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Cobalt is a ferromagnetic metal with extensive industrial and biological applications. To assess the toxic effects of, and mechanisms involved in cobalt chloride (CoCl2)-induced cardio-renal dysfunctions. Male Wistar rats were exposed orally, daily through drinking water to 0 ppm (control), 150 ppm, 300 ppm, and 600 ppm of CoCl2, respectively. Following exposure, results revealed significant (p < 0.05) rise in markers of oxidative stress, but decreased activities of catalase, glutathione peroxidase, glutathione-S-transferase, and reduced glutathione content in cardiac and renal tissues. There were significant increases in systolic, diastolic, and mean arterial blood pressure at the 300- and 600-ppm level of CoCl2-exposed rats relative to the control. Prolongation of QT and QTc intervals was observed in CoCl2 alone treated rats. Also, there were significant increases in the heart rates, and reduction in P wave, and PR duration of rats administered CoCl2. Histopathology of the kidney revealed peritubular and periglomerular inflammation, focal glomerular necrosis following CoCl2 exposure. Further, cyclooxygenase-2 and B-cell associated protein X expressions were upregulated in the cardiac and renal tissues of CoCl2-exposed rats relative to the control. Combining all, results from this study implicated oxidative stress, inflammation, and apoptosis as pathologic mechanisms in CoCl2-induced hypertension and cardiovascular complications of rats. [ABSTRACT FROM AUTHOR]

The modulating effect of peroxisome proliferator-activated receptor α ligand on haemodynamic effects of phenylepherine (PE), angiotensin II (AII), endothelin 1 (ET1), acetylcholine (Ach), sodium nitroprusside (SNP) and isoproterenol (ISO) were evaluated in glycerol-induced acute kidney injury in rats. The effect of PE on fenofibrate-treated animals was a dose-dependent increase in mean arterial blood pressure (MAP). For AII and ET1, MAP was also increased for the fenofibrate group but not in a dose-dependent fashion. On the medullary blood flow (MBF), while the lower doses of PE and AII increased the perfusion unit on the fenofibrate-treated group, the higher doses decreased the perfusion unit. The ET1 increased the perfusion unit on this group but not in dose-dependent fashion. The effects of PE and AII on the cortical blood flow (CBF) of fenofibrate-treated group is similar to that of MBF for the same group but not for ET1. The effect of Ach, SNP and ISO in all the groups was the decrease in MAP. ISO caused dose-dependent increase in MBF of fenofibrate-treated group. The effect of Ach, SNP and ISO on the CBF perfusion unit was that of the increase for the fenofibrate-treated group. The study showed that fenofibrate did not attenuate increased blood pressure induced by PE, AII and ET1 but caused enhanced vasodilation by Ach, SNP and ISO. [ABSTRACT FROM AUTHOR]

Background. Acokanthera oppositifolia Lam (family: Apocynaceae) is a shrub or small tree with white latex, and the leaves of this plant are used in the form of a snuff to treat headaches and in infusions for abdominal pains and convulsions and septicaemia. Adenia gummifera Harv of the family Passifloraceae is a distinctive woody climber whose infusions are used as emetics and are said to help with some forms of depression. Lipid peroxidation has gained more importance today because of its involvement in pathogenesis of many diseases. Free radicals are the main agents in lipid peroxidation. Antioxidants thus play an important role of protecting the human body against damage by the free radicals. Plants containing phenolic compounds have been reported to possess strong antioxidant properties.Methods. The antioxidant activities and phenolic contents of the methanol extracts of the stems of Acokanthera oppositifolia and Adenia gummifera were evaluated using in vitro standard procedures. Spectrophotometry was the basis for the determinations of total phenol, total flavonoids, flavonols, and proanthocyanidins. Tannins, quercetin and catechin equivalents were used for these parameters. The antioxidant activities of the stem extract of Acokanthera oppositifolia were determined by the 2,2'-azinobis-3- ethylbenzothiazoline-6-sulfonic acid (ABTS), 1,1-Diphenyl-2-picrylhydrazyl (DPPH), and ferrous reducing antioxidant property (FRAP) methods.Results. The results from this study showed that the antioxidant activities of the stem extract of Acokanthera oppositifolia as determined by the 1,1-Diphenyl-2-picrylhydrazyl (DPPH), and ferrous reducing antioxidant property (FRAP) methods, were higher than that of Adenia gummifera. The levels of total phenols and flavonols for A. oppositifolia were also higher. On the other hand, the stem extract of Adenia gummifera had higher level of total flavonoids and proanthocyanidins than that of Acokanthera oppositifolia. The 2, 2'-azinobis-3- ethylbenzothiazoline-6-sulfonic acid (ABTS) activities of the 2 plant extracts were similar and comparable to that of BHT.Conclusion. Thus, the present results indicate clearly that the extracts of Acokanthera oppositifolia and Adenia gummifera possess antioxidant properties and could serve as free radical inhibitors or scavengers, acting possibly as primary antioxidants. This study has to some extent validated the medicinal potential of the stems of Acokanthera oppositifolia and Adenia gummifera. [ABSTRACT FROM AUTHOR]

Background. In South Africa, Calpurnia aurea (Ait.) Benth is used to destroy lice and to relieve itches, to destroy maggots and to treat allergic rashes, particularly those caused by caterpillars. Antioxidants play an important role protecting against damage by reactive oxygen species. Plants containing flavonoids have been reported to possess strong antioxidant properties.Methods. The antibacterial, antioxidant activities and phenolic contents of the methanol extracts of the leaves and stems of Calpurnia aurea were evaluated using in vitro standard methods. Spectrophotometry was the basis for the determinations of total phenol, total flavonoids, flavonols, and proanthocyanidins. Tannins, quercetin and catechin equivalents were used for these parameters. The antioxidant activities of the stem extract of Calpurnia aurea were determined by ABTS, DPPH, and ferrous reducing antioxidant property (FRAP) methods. Laboratory isolates of 10 bacteria species which included five Gram-positive and five Gram-negative strains were used to assay for antibacterial activity of this plant.Results. The results from this study showed that the antioxidant activities of the stem extract of Calpurnia aurea as determined by the total phenol, flavonoids, and FRAP methods were higher than that of the leaves. On the other hand, the leaf extract of the plant has higher level of total flavonols and proanthocyanidins. The leaf extract also has higher radical scavenging activity as shown in 1, 1-Diphenyl-2-picrylhydrazyl (DPPH), and 2,2¿-azinobis-3- ethylbenzothiazoline-6-sulfonic acid (ABTS) assay. The leaf extract showed activity against seven of the bacterial organisms.Conclusion. The results from this study indicate that the leaves and stem extracts of Calpurnia aurea possess antioxidant properties and could serve as free radical inhibitors or scavenger or, acting possibly as primary antioxidants. Although, the antibacterial properties of Calpurnia aurea are not as effective as the standard drugs- Chloramphenicol and Streptomycin, they still possess some activity against bacterial strains used in this study. Calpurnia aurea may therefore be a good candidate for functional foods as well as pharmaceutical plant-based products. [ABSTRACT FROM AUTHOR]

