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Inhibitory and in silico molecular docking of Xeroderris stuhlmannii (Taub.) Mendonca & E.P. Sousa phytochemical compounds on human α-glucosidases
Abstract
Ethnopharmacological relevance: Herbal traditional medicine is used by millions of people in Africa for treatment
of ailments such as diabetes mellitus, stomach disorders and respiratory diseases. Xeroderris stuhlmannii (Taub.)
Mendonca & E.P. Sousa (X. stuhlmannii (Taub.)) is a medicinal plant used traditionally in Zimbabwe to treat type
2 diabetes mellitus (T2DM) and its complications. However, there is no scientific evidence to support its
inhibitory effect against digestive enzymes (α-glucosidases) that are linked to high blood sugar in humans.
Aim of the study: This work aims to investigate whether bioactive phytochemicals of crude X. stuhlmannii (Taub.)
can scavenge free radicals and inhibit α-glucosidases in order to reduce blood sugar in humans.
Materials and methods: Here we examined the free radical scavenging potential of crude aqueous, ethyl acetate
and methanolic extracts of X. stuhlmannii (Taub.) using the diphenyl-2-picrylhydrazyl assay in vitro. Furthermore,
we carried out in vitro inhibition of α-glucosidases (α-amylase and α-glucosidase) by the crude extracts using
chromogenic 3,5-dinitrosalicylic acid and p-nitrophenyl-α-D-glucopyranoside substrates. We also used molecular
docking approaches (Autodock Vina) to screen for bioactive phytochemical compounds targeting the digestive
enzymes.
Results: Our results showed that phytochemicals in X. stuhlmannii (Taub.) aqueous, ethyl acetate and methanolic
extracts scavenged free radicals with IC50 values ranging from 0.002 to 0.013 μg/mL. Furthermore, crude
aqueous, ethyl acetate and methanolic extracts significantly inhibited α-amylase and α-glucosidase with IC50
values of 10.5–29.5 μg/mL (versus 54.1 ± 0.7 μg/mL for acarbose) and 8.8–49.5 μg/mL (versus 161.4 ± 1.8 μg/
mL for acarbose), respectively. In silico molecular docking findings and pharmacokinetic predictions showed that
myricetin is likely a novel plant-derived α-glucosidase inhibitor.
Conclusion: Collectively, our findings suggest pharmacological targeting of digestive enzymes by X. stuhlmannii
(Taub.) crude extracts may reduce blood sugar in humans with T2DM via inhibition of α-glucosidases.
... Nyathi et al. [23] Elephantorrhiza elephantine Fabaceae L, RT Alpha amylase Glucose utilization assay ...
Background: Despite increasing popularity of ethnomedicinal plants in diabetes type 2 management nowadays, indigenous knowledge of their use is often not documented but rather passed on orally from generation to generation. Thus, the present study was designed to collect, analyze, document and generate useful information on ethnomedicinal plants used in management of Diabetes Mellitus Type 2 (DMT2). Materials and Methods: Data on ethnomedicinal use was collected using guided interviews, tour guides and information compared with literature search. Model in vitro enzyme inhibition assays were employed to investigate antidiabetic activity of the plants ethanol/water (60/40) extracts. Shinoda, Mayer Salkowski test and LC-MS/MS coupled with library search software's was used to determine phytochemical composition of the most active extracts. Results: The ethnobotanical survey identified 30 medicinal plant species belonging to 18 plant families of which 14 (46.7)% are newly reported here for their claim as anti DMT2 medicine. Among the 30 plant species reported, 10 were very popular with informant consensus factor of ≥60%. The ethanolic/water (60/40) mixture extract of Zanthoxylum chalybeum, Xeroderris stuhlmannii, Syzygium cordatum and Eureiandra fasciculate showed the greatest in vitro antidiabetic activity, >70%. The present results shows that ethnomedicine plays an important part in the management of DMT2 with Zanthoxylum chalybeum, Xeroderris stuhlmannii, Syzygium cordatum and Eureiandra fasciculate being the most appraised ethnomedicinal plants. Standard chemical tests and LC-MS/MS analysis showed that the extracts consist of mostly C-glycosylated flavonoids and to lesser extent O-glycosylated flavonoids, alkaloids and phenolic acids. Conclusion: The generated results will be important in the prioritization of the plant species for polyherbal drug formulation and further investigation.
... In-silico testing of plants for anti-diabetic benefits (Nyathi, et al., 2023). According to Table 4, in each of these three countries more papers were published of work based on non-animal research. ...
A study examining animal use in research, testing and education in Africa, as well as alternative, non-animal, approaches across the continent. The report also looks at legislation of animal research, animal welfare across the continent and other related issues.
... The lower value of Van der Waals energy suggests the significant influence of the hydrogen bonding characteristic of these compounds in their interactions with proteins/enzymes (Sharma et al., 2016). Nyathi et al. (2023) reported similar results with the isolated phytochemical, Myricetin from the leaf extract of a terrestrial plant, Xeroderris stuhlmannii (Taub.) Mendonca and E.P. Sousa. ...
... The lower value of Van der Waals energy suggests the significant influence of the hydrogen bonding characteristic of these compounds in their interactions with proteins/enzymes (Sharma et al., 2016). Nyathi et al. (2023) reported similar results with the isolated phytochemical, Myricetin from the leaf extract of a terrestrial plant, Xeroderris stuhlmannii (Taub.) Mendonca and E.P. Sousa. ...
JeopardizedglucosehemostasisleadstocronicmetaboicdisorderlikeDiabetesmellitusanditispredictedtooccurin»700millionpeopleinthecoming20years.OurstudyaimstoisolatePalmiticacid(C16H32O3),9-HydroxyhexadecanoicacidmetabolitefromSargassumwightiitoinhibitalpha-amylaseandalpha-glucosi-dasetoreducepostprandialhyperglycemiaanddeclinetheriskofdiabetes.Highdockingscoreofpalmiticacidwithbotha-amylaseanda-glucosidaseisobservedinin-silicomoleculardockinganalysis,incompari-sontocommerciallyavailabledrugacarbose.ThethreehydrogenbondinpalmiticacidinteractswiththeimportantaminoacidslikeArg195,Lys200andAsp300inGlideXPdockingmodeforalpha-amylase.Fora-glucosidase,quantum-polarizedliganddocking(QPLD)wasusedwithsimilarthreehydrogenbondinter-actions.Bothdockingstudiesshowedsignificantbindinginteractionofpalmiticacidwitha-amylase(�5.66and�5.14(Kcal/mol))andwitha-glucosidase(�4.52and�3.51(Kcal/mol))withrespecttothestandard,acarbosedockingscore.Thebioactivepalmiticacidisolatedfromthebrownalga,Sargassumwightiiisalreadyseentoinhibitdigestiveenzymewithnon-targetpropertyinArtemianaupliiandzebrafishembryos.Furtherstudiesarerequiredtoinvestigateitsroleininvivoantidiabeticeffectsduetoitsnon-toxicanddigestiveenzymeinhibitoryproperties.Itcanberecommendedinadditionalpharmaceuticalstudiestodevelopnoveltherapeuticstomanagediabetesmellitus.
... Molecular modeling method provides insights into the ligand's binding affinity with the target's active binding site, adopting a variety of binding modes. 38 In silico computational (h) Cumulative caftaric acid response curves (10 −8 to 10 −5 ) in cyclophosphamide-treated isolated rat bladder strips alone and in the presence of barium chloride (4 nM) and methoctramine (1 μM). Data have been presented as mean ± SEM. *P < 0.05, significant compared to that treated with caftaric acid alone; n = 6. ...
Interstitial cystitis (IC) is the principal unwanted effect associated with the use of cyclophosphamide (CYP). It results in increased oxidative stress, overexpression of proinflammatory cytokines, and bladder overactivity. Patients receiving CYP treatment had severely depreciated quality of life, as the treatment available is not safe and effective. The goal of this study was to assess the protective effect of caftaric acid in CYP-induced IC. IC was induced in female Sprague Dawley by injecting CYP (150 mg/kg, i.p.). In the present study, oral administration of caftaric acid (20, 40, and 60 mg/kg) significantly decreased inflammation. Caftaric acid significantly increased SOD (93%), CAT (92%), and GSH (90%) while decreased iNOS (97%), IL-6 (90%), TGF 1-β (83%), and TNF-α (96%) compared to the diseased. DPPH assay showed the antioxidant capacity comparable to ascorbic acid. Molecular docking of caftaric acid with selected protein targets further confirmed its antioxidant and anti-inflammatory activities. The cyclophosphamide-induced bladder overactivity had been decreased possibly through the inhibition of M3 receptors, ATP-sensitive potassium channels, calcium channels, and COX enzyme by caftaric acid. Therefore, our findings demonstrate that caftaric acid has a considerable protective role against CYP-induced IC by decreasing the oxidative stress, inflammation, and bladder smooth muscle hyperexcitability. Thus, caftaric acid signifies a likely adjuvant agent in CYP-based chemotherapy treatments.
