Redox Homeostasis and Prospects for Therapeutic Targeting in Neurodegenerative Disorders.

Reactive species, such as those of oxygen, nitrogen, and sulfur, are considered part of normal cellular metabolism and play significant roles that can impact several signaling processes in ways that lead to either cellular sustenance, protection, or damage. Cellular redox processes involve a balance in the production of reactive species (RS) and their removal because redox imbalance may facilitate oxidative damage. Physiologically, redox homeostasis is essential for the maintenance of many cellular processes. RS may serve as signaling molecules or cause oxidative cellular damage depending on the delicate equilibrium between RS production and their efficient removal through the use of enzymatic or nonenzymatic cellular mechanisms. Moreover, accumulating evidence suggests that redox imbalance plays a significant role in the progression of several neurodegenerative diseases. For example, studies have shown that redox imbalance in the brain mediates neurodegeneration and alters normal cytoprotective responses to stress. Therefore, this review describes redox homeostasis in neurodegenerative diseases with a focus on Alzheimer's and Parkinson's disease. A clearer understanding of the redox-regulated processes in neurodegenerative disorders may afford opportunities for newer therapeutic strategies.

Chromatographic fractions from Chrysophyllum albidum stem bark boost antioxidant enzyme activity and ameliorate some markers of diabetes complications.

BACKGROUND AND AIM: Diabetes, with hyperglycaemia as hallmark, is a global crisis that reduces the antioxidant status and produces complications when poorly managed. The development of complications can be indicated by inflammation, lipid peroxidation and the accumulation of glycation adducts. Thus, the attenuation of hyperglycaemia and boosting of antioxidants status is key in ameliorating markers of diabetes complications. This work evaluated the potency of Chrysophyllum albidum stem bark on some markers of diabetes complications. EXPERIMENTAL PROCEDURE: A total of 100 female rats (180.80 ± 8.50 g) were assigned into ten groups of ten animals each; control received 1.0 ml of distilled water while those in groups DC, RD, F1, F3, F4, F5, F7, F9, F10 were induced into diabetes by intraperitoneal administration of 120 mg/kg body weight of alloxan and were orally administered distilled water, glibenclamide, 2.5 mg/kg of the chromatographic fractions 1, 3, 4, 5, 7, 9, and 10 respectively, once daily for 14 days. F7 was profiled for its bioactive constituents and the pancreas histology of the rats were examined. RESULTS: Chromatographic fractions F5 and F7 significantly decreased fasting blood glucose, glycosylated haemoglobin, C-reactive protein, total cholesterol, triglycerides, atherogenic index, malondialdehyde while insulin, high density lipoprotein, catalase, superoxide dismutase activities significantly increased. Fraction F7 revealed eight compounds and restored the distorted pancreas. CONCLUSION: Fraction F7 ameliorated the markers of diabetes complications considered in this study better than F5, restored the compromised pancreas and can be explored as lead candidate for production of drug for the management of diabetes.

Hypoxia-Inducible Factors as an Alternative Source of Treatment Strategy for Cancer.

Hypoxia-inducible factors (HIFs) are transcription factors that activate the transcription of genes necessary to circumvent to hypoxic (low oxygen level) environments. In carcinogenesis, HIFs play a critical role. Indeed, HIF-1α has been validated as a promising target for novel cancer therapeutics, even as clinical investigations have linked increased levels of HIF-1α with aggressive cancer progression as well as poor patient prognosis. More so, inhibiting HIF-1 activity restricted cancer progression. Therefore, HIF-1 is a viable target for cancer therapy. This may be expected considering the fact that cancer cells are known to be hypoxic. In order to survive the hypoxic microenvironment, cancer cells activate several biochemical pathways via the HIF-1α. Additionally, cellular and molecular insights have proved prospects of the HIF-1α pathway for the development of novel anticancer treatment strategies. The biochemical importance of hypoxia-inducible factors (HIFs) cannot be overemphasized as carcinogenesis, cancer progression, and HIFs are intricately linked. Therefore, this review highlights the significance of these linkages and also the prospects of HIFs as an alternative source of cancer therapies.

