In vitro and computational studies of the antioxidant and anti-diabetic properties of Bridelia ferruginea.

The leaves, stem and root bark of Bridelia ferruginea were sequentially extracted with solvents of increasing polarity to yield the hexane, ethyl acetate, ethanol and aqueous extracts. In vitro analysis revealed the ability of the extracts to scavenge 1,1-diphenyl-2-picryl-hydrazyl (DPPH), nitric oxide (NO) and hydroxyl radical. They also inhibited the activities of α-glucosidase, α-amylase and lipase enzymes. Gas chromatography-mass spectroscopic (GC-MS) analysis of the extracts revealed the presence of sterols, aromatics, aliphatic acids and esters. The identified compounds were molecularly docked with α-glucosidase, α-amylase and lipase enzymes. All compounds showed good binding affinities with the enzymes studied. The strongest binding affinities were observed for ß-amyrin, 4-phenylbenzophenone and lupenone for α-glucosidase, α-amylase and lipase enzymes, respectively. The data suggest antioxidant and antidiabetic potential of the different parts of B. ferruginea, with the leaves having the highest potential. These properties can be explored for development of novel anti-diabetic drugs.Communicated by Ramaswamy H. Sarma.

Studies on the mitochondrial, immunological and inflammatory effects of solvent fractions of Diospyros mespiliformis Hochst in Plasmodium berghei-infected mice.

The use of medicinal plants in the treatment of malaria is gaining global attention due to their efficacy and cost effectiveness. This study evaluated the bioactivity-guided antiplasmodial efficacy and immunomodulatory effects of solvent fractions of Diospyros mespiliformis in mice infected with a susceptible strain of Plasmodium berghei (NK 65). The crude methanol extract of the stem of D. mespiliformis (DM) was partitioned between n-hexane, dichloromethane, ethyl acetate and methanol. Male Swiss mice (20 ± 2 g) infected with P. berghei were grouped and treated with vehicle (10 mL/kg, control), Artemether lumefantrine (10 mg/kg), 100, 200 and 400 mg/kg of n-hexane, dichloromethane, ethyl acetate and methanol fractions of D. mespiliformis for seven days. Blood was obtained for heme and hemozoin contents while serum was obtained for inflammatory cytokines and immunoglobulins G and M assessments. Liver mitochondria were isolated for mitochondrial permeability transition (mPT), mitochondrial F1F0 ATPase (mATPase) and lipid peroxidation (mLPO) assays. The GC-MS was used to identify the compounds present in the most potent fraction. The dichloromethane fraction had the highest parasite clearance and improved hematological indices relative to the drug control. The heme values increased, while the hemozoin content significantly (P < 0.05) decreased compared with the drug control. The highest dose of HF and MF opened the mPT pore while the reversal effects of DF on mPT, mATPase and mLPO were dose-dependent. The levels of IgG, IgM and TNFα in the DF group were significantly higher than the drug control, while the IL-1ß and IL-6 values did not vary linearly with the dose. Lupeol and Stigmastan-3,5-diene were the most abundant phytochemicals in the DF. The outcome of this study showed that the DF has immunomodulatory effects in infected mice, reduced proliferation of the malaria parasite and thus protect liver cells.

Sesquiterpene lactones from Polydora serratuloides and their quorum sensing inhibitory activity.

The leaves of Polydora serratuloides, with the synonym Vernonia perrottetii are widely used as purgative agents for gastrointestinal problems, and other members of Vernonieae have been used in African traditional medicine for decades. A new sesquiterpene lactone of the keto-hirsutinolide type, 13-acetoxy-1(4ß),5(6)ß-diepoxy-8α-(senecioyloxy)-3-oxo-1,7(11)-germacradiene-12,6-olide 1, was isolated from the hexane extract of its leaves, in addition to the known 13-acetoxy-1,4ß-epoxy-8α-(senecioyloxy)-3-oxo-1,5,7(11)-germacratriene-12,6-olide 2. Three common flavonoids (apigenin 3, luteolin 4 and velutin 5) were also isolated. The antibacterial and quorum sensing inhibitory activities of compounds 1 and 2 and crudes extracts showed limited activity on Bacillus subtilis and Staphylococcus aureus, with no activity on Gram negative bacteria. However, quorum sensing (QSI) experiments indicated that 1 and 2, and the four crude extracts had interesting inhibitory activity on the biosensor organism, Chromobacterium violaceum ATCC 12472 in the range of 0.33-5.25 mg mL-1, with compound 1 being the most effective at 0.33 mg mL-1.

