HEMATOLOGICAL PARAMETERS OF ALLOXAN-INDUCED DIABETIC RATS TREATED WITH ETHANOL EXTRACTS AND FRACTIONS OF NAUCLEA LAFILOIA LEAF

Hematological parameters which have been implicated in diabetes mellitus were investigated in this study. N-hexane, ethyl acetate, butanol and methanol fractions of the ethanolic leaf extract of Nauclea latifolia were orally administered once daily for 2 weeks to diabetic rats. The levels of RBC, Hb, HCT, MCV, MCH, MCHC, PLT, PCT, MPV, PDW, WBC, lymphocyte and granulocyte were evaluated in blood. There was significant reduction (P < 0.05) in RBC and HCT levels in the treatment groups of ethyl acetate fraction (250 mg/kg) and ethanol extract (250 mg/kg) with significant increases (P < 0.05) in their MCV and MCH levels when compared with the diabetic control group. Significant increases (P < 0.05) in PLT levels of the treatment groups of ethanol extracts, n-hexane fractions and ethyl acetate fraction (100 mg/kg); PCT levels of ethanol extracts group and MPV levels of ethyl acetate fractions treatment groups was high. The treatment groups of glibenclamide, butanol, methanol, n-hexane, ethyl acetate fractions and ethanol extract (250 mg/kg) showed significant reduction (P < 0.05) in their WBC and lymphocyte levels while significant increase (P < 0.05) in granulocyte levels was noted in the treatment group of ethanol extract (100 mg/kg) when compared with diabetic control group. In conclusion, the ethanol extract proved to have anti-infective property. Some fractions, showed capabilities to boost the immune system

Effect of Combined Leaf Extracts of Vernonia amygdalina (Bitter Leaf) and Gongronema latifolium (Utazi) on the Pancreatic beta-Cells of Streptozotocin- Induced Diabetic Rats

The study evaluated the effect of combined extracts of Vernonia amygdalina (VA) and Gongronema latifolium (GL) on the pancreas of streptozotocin (STZ) induced diabetic Wistar rats. Thirty-two (32) albino rats were divided equally into 4 groups. Groups A and B which served as normal (NC) and diabetic (DC) controls respectively, received placebo treatment. The diabetic test groups C and D were respectively treated with combined extracts of VA and GL (200mg/kg b. w., p. o.) and insulin, (humulin 5 IU/kg, s.c.) for 28 days. Thereafter, the animals were sacrificed and blood and pancreas were collected for serum glucose and histological evaluation, respectively. Changes in animal weight were also measured within the period. From the results it was revealed that both the combined extracts and humulin significantly increased the animals’ body weight (p<0.05) from -10.5% reduction in the DC, to 7.6% and 8.9% respectively. In the same order, serum glucose significantly decreased (p<0.05) by 12.49% and 14.96% after the 28-day treatment compared to DC. The extent of reversal of hyperglycemia in the extract treated animals compared well with the insulin treated group. The biochemical results were corroborated with results of histological evaluations: The pancreatic β-cells of DC animals which were distorted and degenerated with shrunken cell mass as against prominent islet cells with normal exocrine pancreas of NC animals became rapidly proliferated upon intervention with the combined extracts, suggesting a possible regeneration of the islet cells. On the otherhand, intervention with humulin did not produce observable differences in the cyto-architecture of the pancreatic islets compared to the diabetic control, confirming an extra-pancreatic mechanism of insulin

Isolation of a pentacyclic triterpenoid from the antiplasmodial bioactive fraction of Nauclea latifolia (Sm) roots

