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  1. Fulltext Isolation of Antidiabetic Withanolides from Withania coagulans Dunal and Their In Vitro and In Silico Validation
    Maher S, Choudhary MI, Saleem F, Rasheed S, Waheed I, Halim SA, et al.
    Biology (Basel), 2020 Jul 30;9(8).
    PMID: 32751610 DOI: 10.3390/biology9080197
    Withania coagulans (W. coagulans) is well-known in herbal medicinal systems for its high biological potential. Different parts of the plant are used against insomnia, liver complications, asthma, and biliousness, as well as it is reported to be sedative, emetic, diuretic, antidiabetic antimicrobial, anti-inflammatory, antitumor, hepatoprotective, antihyperglycemic, cardiovascular, immuno-suppressive and central nervous system depressant. Withanolides present in W. coagulans have attracted an immense interest in the scientific field due to their diverse therapeutic applications. The current study deals with chemical and biological evaluation of chloroform, and n-butanol fractions of W. coagulans. The activity-guided fractionation of both extracts via multiple chromatographic steps and structure elucidation of pure isolates using spectroscopies (NMR, mass spectrometry, FTIR and UV-Vis) led to the identification of a new withanolide glycoside, withacogulanoside-B (1) from n-butanol extract and five known withanolides from chloroform extract [withanolid J (2), coagulin E (3), withaperuvin C (4), 27-hydroxywithanolide I (5), and ajugin E (6)]. Among the tested compounds, compound 5 was the most potent α-glucosidase inhibitor with IC50 = 66.7 ± 3.6 µM, followed by compound 4 (IC50: 407 ± 4.5 µM) and compound 2 (IC50: 683 ± 0.94 µM), while no antiglycation activity was observed with the six isolated compounds. Molecular docking was used to predict the binding potential and binding site interactions of these compounds as α-glucosidase inhibitors. Consequently, this study provides basis to discover specific antidiabetic compounds from W. coagulans.
  2. New isolate from Salvinia molesta with antioxidant and urease inhibitory activity
    Naheed N, Maher S, Saleem F, Khan A, Wadood A, Rasheed S, et al.
    Drug Dev Res, 2021 12;82(8):1169-1181.
    PMID: 33983647 DOI: 10.1002/ddr.21831
    Urease plays a significant role in the pathogenesis of urolithiasis pyelonephritis, urinary catheter encrustation, hepatic coma, hepatic encephalopathy, and peptic acid duodenal ulcers. Salvinia molesta was explored to identify new bioactive compounds with particular emphasis on urease inhibitors. The aqueous methanol extract was fractionated using solvents of increasing polarity. A series of column chromatography and later HPLC were performed on butanol extract. The structures of the resulting pure compounds were resolved using NMR (1D and 2D), infrared, and mass spectroscopy. The novel isolate was evaluated for antioxidant activity (using DPPH, superoxide anion radical scavenging, oxidative burst, and Fe+2 chelation assays), anti-glycation behavior, anticancer activity, carbonic anhydrase inhibition, phosphodiesterase inhibition, and urease inhibition. One new glucopyranose derivative 6'-O-(3,4-dihydroxybenzoyl)-4'-O-(4-hydroxybenzoyl)-α/β-D-glucopyranoside (1) and four known glycosides were identified. Glycoside 1 demonstrated promising antioxidant potential with IC50 values of 48.2 ± 0.3, 60.3 ± 0.6, and 42.1 ± 1.8 μM against DPPH, superoxide radical, and oxidative burst, respectively. Its IC50 in the Jack bean urease inhibition assay was 99.1 ± 0.8 μM. The mechanism-based kinetic studies presented that compound 1 is a mixed-type inhibitor of urease with a Ki value of 91.8 ± 0.1 μM. Finally, molecular dynamic simulations exploring the binding mode of compound 1 with urease provided quantitative agreement between estimated binding free energies and the experimental results. The studies corroborate the use of compound 1 as a lead for QSAR studies as an antioxidant and urease inhibitor. Moreover, it needs to be further evaluated through the animal model, that is, in vivo or tissue culture-based ex-vivo studies, to establish their therapeutic potential against oxidative stress phosphodiesterase-II and urease-induced pathologies.
