Minimal Active Concentration Research Articles

Compressive Review on Plant Profile, Ethnomedicinal Uses, Phytochemistry and Pharmacology of Paeonia emodi Royle (Himalayan Paeony)

Members of the genus Paeonia, which contains well-known ornamentals as well as traditional medicinal plants with a history reaching back over 1500 years, may be found all throughout the Northern Hemisphere. Many of these ethnomedicinal properties have been studied in animal models. It has been listed as a critically endangered plant species. P. emodi has been shown to have antioxidant, nephroprotective, lipoxygenase inhibitory, cognition and oxidative stress release, cytotoxic, anti-inflammatory, antiepileptic, anticonvulsant, haemaglutination, alphachymotrypsin inhibitory, hepatoprotective, hepatic chromes, and pharmacokinetics of carbamazepine expression. spas Data was acquired from unpublished theses (India, China, Pakistan, and Nepal) and numerous published research articles related to pharmacology, phytochemistry, and other activities using certain keywords. The pertinent information about medicinal uses, taxonomic/common names, parts used, collection and recognition source, authentication, voucher specimen number, plant extracts and their characterization, isolation and characterization of phytochemicals, methods of study (in silico, in vivo, or in vitro), model organism used, dose and time, minimal active concentration, bioactive compound(s), mechanism of action on single or multiple targets, and toxicological information. Triterpenoids, monoterpenoids, phenolics, and tannins are among the natural substances produced by the species. The purpose of this study was to collect broad traditional medicinal uses, phytochemistry, pharmacology, and toxicological data on P. emodi. This work also emphasises taxonomic validity, experimental design quality, and weaknesses in previously published Himalayan paeony material, which may help researchers plan for future research.

Lichen Polyphenolic Compounds for the Eradication of Candida albicans Biofilms.

Lichens, due to their symbiotic nature (association between fungi and algae), constitute a chemical factory of original compounds. Polyphenolic compounds (depsides and depsidones) are the main constituents of lichens and are exclusively biosynthesized by these organisms. A panel of 11 polyphenols was evaluated for their anti-biofilm activity against Candida albicans biofilms on the maturation phase (anti-maturation) (MMIC50) as well as on preformed 24-h-old biofilm (anti-biofilm) (MBIC50) using the XTT assay. Minimum inhibitory concentrations of compounds (MICs) against C. albicans planktonic yeast were also determined using a broth microdilution method. While none of the tested compounds were active against planktonic cells (IC50 > 100 µg/ml), three depsides slowed the biofilm maturation (MMIC50 ≤12.5 µg/ml after 48 h of contact with Candida cells). Evernic acid was able to both slow the maturation and reduce the already formed biofilms with MBIC50 ≤12.5 µg/ml after 48 h of contact with the biofilm. This compound shows a weak toxicity against HeLa cells (22%) at the minimal active concentration and no hemolytic activity at 100 µg/ml. Microscopic observations of evernic acid and optimization of its solubility were performed to further study this compound. This work confirmed the anti-biofilm potential of depsides, especially evernic acid, and allows to establish the structure–activity relationships to better explain the anti-biofilm potential of these compounds.

Herbal Products in Postsurgical Wound Healing - Incision, Excision and Dead Space Wound Models.

The purpose of this review is to summarize current knowledge acquired on preclinical (incision, excision, and dead space wound models) and clinical studies regarding topically used herbal products with wound healing activity. The antimicrobial, anti-inflammatory, and antioxidant mechanisms of their action as well as the adverse effects of herbal therapy will be described. Numerous preclinical and few clinical trials have confirmed the activity of herbal products in the stimulation of wound healing. In contrast to synthetic drugs, for which chemical compositions, purity, efficacy, minimal active concentration, and toxicity are well specified, several herbal formulations require further investigations. Nevertheless, it cannot be precluded that herbal products may be considered as an important support during conventional wound healing therapy or even as synthetic medicament replacements.

