scholarly journals Preclinical Immuno-recognition and Neutralization of Lethality Assessment of a New Polyvalent Antivenom, VINS Snake Venom Antiserum – African IHS®, against Envenomation of Ten African Viperid and Elapid Snakes

2021 ◽  
pp. 25-43
Author(s):  
Djameh, Georgina I. ◽  
Nyarko, Samuel ◽  
Tetteh-Tsifoanya, Mark ◽  
Marfo, Frances M. ◽  
Adjei, Samuel ◽  
...  
Keyword(s):  
Snake Venom ◽  
Sub Saharan Africa ◽  
In Vivo Studies ◽  
Health Concern ◽  
Major Protein ◽  
Snake Species ◽  
Neutralizing Capacity ◽  
Preclinical Efficacy

Snakebite envenomation is a major health concern in developing countries causing significant mortality and morbidity. With over 1.2 million cases annually caused by medically important snake species belonging to the two families Viperidae (Echis spp. and Bitis spp.) and Elapidae (Naja spp. and Dendroaspis spp.). Several antivenoms are being produced and distributed to western sub-Saharan Africa for treatment of envenomation with the absence of preclinical efficacy studies. The present study evaluated the preclinical efficacy of venoms from Echis leucogaster, Echis ocellatus, Bitis arietans, Bitis gabonica, Naja haje, Naja melanoleuca, Naja nigricollis, Dendroaspis jamesoni, Dendroaspis polylepis and Dendroaspis viridis against a polyvalent Snake Venom Antiserum - African IHS (lyophilised), manufactured by VINS Bioproducts Limited (Telangana, India). Our in vitro results showed that, the SVA- AIHS contains antibodies that are capable of recognizing and binding majority of protein components representative of all eight major protein families of venoms of the snake species tested by double immunodiffusion assay and confirmed by western blot. The venom antiserum exhibited high neutralization efficacy against all the viperid and elapid snake species venoms in in vivo studies and confirmed the manufacturer’s recommended neutralization capacity. This is clear evidence that the VINS polyvalent SVA-AIHS batch tested has strong neutralizing capacity and will be useful in treating envenoming by most African viperid and some elapid snake species.

scholarly journals A Review of the Potential of Phytochemicals from Prunus africana (Hook f.) Kalkman Stem Bark for Chemoprevention and Chemotherapy of Prostate Cancer

2017 ◽  
Vol 2017 ◽  
pp. 1-10 ◽  
Author(s):  
Richard Komakech ◽  
Youngmin Kang ◽  
Jun-Hwan Lee ◽  
Francis Omujal
Keyword(s):  
Prostate Cancer ◽  
Cancer Cells ◽  
Treatment Options ◽  
Chemotherapeutic Agents ◽  
Sub Saharan Africa ◽  
In Vivo Studies ◽  
Prostate Cancer Cells ◽  
Prunus Africana

Prostate cancer remains one of the major causes of death worldwide. In view of the limited treatment options for patients with prostate cancer, preventive and treatment approaches based on natural compounds can play an integral role in tackling this disease. Recent evidence supports the beneficial effects of plant-derived phytochemicals as chemopreventive and chemotherapeutic agents for various cancers, including prostate cancer. Prunus africana has been used for generations in African traditional medicine to treat prostate cancer. This review examined the potential roles of the phytochemicals from P. africana, an endangered, sub-Saharan Africa plant in the chemoprevention and chemotherapy of prostate cancer. In vitro and in vivo studies have provided strong pharmacological evidence for antiprostate cancer activities of P. africana-derived phytochemicals. Through synergistic interactions between different effective phytochemicals, P. africana extracts have been shown to exhibit very strong antiandrogenic and antiangiogenic activities and have the ability to kill tumor cells via apoptotic pathways, prevent the proliferation of prostate cancer cells, and alter the signaling pathways required for the maintenance of prostate cancer cells. However, further preclinical and clinical studies ought to be done to advance and eventually use these promising phytochemicals for the prevention and chemotherapy of human prostate cancer.