  3. cis-Clerodane-type furanoditerpenoids from Tinospora crispa
    Choudhary MI, Ismail M, Shaari K, Abbaskhan A, Sattar SA, Lajis NH, et al.
    J Nat Prod, 2010 Apr 23;73(4):541-7.
    PMID: 20356064 DOI: 10.1021/np900551u
    Phytochemical and cytotoxicity investigations on organic solvent extracts of the aerial parts of Tinospora crispa have led to the isolation of 15 cis-clerodane-type furanoditerpenoids. Of these, nine compounds (1-9) were found to be new. Spectroscopic assignments of a previously reported compound, borapetoside A (13), were revised on the basis of HMQC and HMBC correlations. No discernible activity was observed when compounds 10-13 were subjected to evaluation in cytotoxicity assays against human prostate cancer (PC-3) and the normal mouse fibroblast (3T3) cell lines.
  4. Fulltext In vitro antiplasmodial and antioxidant activities of bisbenzylisoquinoline alkaloids from Alseodaphne corneri Kosterm
    Zahari A, Ablat A, Sivasothy Y, Mohamad J, Choudhary MI, Awang K
    Asian Pac J Trop Med, 2016 Apr;9(4):328-332.
    PMID: 27086149 DOI: 10.1016/j.apjtm.2016.03.008
    OBJECTIVE: To study antiplasmodial and antioxidant activities of the isolation of alkaloids from the active dichloromethane extract of Alseodaphne corneri.

    METHODS: Phytochemical studies of the crude extract led to the isolation of six alkaloids using recycle high performance liquid chromatography and preparative thin layer chromatography. The antiplasmodial activity of the isolated compounds was evaluated using the histidine-rich protein II assay. The isolated alkaloids were also tested for their antioxidant activity using three different assays; DPPH, ferric reducing ability of plasma and metal chelating assays.

    RESULTS: Malaria infection caused the formation of free radicals which subsequently led to oxidative stress and apoptosis. The antioxidant properties of the alkaloids under investigation revealed that in addition to the antiplasmodial activity, the alkaloids could also prevent oxidative stress. (+)-laurotetanine and (+)-norstephasubine exhibited strong antiplasmodial activities with IC50 values of 0.189 and 0.116 μM, respectively.

    CONCLUSIONS: Interestingly, the two most potent compounds that exhibit antiplasmodial activity also exhibit good antioxidant activities. The crude dichloromethane extract and the isolated compounds exert substantial antiplasmodial and antioxidative activities which in turn suppress oxidative stress and cause less damage to the host.

  5. Synthesis of novel inhibitors of α-glucosidase based on the benzothiazole skeleton containing benzohydrazide moiety and their molecular docking studies
    Taha M, Ismail NH, Lalani S, Fatmi MQ, Atia-Tul-Wahab, Siddiqui S, et al.
    Eur J Med Chem, 2015 Mar 6;92:387-400.
    PMID: 25585009 DOI: 10.1016/j.ejmech.2015.01.009
    In an effort to design and synthesize a new class of α-glucosidase inhibitor, we synthesized benzothiazole hybrid having benzohydrazide moiety (5). Compound 5 was reacted with various substituted aryl aldehyde to generate a small library of compounds 6-35. Synthesis of compounds was confirmed by the spectral information. These compounds were screened for their α-glucosidase activity. They showed a varying degree of α-glucosidase inhibition with IC50 values ranging between 5.31 and 53.34 μM. Compounds 6, 7, 9-16, 19, 21-30, 32-35 showed superior activity as compared to standard acarbose (IC50 = 906 ± 6.3 μM). This has identified a new class of α-glucosidase inhibitors. The predicted physico-chemical properties indicated the drug appropriateness for most of these compounds, as they obey Lipinski's rule of five (RO5). A hybrid B3LYP density functional theory (DFT) was employed for energy, minimization of 3D structures for all synthetic compounds using 6-311 + G(d,p) basis sets followed by molecular docking to explore their interactions with human intestinal C- and N-terminal domains of α-glucosidase. All compounds bind to the prospective allosteric site of the C- terminal domain, and consequently, may be considered as mixed inhibitors. It was hypothesized that both the dipole moment and H-bond interactions govern the biological activation of these compounds.
