Context: Cisplastin (CDDP) is a chemotherapeutic drug frequently used to manage a variety of cancers. However, its use is associated with hepatorenal toxicity resulting from elevated reactive oxygen species production. Objective: Herein, the hepatorenal protective effect of tert-butylhydroquinone (tBHQ) in cisplatin (CDDP)-treated rats was examined. Methods: Wistar male rats randomly divided into four groups: normal control, tBHQ, CDDP and tBHQ + CDDP received 50 mg/kg b.w./day of tBHQ orally for 14 days while 7 mg/kg b.w of CDDP was administered intraperitoneally on Day 8. Results: CDDP increased serum biomarkers of hepatic (AST, ALP, ALT, GGT) and renal (creatinine, urea, uric acid, kidney injury molecule 1) function. The levels of nuclear factor erythroid-2-related factor 2 protein and the activities of superoxide dismutase, catalase, glutathione peroxidase and glutathione reductase activities were decreased in liver and kidney. Also, CDDP increased hepatic and renal levels of NF-kappa B, TNF alpha, Bax and caspase-3 proteins and decreased hepatorenal levels of Bcl-2 protein in the liver and kidney. Pre-treatment with tBHQ prevented these negative effects. Significance: Pre-intervention with tBHQ attenuates hepatorenal toxicity of CDDP by dampening oxidative stress, inflammation and apoptosis.

Diabetes in humans a chronic metabolic disorder characterised by hyperglycaemia, it is associated with an increased risk of cardiovascular disease, disruptions to metabolism and vascular functions. It is also linked to oxidative stress and its complications. Its role in vascular dysfunctions is generally reported without detailed impact on the molecular mechanisms. Potassium ion channel (K+ channels) are key regulators of vascular tone, and as membrane proteins, are modifiable by oxidant stress associated with diabetes. This review manuscript examined the impact of oxidant stress on vascular K+ channel functions in diabetes, its implication in vascular complications and metabolic and cardiovascular diseases.

The global market for medicinal plants and herbs is on the increase due to their desirability, efficacy, and less adverse effects as complementary and alternative medications to the orthodox pharmaceuticals, perhaps due to their natural components and qualities. Metabolic syndromes are managed with changes in diet, exercise, lifestyle modifications and the use of pharmacological agents. Plants are now known to have potent antioxidant and cholinergic activities which are relevant to the management of several metabolic syndromes, which are unfortunately, co-morbidity factors in the coronavirus disease crisis. This review will focus on the biological activities of some plant products used as complementary and alternative medicines in the management of metabolic syndromes, and on their reported antiviral, antithrombotic, angiotensin-converting enzyme inhibitory properties, which are integral to their usage in the management of viral infections and may give an avenue for prophylactic and therapeutics especially in the absence of vaccines/formulated antiviral therapies.

Imbalance in hepatic lipid metabolism can lead to an abnormal triglycerides deposition in the hepatocytes which can cause non-alcoholic fatty liver disease (NAFLD). Four main mechanisms responsible for regulating hepatic lipid metabolism are fatty acid uptake, de novo lipogenesis, lipolysis and fatty acid oxidation. Controlling the expression of transcription factors at molecular level plays a crucial role in NAFLD management. This paper reviews various medicinal plants and their bioactive compounds emphasising mechanisms involved in hepatic lipid metabolism, other important NAFLD pathological features, and their promising roles in managing NAFLD through regulating key transcription factors. Although there are many medicinal plants popularly investigated for NAFLD treatment, there is still little information and scientific evidence available and there has been no research on clinical trials scrutinised on this matter. This review also aims to provide molecular information of medicinal plants in NALFD treatment that might have potentials for future scientifically controlled studies.

