectroscopic study showed a significant blueshift in the Q bands, accompanied by a decrease in the fluorescence emission intensity and quantum yields of Φ_f = 0.084, Φ_f = 0.06 and Φ_f = 0.03 for H₂-TMPP free-base porphyrin, [Cd(TMPP)] and [Cd(TMPP)(Pyz)] (1) respectively. Singlet oxygen revealed that the H₂-TMPP porphyrin produced the most efficient singlet oxygen quantum yield of (Φ_Δ = 0.73) compared to [CdTMPP] (Φ_Δ = 0.57) and [Cd(TMPP)(Pyz)] (1) (Φ_Δ = 0.13). In the crystal lattice, the [Cd(TMPP)Pyz] was stabilized through non-covalent intermolecular interactions (NCI), such as the hydrogen bonds C-H···N and C-H···Cg. Additionally, crystal explorer software was then utilized to measure the quantitative analysis of the intermolecular interactions in the unit cell of the crystal structure and established that the C-H···π interaction dominated. The Natural bond orbital (NBO) analysis revealed that each molecule is stabilized by hyperconjugation and charge delocalization. As a photocatalyst, the coordination complex 1 showed excellent photocatalytic activity toward the degradation of Levafix Blue CA reactive dye (i.e., dye photo-degradation of 80%).     

Phenolic compounds,essential oil composition,and antioxidant activity of Angelica purpurascens (Avé-Lall.) Gill

In this study, methanol extracts (MEs) and essential oil (EO) of Angelica purpurascens (Avé-Lall.) Gill obtained from different parts (root, stem, leaf, and seed) were evaluated in terms of antioxidant activity, total phenolics, compositions of phenolic compound, and essential oil with the methods of 2,2-azino-bis(3ethylbenzo-thiazoline-6-sulfonic acid (ABTS•⁺), 2,2-diphenyl-1-picrylhydrazil (DPPH•) radical scavenging activities, and ferric reducing/antioxidant power (FRAP), the Folin–Ciocalteu, liquid chromatography−tandem mass spectrometry (LC−MS/MS), and gas chromatography-mass spectrometry (GC−MS), respectively. The root extract of A. purpurascens exhibited the highest ABTS•⁺, DPPH•, and FRAP activities (IC₅₀: 0.05 ± 0.0001 mg/mL, IC₅₀: 0.06 ± 0.002 mg/mL, 821.04 ± 15.96 µM TEAC (Trolox equivalent antioxidant capacity), respectively). Moreover, EO of A. purpurascens root displayed DPPH• scavenging activity (IC₅₀: 2.95 ± 0.084 mg/mL). The root extract had the highest total phenolic content (438.75 ± 16.39 GAE (gallic acid equivalent), µg/mL)). Twenty compounds were identified by LC−MS/MS. The most abundant phenolics were ferulic acid (244.39 ± 15.64 μg/g extract), benzoic acid (138.18 ± 8.84 μg/g extract), oleuropein (78.04 ± 4.99 μg/g extract), and rutin (31.21 ± 2.00 μg/g extract) in seed, stem, root, and leaf extracts, respectively. According to the GC−MS analysis, the major components were determined as α-bisabolol (22.93%), cubebol (14.39%), α-pinene (11.63%), and α-limonene (9.41%) among 29 compounds. Consequently, the MEs and EO of A. purpurascens can be used as a natural antioxidant source.     

Antioxidant and Starch-Hydrolyzing Enzymes Inhibitory Properties of Striga-Resistant Yellow-Orange Maize Hybrids

Most of the health benefits derived from cereals are attributed to their bioactive compounds. This study evaluated the levels of the bioactive compounds, and the antioxidant and starch-hydrolyzing enzymes inhibitory properties of six pipeline Striga-resistant yellow-orange maize hybrids (coded AS1828-1, 4, 6, 8, 9, 11) in vitro. The maize hybrids were grown at the International Institute of Tropical Agriculture (IITA), Nigeria. The bioactive compounds (total phenolics, tannins, flavonoids, and phytate) levels, antioxidant (DPPH^• and ABTS^•+ scavenging capacity and reducing power) and starch-hydrolyzing enzymes (α-amylase and α-glucosidase) inhibitory activities of the maize hybrids were determined by spectrophotometry. At the same time, carotenoids were quantified using a reverse-phase HPLC system. The ranges of the bioactive compounds were: 11.25–14.14 mg GAE/g (total phenolics), 3.62–4.67 mg QE/g (total flavonoids), 3.63–6.29 mg/g (tannins), 3.66–4.31% (phytate), 8.92–12.11 µg/g (total xanthophylls), 2.42–2.89 µg/g (total β-carotene), and 3.17–3.77 µg/g (total provitamin A carotenoids). Extracts of the maize hybrids scavenged DPPH^• (SC₅₀: 9.07–26.35 mg/mL) and ABTS^•+ (2.65–7.68 TEAC mmol/g), reduced Fe³⁺ to Fe²⁺ (0.25 ± 0.64–0.43 ± 0.01 mg GAE/g), and inhibited α-amylase and α-glucosidase, with IC₅₀ ranges of 26.28–52.55 mg/mL and 47.72–63.98 mg/mL, respectively. Among the six clones of the maize hybrids, AS1828-9 had the highest (p < 0.05) levels of tannins and phytate and the strongest antioxidant and starch-hydrolyzing enzymes inhibitory activities. Significant correlations were observed between total phenolics and the following: ABTS^•+ (p < 0.01, r = 0.757), DPPH^• SC₅₀ (p < 0.01, r = −0.867), reducing power (p < 0.05, r = 0.633), α-amylase IC₅₀ (p < 0.01, r = −0.836) and α-glucosidase IC₅₀ (p < 0.05, r = −0.582). Hence, the Striga-resistant yellow-orange maize hybrids (especially AS1828-9) may be beneficial for alleviating oxidative stress and postprandial hyperglycemia.     

In Vitro Analyses of Spinach-Derived Opioid Peptides,Rubiscolins: Receptor Selectivity and Intracellular Activities through G Protein- and β-Arrestin-Mediated Pathways

Activated opioid receptors transmit internal signals through two major pathways: the G-protein-mediated pathway, which exerts analgesia, and the β-arrestin-mediated pathway, which leads to unfavorable side effects. Hence, G-protein-biased opioid agonists are preferable as opioid analgesics. Rubiscolins, the spinach-derived naturally occurring opioid peptides, are selective δ opioid receptor agonists, and their p.o. administration exhibits antinociceptive effects. Although the potency and effect of rubiscolins as G-protein-biased molecules are partially confirmed, their in vitro profiles remain unclear. We, therefore, evaluated the properties of rubiscolins, in detail, through several analyses, including the CellKey^TM assay, cADDis^® cAMP assay, and PathHunter^® β-arrestin recruitment assay, using cells stably expressing µ, δ, κ, or µ/δ heteromer opioid receptors. In the CellKey^TM assay, rubiscolins showed selective agonistic effects for δ opioid receptor and little agonistic or antagonistic effects for µ and κ opioid receptors. Furthermore, rubiscolins were found to be G-protein-biased δ opioid receptor agonists based on the results obtained in cADDis^® cAMP and PathHunter^® β-arrestin recruitment assays. Finally, we found, for the first time, that they are also partially agonistic for the µ/δ dimers. In conclusion, rubiscolins could serve as attractive seeds, as δ opioid receptor-specific agonists, for the development of novel opioid analgesics with reduced side effects.