Objective: Curcuma longa Rhizome (CLR), due to its potent antioxidant phytochemical constituents, was investigated for its effects on bisphenol A (BPA)-induced cardiovascular and renal damage., Materials and Methods: Sixty rats were randomly selected, and grouped as control, BPA (100 mg/ kg), BPA and CLR 100 mg/kg, BPA and CLR 200 mg/kg, CLR 100 mg/kg, and CLR 200 mg/kg for 21 days. Oxidative stress indices, antioxidant status, blood pressure parameters, genotoxicity, and immunohistochemistry were determined., Results: Rats exposed to the toxic effects of BPA had heightened blood pressure, lowered frequency of micronucleated polychromatic erythrocytes, and decreased activities of antioxidant enzymes compared with rats treated with CLR. Moreover, administration of CLR significantly (p<0.05) lowered malondialdehyde content and reduced the serum myeloperoxidase activity. Immunohistochemical evaluation revealed significantly (p<0.05) increased expressions of cardiac troponin and Caspase 3 in the BPA group compared with the CLR-treated groups., Conclusion: C. longa ameliorated cardiotoxic and nephrotoxic actions of bisphenol-A via mitigation of oxidative stress, hypertension, and genotoxicity., Competing Interests: The authors have declared that there is no conflict of interest.

Objective: Lead (Pb) poisoning affects multiple organs including the reproductive system. The experiment was performed to explore the protective effect of naringin on testicular apoptosis, neuronal dysfunction and markers of stress in cockerel chicks., Materials and Methods: Thirty-six cockerel chicks were used for this study, and randomly grouped into six chicks per group viz. control, Pb only (600 ppm), Pb and naringin (80 mg/kg), Pb and Naringin (160 mg/kg), naringin only (80 mg/kg) and naringin only (160 mg/kg), respectively, for eight weeks. Pb was administered via drinking water while naringin was administered via oral gavage. Oxidative stress indices in the brain and testes were assessed, and immunohistochemistry of TNF-α and caspase 3 was done in the brain and testes, respectively., Results: Lead administration induced inflammatory and testicular apoptosis cascade accompanied with increased oxidative stress and upregulation of brain and testicular antioxidant enzymes in comparison to the control and Pb-only-treated cockerels. Immunohistochemistry showed significant immunoreactivity of testicular caspase 3 and TNF-α in the brain., Conclusion: Treatment of Pb-exposed chickens with naringin offered protection to Pb acetate-induced testicular oxidative stress, apoptosis, and neuroinflammation in cockerel chicks., Competing Interests: The authors have declared that there is no conflict of interest.

Lead (Pb) toxicity constitutes a major health hazard to both humans and animals especially in the developing countries. It is a ubiquitous environmental contaminant found in the air essentially because of unregulated mining and other industrial activities. Lead can be found naturally in the soil thus, contaminating crops for human and animal food, as well as run-off water and air pollution. Intensively and extensively reared domestic chickens are exposed to contamination via inhalation and ingestion of contaminated food materials. Naringin, a product from citrus plant has been described to possess excellent metal chelating ability. Naringin is rich in flavonoid with attendant antioxidant, anti-autophagy, anti-inflammatory, hepatoprotective and cardio-nephroprotective properties. This study was conducted to investigate the hepatoprotective and modulation of oxidative stress in commercial cockerel chickens by Naringin. Thirty-six commercial cockerel chickens were randomly assigned into six groups A-F of six birds each viz: Group A served as control group while groups B, C, and D received Lead acetate at 300 ppm via drinking water continuously till the end of the experiment. In addition, groups C and D were treated with Naringin at 80 mg/kg and 160mg/kg, respectively, via oral gavage for 8 weeks. Groups E and F were administered naringin only at 80mg/kg and 160mg/kg respectively for eight weeks. Pb toxicity induced degenerative changes in the histological sections as well as, higher expression of hepatic caspase 3 as shown by immunohistochemistry. There was increased oxidative stress markers (H2O2, MDA) and depletion of the antioxidant defense system markers SOD, GPx, GSH, and GST. It concluded that Co- treatment with Naringin ameliorated oxidative stress, enhanced antioxidant defense system, reduced the expression of hepatic caspase 3 thus, offering protection against lead acetate-induced derangements in the liver of commercial cockerel chickens.

Purpose: Anacardium occidentale commonly known as Cashew is a plant that is widely used in African traditional medicine. It is endowed with phytochemical constituents that are responsible for its medicinal properties., Methods: Twenty-five male Wistar rats were grouped as follows: Control (Group A), Group B (L-NAME 40 mg/kg), Group C (100 mg/kg Anacardium occidentale extract plus 40 mg/kg L-NAME), Group D (200 mg/kg extract plus 40 mg/kg L-NAME) and Group E (10 mg/kg of Lisinopril plus 40 mg/kg L-NAME). The animals were treated with oral administration of either the extracts or Lisnopril daily for 4 weeks. Neuro-behavioural tests such as the Morris Water Maze and Hanging Wire Grip tests were carried out to evaluate memory/spatial learning and muscular strength, respectively. Makers of oxidative stress, antioxidant enzymes and immunohistochemical staining of Glial Fibrillary Acidic Protein and Ionised Calcium Binding Adaptor molecule 1 were assessed., Results: L-NAME administration caused significant increases in biomarkers of oxidative stress, decreased antioxidant status, acetylcholinesterase activity, altered neuro-behavioural changes, astrocytosis, and microgliosis. However, Anacardium occidentale reversed exaggerated oxidative stress biomarkers and improved neuro-behavioural changes., Conclusions: Combining all, Anacardium occidentale enhanced brain antioxidant defence status, improved memory and muscular strength, thus, suggesting the neuroprotective properties of Anacardium occidentale .