The inhibition of renin angiotensin system pathway has been largely documented to be effective in the control of cardiovascular events. The present study investigated the effect of angiotensin converting enzyme (ACE) inhibitor on fasting blood glucose level in hypertension induced by the inhibition of nitric oxide synthase (NOS) in male Wistar rats. Hypertension was induced by the inhibition of NOS using a non-selective NOS inhibitor, NG-nitro-L-arginine methyl ester (L-NAME). The blockade of NOS resulted in an increase in blood pressure, ACE, angiotensin II and endothelin-1 levels, and a decrease in fasting blood glucose and nitric oxide (NO) levels. The hypertensive rats treated with ACE inhibitor (ramipril) recorded a decrease in blood pressure, ACE, angiotensin II, endothelin-1, NO and fasting blood glucose levels, and an increase in prostacyclin level. In conclusion, ACE inhibitor potentiated the hypoglycaemic effect of NOS inhibitor and this effect is independent of NO and pancreatic insulin release.

Context: Global prevalence of obesity is increasing. Objective: To study the effect of bee bread (BB) on serum renal function parameters, oxidative stress, inflammatory and B-cell associated protein X (Bax) in the kidneys of high fat diet (HFD) obese rats. Methods: Thirty-six male Sprague Dawley rats were used. Control: received rat diet and water (1 mL/kg); HFD group: received HFD and water (1 mL/kg): bee bread (BB) preventive or orlistat preventive: received HFD and BB (0.5 g/kg) or HFD and orlistat (10 mg/kg); BB or orlistat treatment: received BB (0.5 g/kg) or orlistat (10 mg/kg). Results: HFD group had increased body weight, Body Mass Index, Lee Obesity Indices, kidney weights, malondialdehyde, inflammatory markers, Bax; decreased glutathione peroxidase, glutathione-S-transferase, superoxide dismutase, total antioxidant activity, no differences (p > .05) in food intakes, serum creatinine, sodium, potassium, chloride, catalase compared to control. Conclusion: BB modulated most of these parameters, as corroborated by histology.

Pollen and bee bread are valuable apitherapeutic products owing to their high-potential medical and nutritional applications. They are rich in nutritional properties such as proteins, amino acids, carbohydrates, lipids and fatty acids, phenolic compounds, enzymes, and coenzymes together with vitamins and bioelements, which are essential for maintaining human health. They demonstrate various potential biological activities with health-promoting properties such as antioxidant, hepatoprotective, antiobesity, antiinflammatory, antimicrobial, antifungal, antiviral, antiradiation, and anticancer attributed to their natural antioxidants, including mostly phenolic compounds. The liver plays a major role in the metabolism of various substances. The intake of dietary components is crucial for liver health which can be beneficial or detrimental to the healthy or diseased liver. This chapter provides a general overview of the functional properties of pollen and bee bread related to liver health, their safety, and future warranted research.

The use of glucocorticoids in the treatment of inflammatory disorders can result in myocardial injury. This study was carried out to investigate the protective effects of ethanolic leaf extract of Gongronema latifolium (GL) in dexamethasone (DEX)-induced myocardial injury. Wistar rats were assigned to 4 groups (n = 6) namely, control, GL, DEX, and DEX+GL groups. DEX (35 μg/kg body weight) was administered subcutaneously to induce myocardial injury, while GL leaf extract (200 mg/kg body weight) was administered orally. Both agents were administered to their respective groups for 14 days. DEX (p < .05) decreased nitric oxide and increased angiotensin-converting enzyme activity compared with the control. Serum superoxide dismutase activity and bilirubin level were decreased (p < .05), while malondialdehyde level was increased (p < .05) in the DEX group. Serum liver enzymes, inflammatory biomarkers (C-reactive protein and interleukin-6), and cardiac injury biomarkers (creatinine kinase, cardiac troponin-T, and lactate dehydrogenase) were significantly (p < .05) increased in the DEX group relative to the control. Administration of GL leaf extract attenuated these changes significantly. The study therefore suggests that GL is beneficial in the treatment of myocardial injury via the downregulation of high serum concentration of cardiac biomarkers, oxidative stress markers, and inflammatory biomarkers released as a result of the insult caused by glucocorticoid administration. PRACTICAL APPLICATIONS: In this study, we demonstrated that prolonged use of dexamethasone resulted in myocardial cell injury via increased production of reactive oxygen species, inflammatory biomarkers, and inhibition of nitric oxide, a potent vasodilator. The leaves extract of Gongronema latifolium elicits the anti-inflammatory and cardioprotective potential as an efficient inhibitor of free radicals with good antioxidant properties. The study provides scientific evidence of the therapeutic ability of the extract of G. latifolium in the treatment of DEX-induced myocardial injury and could be a drug candidate for the treatment of myocardial injury and inflammation in humans.