scholarly journals In vitro and in vivo studies of anti diabetic effect of khaya senegalensis leaves and bark extracts

2019 ◽  
Vol 7 (1) ◽  
pp. 12
Author(s):  
Marvit Osman Widdat Allah ◽  
Ayat Ahmed Alrasheid ◽  
Eltayeb Suliman Elamin
Keyword(s):  
Diabetes Mellitus ◽  
In Vitro Models ◽  
In Vivo Studies ◽  
Health Concern ◽  
Bark Extract ◽  
Diabetes Model ◽  
Ic50 Value ◽  
Khaya Senegalensis

Diabetes mellitus in Sudan is one of public health concern since it causes significant mortality and complications for long term. Though conventional drugs are used in the management of diabetes mellitus they are expensive, unavailable and also have numerous side effects. Khaya senegalensis has traditionally used in the management of diabetes. The present study was conducted to examine the In vitro and In vivo anti-diabetic activity of leaves and bark extracts of Khaya senegalensis. The leaves and bark of the plant were extracted with ethanol 96%, and then tested for anti-diabetic activity in a series of in vitro models and a type 2 diabetes model of rats. In vitro bark extract of k.senegalensis showed higher inhibitory activities against the enzyme with IC50 value 226.14 µg/ml. In vivo oral administration of the extracts of the k. senegalensis exhibited decrease in blood sugar level and was found to be time dependent. Bark extract showed strong in vitro and in vivo anti diabetic activity.  

A Review of Aristolochia indica: Ethnomedicinal Uses, Phytochemistry, Pharmacological and Toxicological Effect

2020 ◽  
Vol 06 ◽  
Author(s):  
Gopal Krishna Padhy
Keyword(s):  
Snake Venom ◽  
Safety Data ◽  
Preclinical Study ◽  
Scorpion Venom ◽  
In Vivo Studies ◽  
In Vivo Models ◽  
Toxicological Effect ◽  
Aristolochic Acids

Background: Aristolochia indica L. of the family Aristolochiaceae is a twining perennial herbs with an ancient history of medicinal use. In the Indian Ayurvedic system, it is mentioned for the treatment of snake venom, scorpion venom, pimple, fever and worm infection. Objective: To make accessible the current information that is existing on the traditional uses, phytochemistry, pharmacology and toxicology of Aristolochia indica . Additionally, to emphasize the potential uses of this plant to treat various diseases and to bring in a foundation for further research. Methods:: The present review is carried out by compiling literature from 1935 to 2020, concerning the morphology, tradional uses, phytochemistry, pharmacological activities and toxicological aspects of Aristolochia indica. Results:: Diverse chemical compounds including Aristolochic acids, aristolactam, Phenanthrenes, alkaloids, lignans, steroids and terpenes have been isolated from this plant. Mostly in-vivo models indicated several evidence in the use of this plant particularly to regulate fertility. Few in-vivo studies also proved usefulness of this plant in inflammation and diabetis. In some in-vitro studies the anti-snake venom, larvicidal, and anti-oxidant potential has been proved. Conclusion: Preclinical studies have demonstrated remarkable activity which support the conventional use of the plant as an antivenum, antifertility, antimicrobial and anti-inflammatory agent. Although few phytochemicals isolated (Aristolic acid, (12S)-7,12-secoishwaran-12-ol, Aristololactam-I N-β-D-glucoside, Aristolochic acids, β-sitosterol, (-) Hinokinin and Aristolactam-I) from the plant exhibited remarkable biological activity, it was only confined to preclinical study. Even though, the isolated aristolochic acids showed significant anti-snake venom activity but it was found to be nephrotoxic and mutagenic. More detailed safety data pertaining to dose of crude extracts or pure compounds needs to be generated.

scholarly journals Liposomes as a Nanoplatform to Improve the Delivery of Antibiotics into Staphylococcus aureus Biofilms

