Sudip Paul

Physicochemical Properties, Minerals, Trace Elements, and Heavy Metals in Honey of Different Origins: A Comprehensive Review

Honey is a popular natural food product with a very complex composition mainly consisting of both organic and inorganic constituents. The composition of honey is strongly influenced by both natural and anthropogenic factors, which vary based on its botanical and geographical origins. Although minerals and heavy metals are minor constituents of honey, they play vital role in determining its quality. There are several different analytical methods used to determine the chemical elements in honey. These methods are typically based on spectroscopy or spectrometry techniques (including atomic absorption spectrometry, atomic emission spectrometry, inductively coupled plasma mass spectrometry, and inductively coupled plasma optical emission spectrometry). This review compiles available scientific information on minerals and heavy metals in honey reported from all over the world. To date, 54 chemical elements in various types of honey have been identified and can be divided into 3 groups: major or macroelements (Na, K, Ca, Mg, P, S, Cl), minor or trace elements (Al, Cu, Pb, Zn, Mn, Cd, Tl, Co, Ni, Rb, Ba, Be, Bi, U, V, Fe, Pt, Pd, Te, Hf, Mo, Sn, Sb, La, I, Sm, Tb, Dy, Sd, Th, Pr, Nd, Tm, Yb, Lu, Gd, Ho, Er, Ce, Cr, As, B, Br, Cd, Hg, Se, Sr), and heavy metals (trace elements that have a specific gravity at least 5 times higher than that of water and inorganic sources). Chemical elements in honey samples throughout the world vary in terms of concentrations and are also influenced by environmental pollution.

Amelioration of Isoproterenol-Induced Oxidative Damage in Rat Myocardium by Withania somnifera Leaf Extract

We investigated the protective role of Withania somnifera leaf extract (WSLEt) on isoproterenol- (ISO-) induced myocardial infarction (MI) in rats. Subcutaneous injection of ISO (85 mg/kg body weight (b.w.)) administered to rats for two consecutive days caused a significant increase in cardiac troponin I (cTnI) levels and serum lipid profiles, as well as the activities of some marker enzymes. In addition to these diagnostic markers, there were increased levels of lipid peroxidation (LPO) and decreased activities of enzymatic antioxidants (superoxide dismutase (SOD), glutathione peroxidase (GPx), glutathione reductase (GRx), and glutathione-S-transferase (GST)) in the myocardium. However, oral pretreatment (100 mg/kg b.w.) with WSLEt for 4 weeks elicited a significant cardioprotective activity by lowering the levels of cTnI, lipid profiles, and marker enzymes. The levels of LPO products were also significantly decreased. Elevated activities of antioxidant enzymes were also observed in rats pretreated with WSLEt. As further confirmed histopathologically, our findings strongly suggest that the cardioprotective effect of WSLEt on myocardium experiencing ISO-induced oxidative damage may be due to an augmentation of the endogenous antioxidant system and an inhibition of LPO in the myocardial membrane. We conclude that WSLEt confers some protection against oxidative damage in ISO-induced MI in rats.

Satkara (Citrus macroptera) Fruit Protects against Acetaminophen-Induced Hepatorenal Toxicity in Rats

Although Citrus macroptera (Rutaceae), an indigenous fruit in Bangladesh, has long been used in folk medicine, however, there is a lack of information concerning its protective effects against oxidative damage. The protective effects of an ethanol extract of Citrus macroptera (EECM) against acetaminophen-induced hepatotoxicity and nephrotoxicity were investigated in rats. Rats (treatment groups) were pretreated with EECM at doses of 250, 500, and 1000 mg/kg, respectively, orally for 30 days followed by acetaminophen administration. Silymarin (100 mg/kg) was administered as a standard drug over a similar treatment period. Our findings indicated that oral administration of acetaminophen induced severe hepatic and renal injuries associated with oxidative stress, as observed by 2-fold higher lipid peroxidation (TBARS) compared to control. Pretreatment with EECM prior to acetaminophen administration significantly improved all investigated biochemical parameters, that is, transaminase activities, alkaline phosphatase, lactate dehydrogenase, γ-glutamyl transferase activities and total bilirubin, total cholesterol, triglyceride and creatinine, urea, uric acid, sodium, potassium and chloride ions, and TBARS levels. These findings were confirmed by histopathological examinations. The improvement was prominent in the group that received 1000 mg/kg EECM. These findings suggested that C. macroptera fruit could protect against acetaminophen-induced hepatonephrotoxicity, which might be via the inhibition of lipid peroxidation.