Purpose: To research the antiplasmodial property of aqueous extract, fractions, and residue of Nauclea latifolia roots and to isolate the components responsible for the antiplasmodial activity.Methods: Roots of N. latifolia were macerated with distilled water; the extract was obtained, successively partitioned with ethyl acetate and butanol. The extract, fractions, and the residue obtained were evaluated for their in vivo antiplasmodial activity and compared with amodiaquine and artesunate. The residue (which exhibited the best therapeutic index) was subjected to column and thin layer chromatography to isolate its components. Purification led to the isolation of betulinic acid, which was characterized with the aid of spectroscopic techniques (1H, 13C NMR, and EI-MS).Results: The residue significantly inhibited parasite growth from 42.8 % (D2) to 77.6 % (D5). Therefore, residue exhibited the highest therapeutic index against Plasmodium berghei in the three in vivo antiplasmodial (prophylactic, suppressive, and curative) models and it compared favourably with amodiaquine (80.5 %) and artesunate (85.9 %). The major component of the residue was betulinic acid.Conclusion: The results validate the antiplasmodial claims of the roots of N. latifolia in folkloric medicine, and demonstrated that the isolate has a high therapeutic index in this regard. Further investigations, however, are required to determine the clinical efficacy and safety of the compound/isolate

Targeted Deletion of HIF-1α Gene in T Cells Prevents their Inhibition in Hypoxic Inflamed Tissues and Improves Septic Mice Survival

Sepsis patients may die either from an overwhelming systemic immune response and/or from an immunoparalysis-associated lack of anti-bacterial immune defence. We hypothesized that bacterial superantigen-activated T cells may be prevented from contribution into anti-bacterial response due to the inhibition of their effector functions by the hypoxia inducible transcription factor (HIF-1alpha) in inflamed and hypoxic areas.Using the Cre-lox-P-system we generated mice with a T-cell targeted deletion of the HIF-1alpha gene and analysed them in an in vivo model of bacterial sepsis. We show that deletion of the HIF-1alpha gene leads to higher levels of pro-inflammatory cytokines, stronger anti-bacterial effects and much better survival of mice. These effects can be at least partially explained by significantly increased NF-kappaB activation in TCR activated HIF-1 alpha deficient T cells.T cells can be recruited to powerfully contribute to anti-bacterial response if they are relieved from inhibition by HIF-1alpha in inflamed and hypoxic areas. Our experiments uncovered the before unappreciated reserve of anti-bacterial capacity of T cells and suggest novel therapeutic anti-pathogen strategies based on targeted deletion or inhibition of HIF-1 alpha in T cells

The evolving SARS-CoV-2 epidemic in Africa: Insights from rapidly expanding genomic surveillance

INTRODUCTION Investment in Africa over the past year with regard to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) sequencing has led to a massive increase in the number of sequences, which, to date, exceeds 100,000 sequences generated to track the pandemic on the continent. These sequences have profoundly affected how public health officials in Africa have navigated the COVID-19 pandemic. RATIONALE We demonstrate how the first 100,000 SARS-CoV-2 sequences from Africa have helped monitor the epidemic on the continent, how genomic surveillance expanded over the course of the pandemic, and how we adapted our sequencing methods to deal with an evolving virus. Finally, we also examine how viral lineages have spread across the continent in a phylogeographic framework to gain insights into the underlying temporal and spatial transmission dynamics for several variants of concern (VOCs). RESULTS Our results indicate that the number of countries in Africa that can sequence the virus within their own borders is growing and that this is coupled with a shorter turnaround time from the time of sampling to sequence submission. Ongoing evolution necessitated the continual updating of primer sets, and, as a result, eight primer sets were designed in tandem with viral evolution and used to ensure effective sequencing of the virus. The pandemic unfolded through multiple waves of infection that were each driven by distinct genetic lineages, with B.1-like ancestral strains associated with the first pandemic wave of infections in 2020. Successive waves on the continent were fueled by different VOCs, with Alpha and Beta cocirculating in distinct spatial patterns during the second wave and Delta and Omicron affecting the whole continent during the third and fourth waves, respectively. Phylogeographic reconstruction points toward distinct differences in viral importation and exportation patterns associated with the Alpha, Beta, Delta, and Omicron variants and subvariants, when considering both Africa versus the rest of the world and viral dissemination within the continent. Our epidemiological and phylogenetic inferences therefore underscore the heterogeneous nature of the pandemic on the continent and highlight key insights and challenges, for instance, recognizing the limitations of low testing proportions. We also highlight the early warning capacity that genomic surveillance in Africa has had for the rest of the world with the detection of new lineages and variants, the most recent being the characterization of various Omicron subvariants. CONCLUSION Sustained investment for diagnostics and genomic surveillance in Africa is needed as the virus continues to evolve. This is important not only to help combat SARS-CoV-2 on the continent but also because it can be used as a platform to help address the many emerging and reemerging infectious disease threats in Africa. In particular, capacity building for local sequencing within countries or within the continent should be prioritized because this is generally associated with shorter turnaround times, providing the most benefit to local public health authorities tasked with pandemic response and mitigation and allowing for the fastest reaction to localized outbreaks. These investments are crucial for pandemic preparedness and response and will serve the health of the continent well into the 21st century