Pharmaceutics ◽  
2021 ◽  
Vol 13 (3) ◽  
pp. 321
Author(s):  
Magda Ferreira ◽  
Sandra N. Pinto ◽  
Frederico Aires-da-Silva ◽  
Ana Bettencourt ◽  
Sandra I. Aguiar ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Fibroblast Cell ◽  
Therapeutic Benefit ◽  
Bacterial Biofilm ◽  
In Vivo Studies ◽  
Health Concern ◽  
Free Form ◽  
Positively Charged

Staphylococcus aureus biofilm-associated infections are a major public health concern. Current therapies are hampered by reduced penetration of antibiotics through biofilm and low accumulation levels at infected sites, requiring prolonged usage. To overcome these, repurposing antibiotics in combination with nanotechnological platforms is one of the most appealing fast-track and cost-effective approaches. In the present work, we assessed the potential therapeutic benefit of three antibiotics, vancomycin, levofloxacin and rifabutin (RFB), through their incorporation in liposomes. Free RFB displayed the utmost antibacterial effect with MIC and MBIC50 below 0.006 µg/mL towards a methicillin susceptible S. aureus (MSSA). RFB was selected for further in vitro studies and the influence of different lipid compositions on bacterial biofilm interactions was evaluated. Although positively charged RFB liposomes displayed the highest interaction with MSSA biofilms, RFB incorporated in negatively charged liposomes displayed lower MBIC50 values in comparison to the antibiotic in the free form. Preliminary safety assessment on all RFB formulations towards osteoblast and fibroblast cell lines demonstrated that a reduction on cell viability was only observed for the positively charged liposomes. Overall, negatively charged RFB liposomes are a promising approach against biofilm S. aureus infections and further in vivo studies should be performed.

scholarly journals Antivenomics and in vivo preclinical efficacy of six Latin American antivenoms towards south-western Colombian Bothrops asper lineage venoms

2021 ◽  
Vol 15 (2) ◽  
pp. e0009073
Author(s):  
Diana Mora-Obando ◽  
Davinia Pla ◽  
Bruno Lomonte ◽  
Jimmy Alexander Guerrero-Vargas ◽  
Santiago Ayerbe ◽  
...  
Keyword(s):  
Costa Rica ◽  
Latin American ◽  
Species Complex ◽  
Sensu Stricto ◽  
Costa Rican ◽  
Snake Species ◽  
Bothrops Asper ◽  
Preclinical Efficacy

