Extraction, identification, and starch-digestion inhibition of phenolics from Euryale ferox seed coat.

BACKGROUND: Euryale ferox is an important cash crop and valuable tonic in traditional medicine. The seeds of E. ferox are rich in starch, which is hard to digest, and the digestion speed is significantly slower than that of rice starch. The goal of this study was to evaluate the effects of E. ferox seed-coat phenolics (EFCPs) on the digestion of E. ferox seed starch. RESULTS: EFCPs were extracted and identified by ultra-high performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry. We optimized the extraction parameters, and the final extraction yield was about 1.49%. We identified seven phenolics from the E. ferox seed-coat extracts: gallic acid, digalloylhexoside, catechin, procyanidin B2, epicatechin, ellagic acid, and epicatechin gallate. Quantitative analysis results showed that the E. ferox seed phenolics mainly distributed in the seed coat and the gallic acid, digalloylhexoside, and epicatechin gallate were three main phenolic compounds. The phenolics displayed strong inhibitory activities on α-glucosidase and α-amylase with an IC50 of 3.25 µg mL-1 and 1.36 mg mL-1 respectively. Furthermore, these phenolics could interact with starch by hydrogen bonds, which might make its starch more difficult to digest. CONCLUSION: Our investigation suggests that the EFCPs can strongly inhibit the digestion of E. ferox seed starch by inhibiting the α-amylase and α-glucosidase activities and interacting with starch by hydrogen bonds; therefore, E. ferox seeds have a promising application prospect in foods for hypoglycemia. © 2023 Society of Chemical Industry.

Chalcone-1-Deoxynojirimycin Heterozygote Reduced the Blood Glucose Concentration and Alleviated the Adverse Symptoms and Intestinal Flora Disorder of Diabetes Mellitus Rats.

Chalcone-1-deoxynojirimycin heterozygote (DC-5), a novel compound which was designed and synthesized in our laboratory for diabetes treatment, showed an extremely strong in vitro inhibitory activity on α-glucosidase in our previous studies. In the current research, its potential in vivo anti-diabetic effects were further investigated by integration detection and the analysis of blood glucose concentration, blood biochemical parameters, tissue section and gut microbiota of the diabetic rats. The results indicated that oral administration of DC-5 significantly reduced the fasting blood glucose and postprandial blood glucose, both in diabetic and normal rats; meanwhile, it alleviated the adverse symptoms of elevated blood lipid level and lipid metabolism disorder in diabetic rats. Furthermore, DC-5 effectively decreased the organ coefficient and alleviated the pathological changes of the liver, kidney and small intestine of the diabetic rats at the same time. Moreover, the results of 16S rDNA gene sequencing analysis suggested that DC-5 significantly increased the ratio of Firmicutes to Bacteroidetes and improved the disorder of gut microbiota in diabetic rats. In conclusion, DC-5 displayed a good therapeutic effect on the diabetic rats, and therefore had a good application prospect in hypoglycemic drugs and foods.

Synthesis, in vitro inhibitory activity, kinetic study and molecular docking of novel N-alkyl-deoxynojirimycin derivatives as potential α-glucosidase inhibitors.

A series of novel N-alkyl-1-deoxynojirimycin derivatives 25 ∼ 44 were synthesised and evaluated for their in vitro α-glucosidase inhibitory activity to develop α-glucosidase inhibitors with high activity. All twenty compounds exhibited α-glucosidase inhibitory activity with IC50 values ranging from 30.0 ± 0.6 µM to 2000 µM as compared to standard acarbose (IC50 = 822.0 ± 1.5 µM). The most active compound 43 was ∼27-fold more active than acarbose. Kinetic study revealed that compounds 43, 40, and 34 were all competitive inhibitors on α-glucosidase with Ki of 10 µM, 52 µM, and 150 µM, respectively. Molecular docking demonstrated that the high active inhibitors interacted with α-glucosidase by four types of interactions, including hydrogen bonds, π-π stacking interactions, hydrophobic interactions, and electrostatic interaction. Among all the interactions, the π-π stacking interaction and hydrogen bond played a significant role in a various range of activities of the compounds.

Autophagy is involved in acetylshikonin ameliorating non-alcoholic steatohepatitis through AMPK/mTOR pathway.

