Presence of metals in herbal extracts

This is the pre-peer-reviewed version of the following article: Amira Guirguis, et al, 'Presence of metals in herbal extracts', The Pharmaceutical Journal, Vol. 289, p. 536, November 2012, URI: 11110858, which has been published in final form at : http://www.pharmaceutical-journal.com/news-and-analysis/news/presence-of-metals-in-herbal-extracts/11110858.article.Do metals from raw herbs transport into herbal preparations during manufacture? Amira Guirguis and colleagues take a look at the issue using St John’s wort as an example.Non peer reviewe

Investigation of the Elemental Profiles of Hypericum perforatum as used in Herbal Remedies

The work presented in this thesis has demonstrated that the use of elemental profiles for the quality control of herbal medicines can be applied to multiple stages of processing. A single method was developed for the elemental analysis of a variety of St John’s Wort (Hypericum perforatum) preparations using Inductively Coupled Plasma – Optical Emission Spectroscopy (ICP-OES). The optimised method consisted of using 5 ml of nitric acid and microwave digestion reaching temperatures of 185⁰C. Using NIST Polish tea (NIST INCT-TL- 1) the method was found to be accurate and the matrix effect from selected St John’s Wort (SJW) preparations was found to be ≤22%. The optimised method was then used to determine the elemental profiles for a larger number of SJW preparations (raw herbs=22, tablets=20 and capsules=12). Specifically, the method was used to determine the typical concentrations of 25 elements (Al, As, B, Ba, Be, Ca, Cd, Co, Cr, Cu, Fe, Hg, In, Mg, Mn, Mo, Ni, Pb, Pt, Sb, Se, Sr, V, Y and Zn) for each form of SJW which ranged from not detected to 200 mg/g. To further interpret the element profiles, Principal Component Analysis (PCA) was carried out. This showed that different forms of SJW could be differentiated based on their elemental profile and the SJW ingredient used (i.e. extract or raw herb) identified. The differences in the profiles were likely due to two factors: (1) the addition of bulking agents and (2) solvent extraction. In order to further understand how the elemental profile changes when producing the extract from the raw plant, eight SJW herb samples were extracted with four solvents (100% water, 60% ethanol, 80% ethanol and 100% ethanol) and analysed for their element content. The results showed that the transfer of elements from the raw herb to an extract was solvent and metal dependent. Generally the highest concentrations of an element were extracted with 100% water, which decreased as the concentration of ethanol increased. However, the transfer efficiency for the element Cu was highest with 60% ethanol. The solvents utilised in industry (60% and 80% ethanol) were found to preconcentrate some elements; Cu (+119%), Mg (+93%), Ni (+183%) and Zn (+12%) were found to preconcentrate in 60 %v/v ethanol extracts and Cu (+5%) and Ni (+30%). PCA of the elemental profiles of the four types of extract showed that differentiation was observed between the different solvents and as the ethanol concentration increased, the extracts became more standardised. Analysis of the bioactive compounds rutin, hyperoside, quercetin, hyperforin and adhyperforin followed by subsequent Correlation Analysis (CA) displayed relationships between the elemental profiles and the molecular profiles. For example strong correlations were seen between hyperoside and Cr as well as Quercetin and Fe. This shows potential for tuning elemental extractions for metal-bioactive compounds for increased bioactivity and bioavailability; however further work in needed in this area

Elemental fingerprinting of Hypericum perforatum (St John's Wort) herb and preparations using ICP-OES and chemometrics

This is a pre-copyedited, author-produced PDF of an article accepted for publication in Journal of Pharmaceutical and Biomedical Analysis following peer review. The version of record [Journal of Pharmaceutical and Biomedical Analysis (June 2016) Vol 125 pp 15-21, first published online March 4, 2016] is available online at doi: http://dx.doi.org/10.1016/j.jpba.2016.02.054 © 2016 Elsevier. This manuscript version is made available under the CC-BY-NC-ND 4.0 license http://creativecommons.org/licenses/by-nc-nd/4.0/St. John's wort (SJW) (Hypericum perforatum) is a herbal remedy commonly used to treat mild depression. The elemental profiles of 54 samples (i.e., dry herbs, tablets and capsules) were evaluated by monitoring 25 elements using Inductively Coupled Plasma Optical Emission Spectroscopy (ICP-OES). The major elemental constituents in the SJW samples were Ca (300-199,000 μg/g), Mg (410-3,530 μg/g), Al (4.4-900 μg/g), Fe (1.154-760 μg/g), Mn (2.4-261 μg/g), Sr (0.88-83.6 μg/g), and Zn (7-64 μg/g). For the sixteen elements that could be reliably quantified, principal component analysis (PCA) was used to investigate underlying patterns in the data. PCA models identified 7 key elements (i.e., Ba, Ca, Cd, Mg, Mo, Ni and Y), which described 85% of the variance in the dataset in the first three principal components. The PCA approach resulted in a general delineation between the three different formulations and provides a basis for monitoring product quality in this manner.Peer reviewe

