Hans Wohlmuth

A combined phase I and II open label study on the effects of a seaweed extract nutrient complex on osteoarthritis

Background: Isolated fucoidans from brown marine algae have been shown to have a range of anti-inflammatory effects. Purpose: This present study tested a Maritech® extract formulation, containing a blend of extracts from three different species of brown algae, plus nutrients in an open label combined phase I and II pilot scale study to determine both acute safety and efficacy in osteoarthritis of the knee. Patients and methods: Participants (n = 12, five females [mean age, 62 ± 11.06 years] and seven males [mean age, 57.14 ± 9.20 years]) with a confirmed diagnosis of osteoarthritis of the knee were randomized to either 100 mg (n = 5) or 1000 mg (n = 7) of a Maritech® extract formulation per day. The formulation contained Maritech® seaweed extract containing Fucus vesiculosis (85% w/w), Macrocystis pyrifera (10% w/w) and Laminaria japonica (5% w/w) plus vitamin B6, zinc and manganese. Primary outcome was the average comprehensive arthritis test (COAT) score which is comprised of four sub-scales: pain, stiffness, difficulty with physical activity and overall symptom severity measured weekly. Safety measures included full blood count, serum lipids, liver function tests, urea, creatinine and electrolytes determined at baseline and week 12. All adverse events were recorded. Results: Eleven participants completed 12 weeks and one completed 10 weeks of the study. Using a multilevel linear model, the average COAT score was reduced by 18% for the 100 mg treatment and 52% for the 1000 mg dose at the end of the study. There was a clear dose response effect seen between the two treatments (P ≤ 0.0005) on the average COAT score and each of the four COAT subscales (pain, stiffness, difficulty with physical activity and overall symptom severity) (P ≤ 0.05). The preparation was well tolerated and the few adverse events were unlikely to be related to the study medication. There were no changes in blood parameters measured over the course of the study with the exception of an increase in serum albumin which was not clinically significant. Conclusion: The seaweed extract nutrient complex when taken orally over twelve weeks decreased the symptoms of osteoarthritis in a dose-dependent manner. It was demonstrated to be safe to use over the study period at the doses tested. The efficacy of the preparation now needs to be demonstrated in a phase III randomized controlled trial (RCT). Australian and New Zealand Clinical Trials Register: ACTRN12607000229471.

Chemical composition and antioxidant and anticandidal activities of essential oils from different wild moroccan thymus species

Samples of the aerial parts of Thymus broussonetii, T. ciliatus, T. leptobotrys, T. maroccanus, T. pallidus, T. satureioides, and T. serpyllum collected from different natural regions in southern and south‐western Morocco were analyzed for their qualitative and quantitative essential oil profiles. In total, 46 compounds, representing more than 99% of the oils, were characterized. Monoterpenes, both hydrocarbons (12.9–58.0%) and oxygenated monoterpenes (38.8–81.1%), were the principal classes of compounds for most of the thyme species studied. Cluster analysis allowed the classification of the species into three main groups: a carvacrol group (Group I), comprising the species T. maroccanus and T. leptobotrys, a linalyl acetate and (E)‐nerolidol group (Group II), represented by T. serpyllum, and a thymol and/or carvacrol, γ‐terpinene, and p‐cymene group (Group III), composed of T. satureioides, T. broussonetii, T. ciliatus, and T. pallidus. The essential oils were screened for their antioxidant and anticandidal activities. The data showed that the oils obtained from T. leptobotrys and T. maroccanus (carvacrol group) possessed the highest antioxidant activities as assessed by the determination of the DPPH free radical‐scavenging ability and the ferric‐reducing potential. The anticandidal assays indicated that the highest activity was noticed for the essential oil isolated from T. leptobotrys.

An in vitro investigation of herbs traditionally used for kidney and urinary system disorders: potential therapeutic and toxic effects

Aim:  Renal fibrosis is central to progression of most chronic renal pathologies. Antioxidants that protect the tubular epithelium and anti‐fibrotics that induce apoptosis of pro‐fibrotic myofibroblasts without adversely affecting tubular epithelium may slow progression of renal fibrosis, while toxic substances may exacerbate renal scarring. We investigated 47 herbs for their in vitro toxic or antioxidant effects on normal renal mammalian fibroblasts (NRK49F) and tubular epithelial cells (NRK52E) to determine their potential value as therapeutic agents in renal fibrosis involving oxidative stress.

The current status of knowledge of herbal medicine and medicinal plants in Fiche, Ethiopia.