... The hydrolysis of carbohydrates involves several enzymes that include human pancreatic α-amylase (HPA) and α-glucosidase. [5,6] The effects of both inhibitors on blood glucose levels are shown in Figure 1. According to the investigation, three catalytic residues (ASP197, GLU233, and ASP300) are present in an eight-stranded parallel beta-barrel in domain A (1-99, 169-404). ...
Type 2 diabetes, which is characterized by hyperglycemia, is a chronic endocrine metabolic condition. α-amylase inhibitors may have a major therapeutic impact in type 2 diabetic mellitus. In the present study, virtual screening database preparation by R-group enumeration, virtual screening, docking study, and pharmacokinetics analysis was performed by taking α-amylase as a target. The results highlight the important binding features of novel thiazolidine-2,4-dione compounds as α-amylase inhibitors. An R-group enumeration study was performed for the generation of novel thiazolidine-2,4-dione derivatives (6250 compounds). These derivatives further proceed for virtual screening study using Lipinski rule of 5, highthroughput virtual screening, standard precision, and extra precision (XP) screening filters. Only the top 4 compounds were selected after the XP docking process. The molecular docking study of virtual screening hits showed that compound 1 showed a good binding score of −9.129 kcal/mole on α-amylase enzyme (Protein Data Bank ID-3BAY). The present study may be used for the further development of potential compounds against type 2 diabetes.
Accurate screening and targeted preparative isolation of active substances in natural medicines have long been two technical challenges in natural medicine research. This study outlines a new approach to improve the efficiency of natural product preparation, focusing on rapidly and accurately screening potential active ingredients in Inonotus obliquus as well as efficiently preparing 5‐lipoxidase (5‐LOX) inhibitors, to provide new ideas for the treatment of asthma with Inonotus obliquus . First, we used ultrafiltration (UF) mass spectrometry to screen for three potential inhibitors of 5‐LOX in Inonotus obliquus . Subsequently, the inhibitory effect of the active ingredients screened in the UF assay on 5‐LOX was verified using the molecular docking technique, and the potential role of the active compounds in Inonotus obliquus for the treatment of asthma was analyzed by network pharmacology. Finally, based on the above activity screening guidelines, we used semi‐preparative liquid chromatography and consecutive high‐speed countercurrent chromatography to isolate three high‐purity 5‐LOX inhibitors such as betulin, lanosterol, and quercetin. Obviously, through the above approach, we have seamlessly combined rapid discovery, screening, and centralized preparation of the active ingredient with molecular‐level interactions between the active ingredient and the protease.
Apigenin is a phytochemical obtained from Chamomilla recutita. Its role in interstitial cystitis is not yet known. The present study is aimed at understanding the uroprotective and spasmolytic effects of apigenin in cyclophosphamide-induced interstitial cystitis. The uroprotective role of apigenin was analyzed by qRT-PCR, macroscopic analysis, Evans blue dye leakage, histological evaluation, and molecular docking. The spasmolytic response was measured by adding cumulative concentrations of apigenin to isolated bladder tissue pre-contracted with KCl (80 mM) and carbachol (10−9–10−4) on non-incubated and pre-incubated tissues with atropine, 4DAMP, methoctramine, glibenclamide, barium chloride, nifedipine, indomethacin, and propranolol. Apigenin inhibited pro-inflammatory cytokines (IL-6, TNF-α and TGF 1-β) and oxidant enzymes (iNOS) while increasing antioxidant enzymes (SOD, CAT, and GSH) in CYP-treated groups compared to the control. Apigenin restored normal tissue of the bladder by decreasing pain, edema, and hemorrhage. Molecular docking further confirmed the antioxidant and anti-inflammatory properties of apigenin. Apigenin produced relaxation against carbachol-mediated contractions, probably via blockade of M3 receptors, KATP channels, L-type calcium channels, and prostaglandin inhibition. While the blockade of M2 receptors, KIR channels, and β-adrenergic receptors did not contribute to an apigenin-induced spasmolytic effect, apigenin presented as a possible spasmolytic and uroprotective agent with anti-inflammatory, antioxidant effects by attenuating TGF-β/iNOS-related tissue damage and bladder muscle overactivity. Thus, it is a potential agent likely to be used in treatment of interstitial cystitis.
Medicinal plants (MPs) are natural sources of active compounds with potential therapeutic benefits in alleviating various illnesses for decades. Fijian people also are using these MPs for the management/prevention of T2DM and associated complications. However, till date, none of these Fijian MP's antidiabetic potential have been explored/or evaluated. Here, we investigated the antidiabetic potential of Fijian MPs scientifically. Phytochemicals such as polyphenols were detected to inhibit the activity of α-amylase and α-glucosidase; the two key carbohydrate enzymes linked to T2DM. Therefore, in this study, TPC, α-amylase and α-glucosidase inhibitory activity of five Fijian MPs were collected & evaluated.The ME extracts of BO (0.102 ± 0.009 mM CE) and DC (0.098 ± 0.09 mM CE) showed a higher TPC compared to the control. The ME extracts of MF and MR inhibited α-glucosidase significantly in compare to acarbose as evidenced from the IC50 values (IC50 of MF = 1.58 ± 0.03 ng/µL; IC50 of MR = 1.87 ± 0.43 ng/µL and IC50 of acarbose = 3.34 ± 0.15 ng/µL). Moreover, DM extracts of MR (IC50 = 1.31 ± 0.29 ng/µL) also showed significantly higher α-glucosidase inhibitory activity. In contrary, MR (IC50 = 16.18 ± 0.16 ng/µL) and CL (IC50 = 9.21 ± 0.51 ng/µL) also showed significant α-amylase inhibitory activity in ME and DM extracts, respectively. These, results suggest that Fijian MPs could be a potential source of natural inhibitors of enzymes involved in carbohydrate digestion and thus may possibly be used in managing T2DM.
Use of medicinal plants and herbs in the treatment and management of diseases, including diabetes mellitus and its complications remains an integral part of African tradition. In Zimbabwe, nearly one million people are living with diabetes mellitus. The prevalence of diabetes mellitus in Zimbabwe is increasing every year due to lifestyle changes, and has accelerated the use of traditional medicines for its treatment and management in urban areas. In addition, the high cost of modern medicine has led many people in rural parts of Zimbabwe to rely on herbal plant medicine for the treatment of diabetes mellitus and its complications. This review highlights a number of studies carried out to evaluate the antidiabetic properties of indigenous plants found in Zimbabwe with the goal of treating diabetes mellitus. Further, we discuss the mechanism of action of various plant extracts in the treatment and management of diabetes mellitus. Together, this review article can open pathways leading to discovery of new plant derived medicines and regularization of use of crude plant remedies to treat diabetes mellitus by the Zimbabwean government and others across Africa.
Due to the numerous adverse effects of synthetic drugs, researchers are currently studying traditional medicinal plants to find alternatives for diabetes treatment. Eucalyptus citriodora is known to be used as a remedy for various illnesses, including diabetes. This study aimed to explore the effects of ethanol extract of Eucalyptus citriodora (EEEC) on in vitro and in vivo systems, including the mechanism/s of action. The methodology used involved the measurement of insulin secretion from clonal pancreatic β-cells, BRIN BD11, and mouse islets. Other in vitro systems further examined EEEC’s glucose-lowering properties. Obese rats fed a high-fat-fed diet (HFF) were selected for in vivo evaluation, and phytoconstituents were detected via RP-HPLC followed by LC-MS. EEEC induced insulin secretion in a concentration-dependent manner with modulatory effects, similar to 1 µM glucagon-like peptide 1 (GLP-1), which were partly declined in the presence of Ca2+-channel blocker (Verapamil), KATP-channel opener (Diazoxide), and Ca2+ chelation. The insulin secretory effects of EEEC were augmented by isobutyl methylxanthine (IBMX), which persisted in the context of tolbutamide or a depolarizing concentration of KCl. EEEC enhanced insulin action in 3T3-L1 cells and reduced glucose absorption, and protein glycation in vitro. In HFF rats, it improved glucose tolerance and plasma insulin, attenuated plasma DPP-IV, and induced active GLP-1 (7-36) levels in circulation. Rhodomyrtosone B, Quercetin-3-O-β-D-glucopyranoside, rhodomyrtosone E, and quercitroside were identified as possible phytoconstituents that may be responsible for EEEC effects. Thus, these findings revealed that E. citriodora could be used as an adjunct nutritional supplement to manage type 2 diabetes.