Acetylshikonin (AS), a naphthoquinone constituent derived from Lithospermum erythrorhizon, has been revealed various pharmacological activities including anti-oxidative, anti-inflammatory and antifertility effects. Our previous study has illuminated the effects of AS on preventing obesity and hepatic steatosis in db/db mice. However, the effects of AS and the molecular mechanisms for curing non-alcoholic steatohepatitis (NASH) have not yet been studied. Autophagy has been considered as a lysosomal degradative pathway responsible for the removal of cellular lipid droplets through a process called lipophagy, which is recognized as a potential therapeutic approach for NASH. Here we hypothesize that autophagy is involved in the beneficial effects of AS on methionine-choline deficient (MCD) diet-induced NASH of mice. In this study, we observed that AS treatment ameliorated the pathological signs of NASH, and markedly suppressed the levels of hepatic IL-1ß and TNF-α cytokines, and hepatocyte apoptotic cells in MCD diet-induced mice. Moreover, immunological analyses showed that the elevated expression of the fibrotic markers including α-SMA, collegen I, collegen III and fibronectin in MCD diet-induced mice were notably down-regulated by AS treatment. Nevertheless, the beneficial effects of AS on ameliorating NASH were notably counteracted by co-administration of chloroquine, an autophagy inhibitor. Furthermore, our data suggested that AS treatment increased hepatocyte autophagy in MCD diet-induced mice via AMPK/mTOR pathway. These findings suggest that AS could be therapeutically effective in the development of NASH by ameliorating steatosis, inflammation, liver injury and fibrosis.

Carnosic acid, a novel food-source AT1R antagonist and its anti-hypertension mechanism.

Hypertension is the most prevalent non-communicable disease, affecting billions of people worldwide. Discovery and development of natural antihypertensive lead compounds or drugs are important to resolve the limitations of existing antihypertensive drug safety and resistance. This investigation verified that carnosic acid (CA), an important active ingredient of rosemary, an edible spice plant, indicates a significant anti-hypertensive activity in spontaneous hypertension rats by targeting AT1R. Moreover, our research indicated that CA shared a comparable antagonistic mechanism with established synthetic angiotensin II receptor blockers (ARBs), as it occupies the binding sites of Angiotensin II (AngII) at His6 and Pro7 within the AT1R's ligand-binding pocket. Notably, CA exerted better anti-hypertensive activity since it could not break the Asn1113.35-Asn2957.46 hydrogen bond to stabilize the AT1R inactive state. As the first potent AT1R antagonist identified in a natural food source, CA is poised to become a novel anti-hypertensive lead compound, distinguished by its unique skeleton structure different from conventional ARBs. This research lays a valuable theoretical groundwork for the future exploration of CA and rosemary extract in both fundamental studies and clinical applications.

Multimodal Local Resonators for Low-Frequency Amelioration of Acoustic Black Holes.

Acoustic black holes (ABHs) are effective at suppressing vibrations at high frequencies, but their performance at low frequencies is limited. This paper aims to improve the low-frequency performance of ABH plates through the design of a metamaterial acoustic black hole (MMABH) plate. The MMABH plate consists of a double-layer ABH plate with a set of periodic local resonators installed between the layers. The resonators are tuned to the low-frequency peak points of the ABH plate, which are identified using finite element analysis. To dissipate vibration energy, the beams of the resonators are covered with damping layers. A modal analysis of the MMABH plate is performed, confirming its damping effect over a wide frequency band, especially at low frequencies.

Processing, digestion property and structure characterization of slowly digestible gorgon nut starch.

Slowly digestible gorgon nut starch (GN-SDS) was prepared by heating-cooling treatment (HCT), meanwhile its morphological and structural features were characterized in detail by SEM, DSC, XRD and IR detection. The optimized parameters of GN-SDS processing were as following: starch milk (20%) was heated at 100 °C for 20 min, and then cooled under 4 °C for 24 h. Under the optimized parameters, the SDS content increased from 20.49 to 61.74%. GN-SDS showed typical SDS characteristics in in vivo digestion with a low postprandial blood glucose. SEM images suggested that GN-S particles changed from uniform regular polyhedron with smooth surface to irregular gravel-like particles with coarse surface and obvious layered structure inside after HCT. The results of SEM, DSC, XRD and IR determination indicated that HCT changed the granule morphology, interior structure, gelatinization temperature and crystal type (A to B-type) of GN-S, and therefore made it hard to be digested accordingly. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s10068-021-01007-6.

Theoretical insight into the multiple interactions of quinazoline inhibitors with breast cancer resistance protein (BCRP/ABCG2).

Communicated by Ramaswamy H. Sarma.

Theoretical Insights into the Cotransport Mechanism of GSH with Anticancer Drugs by MRP1.