Lead is one of the major pollutants that is harmful to both animals and humans. It is found in every aspect of the environment such as the air, water, and soil. This pollutant affects both wild and domestic birds. Naringin has an active principle called flavonoid that has been found to have medicinal properties, mostly because of its antioxidant and metal chelating properties. This study was carried out to investigate the protective effect of naringin as an antioxidant against lead-induced anemia, cardio and nephrotoxicity, and hypertension. This study also aimed at elucidating the use of naringin as a heavy metal binder in poultry feed. Thirty-six cockerel chicks were used for this study, and randomly grouped into six groups per group; group A served as the control, group B received Pb-only (300 ppm), group C (Pb and naringin; 80 mg/kg), group D (Pb and naringin; 160 mg/kg), group E (naringin 80 mg/kg), and group F (naringin 160 mg/kg), respectively, for 8 weeks. Lead (Pb) was administered via drinking water, while naringin was administered via oral gavage. Lead acetate intoxication precipitated anemia as indicated by significant reductions in the values of PCV, RBC, and Hb concentration in lead-treated chicks when compared with the controls. Also, lead administration induced hypertension together with increased oxidative stress, depletion of the antioxidant defense system, reduced nitric oxide production, and an increase in high blood pressure. Immunohistochemistry indicated high expressions of cardiac troponin, renal angiotensin-converting enzymes, and renal neutrophil gelatinase-associated lipocalin. Treatment with naringin corrected anemia, reduced oxidative stress, improved antioxidant system, reduced high blood pressure, and offered protection against lead acetate-induced cardio-renal dysfunction in cockerel chicks. We recommend that naringin should be incorporated poultry feeds as a metal binder., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Purpose The persistent and alarming rates of increase in cardiovascular and renal diseases caused by chemicals such as cobalt chloride (CoCl 2 ) in mammalian tissues have led to the use of various drugs for the treatment of these diseases. This study aims at evaluating the nephron-protective action of Naringin (NAR), a metal-chelating antioxidant against CoCl 2 -induced hypertension and nephrotoxicity. Methods Forty-two male Wistar rats were randomly distributed to seven rats of six groups and classified into Group A (Control), Group B (300 part per million; ppm CoCl 2 ), Group C (300 ppm CoCl 2 + 80 mg/kg NAR), Group D (300 ppm CoCl 2 + 160 mg/kg NAR), Group E (80 mg/kg NAR), and Group F (160 mg/kg NAR). NAR and CoCl 2 were administered via oral gavage for seven days. Biomarkers of renal damage, oxidative stress, antioxidant status, blood pressure parameters, immunohistochemistry of renal angiotensin-converting enzyme and podocin were determined. Results Cobalt chloride intoxication precipitated hypertension, renal damage, and oxidative stress. Immunohistochemistry revealed higher expression of angiotensin-converting enzyme (ACE) and podocin in rats administered only CoCl 2 . Conclusion Taken together, the antioxidant and metal-chelating action of Naringin administration against cobalt chloride-induced renal damage and hypertension could be through abrogation of angiotensin-converting enzyme and podocin signalling pathway.

Sodium fluoride (NaF) is one of the neglected environmental toxicants that has continued to silently cause toxicity to both humans and animals. NaF is universally present in water, soil, and atmosphere. The persistent and alarming rate of increase in cardiovascular and renal diseases caused by chemicals such as NaF in mammalian tissues has led to the use of various drugs for the treatment of these diseases. The present study aimed at evaluating the renoprotective and antihypertensive effects of L-arginine against NaF-induced nephrotoxicity. Thirty male Wistar rats (150-180 g) were used in this study. The rats were randomly divided into five groups of six rats each as follows: Control, NaF (300 ppm), NaF + L-arginine (100 mg/kg), NaF + L-arginine (200 mg/kg), and NaF + lisinopril (10 mg/kg). Histopathological examination and immunohistochemistry of renal angiotensin-converting enzyme (ACE) and mineralocorticoid receptor (MCR) were performed. Markers of renal damage, oxidative stress, antioxidant defense system, and blood pressure parameters were determined. L-arginine and lisinopril significantly (P < 0.05) ameliorated the hypertensive effects of NaF. The systolic, diastolic, and mean arterial blood pressure of the treated groups were significantly (P < 0.05) reduced compared with the hypertensive group. This finding was concurrent with significantly increased serum bioavailability of nitric oxide in the hypertensive rats treated with L-arginine and lisinopril. Also, there was a significant reduction in the level of blood urea nitrogen and creatinine of hypertensive rats treated with L-arginine and lisinopril. There was a significant (P < 0.05) reduction in markers of oxidative stress such as malondialdehyde and protein carbonyl and concurrent increase in the levels of antioxidant enzymes in the kidney of hypertensive rats treated with L-arginine and lisinopril. The results of this study suggest that L-arginine and lisinopril normalized blood pressure, reduced oxidative stress, and the expression of renal ACE and mineralocorticoid receptor, and improved nitric oxide production. Thus, L-arginine holds promise as a potential therapy against hypertension and renal damage., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Launaea taraxacifolia has been traditionally used for the management of conditions such as cardiovascular, respiratory, and metabolic diseases. High blood pressure was established by oral administration of L-Nitro Arginine Methyl Ester (L-NAME) a non-selective inhibitor of endothelial nitric oxide synthase (eNOS). The antihypertensive action of the methanol leaf extract of L. taraxacifolia was examined. Fifty male Wistar rats were divided into 5 groups of 10 animals per group: Group A (Distilled water), Group B (Hypertensive rats; 40mg/kg L-NAME), Group C (Hypertensive rats plus 100mg/kg extract), Group D (Hypertensive rats plus 200 mg/kg extract) and Group E (Hypertensive rats plus 10mg/kg of Lisinopril). The treatments were orally administered for five weeks. Haemodynamic parameters, urinalysis, indices of oxidative stress and immunohistochemistry were determined. Findings from this study showed that blood pressure parameters, urinary sodium and indices of oxidative stress increased significantly while In-vivo antioxidant defence systems decreased significantly in hypertensive rats. Immunohistochemistry revealed significant increases in expressions of mineralocorticoid receptor, angiotensin converting enzyme activity and kidney injury molecule-1 in kidney of hypertensive rats. Treatment with Launeae taraxacifolia normalized blood pressure parameters, urinary sodium, oxidative stress indices, antioxidant defence system, and serum nitric oxide bioavailability.

