Phase 1 clinical study of the acute and subacute safety and proof-of-concept efficacy of carbohydrate-derived fulvic acid

BACKGROUND: The purpose of this research was to determine the acute and subacute safety and proof-of-concept efficacy of carbohydrate-derived fulvic acid (CHD-FA). METHODS: In this double-blind study, 30 male volunteers with predetermined atopy were randomly assigned to either Group A or Group B, each consisting of 15 participants. In part 1 of the study, the groups were administered increasing amounts of CHD-FA, ranging from 5 mL to 40 mL, provided that no adverse events had occurred at the previous dosage. In part 2, Group A participants received 20 mL of 3.8% CHD-FA twice daily for 3 days and were monitored for a week. Because no adverse events occurred, Group B received 40 mL of 3.8% CHD-FA twice daily for a period of 3 days. In part 3, both groups received either 40 mL of 3.8% CHD-FA or placebo twice daily for a period of one week, followed by a one-week washout period before crossover to the alternative treatment schedule. Parameters used to establish safety were electrocardiography, a physical examination, a health questionnaire, and hematology and biochemistry, determined at baseline, during regular calculated intervals, and at the end of each part of the study. A skin prick test was done as part of the screening process and, from the result, the allergen the participant was most allergic to was then selected, along with the positive histamine and negative control to be repeated at the start and end of each respective stage. RESULTS: Safety parameters remained constant throughout the trial. A significant decrease in skin prick test results was observed. CONCLUSION: No severe adverse events occurred, establishing that CHD-FA to be safe at doses up to 40 mL twice daily for a week and that at this dosage CHD-FA acts as an anti-inflammatory agent. These findings confirm earlier animal data.http://www.dovepress.com/clinical-pharmacology-advances-and-applications-journa

The In Vitro Antitumour Activity of Novel, Mitochondrial-Interactive, Gold-Based Lipophilic Cations

In this study we compared the effects of two previously described antimitochondrial gold complexes, that is, [A] [Au(dppe)2]Cl and [B] [Au(d4pype)2]Cl with two novel lipophilic cations, that is, [C] [Au(dpmaaH2)(dpmaaSnMe2)]Cl and [D] [Au(dpmaaSnMe2)2]Cl as antimitochondrial agents. The results of this study indicate that [C] and [D] have intermediate partition coefficients and exhibited a selective uptake by cells. They exhibited a higher selectivity for the various cell lines than [A] but were more cytotoxic than [B]. There is a significant correlation between the cytotoxic potential of [A], [B], [C], and [D] and their octanol/water partition coefficients in both MCF-7 (breast cancer) and MCF-12A (nonmalignant breast) cells, whereas their cytotoxic potential and ability to induce the release of cytochrome c correlated only in the case of the MCF-12A cells. Complexes [C] and [D] are promising new chemotherapeutic drugs. These compounds target the mitochondrial membranes of certain cancer cells exploiting the differences between the mitochondrial membrane potential of these cells and normal cells. Although the concentrations of these compounds necessary to eradicate cancer cells are very high, the results provide a basis for the synthesis of a new family of compounds with intermediate partition coefficients compared to [A] and [B] but with increased activity against cancer cells

Carbohydrate-derived fulvic acid (CHD-FA) inhibits carrageenan-induced inflammation and enhances wound healing : efficacy and toxicity study in rats

The objectives of this study were to evaluate the safety and anti-inflammatory and wound healing characteristics of carbohydrate derived fulvic acid (CHD-FA) in rats. A daily oral dosage of CHD-FA at 100mg/kg and higher effectively reduced carrageenan-induced paw oedema in rats which was comparable to an oral dosage of 10mg/kg indomethacin. Furthermore, the topical application of CHD-FA formulated to contain 1.75% active product in an cetomicrogol cream at pH 1.98, compared favourably with fusidic acid cream (10mg/g) in accelerating the healing of excised wounds infected with S. aureus. No signs of toxicity were observed in rats during the 6-day acute and 6 month chronic oral treatment with CHD-FA at 100mg/Kg bodyweight. Topical application of CHD-FA, formulated in UEA cream and applied to the right ears of mice at 400mg/Kg bodyweight on days one, and 7 to 38 produced no adverse events. No signs of toxicity were observed in the teratogenicity study where CHD-FA was administered at 100mg/kg bodyweight to pregnant female mice by gavage 3 days before fertilization to 14 days of pregnancy. In conclusion, CHD-FA is a safe compound with anti-inflammatory and wound healing properties and merits further evaluation in the treatment of patients suffering from similar conditions.Fulvimed (Pty) Ltd, The Technology and Human Resources for Industry Programme of the National Research Foundation and the Department of Trade and Industry (THRIP)http://onlinelibrary.wiley.com/journal/10.1002/(ISSN)1098-2299dm201

Potassium humate inhibits carrageenan induced paw oedema and a graft-vs-host reaction in rats