The multidrug resistance protein MRP1 is an ATP binding cassette (ABC) transporter that confers resistance to many anticancer drugs and regulates redox homeostasis, inflammation, and hormone secretion. MRP1 actively transports compounds across cell membranes, and the presence of glutathione (GSH) is required in many cases. However, the process of MRP1-mediated substrate transportation has been poorly understood. With extensive molecular dynamics simulations, we have found a sandwich-like structure which is generated by GSH, a transmembrane α-helices 11 (TM11)-TM17 axis, and anticancer drugs. This structure is crucial in MRP1 transportation. It triggers the motion of TM11 and TM17, followed by the movement of nucleotide-binding domains 1 (NBD1) and 2 (NBD2), and finally an occluded structure is formed. Trp1246, Lys332, and Phe594 were identified as the main contributors in the formation of the sandwich-like structure. Our findings clearly explain the synergy of GSH with an anticancer drug in MRP1 transportation and have significant meanings for the rational design of novel inhibitors against MRP1.

Ionic liquid assisted electrochemical coating zinc nanoparticles on carbon cloth as lithium dendrite suppressing host.

The application of lithium metal anode with high specific capacity and energy density is limited by the volume expansion and pulverization caused by dendrite growth during cycle process. We propose a composite lithium anode by immersing molten lithium on the flexible three-dimensional (3D) carbon cloth scaffold with the zinc nanoparticles. The lithiophilic zinc nanoparticles layer of framework is synthesized by fast and easy electrochemical deposition from ionic liquid avoiding high temperature, high pressure and toxic reagent. The lithium is infused into the 3D lithiophilic framework, the composite anode is obtained. The steady network structure can confine the lithium and lead to Li dendrite restraining and reducing volume change due to the low interfacial resistance and reduce the effective current density, which induced the homogeneous Li growth. Benefiting from this, the Li infused 3D carbon cloth-Zn symmetric battery exhibits a low stripping/plating overpotential (~30 mV) and can be stable over 900 h at 1 mA cm-2. The Li//LiFePO4 battery delivers higher reversible capacity (140 mAh g-1 at 2 C and 120 mAh g-1 at 5 C) and stable cycling for 1500 and 2000 cycles than bare Li.

Acetylshikonin stimulates glucose uptake in L6 myotubes via a PLC-ß3/PKCδ-dependent pathway.

Acetylshikonin, a naphthoquinone derivative derived from Lithospermum erythrorhizon, has been shown to have various pharmacological activities; however, its effect on diabetes has rarely been reported. We investigated the hypoglycemic effect of acetylshikonin and found that it decreased blood glucose to a greater extent than insulin and improved glucose tolerance in mice. It also increased glucose uptake in L6 myotubes by inducing the expression and translocation of glucose transporter 4 via decomposition of phosphatidylinositol, increased generation of diacylglycerol, and activation of protein kinase C delta cascades; this is an insulin-, reactive oxygen species-, and AMP-activated protein kinase-independent pathway for glucose uptake. Our findings highlight the antidiabetic potential of acetylshikonin via a possible novel pathway for glucose uptake in L6 myotubes.

Acetylshikonin from Zicao attenuates cognitive impairment and hippocampus senescence in d-galactose-induced aging mouse model via upregulating the expression of SIRT1.

Zicao acts as a pleiotropic medicine in various diseases due to its particular pharmacological properties, including anti-inflammatory, anti-tumor, anti-oxidative, and wound healing effects. However, few studies have focused on the function in neurodegenerative diseases of Zicao. In this study, we investigated the neuroprotective effect of Acetylshikonin (AS) from Zicao on the hippocampus of the d-galactose (d-gal)-induced sub-acute aging mouse model of Alzheimer's disease (AD). The aging model was established in male Kunming mice by subcutaneous injection of d-gal (150 mg/kg/d) for 60 days, and the mice were given AS (270, 540 and 1080 mg/kg/d) or distilled water intragastrically for 30 days after 30 days of d-gal injection. The behavioral results test by Morris Water Maze (MWM) revealed that chronic AS treatment alleviated d-gal-induced learning and memory deficits compared with the d-gal-treated mice. In addition, AS also ameliorated the oxidative stress and neuroinflammation induced by d-gal through decreasing the level of interleukin-1ß (IL-1ß), tumor necrosis factor α (TNF-α), malondialdehyde (MDA) and enhancing the activity of the antioxidant enzymes superoxide dismutase (SOD). Moreover, western blot results showed that AS can up-regulate the expression of Sirtuin 1 (SIRT1) and inhibit d-gal-induced activation of p53/p21 signaling pathway in the hippocampus of mice. These results suggest that AS can execute the prevention and treatment of d-gal-induced brain aging by SIRT1/P53/P21 pathway.