Phytochemical Analysis and Antimalarial Activity Aqueous Extract of Lecaniodiscus cupanioides Root.

Root aqueous extract of Lecaniodiscus cupanioides was evaluated for antimalarial activity and analyzed for its phytochemical constituents. Twenty-four (24) albino mice were infected by intraperitoneal injection of standard inoculum of chloroquine sensitive Plasmodium berghei (NK 65). The animals were randomly divided into 6 groups of 3 mice each. Group 1 served as the control while groups II-IV were orally administered 50, 150, and 250 mg/kg body weights of extract. Groups 5 and 6 received 1.75 and 5 mg/kg of artesunate and chloroquine, respectively. The results of the phytochemical analysis showed the presence of alkaloids (2.37%), saponin (0.336), tannin (0.012 per cent), phenol (0.008 per cent), and anthraquinone (0.002 per cent). There was 100 per cent parasite inhibition in the chloroquine group and 70 per cent in the 50 mg/kg body weight on day 12, respectively. The mean survival time (MST), for the control group was 14 days, artesunate 16 days, and chloroquine 30 days, while the groups that received 50 and 250 mg/kg body weight recorded similar MST of 17 days and the 150 mg/kg body weight group recorded 19 days. The results obtained indicated that the aqueous extract of Lecaniodiscus cupanioides may provide an alternative antimalarial.

Effects of aqueous extract of Musa paradisiaca root on testicular function parameters of male rats.

BACKGROUND: There is an age-long claim that the Musa paradisiaca root is used to manage reproductive dysfunction, most especially sexual dysfunction (as an aphrodisiac), but there are no data in the open scientific literature that have refuted or supported this claim and the effects of M. paradisiaca root on the testes. Therefore, this study was aimed at investigating the effect of oral administration of the aqueous extract of M. paradisiaca root on the testicular function parameters of male rat testes. METHODS: Sexually matured male albino rats (138.67±5.29 g) were randomly assigned into four groups, A, B, C, and D, that respectively received 0.5 mL (3.6 mL/kg body weight) of distilled water and 25, 50, and 100 mg/kg body weight of the extract, orally, once daily, for 14 days. RESULTS: The extract significantly increased (p<0.05) the testes-body weight ratio, total protein, sialic acid, glycogen, cholesterol, activities of alkaline phosphatase, γ-glutamyltransferase, acid phosphatase, and the concentration of testicular testosterone. In contrast, the extract decreased the concentrations of both luteinizing and follicle-stimulating hormones in the serum of the animals. The results revealed that oral administration of M. paradisiaca root extract at doses of 25, 50, and 100 mg/kg body weight enhanced the testosterone-dependent normal functioning of the testes. CONCLUSIONS: Overall, the aqueous extract of M. paradisiaca stimulated the normal functioning of the testes and exhibited both androgenic and anabolic properties. The results may explain the rationale behind the folkloric beneficial effect of the plant in the management of reproductive dysfunction.

Diethylnitrosamine-induced redox imbalance in rat microsomes: protective role of polyphenolic-rich extract from Sorghum bicolor grains.

