Exploring the antidiabetic potential of Salvia officinalis using network pharmacology, molecular docking and ADME/drug-likeness predictions

A combination of network pharmacology, molecular docking and ADME/drug-likeness predictions was employed to explore the potential of Salvia officinalis compounds to interact with key targets involved in the pathogenesis of T2DM. These were predicted using the SwissTargetPrediction, Similarity Ensemble Approach and BindingDB databases. Networks were constructed using the STRING online tool and Cytoscape (v.3.9.1) software. Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways analysis and molecular docking were performed using DAVID, SHINEGO 0.77 and MOE suite, respectively. ADME/drug-likeness parameters were computed using SwissADME and Molsoft L.L.C. The top-ranking targets were CTNNB1, JUN, ESR1, RELA, NR3C1, CREB1, PPARG, PTGS2, CYP3A4, MMP9, UGT2B7, CYP2C19, SLCO1B1, AR, CYP19A1, PARP1, CYP1A2, CYP1B1, HSD17B1, and GSK3B. Apigenin, caffeic acid, oleanolic acid, rosmarinic acid, hispidulin, and salvianolic acid B showed the highest degree of connections in the compound-target network. Gene enrichment analysis identified pathways involved in insulin resistance, adherens junctions, metabolic processes, IL-17, TNF-α, cAMP, relaxin, and AGE-RAGE in diabetic complications. Rosmarinic acid, caffeic acid, and salvianolic acid B showed the most promising interactions with PTGS2, DPP4, AMY1A, PTB1B, PPARG, GSK3B and RELA. Overall, this study enhances understanding of the antidiabetic activity of S. officinalis and provides further insights for future drug discovery purposes

Phytochemical, Nutritional Composition and Heavy Metals Content of Allium cepa (Onion) and Allium sativum (Garlic) from Wudil Central Market, Kano State, Nigeria

Allium plants are common spices used as food ingredients. Allium cepa (onion) and Allium sativum (garlic) are cultivated in Wudil town. In this study the qualitative and quantitative phytochemicals in Allium cepa revealed the presence of alkaloids (6.45mg/kg), tannins (1.25mg/kg), flavonoids (1.51mg/kg), total phenolic (20.68mg/kg) while saponin was absent. On the other hand Allium sativum shows alkaloids (4.68mg/kg), tannin (0.25mg/kg) and saponin (0.44mg/kg). Proximate composition of garlic show (p<0.05) increase in fat (2.82%), carbohydrate (24.55%), fibre (2.74%), and ash (4.22%) when compared with onion, while protein (2.96%) and moisture (87.36%) are (p<0.005) higher in onion. Anti-nutritional factors present in onion show (p<0.05) increase in oxalate (11.85mg/kg) and tannins (0.76mg/kg), while garlic shows (p<0.05) increase in phytate (1.79mg/kg) and hydrogen cyanide (0.39mg/kg). Heavy metals in onion were (p<0.05) higher in Cd, Cu, Fe, Pb, and Mn, while garlic only show (p<0.05) increase in Zn and Co. The Cr in onion shows (p>0.05) difference when compared with garlic. Cd and Pb in onion and garlic were above WHO recommended safe limits in vegetables. From this study it is observed that the agro-climatic condition may have effect on the phytochemicals of both plants samples from Wudil, while sources of the heavy metals need to be investigated and controlled from level of cultivation to that of processing

Drug-Induced Hepatotoxicity

This chapter aims at discussing the consequential effects of drug-induced hepatotoxicity on man. The liver carries out drug detoxification among other roles, but sometimes, drug toxicity can occur caused by either medication overdose or imbalance drug metabolic reactions (Phase 1 & 2), resulting in the formation of reactive (toxic) metabolites (electrophilic compounds or free radicals) that binds covalently to hepatocytes, leading to liver injury/diseases like acute and chronic hepatitis, cholestasis, steatosis among others. Mitochondrial dysfunction, oxidative stress and lipid peroxidation are some of the mechanisms of liver injury. Furthermore, drug hepatotoxicity results in hepatocellular, gastroenterological, cholestatic as well as immunological disorders. The clinical manifestations of drug toxicity arise from the abnormalities observed in liver’s biochemical and molecular indicators. Our findings, revealed that in the event of liver injury, liver function indices like aspartate and alanine aminotransferases, ALP (alkaline phosphatase) and gamma glutamyl transferase (GGT) activities, intracellular calcium (Ca2+) and lipid peroxidation increases whereas indices of oxidative stress such as glutathione and its allies, catalase and superoxide dismutase activity deplete. At molecular level, the gene expression levels of Bcl-2 mRNA and microRNA genes (miR-122, 192 and 194) reduces while mitochondrial genes (MMP-2 and MMP-9) overexpresses. Since drug abuse is deleterious to human health, therefore, adherence to doctors’ prescription guidelines should be followed