Background: Murraya koenigii (L.) Spreng. (Rutaceae) has been reported to positively affect liver function. However, the effect of M. koenigii leaves on N ω -Nitro-L-Arginine Methyl Ester (L-NAME) induced liver dysfunction is unknown. The aim of the present study was therefore to investigate the effect of M.koenigii leaves as tea on L-NAME induced liver dysfunction., Methods: Two variants of curry tea were formulated; one was formulated entirely from leaves of M. koenigii, the other was formulated with thaumatin-rich aril obtained from seeds of Thaumatococcus danielii (Benn.) Benth. (Marantaceae). Group I animals served as control and were untreated. Groups II and V animals were administered curry tea (CT). Group III and VI animals received curry-thaumatin tea (CTT). Concurrently, L-NAME (40 mg/kg) was administered to groups IV-VI respectively for 21 days. Blood and liver samples were collected at the end of the study for biochemical, histological, and immunohistochemical analysis., Results: L-NAME induced liver dysfunction evidenced by liver histology, increased activities of ALT, AST, hyperlipidemia, hepatic oxidative stress and increased hepatic NF-kB expression. Administration of CT and CTT ameliorated the L-NAME induced liver dysfunction evidenced by liver histology, increased NO hepatic bioavailability, reduced activity of ALT and AST, increased hepatic antioxidant system and decreased hepatic NF-kB expression. Thaumatin taste/flavor enhancer did not significantly reduce or potentiate the hepatoprotective, antioxidant and anti-lipidemic property of aqueous curry tea extracts in rats., Conclusion: L-NAME impaired liver function in rats. CT and CTT interfered with the ability of L-NAME to inhibit NO synthesis which was associated with ameliorated hepatic dysfunction., Practical Applications: The study reports that non-selective inhibition of nitric oxide by L-NAME in rats impairs liver function and formulated curry tea types interfered with the ability of L-NAME to inhibit NO synthesis which was associated with ameliorated hepatic dysfunction in rats., (© 2022 Wiley Periodicals LLC.)

Sodium fluoride (NaF) is one of the neglected environmental pollutants. It is ubiquitously found in the soil, water, and environment. Interestingly, fluoride has been extensively utilized for prevention of dental caries and tartar formation, and may be added to mouthwash, mouth rinse, and toothpastes. This study is aimed at mitigating fluoride-induced hypertension and nephrotoxicity with clofibrate, a peroxisome proliferator-activated receptor-alpha (PPARα) agonist. For this study, forty male Wistar rats were used and randomly grouped into ten rats per group, control, sodium fluoride (NaF; 300 ppm) only, NaF plus clofibrate (250 mg/kg) and NaF plus lisinopril (10 mg/kg), respectively, for 7 days. The administration of NaF was by drinking water ad libitum, while clofibrate and lisinopril were administered by oral gavage. Administration of NaF induced hypertension, and was accompanied with exaggerated oxidative stress; depletion of antioxidant defence system; reduced nitric oxide production; increased systolic, diastolic and mean arterial pressure; activation of angiotensin-converting enzyme activity and nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB); and testicular apoptosis. Treatment of rats with clofibrate reduced oxidative stress, improved antioxidant status, lowered high blood pressure through the inhibition of angiotensin-converting enzyme activity, mineralocorticoid receptor over-activation, and abrogated testicular apoptosis. Taken together, clofibrate could offer exceptional therapeutic benefit in mitigating toxicity associated with sodium fluoride., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Environmental and occupational exposure to chromium compounds has become potential aetiologic agent for kidney disease with excessive generation of free radicals, apoptosis, and inflammatory. These pathophysiologic mechanisms of potassium dichromate (K 2 Cr 2 O 7 ) have been well correlated with nephrotoxicity and cardiotoxicity. The cardioprotective and nephroprotective effects of Luteolin, a known potent antioxidant were evaluated in this study with 40 healthy rats in four experimental groups: Group A (normal saline), Groups B (30 mg/kg K 2 Cr 2 O 7 ), Group C (Luteolin 100 mg/kg and K 2 Cr 2 O 7 30 mg/kg), and Group D (Luteolin 200 mg/kg and K 2 Cr 2 O 7 30 mg/kg), respectively. Markers of antioxidant defense system, oxidative stress, blood pressure and micronucleated polychromatic erythrocytes (MnPEs), immunohistochemistry of Kidney, injury molecule (Kim-1), nuclear factor erythroid 2-related factor 2 (Nrf2), and cardiac troponin I were determined. Administration of K 2 Cr 2 O 7 increased blood pressure parameters in systolic, diastolic and mean arterial blood pressures, markers of oxidative stress, and frequency of micronucleated polychromatic erythrocytes, together with reduction in serum nitric oxide level. Renal Kim-1 and cardiac troponin I expressions were higher, but lower expressions of renal and cardiac Nrf2 were recorded with immunohistochemical analysis. Pre-treatment with Luteolin restored blood pressure parameters, with concomitant reduction in oxidative stress indicators, augmented antioxidant mechanisms and serum Nitric oxide level, lowered the expressions of Kim-1, cardiac troponin I and up-regulated of both cardiac and renal Nrf2, reduced the frequency of micronucleated polychromatic erythrocytes. Taken together, this study therefore demonstrates the cardioprotective, nephro protective and antigenotoxic effects of Luteolin through antioxidantive and radical scavenging mechanisms., (© 2021 Wiley Periodicals LLC.)

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the etiological agent of coronavirus disease 2019 (COVID-19). This virus has become a global pandemic with unprecedented mortality and morbidity along with attendant financial and economic crises. Furthermore, COVID-19 can easily be transmitted regardless of religion, race, sex, or status. Globally, high hospitalization rates of COVID-19 patients have been reported, and billions of dollars have been spent to contain the pandemic. Angiotensin-converting enzyme (ACE) 2 is a receptor of SARS-CoV-2, which has a significant role in the entry of the virus into the host cell. ACE2 is highly expressed in the type II alveolar cells of the lungs, upper esophagus, stratified epithelial cells, and other tissues in the body. The diminished expressions of ACE2 have been associated with hypertension, arteriosclerosis, heart failure, chronic kidney disease, and immune system dysregulation. Overall, the potential drug candidates that could serve as ACE2 activators or enhance the expression of ACE2 in a disease state, such as COVID-19, hold considerable promise in mitigating the COVID-19 pandemic. This study reviews the therapeutic potential and pharmacological benefits of the novel ACE2 in the management of COVID-19 using search engines, such as Google, Scopus, PubMed, and PubMed Central., (Copyright: © Oyagbemi, et al.)

