The goal of our study was to evaluate the effects of different medicinal herbs rich in polyphenol (Lemon balm, Sage, St. John's wort and Small-flowered Willowherb) used as dietary supplements on bioaccumulation of some essential metals (Fe, Mn, Zn and Cu) in different chicken meats (liver, legs and breast).
In different type of chicken meats (liver, legs and breast) from chickens fed with diets enriched in minerals and medicinal herbs, beneficial metals (Fe, Mn, Zn and Cu) were analysed by flame atomic absorption spectrometry. Fe is the predominant metal in liver and Zn is the predominant metal in legs and breast chicken meats. The addition of metal salts in the feed influences the accumulations of all metals in the liver, legs and breast chicken meat with specific difference to the type of metal and meat. The greatest influences were observed in legs meat for Fe and Mn. Under the influence of polyphenol-rich medicinal herbs, accumulation of metals in the liver, legs and breast chicken meat presents specific differences for each medicinal herb, to the control group that received a diet supplemented with metal salts only. Great influence on all metal accumulation factors was observed in diet enriched with sage, which had significantly positive effect for all type of chicken meats.
Under the influence of medicinal herbs rich in different type of polyphenol, accumulation of metals in the liver, legs and breast chicken meat presents significant differences from the group that received a diet supplemented only with metal salts. Each medicinal herb from diet had a specific influence on the accumulation of metals and generally moderate or poor correlations were observed between total phenols and accumulation of metals. This may be due to antagonism between metal ions and presence of other chelating agents (amino acids and protein) from feeding diets which can act as competitor for complexation of metals and influence accumulation of metals in chicken meat.
Chicken liver; Chicken legs meat; Chicken breast meat; Medicinal herbs; Beneficial metals; Feeding diets; Polyphenol
Lead, mercury, and arsenic have been detected in a substantial proportion of Indian-manufactured traditional Ayurvedic medicines. Metals may be present due to the practice of rasa shastra (combining herbs with metals, minerals, and gems). Whether toxic metals are present in both US- and Indian-manufactured Ayurvedic medicines is unknown.
To determine the prevalence of Ayurvedic medicines available via the Internet containing detectable lead, mercury, or arsenic and to compare the prevalence of toxic metals in US- vs Indian-manufactured medicines and between rasa shastra and non–rasa shastra medicines.
A search using 5 Internet search engines and the search terms Ayurveda and Ayurvedic medicine identified 25 Web sites offering traditional Ayurvedic herbs, formulas, or ingredients commonly used in Ayurveda, indicated for oral use, and available for sale. From 673 identified products, 230 Ayurvedic medicines were randomly selected for purchase in August–October 2005. Country of manufacturer/Web site supplier, rasa shastra status, and claims of Good Manufacturing Practices were recorded. Metal concentrations were measured using x-ray fluorescence spectroscopy.
Main Outcome Measures
Prevalence of medicines with detectable toxic metals in the entire sample and stratified by country of manufacture and rasa shastra status.
One hundred ninety-three of the 230 requested medicines were received and analyzed. The prevalence of metal-containing products was 20.7% (95% confidence interval [CI], 15.2%–27.1%). The prevalence of metals in US-manufactured products was 21.7% (95% CI, 14.6%–30.4%) compared with 19.5% (95% CI, 11.3%–30.1%) in Indian products (P=.86). Rasa shastra compared with non–rasa shastra medicines had a greater prevalence of metals (40.6% vs 17.1%; P=.007) and higher median concentrations of lead (11.5 μg/g vs 7.0 μg/g; P=.03) and mercury (20 800 μg/g vs 34.5 μg/g; P=.04). Among the metal-containing products, 95% were sold by US Web sites and 75% claimed Good Manufacturing Practices. All metal-containing products exceeded 1 or more standards for acceptable daily intake of toxic metals.
One-fifth of both US-manufactured and Indian-manufactured Ayurvedic medicines purchased via the Internet contain detectable lead, mercury, or arsenic.
