Synthesis, and evaluation of α-amylase and α-glucosidase inhibitory potential of new pyrazolo[3,4-d]pyrimidine derivatives

A series of new pyrazolo[3,4-d]pyrimidine compounds were synthesized in excellent yields via sulfuration and 1,3-dipolar cycloaddition and confirmed by MS, FT-IR and NMR techniques. All the prepared compounds were screened in vitro for their α-amylase and α-glucosidase inhibitory activities. Preliminary results indicated that some target compounds exhibited promising α-amylase and α-glucosidase inhibitory activity potency. Among the tested products, the cycloadduct f was found most active inhibitor (IC50 = 134.30 μM) for α-amylase, and the sulphur product b is the most active inhibitor (IC50 = 16.37 μM) for α-glucosidase

Antioxidant Activity and Inhibitory Potential of Cistus salviifolius (L.) and Cistus monspeliensis (L.) Aerial Parts Extracts against Key Enzymes Linked to Hyperglycemia

Cistus genus (Cistaceae) comprises several medicinal plants used in traditional medicines to treat several pathological conditions including hyperglycemia. These include Cistus salviifolius L. (CS) and Cistus monspeliensis L. (CM), still not fully explored as a source of metabolites with therapeutic potential for human diseases. In this study, the antioxidant α-amylase and α-glucosidase enzyme inhibitory effects of aqueous and hydromethanolic extracts from the aerial parts of Moroccan CS and CM were investigated. Antioxidant activity has been assessed using 1,1-diphenyl-2-picrylhydrazyl (DPPH) and 2,2′-azinobis(3-ethylbenzothiazoline-6-sulfonic acid) diammonium salt (ABTS) radicals and ferric reducing/antioxidant power (FRAP) methods. The α-amylase and α-glucosidase inhibitory activity has been assessed using an in vitro model. Moreover, mineral and phenolic contents of CS and CM were analyzed. The extracts of both species exhibited potent antioxidant activity in all used systems and possess strong inhibitory effect towards α-glucosidase (IC50: 0.95±0.14 to 14.58±1.26 μg/mL) and significant inhibitory potential against α-amylase (IC50: 217.10±0.15 to 886.10±0.10 μg/mL). Furthermore, the result showed high levels of phenolic content and unexpectedly some higher levels of mineral content in CS. The results suggest that the phenolic rich extracts of CS and CM may have a therapeutic potential against diseases associated with oxidative stress and may be useful in the management of hyperglycemia in diabetic patients

The Extract of Corydalis yanhusuo Prevents Morphine Tolerance and Dependence

The opioid epidemic was triggered by an overprescription of opioid analgesics. In the treatment of chronic pain, repeated opioid administrations are required which ultimately lead to tolerance, physical dependence, and addiction. A possible way to overcome this conundrum consists of a co-medication that maintains the analgesic benefits of opioids while preventing their adverse liabilities. YHS, the extract of the plant Corydalis yanhusuo, has been used as analgesic in traditional Chinese medicine for centuries. More recently, it has been shown to promote analgesia in animal models of acute, inflammatory, and neuropathic pain. It acts, at least in part, by inhibiting the dopamine D2 receptor, suggesting that it may be advantageous to manage addiction. We first show that, in animals, YHS can increase the efficacy of morphine antinociceptive and, as such, decrease the need of the opioid. We then show that YHS, when coadministered with morphine, inhibits morphine tolerance, dependence, and addiction. Finally, we show that, in animals treated for several days with morphine, YHS can reverse morphine dependence and addiction. Together, these data indicate that YHS may be useful as a co-medication in morphine therapies to limit adverse morphine effects. Because YHS is readily available and safe, it may have an immediate positive impact to curb the opioid epidemic

Secondary-metabolites fingerprinting of Argania spinosa kernels using liquid chromatography–mass spectrometry and chemometrics, for metabolite identification and quantification as well as for geographic classification

