ABSTRACT
Previously transgenic Kalanchoe pinnata plants producing an antimicrobial peptide cecropin P1 (CecP1) have been reported. Now we report biological testing K. pinnata extracts containing CecP1 as a candidate drug for treatment of wounds infected with Candida albicans. The drug constitutes the whole juice from K. pinnata leaves (not ethanol extract) sterilized with nanofiltration. A microbicide activity of CecP1 against an animal fungal pathogen in vivo was demonstrated for the first time. However, a favorable therapeutic effect of the transgenic K. pinnata extract was attributed to a synergism between the fungicide activity of CecP1 and wound healing (antiscar), revascularizing, and immunomodulating effect of natural biologically active components of K. pinnata. A commercial fungicide preparation clotrimazole eliminated C. albicans cells within infected wounds in rats with efficiency comparable to CecP1-enriched K. pinnata extract. But in contrast to K. pinnata extract, clotrimazole did not exhibit neither wound healing activity nor remodeling of the scar matrix. Taken together, our results allow assumption that CecP1-enriched K. pinnata extracts should be considered as a candidate drug for treatment of dermatomycoses, wounds infected with fungi, and bedsores.
Subject(s)
Candidiasis/drug therapy , Immunomodulation , Kalanchoe/chemistry , Peptides/therapeutic use , Plant Extracts/therapeutic use , Wound Healing/drug effects , Wound Infection/drug therapy , Animals , Antifungal Agents/administration & dosage , Antifungal Agents/chemistry , Antifungal Agents/isolation & purification , Antifungal Agents/therapeutic use , Candida albicans/drug effects , Candidiasis/microbiology , Clotrimazole/therapeutic use , Dermatomycoses/drug therapy , Drug Synergism , Kalanchoe/genetics , Peptides/administration & dosage , Peptides/metabolism , Phytotherapy , Plant Extracts/administration & dosage , Plant Extracts/chemistry , Plant Extracts/isolation & purification , Plant Leaves/chemistry , RatsABSTRACT
Procedure of manufacturing K. pinnata water extracts containing cecropin P1 (CecP1) from the formerly described transgenic plants is established. It included incubation of leaves at +4°C for 7 days, mechanical homogenization of leaves using water as extraction solvent, and heating at +70°C for inactivating plant enzymes. Yield of CecP1 (after heating and sterilizing filtration) was 0.3% of total protein in the extract. The water extract of K. pinnata + CecP1 exhibits favorable effect on healing of wounds infected with S. aureus (equal to Cefazolin) and with a combination of S. aureus with P. aeruginosa (better than Cefazolin). Wild-type K. pinnata extract exhibited evident microbicide activity against S. aureus with P. aeruginosa but it was substantially strengthened in K. pinnata + CecP1 extract. K. pinnata extracts (both wild-type and transgenic) did not exhibit general toxicity and accelerated wound recovery. Due to immunomodulating activity, wild-type K. pinnata extract accelerated granulation of the wound bed and marginal epithelialization even better than K. pinnata + CecP1 extract. Immunomodulating and microbicide activity of K. pinnata synergizes with microbicide activity of CecP1 accelerating elimination of bacteria.
Subject(s)
Anti-Infective Agents/therapeutic use , Kalanchoe/genetics , Peptides/therapeutic use , Plant Extracts/therapeutic use , Pseudomonas Infections/drug therapy , Pseudomonas aeruginosa/physiology , Recombinant Proteins/therapeutic use , Staphylococcal Infections/drug therapy , Staphylococcus aureus/physiology , Wound Infection/drug therapy , Animals , Cefazolin/therapeutic use , Humans , Immunomodulation , Male , Peptides/genetics , Plants, Genetically Modified , Rats , Rats, Wistar , Recombinant Proteins/genetics , Swine , Wound Healing/drug effectsABSTRACT
The ADMA-like pre-eclampsia in pregnant rats was modeled by daily introduction of L-NAME in a dose of 25 mg/kg for 7 days. L-arginine (200 mg/kg) prevented the development of arterial hypertension and a decrease in placentary microcirculation and microalbuminuria. The possibility of using L-arginine for the prevention of competitive eNOS inhibition by ADMA is discussed.
Subject(s)
Arginine/administration & dosage , Endothelium/drug effects , Hypertension/prevention & control , Placenta/drug effects , Pre-Eclampsia/drug therapy , Albuminuria/prevention & control , Animals , Arginine/therapeutic use , Blood Pressure/drug effects , Endothelium/physiology , Female , Humans , Injections, Intraperitoneal , Microcirculation/drug effects , Microcirculation/physiology , NG-Nitroarginine Methyl Ester/administration & dosage , NG-Nitroarginine Methyl Ester/adverse effects , Nitric Oxide Synthase Type III/metabolism , Placenta/blood supply , Pre-Eclampsia/chemically induced , Pre-Eclampsia/metabolism , Pregnancy , RatsABSTRACT
L-arginine (200 mg/kg), vitamin B(6) (2 mg/kg), and folic acid (0.2 mg/kg) exert a protective effect on endothelial function in L-NAME-induced NO deficiency in male and pregnant female Wistar rats. Combined administration of these agents effectively prevented the development of endothelial dysfunction and L-NAME-induced preeclampsia.
Subject(s)
Arginine/pharmacology , Endothelium/physiopathology , Folic Acid/pharmacology , Nitric Oxide/deficiency , Placenta/blood supply , Vitamin B 6/pharmacology , Animals , Arginine/therapeutic use , Drug Therapy, Combination , Endothelium/drug effects , Endothelium/metabolism , Female , Folic Acid/therapeutic use , Male , Microcirculation/drug effects , NG-Nitroarginine Methyl Ester , Nitric Oxide Synthase Type III/metabolism , Placenta/drug effects , Placenta/metabolism , Pre-Eclampsia/chemically induced , Pre-Eclampsia/drug therapy , Pre-Eclampsia/metabolism , Pregnancy , Rats , Rats, Wistar , Vitamin B 6/therapeutic useABSTRACT
Intragastric methionine (3 g/kg daily for 7 days) elevates homocysteine concentration and increases the endothelial dysfunction coefficient. This protocol of methionine treatment is an adequate model of hyperhomocysteine-induced endothelial dysfunction and can be used for studies of the endothelio- and cardioprotective effects of drugs.
Subject(s)
Endothelium, Vascular/pathology , Hyperhomocysteinemia/physiopathology , Vascular Diseases/physiopathology , Animals , Endothelium, Vascular/drug effects , Hyperhomocysteinemia/complications , Hyperhomocysteinemia/drug therapy , Methionine/therapeutic use , Rats , Vascular Diseases/drug therapy , Vascular Diseases/etiologyABSTRACT
Modeling of NO deficiency by administration of L-NAME to rats led to the development of arterial hypertension and endothelial dysfunction. Pronounced endothelium and cardioprotective effects of impaza under these experimental conditions manifested more markedly during combined administration of the preparation with standard hypotensive preparations enalapril and losartan.
Subject(s)
Antibodies/therapeutic use , Enalapril/therapeutic use , Hypertension/drug therapy , Losartan/therapeutic use , Nitric Oxide/deficiency , Animals , Hypertension/chemically induced , Male , NG-Nitroarginine Methyl Ester/pharmacology , Rats , Rats, WistarABSTRACT
Experimental NO deficiency induced by L-NAME injection led to the development of arterial hypertension, endothelial dysfunction, and cardiomyocyte hypertrophy and reduced blood content of nitrates and nitrites. Impaza, NO donors, activators of NO-synthase, antioxidants, and antihypertensive preparations produced endothelium-protective effect of different degree.