Barbeya oleoides Leaves Extracts: In Vitro Carbohydrate Digestive Enzymes Inhibition and Phytochemical Characterization

This study investigated the in vitro inhibitory potential of different solvent extracts of leaves of Barbeya oleoides on key enzymes related to type 2 diabetes mellitus (α-glucosidase and α-amylase) in combination with an aggregation assay (using 0.01% Triton X-100 detergent) to assess the specificity of action. The methanol extract was the most active in inhibiting α-glucosidase and α-amylase, with IC50 values of 6.67 ± 0.30 and 25.62 ± 4.12 µg/mL, respectively. However, these activities were significantly attenuated in the presence of 0.01% Triton X-100. The chemical analysis of the methanol extract was conducted utilizing a dereplication approach combing LC-ESI-MS/MS and database searching. The chemical analysis detected 27 major peaks in the negative ion mode, and 24 phenolic compounds, predominantly tannins and flavonol glycosides derivatives, were tentatively identified. Our data indicate that the enzyme inhibitory activity was probably due to aggregation-based inhibition, perhaps linked to polyphenols.

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The Repurposed Drugs Suramin and Quinacrine Cooperatively Inhibit SARS-CoV-2 3CLpro In Vitro

Viruses ◽

10.3390/v13050873 ◽

2021 ◽

Vol 13 (5) ◽

pp. 873

Author(s):

Raphael J. Eberle ◽

Danilo S. Olivier ◽

Marcos S. Amaral ◽

Ian Gering ◽

Dieter Willbold ◽

...

Keyword(s):

Binding Mode ◽

Drug Candidates ◽

Main Protease ◽

Ic50 Values ◽

Repurposed Drugs ◽

Antiparasitic Drugs ◽

Inhibitory Potential ◽

Dynamics Simulations ◽

Micromolar Range

Since the first report of a new pneumonia disease in December 2019 (Wuhan, China) the WHO reported more than 148 million confirmed cases and 3.1 million losses globally up to now. The causative agent of COVID-19 (SARS-CoV-2) has spread worldwide, resulting in a pandemic of unprecedented magnitude. To date, several clinically safe and efficient vaccines (e.g., Pfizer-BioNTech, Moderna, Johnson & Johnson, and AstraZeneca COVID-19 vaccines) as well as drugs for emergency use have been approved. However, increasing numbers of SARS-Cov-2 variants make it imminent to identify an alternative way to treat SARS-CoV-2 infections. A well-known strategy to identify molecules with inhibitory potential against SARS-CoV-2 proteins is repurposing clinically developed drugs, e.g., antiparasitic drugs. The results described in this study demonstrated the inhibitory potential of quinacrine and suramin against SARS-CoV-2 main protease (3CLpro). Quinacrine and suramin molecules presented a competitive and noncompetitive inhibition mode, respectively, with IC50 values in the low micromolar range. Surface plasmon resonance (SPR) experiments demonstrated that quinacrine and suramin alone possessed a moderate or weak affinity with SARS-CoV-2 3CLpro but suramin binding increased quinacrine interaction by around a factor of eight. Using docking and molecular dynamics simulations, we identified a possible binding mode and the amino acids involved in these interactions. Our results suggested that suramin, in combination with quinacrine, showed promising synergistic efficacy to inhibit SARS-CoV-2 3CLpro. We suppose that the identification of effective, synergistic drug combinations could lead to the design of better treatments for the COVID-19 disease and repurposable drug candidates offer fast therapeutic breakthroughs, mainly in a pandemic moment.

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In vitro Antidiabetic, anti-obesity and antioxidant proprities of Rosemary extracts

JOURNAL OF ADVANCES IN CHEMISTRY ◽

10.24297/jac.v10i2.5497 ◽

2014 ◽

Vol 10 (2) ◽

pp. 2305-2316 ◽

Cited By ~ 4

Author(s):

Manel Ben Ali ◽

Kais Mnafgui ◽

Abdelfattah Feki ◽

Mohamed Damak ◽

Noureddine Allouche

Keyword(s):