How Icebreaking Governance Interacts with Inuit Rights and Livelihoods in Nunavut: A Policy Review

Sea ice is a contested space when it comes to navigation in ice-covered regions. For Inuit in Nunavut, Canada, sea ice is an integral platform of coastal connectivity, allowing access to areas of subsistence and cultural value. For vessels transiting Arctic waters, sea ice poses potential risks to vessel, crew, and passenger safety consequently, icebreaking is considered an essential service. Yet, many communities in Nunavut have described icebreaking as having, or potentially having significant negative impacts on community and ecological wellbeing. Several policies regulate and provide guidance to icebreakers operating in ice-covered waters. With anticipated increases to icebreaking demand in Arctic waters supporting destinational shipping, a policy review was conducted to explore how current regulations governing icebreaking activities in the Canadian Arctic interact with the rights and livelihoods of Inuit who live in Nunavut. Policy instruments governing icebreaking activities were framed, assessed, and aligned to Inuit rights, as set forth by international, national, and territorial provisions. International instruments provide minimal attention to environmental impacts of icebreaking and even less to its cultural and social impacts. Canadian instruments refer to both environmental impacts and Inuit use of sea ice for winter travel routes, framing both as elements that should be taken into consideration during route planning. Despite this, Inuit have had little involvement in developing current icebreaking regulations and guidelines beyond those under territorial jurisdiction. From this review, opportunities and recommendations are identified that could allow for future icebreaking policies to better account for Inuit rights and governance values

Hereditary Angioedema patient experiences of medication use and emergency care

Background: Hereditary angioedema (HAE) is a rare inherited illness characterised by recurrent swellings. Four percent of HAE attacks are life threatening throat swellings requiring urgent medical intervention. The aim of this study was to gain an in depth understanding of patient experiences of use of treatment and emergency care. Methods: 65 participants completed an online survey including open ended questions about their experiences and/or completed an in-depth interview. Interview participants were asked to share and talk about up to five images that they felt best represented their life experiences with HAE. Data were analysed using reflexive thematic analysis. Results: Treatment experiences highlighted the life changing nature of new treatments and benefits for quality of life, but also illustrated common barriers to treatment administration. Emergency care experiences illustrated how throat attacks and fear of their future occurrence could be traumatic. Discussion: Findings indicate that HAE patients need psychological support to process fears and negative experiences. In addition, psychological barriers to treatment administration must be addressed to ensure treatment is used effectively. Education for emergency practitioners is also needed to improve emergency treatment and reduce the psychological burden of delayed emergency care.</p

The association between pain-induced autonomic reactivity and descending pain control is mediated by the periaqueductal grey.

There is a strict interaction between the autonomic nervous system (ANS) and pain, which might involve descending pain modulatory mechanisms. The periaqueductal grey (PAG) is involved both in descending pain modulation and ANS, but its role in mediating this relationship has not yet been explored. Here, we sought to determine brain regions mediating ANS and descending pain control associations. Thirty participants underwent conditioned pain modulation (CPM) assessments, in which they rated painful pressure stimuli applied to their thumbnail, either alone or with a painful cold contralateral stimulation. Differences in pain ratings between ‘pressure-only’ and ‘pressure + cold’ stimuli provided a measure of descending pain control. In 18 of the 30 participants, structural scans and two functional MRI assessments, one pain-free and one during cold-pain were acquired. Heart rate variability (HRV) was simultaneously recorded. Normalised low-frequency HRV (LF-HRVnu) and the CPM score were negatively correlated; individuals with higher LF-HRVnu during pain reported reductions in pain during CPM. PAG-ventro-medial prefrontal cortex (vmPFC) and PAG-rostral ventromedial medulla (RVM) functional connectivity correlated negatively with the CPM. Importantly, PAG-vmPFC functional connectivity mediated the strength of the LF-HRVnu-CPM association. CPM response magnitude was also negatively correlated with vmPFC GM volume. Our multi-modal approach, using behavioural, physiological and MRI measures, provides important new evidence of interactions between ANS and descending pain mechanisms. ANS dysregulation and dysfunctional descending pain modulation are characteristics of chronic pain. We suggest that further investigation of body-brain interactions in chronic pain patients may catalyse the development of new treatments

Sustained perturbation in functional connectivity induced by cold pain.