BACKGROUND: This study investigates the protective role of polyphenolic-rich extract from Sorghum bicolor against diethylnitrosamine (DEN)-induced redox imbalance in rat microsomes. METHODS: Reactive oxygen species (ROS) scavenging potentials of the polyphenolic extract from S. bicolor (0.2-1.0 mg/mL) was investigated using 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical, superoxide ion, hydrogen peroxide, hydroxyl radical, and ferric ion reducing system. The detoxification of ROS was evaluated in DEN-induced redox imbalance in rat microsomes. RESULTS: Sorghum bicolor polyphenolic extract at 1.0 mg/mL scavenged the DPPH, superoxide ion, hydrogen peroxide, and hydroxyl radical at 75%, 76%, 79%, and 81%, respectively; it also reduced ferric ion significantly. The polyphenolic extract significantly (p<0.05) attenuated DEN-mediated decrease in the activities of ROS detoxifying enzymes (superoxide dismutase, catalase, glutathione peroxidase and reductase, and glucose-6-phosphate dehydrogenase). The concentrations of malondialdehyde, conjugated dienes, lipid hydroperoxide, protein carbonyl, and percentage DNA fragmentation in DEN-treated microsomes were significantly reduced by the polyphenolic extract. CONCLUSIONS: The results of the present study indicated that S. bicolor polyphenolic extract possessed in vitro antioxidant activity and protected microsomes from DEN-mediated oxidative stress by scavenging free radicals and ROS scavenger and inducer of ROS detoxifying enzymes.

Androgenic potentials of aqueous extract of Massularia acuminata (G. Don) Bullock ex Hoyl. stem in male Wistar rats.

UNLABELLED: The use of medicinal plants in the management of several ailments is gaining popularity nowadays. Massularia acuminata, one of such plants is commonly used as chewing sticks due to its antimicrobial activity and the aqueous extract of its stem as an aphrodisiac. Aphrodisiac activity in some plants may be due to androgen increasing property of its phytochemicals. AIM OF THE STUDY: This study therefore sought to assess the androgenic potentials of aqueous extract of Massularia acuminata stem in male rats for 21 days. MATERIALS AND METHODS: Male rats weighing between 220 and 260 g were completely randomized into four groups: A, B, C and D. Group A, the control received orally 1 ml of distilled water (the vehicle) while groups B, C and D were orally administered with 1 ml each corresponding to 250, 500 and 1000 mg/kg body weight of the plant extract, respectively for 21 days. Rats were sacrificed 24h after 1, 7 and 21 days. RESULTS: Compared with the control, extract administration at all the doses produced significant increase (P<0.05) in testes-body weight ratio, testicular protein, glycogen, sialic acid, cholesterol, testosterone, luteinizing and follicle stimulating hormone concentrations throughout the period of administration. Testicular gamma glutamyl transferase activities were decreased significantly (P<0.05) after the first dose and was sustained throughout the experimental period. CONCLUSION: The available evidence in this study suggests that aqueous extract of Massularia acuminata stem has androgenic potential which may stimulate male sexual maturation and enhance normal testicular function.

Effects of oral administration of aqueous extract of Fadogia agrestis (Schweinf. Ex Hiern) stem on some testicular function indices of male rats.

AIM OF THE STUDY: The effects of administration of aqueous extract of Fadogia agrestis (Schweinf. Ex Hiern) stem on some testicular function indices of male rats (Rattus norvegicus) and their recovery potentials for 10 days were investigated. MATERIALS AND METHODS: Rats were grouped into four: A, B, C and D where A (the control) received orally 1 ml of distilled water (the vehicle), B, C and D (the test groups) received orally on daily basis graded doses of 18, 50 and 100mg/kg body weight of the plant extract, respectively, for 28 days. RESULTS: Compared with the control, extract administration for 28 days at all the doses resulted in significant increase (P<0.05) in percentage testes-body weight ratio, testicular cholesterol, sialic acid, glycogen, acid phosphatase and gamma-glutamyl transferase activities while there was significant decrease (P<0.05) in the activities of testicular alkaline phosphatase, acid phosphatase, glutamate dehydrogenase and concentrations of protein. Recoveries were made by the animals on some of the testicular function indices mainly at 18 mg/kg body weight. CONCLUSIONS: The alterations brought about by the aqueous extract of Fadogia agrestis stem are indications of adverse effects on the male rat testicular function and this may adversely affect the functional capacities of the testes. The recovery made at the dose of 18 mg/kg body weight as used in folklore medicine suggests that it does not exhibit permanent toxicity at this dose.