The levels of some heavy metals in 27 medicinal plant species from Ghana were studied in order to evaluate their health implications. These plant species, especially those used in the treatment of diseases such as hypertension, diabetes and asthma may require long term usage. The metals were copper, zinc, iron, manganese, nickel and cadmium. Atomic Absorption Spectrophotometry (wet digestion) was used for the analyses, and content of metals per sample was expressed as percent µg/g. Daily total intake of these metals is discussed based on the recommended daily intake of the medicinal plants or their corresponding formulations. From the results of the study zinc, copper and cadmium were present in all the plant species examined. Manganese was present in all species except V. amygdalina. Iron was found in all except five species (82%), whilst nickel was (rather rare) detected in only eight (30%) of the plant species. Significant variations in metal content existed (P<0.05) among the medicinal plant species with respect to the heavy metals evaluated. The concentrations of copper, zinc, cadmium and manganese were within their respective maximum permissible daily levels. However, some species, especially Ocimum canum (8), Clausena anisata and Rauwolfia vomitoria had levels of iron higher than the maximum permissible level of 1000 µg/day and may require care to avoid iron toxicity. The results also highlighted the differences in contents of minerals in Lippia multiflora obtained from different locations in Ghana. The findings generally suggest that the use of these plant species for the management of diseases will not cause heavy metal toxicity and may be beneficial to the users in cases of micronutrient deficiency, as these metals were found to be present in readily bioavailable form.
Health implications; heavy metals; herbal formulations; medicinal plant
Heavy metal and pesticide contamination has previously been reported in Chinese Herbal Medicines (CHMs), in some cases at potentially toxic levels. This study was conducted to determine general patterns and toxicological significance of heavy metal and pesticide contamination in a broad sample of raw CHMs. Three-hundred-thirty-four samples representing 126 species of CHMs were collected throughout China and examined for arsenic, cadmium, chromium, lead, and mercury. Of the total, 294 samples representing 112 species were also tested for 162 pesticides. At least 1 metal was detected in all 334 samples (100%) and 115 samples (34%) had detectable levels of all metals. Forty-two different pesticides were detected in 108 samples (36.7%), with 1 to 9 pesticides per sample. Contaminant levels were compared to toxicological reference values in the context of different exposure scenarios. According to a likely scenario of CHM consumption, only 3 samples (1%) with heavy metals and 14 samples (5%) with pesticides were found with concentrations that could contribute to elevated background levels of contaminant exposure. According to the most conservative scenario of CHM consumption, 231 samples (69%) with heavy metals and 81 samples (28%) with pesticides had contaminants that could contribute to elevated levels of exposure. Wild collected plants had higher contaminant levels than cultivated samples. Cadmium, chromium, lead, and chlorpyrifos contamination showed weak correlations with geographic location. Based on our assumptions of the likely mode of consumption of raw CHMs, the vast majority (95%) of the 334 samples in this study contained levels of heavy metals or pesticides that would be of negligible concern. However, given the number of samples with detectable contaminants and the range between the more likely and more conservative scenarios of contaminant exposure, more research and monitoring of heavy metals (especially cadmium and chromium) and pesticide residues (especially chlorpyrifos) in raw CHMs are advised.
Traditional Chinese Medicine (TCM); heavy metals; pesticide residues; herbal products; exposure assessment
Metal ions play an important role in biological processes and in metal homeostasis. Metal imbalance is the leading cause for many neurodegenerative diseases such as Alzheimer’s disease, Parkinson’s disease, and multiple sclerosis. 8-Hydroxyquinoline (8HQ) is a small planar molecule with a lipophilic effect and a metal chelating ability. As a result, 8HQ and its derivatives hold medicinal properties such as antineurodegenerative, anticancer, antioxidant, antimicrobial, anti-inflammatory, and antidiabetic activities. Herein, diverse bioactivities of 8HQ and newly synthesized 8HQ-based compounds are discussed together with their mechanisms of actions and structure–activity relationships.
metal binding compound; antineurodegenerative; anticancer; antidiabetic; multifunctional actions; structure-activity relationships
The fields of phototherapy and of inorganic chemotherapy both have long histories. Inorganic photoactivated chemotherapy (PACT) offers both temporal and spatial control over drug activation and has remarkable potential for the treatment of cancer. Following photoexcitation, a number of different decay pathways (both photophysical and photochemical) are available to a metal complex. These pathways can result in radiative energy release, loss of ligands or transfer of energy to another species, such as triplet oxygen. We discuss the features which need to be considered when developing a metal-based anticancer drug, and the common mechanisms by which the current complexes are believed to operate. We then provide a comprehensive overview of PACT developments for complexes of the different d-block metals for the treatment of cancer, detailing the more established areas concerning Ti, V, Cr, Mn, Re, Fe, Ru, Os, Co, Rh, Pt, and Cu and also highlighting areas where there is potential for greater exploration. Nanoparticles (Ag, Au) and quantum dots (Cd) are also discussed for their photothermal destructive potential. We also discuss the potential held in particular by mixed-metal systems and Ru complexes.