The present study aims to find the effective natural enzyme inhibitors against alpha-amylase and alpha-glucosidase from the array of compounds identified in plants of the Simaroubaceae family using molecular docking and ADME/Toxicity studies. Among the 218 compounds docked against seven enzymes, buddlenol-A and citrusin-B showed the best binding energies (kcal/mol) of -7.830 and -7.383 against human salivary alpha-amylase and pancreatic alpha-amylase respectively. The other two compounds 9-hydroxycanthin-6-one and bruceolline-B had the best binding energy of -6.461 and -7.576 against N-terminal and C-terminal maltase glucoamylase respectively. Whereas the binding energy of prosopine (-6.499) and fisetinidol (-7.575) was considered as the best against N-terminal and C-terminal sucrase-isomaltase respectively. Picrasidine-X showed the best binding energy (-7.592) against yeast alpha-glucosidase. The study revealed that the seven compounds which showed the best binding energy against respective enzymes are considered as the ‘lead hit compounds’. Even though the ‘lead hit compounds’ are not obeying all the laws of ADMET, the drug-likeness properties of 9-hydroxycanthin-6-one, fisetinidol, picrasidine-X, and prosopine were considerable. Also, kaempferol-3-O-pentoside was the recent compound identified from the Simarouba glauca plant extract found to be one among the top five lead hit compounds against four enzymes. This study provides valuable insight into the direction of developing natural compounds as potential starch hydrolysing enzyme inhibitors for managing type 2 diabetes.
Africa has a rich biodiversity of plants and an active traditional medicine system that takes advantage of the rich biodiversity to treat various diseases, including diabetes mellitus (DM). The folkloric use of some of these plants in treating diabetes has been documented in various databases and publications, and validated with in vitro and in vivo models. In this regard ethnopharmacology remains the major tool in the search for bioactive compounds from African medicinal plants. Our previous review, covering 1977–2014, revealed that fifty-three (53) compounds isolated from African medicinal plants showed varying levels of antidiabetic activity. Since then, several further antidiabetic agents have been isolated from African plants, mostly based on ethnomedicinal information, but they have not been critically reviewed in any previous publication. Therefore, this article provides an insightful commentary on the antidiabetic compounds from African medicinal plants, along with an attempt to highlight the structure-activity relationships. Relevant literature, from 2015 to 2020, was collected by searching the major electronic scientific databases including PubMed, ScienceDirect, Web of Science, and Google Scholar, using appropriate keyword combinations. A total of eighty-four (84) compounds, isolated from different parts of twenty-four (24) African medicinal plants, including, leaves, stem barks, roots, tubers, and aerial parts, were investigated as possible antidiabetic agents. The flavonoids quercetin, kaempferol and apigenin, and the triterpenoids convallatoxin and combretin B are the most promising antidiabetic compounds. In spite of the interesting in vitro and in vivo evidence for antidiabetic activity, not a single compound was investigated in a clinical study. Several compounds from African ethnomedicinal plants have shown promising in vitro or in vivo antidiabetic activity. Some of these compounds are ubiquitous plants metabolites with known non-specific biological activities, but some others are rare phytochemicals that show structure specific bioactivities and should be further investigated. It is hoped that this review would motivate the further studies of these compounds along the drug discovery pipeline. In addition, this review shows that selection of plants based on ethnopharmacological information from African plants is a promising drug discovery strategy.
Because undesirable pharmacokinetics and toxicity of candidate compounds are the main reasons for the failure of drug development, it has been widely recognized that absorption, distribution, metabolism, excretion and toxicity (ADMET) should be evaluated as early as possible. In silico ADMET evaluation models have been developed as an additional tool to assist medicinal chemists in the design and optimization of leads. Here, we announced the release of ADMETlab 2.0, a completely redesigned version of the widely used AMDETlab web server for the predictions of pharmacokinetics and toxicity properties of chemicals, of which the supported ADMET-related endpoints are approximately twice the number of the endpoints in the previous version, including 17 physicochemical properties, 13 medicinal chemistry properties, 23 ADME properties, 27 toxicity endpoints and 8 toxicophore rules (751 substructures). A multi-task graph attention framework was employed to develop the robust and accurate models in ADMETlab 2.0. The batch computation module was provided in response to numerous requests from users, and the representation of the results was further optimized. The ADMETlab 2.0 server is freely available, without registration, at https://admetmesh.scbdd.com/.
Background:
The leaves of Hagenia abyssinica have been used in the management of diabetes mellitus in Ethiopian folk medicine. Thus, this study is aimed at investigating the in vitro α-amylase and α-glucosidase inhibitory and antioxidant activities of the crude extract and solvent fractions of H. abyssinica leaves.
Methods:
The in vitro α-amylase and α-glucosidase inhibitory and antioxidant activities of the plant extract were assessed using 3,5-dinitrosalicylic acid (DNSA), p-nitro-phenyl-a-D glucopyranoside (p-NPG), and 1,1-diphenyl-2-picrylhydrazyl (DPPH) assays, respectively. Each value of percent inhibition of α-amylase, α-glucosidase, and DPPH scavenging effect was presented as means ± SEM (n = 3).
Results:
The α-amylase inhibitory activity of the crude extract and solvent fractions was found to be concentration-dependent. The strongest activity was exhibited by the crude extract at the highest concentration with a percentage inhibition of 74.52% (IC50, 14.52 μg/ml) followed by water fraction 68.24% (IC50, 16.31 μg/ml), ethyl acetate fraction 61.57% (IC50, 18.73 μg/ml), and chloroform fraction 56.87% (IC50, 21.57 μg/ml) of H. abyssinica leaves. In the α-glucosidase inhibition assay, the maximum activity was exhibited by the aqueous fraction 62.54% (IC50, 11.67 μg/ml) followed by ethyl acetate fraction 54.97% (IC50, 15.89 μg/ml), crude extract 46.79% (IC50, >16.5 μg/ml), and chloroform fraction 36.44% (IC50, >16.5 μg/ml). In the antioxidant assay, the crude extract exhibited the highest antioxidant activity 86.36% (IC50, 10.25 μg/ml) followed by water fraction 78.59% (IC50, 13.86 μg/ml), ethyl acetate fraction 71.58% (IC50, 16.34 μg/ml), and chloroform fraction 63.65% (IC50, 18.83 μg/ml).
Conclusion:
This study has revealed that H. abyssinica leaves possess noticeable in vitro α-amylase and α-glucosidase inhibitory and antioxidant activities.
Insulin resistance (IR) is apparent when tissues responsible for clearing glucose from the blood, such as adipose and muscle, do not respond properly to appropriate signals. IR is estimated based on fasting blood glucose and insulin, but some measures also incorporate an oral glucose challenge. Certain (poly)phenols, as supplements or in foods, can improve insulin resistance by several mechanisms including lowering postprandial glucose, modulating glucose transport, affecting insulin signalling pathways, and by protecting against damage to insulin-secreting pancreatic β-cells. As shown by intervention studies on volunteers, the most promising candidates for improving insulin resistance are (−)-epicatechin, (−)-epicatechin-containing foods and anthocyanins. It is possible that quercetin and phenolic acids may also be active, but data from intervention studies are mixed. Longer term and especially dose-response studies on mildly insulin resistant participants are required to establish the extent to which (poly)phenols and (poly)phenol-rich foods may improve insulin resistance in compromised groups.
Background: Red amaranth (Amaranthus gangeticus L.) has great diversity in Bangladesh, India, and South East Asia with multipurpose uses. The bright red-violet colored A. gangeticus is a popular and low-cost leafy vegetable in the Asian continent including Bangladesh and India because of attractive leaf color, taste, adequate nutraceuticals, phenolic compounds, and sole source of betalains. The natural colors and phenolic compounds of this species have a significant role in promoting the health-benefit including the scavenging capacity of radicals, the colorant of food products, and play a vital role in the industry of foods. However, phenolic profiles and radical scavenging activity of this species have not been evaluated. Hence, for the first time, four selected advance lines of A. gangeticus were characterized for phenolic profiles, antioxidant constituents, and antioxidant potentiality.
Results: A. gangeticus genotypes are abundant sources of phenolic profiles and antioxidant constituents with good radical quenching capacity that differed across the genotypes. Twenty-five phenolic acids and flavonoids, such as protocatechuic acid, salicylic acid, gentisic acid, gallic acid, β-resorcylic acid, vanillic acid, p-hydroxybenzoic acid, chlorogenic acid, ellagic acid, syringic acid, ferulic acid, kaempferol, m-coumaric acid, trans-cinnamic acid, quercetin, p-coumaric acid, apigenin, caffeic acid, rutin, sinapic acid, isoquercetin, naringenin, myricetin, catechin, and hyperoside were identified in A. gangeticus accessions. A. gangeticus accessions LS7 and LS9 demonstrated ample phenolic acids, flavonoids, antioxidant constituents, and antioxidant potentiality. It revealed from the correlation study that antioxidant components of A. gangeticus genotypes exhibited good radical scavenging activities. The genotypes LS7 and LS9 could be directly used as phenolic profiles, antioxidant constituents, and antioxidant activity enrich cultivars.
Conclusions:The identified compounds of phenolic acids and flavonoids in A. gangeticus privilege the comprehensive study of pharmacology. The basic information on phenolic profiles and antioxidant constituents achieved in the present study will provide the scientist’s forum for the scientific assessment of these compounds in A. gangeticus.