Background Bothrops asper represents the clinically most important snake species in Central America and Northern South America, where it is responsible for an estimated 50–80% of snakebites. Compositional variability among the venom proteomes of B. asper lineages across its wide range mirrors clinical differences in their envenomings. Bothropic antivenoms generated in a number of Latin American countries commonly exhibit a certain degree of paraspecific effectiveness in the neutralization of congeneric venoms. Defining the phylogeographic boundaries of an antivenom's effectivity has implications for optimizing its clinical use. However, the molecular bases and impact of venom compositions on the immune recognition and neutralization of the toxic activities of across geographically disparate populations of B. asper lineages has not been comprehensively studied. Methodology/Principal findings Third-generation antivenomics was applied to quantify the cross-immunorecognizing capacity against the individual components of venoms of three B. asper lineages (B. asper (sensu stricto), B. ayerbei and B. rhombeatus) distributed in south-western (SW) Colombia, of six Latin American antivenoms, produced against homologous (Colombia, INS-COL and PROBIOL) and Costa Rica (ICP)), and heterologous (Argentina (BIOL), Perú (INS-PERU) and Venezuela (UCV)) bothropic venoms. In vivo neutralization assays of the lethal, hemorrhagic, coagulant, defibrinogenating, myotoxic, edematogenic, indirect hemolytic, and proteolytic activities of the three SW Colombian B. asper lineage venoms were carried to compare the preclinical efficacy of three (Colombian INS-COL and PROBIOL, and Costa Rican ICP) antivenoms frequently used in Colombia. Antivenomics showed that all the six antivenom affinity matrices efficiently immunoretained most of the B. asper lineages venom proteins and exhibited impaired binding towards the venoms' peptidomes. The neutralization profile of the INS-COL, PROBIOL and ICP antivenoms towards the biological activities of the venoms of SW Colombian B. asper (sensu stricto), B. ayerbei and B. rhombeatus lineages was coherent with the antivenomics outcome. In addition, the combination of in vitro (antivenomics) and in vivo neutralization results allowed us to determine their toxin-specific and venom neutralizing antibody content. Noteworthy, heterologous INS-PERU, BIOL, and UCV bothropic antivenoms had equal or higher binding capacity towards the venoms components of SW Colombian B. asper lineages that the homologous Colombian and Costa Rican antivenoms. Conclusions/Significance The combined in vitro and in vivo preclinical outcome showed that antivenoms manufactured in Colombia and Costa Rica effectively neutralize the major toxic activities of SW Colombian B. asper lineage venoms. The antivenomics profiles of the heterologous antivenoms manufactured in Argentina, Venezuela, and Perú strongly suggests their (pre)clinical adequacy for the treatment of B. asper lineage envenomings in SW Colombia. However, their recommendation in the clinical setting is pending on in vivo neutralization testing and clinical testing in humans. Bothrops asper is a highly adaptable snake species complex, which is considered the most dangerous snake throughout much of its distribution range from the Atlantic lowland of eastern México to northwestern Perú. Antivenoms are the only scientifically validated treatment of snakebite envenomings. Venom variation is particularly common in wide ranging species, such as B. asper, and may result in variable clinical presentations of envenomings, as is the case for the B. asper species complex, potentially undermining the efficacy of snakebite treatments depending on the immunization mixture used in the generation of the antivenom. Conversely, phylogenetic conservation of antigenic determinants confers an unpredictable degree of paraspecificity to homologous antivenoms produced for a geographic area, but also to heterologous congeneric antivenoms, towards the venom components of allopatric conspecific populations. This work aimed at comparing the preclinical profile of a panel of Latin American homologous and heterologous antivenoms against the venoms of B. asper lineages distributed in SW Colombia. The outcome of this study strongly suggests the suitability of considering the heterologous antivenoms BIOL (Argentina), UCV (Venezuela) and INS-PERU (Perú) as alternatives to homologous Colombian INS-COL and PROBIOL and Costa Rican ICP antivenoms for the treatment of envenomings by B. asper (sensu stricto) in W Colombia and Ecuador, B. ayerbei in Cauca and Nariño (Colombia), and B. rhombeatus in Cauca river valley, SW Colombia.

scholarly journals Bioactive Peptides as Potential Nutraceuticals for Diabetes Therapy: A Comprehensive Review

2021 ◽  
Vol 22 (16) ◽  
pp. 9059
Author(s):  
Priya Antony ◽  
Ranjit Vijayan
Keyword(s):  
Molecular Mechanisms ◽  
Bioactive Peptides ◽  
Nutritional Intervention ◽  
Food Sources ◽  
In Vivo Studies ◽  
Health Concern ◽  
Antidiabetic Activity ◽  
Wide Range

Diabetes mellitus is a major public health concern associated with high mortality and reduced life expectancy. The alarming rise in the prevalence of diabetes is linked to several factors including sedentary lifestyle and unhealthy diet. Nutritional intervention and increased physical activity could significantly contribute to bringing this under control. Food-derived bioactive peptides and protein hydrolysates have been associated with a number health benefits. Several peptides with antidiabetic potential have been identified that could decrease blood glucose level, improve insulin uptake and inhibit key enzymes involved in the development and progression of diabetes. Dietary proteins, from a wide range of food, are rich sources of antidiabetic peptides. Thus, there are a number of benefits in studying peptides obtained from food sources to develop nutraceuticals. A deeper understanding of the underlying molecular mechanisms of these peptides will assist in the development of new peptide-based therapeutics. Despite this, a comprehensive analysis of the antidiabetic properties of bioactive peptides derived from various food sources is still lacking. Here, we review the recent literature on food-derived bioactive peptides possessing antidiabetic activity. The focus is on the effectiveness of these peptides as evidenced by in vitro and in vivo studies. Finally, we discuss future prospects of peptide-based drugs for the treatment of diabetes.