  6. Fulltext Phenoxyacetohydrazide Schiff bases: β-glucuronidase inhibitors
    Jamil W, Perveen S, Shah SA, Taha M, Ismail NH, Perveen S, et al.
    Molecules, 2014 Jun 25;19(7):8788-802.
    PMID: 24968334 DOI: 10.3390/molecules19078788
    Phenoxyacetohydrazide Schiff base analogs 1-28 have been synthesized and their in vitro β-glucouoronidase inhibition potential studied. Compounds 1 (IC50=9.20±0.32 µM), 5 (IC50=9.47±0.16 µM), 7 (IC50=14.7±0.19 µM), 8 (IC50=15.4±1.56 µM), 11 (IC50=19.6±0.62 µM), 12 (IC50=30.7±1.49 µM), 15 (IC50=12.0±0.16 µM), 21 (IC50=13.7±0.40 µM) and 22 (IC50=22.0±0.14 µM) showed promising β-glucuronidase inhibition activity, better than the standard (D-saccharic acid-1,4-lactone, IC50=48.4±1.25 µM).
  7. Synthesis and structure-activity relationship of thiobarbituric acid derivatives as potent inhibitors of urease
    Khan KM, Rahim F, Khan A, Shabeer M, Hussain S, Rehman W, et al.
    Bioorg Med Chem, 2014 Aug 1;22(15):4119-23.
    PMID: 24986232 DOI: 10.1016/j.bmc.2014.05.057
    A series of thiobarbituric acid derivatives 1-27 were synthesized and evaluated for their urease inhibitory potential. Exciting results were obtained from the screening of these compounds 1-27. Compounds 5, 7, 8, 11, 16, 17, 22, 23 and 24 showed excellent urease inhibition with IC50 values 18.1 ± 0.52, 16.0 ± 0.45, 16.0 ± 0.22, 14.3 ± 0.27, 6.7 ± 0.27, 10.6 ± 0.17, 19.2 ± 0.29, 18.2 ± 0.76 and 1.61 ± 0.18 μM, respectively, much better than the standard urease inhibitor thiourea (IC₅₀=21 ± 0.11 μM). Compound 3, 4, 10, and 26 exhibited comparable activities to the standard with IC₅₀ values 21.4 ± 1.04 and 21.5 ± 0.61 μM, 22.8 ± 0.32, 25.2 ± 0.63, respectively. However the remaining compounds also showed prominent inhibitory potential The structure-activity relationship was established for these compounds. This study identified a novel class of urease inhibitors. The structures of all compounds were confirmed through spectroscopic techniques such as EI-MS and (1)H NMR.
  8. Synthesis and β-glucuronidase inhibitory activity of 2-arylquinazolin-4(3H)-ones
    Khan KM, Saad SM, Shaikh NN, Hussain S, Fakhri MI, Perveen S, et al.
    Bioorg Med Chem, 2014 Jul 1;22(13):3449-54.
    PMID: 24844756 DOI: 10.1016/j.bmc.2014.04.039
    2-Arylquinazolin-4(3H)-ones 1-25 were synthesized by reacting anthranilamide with various benzaldehydes using CuCl2·2H2O as a catalyst in ethanol under reflux. Synthetic 2-arylquinazolin-4(3H)-ones 1-25 were evaluated for their β-glucuronidase inhibitory potential. A trend of inhibition IC50 against the enzyme in the range of 0.6-198.2μM, was observed and compared with the standard d-saccharic acid 1,4-lactone (IC50=45.75±2.16μM). Compounds 13, 19, 4, 12, 14, 22, 23, 25, 15, 8, 17, 11, 21, 1, 3, 18, 9, 2, and 24 with the IC50 values within the range of 0.6-44.0μM, indicated that the compounds have superior activity than the standard. The compounds showed no cytotoxic effects against PC-3 cells. A structure-activity relationship is established.