Cytotoxic action of the leaves of Uvaria chamae P.Beauv. and Dicliptera paniculata (Forssk.) I.Darbysh. from Nigeria mediated through intrinsic apoptotic pathway induction in four cancer cell lines

Background: Over the years, the morbidity and mortality due to cancer have continued to increase worldwide. Plants are well utilized in Nigeria ethno-medicine for cancer treatment. However, scientific evidence, particularly at the molecular level, has been lacking, and biodiversity loss is a threat. Aim of the study: The cytotoxic activity of the leaves of six plants used in Nigeria ethno-medicine was investigated and the molecular pathway of cytotoxic action of two active extracts on four cancer cell lines (A549, RD, MCF-7, and HeLa) was also assessed. Materials and methods: Cytotoxic activities of the plant extracts were assessed on breast (MCF-7), lung (A549), cervical (HeLa), adenocarcinoma and rhabdomyosarcoma (RD) cells using MTT cell viability assay in a time-dependent manner. The sandwich ELISA method was used to assess the protein expressions (Bcl-2, BAX, and executioner caspase 3) involved in the apoptotic pathway in cancer cells after treatment with cytotoxic extracts. UHPLC-MS/MS approach was used to analyze the possible bioactive phytochemicals of the cytotoxic plant extract. Results: Uvaria chamae and Dicliptera paniculata extracts displayed good cytotoxicity across all cell lines in a time- and concentration-dependent manner (CC50 <30 µg/mL). Increased pro-apoptotic BAX and lowered expression of anti-apoptotic Bcl-2 show the cytotoxic action of the two extracts followed the intrinsic apoptotic pathway compared to untreated cells. The increased expression of executioner caspase 3 indicated that the intrinsic apoptotic pathway was caspase-dependent. Conclusion: The anticancer potential of U. chamae and D. paniculata in this study validates the use of these plants in Nigerian ethno-medicine, highlighting apoptosis as a molecular pathway of their cytotoxicity

Lipid profile and hepatoprotective effects of combined leaf extracts of Azadirachta Indica (Neem) and Peristrophe bicalyculata in Alloxan-induced diabetic rats.

Abstract  Purpose of the study: This study was designed to investigate the protective efficacy of ethanolic extracts of leaves of Azadirachta indica (AI) and Peristrophe bicalyculata (PB) on the liver of alloxan-induced diabetic albino wistar as well as their effect on serum lipid profile. Main findings: A significant decrease (P&lt;0.05) was observed in HDL, VLDL and triglyceride values while an increase (P&lt;0.05) was observed in LDL and total cholesterol values in the diabetic control (DC) compared with the normal control (NC). Treatment with PB reversed the decrease in HDL levels comparable to the reversal by insulin. All the extracts caused an increase in the value of VLDL compared to DC. The values of LDL decreased significantly (p&lt;0.05) in all the extract-treated rats relative to DC with the combine extracts showing a synergistic decrease. The decrease in TG was significantly (p&lt;0.05) reversed by treatment with all the extracts and insulin while the increase in TC was reversed only by AI. There was an increase in AST and ALT and a decrease in ALP levels in DC, relative to NC. Only the combined extract resulted in a reduction in AST level, relative to DC, comparable to the Insulin value. There was a significant decrease (p&lt;0.05) in ALT level in all treated animals compared to DC. Except for AI, no reversals were observed for ALP levels in all the treatment groups. Summary of findings: The results show that a combination of the two plant extracts will be most appropriate for a total normalization of the diabetes-induced hyperlipidemia and protection of the liver against diabetes-induced injury