Biochemical investigation of anti-cancer activity of Tulbaghia violacea

Philosophiae Doctor - PhDNatural products have been a source of many pharmaceutical drugs and a number of drugs that are currently used in the treatment of cancer are derivatives of compounds originally isolated from natural products. There is evidence that extracts of Tulbaghia violacea can be used to treat cancer. The activation of apoptosis in cancer cells is a target for the development of novel anti-cancer drugs since one of the characteristics of cancer cells is resistance to apoptosis due to the deregulation of biochemical pathways leading to apoptosis. In fact, many current anti-cancer drugs exert their effects through the activation of apoptosis. Previous studies showed that extracts of T.violacea induce apoptosis in cancer cells and one study reported on the isolation of a compound (methyl-ԃ-D-glucopyranoside), which is responsible for the pro-apoptotic activity of the T.violacea extract. Therefore the aim of this study was to investigate the anti-cancer activity of methyl-ԃ-Dglucopyranoside and extracts prepared from T.violacea. In this study the pro-apoptotic activity of methyl-ԃ-D-glucopyranoside and extracts prepared from T.violacea were investigated on a panel of human cancer cell lines, which included HepG2, MCF7, H157, HT29 and the non-cancerous cell line, KMST6. The induction of apoptosis was evaluated by flow cytometry using several bioassays which measures biochemical events (caspase activation, phosphatidylserine externalisation and reactive oxygen species (ROS) production that is associated with the induction of apoptosis. The results demonstrated that the effects of methyl--D-glucopyranoside on cultured cells are transient and that the cells recover from the effects of methyl--D-glucopyranoside. This suggested thatmethyl-ԃ-D-glucopyranoside is not the compound responsible for the pro-apoptotic bioactivity in the T.violacea extract. This study also showed that cytotoxic and pro-apoptotic bioactivity of the leaf-extract was significantly higher in comparison to the tuber-extract. The bioactivity of the organic solvent extracts (dichloromethane, hexane, methanol and 50% methanol/water) of T.violacea leaves was also significantly higher than water extracts of T.violacea leaves. A comparison of the different organic extracts prepared from the T.violacea leaves showed that the highest activity was observed for the dichloromethane and hexane extracts. In an effort to identify the bioactive compound(s) the dichloromethane extract was subjected to Versaflash® column chromatography. However, due to problems experienced with the solubility of the dichloromethane sub-fractions, these compounds could not be tested for their bioactivity. Palmitone (16-hentriacontanone) was identified as one of the major compounds present in the dichloromethane sub-fractions. This compound was previously shown to have anticonvulsant bioactivity but there is no evidence in the literature that it has anti-cancer or pro-apoptotic activities. Fingerprinting of the methanol extract showed the presence of long chain fatty acid derivatives, flavonoids and allicin derivatives in the methanol extract. Although, this study failed to isolate the pro-apoptotic bioactive compound(s) present in the extracts of T.violacea, it confirmed that extracts of this plant induce apoptosis in cultured human cancer cell lines

Gene expression modulation of apoptotic and oestrogen receptor alpha genes by active fractions of selected Nigerian plants on cervical cancer cell line (hela)

The roles of natural product in drug discovery and development cannot be over emphasised. It plays a vital role in human therapy and gives a better understanding on the cellular pathways.This study investigated the modulatory effects of partially purified fractions of Piper guineense Schumach. & Thonn. (Piperaceae), Zanthoxylum zanthoxyloides Lam. (Rutaceae), Amaranthus viridis L. (Amaranthaceae), Costus afer Ker-Gawl. (Zingiberaceae) and Catharanthus roseus (L.) G. Don. (Apocynaceae) on oestrogen receptor-α (ESR-α), tumour protein p53 (TP-53), retinoblastoma (RB) and NAD(P) H quinine oxidoreductase (NQO1) genes in cervical cancer cell line (HeLa cells). n-Hexane, ethylacetate, chloroform, and water fractions of 80% ethanol extracts of study plants were screened with brine shrimp lethality and water-soluble tetrazolium-1 (WST-1) cytotoxicity assay. HeLa cells were treated with 1:10 dilutions of IC50 concentrations of test fractions for 24 hours, total RNA was extracted, RNA quality was checked, and normalized to a baseline concentration. Gene expression were monitored by semi-quantitative reverse transcription-polymerase chain reaction (RT-PCR). Results showed that ESR-α was downregulated (p < 0.05) by P. guineense-hexane, C. roseuschloroform and A. viridis-ethylacetate fractions