Oxidative stress and inflammation arising from hyperglycaemia have been identified as important targets in mitigating hyperglycaemia-induced organ dysfunction in diabetics. Chrysophyllum albidum fruit is commonly consumed as fruit snacks because of its beneficial effects in diabetes management. This study aim to evaluate the protective mechanisms of Chrysophyllum albidum fruit extract (CAFE) in streptozotocin-induced rats involving attenuation of oxidative stress, nuclear factor-kappa B (NF-κB) and peroxisome proliferator-activated receptor-gamma (PPAR-γ). CAFE was investigated for in vitro antioxidant and alpha amylase inhibitory activity. Male Wistar rats were made diabetic by single intraperitoneal injection of streptozotocin (60 mg/kg). The rats were then treated with CAFE (100 and 200 mg/kg) and pioglitazone (10 mg/kg) for two weeks. Fasting blood sugar (FBS), blood pressure parameters, lipid profile, oxidative stress parameters, NF-κB and PPAR-γ were determined. The extract showed antioxidant and alpha amylase inhibitory activities. CAFE significantly reduced STZ-induced hyperglycaemia after 7 and 14 days of treatment. CAFE also reduced STZ-induced elevation of diastolic blood pressure and mean arterial pressure and as well reduced atherogenic index in diabetic rats. It significantly decreased lipid peroxidation but increased the enzymatic and non-enzymatic antioxidant markers in the plasma, liver, kidney and pancreas. The immunohistochemical analysis revealed that CAFE significantly decreased hepatic and renal tissues NF-κB while increasing PPAR-γ gene expressions. The results of this study collectively showed the protective effect of Chrysophyllum albidum fruit extract in streptozotocin-induced diabetic rats via modulation of oxidative stress and NF-κB/ PPAR-γ expressions., (Copyright © 2021. Published by Elsevier Masson SAS.)

Biologically active compounds such as caffeine and caffeic acid can be obtained in plants especially cocoa and coffee. Hence, the combinatory effect of caffeine and caffeic acid as well as their individual effect were assessed on the activities of arginase, angiotensin-1-converting enzyme (ACE) as well as nitric oxide (NOx), and malondialdehyde (MDA) level in the Nω-Nitro-L-arginine-methylester (L-NAME)-induced hypertensive rats. The individual and combinatory effect of caffeine and caffeic acid were investigated in L-NAME-induced rats. Animals were grouped into eleven containing six animals each. Hemodynamic parameter was determined by tail-cuff plethysmography. Furthermore, the result showed a notable rise in ACE and arginase activities of L-NAME-induced group compared with the control group. However, pretreatment with test compounds lowered ACE, arginase activities, and MDA content with rise in NOx. This study supports that caffeine and caffeic acid combinations demonstrated antihypertensive properties by lowering the systolic blood pressure in L-NAME-induced rats. PRATICAL APPLICATIONS: This duo bioactive compounds; caffeine (alkaloid) and caffeic acid (phenolic acid) are lavishly distributed in coffee. Their cardiopotective and cardiomodulatory roles have been investigated due to their biological activities. As far as we are aware, this could be foremost in-depth study on the antihypertensive and cardioprotective effect of the combinations of caffeine and caffeic acid targeting the key enzymes system relevant to hypertension. Decreased ACE and arginase activities as well as high nitric oxide (NOx) and low MDA level may be associated with its antihypertensive effect. This present study suggests that the combinations of this phenolics and alkaloid compound might proffer a therapeutic strategy in the management of hypertension., (© 2020 Wiley Periodicals LLC.)

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the etiological agent for the Coronavirus Disease 2019 (COVID-19). The COVID-19 pandemic has created unimaginable and unprecedented global health crisis. Since the outbreak of COVID-19, millions of dollars have been spent, hospitalization overstretched with increasing morbidity and mortality. All these have resulted in unprecedented global economic catastrophe. Several drugs and vaccines are currently being evaluated, tested, and administered in the frantic efforts to stem the dire consequences of COVID-19 with varying degrees of successes. Zinc possesses potential health benefits against COVID-19 pandemic by improving immune response, minimizing infection and inflammation, preventing lung injury, inhibiting viral replication through the interference of the viral genome transcription, protein translation, attachment, and host infectivity. However, this review focuses on the various mechanisms of action of zinc and its supplementation as adjuvant for vaccines an effective therapeutic regimen in the management of the ravaging COVID-19 pandemic. PRACTICAL APPLICATIONS: The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the etiological agent for the Coronavirus Disease 2019 (COVID-19), has brought unprecedented untold hardship to both developing and developed countries. The global race for vaccine development against COVID-19 continues with success in sight with attendant increasing hospitalization, morbidity, and mortality. Available drugs with anti-inflammatory actions have become alternative to stem the tide of COVID-19 with attendant global financial crises. However, Zinc is known to modulate several physiological functions including intracellular signaling, enzyme function, gustation, and olfaction, as well as reproductive, skeletal, neuronal, and cardiovascular systems. Hence, achieving a significant therapeutic approach against COVID-19 could imply the use of zinc as a supplement together with available drugs and vaccines waiting for emergency authorization to win the battle of COVID-19. Together, it becomes innovative and creative to supplement zinc with currently available drugs and vaccines., (© 2021 Wiley Periodicals LLC.)

Acute renal failure (ARF) has been documented as a life-threatening disease with high morbidity and mortality. We investigated the protective effect of Luteolin against ARF. In this study, forty-male Wistar albino rats were randomly divided into four groups ( n  = 10). Group A received normal saline. Group B received glycerol (10 ml/kg BW, 50% v/v in sterile saline, i.m.). Groups C and D were pretreated with Luteolin 100 and 200 mg/kg for 7 days, and thereafter administered Glycerol (10 ml/kg BW, 50% v/v in sterile saline, i.m.). Administration of glycerol significantly increased systolic blood pressure, diastolic blood pressure and mean arterial pressure. Renal protein carbonyl and xanthine oxidase increased significantly while significant reduction in the activity of renal glutathione peroxidase, glutathione S-transferase and glutathione reductase was observed in the glycerol intoxicated rats. Furthermore, administration of glycerol led to significant increases in serum creatinine and blood urea nitrogen together with reduction in nitric oxide (NO) bioavailability. Immunohistochemistry revealed that glycerol intoxication enhanced expressions of kidney injury molecule 1, nuclear factor kappa beta and cardiac troponin (CTnI). However, Luteolin pretreatment normalized blood pressure, reduced markers of oxidative stress, renal damage, and improved NO bioavailability. Luteolin also downregulated the expressions of kidney injury molecule 1, nuclear factor kappa beta and cardiac troponin. Together, Luteolin might open a novel therapeutic window for the treatment of acute renal failure and cardiac complication.