  9. Synthesis and molecular docking studies of potent α-glucosidase inhibitors based on biscoumarin skeleton
    Khan KM, Rahim F, Wadood A, Kosar N, Taha M, Lalani S, et al.
    Eur J Med Chem, 2014 Jun 23;81:245-52.
    PMID: 24844449 DOI: 10.1016/j.ejmech.2014.05.010
    In our effort directed toward the discovery of new anti-diabetic agent for the treatment of diabetes, a library of biscoumarin derivative 1-18 was synthesized and evaluated for α-glucosidase inhibitory potential. All eighteen (18) compounds displayed assorted α-glucosidase activity with IC50 values 16.5-385.9 μM, if compared with the standard acarbose (IC50 = 906 ± 6.387 μM). In addition, molecular docking studies were carried out to explore the binding interactions of biscoumarin derivatives with the enzyme. This study has identified a new class of potent α-glucosidase inhibitors.
  10. Presence of calcium antagonist activity explains the use of Syzygium samarangense in diarrhoea
    Ghayur MN, Gilani AH, Khan A, Amor EC, Villaseñor IM, Choudhary MI
    Phytother Res, 2006 Jan;20(1):49-52.
    PMID: 16397921
    Syzygium samarangense (Family; Myrtaceae) or 'makopa', as it is commonly known, is native to Malaysia, some islands of Indonesia and to Far East in general. This study was undertaken to rationalize the use of this plant in hypermotility states of the gut. The hexane extract of S. samarangense (Ss.Hex) was found to dose-dependently (10-3000 microg/mL) relax the spontaneously contracting isolated rabbit jejunum. When tested for a possible calcium channel blocking (CCB) activity, the extract (10-1000 microg/mL) relaxed the high K+-induced contractions and also decreased the Ca++ dose-response curves in a dose-dependent manner (30-100 microg/mL), confirming the CCB activity. Four flavonoids isolated from the hexane extract were tested for a possible spasmolytic activity. All flavonoids, identified as: 2'-hydroxy-4',6'-dimethoxy-3'-methylchalcone (SS1), 2',4'-dihydroxy-6'-methoxy-3',5'-dimethylchalcone (SS2), 2',4'-dihydroxy-6'-methoxy-3'-methylchalcone (SS3) and 7-hydroxy-5-methoxy-6,8-dimethylflavanone (SS4), showed dose-dependent (10-1000 microg/mL) spasmolytic activity with SS2 being the most potent. These results indicate that the presence of compounds with spasmolytic and calcium antagonist activity may be responsible for the medicinal use of the plant in diarrhoea.
  11. Fulltext Immunosuppressive phenolic compounds from Hydnora abyssinica A. Braun
    Koko WS, Mesaik MA, Ranjitt R, Galal M, Choudhary MI
    BMC Complement Altern Med, 2015;15:400.
    PMID: 26553149 DOI: 10.1186/s12906-015-0931-x
    Hydnora abyssinica (HA) A. Braun is an endemic Sudanese medicinal plant traditionally used as anti-inflammatory and against many infectious diseases. However, it proved to be very rich in phenols and tannins, so the present study was undertaken to investigate the immunomodulatory potential of the whole plant ethanolic extract and its isolated compounds.
  12. Evaluation of 2-indolcarbohydrazones as potent α-glucosidase inhibitors, in silico studies and DFT based stereochemical predictions
    Taha M, Ismail NH, Javaid K, Imran S, Anouar el H, Wadood A, et al.
    Bioorg Chem, 2015 Dec;63:24-35.