The aim of the study was to determine the chemical profile, antioxidant properties and antimicrobial activities of Heterotrigona itama bee bread from Malaysia. The pH, presence of phytochemicals, antioxidant properties, total phenolic content (TPC) and total flavonoid content (TFC), as well as antimicrobial activities, were assessed. Results revealed a decrease in the pH of bee bread water extract (BBW) relative to bee bread ethanolic extract (BBE) and bee bread hot water extract (BBH). Further, alkaloids, flavonoids, phenols, tannins, saponins, terpenoids, resins, glycosides and xanthoproteins were detected in BBW, BBH and BBE. Also, significant decreases in TPC, TFC, DPPH activity and FRAP were detected in BBW relative to BBH and BBE. We detected phenolic acids such as gallic acid, caffeic acid, trans-ferulic acid, trans 3-hydroxycinnamic acid and 2-hydroxycinnamic acid, and flavonoids such as quercetin, kaempferol, apigenin and mangiferin in BBE using high-performance liquid chromatography analysis. The strongest antimicrobial activity was observed in Klebsilla pneumonia (MIC50 1.914 µg/mL), followed by E. coli (MIC50 1.923 µg/mL), Shigella (MIC50 1.813 µg/mL) and Salmonella typhi (MIC50 1.617 µg/mL). Bee bread samples possess antioxidant and antimicrobial properties. Bee bread contains phenolic acids and flavonoids, and could be beneficial in the management and treatment of metabolic diseases.

Obesity and hyperlipidemia are major risk factors for developing vascular diseases. Bee bread (BB) has been reported to exhibit some biological actions, including anti-obesity and anti-hyperlipidemic. This study aims to investigate whether bee bread can ameliorate vascular inflammation and impaired vasorelaxation activity through eNOS/NO/cGMP pathway in obese rats. Forty male Sprague-Dawley rats were randomly divided into four groups (n = 10/group), namely: control (normal group), obese rats (OB group), obese rats treated with bee bread (0.5 g/kg/day, OB/BB group) and obese rats treated with orlistat (10 mg/kg/day, OB/OR group). The latter three groups were given a high-fat diet (HFD) for 6 weeks to induced obesity before being administered with their respective treatments for another 6 weeks. After 12 weeks of the total experimental period, rats in the OB group demonstrated significantly higher Lee obesity index, lipid profile (total cholesterol, triglyceride, low-density lipoprotein), aortic proinflammatory markers (tumor necrosis factor-α, nuclear factor-κβ), aortic structural damage and impairment in vasorelaxation response to acetylcholine (ACh). Bee bread significantly ameliorated the obesity-induced vascular damage manifested by improvements in the lipid profile, aortic inflammatory markers, and the impaired vasorelaxation activity by significantly enhancing nitric oxide release, promoting endothelial nitric oxide synthase (eNOS) and cyclic guanosine monophosphate (cGMP) immunoexpression. These findings suggest that the administration of bee bread ameliorates the impaired vasorelaxation response to ACh by improving eNOS/NO/cGMP-signaling pathway in obese rats, suggesting its vascular therapeutic role.