Essential Oil ◽

Ethyl Acetate ◽

Pancreatic Lipase ◽

Antioxidant Properties ◽

Methanolic Extracts ◽

Ic50 Values ◽

Inhibitory Potential ◽

Prevention Of Diabetes ◽

First Time

Diabetes mellitus is a serious health problem worldwide that has adverse and long-lasting consequences for individuals, families, and communities. Hence, this study sought to investigate the inhibitory potential of rosemary extracts on key-enzymes related to diabetes such as α-amylase and pancreatic lipase activities, as well as to assess their antioxidant properties in vitro. The IC50 values of Rosemary essential oil, ethyl acetate and methanolic extracts against α-amylase were 28.36, 34.11 and 30.39 µg/mL respectively, and those against pancreatic lipase were 32.25, 36.64 and 34.07 µg/mL, suggesting strong anti-diabetic and anti-obesity effects of Rosemary. The methanolic extract was found to be the highest in levels of phenolic (282.98 µgGAE/mg extract) and flavonoids (161.05 µg QE /mg extract) contents as well as in the antioxidant activity (IC50 = 15.82 µg/mL) as compared to other extracts ethyl acetate (IC50 = 32.23 µg/mL) and essential oil (IC50 = 96.12 µg/mL).Antioxidant efficacy of Rosemary extracts has been estimated in the stabilization of sunflower oil (SFO) at three different concentrations, i.e. 200 (SFO-200), 500 (SFO-500) and 1000 ppm (SFO-1000). Results showed the highest efficiency of SFO-1000.The results obtained in this study demonstrated for the first time that Rosemary is a potent source of natural inhibitors of α-amylase and pancreatic lipase with powerful antioxidants proprieties that might be used in the food stabilization and the prevention of diabetes and obesity complications as a complementary pharmacological drug.

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Chemical profiling, in vitro antioxidant and antidiabetic assessment of flavonoids from the ethanol extract of Hermannia geniculata root

Sokoto Journal of Veterinary Sciences ◽

10.4314/sokjvs.v19i1.1 ◽

2021 ◽

Vol 19 (1) ◽

pp. 1-13

Author(s):

L.A. Adeniran ◽

C.P. Palanisamy ◽

A.O.T. Ashafa

Keyword(s):

Competitive Inhibition ◽

Antioxidant Properties ◽

Reactive Oxygen ◽

Ethanol Extract ◽

Kinetic Studies ◽

Retention Factor ◽

Chemical Profiling ◽

Ic50 Values ◽

Inhibitory Potential

Determination of the in vitro antioxidant and the inhibitory potential of flavonoids from Hermannia geniculata (FHG) roots on diabetes-linked enzymes was carried out. The chemical profiling of FHG roots extract was investigated using High Pressure Thin Layer Chromatography (HPTLC) fingerprint analysis. The reactive oxygen scavenging potential of the extract was analyzed. Starch solution (1%) was reacted with different concentrations of FHG extract to determine the α-amylase inhibitory potential of the extract while α- glucosidase inhibition assay was carried out through incubation of different concentrations of the extract followed by addition of p-ntrophenyl-α-Dglucopyranoside solution. HPTLC results indicated the presence of flavonoids/ phenolcarboxylic acid, and Kaemferol (Rf 0.80) were detected in the extract with retention factor Rf. ranging from 0.08 to 0.95. FHG extract showed commendable antioxidant properties with IC50 values (3.07± 0.12, 2.13± 0.67) µg/mL for 1, 1-diphenyl-2- picrylhydrazyl (DPPH) and 2, 2-azino-bis (3- ethylbenzothiazoline-6-sulphonic) acid (ABTS) radicals which were lower and significantly different (p<0.05) compared to standard silymarin with IC50: (3.55± 0.10, 2.77± 0.75) µg/mL for DPPH and ABTS respectively. The results indicated mild inhibition of α-amylase with IC50: (5.55± 0.37) µg/mL which was higher and significantly different (p<0.05) from acarbose with IC50: (3.81± 0.29) µg/mL. Moreover, the extract showed 73% inhibition of α-glucosidase. Kinetic studies of FHG extract revealed competitive and mixed non-competitive inhibition of α- amylase and α-glucosidase respectively. This study indicated FHG capabilities of scavenging reactive oxygen species and reducing hydrolysis of starch responsible for post-prandial hyperglyceamia seen in type 2 diabetes mellitus. Keywords: Antidiabetic, Antioxidant, Flavonoids, Hermannia geniculate, HPTLC

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Anti-plasmodial Effects of Zanthoxylum zanthoxyloides

Planta Medica ◽

10.1055/a-0973-0067 ◽

2019 ◽

Vol 85 (13) ◽

pp. 1073-1079 ◽

Cited By ~ 1

Author(s):

Christopher Dean Goodman ◽

An Thuy Hoang ◽

Drissa Diallo ◽

Karl Egil Malterud ◽

Geoffrey I. McFadden ◽

...