scholarly journals Protection of human ACE2 transgenic Syrian hamsters from SARS CoV-2 variants by human polyclonal IgG from hyper-immunized transchromosomic bovines

2021 ◽  
Author(s):  
Theron Gilliland ◽  
Yanan Liu ◽  
Rong Li ◽  
Matthew Dunn ◽  
Emily Cottle ◽  
...  
Keyword(s):  
Protective Efficacy ◽  
Rapid Evolution ◽  
Clinical Signs ◽  
In Vivo Studies ◽  
Hamster Model ◽  
S Protein ◽  
Neutralizing Capacity ◽  
Polyclonal Igg

Pandemic SARS CoV-2 has been undergoing rapid evolution during spread throughout the world resulting in the emergence of many Spike protein variants, some of which appear to either evade antibody neutralization, transmit more efficiently, or potentially exhibit increased virulence. This raises significant concerns regarding the long-term efficacy of protection elicited after primary infection and/or from vaccines derived from single virus Spike (S) genotypes, as well as the efficacy of anti-S monoclonal antibody based therapeutics. Here, we used fully human polyclonal human IgG (SAB-185), derived from hyperimmunization of transchromosomic bovines with DNA plasmids encoding the SARS-CoV-2 Wa-1 strain S protein or purified ectodomain of S protein, to examine the neutralizing capacity of SAB-185 in vitro and the protective efficacy of passive SAB-185 antibody (Ab) transfer in vivo. The Ab preparation was tested for neutralization against five variant SARS-CoV-2 strains: Munich (Spike D614G), UK (B.1.1.7), Brazil (P.1) and SA (B.1.3.5) variants, and a variant isolated from a chronically infected immunocompromised patient (Spike del144-146). For the in vivo studies, we used a new human ACE2 (hACE2) transgenic Syrian hamster model that exhibits lethality after SARS-Cov-2 challenge and the Munich, UK, SA and del144-146 variants. SAB-185 neutralized each of the SARS-CoV-2 strains equivalently on Vero E6 cells, however, a control convalescent human serum sample was less effective at neutralizing the SA variant. In the hamster model, prophylactic SAB-185 treatment protected the hamsters from fatal disease and minimized clinical signs of infection. These results suggest that SAB-185 may be an effective treatment for patients infected with SARS CoV-2 variants.

Covalent cofactor attachment to proteins: cytochrome c biogenesis

2005 ◽  
Vol 33 (4) ◽  
pp. 792-795 ◽  
Author(s):  
J.M. Stevens ◽  
T. Uchida ◽  
O. Daltrop ◽  
S.J. Ferguson
Keyword(s):  
Cytochrome C ◽  
Protoporphyrin Ix ◽  
Covalent Bond ◽  
Binding Mode ◽  
In Vivo Studies ◽  
Major Protein ◽  
Covalent Bonds ◽  
Cytochrome C Biogenesis

Haem (Fe-protoporphyrin IX) is a cofactor found in a wide variety of proteins. It confers diverse functions, including electron transfer, the binding and sensing of gases, and many types of catalysis. The majority of cofactors are non-covalently attached to proteins. There are, however, some proteins in which the cofactor binds covalently and one of the major protein classes characterized by covalent cofactor attachment is the c-type cytochromes. The characteristic haem-binding mode of c-type cytochromes requires the formation of two covalent bonds between two cysteine residues in the protein and the two vinyl groups of haem. Haem attachment is a complex post-translational process that, in bacteria such as Escherichia coli, occurs in the periplasmic space and involves the participation of many proteins. Unexpectedly, it has been found that the haem chaperone CcmE (cytochrome cmaturation), which is an essential intermediate in the process, also binds haem covalently before transferring the haem to apocytochromes. A single covalent bond is involved and occurs between a haem vinyl group and a histidine residue of CcmE. Several in vitro and in vivo studies have provided insight into the function of this protein and into the overall process of cytochrome c biogenesis.

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