Genotoxic and clastogenic activity of saponins extracted from Nauclea bark as assessed by the micronucleus and the comet assays in Chinese Hamster Ovary cells

Bark extracts of Nauclea latifolia, Nauclea diderrichii, Nauclea pobeguinii and Nauclea vandergutchii are used in traditional medicine in West and South Africa for the treatment of fevers, diarrhea and malaria. To estimate the possible long-term toxicity and genotoxicity of plant extracts (dichloromethane, methanol, water/methanol, water) and saponins. The clastogenicity of plant extracts and saponins was assessed by the micronucleus assay performed on Chinese Hamster Ovary cells. The DNA-damaging activity of saponin mixture was assessed by the comet assay on Chinese Hamster ovary cells. Hydromethanolic extracts from Nauclea latifolia, Nauclea diderrichii and Nauclea pobeguinii exhibited a significant clastogenic/aneugenic activity without S9 mix. The hydromethanolic extract from Nauclea diderrichii was the most clastogenic/aneugenic fraction with a Minimal Active Concentration (MAC) of 23.1 μgm L(-1). It was submitted to a separation step leading to six main saponins identified as quinovic acid glycosides (saponins A, D, E, G, J, K). None of the isolated saponins exerted a significant clastogenic/aneugenic activity by the micronucleus assay, however a mixture made with equal quantities of each of the six saponins exhibited a direct genotoxic/clastogenic activity as assessed by both the micronucleus assay and the comet assay on Chinese Hamster Ovary cells. Saponins present in the hydromethanolic extracts of Nauclea induced synergistic in vitro DNA-damage and chromosome mutations in mammalian cells. This genotoxic activity was probably due to the capacity of Nauclea saponins to reduce cell defense against oxidative stress through the inhibition of glutathione-S-transferase activity.

Chain length dependence of antimicrobial peptide–fatty acid conjugate activity

The rise of resistant bacteria has prompted the search for new antimicrobial agents. Antimicrobial membrane lytic peptides have potential as future microbial agents due to their novel mode of action. Recently conjugation of a fatty acid to antimicrobial peptides has been explored as a method to modulate the activity and selectivity of the peptide. Our work further explores these phenomena by testing two peptides, YGAAKKAAKAAKKAAKAA (AKK) and LKKLLKLLKLLKL (LKK), conjugated to fatty acids of varying length for their activity, structure, solution assembly properties and the ability to bind model membranes. We found that increasing the length of fatty acids conjugated to peptide AKK, up to a 16 carbons in length, increases the antimicrobial activity. Peptide AKK appears to lose activity when the minimal active concentration is higher than the critical miscelle concentration (CMC) of the molecule. Thus, if the CMC of the peptide conjugate is too low the activity is lost. Peptide LKK has no activity when conjugated to lauric acid and appears to aggregate at very low concentrations. Conjugation of AKK with a fatty acid increases its affinity to model supported lipid membranes. It appears that the increased hydrophobic interaction imparted by the fatty acid increases the affinity of the peptide to the surface thus increasing its activity. At concentrations above the CMC, solution self-assembly inhibits binding of the peptide to cell membranes.

S 12911-2 inhibits osteoclastic bone resorption in vitro.

The potential anti-osteoporotic activity of the strontium compound, S12911, was tested on osteoclast-like cells and on cultured fetal mouse long bones. From 1 mM Sr2+, S12911 reduced both basal and stimulated bone resorption by decreasing osteoclast activity and ruffled border formation. The aim of this study was to evaluate the effects of S 12911-2 on osteoclastic bone resorption using in vitro systems. Osteoclast-like cells, produced in vitro by co-culture of mouse bone marrow cells with primary osteoblasts, were allowed to settle on dentine slices, and the area of resorption pits formed after 48 h was measured using an image analysis system. S 12911-2, at a minimal active concentration of 1 mM Sr2+, significantly reduced pit formation by these cells (p < 0.05). Pretreatment of slices for 48 h with S 12911-2 (5 mM Sr2+) did not produce appreciable inhibition of resorption. Bone resorption in cultured fetal mouse long bones was assessed by measuring the release of pre-incorporated 45calcium. S 12911-2 inhibited resorption in control cultures (18.9%, p < or = 0.05) and in bones cultured with the active form of vitamin D3 [1,25(OH)2D3] (44.5%, p < or = 0.05). S 12911-2 had no effect on the number of osteoclasts observed histochemically in longitudinal sections prepared from fetal mouse long bones. Electron microscopy of mouse long bones treated with S 12911-2 (3 mM Sr2+) showed osteoclasts with clear zones facing the bone surface, but without well-developed ruffled borders; untreated bones contained osteoclasts with normal ruffled borders. These results indicate that S 12911-2 inhibits osteoclast activity. This effect is directly linked to the presence of strontium, is effective on basal and stimulated resorption, and involves a decrease in ruffled border formation by osteoclasts.

