α-Glucosidase Inhibition, Antioxidant and Docking Studies of Hydroxycoumarins and their Mono and Bis O-alkylated/acetylated Analogs

2018 ◽  
Vol 15 (2) ◽  
pp. 127-135 ◽  
Author(s):  
Parvesh Singh ◽  
Nomandla Ngcoya ◽  
Ramgopal Mopuri ◽  
Nagaraju Kerru ◽  
Neha Manhas ◽  
...  

Background: Diabetes Mellitus (DM) is a complex metabolic disease illustrated by abnormally high levels of plasma glucose or hyperglycaemia. Accordingly, several α-glucosidase inhibitors have been developed for the treatment of diabetes and other degenerative disorders. While, a coumarin ring has the privilege to represent numerous natural and synthetic compounds with a wide spectrum of biological activities e.g. anti-cancer, anti-HIV, anti-viral, anti-malarial, anti-microbial, anti-convulsant, anti-hypertensive properties. Besides this, coumarins have also shown potential to inhibit α-glucosidase leading to a generation of new promising antidiabetic agents. However, the testing of O-substituted coumarins for α-glucosidase inhibition has evaded the attention of medicinal chemists. Methods: For O-alkylation/acetylation reactions, the hydroxyl coumarins (A-B) initially activated by K2CO3 in dry DMF were reacted with variedly substituted haloalkanes at room temperature under nitrogen. The synthesized compounds were tested for their α-glucosidase (from Saccharomyces cerevisiae) inhibitory activity and anti-oxidant activity using DPPH radical scavenging activity. In silico docking simulations were conducted using CDocker module in DS (Accelrys) to explore the binding modes of the representative compounds in the catalytic site of α-glucosidase. Results: All the coumarin analogues (A1, B1, A2-A10, B2-B8) including their precursors (A-B) were evaluated for their in vitro α-glucosidase inhibition using acarbose as a standard inhibitor. All the mono O-alkylated coumarins (except A1) showed significant (p <0.05) α-glucosidase inhibition relative to the hydroxyl coumarin (A) with IC50 values ranging between 11.084±0.117 to 145.24± 29.22 µg/mL. Compound 7-(benzyloxy)-4, 5-dimethyl-2H-chromen-2-one (A9) bearing a benzyl group (Ph-CH2-) at position 7 showed a remarkable (p <0.05) increase in the activity (IC50 = 11.084±0.117 µg/mL), almost four-fold more than acarbose (IC50 = 40.578±5.999 µg/mL). The introduction of –NO2 group dramatically improved the anti-oxidant activity of coumarin, while the O-alkylation/acetylation decreased the activity. Conclusion: The present study describes the synthesis of functionalized coumarins and their evaluation for α-glucosidase inhibition and antioxidant activity under in vitro conditions. Based on IC50 data, the mono O-alkylated coumarins were observed to be stronger inhibitors of α-glucosidase with respect to their bis O-alkylated analogues. Coumarin (A9) bearing O-benzyloxy group displayed the strongest α-glucosidase inhibition, even higher than the standard inhibitor acarbose. The coumarin (A10) bearing –NO2 group showed the highest anti-oxidant activity amongst the synthesized compounds, almost comparable to the ascorbic acid. Finally, in silico docking simulations revealed the role of hydrogen bonding and hydrophobic forces in locking the compounds in catalytic site of α-glucosidase.

2018 ◽  
Vol 8 (5-s) ◽  
pp. 126-131
Author(s):  
ND Rekha ◽  
Dattatri K. Nagesha ◽  
PH Rajasree ◽  
N Shruthi