Metabolic dysfunction-associated fatty liver disease (MAFLD) is a pathological accumulation of hepatic lipid closely linked with many metabolic disorders, oxidative stress and inflammation. We aimed to evaluate the hepatoprotective effect of bee bread on oxidative stress and inflammatory parameters in MAFLD rats. Twenty-eight male Sprague-Dawley rats were assigned into four groups (n = 7/group): normal control (NC), high-fat diet (HFD), bee bread (HFD + Bb, HFD + 0.5 g/kg/day bee bread) and orlistat (HFD + Or, HFD + 10 mg/kg/day orlistat) groups. After 12 weeks, the HFD group demonstrated significantly higher body weight gain, serum levels of lipids (TG, TC, LDL), liver enzymes (AST, ALT, ALP) and adiponectin, liver lipids (TG, TC) and insulin resistance (HOMA-IR). Furthermore, the HFD group showed significantly decreased antioxidant enzyme activities (GPx, GST, GR, SOD, CAT) and GSH level, and increased liver oxidative stress (TBARS, NO), translocation of Nrf2 to the nucleus, Keap1 expression and inflammation (TNF-α, NF-κβ, MCP-1) together with histopathological alterations (steatosis, hepatocyte hypertrophy, inflammatory cell infiltration, collagen deposition), which indicated the presence of non-alcoholic steatohepatitis (NASH) and fibrosis. Bee bread significantly attenuated all these changes exerted by HFD feeding. In conclusion, our results suggest that bee bread might have antioxidant, anti-inflammatory, anti-steatotic and anti-fibrotic effects that are beneficial in protecting liver progression towards NASH and fibrosis.

The effect of bee bread (BB) on the biochemical parameters-body weights, calorie intake, Lee obesity indices, serum amylase, aspartate and alanine amino transferases, skeletal muscle activities of creatine kinase, superoxide dismutase, glutathione peroxidase, catalase, malondialdehyde, glutathione-S-transferase, total antioxidant activity, endogenous secretory receptor for advanced glycation end products (esRAGE), and muscle histology of high-fat diet (HFD) obese rats-was studied. Thirty-six male Sprague-Dawley rats were divided into six groups: Control: received rat feed and water (1 ml/kg); HFD: received HFD and water (1 ml/kg): BB or orlistat preventive: received HFD and BB (0.5 g/kg) or HFD and orlistat (10 mg/kg; weeks 1 to 12); BB or orlistat treated: received HFD and BB (0.5 g/kg) or HFD and orlistat (10 mg/kg; weeks 6 to 12), following obesity induction. At week 12, HFD group had altered (p < .05) levels of some biochemical parameters which were modulated by BB and corroborated by muscle histology. Practical applications Obesity is a global health problem, which prevalence has continued to be on the increase due to changes in lifestyle and dietary behavior. Additionally, the approaches that currently are being used for the treatment of this disease have not been able to successfully reverse obesity and its associated complications. The current study which showed that bee bread prevented or attenuated obesity-induced muscular pathology, places bee bread in the spotlight as a functional food that could be useful in preventing or mitigating obesity-induced muscular pathology.

Obesity, a disorder of body weight regulatory systems that is characterized by the accumulation of excess body fat is increasingly becoming a global pandemic. Despite several approaches that have been applied to mitigate obesity, they have not been able to totally reverse the obesity and its mediated complication. Advanced glycation end products (AGEs) refer to a group of prooxidant heterogenous compounds whose formation results from nonenzymatic reactions between reactive sugars and proteins, lipids and nucleic acids. While supporting evidence has suggested that AGEs may have contributory roles in the pathogenesis of obesity, there are indications that increased consumption of dietary AGEs increases the circulating AGEs levels and their deposition in the tissues including the adipose tissue, increasing the risk of development of obesity and its comorbidities. Identification of the underlying mechanism may provide an important strategy for novel therapeutic approaches against obesity. This chapter therefore provided novel insights into the role of dietary AGEs in the pathogenesis of obesity and the purported mechanisms of action.