Pyrethroid resistance in the Sudan Savannah Region in Nigeria: a study of the resistance profile and resistance mechanism of Anopheles populations from Hadejia Town in Jigawa State

Insecticide-based control measures are key strategies against malaria vectors, and pyrethroid is the only recommended class of insecticide for public health use. The work aimed at determining the pyrethroid resistance in Anopheline mosquitoes and the frequency of the knockdown resistance (kdr) gene determinant. Larval samples were collected from two sites in Hadejia Town, Jigawa State in April 2020 and November/December 2020, and reared to adulthood in Bayero University Kano Biochemistry's insectary. Samples were identified by morphological and molecular techniques. Three to five-day-old adult mosquitoes were exposed to standard concentrations of 0.75% permethrin and 0.05% deltamethrin according to WHO criteria. Kdr mutations were investigated using PCR. Results of morphological identification showed an abundance (100%) of the Anopheles gambiae complex. However, molecular identification showed varying percentages of An. gambiae s.s (15% and 35%), An. coluzzii (80% and 45%), and An. arabiensis (5% and 20%) each for agricultural and industrial sites, respectively. The result also revealed relatively higher KT50 and KT50 in the agricultural site and was relatively higher with permethrin based on the KT50. Higher insecticide resistance of Anopheles mosquitoes observed in the agricultural site suggests that the practice may affect resistance development. The frequency of negative (homozygous) L1014F kdr mutation genotype was 70% in the resistant (alive) mosquito population and 50% in the susceptible (dead) mosquito population. The frequency of kdr mutation for agricultural and industrial sites was 35% and 15%, respectively. This finding suggests that the kdr gene determinant may not be the only mechanism involved in the resistance of the Anopheline mosquito to pyrethroid

In vitro and in vivo anti-diabetic and anti-oxidant activities of methanolic leaf extracts of Ocimum canum

Background: Diabetes is a metabolic disorder with a highly complex, multifaceted and intricate etiologies and thus may require management options that proffers multimodal mechanism of action. This present study evaluated the antidiabetic and antioxidant potential of the methanolic extract/fractions of leaves of Ocimum canum. Methods: The antidiabetic potential was evaluated and using STZ-induced diabetic Wistar rat model (in vivo) and inhibition of α-amylase and α-glucosidase activity (in vitro).  Antioxidant activity was assessed in vitro by free radical scavenging and reducing power assays and in vivo via monitoring SOD and CAT activities; GSH and MDA levels. Results: The total phenolic content (221.0±3.0 mg catechol/g of sample) and tannins (146.0±4.0 mg tannic acid/g of sample) of the crude extract; and flavonoid of the aqueous-methanol fraction (216.0.0±1.0 mg of rutin/g of sample) were found to be significantly higher relative to others. The crude extract and the aqueous-methanol fraction exhibited a significantly (p<0.05) higher percentage reduction in fasting blood glucose and a concomitant increase in serum insulin level relative to the diabetic control group. The highest radical scavenging activity and reducing power were observed in the aqueous-methanol fraction. The aqueous-methanol solvent fraction also significantly reversed the alterations in oxidative stress markers occasioned by the diabetic condition. Conclusion: In conclusion, the result of the present study has demonstrated evidently that extracts of Ocimum canum leaves ameliorates hyperglycemia and the associated oxidative stress in STZ-induced rats

Therapeutic effect of the solvent fraction of hexane leaf extract of Tapinanthus bangwensis (Engl. & K. Krause) (Loranthaceae) in alloxan-induced pathology in diabetic rats