Hypertension is the most common cardiovascular disease that affects approximately 26% of adult population, worldwide. Rutin is one of the important flavonoids that is consumed in the daily diet, and found in many food items, vegetables, and beverages. Uninephrectomy (UNX) of the left kidney was performed, followed by induction of hypertension. The rats were randomly divided into four groups of 10 rats: group 1-Sham-operated rats; group 2-UNX rats, group 3-UNX-L-NAME (40 mg/kg) plus rutin (100 mg/kg bwt), and groups 4-UNX-L-NAME plus lisinopril (10 mg/kg bwt), orally for 3 weeks. Results revealed significant heightening of arterial pressure and oxidative stress indices, while hypertensive rats treated with rutin had lower expressions of angiotensin converting enzyme (ACE) and mineralocorticoid receptor in uninephrectomized rats. Together, rutin as a novel antihypertensive flavonoid could provide an unimaginable benefits for the management of hypertension through inhibition of angiotensin converting enzyme and mineralocorticoid receptor. PRACTICAL APPLICATIONS: Hypertension has been reported to be the most common cardiovascular disease, affecting approximately 26% of the adult population worldwide with predicted prevalence to increase by 60% by 2025. Recent advances in phytomedicine have shown flavonoids to be very helpful in the treatment of many diseases. Flavonoids have been used in the treatment and management of cardiovascular diseases, obesity and hypertension. The study revealed that rutin, a known flavonoid inhibited angiotensin converting enzyme (ACE), angiotensin 2 type 1 receptor (ATR1), and mineralocorticoid receptor (MCR), comparable to the classic ACE inhibitor, Lisinopril, indicating the novel antihypertensive property of rutin. Therefore, flavonoids such as rutin found in fruits and vegetables could, therefore, serve as an antihypertensive drug regimen. Combining all, functional foods rich in flavonoids could be used as potential therapeutic candidates for managing uninephrectomized hypertensive patients., (© 2020 Wiley Periodicals LLC.)

Objectives: Acute kidney injury (AKI) is a malady with a sudden onset resulting in buildup of waste matters in the body, but a specific cure hasn't been found as a lasting solution to AKI. In this study, ramipril was evaluated for its potential therapy in glycerol-induced AKI in rats., Methods: Twenty animals were divided into four groups of five animals each. Group I was the control while group II was given glycerol on day 8 only, groups III and IV were administered with pioglitazone (reference drug) and ramipril for seven days respectively and on day 8 received glycerol. On the ninth day, blood and tissue samples were taken to assay for serum indicators of oxidative damage, enzymatic and nonenzymatic antioxidants, and creatinine and blood urea nitrogen. Animals were sacrificed thereafter; kidney was harvested for histological and immunohistochemical analysis. Expressions of caspase 3, renin receptor, NK-KB, and KIM-1 were carried out., Results: Ramipril significantly inhibited indicators of oxidative damage while also significantly increasing levels of enzymatic and nonenzymatic antioxidant markers. These drugs also significantly lowered the levels of creatinine and blood urea nitrogen. Histology also indicated that while there were massive infiltration of leucocytes and congestion of the kidney in toxicant group, the ramipril-treated group showed a milder condition. In immunohistochemistry, the two drugs significantly inhibited the expressions of the four proteins, which were highly expressed in the toxicant group., Conclusions: The study showed that ramipril and pioglitazone have nephroprotective effect and thus have the ability to blunt AKI through their anti-inflammatory, antiapoptosis, antirenin, and antioxidant properties., (© 2020 Adeolu Alex Adedapo et al., published by De Gruyter, Berlin/Boston.)

Cobalt-induced cardiomyopathy and renal toxicity have been reported in workers in processing plants, hard metal industries, diamond polishing and manufacture of ceramics. This study was designed to investigate the influence of Luteolin supplementation on cobalt-induced cardiac and renal toxicity in rats. Exposure of rats to cobalt chloride (CoCl 2 ) alone caused significant (p < 0.05) increases in cardiac and renal H 2 O 2 , malondialdehyde (MDA) and nitric oxide (NO), along with increased serum myeloperoxidase (MPO) activity. In addition, there were significant (p < 0.05) reductions in cardiac and renal glutathione peroxidase (GPx), glutathione S-transferase (GST) and reduced glutathione (GSH). CoCl 2 induced higher immuno-staining of nuclear factor kappa beta (NF-κB) in the heart and kidneys, and the kidney injury molecule (Kim-1) in the kidneys. Treatment with Luteolin or Gallic acid produced significant reversal of the oxidative stress parameters with reductions in NF-κB and Kim-1 expressions, leading to suppression of histopathological lesions observed in the tissues., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Objectives: Hypertension is the number one risk factor and primary contributor of cardiovascular diseases. Caesalpinia benthamiana is a valuable medicinal plant with unvalidated anti-hypertensive activity. This study was carried out to explore the antihypertensive effect of C. benthamiana on uninephrectomized hypertensive rats., Methods: Fifty rats were grouped into five groups, each containing 10 animals: Group A-normal control (normotensive); B-uninephrectomized control; C-uninephrectomized treated with 50 mg/kg C. benthamiana extract; D-uninephrectomized treated with 100 mg/kg C. benthamiana ; and E- uninephrectomized treated with 10 mg/kg of Lisinopril., Results: Significant increases were observed in systolic, diastolic and mean blood pressure of uninephrectomized control rats. Furthermore, markers of oxidative stress (malondialdehyde, hydrogen peroxide, protein carbonyl, myeloperoxidase and the advanced oxidative protein products) increased significantly while antioxidant status (reduced glutathione, glutathione peroxidase, glutathione S-transferase and superoxide dismutase), reduced significantly in uninephrectomized hypertensive rats. Histopathology revealed thrombosis and occlusion of coronary vessels in the heart, and congestion in the kidney. However, the observed high blood pressure parameters were remarkably normalized together with reduction in markers of oxidative stress and improvement in antioxidant defence system of uninephrectomized hypertensive rats treated with C. benthamiana extract similar to normotensive rats., Conclusions: C. benthamiana extract exhibited antihypertensive action, strong antioxidant ability, attenuated oxidative stress-mediated hypertension and lessened the development of cardiac and renal damage associated with hypertension induced by uninephrectomy and high dietary intake of salt. Together, C. benthamiana extract might be useful in the management of hypertension due to volume overload in the cardiovascular system., (© 2020 Walter de Gruyter GmbH, Berlin/Boston.)