Impacts of Nonsynonymous Single Nucleotide Polymorphisms of Adiponectin Receptor 1 Gene on Corresponding Protein Stability: A Computational Approach

Despite the reported association of adiponectin receptor 1 (ADIPOR1) gene mutations with vulnerability to several human metabolic diseases, there is lack of computational analysis on the functional and structural impacts of single nucleotide polymorphisms (SNPs) of the human ADIPOR1 at protein level. Therefore, sequence- and structure-based computational tools were employed in this study to functionally and structurally characterize the coding nsSNPs of ADIPOR1 gene listed in the dbSNP database. Our in silico analysis by SIFT, nsSNPAnalyzer, PolyPhen-2, Fathmm, I-Mutant 2.0, SNPs&GO, PhD-SNP, PANTHER, and SNPeffect tools identified the nsSNPs with distorting functional impacts, namely, rs765425383 (A348G), rs752071352 (H341Y), rs759555652 (R324L), rs200326086 (L224F), and rs766267373 (L143P) from 74 nsSNPs of ADIPOR1 gene. Finally the aforementioned five deleterious nsSNPs were introduced using Swiss-PDB Viewer package within the X-ray crystal structure of ADIPOR1 protein, and changes in free energy for these mutations were computed. Although increased free energy was observed for all the mutants, the nsSNP H341Y caused the highest energy increase amongst all. RMSD and TM scores predicted that mutants were structurally similar to wild type protein. Our analyses suggested that the aforementioned variants especially H341Y could directly or indirectly destabilize the amino acid interactions and hydrogen bonding networks of ADIPOR1.

Antioxidant Properties and Cardioprotective Mechanism of Malaysian Propolis in Rats

Propolis contains high concentrations of polyphenols, flavonoids, tannins, ascorbic acid, and reducing sugars and proteins. Malaysian Propolis (MP) has been reported to exhibit high 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical-scavenging activity and ferric reducing antioxidant power (FRAP) values. Herein, we report the antioxidant properties and cardioprotective properties of MP in isoproterenol- (ISO-) induced myocardial infarction in rats. Male Wistar rats (n = 32) were pretreated orally with an ethanol extract of MP (100 mg/kg/day) for 30 consecutive days. Subcutaneous injection of ISO (85 mg/kg in saline) for two consecutive days caused a significant increase in serum cardiac marker enzymes and cardiac troponin I levels and altered serum lipid profiles. In addition significantly increased lipid peroxides and decreased activities of cellular antioxidant defense enzymes were observed in the myocardium. However, pretreatment of ischemic rats with MP ameliorated the biochemical parameters, indicating the protective effect of MP against ISO-induced ischemia in rats. Histopathological findings obtained for the myocardium further confirmed the biochemical findings. It is concluded that MP exhibits cardioprotective activity against ISO-induced oxidative stress through its direct cytotoxic radical-scavenging activities. It is also plausible that MP contributed to endogenous antioxidant enzyme activity via inhibition of lipid peroxidation.

Minerals, Toxic Heavy Metals, and Antioxidant Properties of Honeys from Bangladesh

The study reports on major and trace elements as well as antioxidant properties of honey samples from Bangladesh. Four major cationic elements, seven trace elements, and three heavy metals were determined in the 12 honey samples using atomic absorption spectrophotometer. Nutritional values in these honey samples were further investigated according to their antioxidant properties. The content of major elements was in the range of 62.75–616.58, 579.48–2219.43, 69.42–632.25, and 0.13–1.20 mg/kg for sodium, potassium, magnesium, and calcium, respectively. The trace elements varied in the range of 0.41–28, 0.12–3.54, 1.54–2.85, 0.29–0.59, 0.02–0.35, and 0.01–0.06 mg/kg for iron, zinc, copper, nickel, cobalt, and cadmium, respectively. Among the heavy metals, only lead (0.17–2.19 mg/kg) was detected. The results of antioxidant analysis based on phenolics, flavonoids, ascorbic acid, reducing sugar, and proteins (as nonphenolic antioxidants) revealed that multifloral raw honey samples contain significantly higher levels of reducing agents than monofloral and commercial brand honeys. The study provides a useful insight on the minerals, heavy metals, and antioxidant properties of honey samples commonly consumed in Bangladesh and found to be rich source of antioxidants and minerals. Some samples might pose some risk to the health due to lead contamination.

In silico analysis of nonsynonymous single nucleotide polymorphisms of the human adiponectin receptor 2 (ADIPOR2) gene

Polymorphisms of the ADIPOR2 gene are frequently linked to a higher risk of developing diseases including obesity, type 2 diabetes and cardiovascular diseases. Though mutations of the ADIPOR2 gene are detrimental, there is a lack of comprehensive in silico analyses of the functional and structural impacts at the protein level. Considering the involvement of ADIPOR2 in glucose uptake and fatty acid oxidation, an in silico functional analysis was conducted to explore the possible association between genetic mutations and phenotypic variations. A genomic analysis of 82 nonsynonymous SNPs in ADIPOR2 was initiated using SIFT followed by the SNAP2, nsSNPAnalyzer, PolyPhen-2, SNPs&GO, FATHMM and PROVEAN servers. A total of 10 mutations (R126W, L160Q, L195P, F201S, L235R, L235P, L256R, Y328H, E334K and Q349H) were predicted to have deleterious effects on the ADIPOR2 protein and were therefore selected for further analysis. Theoretical models of the variants were generated by comparative modeling via MODELLER 9.16. A protein structural analysis of these amino acid variants was performed using SNPeffect, I-Mutant, ConSurf, Swiss-PDB Viewer and NetSurfP to explore their solvent accessibility, molecular dynamics and energy minimization calculations. In addition, FTSite was used to predict the ligand binding sites, while NetGlycate, NetPhos2.0, UbPerd and SUMOplot were used to predict post-translational modification sites. All of the variants showed increased free energy, though F201S exhibited the highest energy increase. The root mean square deviation values of the modeled mutants strongly indicated likely pathogenicity. Remarkably, three binding sites were detected on ADIPOR2, and two mutations at positions 328 and 201 were found in the first and second binding pockets, respectively. Interestingly, no mutations were found at the post-translational modification sites. These genetic variants can provide a better understanding of the wide range of disease susceptibility associated with ADIPOR2 and aid the development of new molecular diagnostic markers for these diseases. The findings may also facilitate the development of novel therapeutic elements for associated diseases.