Argan (Argania spinosa L.) fruit kernels' composition has been poorly studied and received less research intensity than the resulting Argan oil. The Moroccan Argan kernels contain a wealth of metabolites and can be investigated for nutritional and health aspects as well as for economic benefits. Ultra-Performance Liquid Chromatography Mass Spectrometry (UPLC-MS) was employed to trace the geographical origin of Argan kernels based on secondary-metabolite profiles. One-hundred and twenty Argan fruit kernels from five regions ('Agadir', 'Ait-Baha' 'Essaouira', 'Tiznit' and 'Taroudant') were studied. Characterization and quantification of 36 secondary metabolites (33 polyphenolic and 3 non-phenolic) were achieved. Those metabolites are highly influenced by the geographic origin. Then, the untargeted UPLC-MS fingerprint was decomposed by metabolomic data handling tools, such as multivariate curve resolution alternating least squares (MCR-ALS) and XCMS. The two resulting data matrices were pretreated and prepared separately by chemometric tools and then two data fusion strategies (low-and mid-levels) were applied on them. The four data sets were comparatively investigated. Principal component analysis (PCA), Partial Least Squares Discriminant Analysis (PLS-DA), and Soft Independent Modeling of Class Analogies (SIMCA) were used to classify samples. The exploration or classification models demonstrated a good ability to discriminate and classify the samples in the geographical-origin based classes. Summarized, the developed fingerprints and their metabolomics-based data handling successfully allowed geographical traceability evaluation of Moroccan Argan kernels.(c) 2022 Elsevier B.V. All rights reserved.Peer reviewe

Authentication of extra virgin Argan oil by selected-ion flow-tube mass-spectrometry fingerprinting and chemometrics

Recognized for its nutritional and therapeutic use, extra-virgin Argan Oil (EVAO) is frequently adulterated. Selected-Ion Flow-Tube Mass Spectrometry (SIFT-MS) spectra were applied to quantify adulterants (i.e., Argan oil of lower quality (LQAO), olive oil (OO), and sunflower oil (SO)) in EVAO. Four data sets, i.e., using H3O+, NO+, O-2(+center dot) reagent ions, and the combined data were considered. Soft independent modelling of class analogy (SIMCA), and partial least squares discriminant analysis (PLS-DA) were assessed to distinguish adulterated-from pure EVAO. The effectiveness of SIFT-MS associated with PLS and support vector machine (SVM) regression to quantify trace adulterants in EVAO was evaluated. Variable Importance in Projection (VIP), and interval-PLS (iPLS) were also investigated to extract useful features. Different models were built to predict the EVAO authenticity and the degree of adulteration. High accuracy was achieved. SIFT-MS spectra handled with the appropriate chemometric tools were found suitable for the quality evaluation of EVAO

Comparative Study of Leaf and Rootstock Aqueous Extracts of Foeniculum vulgare on Chemical Profile and In Vitro Antioxidant and Antihyperglycemic Activities

Foeniculum vulgare is a medicinal plant used in Moroccan folk medicine to treat several diseases such as diabetes. The aim of this study was to determine the phenolic bioactive compounds and to evaluate the antioxidant and antihyperglycemic activities of Foeniculum vulgare leaf and rootstock extracts. Phenolic compounds of F. vulgare rootstock and leaf extracts were determined using HPLC-DAD-QTOFMS analysis. The antioxidant activity was evaluated using 1,1-diphenyl-2-picrylhydrazyl (DPPH) and 2,2’-azinobis-(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS•+) radicals. Moreover, the in vitro antihyperglycemic effects were tested by measuring the inhibition of α-amylase and α-glucosidase activities. HPLC-DAD-QTOFMS analysis identified thirty-two phenolic components in both leaf and rootstock extracts. Caffeic acid, quinic acid, and chlorogenic acid were the major compounds of F. vulgare leaf extract (FVLE), while the main compound of F. vulgare rootstock extracts (FVRE) was quinic acid. In the DPPH assay, F. vulgare leaf extract showed important antioxidant activity (IC50 = 12.16 ± 0.02 μg/mL) than F. vulgare rootstock extract (IC50 = 34.36 ± 0.09 μg/mL). Moreover, fennel leaf extracts revealed also the most powerful antioxidant activity (IC50 = 22.95 ± 0.4 μg/mL) in the ABTS assay. The in vitro antihyperglycemic activity showed that F. vulgare rootstock extract exhibited a remarkable inhibitory capacity (IC50 = 194.30 ± 4.8 μg/mL) of α-amylase compared with F. vulgare leaf extract (IC50 = 1026.50 ± 6.5 μg/mL). Furthermore, the inhibition of α-glucosidase was more importantly with F. vulgare rootstock (IC50 of 165.90 ± 1.2 μg/mL) than F. vulgare leaf extracts (203.80 ± 1.3 μg/mL). The funding of this study showed that F. vulgare rootstock and leaf extracts presented several phenolic compounds and showed important antioxidant and antidiabetic effects. We suggest that the identified molecules are responsible for the obtained activities. However, further studies focusing on the isolation and the determination of antioxidant and antidiabetic effects of F. vulgare rootstock and leaf main compounds are required