Plant-based products are gradually replacing pharmaceuticals in treating ailments, including diabetes, due to their safety, cost-effectiveness, potency, and availability. Therefore, the current study looked into the therapeutic effect of the solvent fraction of hexane leaf extract of Tapinanthus bangwensis (HEXETACF) (Loranthaceae) in alloxan-induced pathology in diabetic rats. The biochemical parameters were estimated using analytical grade kits via spectrophotometric method. The laboratory rats were distributed into group W (five rats on feed and water), group X (seven rats + 150 mg/kg alloxan solution only), group Y (seven rats + 150 mg/kg alloxan solution + 200 mg/kg BW silymarin for 21 days), and group Z (seven rats + 150 mg/kg alloxan solution + 250 mg/kg BW HEXETACF for 21 days). The results showed that HEXETACF and silymarin (SILY) reduced blood glucose concentration by 33.77% and 34.80%, respectively, after the 21st day of treatment (p < 0.05). Additionally, alkaline phosphatase (ALP) and alanine aminotransferase (ALT) activity in SILY and HEXETACF were significantly decreased compared to the diabetic group (p < 0.05), but no significant decrease in aspartate aminotransferase (AST) activity was observed between the test samples and the diabetic group. Furthermore, the test samples lowered malondialdehyde (MDA) levels, by improving glutathione, superoxide dismutase (SOD), and catalase (CAT) activity. The HEXETACF and SILY significantly decreased triglyceride levels (TG) compared to the diabetic group at p < 0.05. They also reduced low-density lipoprotein (LDL) and cholesterol levels and increased the high-density lipoprotein levels compared to the diabetic group. Additionally, no significant decrease in serum electrolytes (Na+, K+, and Cl-), urea, and creatinine (including albumin and total protein) values was observed in HEXETACF and SILY, while hematological indices increased compared to the diabetic group. Histology results revealed that the test samples had normalized glomeruli, β-islet cells, and hepatocytes. However, a trace of mild congestion was noticed in the STDG. But edemic blood congestion was observed in the diabetic group. In conclusion, the current result demonstrated that HEXETACF may be a promising antidiabetic agent that could replace mSILY

Molecular docking and prediction of ADME/drug-likeness properties of potentially active antidiabetic compounds isolated from aqueous-methanol extracts of Gymnema sylvestre and Combretum micranthum

Gymnema sylvestre and Combretum micranthum are well known for their ethno-medicinal uses in the northwest of Nigeria. In our recent study, we demonstrated the antidiabetic and antioxidant activities of the aqueous-methanol extracts of the two plants and identified some potentially active compounds. The present study aimed to conduct molecular docking and ADME/drug-likeness screening of the identified potentially active candidate compounds from aqueous-methanol extracts of G. sylvestre and C. micranthum leaves by using in silico techniques. Molecular docking of compounds on target proteins (α-amylase, α-glucosidase, and phosphorylated insulin receptor tyrosine kinase) was performed using Molsoft ICM-pro 3.8-3. The physicochemical, ADME, and drug-likeness parameters were computed using the SwissADME online program. The result corroborated the antidiabetic activities of the plants with significant binding interactions between compounds A (2,2-dimethyl-3-[4-(acetyloxy)phenyl]-4-ethyl2H-1-benzopyran-7-ol acetate), D (9,13-di-cis-retinoic acid), E (4-hydroxycinnamic acid), F ((-)-11-hydroxy-9,10-dihydrojasmonic acid), G (colnelenic acid), H (glyinflanin A), I (6,8a-seco-6,8a-deoxy-5-oxoavermectin “2a” aglycone), and J (3-deshydroxysappanol trimethyl ether) and at least one of the three target proteins. Four compounds, namely A (2,2-dimethyl-3-[4-(acetyloxy)phenyl]-4-ethyl-2H-1-benzopyran-7-ol acetate), E (4-hydroxycinnamic acid), H (glyinflanin A), and J (3-deshydroxysappanol trimethyl ether), yielded the best docking scores with respect to the target proteins, of which three (E (4-hydroxycinnamic acid), H (glyinflanin A), and J (3-deshydroxysappanol trimethyl ether)) were identified to have relatively optimal drug-likeness and medicinal chemistry characteristics. Thus, the present study concluded that these compounds may have contributed to the observed antidiabetic properties of these plants and can be investigated further as drugs or drug-like compound candidates