Specificity of the test based on modification of cell morphology for detection of lipophilic inhibitors of protein phosphatases

The test based on morphological changes in KB cells was assayed with different toxins. Only lipophilic inhibitors of protein phosphatases, such as okadaic acid or calyculin A, induced visible changes in cell morphology. The activity of contaminated mussel extracts on KB cells was evaluated comparatively by direct interpretation of morphological changes and by a colorimetric method estimating the number of viable cells after staining. The latter technique revealed interferences (not detected by the former) with mussel cytotoxins. These results show that the technique, based on determination of the minimal active concentration of toxic extracts inducing morphological changes, is more specific, faster and preferable to the determination of ic 50 for the detection of protein phosphatase inhibitors in shellfish.

Adrenergic Modulation of Human Polymorphonuclear Leukocyte Activation. Potentiating Effect of Adenosine

Abstract The activation of polymorphonuclear leukocytes (PMN) is an important step in the development of tissue damage associated with inflammatory and ischemic conditions. Catecholamines have been reported to inhibit PMN functions, but the high concentrations required cast doubt on their actual relevance as a defense mechanism. We report here that adenosine, which is actively released in ischemic conditions, potentiates the effect of epinephrine and reduces the minimal active concentration required to inhibit PMN activation by at least two orders of magnitude. Epinephrine caused a dose-related reduction of chemiluminescence, superoxide anion generation, enzyme release (lysozyme and beta- glucuronidase), and adhesion to endothelial cell (EC) monolayers in human PMN activated by N-formyl-methionyl-leucyl-phenyl-alanine (fMLP). This effect was only apparent at 10(-7) to 10(-6) mol/L. As expected, adenosine caused dose-dependent reductions of superoxide anion production and PMN adhesion to EC. Adenosine and epinephrine combined had an additive effect on PMN superoxide production and adhesion to EC. The minimal effective concentration of epinephrine in combination with 10(-8) mol/L adenosine was in the range of 10(-10) to 10(-9) mol/L. In contrast, adenosine inhibited only slightly enzyme release and did not significantly enhance the inhibition by epinephrine on this parameter. Studies with adenosine analogs suggested that the potentiating effect of adenosine was mediated by A2 receptors. The mechanism of potentiation was not related to additive effect on intracellular cyclic adenosine monophosphate levels. Epinephrine's ability to modulate PMN activation and the potentiating effect of adenosine may constitute a form of physiologic protection against tissue injury in inflammatory and ischemic processes.

Adrenergic modulation of human polymorphonuclear leukocyte activation. Potentiating effect of adenosine

The activation of polymorphonuclear leukocytes (PMN) is an important step in the development of tissue damage associated with inflammatory and ischemic conditions. Catecholamines have been reported to inhibit PMN functions, but the high concentrations required cast doubt on their actual relevance as a defense mechanism. We report here that adenosine, which is actively released in ischemic conditions, potentiates the effect of epinephrine and reduces the minimal active concentration required to inhibit PMN activation by at least two orders of magnitude. Epinephrine caused a dose-related reduction of chemiluminescence, superoxide anion generation, enzyme release (lysozyme and beta-glucuronidase), and adhesion to endothelial cell (EC) monolayers in human PMN activated by N-formyl-methionyl-leucyl-phenyl-alanine (fMLP). This effect was only apparent at 10(-7) to 10(-6) mol/L. As expected, adenosine caused dose-dependent reductions of superoxide anion production and PMN adhesion to EC. Adenosine and epinephrine combined had an additive effect on PMN superoxide production and adhesion to EC. The minimal effective concentration of epinephrine in combination with 10(-8) mol/L adenosine was in the range of 10(-10) to 10(-9) mol/L. In contrast, adenosine inhibited only slightly enzyme release and did not significantly enhance the inhibition by epinephrine on this parameter. Studies with adenosine analogs suggested that the potentiating effect of adenosine was mediated by A2 receptors. The mechanism of potentiation was not related to additive effect on intracellular cyclic adenosine monophosphate levels. Epinephrine's ability to modulate PMN activation and the potentiating effect of adenosine may constitute a form of physiologic protection against tissue injury in inflammatory and ischemic processes.