The present study was undertaken to formulate and evaluate the anti-inflammatory, anti-oxidant and anti-angiogenic activities of nanoemulsion of Memecylaene.  Memecylaene was isolated from the leaves of Memecylon malabaricum by using various chromatographic methods. An oil-in-water (O/W) nanoemulsion of Memecylaene was formulated by sonication method using sunflower oil (oil phase), Tween 80 (Surfactant) and Ethanol (co-surfactant). The prepared nanoemulsion was characterized for its droplet size, poly dispersity index and zeta potential. Stability studies were performed and the nanoemulsions were subjected to different biological activities. The formulated nanoemulsion had a particle size range of 52.02 nm to 59.47 nm and zeta potential of -1.27 mV. The enhanced activity of Memecylaene, encapsulated in O/W emulsions is evidenced by the inhibition of phospholipase (PLA2) enzyme and H+, K+ -ATPase and thus showing anti-inflammatory and anti-secretagogues effects. The in vitro anti-oxidant activity was evaluated by DPPH radical and Nitric oxide radical scavenging activity. Further, the inhibition of the growth of neo vessels formation in the in-vivo model system of chick chorioallantoic membrane (CAM) assay, which is angiogenesis dependent, was also observed. The above findings would help in understanding the putative potential of Memecylaene-loaded nanoemulsion as a therapeutic agent. Keywords: Anti-angiogenesis, Anti-oxidant, Gastric (H+ K+), Memecylaene, Nanoemulsion, Phospholipase A2 (PLA2).


Biomolecules ◽  
2020 ◽  
Vol 10 (5) ◽  
pp. 731 ◽  
Author(s):  
Nabeelah Bibi Sadeer ◽  
Kouadio Ibrahime Sinan ◽  
Zoltán Cziáky ◽  
József Jekő ◽  
Gokhan Zengin ◽  
...  

Bruguiera gymnorhiza (L.) Lam. is claimed to effectively manage a number of ailments including diabetes and associated complications. Nonetheless, no attempt has been made to delineate its pharmacological propensities and phytochemical profile. This study was designed to appraise the antioxidant and enzymatic inhibitory properties relevant to the management of diabetes mellitus, obesity, and neurodegenerative and skin disorders. A combination of colorimetric assays and ultra-high-performance liquid chromatography/electrospray ionization tandem mass spectrometry (UHPLC-ESI-MS/MS) were applied for the phytochemical screening of leaf, root, twig, and fruit extracts (methanol and ethyl acetate). In vitro antioxidant evaluations were via radical scavenging abilities (DPPH, ABTS), reducing potential (FRAP, CUPRAC), chelating power, and total antioxidant capacity (phosphomolybdenum). Seven key metabolic enzymes (α-amylase, α-glucosidase, tyrosinase, elastase, lipase, AChE, and BChE) were targeted to determine the inhibitory effects. Multivariate and in silico docking analysis were performed on collected data. Methanolic fruit extract yielded the highest total phenolic, tannin, and triterpenoid contents (174.18 ± 4.27 mg GAE/g, 176.24 ± 3.10 mg CE/g, 63.11 ± 3.27 mg OAE/g, respectively); significantly depressed tyrosinase, elastase, and α-amylase activities (155.35 ± 0.29 mg KAE/g, 4.56 ± 0.10 mg CAE/g, 1.00 ± 0.05 mmol ACAE/g, accordingly); and harboured the most potent antioxidant capacities with DPPH, CUPRAC, FRAP (492.62 ± 5.31, 961.46 ± 11.18, 552.49 ± 8.71 mg TE/g, respectively), and phosphomolybdenum (4.17 ± 0.31 mmol TE/g) assays. Multivariate analysis suggested that the type of solvents used influenced the biological activities more compared to plant parts. Docking analysis showed that azelaic acid binds with tyrosinase by Van der Waals and conventional hydrogen bonds. We anticipate that the present study may establish baseline data on this halophyte that could open new avenues for the development of biomedicine.


Biomolecules ◽  
2021 ◽  
Vol 11 (1) ◽  
pp. 53
Author(s):  
Adeel Arshad ◽  
Saeed Ahemad ◽  
Hammad Saleem ◽  
Muhammad Saleem ◽  
Gokhan Zengin ◽  
...  