chemotherapy; metal; photochemistry
Rasagenthi Mezhugu (RGM) is a herbomineral formulation in the Siddha system of traditional medicine and is prescribed in the southern parts of India as a remedy for all kinds of cancers. However, scientific evidence for its therapeutic efficacy in cervical cancer is lacking, and it contains heavy metals. To overcome these limitations, RGM was extracted, and the fractions were tested on HPV-positive cervical cancer cells, ME-180 and SiHa. The extracts, free from the toxic heavy metals, affected the viability of both the cells. The chloroform fraction (cRGM) induced DNA damage and apoptosis. Mitochondria-mediated apoptosis was indicated. Though both the cells responded to the treatment, ME-180 was more responsive. Thus, this study brings up scientific evidence for the efficacy of RGM against the HPV-mediated cervical cancer cells and, if the toxic heavy metals are the limitation in its use, cRGM would be a suitable candidate as evidence-based complementary and alternative medicine for HPV-positive cervical cancers.
This short review highlights some of the exciting new experimental and theoretical developments in the field of photoactivatable metal complexes and their applications in biotechnology and medicine. The examples chosen are based on some of the presentations at the Royal Society Discussion Meeting in June 2012, many of which are featured in more detail in other articles in this issue. This is a young field. Even the photochemistry of well-known systems such as metal–carbonyl complexes is still being elucidated. Striking are the recent developments in theory and computation (e.g. time-dependent density functional theory) and in ultrafast-pulsed radiation techniques which allow photochemical reactions to be followed and their mechanisms to be revealed on picosecond/nanosecond time scales. Not only do some metal complexes (e.g. those of Ru and Ir) possess favourable emission properties which allow functional imaging of cells and tissues (e.g. DNA interactions), but metal complexes can also provide spatially controlled photorelease of bioactive small molecules (e.g. CO and NO)—a novel strategy for site-directed therapy. This extends to cancer therapy, where metal-based precursors offer the prospect of generating excited-state drugs with new mechanisms of action that complement and augment those of current organic photosensitizers.
metal complexes; excited states; photochemistry; phototherapy; imaging; theory and computation
A Chinese medicinal fern Blechnum orientale (Linn) was separately collected from polluted and unpolluted sites to determine whether it could accumulate hazardous pollutants or not. Metal concentrations (Cu, Zn, Mn, Pb, Cd, Cr, As, and Hg) both in the fronds and roots and polycyclic aromatic hydrocarbons (PAHs) in the fronds of this fern were quantified. At both sites, roots of B. orientale had significantly higher heavy metals than the fronds. Concentrations of Pb, As, Hg, Cd, and Cu in the fronds at the polluted site were more than 2, 6, 7, 14, 5, and 13 times of those at the unpolluted site. Translocation factor and bioaccumulation factor implied that B. orientale did not have a good ability to transport heavy metals from the roots to the fronds. Total PAHs in the fronds at the polluted site were significantly higher than those at the unpolluted site, indicating the physiological PAHs absorption by B. orientale growing at polluted sites. Uptake of pollutants via stomata might be the main reason causing the significant accumulation of hazardous pollutants in the fronds of B. orientale. Large-scale systematical survey and intensive monitoring on pollutants in this medicinal fern should be necessarily strengthened.
Background and Aims
Merwilla plumbea is an important African medicinal plant. As the plants grow in soils contaminated with metals from mining activities, the danger of human intoxication exists. An experiment with plants exposed to cadmium (Cd) was performed to investigate the response of M. plumbea to this heavy metal, its uptake and translocation to plant organs and reaction of root tissues.
Plants grown from seeds were cultivated in controlled conditions. Hydroponic cultivation is not suitable for this species as roots do not tolerate aquatic conditions, and additional stress by Cd treatment results in total root growth inhibition and death. After cultivation in perlite the plants exposed to 1 and 5 mg Cd L−1 in half-strength Hoagland's solution were compared with control plants. Growth parameters were evaluated, Cd content was determined by inductively coupled plasma mass spectroscopy (ICP-MS) and root structure was investigated using various staining procedures, including the fluorescent stain Fluorol yellow 088 to detect suberin deposition in cell walls.
The plants exposed to Cd were significantly reduced in growth. Most of the Cd taken up by plants after 4 weeks cultivation was retained in roots, and only a small amount was translocated to bulbs and leaves. In reaction to higher Cd concentrations, roots developed a hypodermal periderm close to the root tip. Cells produced by cork cambium impregnate their cell walls by suberin.