Heparin and glutathione: Physiological decondensing agents of human sperm nuclei

It has been proposed that reduced glutathione (GSH) or other thiol reagents may participate in the basic mechanism by which sperm-decondensing activity is accomplished. However, in vitro, these reagents seem to be inactive and require the presence of other chemicals, usually detergents. Heparin binds specifically to the sperm membrane and provokes the decondensation of human sperm and the activation of DNA transcription and synthesis. However, the concentrations at which these effects occur seem to be higher than those expected under physiological conditions. In the present study, thiol reagents at 10 mM concentration, either alone or combined, were completely ineffective in inducing any significant nuclear decondensation after prolonged exposures (24 hr) of incubation. Heparin, 153.8 microM, was capable of inducing only a small increase in nuclear swelling. However, GSH at concentrations as low as 0.1 mM in combination with heparin induces decondensation of human sperm nuclei in vitro. When GSH concentration was kept constant at 5 mM, nuclear decondensation was induced with heparin at concentrations as low as 11.6 microM, and a maximal decondensation (90%) was obtained with only 21.6 microM of heparin. The latter is more than ten times less than the minimal active concentration of heparin used alone.

Dose-activity relationships in chemotherapy.

The in vitro antibacterial effects of subinhibitory and suprainhibitory concentrations of a number of beta-lactam antibiotics and aminoglycosides on microbial growth are presented. The type and extent of the subinhibitory activity of a drug can be well defined by means of growth curves obtained with different subinhibitory concentrations; from these values one can deduce and define the minimal active concentration (MAC) as the concentration at which morphological alterations or inhibition of growth of the bacteria can be seen. The effect of suprainhibitory concentrations can be evaluated by studying the kinetics of the bactericidal activity of a drug. Different types of bactericidal dose-activity relationships can be observed; in many cases a minimal optimal concentration (MOC) can be defined as the lowest concentration of a drug which causes no further appreciable enhancement of efficacy on increasing the concentration. Usually chemotherapy is carried out at subinhibitory drug levels--with decreasing and increasing concentrations--and at present it would appear difficult to assess these constant changes in an in vitro test. Bacteriologists should thus take into account the clinicians' demands for more precise bacteriological data on antibacterial agents.

Method for Antiglaucoma Drug Screening on Rabbits

α-Chymotrypsin-induced elevation of intraocular pressure in rabbits was found to be a suitable model for the screening of potential antiglaucoma agents. Pilocarpine shows minimal active concentration

The coronary vasodilator action of khellin

The experimental observations show that khellin is a potent coronary vasodilator; the minimal active concentration of the drug is 10 −6. Khellin has a very prolonged action and remains in the circulation for many hours. Its action in dilating the coronary arteries was compared with the similar action of aminophyllin; khellin was found to be at least four times stronger than aminophyllin. Khellin can be used continuously in the treatment of angina pectoris and also for the relief of individual attacks of pain. It can be administered orally in doses of 50 to 100 mg. three times per day, or as an intramuscular injection in doses of 100 to 200 milligrams. The drug produces a few side effects but is not toxic even after prolonged administration. It does not affect the bleeding or coagulation time. Altogether 250 patients with angina pectoris were treated with khellin with distinct improvement in 140 cases, with moderate improvement in eighty-five cases, and with no effect in twenty-five cases. In many patients clinical improvement was confirmed electrocardiographically. The drug was used also in fifty patients with recent coronary thrombosis with the object of improving the collateral circulation and relieving any associated anginal symptoms. The latter, at least, seemed to have been accomplished.