    PMID: 26398141 DOI: 10.1016/j.bioorg.2015.09.001
    2-Indolcarbohydrazones 1-28 were synthesized and evaluated for their α-glucosidase inhibitory potential. A varying degree of inhibitory potential with IC50 values in the range of 2.3±0.11-226.4±6.8μM was observed while comparing these outcomes with the standard acarbose (IC50=906.0±6.3μM). The stereochemistry of ten (10) randomly selected compounds (1, 3, 6, 8, 12, 18, 19, 23, 25 and 28) was predicted by Density Functional Theory (DFT). The stability of E isomer was deduced by comparing the calculated and experimental vibration modes of νCO, νNC and νCH (CH in NCH-R). It was observed that except compound 18, all other compounds were deduced to have E configuration while molecular modeling studies revealed the key interactions between enzyme and synthesized compounds.
  13. Synthesis, biological evaluation, and docking studies of novel thiourea derivatives of bisindolylmethane as carbonic anhydrase II inhibitor
    Imran S, Taha M, Ismail NH, Fayyaz S, Khan KM, Choudhary MI
    Bioorg Chem, 2015 Oct;62:83-93.
    PMID: 26275866 DOI: 10.1016/j.bioorg.2015.08.001
    This article describes discovery of 29 novel bisindolylmethanes consisting of thiourea moiety, which had been synthesized through three steps. These novel bisindolylmethane derivatives evaluated for their potential inhibitory activity against carbonic anhydrase (CA) II. The results for in vitro assay of carbonic anhydrase II inhibition activity showed that some of the compounds are capable of suppressing the activity of carbonic anhydrase II. Bisindoles having halogen at fifth position showed better inhibitory activity as compared to unsubstituted bisindoles. Derivatives showing inhibition activity docked to further, understand the binding behavior of these compounds with carbonic anhydrase II. Docking studies for the active compound 3j showed that nitro substituent at para position fits into the core of the active site. The nitro substituent of compound 3j is capable of interacting with Zn ion. This interaction believed to be the main factor causing inhibition activity to take place.
  14. Benzimidazole derivatives protect against cytokine-induced apoptosis in pancreatic β-Cells
    Zawawi NK, Rajput SA, Taha M, Ahmat N, Ismail NH, Abdullah N, et al.
    Bioorg Med Chem Lett, 2015 Oct 15;25(20):4672-6.
    PMID: 26330080 DOI: 10.1016/j.bmcl.2015.08.022
    Apoptotic cell death is the cause of the loss of insulin-producing β-cells in all forms of diabetes mellitus. The identification of small molecules capable of protecting cytokine-induced apoptosis could form the basis of useful therapeutic interventions. Here in, we present the discovery and synthesis of new benzimidazole derivatives, capable of rescuing pancreatic β-cells from cytokine-induced apoptosis. Three hydrazone derivatives of benzimidazole significantly increased the cellular ATP levels, reduced caspase-3 activity, reduced nitrite production and increased glucose-stimulated insulin secretion in the presence of proinflammatory cytokines. These findings suggest that these compounds may protect β-cells from the harmful effects of cytokines and may serve as candidates for therapeutic intervention for diabetes.
  15. Synthesis of 2-methoxybenzoylhydrazone and evaluation of their antileishmanial activity
    Taha M, Baharudin MS, Ismail NH, Khan KM, Jaafar FM, Samreen, et al.
    Bioorg Med Chem Lett, 2013 Jun 1;23(11):3463-6.
    PMID: 23608761 DOI: 10.1016/j.bmcl.2013.03.051
    Compounds 1-25 showed varying degree of antileishmanial activities with IC50 values ranging between 1.95 and 88.56 μM. Compounds 2, 10, and 11 (IC50=3.29±0.07 μM, 1.95±0.04 μM, and 2.49±0.03 μM, respectively) were found to be more active than standard pentamidine (IC50=5.09±0.04 μM). Compounds 7 (IC50=7.64±0.1 μM), 8 (IC50=13.17±0.46 μM), 18 (IC50=13.15±0.02 μM), and 24 (IC50=15.65±0.41 μM) exhibited good activities. Compounds 1, 3, 4, 5, 9, 12, 15, 18, and 19 were found to be moderately active. Compounds 13, 14, 16, 17, 20-25 showed weak activities with IC50 values ranging between 57 and 88 μM.