Diabetes mellitus is a leading cause of mortality and reduced life expectancy. We aim to estimate the burden of diabetes by type, year, regions, and socioeconomic status in 195 countries and territories over the past 28 years, which provide information to achieve the goal of World Health Organization Global Action Plan for the Prevention and Control of Noncommunicable Diseases in 2025. Data were obtained from the Global Burden of Disease Study 2017. Overall, the global burden of diabetes had increased significantly since 1990. Both the trend and magnitude of diabetes related diseases burden varied substantially across regions and countries. In 2017, global incidence, prevalence, death, and disability-adjusted life-years (DALYs) associated with diabetes were 22.9 million, 476.0 million, 1.37 million, and 67.9 million, with a projection to 26.6 million, 570.9 million, 1.59 million, and 79.3 million in 2025, respectively. The trend of global type 2 diabetes burden was similar to that of total diabetes (including type 1 diabetes and type 2 diabetes), while global age-standardized rate of mortality and DALYs for type 1 diabetes declined. Globally, metabolic risks (high BMI) and behavioral factors (inappropriate diet, smoking, and low physical activity) contributed the most attributable death and DALYs of diabetes. These estimations could be useful in policy-making, priority setting, and resource allocation in diabetes prevention and treatment.
Type 2 diabetes mellitus is increasing worldwide, and the United Arab Emirates is presenting one of the world’s highest prevalence rates. Dietary polyphenols exert an antidiabetic effect by modulating carbohydrates digestion and cellular glucose uptake. Due to their particularly high content in polyphenols, date seeds represent a potential antidiabetic agent. This study aims to determine if date seed polyphenols inhibit the activity of the enzymes (α-amylase and α-glucosidase), responsible for the digestion of carbohydrates and modulating the glucose uptake by human liver cells. In vitro activity of the intestinal α-glucosidase, pancreatic α-amylase, the glucose uptake by HepG2 cells, and the expression of GLUT4 and AMPK analyzed by western blotting (with and without date seeds extract). Our result showed that the maximum enzymes inhibition was obtained with 400 μg/mL and 900 μg/mL DSE for α-amylase and α-glucosidase, respectively. The HepG2 cell viability significantly decreased up to 80% at 4000 μg/mL DSE. The expression of GLUT4 was higher at 100 μg/mL DSE (with insulin and without insulin). However, the expressions of P-AMPK and AMPK were increased by DSE, mainly in a non-insulin-dependent manner. Therefore, DSE, by inhibiting carbohydrate digestion and stimulating glucose uptake by HepG2, can potentially demonstrate the therapeutic potential for diabetes management.
Metabolic syndrome (MetS) is a prevalent, multifactorial and complex disease that is
associated with an increased risk of developing diabetes and other major cardiovascular complications. The rise in the global prevalence of MetS has been attributed to genetic, epigenetic, and environmental factors. The adoption of sedentary lifestyles that are characterized by low physical activity and the consumption of high-energy diets contributes to MetS development. Current management criteria for MetS risk factors involve changes in lifestyle and the use of pharmacological agents that target
specific biochemical pathways involved in the metabolism of nutrients. Pharmaceutical drugs are usually expensive and are associated with several undesirable side e�ects. Alternative management strategies of MetS risk factors involve the use of medicinal plants that are considered to have multiple therapeutic targets and are easily accessible. Medicinal plants contain several di�erent biologically active compounds that provide health benefits. The impact of phytochemicals present in local medicinal plants on sustainable health and well-being of individuals has been studied for many years
and found to involve a plethora of complex biochemical, metabolic, and physiological mechanisms. While some of these phytochemicals are the basis of mainstream prescribed drugs (e.g., metformin, reserpine, quinine, and salicin), there is a need to identify more medicinal plants that can be used for the management of components of MetS and to describe their possible mechanisms of action. In this review, we assess the potential health benefits of South African ethnomedicinal plants in protecting
against the development of health outcomes associated with MetS. We aim to provide the state of the current knowledge on the use of medicinal plants and their therapeutically important phytochemicals by discussing the current trends, with critical examples from recent primary references of how medicinal plants are being used in South African rural and urban communities.
Drug discovery is a rigorous process that requires billion dollars of investments and decades of research to bring a molecule “from bench to a bedside”. While virtual docking can significantly accelerate the process of drug discovery, it ultimately lags the current rate of expansion of chemical databases that already exceed billions of molecular records. This recent surge of small molecules availability presents great drug discovery opportunities, but also demands much faster screening protocols. In order to address this challenge, we herein introduce Deep Docking (DD), a novel deep learning platform that is suitable for docking billions of molecular structures in a rapid, yet accurate fashion. The DD approach utilizes quantitative structure–activity relationship (QSAR) deep models trained on docking scores of subsets of a chemical library to approximate the docking outcome for yet unprocessed entries and, therefore, to remove unfavorable molecules in an iterative manner. The use of DD methodology in conjunction with the FRED docking program allowed rapid and accurate calculation of docking scores for 1.36 billion molecules from the ZINC15 library against 12 prominent target proteins and demonstrated up to 100-fold data reduction and 6000-fold enrichment of high scoring molecules (without notable loss of favorably docked entities). The DD protocol can readily be used in conjunction with any docking program and was made publicly available.
Dietary polyphenols have been widely investigated as antidiabetic agents in cell, animals, human study, and clinical trial. The number of publication (Indexed by Web of Science) on “polyphenols and diabetes” significantly increased since 2010. This review highlights the advances and opportunities of dietary polyphenols as antidiabetic agents. Dietary polyphenols prevent and manage Type 2 diabetes mellitus via the insulin‐dependent approaches, for instance, protection of pancreatic islet β‐cell, reduction of β‐cell apoptosis, promotion of β‐cell proliferation, attenuation of oxidative stress, activation of insulin signaling, and stimulation of pancreas to secrete insulin, as well as the insulin‐independent approaches including inhibition of glucose absorption, inhibition of digestive enzymes, regulation of intestinal microbiota, modification of inflammation response, and inhibition of the formation of advanced glycation end products. Moreover, dietary polyphenols ameliorate diabetic complications, such as vascular dysfunction, nephropathy, retinopathy, neuropathy, cardiomyopathy, coronary diseases, renal failure, and so on. The structure–activity relationship of polyphenols as antidiabetic agents is still not clear. The individual flavonoid or isoflavone has no therapeutic effect on diabetic patients, although the clinical data are very limited. Resveratrol, curcumin, and anthocyanins showed antidiabetic activity in human study. How hyperglycemia influences the bioavailability and bioactivity of dietary polyphenols is not well understood. An understanding of how diabetes alters the bioavailability and bioactivity of dietary polyphenols will lead to an improvement in their benefits and clinical outcomes. Anti‐diabetic mechanisms of dietary polyphenols .
Background
There has been an appreciable increase in the number of people in Africa with metabolic syndrome and Type 2 diabetes (T2DM) in recent years as a result of a number of factors. Factors include lifestyle changes, urbanisation, and the growing consumption of processed foods coupled with increasing levels of obesity. Currently there are 19 million adults in Africa with diabetes, mainly T2DM (95%), estimated to grow to 47 million people by 2045 unless controlled. This has a considerable impact on morbidity, mortality and costs in the region. There are a number of issues to address to reduce the impact of T2DM including improving detection rates and current access to services alongside addressing issues of adherence to prescribed medicines. There are also high rates of co-morbidities with infectious diseases such as HIV and tuberculosis in patients in Africa with T2DM that require attention.
Objective
Document ongoing activities across Africa to improve the care of patients with T2DM especially around issues of identification, access, and adherence to changing lifestyles and prescribed medicines. In addition, discussing potential ways forward to improve the care of patients with T2DM based on ongoing activities and experiences including addressing key issues associated with co-morbidities with infectious diseases.
Our Approach
Contextualise the findings from a wide range of publications including internet based publications of national approaches coupled with input from senior level government, academic and other professionals from across Africa to provide future guidance.
Ongoing Activities
A number of African countries are actively instigating programmes to improve the care of patients with T2DM starting with improved diagnosis. This recognises the growing burden of non-communicable diseases across Africa, which has been neglected in the past. Planned activities include programmes to improve detection rates and address key issues with diet and lifestyle changes, alongside improving monitoring of care and activities to enhance adherence to prescribed medicines. In addition, addressing potential complexities involving diabetes patients with infectious disease co-morbidities. It is too early to fully assess the impact of such activities,
Conclusion
There are a number of ongoing activities across Africa to improve the management of patients with diabetes including co-morbidities. However, more needs to be done considering the high and growing burden of T2DM in Africa. Ongoing research will help further benefit resource allocation and subsequent care.