BackgroundA majority of Ethiopians rely on traditional medicine as their primary form of health care, yet they are in danger of losing both their knowledge and the plants they have used as medicines for millennia. This study, conducted in the rural town of Fiche in Ethiopia, was undertaken with the support of Southern Cross University (SCU) Australia, Addis Ababa University (AAU) Ethiopia, and the Ethiopian Institute of Biodiversity (EIB), Ethiopia. The aim of this study, which included an ethnobotanical survey, was to explore the maintenance of tradition in the passing on of knowledge, the current level of knowledge about medicinal herbs and whether there is awareness and concern about the potential loss of both herbal knowledge and access to traditional medicinal plants.MethodsThis study was conducted using an oral history framework with focus groups, unstructured and semi-structured interviews, field-walk/discussion sessions, and a market survey. Fifteen people were selected via purposeful and snowball sampling. Analysis was undertaken using a grounded theory methodology.ResultsFourteen lay community members and one professional herbalist provided information about 73 medicinal plants used locally. An ethnobotanical survey was performed and voucher specimens of 53 of the plants, representing 33 families, were collected and deposited at the EIB Herbarium. The community members are knowledgeable about recognition of medicinal plants and their usage to treat common ailments, and they continue to use herbs to treat sickness as they have in the past. A willingness to share knowledge was demonstrated by both the professional herbalist and lay informants. Participants are aware of the threat to the continued existence of the plants and the knowledge about their use, and showed willingness to take steps to address the situation.ConclusionThere is urgent need to document the valuable knowledge of medicinal herbs in Ethiopia. Ethnobotanical studies are imperative, and concomitant sustainable programmes that support the sustainability of herbal medicine traditions may be considered as a way to collect and disseminate information thereby supporting communities in their efforts to maintain their heritage. This study contributes to the documentation of the status of current traditional herbal knowledge in Ethiopia.

Factors affecting pharmacists’ recommendation of complementary medicines – a qualitative pilot study of Australian pharmacists

BackgroundComplementary medicines (CMs) are widely used by the Australian public, and pharmacies are major suppliers of these medicines. The integration of CMs into pharmacy practice is well documented, but the behaviours of pharmacists in recommending CMs to customers are less well studied. This study reports on factors that influence whether or not pharmacists in Australia recommend CMs to their customers.MethodsData were collected from semi-structured interviews with twelve practicing pharmacists based in Brisbane, Australia. The qualitative data were analysed by thematic analysis.ResultsThe primary driver of the recommendation of CMs was a desire to provide a health benefit to the customer. Other important drivers were an awareness of evidence of efficacy, customer feedback and pharmacy protocols to recommend a CM alongside a particular pharmaceutical medication. The primary barrier to the recommendation of CMs was safety concerns around patients on multiple medications or with complex health issues. Also, a lack of knowledge of CMs, a perceived lack of evidence or a lack of time to counsel patients were identified as barriers. There was a desire to see a greater integration of CM into formal pharmacy education. Additionally, the provision of good quality educational materials was seen as important to allow pharmacists to assess levels of evidence for CMs and educate them on their safe and appropriate use.ConclusionsPharmacists who frequently recommend CMs identify many potential benefits for patients and see it as an important part of providing a ‘healthcare solution’. To encourage the informed use of CMs in pharmacy there is a need for the development of accessible, quality resources on CMs. In addition, incorporation of CM education into pharmacy curricula would better prepare graduate pharmacists for community practice. Ultimately, such moves would contribute to the safe and effective use of CMs to the benefit of consumers.

A combined Phase I and II open-label study on the immunomodulatory effects of seaweed extract nutrient complex

Background: Isolated fucoidans from brown marine algae have been shown to have a range of immune-modulating effects. This exploratory study aimed to determine whether a seaweed nutrient complex containing a blend of extracts from three different species of brown algae plus nutrients is safe to administer and has biological potential as an immune modulator. The study was undertaken as an open-label combined Phase I and II study. Methods: Participants (n = 10) were randomized to receive the study medication at either a 100 mg (n = 5) or 1000 mg (n = 5) dose over 4 weeks. The primary outcome measurement was in vivo changes in lymphocyte subsets. The secondary outcome measures were ex vivo changes in T-lymphocyte (CD4 and CD8) activation, phagocytosis of granulocytes and monocytes, T helper 1/T helper 2 cytokines, and serum oxygen radical absorbance capacity. Results: The preparation was found to be safe over the 4 weeks at both doses tested. There were no clinically relevant changes to blood measurements of hemopoietic, hepatic, or renal function. Immunomodulatory measurements showed no dose response between the two doses. The combined results from the two doses demonstrated a significant increase in cytotoxic T cell numbers and phagocytic capacity in monocytes, and a significant decrease in levels of the inflammatory cytokine interleukin 6. A separate analysis of the 100 mg dose (n = 5) alone showed a significant linear component over time (P < 0.05) for phagocytosis by both granulocytes and monocytes. Conclusion: The seaweed nutrient complex was safe to use when taken orally over 4 weeks. The preparation was demonstrated to have potential as an immune modulator, and this bioactivity deserves further exploration.