Keyword(s):

Brine Shrimp ◽

Methanol Extract ◽

Stem Bark ◽

Artemia Salina ◽

Root Bark ◽

Ic50 Values ◽

Zanthoxylum Zanthoxyloides ◽

Parasitic Activity ◽

Resistant Strains

Abstract Zanthoxylum zanthoxyloides, syn. Fagara zanthoxyloides, is a tree growing in West Africa and is used in traditional medicine against a variety of diseases, including malaria. In the work reported here, root bark and stem bark extracts of this tree, as well as compounds isolated from the extracts, have been investigated for activity in vitro against chloroquine-sensitive and chloroquine-resistant strains of Plasmodium falciparum. In addition, toxicity against nauplii of the brine shrimp Artemia salina has been studied. Dichloromethane extracts of the root bark and stem bark, and a methanol extract of the stem bark, showed anti-parasitic activity towards chloroquine-sensitive as well as chloroquine-resistant P. falciparum, with IC50 values between 1 and 10 µg/mL. Among the isolated compounds, bis-dihydrochelerythrinyl ether, buesgenine, chelerythrine, γ-fagarine, skimmianine, and pellitorine were the most active, with IC50 values of less than 5 µg/mL. The dichloromethane extracts were toxic to brine shrimp nauplii, with LC50 values of less than 1 µg/mL. Methanol extracts were much less toxic (LC50 between 50 and 100 µg/mL). Among the isolated substances, bis-dihydrochelethrinyl ether was the most toxic (LC50 ca. 2 µg/mL).

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Design, Synthesis and Biological Evaluation of Aromatase Inhibitors based on Sulfonates and Sulfonamides of Resveratrol

Pharmaceuticals ◽

10.3390/ph14100984 ◽

2021 ◽

Vol 14 (10) ◽

pp. 984

Author(s):

Marialuigia Fantacuzzi ◽

Marialucia Gallorini ◽

Nicola Gambacorta ◽

Alessandra Ammazzalorso ◽

Zeineb Aturki ◽

...

Keyword(s):

Aromatase Inhibitors ◽

Biological Response ◽

Docking Studies ◽

Biological Evaluation ◽

Design Synthesis ◽

Ic50 Values ◽

Mcf7 Cell Line ◽

Nano Liquid Chromatography ◽

Inhibitory Potential

A library of sulfonate and sulfonamide derivatives of Resveratrol was synthesized and tested for its aromatase inhibitory potential. Interestingly, sulfonate derivatives were found to be more active than sulfonamide bioisosteres with IC50 values in the low micromolar range. The sulfonate analogues 1b–c and 1j exhibited good in vitro antiproliferative activity on the MCF7 cell line, evidenced by MTT and LDH release assays. Structure–activity relationships suggested that electronic and lipophilic properties could have a different role in promoting the biological response for sulfonates and sulfonamides, respectively. Docking studies disclosed the main interactions at a molecular level of detail behind the observed inhibition of the more active compounds whose chemical stability has been evaluated with nano-liquid chromatography. Finally, 1b–c and 1j were highlighted as sulfonates to be further developed as novel and original aromatase inhibitors.

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Secondary metabolite profiling and characterization of diterpenes and flavones from the methanolic extract of Andrographis paniculata using HPLC-LC-MS/MS

Future Journal of Pharmaceutical Sciences ◽

10.1186/s43094-021-00292-6 ◽

2021 ◽

Vol 7 (1) ◽

Author(s):

Manish Kumar Dwivedi ◽

Shruti Sonter ◽

Shringika Mishra ◽

Priyanka Singh ◽

Prashant Kumar Singh

Keyword(s):