To test the hypothesis that myricitrin (MYR) improves type 2 diabetes, we examined the effect of MYR on hyperglycemia, glucose intolerance, hepatic steatosis, and inflammation in high-fat diet (HFD) and streptozotocin (STZ)-induced type 2 diabetic mice. Male C57BL/6J mice were randomly divided into three groups: non-diabetic, diabetic control, and MYR (0.005%, w/w)-supplemented diabetic groups. Diabetes was induced by HFD and STZ, and MYR was administered orally for 5 weeks. Myricitrin exerted no significant effects on food intake, body weight, fat weight, or plasma lipids levels. However, MYR significantly decreased fasting blood glucose levels, improved glucose intolerance, and increased pancreatic β-cell mass compared to the diabetic control group. Myricitrin administration also markedly increased glucokinase mRNA expression and activity as well as lowered glucose-6-phosphatase and phosphoenolpyruvate carboxykinase mRNA expression and activity in the liver. In addition, liver weight, hepatic triglyceride content, and lipid droplet accumulation were markedly decreased following MYR administration. These changes were seemingly attributable to the suppression of the hepatic lipogenic enzymes—fatty acid synthase and phosphatidate phosphohydrolase. Myricitrin also significantly lowered plasma MCP-1 and TNF-α levels and the mRNA expression of hepatic pro-inflammatory genes. These results suggest that MYR has anti-diabetic potential.
The rising burden of type 2 diabetes is a major concern in healthcare worldwide. This research aimed to analyze the global epidemiology of type 2 diabetes. We analyzed the incidence, prevalence, and burden of suffering of diabetes mellitus based on epidemiological data from the Global Burden of Disease (GBD) current dataset from the Institute of Health Metrics, Seattle. Global and regional trends from 1990 to 2017 of type 2 diabetes for all ages were compiled. Forecast estimates were obtained using the SPSS Time Series Modeler. In 2017, approximately 462 million individuals were affected by type 2 diabetes corresponding to 6.28% of the world’s population (4.4% of those aged 15–49 years, 15% of those aged 50–69, and 22% of those aged 70+), or a prevalence rate of 6059 cases per 100,000. Over 1 million deaths per year can be attributed to diabetes alone, making it the ninth leading cause of mortality. The burden of diabetes mellitus is rising globally, and at a much faster rate in developed regions, such as Western Europe. The gender distribution is equal, and the incidence peaks at around 55 years of age. Global prevalence of type 2 diabetes is projected to increase to 7079 individuals per 100,000 by 2030, reflecting a continued rise across all regions of the world. There are concerning trends of rising prevalence in lower-income countries. Urgent public health and clinical preventive measures are warranted.
Diabetes mellitus (DM) is a metabolic disorder characterized by chronic hyperglycemia together with disturbances in the metabolism of carbohydrates, proteins and fat, which in general results from an insulin availability and need imbalance. In a great number of patients, marketed anti-glycemic agents have shown poor effectiveness in maintaining a long-term glycemic control, thus being associated with severe adverse effects and leading to an emerging interest in natural compounds (e.g., essential oils and other secondary plant metabolites, namely, flavonoid-rich compounds) as a novel approach for prevention, management and/or treatment of either non-insulin-dependent diabetes mellitus (T2DM, type 2 DM) and/or Metabolic Syndrome (MS). In this review, some of these promising glucose-lowering agents will be comprehensively discussed.
Background: The loss of biodiversity in Nigeria is escalating alarmingly. However, there is
generally a paucity of information as to what taxa are endangered because of a dearth of
functioning conservation agencies in Nigeria.
Objectives: The aim of this research is to record the endangered medicinal and other economic plant species in the Sudan Savanna vegetation in Katsina and to provide an assessment of the various threats faced by these plants.
Method: Medicinal plants were identified through oral interviews with traditional medical
practitioners within the study area. Conservation statuses were assessed using a bespoke data collection and assessment form; the data were then evaluated using the International Union for the Conservation of Nature Red List categories and criteria.
Results: A total of 169 species belonging to 62 families were recorded. Of these, 43 taxa were reported to be used for ethnomedicinal practices. It was found that more than half (108) of the 169 species were threatened with extinction and one taxon (Xeroderris stuhlmannii [Taub.] Mendonca & Sousa) qualifies as being Extinct locally. Threats recorded include overexploitation (24%), agriculture (15%), deforestation and desertification (12% each), invasive plants (11%), urban residential development (7%) and erosion (6%).
Conclusion: Most of the plants are already under threat and require urgent conservation
measures. The data point to the critical need for further research into conservation strategies and a more sustainable use of threatened plants. We recommend that the Nigerian government should establish a national Red List agency and ensure effective protected area management and community-based natural resources management.
Keywords: conservation; endangered species; Hausa community; IUCN; threat categories;
Nigeria; Sudan Savanna.
Background
Different plant parts of Roylea cinerea (D. Don) Baill. (Lamiaceae), Clematis grata Wall. (Ranunculaceae), Cornus capitata Wall. (Cornaceae) are traditionally used in the management of diabetes and various other diseases.
Method
The air-dried plant parts from different plants were coarsely powdered and macerated in methanol to obtain their crude extracts. The crude extracts were evaluated for their α-glucosidase inhibitory activity. On the basis of results obtained, the methanolic crude extract of Cornus capitata Wall. was further sequentially fractionated in hexane, diethyl ether, ethyl acetate, n-butanol. Fractions obtained were also evaluated for their α-glucosidase inhibitory potential. The kinetic study was performed using Lineweaver Burk plot to evaluate the type of inhibition. Furthermore, in silico analysis was also carried with active sites of the enzyme (PDB ID: 3WY1) using Autodock4.
Results
Among all the plant extracts, Cornus capitata extract showed maximum inhibitory activity. Therefore its methanolic extract was further fractionated with the help of different solvents and the maximum activity was shown by the ethyl acetate fraction (IC50 50 μg/mL). Kinetic analysis indicated that Vmax and Km were increased indicating a competitive type of inhibition. In docking studies, among different constituents known in this plant, betulinic acid showed minimum binding energy (− 10.21 kcal/mol). The kinetic and docking studies have strengthened the observation made in the present study regarding the α-glucosidase inhibitory activity of Cornus capitata.
Conclusion
The study provided partial evidence for pharmacological basis regarding clinical applications of Cornus capitata in the treatment of diabetes suggesting it to be a suitable candidate for the treatment of postprandial hyperglycemia.
Aging is the progressive loss of organ and tissue function over time. Growing older is positively linked to cognitive and biological degeneration such as physical frailty, psychological impairment, and cognitive decline. Oxidative stress is considered as an imbalance between pro- and antioxidant species, which results in molecular and cellular damage. Oxidative stress plays a crucial role in the development of age-related diseases. Emerging research evidence has suggested that antioxidant can control the autoxidation by interrupting the propagation of free radicals or by inhibiting the formation of free radicals and subsequently reduce oxidative stress, improve immune function, and increase healthy longevity. Indeed, oxidation damage is highly dependent on the inherited or acquired defects in enzymes involved in the redox-mediated signaling pathways. Therefore, the role of molecules with antioxidant activity that promote healthy aging and counteract oxidative stress is worth to discuss further. Of particular interest in this article, we highlighted the molecular mechanisms of antioxidants involved in the prevention of age-related diseases. Taken together, a better understanding of the role of antioxidants involved in redox modulation of inflammation would provide a useful approach for potential interventions, and subsequently promoting healthy longevity.
Pompe disease, a rare lysosomal storage disease caused by deficiency of the lysosomal acid α-glucosidase (GAA), is characterized by glycogen accumulation, triggering severe secondary cellular damage and resulting in progressive motor handicap and premature death. Numerous disease-causing mutations in the gaa gene have been reported, but the structural effects of the pathological variants were unknown. Here we present the high-resolution crystal structures of recombinant human GAA (rhGAA), the standard care of Pompe disease. These structures portray the unbound form of rhGAA and complexes thereof with active site-directed inhibitors, providing insight into substrate recognition and the molecular framework for the rationalization of the deleterious effects of disease-causing mutations. Furthermore, we report the structure of rhGAA in complex with the allosteric pharmacological chaperone N-acetylcysteine, which reveals the stabilizing function of this chaperone at the structural level.
Myricetin (Myc) is one of the most important flavonoids in diet due to its abundance in foods with the highest antioxidant activity. The antioxidant activity of Myc was studied in cell-free and cell-based systems to evaluate the ROS protection efficiency of Myc. The studies were based on the assessment of reducing power of Myc according to ferric ion reduction and intracellular ROS level measurement by assaying the cellular fluorescence intensity using dichlorodihydrofluorescein (DCF) probe as an indicator for ROS in cells. Moreover, the antitoxic capability of Myc was assessed using MTT method. Data indicated that intracellular ROS are highly toxic and applying low concentration of Myc not only inhibited cellular ROS production but also was accompanying with the protection of cells against the highly toxic and the lethal effects of peroxide compounds. Because of strong correlation between cellular ROS and their cell toxic properties, the higher antioxidant potency of Myc in cell medium resulted in effectively blocking intracellular ROS and protecting cell death. This property is achieved by the help of high polar solubility and cell membrane permeability of Myc.