Epidemiological survey of hypertension in Anambra state, Nigeria

Background: Hypertension is a major public health problem worldwide. Estimating the prevalence of disease in populations of Nigeria would be useful in developing intervention programs to control it and prevent its consequences.Objective: This survey was carried out to assess the prevalence, awareness, treatment, detection and risk factors of hypertension in three major populations - Onitsha, Nnewi and Awka cities of Anambra State.Methods: The study was a church based cross sectional study involving 912 participants randomly selected from the three major zones in Anambra State. The age range of the participants was 17-79 years. Participants were administered with a well-structured questionnaire and their blood pressures (BP) as well as anthropometric measurements were taken using standard instruments.Results: The study population (n = 912) consists, 476 (52.16%) females and 436 (47.81%) males; sampled randomly from Awka, Onitsha and Nnewi. The overall crude prevalence of hypertension and prehypertension in the study population were 22.81% and 42.54% respectively. The crude prevalence of hypertension in the three cities - Onitsha, Awka and Nnewi were 32.56%, 19.665 and 16.40% respectively. The prevalence of hypertension was significantly higher in Onitsha (P = 0.0001). The prevalence of hypertension in both sexes was not statistically different (male, 22.01% and female, 23.5% P = 0.587). Mean BMI, Systolic, and Diastolic BP for the study population was 25.43 ± 4.2, 120.7 ± 18.39 and 78.21 ± 12.57 respectively. Systolic and diastolic BP correlated with age and anthropometric measures such as waist circumference, BMI, Hip circumference, weight and height. The following factors were strongly associated with the prevalence of hypertension in our study population: Age (χ2 = 110.87, P = 0.000); Zone (χ2 = 25.19, P = 0.000); BMI (χ2 = 45.51, P = 0.000); Physical Activity(χ2 = 58.08, P = 0.000);Alcohol Consumption (χ2 = 32.27, P = 0.000); Smoking (χ2 = 7.892, P = 0.000); General Health status (χ2 = 46,62, P = 0.000); Consumption of fatty food (χ2 = 29.35, P = 0.000). A low percentage of the population, 9.76% reported previous diagnosis of high BP and 34.59% of 910 of the participants also reported previous BP diagnosis of any relative. Our result shows that the prevalence of hypertension and prehypertension in this population was high and associated with some modifiable risk factors. In addition, poor detection, treatment and control of hypertension in this population were observed. This underscores the need for comprehensive evaluation of the prevalence of hypertension and other cardiovascular diseases in Nigeria.Keywords: Anambra state, epidemiology, hypertension, prevalence, risk factor

Lipase-Catalyzed Synthesis, Antioxidant Activity, Antimicrobial Properties and Molecular Docking Studies of Butyl Dihydrocaffeate

Green chemistry approaches, such as lipase-catalyzed esterification, are promising methods for obtaining valuable chemical compounds. In the case of the use of lipases, unlike in aqueous environments, the processes of the ester bond formations are encountered in organic solvents. The aim of the current research was to carry out the lipase-catalyzed synthesis of an ester of dihydrocaffeic acid. The synthesized compound was then evaluated for antioxidant and antimicrobial activities. However, the vast majority of its antioxidant activity was retained, which was demonstrated by means of DPPH· (2,2-diphenyl-1-picrylhydrazyl) and CUPRAC (cupric ion reducing antioxidant capacity) methods. Regarding its antimicrobial properties, the antifungal activity against Rhizopus oryzae is worth mentioning. The minimum inhibitory and fungicidal concentrations were 1 and 2 mM, respectively. The high antifungal activity prompted the use of molecular docking studies to verify potential protein targets for butyl ester of dihydrocaffeic ester. In the case of one fungal protein, namely 14-α sterol demethylase B, it was observed that the ester had comparable binding energy to the triazole medication, isavuconazole, but the interacted amino acid residues were different

Cytotoxic and Hepatocurative Effect of Aqueous Fraction of Against Paracetamol-Induced Hepatotoxicity

Medicinal plants over time have proven to have potential to manage a huge number of diseases and disorders and thus have become a great source of pharmaceutical drugs. One of such plants is Tapinanthus bangwensis (African mistletoe). It is a semiparasitic and epiphytic plant growing on citrus tree, obtaining its food photosynthetically while its nutrient and water is got from the host plant. The aim of this study was to determine the cytotoxicological and hepatocurative effect of aqueous fraction of T bangwensis in acetaminophen (paracetamol)-induced Wistar rats. The antioxidant potential of the plant was determined by 2,2-diphenyl-1-picrylhydrazine scavenging and ferric reducing power assays. The cytotoxic effect was determined using Allium cepa test while the liver biochemical indices were determined by standard protocols. Data obtained were analyzed by 2-way analysis of variance at 95% confidence level and reported as mean ± standard deviation. The concentrated aqueous fraction of T bangwensis was found to be 23.3 g (58.25%). Quantitative determination of some vital phytochemicals revealed the following: flavonoid (84.6 ± 0.41 mg/100 g), phenol (147.5 ± 1.07 mg/100 g), tannin (31 ± 0.85 mg/ 100 g), alkaloid (23.45 ± 0.09 mg/100 g), and saponin (0.146 ± 0.0 mg/100 g). Treatment of rats with the aqueous extract of T bangwensis significantly decreased paracetamol-induced elevation of activities of liver function indices, alkaline phosphatase, alanine aminotransferase, aspartate aminotransferase, triglyceride, total cholesterol level and increased the albumin, total protein, and high-density lipoprotein levels. The plant extract also attenuated the paracetamol elevated lipid peroxidation product, malondialdehyde. The research findings suggest that aqueous extract of T bangwensis is slightly cytotoxic, possesses appreciable antioxidant property and exhibited hepatocurative effect against paracetamol-induced hepatoxicity