It is suggested that the hypodermal periderm is developed in young root parts in reaction to Cd toxicity to protect the root from radial uptake of Cd ions. Secondary meristems are usually not present in monocotyledonous species. Another interpretation explaining formation of protective suberized layers as a result of periclinal divisions of the hypodermis is discussed. This process may represent an as yet unknown defence reaction of roots when exposed to elemental stress.
Cadmium; environmental stress; medicinal plants; Merwilla plumbea; monocotyledonous plants; periderm; plant anatomy; root structure
Several traditional medicines contain potentially toxic heavy metals. Heavy metal poisoning is not an uncommon cause of renal damage, although the diagnosis can be easily missed. We report a case of chronic ingestion of an ayurvedic medicine containing mercury in a 2-year-old girl, resulting in anuric renal failure due to acute interstitial nephritis.
Children; d-Penicillamine; heavy metal poisoning; hemodialysis; mercury intoxication; tubulointerstitial nephritis
Shadbindu Taila (ST) is an Ayurvedic formulation used as a remedy for loosening of tooth, weakness of the eyesight, loss of hair, diseases of head, etc., Present study is an attempt to develop some newer approaches for the quality control and standardization of ST. Standardized operating procedure for the preparation of ST was developed in accordance with Ayurvedic Formulary of India. Preliminary phytochemical, physicochemical, and chromatographic evaluation of ST was carried out. Safety of ST was evaluated in terms of skin irritation test and presence of heavy metals. Chemical characterization of ST was done on the basis of kaempferol using validated -High Performance Thin Layer Chromatographic (HPTLC) method. ST did not show presence of any of the heavy metals analyzed and was found non-irritant on rabbit skin. The quality control parameters resulted after scientific evaluation of ST can be used as reference standard for quality control/assurance laboratory of a pharmaceutical firm in order to have a proper quality check over its preparation and processing.
High performance thin layer chromatography; kaempferol; safety; Shadbindu Taila; standardization
The Workshop was attended by 61 participants from 20 countries. Most of the speakers were
industrialists and the Chairpersons and Discussion Leaders were academics.
The area “Chemistry of Metals in Medicine” has the potential for producing innovative, high quality, and original research.
This is a new and emerging area of biomedical chemistry. Small firms are already being established which are devoted to the new elemental medicine. Major pharmaceutical and healthcare industries too are becoming aware of the major impact which metal chemistry is likely to have on traditional organic pharmacology and of the new opportunities which it presents for advances including the development of metalloenzyme-specific inhibitors, targeted radionuclide complexes for diagnosis and therapy, contrast agents for magnetic resonance imaging, safer mineral and vitamin supplements, new agents for the treatment of neurological, gastrointestinal and cardiovascular disease, skin conditions, cancer, and microbial and viral infections.
The European scientific and technological research base in this area is potentially attractive for business. Industrial collaboration and cooperation can be accommodated within the COST framework.
Melanins are high molecular weight pigments that are ubiquitous in nature and can also be synthesized in the laboratory from the variety of precursors. Melanins possess numerous interesting physico-chemical characteristics including electromagnetic radiation absorption properties and the ability to chelate metals. We have recently reported that melanin has remarkable ionizing radiation shielding properties, possibly because it can interact with photons via Compton scattering. We hypothesized that, if administered internally, in addition to radiation shielding, melanin could play a beneficial role by scavenging various radionuclides.
Three melanins were synthesized from dopamine, 3,4-dihydroxyphenylalanine (L-Dopa) and from combination of L-Cysteine and L-Dopa. For control synthetic melanin made from tyrosine polymerization (Sigma) was used. Melanins were characterized by elemental analysis. The chemosorption of 111In, 225Ac and 213Bi by melanins was studied at 37°C for up to 48 hrs.
The C to N molar ratios for dopamine, L-Dopa and tyrosine melanins were very close at 7.92, 8.39, and 8.48, respectively, while in mixed L-cysteine/L-Dopa melanin that ratio was much lower at 3.63. This mixed melanin also contained 22.33% sulfur, thus confirming incorporation of S-containing motifs into its structure. Dopamine, L-Dopa and tyrosine melanins were very similar in their ability to decrease the activity of 111In, 225Ac and 213Bi and their radioactive daughters in the supernatants more than 10-fold in comparison with the starting levels while mixed L-cysteine/L-Dopa melanin was able to chemosorb only 111In.