Alpha-glucosidase inhibitors (AGIs) was reported to be associated with several rare adverse hepatic events, but with inconsistent results. We aimed to investigate the risk of hepatotoxicity associated with the use of AGIs in patients with type 2 diabetes mellitus (T2DM), and performed a systematic review and meta-analysis. Fourteen studies (n = 2881) were eligible, all of which were RCTs. Meta-analysis of data regarding elevation of more than 3-fold the upper limit of normal (ULN) of AST and ALT showed statistically significant differences between AGIs treatment versus control (OR 6.86, 95% CI 2.50 to 18.80; OR 6.48, 95% CI 2.40 to 17.49). Subgroup analyses of elevation of more than 1.8-fold ULN of AST and ALT by dose of AGIs showed differential effects on AST and ALT (AST: OR 0.38 vs 7.31, interaction P = 0.003; ALT: OR 0.32 vs 4.55, interaction p = 0.02). Meta-analysis showed that AGIs might increase the risk of hepatotoxicity, and higher dose appeared to be associated with higher risk of hepatotoxicity. However, the evidence is limited with surrogate measures (i.e. ALT and AST), and no clinically important adverse events were observed.
Objective
. Treating complications associated with diabetes and hypertension imposes significant costs on health care systems. This study estimated the hospitalization costs for inpatients in a public hospital in Zimbabwe.
Methods
. The study was retrospective and utilized secondary data from medical records. Total hospitalization costs were estimated using generalized linear models.
Results
. The median cost and interquartile range (IQR) for patients with diabetes, 1319 (95% CI: 981–1657), was higher than patients with hypertension, 914 (95% CI: 825–1003). Female patients aged below 65 years with diabetes had the highest estimated mean costs (2884 (95% CI: 2004–4149) for patients with diabetes and $2239 (95% CI: 1589–3156) for patients with hypertension. Age below 65 years, medical procedures (amputation, wound care, dialysis, and physiotherapy), the presence of two or more comorbidities, and being prescribed two or more drugs were associated with significantly higher hospitalization costs.
Conclusion
. Our estimated costs could be used to evaluate and improve current inpatient treatment and management of patients with diabetes and hypertension and determine the most cost-effective interventions to prevent complications and comorbidities.
Growing evidence from animal studies supports the anti-diabetic properties of some dietary polyphenols, suggesting that dietary polyphenols could be one dietary therapy for the prevention and management of Type 2 diabetes. This review aims to address the potential mechanisms of action of dietary polyphenols in the regulation of glucose homeostasis and insulin sensitivity based on in vitro and in vivo studies, and to provide a comprehensive overview of the anti-diabetic effects of commonly consumed dietary polyphenols including polyphenol-rich mixed diets, tea and coffee, chocolate and cocoa, cinnamon, grape, pomegranate, red wine, berries and olive oil, with a focus on human clinical trials. Dietary polyphenols may inhibit α-amylase and α-glucosidase, inhibit glucose absorption in the intestine by sodium-dependent glucose transporter 1 (SGLT1), stimulate insulin secretion and reduce hepatic glucose output. Polyphenols may also enhance insulin-dependent glucose uptake, activate 5' adenosine monophosphate-activated protein kinase (AMPK), modify the microbiome and have anti-inflammatory effects. However, human epidemiological and intervention studies have shown inconsistent results. Further intervention studies are essential to clarify the conflicting findings and confirm or refute the anti-diabetic effects of dietary polyphenols.
Virtual molecular screening is used to dock small-molecule libraries to a macromolecule in order to find lead compounds with desired biological function. This in silico method is well known for its application in computer-aided drug design. This chapter describes how to perform small-molecule virtual screening by docking with PyRx, which is open-source software with an intuitive user interface that runs on all major operating systems (Linux, Windows, and Mac OS). Specific steps for using PyRx, as well as considerations for data preparation, docking, and data analysis, are also described.
Objective: Diabetes appears to be a growing problem in the African region. This study aims to estimate the prevalence of diabetes in Zimbabwe by collating and analyzing previously published data.
Methods: Systematic review and meta-analysis of data reporting prevalence of diabetes in Zimbabwe was conducted based on the random effects model. We searched for studies published between January 1960 and December 2013 using MEDLINE, EMBASE and Scopus and University of Zimbabwe electronic publication libraries. In the meta-analysis, sub-groups were created for studies conducted before 1980 and after 1980, to understand the potential effect of independence on prevalence.
Results: Seven studies were included in the meta-analysis with a total of 29,514 study participants. The overall pooled prevalence of diabetes before 1980 was 0.44 % (95 % CI 0.0–1.9 %), after 1980 the pooled prevalence was 5.7 % (95 % CI 3.3–8.6 %).
Conclusions: This study showed that the prevalence of diabetes in Zimbabwe has increased significantly over the past three decades. This poses serious challenges to the provision of care and prevention of disabling co-morbidities in an already disadvantaged healthcare setting.
In Africa, up to 80% of the population relies on herbal concoctions for their primarily health care. In Togo, western Africa, Tem tribe is a population with old knowledge of medicinal plants, however, still very little is known about their medical practices. The present study was conducted to access for the apprehension of adverse effects of traditional remedies by Tem traditional healers (TH). Enquiry was performed by interviews with healers from August to October 2007 in Tchaoudjo prefecture (Togo). The study allowed us to interview 54 TH including 41(75.93%) males and 13(24.07%) females, who cited 102 recipes assumed to have adverse effects. The recipes were used alone to cure several diseases including haemorrhoids (22.55%), female sexual disorders and infertility (21.57%), gastrointestinal disorders (18.63%), and malaria (6.86%). A total of 34 plants belonging to 21 families were cited to be components of the recipes. Euphorbiaceae and Mimosaceae families were the most represented, however, Nauclea latifolia, Khaya senegalensis, Pseudocedrela kotschyi and Xeroderris stuhlmannii were the main components of recipes linked to adverse effects. A total of 20 adverse effects were linked to the administration of theses drugs, and among them; diarrhoea, abdominal pains, polyuria, general weakness and vomiting were the most frequently encountered. These findings were in accordance with several reports of the literature concerning medicinal plants, although they were based on empirical observations. Laboratory screenings are needed to access for the effectiveness as well as the possible toxic effects of the recipes.
The Tem tribe in the Central Region of Togo is a population with an extensive knowledge of medicinal plants. However, little is known about their medical practices, principally the use of plants in the management of diabetes mellitus (DM) and hypertension (HTN).
The present study documented the indigenous medicinal plant utilization for the management of DM and HTN in the Togo Central Region.
From March to October 2010, 55 traditional healers were interviewed about their knowledge on the use of plants for DM and HTN treatment.
The results revealed that 35/55 (63.64%) healers had treated at least one case of DM and/or HTN. They highlighted the use of 64 species belonging to 31 families in the treatment of DM and/or HTN. The most used plants against diabetes were Psidium guajava L. (Myrtaceae), Khaya senegalensis A. Juss. (Meliaceae), Sarcocephalus latifolius (Sm.) E.A. Bruce (Rubiaceae), Annona muricata L. (Annonaceae), Bridelia ferruginea Benth. (Phyllanthaceae), and Securidaca longepedunculata Fresen. (Polygalacae), while Allium sativum L. (Liliaceae) and Parkia biglobosa Benth. (Fabaceae), followed by Khaya senegalensis A. Juss. (Meliaceae), Gardenia ternifolia Schumach. (Rubiaceae), and Persea americana Mill. (Lauraceae) were the most commonly cited as antihypertensive.
The issue revealed that traditional healers of the above mentioned region have basic knowledge regarding herbal medicine for DM and HTN in comparison with previous published reports. Further pharmacological screening of the identified plants should be conducted to ascertain the effectiveness of these plants.
Molecular docking has become an increasingly important tool for drug discovery. In this review, we present a brief introduction of the available molecular docking methods, and their development and applications in drug discovery. The relevant basic theories, including sampling algorithms and scoring functions, are summarized. The differences in and performance of available docking software are also discussed. Flexible receptor molecular docking approaches, especially those including backbone flexibility in receptors, are a challenge for available docking methods. A recently developed Local Move Monte Carlo (LMMC) based approach is introduced as a potential solution to flexible receptor docking problems. Three application examples of molecular docking approaches for drug discovery are provided.
The Konstanz Information Miner is a modular environment which enables easy visual assembly and interactive execution of a data pipeline. It is designed as a teaching, research and collaboration platform, which enables easy integration of new algorithms, data manipulation or visualization methods as new modules or nodes. In this paper we describe some of the design aspects of the underlying architecture and briefly sketch how new nodes can be incorporated. OVERVIEW Large volumes of data are often generated during simulations and the need for modular data analysis environments has increased dramatically over the past years. In order to make use of the vast variety of data analysis
An ethnobotanical study was conducted in the Wechiau Community Hippopotamus Sanctuary area in Ghana, through interviews and quadrate studies, to investigate the range and abundance of species used in the treatment of malaria. Forty-one species belonging to 17 families were encountered during the study. Of the 17 families studied Leguminosae and Anacardiaceae predominated in terms of number of species used to treat malaria. Eight plant species namely, Afraegle paniculata (Rutaceae), Haematostaphis barteri (Anacardiaceae), Indigo era pulchra (Leguminosae), Monanthotaxis sp. (Annonaceae), Ozoroa insignis (Anacardiaceae), Strychnos innocua (Loganiaceae), Strychnos spinosa (Loganiaceae) and Xeroderris stuhlmannii (Leguminosae) have not previously been documented for the treatment of malaria in Ghana. The results are discussed and recommendations made for future research to support the conservation and sustainable harvesting of the species reported to have medicinal properties.