Methanolic Extract ◽

Rapid Identification ◽

Andrographis Paniculata ◽

Negative Ion ◽

Spectroscopic Techniques ◽

Lead Compounds ◽

Methoxy Flavone ◽

Negative Ion Mode

Abstract Background Andrographis paniculata is a well-known medicinal plant that contains various classes of bioactive secondary metabolites. It is widely used by the traditional medicinal healers for treatment of malaria and other diseases. There is an urgent need for screening of potent novel compounds from the methanol extract of A. paniculata. Earlier, we obtained appreciable in vitro anti-malarial activity (IC50-10.75 μg/ml) in the same plant. In current study, we developed novel analytical methods for rapid identification and characterization of diterpenes and flavones using chromatographic and spectroscopic techniques and identified major compounds that might possess anti-malarial activities. Results Based on the chromatographic and mass spectrometric features, we have identified a total of 74 compounds (25 compounds from positive ion mode; 49 compounds from negative ion mode). The mass spectrum data predicted andrographolide (15%) presence in the highest amount in both positive and negative ion modes. Based on the percentage purity, Andrographolide and skullcapflavone I was selected as representative class of diterpenes and flavones for fragmentation studies. Conclusions The result led to identification of Neoandrographolide, andrographolactone, 14-dehydroxy-11,12-didehydroandrographolide, skullcapflavone I, and 5-Hydroxy-2′,7,8-tri methoxy flavone from the methanolic extract of A. paniculata that is used in traditional medicine by tribal healers of Amarkantak region for treating malaria. These could be lead compounds for the development of novel anti-malarial drugs.

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Antiurolithiasis Activity of Bioactivity Guided Fraction ofBergenia ligulataagainst Ethylene Glycol Induced Renal Calculi in Rat

BioMed Research International ◽

10.1155/2017/1969525 ◽

2017 ◽

Vol 2017 ◽

pp. 1-11 ◽

Cited By ~ 5

Author(s):

Ikshit Sharma ◽

Washim Khan ◽

Rabea Parveen ◽

Md. Javed Alam ◽

Iftekhar Ahmad ◽

...

Keyword(s):

Ethylene Glycol ◽

Ex Vivo ◽

Histological Study ◽

Renal Calculi ◽

Rat Plasma ◽

Scientific Basis ◽

Aggregation Assay ◽

Wide Range ◽

Inhibitory Potential

Dried rhizome ofBergenia ligulata(pashanbhed) is commonly used as a traditional herbal medicine with a wide range of therapeutic applications including urolithiasis. Aqueous extract ofB. ligulatawas prepared through maceration followed by decoction (mother extract, 35.9% w/w). Further, polarity based fractions were prepared successively from mother extract which yielded 3.4, 2.9, 5.4, 7.5, and 11.3% w/w of hexane, toluene, dichloromethane (DCM),n-butanol, and water fractions, respectively. The in vitro, ex vivo, and real-time antiurolithiasis activity of mother extract and fractions were carried out using aggregation assay in synthetic urine and in rat plasma. The study revealed that DCM fraction has significantly (p<0.05) greater inhibitory potential than other fractions. Ethylene glycol in drinking water (0.75%, v/v) for 28 days was used for induction of urolithiasis and the curative effects of mother extract and DCM fraction were checked for the level of oxalate, calcium, creatinine, uric acid, and urea of both urine and serum. Treatment with mother extract and DCM fraction at a dose of 185 mg/kg and 7 mg/kg, respectively, in ethylene glycol induced rats resulted in a significant (p<0.05) decrease in serum and urine markers. Histological study revealed lower number of calcium oxalate deposits with minimum damage in the kidneys of mother extract and DCM fraction treated rats. This result provides a scientific basis for its traditional claims.

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Simultaneous Quantification of Propylthiouracil and Its N-β-d Glucuronide by HPLC-MS/MS: Application to a Metabolic Study

Pharmaceuticals ◽

10.3390/ph14111194 ◽

2021 ◽

Vol 14 (11) ◽

pp. 1194

Author(s):

Min Li ◽

Qingfeng He ◽

Li Yao ◽

Xiaofeng Wang ◽

Zhijia Tang ◽

...

Keyword(s):