Heliotropium is one of the most important plant genera to have conventional folklore importance, and hence is a potential source of bioactive compounds. Thus, the present study was designed to explore the therapeutic potential of Heliotropium crispum Desf., a relatively under-explored medicinal plant species. Methanolic extracts prepared from a whole plant of H. crispum were studied for phytochemical composition and possible in vitro and in silico biological properties. Antioxidant potential was assessed via six different assays, and enzyme inhibition potential against key clinical enzymes involved in neurodegenerative diseases (acetylcholinesterase (AChE) and butyrylcholinesterase (BChE)), diabetes (α-amylase and α-glucosidase), and skin problems (tyrosinase) was assayed. Phytochemical composition was established via determination of the total bioactive contents and reverse phase ultra-high performance liquid chromatography mass spectrometry (RP-UHPLC-MS) analysis. Chemical profiling revealed the tentative presence of 50 secondary metabolites. The plant extract exhibited significant inhibition against AChE and BChE enzymes, with values of 3.80 and 3.44 mg GALAE/g extract, respectively. Further, the extract displayed considerable free radical scavenging activity against DPPH and ABTS radicals, with potential values of 43.19 and 41.80 mg TE/g extract, respectively. In addition, the selected compounds were then docked against the tested enzymes, which have shown high inhibition affinity. To conclude, H. crispum was found to harbor bioactive compounds and showed potent biological activities which could be further explored for potential uses in nutraceutical and pharmaceutical industries, particularly as a neuroprotective agent.


2021 ◽  
Vol 25 (1) ◽  
pp. 75-79
Author(s):  
S.O. Olubodun ◽  
G.E. Eriyamremu ◽  
M.E. Ayevbuomwan ◽  
C.I. Nzoputa

The presence of various bioactive components makes it necessary to analyse plants for their potential to act as a source of useful treatments and cures for many inflammatory, infectious and pathogenic diseases. This study was carried out to determine phytochemicals and in-vitro antioxidant activities of the leaf extracts of Acalypha godseffiana. The leaves of A. godseffiana were collected, dried, pulverized and extracted separately with methanol and water using maceration method. The extract was concentrated in vacuo with rotary evaporator at 40oC. The extracts were subjected to quantitative phytochemical analysis and different anti-oxidant analytical procedures like FRAP, DPPH etc to determine the radical scavenging capabilities. The results of phytochemical analysis estimated the quantities and revealed the presence of alkaloids, flavonoids, tannins, saponins and terpenoids which varied in both extracts. The methanol and aqueous extracts exhibited antioxidant activities with relatively high IC50 (IC50 = 3.67 ìg/ml and 4.42ìg/ml respectively) which accounted for a low free radical-scavenging activity when compared with the reference antioxidant, vitamin C (IC50 = 1.51ìg/ml). The results of the study indicates that A. godseffiana leaf extracts contain secondary metabolites and possesses antioxidant properties.


Author(s):  
Mrinmoy Basak ◽  
Moksood Ahmed Laskar ◽  
Priyanka Goswami

Most of the synthetic drugs used at present as analgesic and anti-inflammatory agents cause many side effects and toxic effects. Many medicines of plant origin with analgesic and anti-inflammatory activity have been used since long time without adverse effects. The purpose of the study was to explore the anti-pyretic and anti-oxidant activity of fruits of Garcinia pedunculata. The fruit of G. pedunculata was collected from Shillong, Meghalaya and extraction is done by using methanol as a solvent. The methanol extract shows the presence of carbohydrate, glycoside, alkaloids, phenol and flavonoids. Acute anti-pyretic activity for the extract was investigated in pyrexia rat. Temperature level was determined after 1hours, 4 hours, 8 hours and 12 hours after giving the extract dose of 100mg/kg and 200mg/kg body weight, and it was found to produce a significant reduce in fever. DPPH radical scavenging activity (In-vitro anti-oxidant activity of G. pedunculata) of methanolic extract shows 38.31 as IC50 (µg/ml) whereas Ascorbic acid as standard in the same concentration shows 34.81 IC50 (µg/ml). The obtained result justified the traditional use of G. pedunculata as anti-pyretic and antioxidant purpose.


Author(s):  
Saira Tabassum ◽  
Muhammad Zia ◽  
Esperanza J. Carcahe de Blanco ◽  
Riffat Batool ◽  
Roohi Aslam ◽  
...  