Traditional medicines play an important role in health care provision in developing countries as primary therapies and/or as complementary medicines. The aim of this study was to document medicinal plants used in Gokwe South District in Zimbabwe. Forty six participants from 12 wards were interviewed between October 2020 and April 2021 using a semi-structured questionnaire. Ethnobotanical data including local names of the plants, plant parts used, medicinal uses, methods of preparation and administration were documented. The ethnomedicinal data were analysed using different quantitative indices including informant consensus factor (ICF), fidelity level (FL), relative frequency of citation (RFC) and use value (UV). One hundred and twenty seven plant species from 49 families were documented for treating and managing 23 medical categories. Gastro-intestinal disorders (60 citations), respiratory infections (47 citations), reproductive system and health (33 citations) and sexually transmitted infections (21 citations) were commonly treated with medicinal plants within the study area. Nineteen species were recorded for the first time as sources of traditional medicines with no prior record of being used as medicinal plants for any specific disease or ailment in the country. Trees (58.0%) were the main sources of traditional medicines, followed by shrubs (27.0%), herbs and climbers (10.0% and 5.0%, respectively). The most frequently used plant parts were roots (48.8%), followed by bark (37.8%) and leaves (34.6%). The variety of plants that are used to treat and manage human diseases and ailments in the study area emphasizes the importance that medicinal plants play in primary health care system of the rural people in Gokwe South District. Some of the plants used in the study area were characterized by high frequency of citation and use values, and species such as Xeroderris stuhlmannii (Taub.) Mendonça & E.P.Sousa and Zanthoxylum chalybeum Engl., if adequately explored could be instrumental in the discovery and development of health promoting, pharmaceutical products and drugs.
Six indigenous medicinal plants species, Agapanthus inapertus, Cheilanthes hirta, Crassula capitella, Eriospermum flagelliforme, Euphorbia clavarioides and Pelargonium alchemilloides are used traditionally in South Africa to treat wounds without scientific evidence as wound healing agents. Consequently, this study sought to investigate the antioxidant and anti-inflammatory activities of these plants species as a first step towards their validation as wound healing agents. The 2,2-diphenyl-1-picrylhydrazyl (DPPH), nitric oxide (NO), ferric reducing antioxidant power (FRAP), and β-carotene-linoleic acid model system (β-CLAMS) assays were used to test for antioxidant activity. The inhibition of the xanthine oxidase (XO), cyclooxygenase -2 (COX-2) and 15- lipoxygenase (15-LOX) as well as the extracts’ ability to preserve the cyclooxygenase-1 (COX-1) enzyme activity were used as anti-inflammatory models. Furthermore, the total phenolics, flavonoids and proanthocyanidins content were quantified using standard methods. Species, C. hirta displayed high flavonoid and proanthocyanidin content whilst C. capitella displayed high phenolic content, and good activity against the four used antioxidant models compared to standards, butylated hydroxytoluene and ascorbic acid. Majority of the extracts displayed significantly higher anti-xanthine oxidase activity, outperforming standard quercetin. The acetone extracts of A. inapertus (IC50 = 57.33 ± 0.30 µg/mL), E. flagelliforme (IC50 = 52.10 ± 0.98 µg/mL), P. alchemilloides (IC50 = 58.28 ± 0.94 µg/mL) and E. clavarioides water (IC50 = 50.53 ± 0.47 µg/mL) extract displayed moderate 15-LOX inhibition compared to standard, nordihydroguaiaretic acid (IC50 = 0.45 ± 0.01 µg/mL). The acetone extracts of C. capitella (IC50 = 3.16 ± 0.06 µg/mL), E. flagelliforme (IC50 = 1.13 ± 0.09 µg/mL), E. clavarioides (IC50 = 1.84 ± 0.18 µg/mL), P. alchemilloides (IC50 = 1.13 ± 0.14 µg/mL), and the E. clavarioides water extract (IC50 = 1.18 ± 0.11 µg/mL) displayed COX-2 inhibition comparable to that of standard, aspirin (IC50 = 1.11 ± 0.03 µg/mL). At some degree, all tested extracts preserved the activity of the COX-1 enzyme with the E. clavarioides acetone extract significantly preserving the activity of COX-1 (IC50 = 96.21 ± 0.18 µg/mL), compared to standard, aspirin (IC50 = 0.98 ± 0.06 µg/mL). The antioxidant and anti-inflammatory activities displayed by these medicinal plants support their application and beneficial effect in wounds healing and hold promising prospects as natural alternatives to the existing conventional treatments.
Aims
To provide global, regional, and country-level estimates of diabetes prevalence and health expenditures for 2021 and projections for 2045.
Methods
A total of 219 data sources meeting pre-established quality criteria reporting research conducted between 2005 and 2020 and representing 215 countries and territories were identified. For countries without data meeting quality criteria, estimates were extrapolated from countries with similar economies, ethnicity, geography and language. Logistic regression was used to generate smoothed age-specific diabetes prevalence estimates. Diabetes-related health expenditures were estimated using an attributable fraction method. The 2021 diabetes prevalence estimates were applied to population estimates for 2045 to project future prevalence.
Results
The global diabetes prevalence in 20–79 year olds in 2021 was estimated to be 10.5% (536.6 million people), rising to 12.2% (783.2 million) in 2045. Diabetes prevalence was similar in men and women and was highest in those aged 75–79 years. Prevalence (in 2021) was estimated to be higher in urban (12.1%) than rural (8.3%) areas, and in high-income (11.1%) compared to low-income countries (5.5%). The greatest relative increase in the prevalence of diabetes between 2021 and 2045 is expected to occur in middle-income countries (21.1%) compared to high- (12.2%) and low-income (11.9%) countries. Global diabetes-related health expenditures were estimated at 966 billion USD in 2021, and are projected to reach 1,054 billion USD by 2045.
Conclusions
Just over half a billion people are living with diabetes worldwide which means that over 10.5% of the world’s adult population now have this condition.
α-Glucosidase inhibition of 11 flavonoids, including myricetins, quercetins and catechins were studied through initial reaction velocity, IC50 value, inhibition kinetics, fluorescence quenching and molecular docking. It was found that C4=O, C2=C3, 3-OH and 5’-OH were essential moieties for α-glucosidase inhibition of myricetin that was shown with the highest inhibitory activity. The trans-conformational catechins was shown with stronger inhibition effects than the cis-conformational ones. Further, gallocatechin was an uncompetitive inhibitor, while myricetin, myricetrin, quercetin and catechin were competitive ones. 3-OH and 5’-OH promoted myricetin to bind with the enzyme active site through hydrogen bondings. The presence of C4=O and C2=C3 increased electron delocalization in ring A-C for myricetin and quercetin, and this enhanced stability of π-conjugations with aromatic residues of amino acids. However, 5’-OH decreased the quenching effects because it limited π-conjugations of ring B with key fluorescent residues. Notably, for same flavonoid sort, the constants that indicate binding affinity of flavonoids to α-glucosidase, including reciprocal of competitive inhibition constant, fluorescence quenching constant and binding energy followed same order as the inhibitory activity, indicating that α-glucosidase inhibition of the flavonoids resulted from binding interactions between them, and that the methods above can be combined reasonably to characterize flavonoid-enzyme binding interactions.
Herbal medicine use is common in rural communities of Zimbabwe since generic drugs are expensive and not readily available. In this work, we carried out phytochemical screening of secondary metabolites and used GC MS and tandem mass spectroscopy (LC MS/MS) to characterize Xeroderris stuhlmannii (Taub.) Mendonca & E.P. Sousa bark extracts. The activity of bark extracts on six bacterial strains were tested in vitro using the disc diffusion method. Qualitative screening of secondary metabolites confirmed the presence of alkaloids, flavonoids, terpenoids, steroids and polyphenols in the crude bark extracts. Methanol extracted more secondary metabolites compared to other solvents. The minimum inhibitory concentrations (MICs) values for the crude extracts on six bacterial strains ranged from 0.23–0.80 mg/mL. Antibacterial tests showed higher potency for crude bark extracts on E. Coli (MIC, 0.232 mg/mL) and lower potency on coliform (MIC, 0.798 mg/mL). LC-MS/MS analysis of various fractions confirmed the presence of twenty-eight phytochemicals whereas, twelve phytochemicals were identified using GC-MS. Both techniques confirmed the presence of ursolic acid, roburic acid, reticuline, rotenone and p-coumaric acid glucoside in hexane and methanol extracts. Our findings demonstrate that Xeroderris stuhlmannii (Taub.) Mendonca & E.P. Sousa contain many phytochemical compounds that have antibacterial activity. Some of these compounds in the bark extract possess antioxidant, antiviral, antitumor and anti-inflammatory properties. Thus, Xeroderris stuhlmannii (Taub.) Mendonca & E.P. Sousa barks can act as a useful herbal supplement for treatment of a number of diseases in rural communities. Future work will involve isolation of bioactive phytochemicals and their full characterization using LC MS/MS as well as testing their antioxidant, antidiabetic, anticancer properties and toxicity.