Modulation of PON2 and Proinflammatory Cytokine Genes in Rat Tissue Exposed to Combined oral Contraceptive Ethinylestradiol and Levonorgestrel

Paraoxonase (PON2) was identified as a genetic risk factor for cardiovascular disease (CVD) and usage of oral contraceptive (OC) is associated with increased cervical cancer and cardiovascular risk. PON2 protect against atherosclerosis development at the cellular level and this phenomenon could be related to their antioxidative properties. Therefore, the aim of the present study was to investigate the effect of OC on the expression of PON2, pro-inflammatory cytokines interleukin one alpha (IL1α) and tumor necrosis factor alpha (TNFα) in the liver, kidney and brain of rats. Different dosage groups of eight female rats were treated with oral contraceptive (0.15mg levonorgestrel 0.03mg ethinylestradiol(A); 0.3mg levonorgestrel 0.06 mg ethinylestradiol (B) and 0.075 mg levonorgestrel 0.015 mg ethinylestradiol (C))/kg body-weight(bw)). Two groups of eight rats were included in the study for a control group (D) and ≤0.1% DMSO (drug vehicle) group (E), which were not subject to drug administration for 21days. The levels of expression of the gene were assessed using quantitative reverse polymerase chain reaction technique. Combined oral contraceptive treatment produced a significant increase(p<0.001) in the level expression of renal IL1α and TNFα in all the groups compared to control in a dose-dependent manner but has no significant effect on PON2. Meanwhile, OC resulted in significantly (p<0.0001) reduced level of expression of hepatic IL1α with no significant effect on hepatic PON2 and TNFα level. In the brain, OC resulted in significantly (p<0.0001) reduced level of expression of TNFα in all dose groups and IL1α level at 0.015mg/bw. Although OC treatment did increase the expression of brain PON2 significantly (p<0.05) at the lowest dose. Therefore, pharmacological modulation of the expression of genes could constitute a useful approach for preventing atherosclerosi

In vitro study on the hypoglycemic potential of Nicotiana tabacum leaf extracts

Inhibition of some carbohydrate metabolizing enzymes is one of the modes of action of antihyperglycemic agents. The aim of this study was to investigate the in vitro inhibition of α-amylase and α-glucosidase by extracts of N. tabacum leaf. Powdered leaves were extracted with acetone, ethanol and water, and tested for their ability to inhibit α-amylase from Aspergilus oryzae and α-glucosidase from Saccharomyces cerevisae. The results revealed that aqueous extract of the plant was most effective inhibitor of α-amylase (IC50 5.70 mg/mL) while acetone extract exhibited the best inhibitory potential on α-glucosidase (IC50 4.50 mg/mL). Kinetic studies showed that the mode of inhibition of α-amylase by aqueous extract was non-competitive while that of the acetone extract on α-glucosidase was competitive. The observed inhibitions of α-amylase and α-glucosidase suggest that the leaf extracts of N. tabacum may be useful in the management of Diabetes mellitus, which may due to the presence of phytochemicals

Imino-quinolyl palladium(II) and platinum(II) complexes: synthesis, characterization, molecular structures and cytotoxic effect

Imino-quinolyl ligands L1-L5 were synthesized by condensation reactions and obtained in good yields. Reactions of the ligands with either PdCl2(cod) or K2[PtCl4] gave the corresponding palladium(II) and platinum(II) complexes 1-10 also in good yields. All the compounds were characterized by elemental analysis, IR, 1H and 13C NMR spectroscopy. X-ray crystallography was used to confirm the structures of these compounds. Molecular structures of 3 and 5 showed that the ligands coordinate to the metal centre through the two nitrogen atoms, generating a distorted square planar geometry around the palladium atom. The new complexes exhibited remarkable cytotoxic activities against MCF-7 and HT-29 cancer cell lines.Web of Scienc

Imino-phospine palladium (II) and platinum (II) complexes: Synthesis, molecular structures and evaluation as antitumor agents