Abstract Background Arisaema jacquemontii is traditionally used in treatment of different diseases. In this study, phytochemical, in vitro biological and chemo-preventive screening of A. jacquemontii was carried out to explore its pharmacological potential. Methods The dried tuber of A. jacquemontii was extracted in 11 organic solvent mixture of different polarity. The extracts were screened for phytochemical assays (phenolics and flavonoids), antioxidants potential (free radical scavenging activity, total antioxidant activity, reducing power), biological activities (antibacterial, antifungal, cytotoxic, antileishmanial, protein kinase inhibition), and chemopreventive activities using different cell lines through standard protocols. Results Significant amount phenolic contents were determined in EtOH and MeOH extracts (210.3 ± 3.05 and 193.2 ± 3.15 μg GAE/mg, respectively). Maximum flavonoid content was determined in MeOH extract (22.4 ± 4.04 μg QE/mg). Noteworthy, DPPH scavenging activity was also recorded for MeOH extract (87.66%) followed by MeOH+EtOAc extract (85.11%). Considerable antioxidant capacity (7.8 ± 0.12 μg AAE/mg) and reducing power (3.1 ± 0.15 μg AAE/mg) was observed in extract of MeOH. The LC50 against brine shrimp and leishmanial parasite was found 9.01 and 12.87 μg/mL for n-Hex and CHCl3 extracts, respectively. The highest zone of inhibition against Streptomyces hyphae formation (12.5 ± 1.77 mm) by n-Hex extract. Growth zone of inhibition 13.8 ± 1.08 mm was recorded for EtOAc and MeOH extracts, respectively against Micrococcus luteus while 10.0 ± 0.11 mm for MeOH extract against Aspergillus flavus. In-vitro cytotoxic assay showed that n-Hex extract had higher cytotoxicity against DU-145 prostate cancer and HL-60 cancer cell lines. NF-kB and MTP potential showed 34.01 and 44.87 μg/mL for n-Hex and CHCl3 extracts, respectively in chemo-preventive potential. Conclusion The study concludes that Arisaema jacquemontii bears significant phytochemical activity and pharmacological activities, this plant can be further explored for isolation of active component against a number of aliments.


Plants ◽  
2019 ◽  
Vol 8 (8) ◽  
pp. 265 ◽  
Author(s):  
Immacolata Faraone ◽  
Dilip K. Rai ◽  
Daniela Russo ◽  
Lucia Chiummiento ◽  
Eloy Fernandez ◽  
...  

Oxidative stress is involved in different diseases, such as diabetes and neurodegenerative diseases. The genus Azorella includes about 70 species of flowering plant species; most of them are commonly used as food and in particular as a tea infusion in the Andean region of South America in folk medicine to treat various chronic diseases. Azorella glabra Wedd. aerial parts were firstly analyzed for their in vitro antioxidant activity using different complementary assays. In particular, radical scavenging activity was tested against biological neutral radical DPPH; ferric reducing power and lipid peroxidation inhibitory capacity (FRAP and Beta-Carotene Bleaching tests) were also determined. The Relative Antioxidant Capacity Index (RACI) was used to compare data obtained by different assays. Then, the inhibitory ability of samples was investigated against α-amylase and α-glucosidase enzymes involved in diabetes and against acetylcholinesterase and butyrylcholinesterase enzymes considered as strategy for the treatment of Parkinson’s or Alzheimer’s diseases. Moreover, the phytochemical profile of the sample showing the highest RACI (1.35) and interesting enzymatic activities (IC50 of 163.54 ± 9.72 and 215.29 ± 17.10 μg/mL in α-glucosidase and acetylcholinesterase inhibition, respectively) was subjected to characterization and quantification of its phenolic composition using LC-MS/MS analysis. In fact, the ethyl acetate fraction derived from ethanol extract by liquid/liquid extraction showed 29 compounds, most of them are cinnamic acid derivatives, flavonoid derivatives, and a terpene. To the best of our knowledge, this is the first report about the evaluation of significant biological activities and phytochemical profile of A. glabra, an important source of health-promoting phytochemicals.