Hypertension is a condition with chronic elevation of blood pressure and a common preventable risk factor for cardiovascular disease with attendant global morbidity and mortality. The present study investigated the novel antihypertensive and neuroprotective effect of Naringenin on L-N G -Nitro arginine methyl ester (L-NAME) induced hypertension together with possible molecular mechanism of action. Rats were divided into four groups. Rats in Group A were normotensive. The hypertensive group (Group B) received 40 mg/kg) of L-NAME alone while Groups C and D were concurrently administered Naringenin (50 mg/kg) or Lisinopril (10 mg/Kg) together with L-NAME orally for 3 weeks. Blood pressure parameters, markers of oxidative stress and renal damage were measured. The immunohistochemistry of kidney injury molecule 1, mineralocorticoid receptor and angiotensin converting enzyme were also determined. Results indicated significant increases in malondialdehyde, advanced oxidation protein products, protein carbonyl contents and decrease in serum nitric oxide bioavailability in hypertensive rats. Furthermore, there were significant increases in serum myeloperoxidase, urinary creatinine, albumin and blood urea nitrogen in hypertensive rats in comparison to hypertensive rats treated with either Naringenin or Lisinopril. Immunohistochemistry reveal significant expressions of kidney injury molecule 1, mineralocorticoid receptor and angiotensin converting enzyme in hypertensive rats. However, co-treatment with either Naringenin or Lisinopril mitigated both renal and neuronal oxidative stress, normalized blood pressure and lowered the expressions of kidney injury molecule 1, mineralocorticoid receptor and angiotensin converting enzyme. Collectively, Naringenin offered a novel antihypertensive and neuroprotective effect through down regulation of kidney injury molecule 1, mineralocorticoid receptor and angiotensin converting enzyme., Competing Interests: Declaration of competing interest The authors declare no conflicts of interest., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Background and Aim: Momordica charantia is a highly valued plant, widely distributed in the tropical and subtropical regions. The plant is reported to have a wide range of medicinal uses. This study was designed to explore the ameliorative potential of M. charantia methanol leaf extract in alloxan-induced diabetic animal model with a particular focus on the liver., Materials and Methods: Hepatoprotective effect of methanol leaf extract of M. charantia was assessed in alloxan-induced toxicity in 50 rats divided into five groups (A-E) (n=10). Group A normal control, Group B was toxicant group, and Group C animals received glibenclamide treatment while Groups D and E received extracts at 200 and 400 mg/kg doses, respectively. The experiment lasted for 28 days. Histopathological changes, blood glucose level, and serum enzymes such as aspartate aminotransferase, alanine aminotransferase, and alkaline phosphatase, oxidative status and caspase-9, and interleukin-1β (IL-1β) were evaluated., Results: Extract-treatment caused a decreased blood glucose level, markers of oxidative stress such as malondialdehyde and hydrogen peroxide (H 2 O 2 ). Treatment of rats with leaf extract of M. charantia resulted in increased levels and activities of protein thiols, non-protein thiols, glutathione (GSH), glutathione peroxidase, glutathione S-transferase, and superoxide dismutase indicating its antioxidant potential. The liver section revealed mild distortion of the hepatic architecture compared to the toxicant group, while decreased expressions of caspase-9 and IL-1β in extract-treated groups was observed., Conclusion: The plant extract exhibited antioxidant, anti-apoptotic, and anti-inflammatory effects, thus showing its hepatoprotective property., (Copyright: © Ofuegbe, et al.)

Ethnopharmacological Relevance: Phragmanthera incana (Schum) Balle is a member of the African mistletoes that has been reported to be used in ethnomedicine for the treatment of hypertension., Aim: The aim of this study was to investigate the antihypertensive effect of Phragmanthera incana leaf ethanol extract (PILEE) in NG-nitro-L-arginine methyl ester (L-NAME)-induced hypertensive rats., Materials and Methods: Phytochemical analysis of PILEE was determined using the Gas chromatography - Mass spectrophotometry (GC-MS) method. Antihypertensive activity was investigated in rats that received PILEE (50, 100 and 200 mg/kg) or captopril (40 mg/kg) daily for 28 days together with oral administration of L-NAME (40 mg/kg). Blood pressure parameters were measured on day 7, 14, 21 and 28. Blood was obtained for determination of serum nitrite, interleukin-6 (IL-6) and tumor necrosis factor, TNF-α. The heart, liver and kidneys were used to determine oxidative stress indices (malondialdehyde, reduced glutathione and catalase). The cardiac tissue was processed for histopathological changes., Results: The GC-MS profiling of PILEE identified 20 compounds namely fatty acid esters. Administration of PILEE (50, 100 and 200 mg/kg) dose dependently and significantly reduced systolic blood pressure and mean arterial pressure in hypertensive rats. PILEE administration significantly (p < 0.05) reversed elevated IL-6 and TNF-α in hypertensive rats. PILEE demonstrated antioxidant activity by attenuating L-NAME-induced elevated malondialdehyde and depletion of reduced glutathione and catalase activity in rat tissues. PILEE treatment demonstrated cardioprotective effect in L-NAME-induced cardiac hyperplasia and necrosis in rats., Conclusion: It can be concluded that Phragmanthera incana leaf ethanol extract possess antihypertensive, antioxidant and anti-inflammatory properties, suggesting a protective role in cardiovascular diseases., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Fluoride is an environmental contaminant that is ubiquitously present in air, water, and soil. It is commonly added in minute quantity to drinking water, toothpaste, and mouth rinses to prevent tooth decay. Epidemiological findings have demonstrated that exposure to fluoride induced neurodevelopmental toxicity, developmental neurotoxicity, and motor disorders. The neuroprotective effect of clofibrate, a peroxisome proliferator-activated receptor alpha agonist, was investigated in the present study. Forty male Wistar rats were used for this study and randomly grouped into 10 rats per group as control, sodium fluoride (NaF) alone (300 ppm), NaF plus clofibrate (250 mg/kg), and NaF plus lisinopril (10 mg/kg), respectively, for 7 days. NaF was administered in drinking water while clofibrate and lisinopril were administered by oral gavage. Markers of neuronal inflammation and oxidative stress, acetylcholinesterase activity, and neurobehavioral (hanging wire and open field) tests were performed. Immunohistochemistry was performed on brain tissues, and they were probed with glial fibrillary acidic protein, ionized calcium-binding adaptor molecule 1, and cerebellar Ca 2+ -binding protein calbindin-D28k. The results showed that NaF significantly increased of oxidative stress and neuroinflammation and inhibited AChE activity. Immunostaining showed reactive astrocytes, microgliosis, loss of dendritic spines, and arborization in Purkinje cells in rats administered only NaF. Neurobehavioral results showed that cotreatment of NaF with clofibrate improved muscular strength and locomotion, reduced anxiety, and significantly reduced astrocytic count. Overall, cotreatment of NaF with either clofibrate or lisinopril showed neuroprotective effects by mitigating neuronal inflammation and oxidative and motor incoordination. Hence, clofibrate could be seen as a novel drug candidate against neurodegeneration and motor disorders., (© 2019 Wiley Periodicals, Inc.)