The effects of Ficus carica on the activity of enzymes related to metabolic syndrome.

The present study aimed to investigate the effects of the various parts of Ficus carica L. (figs) on antioxidant, antidiabetic, and antiobesogenic effects in vitro. Fruit, leaves, and stembark of the F. carica plant were sequentially extracted using organic and inorganic solvents and their total polyphenol and flavonoid contents were estimated. The effects of the extracts on antioxidative, antidiabetic (inhibition of α-amylase and α-glucosidase enzymes), and antiobesogenic (antilipase) activities were measured using several experimental models. The fruit ethanolic extract contained a high quantity of polyphenols and flavonoids (104.67±5.51 µg/mL and 81.67±4.00 µg/mL) compared with all other extracts. The activity of the ethanolic extract of F. carica fruit was significantly (p<0.05) higher than all other extracts and parts of the plant in terms of antioxidative, antidiabetic, and antiobesogenic effects. The IC50 values of the fruit ethanolic extract in terms of antioxidative (134.44±18.43 µg/mL), and inhibition of α-glucosidase (255.57±36.46 µg/mL), α-amylase (315.89±3.83 µg/mL), and pancreatic lipase (230.475±9.65 µg/mL) activity indicate that the activity of fruit ethanolic extract is better than all other extracts of the plant. The gas chromatography-mass spectroscopy analysis of the fruit ethanolic extract showed the presence of a number of bioactive compounds such as butyl butyrate, 5-hydroxymethyl furfural, 1-butoxy-1-isobutoxy butane, malic acid, tetradecanoic acid, phytol acetate, trans phytol, n-hexadecanoic acid, 9Z,12Z-octadecadienoic acid, stearic acid, sitosterol, 3,5-dihydroxy-6-methyl-2,3-dihydro-4H-pyran-4-one, and 2,4,5-trimethyl-2,4-dihydro-3H-pyrazol-3-one. The results of this study suggest that the ethanolic extract of the fruit of F. carica may have potential antidiabetic and antiobesogenic agents.

Inhibition of key enzymes linked to type 2 diabetes by compounds isolated from Aframomum melegueta fruit.

CONTEXT: The use of Aframomum melegueta K. Schum. (Zingiberaceae) fruit for treatment of diabetes has recently been established in Nigeria. However, compounds responsible for the antidiabetic action have not been identified. OBJECTIVE: The present study carried out the bioassay-guided isolation of possible bioactive compounds responsible for the antidiabetic action of A. melegueta fruit. MATERIALS AND METHODS: The A. melegueta fruit was sequentially extracted using ethyl acetate (EtOAc), ethanol and water, and the most active extract (EtOAc) was subjected to column chromatography on a silica gel column using solvent gradient systems of hexane (HEX):EtOAc and EtOAc:MeOH and the isolation of compounds was guided by α-glycosidase and α-amylase inhibitory activities at various concentrations (30-240 µg/mL). RESULTS: According to the results, 3 arylalkanes, 6-paradol (1), 6-shogaol (2) and 6-gingerol (3) and a pentacyclic triterpene, oleanolic acid (4) were isolated from A. melegueta fruit. All the compounds exhibited inhibitory effects against α-amylase and α-glucosidase. 6-Gingerol (3) and oleanolic acid (4) showed higher inhibitory activity against α-amylase (IC50: 6-gingerol: 81.78 ± 7.79 µM; oleanolic acid: 91.72 ± 1.63 µM) and α-glucosidase (IC50: 6-gingerol: 21.55 ± 0.45 µM; oleanolic acid: 17.35 ± 0.88 µM) compared to the standard drug, acarbose and other isolated compounds. The kinetics of the enzyme action of the compounds showed a noncompetitive mode of inhibition. CONCLUSION: The data of this study suggest that the 6-gingerol (3) and oleanolic acid (4) showed higher α-amylase and α-glucosidase inhibitory action and therefore could be responsible for the antidiabetic activity of A. melegueta fruit.

PHYTOCHEMISTRY, ANTIOXIDATIVE ACTIVITY AND INHIBITION OF KEY ENZYMES LINKED TO TYPE 2 DIABETES BY VARIOUS PARTS OF AFRAMOMUM MELEGUETA IN VITRO.