Adulteration of Ginkgo biloba products and a simple method to improve its detection

Extracts of ginkgo (Ginkgo biloba) leaf are widely available worldwide in herbal medicinal products, dietary supplements, botanicals and complementary medicines, and several pharmacopoeias contain monographs for ginkgo leaf, leaf extract and finished products. Being a high-value botanical commodity, ginkgo extracts may be the subject of economically motivated adulteration. We analysed eight ginkgo leaf retail products purchased in Australia and Denmark and found compelling evidence of adulteration with flavonol aglycones in three of these. The same three products also contained genistein, an isoflavone that does not occur in ginkgo leaf. Although the United States Pharmacopeia - National Formulary (USP-NF) and the British and European Pharmacopoeias stipulate a required range for flavonol glycosides in ginkgo extract, the prescribed assays quantify flavonol aglycones. This means that these pharmacopoeial methods are not capable of detecting adulteration of ginkgo extract with free flavonol aglycones. We propose a simple modification of the USP-NF method that addresses this problem: by assaying for flavonol aglycones pre and post hydrolysis the content of flavonol glycosides can be accurately estimated via a simple calculation. We also recommend a maximum limit be set for free flavonol aglycones in ginkgo extract.

Dioscorea villosa (wild yam) induces chronic kidney injury via pro-fibrotic pathways

Dioscorea villosa (wild yam) rhizome extract is a medicinal herb that is commonly used to treat symptoms of menopause and rheumatoid arthritis. We had evidence from previous in vitro experiments that this extract is toxic and pro-fibrotic in renal cells and aimed to test whether this occurs in vivo. Sprague-Dawley rats received 0.79g/kg/d D. villosa extract in their food or no treatment over 7, 14 and 28d (n=4 per group). Kidney and liver tissues were collected for protein extraction and Western immunoblots or fixed for special histologic stains, immunohistochemistry (IHC) and microscopy. Collagen deposition was assessed using Massons trichrome staining and morphometry. Macrophage infiltration (ED-1), epithelial-to-mesenchymal transdifferentiation or activation of fibroblasts (vimentin, alpha-SMA), and pro-fibrotic growth factors (TGFss1, CTGF) were assessed using IHC. Protein expression levels of the pro-inflammatory cytokine, TNF-alpha, the pro-fibrotic transcription factor, NFkappaB, a measure of oxidative stress (heme oxygenase-1), alpha-SMA, vimentin and TGFss1 were determined. Results showed that kidneys of the treated animals had significantly increased collagen, vimentin, TGFbeta1, NFkappaB, EDI, CTGF and alpha-SMA by 28d. In the liver, there was increased ED-1 and TGFbeta1 in the centrilobular zone at 28d in treated animals. In conclusion, there was no acute reno- or hepato-toxicity associated with administration of D. villosa. However, there was an increase in fibrosis in the kidneys and in inflammation in livers of rats consuming D. villosa for 28 days. Long term supplementation with D. villosa may be best avoided, especially in people with compromised renal function and in those who need to take other drugs which may alter kidney function.

Essential oil composition of Zingiberaceae species from Mauritius

Abstract The chemical composition of the essential oils obtained from the hydrodistillation of the rhizomes of the common ginger (Zingiber officinale) and three ginger-lilies (Hedychium coccineum, H. flavescens and H. coronarium) grown in Mauritius has been investigated by GC and GC/MS. Zingiber officinale oil was characterized by the presence of geranial (16.3%), neral (10.3%), zingiberene (9.5%), β-sesquiphellandrene (6.3%) and ar-curcumene (5.1%). The oils of the ginger lilies were characterized as follows: H. coccineum: (E)-nerolidol (44.4%), trans-sesquisabinene hydrate (24.2%); H. flavescens: linalool (35.0%), 1, 8-cineole (15.3%), β-pinene (14.7%), α-terpineol (14.5%) and α-pinene (5.3%); H. coronarium: α-muurolol (16.8%), α-terpineol (15.9%), 1, 8-cineole (11.2%), an unknown sesquiterpene alcohol (7.0%), α-fenchyl acetate (5.6%), citronellal (5.5%) and (E)-methyl cinnamate (5.1%).

Detection of Panax quinquefolius in Panax ginseng using 'subtracted diversity array'.

BACKGROUND Food adulteration remains a major global concern. DNA fingerprinting has several advantages over chemical and morphological identification techniques. DNA microarray-based fingerprinting techniques have not been used previously to detect adulteration involving dried commercial samples of closely related species. Here we report amplification of low-level DNA obtained from dried commercial ginseng samples using the Qiagen REPLI-g Kit. Further, we used a subtracted diversity array (SDA) to fingerprint the two ginseng species, Panax ginseng and Panax quinquefolius, that are frequently mixed for adulteration. RESULTS The two ginseng species were successfully discriminated using SDA. Further, SDA was sensitive enough to detect a deliberate adulteration of 10% P. quinquefolius in P. ginseng. Thirty-nine species-specific features including 30 P. ginseng-specific and nine P. quinquefolius-specific were obtained. This resulted in a feature polymorphism rate of 10.5% from the 376 features used for fingerprinting the two ginseng species. The functional characterization of 14 Panax species-specific features by sequencing revealed one putative ATP synthase, six putative uncharacterized proteins, and two retroelements to be different in these two species. CONCLUSION SDA can be employed to detect adulterations in a broad range of plant samples.