Potent Nrf2-inducing, antioxidant, and anti-inflammatory effects and identification of constituents validate the anti-cancer use of Uvaria chamae and Olax subscorpioidea.

BACKGROUND: Uvaria chamae (UC) and Olax subscorpioidea (OS) roots are included in traditional anti-cancer remedies and some studies have identified their chemopreventive/chemotherapeutic potential. This study aimed to identify some cellular/molecular mechanisms underlying such potential and the associated chemical constituents. METHODS: Effect on the viability of cancer cells was assessed using the Alamar Blue assay; ability to modulate oxidative stress was assessed using the 2',7'-dichlorofluorescein diacetate (DCFDA) assay; potential to modulate Nuclear factor erythroid 2-related factor like-2 (Nrf2) activity was assessed in the AREc32 luciferase reporter cell line; and anti-inflammatory effect was assessed using lipopolysaccharide-induced nitric oxide release model in the RAW264.7 cells (Griess Assay). Chemical constituents were identified through liquid chromatography-mass spectrometry (LC-MS). RESULTS: Extracts up to 100 µg/ml were non-toxic or mildly toxic to HeLa, AREc32, PC3 and A549 cells (IC50 > 200 µg/ml). Each extract reduced basal and peroxide-induced levels of reactive oxygen species (ROS) in HeLa cells. OS and UC activated Nrf2, with UC producing nearly four-fold induction. Both extracts demonstrated anti-inflammatory effects. Chamanetin, isochamanetin, isouvaretin, uvaricin I and other compounds were found in U. chamae root extract. CONCLUSION: As Nrf-2 induction, antioxidant and anti-inflammatory activities are closely linked with chemoprevention and chemotherapy of cancers, the roles of these plants in traditional anti-cancer remedies are further highlighted, as is their potential as sources of drug leads.

Bioactivity and modulatory functions of Napoleona vogelii on oxidative stress-induced micronuclei and apoptotic biomarkers in mice.

Napoleona vogelii is used in traditional medicine for the management of pain, inflammatory conditions and cancer. This study was conducted to investigate the modulatory mechanisms of methanol stem bark extract of N. vogelii on induction of micronuclei, apoptotic biomarkers and in vivo antioxidant enzymes in mice. Forty male albino mice were randomly divided into eight groups (n = 5) and were administered distilled water (DW, 5 mL/kg) as negative control, 100, 200 or 400 mg/kg of the extract respectively for 28 days before the injection of cyclophosphamide (CP, 40 mg/kg) i.p. on the 28th day. The remaining groups were administered 100, 200 or 400 mg/kg of the extract only for 28 days. Twenty four hours after injection of CP or administration of the last dose of extract, animals were euthanized by cervical dislocation and blood samples collected for determination of in vivo antioxidants, the spleen harvested for immunohistochemical expression of NFκB, Bcl-2, Bax and p53. Bone marrow smears were also made for the micronucleus assay. Treatment with the extract resulted in a significant (p < 0.0001) reduction in frequency of micronucleated polychromatic erythrocytes (MNPCEs) compared to CP exposed control conferring protection of 75.09, 94.74 and 96.84% at 100, 200 or 400 mg/kg respectively. In extract and CP exposed animals, there were significant (p < 0.05) increases in GSH, GST and SOD with a corresponding significant (p < 0.05) reduction in MDA. In addition, the extract significantly downregulated cytoplasmic levels of NFκB and Bcl-2 and upregulated Bax and p53. These findings demonstrate that N. vogelli may serve as an interesting lead for chemo-preventive drug development.

Antioxidative, antimitotic, and DNA-damaging activities of Garcinia kola stem bark, Uvaria chamae root, and Olax subscorpioidea root used in the ethnotherapy of cancers.