This study investigated and compared the antioxidative, antidiabetic effects and possible active compounds present in various solvent extracts of fruit, leaf and stem of Aframomum melegueta (Rosc.) K. Schum. Samples were sequentially extracted using solvents of increasing polarity. They were investigated for 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical scavenging activity, ferric reducing power, inhibition of hemoglobin glycosylation, α-amylase and α-glucosidase activities as markers of in vitro antidiabetic effects at various doses (30-240 µg/mL). Possible compounds were analyzed using gas chromatography-mass spectrometry (GC-MS) analysis. From the results, fruit ethanolic (EtOH) extract showed higher total polyphenol (12.52 ± 0.13 mg/g GAE) and flavonoid (4.92 ± 0.12 mg/g QE) contents compared to other extracts. Similarly, for all the in vitro models used in this study, fruit EtOH extract exhibited lower IC50 values compared to other extracts, comparable to standards used in this study (DPPH 0.04 ± 0.01 mg/mL; ascorbic acid: 0.03 ± 0.02 mg/mL; gallic acid: 0.05 ± 0.01 mg/mL; hemoglobin glycosylation: 0.7 2 ± 0.03 mg/mL; gallic acid: 0.20 ± 0.01 mg/mL; α-amylase: 0.62 ± 0.01 mg/mL; acarbose: 4.91 ± 0.80 mg/mL; α-glucosidase: 0.06 ± 0.01 mg/mL; acarbose: 0.34 ± 0.02 mg/mL). Additionally, EtOH extract of the fruit demonstrated significantly (p < 0.05) higher reducing potentials of Fe3+ to Fe2+ compared to other solvent extracts. The GC-MS analysis of fruit and leaf EtOH extracts revealed the presence of some phenolics and other fatty acids derivatives as possible compounds present. Conclusively, fruit EtOH extract exhibited higher antioxidative and antidiabetic effects compared to other solvent extracts in vitro and thus require further work to fully validate these effects in vivo.

Butanol fraction of Parkia biglobosa (Jacq.) G. Don leaves enhance pancreatic ß-cell functions, stimulates insulin secretion and ameliorates other type 2 diabetes-associated complications in rats.

ETHNOPHARMACOLOGICAL RELEVANCE: Ethnopharmacological surveys have reported that Parkia biglobosa (Jacq.) G. Don (Leguminosae) is among the plants commonly used in the traditional management of diabetes mellitus in Nigeria and Togo. AIM OF THE STUDY: This study investigated the anti-diabetic activity of the butanol fraction of P. biglobosa leaves (PBBF) in a type 2 diabetes (T2D) model of rats and a possible bioactive compound in the fraction. MATERIALS AND METHODS: T2D was induced by feeding rats with a 10% fructose solution ad libitum for two weeks followed by an intraperitoneal injection of 40mg/kg body weight streptozotocin and the animals were orally treated with 150 and 300mg/kg BW of the PBBF for five days in a week. Another group of rats was non-diabetic but similarly administered with 300mg/kg BW of the PBBF. Food and fluid intakes, body weight changes and blood glucose levels were monitored during the experiment while other relevant diabetes-associated parameters were measured at the end of the experiment. RESULTS: The PBBF treatments significantly (P<0.05) decreased the blood glucose levels and improved the glucose tolerance ability compared to untreated diabetic rats. Furthermore, the treatments were found to improve pancreatic ß cell function (HOMA-ß), stimulate insulin secretions, decrease insulin resistance (HOMA-IR), restore liver glycogen, ameliorate serum dyslipidaemia and prevent hepatic and renal damages compared to untreated diabetic rats. Phytochemical analysis of the fraction led to the isolation of lupeol which inhibited α-glucosidase and α-amylase in non-competitive and uncompetitive inhibition patterns respectively. CONCLUSION: It was concluded that PBBF possessed remarkable anti-T2D activity which is mediated through modulation of ß-cell function and stimulation of insulin secretion and the lower dose (150mg/kg BW) was found optimum for anti-T2D activity compared to the high dose (300mg/kg BW) in this study.

Anti-diabetic effect of Xylopia aethiopica (Dunal) A. Rich. (Annonaceae) fruit acetone fraction in a type 2 diabetes model of rats.