  16. Evaluation of bisindole as potent β-glucuronidase inhibitors: synthesis and in silico based studies
    Khan KM, Rahim F, Wadood A, Taha M, Khan M, Naureen S, et al.
    Bioorg Med Chem Lett, 2014 Apr 1;24(7):1825-9.
    PMID: 24602903 DOI: 10.1016/j.bmcl.2014.02.015
    Bisindole analogs 1-17 were synthesized and evaluated for their in vitro β-glucuronidase inhibitory potential. Out of seventeen compounds, the analog 1 (IC50=1.62±0.04 μM), 6 (IC50=1.86±0.05 μM), 10 (IC50=2.80±0.29 μM), 9 (IC50=3.10±0.28 μM), 14 (IC50=4.30±0.08 μM), 2 (IC50=18.40±0.09 μM), 19 (IC50=19.90±1.05 μM), 4 (IC50=20.90±0.62 μM), 7 (IC50=21.50±0.77 μM), and 3 (IC50=22.30±0.02 μM) showed superior β-glucuronidase inhibitory activity than the standard (d-saccharic acid 1,4-lactone, IC50=48.40±1.25 μM). In addition, molecular docking studies were performed to investigate the binding interactions of bisindole derivatives with the enzyme. This study has identified a new class of potent β-glucouronidase inhibitors.
  17. Synthesis of novel bisindolylmethanes: New carbonic anhydrase II inhibitors, docking, and 3D pharmacophore studies
    Imran S, Taha M, Ismail NH, Fayyaz S, Khan KM, Choudhary MI
    Bioorg Chem, 2016 10;68:90-104.
    PMID: 27474804 DOI: 10.1016/j.bioorg.2016.07.011
    In this study, 45 bisindolylmethanes having sulfonamide moiety had been synthesized through 3 steps. In vitro assay for inhibition of carbonic anhydrase showed that some of the compounds having sulfonamide moiety are capable of inhibiting carbonic anhydrase II. Bisindoles having halogens at fifth position showed better inhibitory activity as compared to unsubstituted bisindoles. The results obtained from in vitro inhibitory activity were subjected through 3D QSAR and docking studies to identify important features contributing to the activity and further improve the structure. Pharmacophore studies suggest that bisindolylmethane moiety is contributing significantly towards the inhibition activity. Docking studies showed that compounds having nitro substituent (5g and 5i) were found to be able interact with Zn(2+) ion, Thr199, His94, His96, and His119, which interferes with the ZnOHThr199Glu106 hydrogen bond network. Bulky nitro substituent at ortho position for compound 5g prevents the compound from interacting with other residues like Thr199 and Thr200. Methyl substituent at ortho position for Compound 5i induces less steric hindrance effect, thus allowing second oxygen atom of sulfonamide to interact with Thr199 (2.51Å). Hydrogen bonding between NH on indole ring with Glu69 might have increased stability of ligand-receptor complex.
  18. Carbohydrazones as new class of carbonic anhydrase inhibitors: Synthesis, kinetics, and ligand docking studies
    Iqbal S, Saleem M, Azim MK, Taha M, Salar U, Khan KM, et al.
    Bioorg Chem, 2017 06;72:89-101.
    PMID: 28390994 DOI: 10.1016/j.bioorg.2017.03.014
    Discovery and development of carbonic anhydrase inhibitors is crucial for their clinical use as antiepileptic, diurectic and antiglaucoma agents. Keeping this in mind, we have synthesized carbohydrazones 1-27 and evaluated them for their in vitro carbonic anhydrase inhibitory potential. Out of twenty-seven compounds, compounds 1 (IC50=1.33±0.01µM), 2 (IC50=1.85±0.24µM), 3 (IC50=1.37±0.06µM), and 9 (IC50=1.46±0.12µM) have showed carbonic anhydrase inhibition better than the standard drug zonisamide (IC50=1.86±0.03µM). Moreover, compounds 4 (IC50=2.32±0.04µM), 5 (IC50=3.96±0.35µM), 7 (IC50=2.33±0.02µM), and 8 (IC50=2.67±0.01µM) showed good inhibitory activity. Cheminformatic analysis has shown that compounds 1 and 2 possess lead-like properties. In addition, kinetic and molecular docking studies were also performed to investigate the binding interaction between carbohydrazones and carbonic anhydrase enzyme. This study has identified a novel and potent class of carbonic anhydrase inhibitors with the potential to be investigated further.