Aims:
To provide global estimates of diabetes prevalence for 2019 and projections for 2030 and 2045.
Methods:
A total of 255 high-quality data sources, published between 1990 and 2018 and representing 138 countries were identified. For countries without high quality in-country data, estimates were extrapolated from similar countries matched by economy, ethnicity, geography and language. Logistic regression was used to generate smoothed age-specific diabetes prevalence estimates (including previously undiagnosed diabetes) in adults aged 20-79 years.
Results:
The global diabetes prevalence in 2019 is estimated to be 9.3% (463 million people), rising to 10.2% (578 million) by 2030 and 10.9% (700 million) by 2045. The prevalence is higher in urban (10.8%) than rural (7.2%) areas, and in high-income (10.4%) than low-income countries (4.0%). One in two (50.1%) people living with diabetes do not know that they have diabetes. The global prevalence of impaired glucose tolerance is estimated to be 7.5% (374 million) in 2019 and projected to reach 8.0% (454 million) by 2030 and 8.6% (548 million) by 2045.
Conclusions:
Just under half a billion people are living with diabetes worldwide and the number is projected to increase by 25% in 2030 and 51% in 2045.
The cytochrome P450 (P450) enzymes first attracted interest because of their relevance to the metabolism of drugs, steroids, and carcinogens. Collectively, the 57 human P450s are involved in approximately three fourths of the metabolism of marketed drugs. Many of the steroid-oxidizing P450s have important roles in endocrinology. The roles of individual P450s can be predicted during drug development, and many drug–drug interactions are understood in the context of P450s. The human P450s involved in the metabolism of many carcinogens have been identified, and this information forms the basis for investigation into the human risk of these chemicals. Many questions still remain about the physiological roles of many human P450s, the relevance of the reactions they catalyze, and even the chemistry of some of the reactions. In this chapter, each of the 57 human P450s is discussed regarding current information about sites of expression, regulation, genetic variation, substrates and reactions, structures, inhibitors, and clinical issues.
Background:
The effect of in vivo treatment with ursolic acid (UA) on glycemia in hyperglycemic rats and its mechanism of action on muscle were studied.
Methods:
The UA effects on glycemia, glycogen, LDH, calcium and on insulin levels were evaluated after glucose tolerance curve. The β-cells were evaluated through the transmission electron microscopy. UA mechanism of action was studied on muscles through the glucose uptake with/without specific insulin signaling inhibitors. The nuclear effect of UA and the GLUT4 expression on muscle were studied using thymidine, GLUT4 immunocontent, immunofluorescence and RT-PCR.
Results:
UA presented a potent antihyperglycemic effect, increased insulin vesicle translocation, insulin secretion and augmented glycogen content. Also, UA stimulates the glucose uptake through the involvement of the classical insulin signaling related to the GLUT4 translocation to the plasma membrane as well as the GLUT4 synthesis. These were characterized by increasing the GLUT4 mRNA expression, the activation of DNA transcription, the expression of GLUT4 and its presence at plasma membrane. Also, the modulation of calcium, phospholipase C, protein kinase C and PKCaM II is mandatory for the full stimulatory effect of UA on glucose uptake. UA did not change the serum LDH and serum calcium balance.
Conclusions:
The antihyperglycemic role of UA is mediated through insulin secretion and insulinomimetic effect on glucose uptake, synthesis and translocation of GLUT4 by a mechanism of cross-talk between calcium and protein kinases.
General significance:
UA is a potential anti-diabetic agent with pharmacological properties for insulin resistance and diabetes therapy.
It is increasingly apparent that not only is a cure for the current worldwide diabetes epidemic required, but also for its major complications, affecting both small and large blood vessels. These complications occur in the majority of individuals with both type 1 and type 2 diabetes. Among the most prevalent microvascular complications are kidney disease, blindness, and amputations, with current therapies only slowing disease progression. Impaired kidney function, exhibited as a reduced glomerular filtration rate, is also a major risk factor for macrovascular complications, such as heart attacks and strokes. There have been a large number of new therapies tested in clinical trials for diabetic complications, with, in general, rather disappointing results. Indeed, it remains to be fully defined as to which pathways in diabetic complications are essentially protective rather than pathological, in terms of their effects on the underlying disease process. Furthermore, seemingly independent pathways are also showing significant interactions with each other to exacerbate pathology. Interestingly, some of these pathways may not only play key roles in complications but also in the development of diabetes per se. This review aims to comprehensively discuss the well validated, as well as putative mechanisms involved in the development of diabetic complications. In addition, new fields of research, which warrant further investigation as potential therapeutic targets of the future, will be highlighted.
The increasing prevalence of diabetes has accelerated the search for new drugs derived from natural sources. To define the functional features of two such families of compounds, the flavonols and the ethyl caffeates, we have determined the high-resolution structures of representative inhibitors in complex with human pancreatic α-amylase. Myricetin binds at the active site and interacts directly with the catalytic residues despite its bulky planar nature. Notably, it reduces the normal conformational flexibility of the adjacent substrate binding cleft. In contrast, bound ethyl caffeate acts by disordering precisely those polypeptide chain segments that make up the active site binding cleft. It also operates from binding sites far removed from the active site, a property not observed in any other class of human α-amylase inhibitor studied to date. Given the current inadequacy of drugs directed at diabetes, the use of optimized flavonols and ethyl caffeates may present an alternative therapeutic route.
Two household surveys undertaken in Zimbabwe between 1981 and 1983 revealed extensive use of indigenous plant remedies in the home-management of childhood diarrhoea and many adult illnesses. Names of the local plants, trees and shrubs are listed, together with the part of the plant used and the type of condition treated. The usage of medicinal plants underscores the need for further study of indigenous pharmacopoeias and the therapeutic properties of plants. The role of indigenous plant remedies within local health care systems is also worthy of closer investigation.
A mechanistic study of the essential allosteric activation of human pancreatic alpha-amylase by chloride ion has been conducted by exploring a wide range of anion substitutions through kinetic and structural experiments. Surprisingly, kinetic studies indicate that the majority of these alternative anions can induce some level of enzymatic activity despite very different atomic geometries, sizes, and polyatomic natures. These data and subsequent structural studies attest to the remarkable plasticity of the chloride binding site, even though earlier structural studies of wild-type human pancreatic alpha-amylase suggested this site would likely be restricted to chloride binding. Notably, no apparent relationship is observed between anion binding affinity and relative activity, emphasizing the complexity of the relationship between chloride binding parameters and the activation mechanism that facilitates catalysis. Of the anions studied, particularly intriguing in terms of observed trends in substrate kinetics and their novel atomic compositions were the nitrite, nitrate, and azide anions, the latter of which was found to enhance the relative activity of human pancreatic alpha-amylase by nearly 5-fold. Structural studies have provided considerable insight into the nature of the interactions formed in the chloride binding site by the nitrite and nitrate anions. To probe the role such interactions play in allosteric activation, further structural analyses were conducted in the presence of acarbose, which served as a sensitive reporter molecule of the catalytic ability of these modified enzymes to carry out its expected rearrangement by human pancreatic alpha-amylase. These studies show that the largest anion of this group, nitrate, can comfortably fit in the chloride binding pocket, making all the necessary hydrogen bonds. Further, this anion has nearly the same ability to activate human pancreatic alpha-amylase and leads to the production of the same acarbose product. In contrast, while nitrite considerably boosts the relative activity of human pancreatic alpha-amylase, its presence leads to changes in the electrostatic environment and active site conformations that substantially modify catalytic parameters and produce a novel acarbose rearrangement product. In particular, nitrite-substituted human pancreatic alpha-amylase demonstrates the unique ability to cleave acarbose into its acarviosine and maltose parts and carry out a previously unseen product elongation. In a completely unexpected turn of events, structural studies show that in azide-bound human pancreatic alpha-amylase, the normally resident chloride ion is retained in its binding site and an azide anion is found bound in an embedded side pocket in the substrate binding cleft. These results clearly indicate that azide enzymatic activation occurs via a mechanism distinct from that of the nitrite and nitrate anions.
AutoDock Vina: improving the speed and accuracy of docking with a new scoring function, efficient optimization, and multithreading
- Trott
Trott, O., Olson, A.J., 2009. AutoDock Vina: improving the speed and accuracy of
docking with a new scoring function, efficient optimization, and multithreading.
J. Comput. Chem. 455-461. https://doi.org/10.1002/jcc.21334.