BACKGROUND: Functional connectivity (FC) perturbations have been reported in multiple chronic pain phenotypes, but the nature of reported changes varies between cohorts and may relate to the consequences of living with chronic-pain related comorbidities, such as anxiety and depression. Healthy volunteer studies provide opportunities to study the effects of tonic noxious stimulation independently of these sequelae. Connectivity changes in task negative and positive networks, for example, the default mode and salience networks (DMN/SN), respectively, have been described, but how these and other connectivity networks, for example, those governing descending pain control are affected by the presence of tonic, noxious stimulation in healthy, pain-free individuals, remains unknown. METHOD: In 20 healthy volunteers, we assessed FC prior to, during, and following tonic cold painful stimulation in the ventromedial prefrontal cortex (vmPFC), rostral anterior insula (rAI), subgenual anterior cingulate cortex (ACC) and periaqueductal grey (PAG). We also recorded subjectively reported pain using a computerised visual analogue scale. RESULTS: We saw DMN FC changes during painful stimulation and that inter-network connectivity between the rAI with the vmPFC increased during pain, whereas PAG-precuneus FC decreased. Pain-induced FC alterations persisted following noxious stimulation. FC changes related to the magnitude of individuals' subjectively reported pain. CONCLUSIONS: We demonstrate FC changes during and following tonic cold-pain in healthy participants. Similarities between our findings and reports of patients with chronic pain suggest that some FC changes observed in these patients may relate to the presence of an ongoing afferent nociceptive drive. SIGNIFICANCE: How pain-related resting state networks are affected by tonic cold-pain remains unknown. We investigated functional connectivity alterations during and following tonic cold pain in healthy volunteers. Cold pain perturbed the functional connectivity of the ventro-medial prefrontal cortex, anterior insula, and the periacquaductal grey area. These connectivity changes were associated with the magnitude of individuals' reported pain. We suggest that some connectivity changes described in chronic pain patients may be due to an ongoing afferent peripheral drive.This work was funded by a Medical Research Council Experimental Medicine Challenge Grant (MR/N026969/1). MAH, SM, OO and SW are also supported by the NIHR Biomedical Research Centre for Mental Health at the South London and Maudsley NHS Trust. JOM is supported by a Sir Henry Dale Fellowship jointly funded by the Welcome Trust and the Royal Society (grant number 206675/Z/17/Z) and a Medical Research Council (MRC) Centre grant (MR/N026063/1)

Linking Pain Sensation to the Autonomic Nervous System: The Role of the Anterior Cingulate and Periaqueductal Gray Resting-State Networks.

There are bi-directional interactions between the autonomic nervous system (ANS) and pain. This is likely underpinned by a substantial overlap between brain areas of the central autonomic network and areas involved in pain processing and modulation. To date, however, relatively little is known about the neuronal substrates of the ANS-pain association. Here, we acquired resting state fMRI scans in 21 healthy subjects at rest and during tonic noxious cold stimulation. As indicators of autonomic function, we examined how heart rate variability (HRV) frequency measures were influenced by tonic noxious stimulation and how these variables related to participants' pain perception and to brain functional connectivity in regions known to play a role in both ANS regulation and pain perception, namely the right dorsal anterior cingulate cortex (dACC) and periaqueductal gray (PAG). Our findings support a role of the cardiac ANS in brain connectivity during pain, linking functional connections of the dACC and PAG with measurements of low frequency (LF)-HRV. In particular, we identified a three-way relationship between the ANS, cortical brain networks known to underpin pain processing, and participants' subjectively reported pain experiences. LF-HRV both at rest and during pain correlated with functional connectivity between the seed regions and other cortical areas including the right dorsolateral prefrontal cortex (dlPFC), left anterior insula (AI), and the precuneus. Our findings link cardiovascular autonomic parameters to brain activity changes involved in the elaboration of nociceptive information, thus beginning to elucidate underlying brain mechanisms associated with the reciprocal relationship between autonomic and pain-related systems