  19. Fulltext Synthesis of 4-methoxybenzoylhydrazones and evaluation of their antiglycation activity
    Taha M, Naz H, Rasheed S, Ismail NH, Rahman AA, Yousuf S, et al.
    Molecules, 2014 Jan 21;19(1):1286-301.
    PMID: 24451249 DOI: 10.3390/molecules19011286
    A series of 4-methoxybenzoylhydrazones 1-30 was synthesized and the structures of the synthetic derivatives elucidated by spectroscopic methods. The compounds showed a varying degree of antiglycation activity, with IC50 values ranging between 216.52 and 748.71 µM, when compared to a rutin standard (IC50=294.46±1.50 µM). Compounds 1 (IC50=216.52±4.2 µM), 3 (IC50=289.58±2.64 µM), 6 (IC50=227.75±0.53 µM), 7 (IC50=242.53±6.1) and 11 (IC50=287.79±1.59) all showed more activity that the standard, and these compounds have the potential to serve as possible leads for drugs to inhibit protein glycation in diabetic patients. A preliminary SAR study was performed.
  20. Fulltext Suppressive Effects ofClerodendrum volubileP Beauv. [Labiatae] Methanolic Extract and Its Fractions on Type 2 Diabetes and Its Complications
    Erukainure OL, Hafizur RM, Kabir N, Choudhary MI, Atolani O, Banerjee P, et al.
    Front Pharmacol, 2018;9:8.
    PMID: 29449808 DOI: 10.3389/fphar.2018.00008
    Type 2 diabetes is the most prominent of all diabetes types, contributing to global morbidity and mortality. Availability and cost of treatment with little or no side effect especially in developing countries, remains a huge burden. This has led to the search of affordable alternative therapies especially from medicinal plants. In this study, the antidiabetic effect of the methanolic extract, dichloromethane (DCM), butanol (BuOH) and aqueous fractions ofClerodendrum volubileleaves were investigated in type 2 diabetic rats for their effect on glucose homeostasis, serum insulin level and hepatic biomarkers, lipid profile, pancreatic redox balance and Ca2+levels, and β-cell distribution and function. The DCM was further fractionated to isolate the active compounds, biochanin and 5,7,4'-trimethoxykaempferol. They were investigated for their toxicity and ADMET properties, α-glucosidase and angiotensin I converting enzyme (ACE) inhibitory activitiesin silico. There were significant (p< 0.05) decrease in blood glucose, cholesterol, LDL-C, vLDL-C, triglyceride, AST and ALT levels in all treated groups, with DCM fraction showing the best activity. All treated rats showed significantly (p< 0.05) improved anti-oxidative activities. Treatment with the DCM fraction led to significant (p< 0.05) increased serum insulin and pancreatic Ca2+levels, as well as improved β-cell distribution and function. DCM fraction also showed improved glucose tolerance. DCM fraction dose-dependently inhibited ACE activity. The toxicity class of the isolated compounds was predicted to be 5. They were also predicted to be potent inhibitors of cytochrome P (CYPs) 1A2, 2D6 and 3A4. They docked well with α-glucosidase and ACE. These results indicate the therapeutic potential of the plant against type 2 diabetes, with the DCM fraction being the most potent which may be attributed to the isolated flavones. It further suggests antihypertensive potentials of the DCM fraction. However, inhibition of CYPs by the flavones may suggest caution in usage with other prescribed drugs metabolized by these enzymes.
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