Diabetic nephropathy is reported to occur as a result of the interactions between several pathophysiological disturbances, as well as renal oxidative stress and inflammation. We examined the effect of Malaysian propolis (MP), which has anti-hyperglycemic, antioxidant and anti-inflammatory properties, on diabetes-induced nephropathy. Diabetic rats were either treated with distilled water (diabetic control (DC) group), MP (300 mg/kg b.w./day), metformin (300 mg/kg b.w./day) or MP + metformin for four weeks. We found significant increases in serum creatinine, urea and uric acid levels, decreases in serum sodium and chloride levels, and increase in kidney lactate dehydrogenase activity in DC group. Furthermore, malondialdehyde level increased significantly, while kidney antioxidant enzymes activities, glutathione level and total antioxidant capacity decreased significantly in DC group. Similarly, kidney immunoexpression of nuclear factor kappa B, tumor necrosis factor-α, interleukin (IL)-1β and caspase-3 increased significantly, while IL-10 immunoexpression decreased significantly in DC group relative to normal control group. Histopathological observations for DC group corroborated the biochemical data. Intervention with MP, metformin or both significantly mitigated these effects and improved renal function, with the best outcome following the combined therapy. MP attenuates diabetic nephropathy and exhibits combined beneficial effect with metformin.

The high-fat diet utilized in the present study induced obesity in the male rats. Bee bread supplementation mitigated impaired steroidogenesis, spermatogenesis, mating behavior, and fertility potential by counteracting the downregulation of steroidogenic genes, thus increasing testosterone levels and suppressing epididymal oxidative stress. These benefits may be due to the abundance of phenolic and flavonoid compounds in bee bread.

Doxorubicin (DOX) is a broad-spectrum chemotherapeutic drug used in the treatment of cancers. It acts by generating reactive oxygen species in target cells. The actions are, however, not limited to cancerous cells as it attacks healthy cells, killing them. This study investigated the benefits of the antioxidant, tert-butylhydroquinone (tBHQ), on testicular toxicity following DOX therapy. Twenty-four adult male albino rats were assigned randomly into four groups (n = 6), namely: normal control (NC), tBHQ, DOX and tBHQ + DOX groups. tBHQ (50 mg/kg body weight in 1% DMSO) was administered orally for 14 consecutive days, while a single DOX dose (7 mg/kg body weight) was administered intraperitoneally on Day 8. DOX decreased sperm count, motility and viability, and decreased the levels of steroidogenesis-related proteins, and reproductive hormones. Furthermore, DOX decreased the expression of antioxidant cytoprotective genes, and decreased the protein level of proliferating cell nuclear antigen in the testis. Conversely, DOX increased the expression of pro-inflammatory and pro-apoptotic genes in the testis. These negative effects were ameliorated following the intervention with tBHQ. Our results suggest that tBHQ protects the testis and preserves both steroidogenesis and spermatogenesis in DOX-treated rats through the suppression of oxidative stress, inflammation and apoptosis.

Obesity and its accompanying complications predispose to abnormal testicular glucose metabolism, penile erectile dysfunction and subfertility. This study examined the potentials of orlistat in attenuating erectile dysfunction and fertility decline in high-fat diet (HFD)-induced obesity in male rats. Eighteen adult male Sprague–Dawley rats whose weights were between 250 and 300 g were divided into three groups (n = 6/group) namely: normal control (NC), HFD and HFD + orlistat (10 mg/kg body weight/day co-administered for 12 weeks) (HFD+O). During the 11th and 12th week, mating behaviour and fertility parameters were evaluated, and parameters of glucose metabolism were assessed at the end of the 12th week. Orlistat increased testicular mRNA levels of glucose transporters (Glut1 and Glut3), monocarboxylate transporters (Mct2 and Mct4) and lactate dehydrogenase type C (Ldhc), decreased intratesticular lactate and glucose levels, and LDH activity in obese rats. Furthermore, orlistat increased superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), glutathione-S-transferase (GST) and glutathione reductase (GR) activities, and total antioxidant capacity (TAC), but decreased malondialdehyde level in the penis of obese rats. Similarly, orlistat improved penile cGMP level, sexual behaviour and fertility outcome in obese rats. Penile cGMP level correlated positively with total mounts and intromissions but correlated negatively with mount/intromission ratio. Orlistat improves fertility potential in obese state by targeting testicular lactate metabolism, penile oxidative stress and sexual behaviour in rats. Therefore, orlistat shows a promising protective effect and may preserve the fertility potential of obese men.