Background: Haemorrhoids are common anorectal conditions seen in surgical practice, with various treatment modalities. This study compared the short-term outcome of injection sclerotherapy with 50% dextrose in water and rubber band ligation in the management of second-and third-degree haemorrhoids, in terms of symptoms improvement, complications, recurrence rate, retreatment rate and acceptability., Methodology: This was a prospective comparative study that was carried out in the endoscopic unit of the Obafemi Awolowo University Teaching Hospitals Complex, Ile-Ife, in southwestern Nigeria. Sixty consecutive patients with second- and third-degree haemorrhoids, who consented, were recruited into the study and were randomised into two groups. Group A had endoscopic injection sclerotherapy and Group B had endoscopic rubber band ligation., Results: With regard to anal protrusion, more patients consistently reported either complete (16 [64.4%]) or partial (9 [40.9%]) resolution of symptoms in Group B, compared to Group A which had 7 (28.0%) and 5 (22.7%) cases, respectively (P = 0.03). Resolution of anal bleeding was initially more in Group B than A (22 [95.7%] vs. 17 [77.3%] patients, respectively), in the first 24-h post-treatment; however, within the 1 st week, this ratio was reversed (P = 0.07). The retreatment rate for Group A and B was 23.3% and 13.3%, respectively,P = 0.34. More patients in Group B experienced severe pain post-treatment compared to Group A (P = 0.01). Three-month post-treatment, two (11.8%) patients in Group A and one (4.5%) in Group B had recurrence of anal bleeding (P = 0.42). There was no recurrence in anal protrusion in both treatment groups., Conclusion: Endoscopic rubber band ligation had a significantly higher success rate than endoscopic injection sclerotherapy, in terms of resolution of anal protrusion, but with higher pain score., Competing Interests: None

Background and Aim: High salt diet and uninephrectomy are associated with high blood pressure with attendant cardiovascular disease conditions such as hypertension, renal damage, myocardial infarction, and stroke. The aim of this study was to investigate the beneficial effects of consumption of cocoa and cocoa-containing products in the management of high blood pressure in uninephrectomized hypertensive rats., Materials and Methods: The effect of cocoa powder on blood pressure, markers of inflammation, oxidative stress, and histopathology were investigated in uninephrectomized animals fed with cocoa feed alone or in combination with a high salt diet. Male rats were randomly divided into five groups: Group A was the control group and fed with normal feed alone, Group B was fed with cocoa feed alone, Group C was fed with high salt diet (8% salt), GroupD was fed with cocoa-feed compounded with 8% salt for 4weeks after uninephrectomy, and GroupE was uninephrectomized rats on a normal diet. The left kidneys of animals in GroupsC, D, and E were removed by surgery. After 4weeks of treatment, the systolic, diastolic, and mean arterial blood pressure was measured. The serum markers of renal damage and oxidative stress were determined. Histological examination was also performed on renal and cardiac tissues., Results: Results showed significant increases in biomarkers of oxidative stress, inflammation, and renal damage with a concomitant decrease in antioxidant status in hypertensive uninephrectomized rats. Cocoa feed, however, significantly improved blood pressure and nitric oxide bioavailability, antioxidant status and reduced markers of inflammation and oxidative stress., Conclusion: These findings show that cocoa powder could be used to maintain blood pressure levels in hypertensive rats through its antioxidant capacity., (Copyright: © Jayeola, et al.)

Azadirachta indica (AI) is a medicinal plant with reported antioxidant and cardio-protective properties. The use of plant-based polyphenols has become greatly increased in the last one decade. The present study investigated the protective effect of the polyphenol-rich fraction (PRF) of the methanol-extract of Azadirachta indica against N ω -Nitro-L-Arginine Methyl Ester (L-NAME) induced hypertension and cardiorenal dysfunction in rats. Fifty (50) Wistar albino rats were grouped into five groups. Group A, the control, was administered potable water. Groups B-E received orally, 40 mg/kg of L-NAME only, 40 mg/kg of L-NAME and 100 mg/kg of AI extract, 40 mg/kg of L-NAME and 200 mg/kg of AI extract, and 40 mg/kg of L-NAME and 25 mg/kg of captopril, respectively for 21 days. The results of the present study revealed that L-NAME administration led to a significant increase in systolic blood pressure, diastolic blood pressure, and mean arterial blood pressure. Markers of oxidative stress (malondialdehyde,protein carbonyl) increased significantly while there was reduction in reduced glutathione level, activities of superoxide dismutase, glutathione peroxidase and glutathione-S-transferase as well nitric oxide bioavailability. Immunohistochemistry revealed higher expressions of nuclear factor kappa beta (NF- k B) and kidney injury molecule 1(Kim-1) and lower expressions of nuclear factor erythroid 2-related factor 2 (Nrf2) in hypertensive rats. Our results indicated that with PRF of AI restored high blood pressure, reduced markers of oxidative stress, normalized serum NO bioavailability and increased the expressions of Nrf2. Hence, PRF of Azadirachta indica could be used for the treatment of hypertension., Competing Interests: The authors have declared no conflict of interest., (© Georg Thieme Verlag KG Stuttgart · New York.)

Caffeic acid (CAA) and chlorogenic acid (CHA) are important members of hydroxycinnamic acid with natural antioxidant and cardio-protective properties. The present study aimed to determine the effect of CAA and CHA on systolic blood pressure, heart rates (HR) as well as on the activity of the angiotensin-1-converting enzyme (ACE), acetylcholinesterase (AChE), butrylcholinesterase (BChE) and arginase in cyclosporine-induced hypertensive rats. Experimental rats were distributed into 7 groups (n = 6): normotensive control rats; hypertensive rats (induced rats) as well as hypertensive- treated groups with captopril (10 mg/kg/day), CAA (10 and 15 mg/kg/day) and CHA (10 and 15 mg/kg/day), respectively. The experiment lasted for 7 days and the systolic blood pressure (SBP) and heart rates were recorded using tail-cuff method. Oral administration of captopril, caffeic acid and chlorogenic acid normalized hypertensive effect caused by cyclosporine administration. CAA and CHA significantly (P < 0.05) reduced SBP and HR, activity of ACE, AChE, BChE and arginase in the treated hypertensive rats compared with cyclosporine induced-hypertensive rats. Likewise, CAA and CHA improved nitric oxide (NO) bioavailability, increased catalase activity and reduced glutathione content while malondialdehyde (MDA) level was reduced compared with cyclosporine hypertensive rats. Findings from this study shows that CAA and CHA exhibited blood pressure lowering properties and reduced activities of key enzymes linked to the pathogenesis of hypertension in cyclosporine-induced rats. These might be some of the possible mechanisms of action by which their cardio-protective properties are exhibited., (Copyright © 2018 Elsevier Masson SAS. All rights reserved.)