Protective mechanism of turmeric (Curcuma longa) on carbofuran-induced hematological and hepatic toxicities in a rat model

Abstract Context: Turmeric (Curcuma longa L. [Zingiberaceae]) is used in the treatment of a variety of conditions including pesticide-induced toxicity. Objective: The study reports the antioxidant properties and the protective effects of turmeric against carbofuran (CF)-induced toxicity in rats. Materials and methods: The antioxidant potential was determined by using free radicals scavenging activity and ferric reducing antioxidant power values. Male Wistar rats were randomly divided into four groups, designated as control, turmeric (100 mg/kg/day), CF (1 mg/kg/day) and turmeric (100 mg/kg/day) + CF (1 mg/kg/day) treatments. All of the doses were administered orally for 28 consecutive days. The biological activity of the turmeric and CF was determined by using several standard biochemical methods. Results: Turmeric contains high concentrations of polyphenols (8.97 ± 0.15 g GAEs), flavonoids (5.46 ± 0.29 g CEs), ascorbic acid (0.06 ± 0.00 mg AEs) and FRAP value (1972.66 ± 104.78 μM Fe2+) per 100 g of sample. Oral administration of CF caused significant changes in some of the blood indices, such as, mean corpuscular volume, corpuscular hemoglobin, white blood cell, platelet distribution width and induced severe hepatic injuries associated with oxidative stress, as observed by the significantly higher lipid peroxidation (LPO) levels when compared to control, while the activities of cellular antioxidant enzymes (including superoxide dismutase and glutathione peroxidase) were significantly suppressed in the liver tissue. Discussion and conclusion: Turmeric supplementation could protect against CF-induced hematological perturbations and hepatic injuries in rats, plausibly by the up-regulation of antioxidant enzymes and inhibition of LPO to confer the protective effect.

Assessment of Toxicity and Beneficiary Effects of Garcinia pedunculata on the Hematological, Biochemical, and Histological Homeostasis in Rats

This study was undertaken to investigate the toxicological profile of a methanolic extract of Garcinia pedunculata fruit in rats by conducting hematological, biochemical, and histopathological examinations. Long Evans rats were divided into four groups, each with 6 animals, and were treated with three oral doses (250, 500, and 1000 mg/kg) once daily for 21 days. The extract did not cause significant changes in body and relative organ weight, percent water content, or hematological parameters at any administered doses. However, a significant dose-dependent positive effect in serum lipid profile and all atherogenic indices including the cardiac risk ratio, Castellis risk index-2, and the atherogenic coefficient were observed. Significant increases in the levels of iron and decreases in serum alkaline phosphatase, alanine transaminase, and lactate dehydrogenase activities and the levels of serum glucose were noted when the extract was administered at the highest dose (1000 mg/kg). Histopathological examination of the target tissues further confirmed that the extract was safe and had no observed toxicological features. Our study indicates that G. pedunculata fruit is nontoxic, has the potential to be effective against atherosclerosis, and may be used as a hepatoprotectant. The fruit extract is also beneficial to those with iron deficiency and hyperglycemia.

Antihyperglycemic, Antidiabetic, and Antioxidant Effects of Garcinia pedunculata in Rats

The antihyperglycemic, antidiabetic, and antioxidant potentials of the methanolic extract of Garcinia pedunculata (GP) fruit in rats were investigated. The acute antihyperglycemic effect of different doses of GP was studied in normal male Wistar rats. Diabetes was induced by streptozotocin (STZ) injection in another cohort of male Wistar rats and they showed significantly higher blood glucose and glycated hemoglobin (HbA1c) levels, altered lipid profiles, and lower insulin levels compared to nondiabetic control animals. There were increased lipid peroxidation and reduced levels of cellular antioxidant enzymes in different tissues of diabetic rats. However, oral administration of GP extracts, especially the highest dose (1000 mg/kg), significantly ameliorated hyperglycemia (42%); elevated insulin levels (165%); decreased HbA1c (29.4%); restored lipid levels (reduction in TG by 25%, TC by 15%, and LDL-C by 75% and increase in HDL-C by 4%), liver and renal function markers, and lipid peroxidation (reduction by 52% in the liver, 39% in the kidney, 44% in the heart, and 46% in the pancreas); and stimulated tissue antioxidant enzymes to near normalcy. Overall, the findings suggest that GP fruit is effective against hyperglycemia and could be used in the treatment of diabetes and its complications and other oxidative stress-mediated pathological conditions.