Garcinia kola (GK) stem bark, Uvaria chamae (UC) root, and Olax subscorpioidea (OS) root are components of various indigenous/traditional anticancer regimens. It is, therefore, possible that they might combat oxidative stress and impair cellular proliferation linked to carcinogenesis. In this study, we investigated the antioxidative, mito-depressive, and DNA-damaging activities of the three plant extracts in order to provide further mechanistic insights into their potential anticancer roles in documented cancer remedies that include them. Antioxidative properties were investigated in the 1,1-diphenyl-2-picrylhydrazyl (DPPH) and nitric oxide (NO) radical scavenging assays and an animal model of drug (cisplatin)-induced oxidative stress. The Allium cepa assay and the single cell gel electrophoresis (SCGE) assay were used to assess mito-depressive and DNA-damaging activities. GK and OS showed significantly higher antioxidant activities in the DPPH assay than ascorbic acid; OS had the lowest IC50 of the three plants in the NO assay, comparable to that of ascorbic acid. Pretreatment with the extracts produced an ameliorative and protective effect against the cisplatin-induced oxidative stress as shown by inhibition of lipid peroxidation and improved or restored reduced glutathione and superoxide dismutase levels. In the Allium test, the three extracts produced significant decreases in root growth and also significant cytotoxicity as evidenced by decreased mitotic index. Each of the extracts also showed significantly increased tail DNA (%) in the SCGE assay, indicating the significant DNA-damaging effect. Taken together, this study demonstrates the possible chemopreventive and chemotherapeutic potentials of the three study extracts, which may explain the roles of their source plants in traditional remedies in the therapy of cancers.

Methyl jasmonate reduces testosterone-induced benign prostatic hyperplasia through regulation of inflammatory and apoptotic processes in rats.

BACKGROUND: Phytotherapy is becoming a treatment option in management of diseases including benign prostatic hyperplasia (BPH). We have shown previously that methyl jasmonate (MeJA) ameliorated BPH, however the underlying mechanism of action remains unknown. This study was designed to investigate in mechanistic terms the protective role of MeJA in BPH. METHODS: BPH was induced by daily injections of testosterone propionate (TP) (3mg/kg) for 28 days. RESULTS: The weight and organo-somatic weight of prostate in BPH rats were 6.8 and 5.1 times higher than castrated-control group, respectively. Inflammatory markers; prostatic myeloperoxidase and total nitric oxide were significantly increased in BPH group. The activity of aniline hydroxylase (Phase I drug metabolizing enzyme) was significantly increased in BPH rats by 22%. In BPH group, immuno-histochemistry revealed strong expression of prostatic inducible nitric oxide synthase, cyclooxygenase-2 and Bcl2, while mild expression of p53 and Bax were seen. Serum triglyceride and total cholesterol were significantly increased, while HDL-c was decreased in BPH. Interestingly, MeJA and finasteride (singly or combination) attenuated inflammatory indices and induced apoptotic parameters in BPH rats. CONCLUSION: MeJA protects against TP-induced BPH via mechanisms that involve anti-inflammation, induction of apoptosis and inhibition of phase I drug metabolizing enzyme.

Selenium status of idiopathic infertile Nigerian males.

Selenium concentration in the sera and seminal plasma of 60 infertile males (40 oligospermia and 20 azoospermia) and 40 males with proven evidence of fertility (normospermia; control group) were estimated using atomic absorption spectrophotometry. Results were correlated with spermatogram and hormonal levels in order to determine their relationship and significance in male infertility. The mean serum concentrations of selenium was found to be significantly increased in oligospermic compared to azoospermic subjects and controls (p < 0.01), whereas the seminal plasma level was significantly higher in azoospermic compared to oligospermic subjects and controls (p < 0.001). Thus, the ratio of serum selenium to seminal plasma selenium was 1: 1 in controls, 4: 1 in oligospermia, and 1: 2 in azoospermic subject.A significant inverse correlation was observed between serum selenium level and sperm count (p < 0.01). Similarly, seminal plasma selenium correlated with spermatozoa motility, viability, and morphology. Serum selenium level shows positive correlation with the serum testosterone level (p < 0.01). In conclusion, there appears to be a physiological balance in the distribution of selenium in serum and seminal plasma compartment of control males. A disturbance in this balance has a significant influence on spermatogenesis. Selenium appears to have a positive influence on Leydig cells, thus influencing the secretion of testosterone.