ETHNOPHARMACOLOGICAL RELEVANCE: In traditional medicine from West Africa, the fruit decoction of Xylopia aethiopica (Dunal) A. Rich. is widely used for the treatment of diabetes mellitus (DM) either alone or in combination with other plants. The present study is designed to investigate the anti-diabetic effects of X. aethiopica acetone fraction (XAAF) from fruit ethanolic extract in a type 2 diabetes (T2D) model of rats. MATERIALS AND METHODS: T2D was induced in rats by feeding a 10% fructose solution ad libitum for 2 weeks followed by a single intraperitoneal injection of streptozotocin (40 mg/kg body weight) and the animals were orally treated with 150 or 300 mg/kg body weight (bw) of the XAAF once daily for four weeks. RESULTS: After 4 weeks study period, diabetic untreated animals (DBC) exhibited significantly higher serum glucose, serum fructosamine, LDH, CK-MB, serum lipids, liver glycogen, insulin resistance (HOMA-IR), AI, CRI and lower serum insulin, ß-cell function (HOMA-ß) and glucose tolerance ability compared to the normal animals. Histopathological examination of their pancreas revealed corresponding pathological changes in the islets and ß-cells. These alterations were reverted to near-normal after the treatment of XAAF at 150 (DXAL) and 300 (DXAH) mg/kg bw with the effects being more pronounced in the DXAH group compared to the DXAL group. Moreover, the effects in the animals of DXAH group were comparable to the diabetic metformin (DMF) treated animals. In addition, no significant alterations were observed in non-diabetic animals treated with 300 mg/kg bw of XAAF (NXAH). CONCLUSION: The results of our study suggest that XAAF treatment showed excellent anti-diabetic effects in a T2D model of rats.

ANTI-OXIDATIVE, (α-GLUCOSIDASE AND α-AMYLASE INHIBITORY ACTIVITY OF VITEX DONIANA: POSSIBLE EXPLOITATION IN THE MANAGEMENT OF TYPE 2 DIABETES.

Vitex doniana is an important African medicinal plant traditionally used for the treatment of many diseases including type 2 diabetes (T2D). In this study, ethyl acetate, ethanol and aqueous extracts of the stem bark, root and leaf of V. doniana were analyzed for in vitro anti-oxidative activity and the results indicated that the ethanolic extract of the leaves had the best anti-oxidative activity. Subsequently, the ethanolic extract of the leaves was partitioned between hexane, dichloromethane, ethyl acetate and water. The aqueous fraction had a significantly ( p < 0.05) higher phenolics content and also showed the best anti-oxidative activity within the fractions. Furthermore, the aqueous fraction demonstrated significantly (p < 0.05) more potent inhibitory activities against α-glucosidase and α-amylase than other fractions. Steady state kinetics analysis revealed that the aqueous fraction inhibited both (α-glucosidase and (α-amylase activities in a non-competitive manner with inhibition binding constant (Ki) values of 5.93 and 167.44 µg/mL, respectively. Analysis of the aqueous fraction by GC-MS showed the presence of resorcinol, 4-hydroxybenzoic acid, 3,4,5-trimethoxyphenol and 2,4'-dihydroxychalcone identified by their mass fragmentation patterns and comparison to standard spectra. The results obtained in this study showed that V doniana leaves have a good in vitro anti-T2D potential possibly elicited through phenolics.

Ethyl acetate fraction of Aframomum melegueta fruit ameliorates pancreatic ß-cell dysfunction and major diabetes-related parameters in a type 2 diabetes model of rats.

ETHNOPHARMACOLOGICAL RELEVANCE: In West Africa, various preparations of the fruit, seed and leaf of Aframomum melegueta K. Schum. are reputably used for the management of diabetes mellitus (DM) and other metabolic disorders. The present study evaluated the anti-diabetic effects of A. melegueta ethyl acetate fraction (AMEF) from fruit ethanolic extract in a type 2 diabetes (T2D) model of rats. MATERIALS AND METHODS: T2D was induced in rats by feeding a 10% fructose solution ad libitum for two weeks followed by a single intraperitoneal injection of streptozotocin (40 mg/kg body weight) and the animals were orally treated with 150 or 300 mg/kg body weight (bw) of the AMEF once daily for four weeks. RESULTS: At the end of the intervention, diabetic untreated animals showed significantly higher serum glucose, serum fructosamine, LDH, CK-MB, serum lipids, liver glycogen, insulin resistance (HOMA-IR), AI, CRI and lower serum insulin, pancreatic ß-cell function (HOMA- ß) and glucose tolerance ability compared to the normal animals. Histopathological examination of their pancreas revealed corresponding pathological changes in the islets and ß-cells. These alterations were reverted to near-normal after the treatment of AMEF at 150 and 300 mg/kg bw when, the effects were more pronounced at 300 mg/kg bw compared to the 150 mg/kg bw. CONCLUSION: The results of our study suggest that AMEF treatment at 300 mg/kg bw showed potent anti-diabetic effect in a T2D model of rats.