Metabolites ◽  
2021 ◽  
Vol 11 (10) ◽  
pp. 676
Author(s):  
Swati Chaturvedi ◽  
Promila Gupta

Fat/carbohydrate-rich diet consumption or elevated secretion of pancreatic lipase (PL) in pancreatic injury results in increased fat digestion and storage. Several metabolites in plant-based diets can help achieve the requirements of nutrition and fitness together. Presently, nutritional metabolites from Amaranthus tricolor, A. viridis, and Achyranthes aspera were assessed and predicted for daily intake. The volatile-metabolite profiling of their extracts using GC-MS revealed various antioxidant and bioactive components. The implication of these specialized components and antioxidant-rich extracts (EC50 free radical scavenging: 34.1 ± 1.5 to 166.3 ± 14.2 µg/mL; FRAP values: 12.1 ± 1.0 to 34.0 ± 2.0 µg Trolox Equivalent/mg) in lipolysis regulation by means of interaction with PL was checked by in-silico docking (Betahistine and vitamins: ΔGbind −2.3 to −4.4 kcal/mol) and in-vitro fluorescence quenching. Out of the various compounds and extracts tested, Betahistine, ATRA and AVLA showed better quenching the PL fluorescence. The identification of potential extracts as source of functional components contributing to nutrition and fat regulation can be improved through such study.


2020 ◽  
Vol 9 (1) ◽  
pp. 1-6
Author(s):  
Earnest Oghenesuvwe Erhirhie ◽  
Emmanuel Emeka Ilodigwe ◽  
Daniel Lotanna Ajaghaku ◽  
Blessing Ogechukwu Umeokoli ◽  
Peter Maduabuchi Eze ◽  
...  

Dryopteris filix mas (D filix-mas) is wildly used in ethnomedicine for the management of rheumatoid arthritis, wounds and other diseases. We investigated the anti-oxidant activities of its leaf extract, and chromatographic fractions. The ethanol leaf extract was partitioned into four fractions; n-hexane, ethyl acetate, n-butanol and water. Ferric reducing anti-oxidant power (FRAP), 1, 1-diphenyl-2-picrylhydrazil (DPPH) and nitric oxide (NO) scavenging in vitro assays were carried out on the extract and fractions at 6.25, 12.5, 25, 50, 100, 200, 400 and 800 µg/mL. The most active fraction (ethyl acetate fraction) was further purified using chromatographic techniques to isolate its major compound whose structure was elucidated using ID nuclear magnetic resonance (NMR) and mass spectrometry. The ethyl acetate fraction produced the highest free radical scavenging activity among the other fractions. The fraction (VLC-E7) from which the bioactive compound, quercetin-3-O-αL-rhamnopyranoside, was isolated had the best FRAP and DPPH scavenging activities with EC50 and IC50 values of 88.81 ± 3.41 and 26.87 ± 0.24 respectively more than the ethyl acetate fraction. This study revealed that the polyphenol flavonoid, quercetin-3-O-αL-rhamnopyranoside could be responsible for antioxidant activity of ethno-medicinal property of D filix-mas leaf.


2020 ◽  
Vol 11 (SPL4) ◽  
pp. 1636-1640
Author(s):  
Manish Deshmukh ◽  
Ashish Budhrani ◽  
Upendra Gandagule ◽  
Sanjay Nagdev ◽  
Mayur Bhurat ◽  
...  

Ventilago maderspatana Gaertn. is a plant having enormous biomedical potential. It is a plant in the Indian system of medicine having a plethora of properties and applications and The root barks powder of Ventilago maderspatana Gaertn.  have many properties and applications like it are used as a stomachic, tonic, carminative, stimulant. It is also useful in the treatment of weakness and fever. For further investigations of activities like anti-oxidant activity, In-vitro  anti-oxidant studies were done on root bark extracts of Ventilago maderspatana Gaertn. (Family Rhamnaceae) by using standard methods like Lipid peroxidation Assay, Estimation of total anti-oxidant capacity (TAC), Hydroxyl radical scavenging activity, Nitric oxide inhibition radical activity by p-Nitroso dimethyl aniline method, and ABTS Radical scavenging method. The root barks of plant Ventilago maderspatana Gaertn. Were subjected to cold maceration process in 3-liter Round bottom flask using ethanol and distilled water and nature and yield was noted and stored at 40C in the refrigerator until further use and both the extracts were labelled as Ventilago maderspatana Gaertn. Root Bark aqueous (VMRBA) and Ventilago maderspatana Gaertn. Root Bark Ethanolic (VMRBE) for convenient identification. Ethanolic extract of Root Bark showed the more potent anti-oxidant activity than aqueous Root Bark extract of Ventilago maderspatana Gaertn.


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