It has been shown in a previous study that brown coal-derived potassium humate is safe and effective in suppressing contact hypersensitivity in rats. In this study the efficacy of potassium humate on other types of inflammation was determined. Preparative TLC followed by mass spectroscopy was used in an attempt to fingerprint the product. The effects of potassium humate, at an oral dose of 60 mg/kg bodyweight, on a delayed type hypersensitivity reaction, a carrageenan-induced inflammation model and an allogeneic graft-versus-host reaction (GVHR) in rats were investigated. Paw oedema was used as a measure of inflammation. It was found that potassium humate had no effect on the delayed type hypersensitivity reaction but significantly inhibited the increase in paw volume of the carrageenan-induced oedema in rats which compared favourably with indomethacin treatment. Furthermore, potassium humate inhibited the GVHR induced in normal and cyclophosphamide-treated immune-incompetent rats. The identification of a naturally occurring compound that is safe and effective in reducing different types of inflammation merits further evaluation in clinical trials.This research was supported by Unique Health Trust and a grant from the South African National Research Foundation (NRF)

Clinical efficacy of potassium humate in the treatment of allergic rhinitis : double-blind placebo-controlled trial

The anti-inflammatory properties of products that contain high levels of humic acid, such as peat, sapropeles, and mumie, are well described. The aim of this study was to establish the clinical efficacy of brown coal-derived potassium humate, as in vivo animal models had suggested similar efficacy of humate to prednisolone. In this double-blind, placebo-controlled study, atopic volunteers were recruited and randomized to placebo or 1.8 g potassium humate/day (three divided dosages) when they presented with hay fever. The efficacy parameters used were skin-prick tests for wheal and flare reactions, nasal smears for inflammatory cell accumulation, and cytokine levels. Patients also filled out daily symptom score cards to determine efficacy against symptoms of hay fever. Potassium humate resulted in a significant decrease in wheal and flare reactions as well as nasal eosinophil counts. These findings were supported by similar changes (not significant) in cytokine levels. Changes in symptom scores did not reach significance. This proof of concept study clearly demonstrated the potential of potassium humate in the treatment of inflammatory conditions such as hay fever.Unique Health Trust and South African National Research Foundation (NRF)

Potassium humate reduces inflammation and clinically improves the outcomes of patients with osteoarthritis of the knee

A pilot study was done to determine if potassium humate, a natural substance derived from brown coal, with known anti-inflammatory properties, is safe and effective in reducing pain and inflammation in osteoarthritis of the knee. This was conducted as a randomized, double-blind, placebo-controlled, single centre, cross-over. Participants were enrolled for a total of 14 weeks, starting with an initial 1-week washout period, after which they were randomly assigned to either potassium humate or lactose, administered orally for 6 weeks at a dosage of 600mg three times daily. Following another 1-week washout period, participants were crossed over to the other treatment for another 6 weeks. Participants were not permitted the use of anti-inflammatory medications. Paracetamol was allowed as rescue medication for the duration of the trial. The primary efficacy variable were the WOMAC™ scores (visual analogue version) for pain, stiffness, physical function and total score and health related issues using the RAND 36 levels, rescue medication use, adverse effects and tolerability. 28 participants were enrolled and 21 participants successfully completed the protocol. A carry-over effect in the stiffness subscale was observed. There was a significantly greater clinical benefit with potassium humate over placebo with reduction in all the WOMAC subscale scores for pain. After adjusting for baseline, potassium humate showed a greater reduction in hs-CRP levels when compared to placebo. Tolerability was good for all groups. Safety parameters remained unchanged, except for an increase in the GGT-levels (n=4 in potassium humate group, n=2 in the placebo group). Levels of GGT returned to baseline within 2 weeks of discontinuation of therapy. In conclusion, potassium humate showed possible benefit over placebo in patients with OA of the knee, with a statistically significant reduction in hs-CRP levels. The small sample size and the carry-over effect limited further interpretation of data.This research was financially supported by Unique Health Trust and a grant from the South African National Research Foundation (NRF)

Amides of gold(I) diphosphines prepared from N-heterocyclic sources and their in vitro and in vivo screening for anticancer activity

A series of new neutral mononuclear or dinuclear gold(I) complexes and a cyclic cationic tetranuclear amidogold(I) complex comprising of the phosphines 1,2- bis(dimethylphosphino)ethane (dmpe), μ-1,2–bis(diphenylphosphino)ethane (dppe), μ-1,3- bis(diphenylphosphino)propane (dppp), μ-1,5-bis(diphenylphosphino)pentane (dpppe), μ-1,6- bis(diphenylphosphino)hexane (dpph) or trimethylphosphine, and several N-heterocyclic ring systems (imidazolate, pyrazolate, 1,2,3-triazolate, 1,2,4-triazolate, pyrrolate, 9H-purine-9-ate or 9H-purine-6-amine-9-ate) as ligands, reveal intermolecular aurophilic interactions and 2D channels available for solvent molecules in some of their crystal structures. The antitumour activity of the acyclic gold(I) compounds is highly dependent on the substituents on the phosphorus atoms being highest for phenyl groups and lower for methyl groups. The activity of these compounds against selected cell lines is linked to the length of the carbon bridge between the two phosphorus atoms being highest with a bridge consisting of 5 or 6 carbons. Two compounds with the highest tumour specifities that contain dpppe and pyrazolate (a lipophilic compound) or 1,2,4-triazolate (a hydrophilic compound) induce the apoptic cell death pathway and tolerate a maximum dose of 1.5 μmol/kg when administered to Balb/C mice.Claude Harris Leon Foundation (UEIH), Alexander von Humboldt Stiftung (HGR and SC), NRF (National Research Foundation, South Africa), Harmony Gold Mining Co. Ltd.through Project Autek and the Research Foundation Flanders – FWO (LD)http:// www.sciencedirect.com/science/journal/0162013