Antioxidative activity and inhibition of key enzymes linked to type-2 diabetes (α-glucosidase and α-amylase) by Khaya senegalensis.

This study evaluated the in vitro antioxidative activity of Khaya senegalensis extracts and inhibitory effects of some solvent fractions on α-glucosidase and α-amylase activities. The stem bark, root and leaf samples of the plant were sequentially extracted with ethyl acetate, ethanol and water and then tested for antioxidative activity. Our findings revealed that the ethanolic extract of the root had the highest antioxidative activity. Solvent-solvent fractionation of the root ethanolic extract yielded a butanol fraction that showed higher antioxidative activity than other fractions. Furthermore, the butanol fraction had significantly higher (p < 0.05) α-glucosidase and α-amylase inhibitory activities with IC50 values of 2.89 ± 0.46 and 97.51 ± 5.72 µg mL⁻¹, respectively. Enzyme kinetic studies indicated that the butanol fraction is a non-competitive inhibitor for α-glucosidase with an inhibition binding constant K(i) of 1.30 µg mL⁻¹ and a competitive inhibitor of α-amylase with a K(i) of 7.50 µg mL⁻¹. GC-MS analysis revealed that the butanol fraction contained two chromones, p-anilinophenol and 3-ethyl-5-(3-ethyl-(3H)-benzothiazol-2-ylidene)-2-(p-tolylvinylamino)-4-thiazolidinone. Data obtained in the study suggest that the butanol fraction derived from the ethanolic extract of K. senegalensis root possessed excellent antioxidative as well as α-glucosidase and a-amylase inhibitory activities while chromones and/or p-anilinophenol could be the main bioactive compounds responsible for the observed activities.

In vitro anti-oxidative activities and GC-MS analysis of various solvent extracts of Cassia singueana parts.

The present study was conducted to investigate the anti-oxidative activities of different solvent extracts of Cassia singueana parts. Our results indicate that all the extracts have reducing power (Fe3+ --> Fe2+) and DPPH radical scavenging abilities. However, the ethyl acetate extract of the stem bark has the highest total reducing power whilst the ethanol extract of the stem bark has more potent free radical scavenging activity than all the other extracts. The ethyl acetate extract of the stem bark exhibited more powerful hydroxyl radical scavenging activity than other extracts whilst the aqueous extract of the leaves displayed more potent nitric oxide inhibition activity than other extracts. The GC-MS analysis of the ethyl acetate extract of the stem bark and the ethanol extract of the root and leaves indicated that several aromatic compounds, including phenolics, fatty acids, amino acids and triterpenoids were present in these extracts. Data from this study suggest that the parts of C. singueana possessed anti-oxidative activities and can be used as a potential alternative medicine for oxidative stress related non-communicable chronic diseases. Further experimental and clinical studies in this regard are warranted.

In vitro antioxidant activities of leaf and root extracts of Albizia antunesiana harms.

The antioxidative activities of the ethanol and aqueous extracts of the leaf and root samples of Albizia antunesiana were determined across a series of four in vitro models. The results showed that all the extracts had reducing power (Fe(3+)- Fe2+), DPPH, hydroxyl and nitric oxide radical scavenging abilities. The ethanol root extract had more potent antioxidant power in all the experimental models and possesses a higher total phenol content of 216.6 +/- 6.7 mg/g. The GC-MS analysis of the aqueous and ethanol extracts of the roots and leaves indicated that several aromatic phenolic compounds, a coumarin and some common triterpenoids were present in these extracts. Data from this study suggest that the leaves and roots of Albizia antunesiana possessed antioxidative activities that varied depending on the solvents.