Pediatric Population ◽

Multiple Reaction Monitoring ◽

Negative Ion ◽

Metabolic Study ◽

Simultaneous Quantification ◽

Mechanistic Investigation ◽

Age Dependent ◽

Carry Over ◽

Negative Ion Mode

Propylthiouracil (PTU) is commonly prescribed for the management of hyperthyroidism and thyrotoxicosis. Although the exact mechanism of action is not fully understood, PTU is associated with hepatoxicity in pediatric population. Glucuronidation mediated by uridine 5′-diphospho-glucuronosyltransferases (UGTs), which possess age-dependent expression, has been proposed as an important metabolic pathway of PTU. To further examine the metabolism of PTU, a reliable HPLC-MS/MS method for the simultaneous quantification of PTU and its N-β-D glucuronide (PTU-GLU) was developed and validated. The chromatographic separation was achieved on a ZORBAX Extend-C18 column (2.1 × 50 mm, 1.8 μm) through gradient delivery of a mixture of formic acid, methanol and acetonitrile. The electrospray ionization (ESI) was operated in its negative ion mode while PTU and PTU-GLU were detected by multiple reaction monitoring (MRM). This analytical method displayed excellent linearity, sensitivity, accuracy, precision, recovery and stability while its matrix effect and carry-over were insignificant. Subsequently, the in vitro metabolism of PTU was assessed and UGT1A9 was identified as an important UGT isoform responsible for the glucuronidation of PTU. The information obtained from this study will facilitate future mechanistic investigation on the hepatoxicity of PTU and may optimize its clinical application.

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Development and Validation of UPLC-MS / MS Method for Obtaining Favipiravir Tablet Dosage form and Evaluation of its Behavior Under forced Conditions

Journal of Pharmaceutical Research International ◽

10.9734/jpri/2021/v33i56a33895 ◽

2021 ◽

pp. 130-140

Author(s):

Süleyman Gökce ◽

Ayşen Höl ◽

Ibrahim Bulduk

Keyword(s):

Active Substance ◽

Uv Light ◽

Thermal Conditions ◽

Test Method ◽

Negative Ion ◽

Ionization Source ◽

Degradation Rates ◽

Negative Ion Mode

Aims: Favipiravir (FVP) is a drug developed against RNA viruses. It is a drug that is used actively in the treatment of coronavirus. In vitro and in vivo investigations have shown that it inhibits the virus. In this study, a recovery study of tablet formulations was carried out by developing a UPLC-MS/MS method, which is used extensively in pandemic conditions. In addition, stability studies of favipiravir agent under forced conditions were conducted. The validated method is selective, robust, simple and applicable for tablet analysis. C18 (4.6 mm × 50 mm, 2.7 μm) column was used as the stationary phase and water-methanol (80-20 v/v) containing 0.1% formic acid was used as the mobile phase. UPLC optimization; It was conducted at a wavelength of 222 nm and a flow rate of 0.8 mL/min at 40 °C, retention time was 1.155 min. The electrospray jet stream ionization source was analyzed using mass spectrometry in negative ion mode. The molecular peak for Favipiravir was [M-1] 155.9, and the daughter ion determined 112.6. The stability test method was carried out in accordance with the ICH procedure. Reaction and degradation rates of the active substance under various forced conditions (acidic, basic, oxidative, UV light and thermal conditions) were investigated. The products formed by the decomposition of the active substance under stress conditions were determined by mass spectroscopy.

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In vitro inhibitory potential of methanolic extract of Celosia argentea var. cristata on tyrosinase, acetylcholinesterase and butyrylcholinesterase enzymes

Bangladesh Journal of Pharmacology ◽

10.3329/bjp.v10i2.22880 ◽

2015 ◽

Vol 10 (2) ◽

pp. 449 ◽

Cited By ~ 3

Author(s):

Fatima Saqib ◽

Khalid Hussain Janbaz ◽

Maryam Khan Sherwani

Keyword(s):

Neurodegenerative Disorders ◽

Inhibitory Activity ◽

Methanol Extract ◽

Methanolic Extract ◽

Microtiter Plate ◽

Tyrosinase Inhibitory Activity ◽

Skin Hyperpigmentation ◽

Celosia Argentea ◽

Inhibitory Potential

In the current study, methanol extract of Celosia argentea var. cristata was tested for its inhibitory potential against tyrosinase, acetylcholinesterase and butyrylcholinesterase enzymes at the concentration of 0.5 mM by ELISA microtiter plate assays. A significant tyrosinase inhibitory activity (63.6%), acetylcholinesterase inhibitory activity (80.3%) and butyrylcholinesterse inhibitory activity (68.24%) was shown by crude methanolic extract of C. argentea var. cristata with respective IC50 values of 268.5 ± 0.2 µg/mL, 73.6 ± 0.1 µg/mL and 132.8 ± 0.9 µg/mL. The result of this study reveals the use of C. argentea var. cristata in skin hyperpigmentation, Parkinson’s disease and neurodegenerative disorders like Alzheimer’s disease and dementia.

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