The imino-phosphine ligands L1 and L2 were prepared via condensation reaction of 2-(diphenylphosphino) benzaldehyde with substituted anilines and obtained in very good yields. An equimolar reaction of L1 and L2 with either PdCl2(cod) or PtCl2(cod) gave new palladium(II) and platinum(II) complexes 1–4. The compounds were characterized by elemental analysis, IR, 1H and 31P NMR spectroscopy. The molecular structures of 2, 3 and 4 were confirmed by X-ray crystallography. All the three molecular structures crystallized in monoclinic C2/c space system. The coordination geometry around the palladiumand platinumatoms in respective structures exhibited distorted square planar geometry at the metal centers. The complexes were evaluated in vitro for their cytotoxic activity against human breast (MCF-7) and human colon (HT-29) cancer cells, and they exhibited growth inhibitory activities and selectivity that were superior to the standard compound cisplatin.Web of Scienc

Public Health Surveillance for Adverse Events Following COVID-19 Vaccination in Africa

Local, national, and international health agencies have advocated multi-pronged public health strategies to limit infections and prevent deaths. The availability of safe and effective vaccines is critical in the control of a pandemic. Several adverse events have been reported globally following reception of different vaccines, with limited or no data from Africa. This cross-sectional epidemiological study investigated adverse events following COVID-19 vaccination in Africans from April–June, 2021 using a structured online questionnaire. Out of 1200 participants recruited, a total of 80.8% (n = 969) respondents from 35 countries, including 22 African countries and 13 countries where Africans live in the diaspora, reported adverse events. Over half of the vaccinees were male (53.0%) and frontline healthcare workers (55.7%), respectively. A total of 15.6% (n = 151) reported previous exposure to SARS-CoV-2, while about one-fourth, 24.8% (n = 240), reported different underlying health conditions prior to vaccination. Fatal cases were 5.1% (n = 49), while other significant heterogenous events were reported in three categories: very common, common, and uncommon, with the latter including enlarged lymph nodes 2.4% (n = 23), menstrual disorder 0.5% (n = 5), and increased libido 0.2% (n = 2). The study provided useful data for concerned authorities and institutions to prepare plans that will address issues related to COVID-19 vaccines

Anti-inflammatory Activity of Ethanolic Leaf Extracts of Thaumatococus Danielli on Iodoacetamide Treated Rats

Anti-inflammatory drugs such as Non-steroidal anti-inflammatory drugs (NSAIDs) are used to reduce swellings and pains caused by inflammation but, long term use of these anti-inflammatory drugs results in the damage of human biological system such as the liver, gastrointestinal tract, etc. Hence, there is need for safer, potent, anti-inflammatory drugs. Hence, the anti-inflammatory activity of ethanol leaf extract of Thaumatococcus danielli on iodoacetamide treated rats was investigated. Forty-two (42) rats were divided into seven groups of six rats each. Group 1 (positive control) received 1ml of 1% CMC; Group 2 (negative control) received 1ml of 1% CMC and 1ml of 0.1% iodoacetamide; Group 3 received 50mg/kg of extract (low dose) and 1ml of 0.1% iodoacetamide; Group 4 received 100mg/kg of extract (high dose) and 1ml of 0.1% iodoacetamide; Group 5 received 50mg/kg of extract (high dose) and 1ml of 1% CMC; Group 6 received 100mg/kg of extract (high dose) and 1ml of 1% CMC; Group 7 received 1ml 1% iodoacetamide and 2.14mg/kg diclofenac. Treatment with T. danielli extract showed no significant difference (p&gt;0.05) in all groups in lymphocyte, RBC, granulocyte, platelet, hemoglobin concentration, hematocrit, mean corpuscular volume and mean corpuscular hemoglobin count but, a significant reduction in all groups was observed in ESR. Moreso, a significant decrease was observed in WBC in the high dose group, and a significant increase in group administered diclofenac.  Ethanolic leaves extract of Thaumaococcus danielli possess an anti-inflammatory potential, possibly due to its embedded phytoconstituents. Keywords: Thaumatococcus danielli, Anti-inflammatory activity, Hematological studies, Erythrocyte sedimentation rate, Nitric oxide concentration DOI: 10.7176/JNSR/13-10-03 Publication date:May 31st 202