Oxidative stress, chronic inflammation and apoptosis are associated with obesity. Herein, we investigated the potential protective effect of bee bread, a natural bee product, on testicular oxidative stress, inflammation and apoptosis, as well as lactate transport in the testis of high-fat diet (HFD)-induced obese rats. Adult male Sprague-Dawley rats were either fed with normal chow (NC), HFD, HFD + bee bread (0.5 g/kg b.w./day) or HFD + orlistat (10 mg/kg b.w./day) for 12 weeks. Our results show significant decreases in the activities and mRNA expression of antioxidant genes (Nrf2, Sod, Cat and Gpx), with significant increase in pro-inflammatory (Nf-κb, Tnf-α, iNos, Il-1β) and pro-apoptotic (p53, Bax, Bax/Bcl2, Caspase-8, Caspase-9 and Caspase-3) genes in the testis of HFD group relative to the NC group. Furthermore, proliferating cell nuclear antigen (PCNA) was poorly expressed in the testis of the HFD group relative to the NC group. Similarly, the mRNA levels of glucose transporters (Glut1 and Glut3), monocarboxylate transporters (Mct2 and Mct4) and lactate dehydrogenase type C (Ldhc) decreased significantly, with decrease in lactate utilisation. Treatment with bee bread upregulated testicular antioxidant enzymes, downregulated inflammation and apoptosis, and increased PCNA immunoexpression, in addition to improving lactate transport. Taken together, our results suggest that bee bread is a promising natural product with the potential to improve male fertility.

Steroidogenesis decline is reported to be one of the mechanisms associated with obesity‐induced male factor subfertility/infertility.

Cisplatin (Cis) is an effective chemotherapeutic intervention against many cancer types. However, the oxidative stress-related toxicities associated with cancer cell resistance-induced dose scaling has limited its long-term use. In the present study, we explored the benefits of the antioxidant, tert-butylhydroquinone (tBHQ; 50 mg/kg b.w./day, for 14 days) against Cis single dose injection (7 mg/kg b.w., i.p on Day 8), on testicular toxicity of male Wistar rats. Cis triggered testicular and epididymal oxidative stress, testicular inflammation (upregulated NF-kappa B, TNF-alpha and IL-1 beta mRNA levels, and downregulated IL-10 mRNA level), increased testicular apoptosis (increased Bax/Bcl2 and caspase-3 mRNA levels) and decreased testicular germ cells proliferation. Further, Cis decreased testicular steroidogenesis (decreased expression of StAR, CYP11A1, 3 beta-HSD and 17 beta-HSD mRNA and proteins) and decreased follicle stimulating hormone, luteinizing hormone and testosterone levels. Cis also decreased sperm count, motility, viability, normal morphology and Johnsen score. However, intervention with tBHQ significantly decreased oxidative stress by upregulating Nrf2 gene, suppressed inflammation, apoptosis and increased testicular germ cells proliferation. tBHQ also increased steroidogenesis and improved sperm parameters. Taken together, tBHQ improves steroidogenesis and spermatogenesis in Cis-intoxicated rats by improving antioxidant status, dampening inflammation and apoptosis, thus improving the proliferative capacity of spermatogenic cells.