We have demonstrated that synthetic melanins made of diverse precursors can chemosorb 111In, 213Bi and 225Ac with dopamine, L-dopa and tyrosine melanins being the most efficient towards all three of these radionuclides. Such properties of synthetic melanins can contribute to the development of the novel melanin-based radioprotective materials.
melanin; chemosorption; 225-Actinium; 213-Bismuth; 111-Indium; radiological attack
Changes in the chemical environment can trigger large motions in chemomechanical polymers. The unique feature of such intelligent materials, mostly in the form of hydrogels, is therefore, that they serve as sensors and actuators at the same time, and do not require any measuring devices, transducers or power supplies. Until recently the most often used of these materials responded to changes in pH. Chemists are now increasingly using supramolecular recognition sites in materials, which are covalently bound to the polymer backbone. This allows one to use a nearly unlimited variety of guest (or effector) compounds in the environment for a selective response by automatically triggered size changes. This is illustrated with non-covalent interactions of effectors comprising of metal ions, isomeric organic compounds, including enantiomers, nucleotides, aminoacids, and peptides. Two different effector molecules can induce motions as functions of their concentration, thus representing a logical AND gate. This concept is particularly fruitful with effector compounds such as peptides, which only trigger size changes if, e.g. copper ions are present in the surroundings. Another principle relies on the fast formation of covalent bonds between an effector and the chemomechanical polymer. The most promising application is the selective interaction of covalently fixed boronic acid residues with glucose, which renders itself not only for sensing, but eventually also for delivery of drugs such as insulin. The speed of the responses can significantly increase by increasing the surface to volume ratio of the polymer particles. Of particular interest is the sensitivity increase which can be reached by downsizing the particle volume.
chemomechanical polymers; hydrogels; molecular recognition; supramolecular complexes; artificial muscles; glucose sensors
Mercury is a major toxic metal ranking top in the Toxic Substances List. Cinnabar (contains mercury sulfide) has been used in traditional medicines for thousands years as an ingredient in various remedies, and 40 cinnabar-containing traditional medicines are still used today. Little is known about toxicology profiles or toxicokinetics of cinnabar and cinnabar-containing traditional medicines, and the high mercury content in these Chinese medicines raises justifiably escalations of public concern. This minireview searched the available database of cinnabar, compared cinnabar with common mercurials, such as mercury vapor, inorganic mercury, and organic mercury, and discusses differences in their bioavailability, disposition, and toxicity. The analysis showed that cinnabar is insoluble and poorly absorbed from the gastrointestinal tract. Absorbed mercury from cinnabar is mainly accumulated in kidney, resembling the disposition pattern of inorganic mercury. Heating cinnabar results in release of mercury vapor, which in turn can produce toxicity similar to inhalation of these vapors. The doses of cinnabar required to produce neurotoxicity are thousands 1000 times higher than methyl mercury. Following long-term use of cinnabar, renal dysfunction may occur. Dimercaprol and succimer are effective chelation therapies for general mercury intoxication including cinnabar. Pharmacology studies of cinnabar suggest sedative and hypnotic effects, but the therapeutic basis of cinnabar is still not clear. In summary, cinnabar is chemically inert with a relatively low toxic potential when taken orally. In risk assessment, cinnabar is less toxic than many other forms of mercury, but the rationale for its inclusion in traditional Chinese medicines remains to be fully justified.
Cinnabar; Traditional medicines; Elementary mercury; Mercuric chloride; Methylmercury; Bioavailability; Disposition; Toxicology
The most common form of optoacoustic generation is thermoelasticity. Thermoelastic transduction is easy to implement and can be very broadband. However, its major drawback has always been poor conversion efficiency when a metallic film is used as the transducer. We have investigated two alternate structures for high efficiency, one based on a thin polymer film and the other using a two-dimensional nanostructure.
Biomaterials (e.g. polymers, metals, or ceramics), cell, and cell cluster (e.g. pancreatic islets) transplantation are beginning to offer novel treatment modalities for some otherwise intractable diseases. The innate immune system is involved in incompatibility reactions that occur when biomaterials or cells are introduced into the blood circulation. In particular the complement, coagulation, and contact systems are involved in the recognition of biomaterials and cells, eliciting activation of platelets and leukocytes. Such treatments are associated with anaphylactoid and thrombotic reactions, inflammation, and rejection of biomaterials and cells, leading to treatment failures and adverse reactions. We discuss here the new technologies that are being developed to shield the biomaterial and cell surfaces from recognition by the innate immune system.
Metal oxides in nanoparticle form such as zinc oxide and titanium dioxide now appear on the ingredient lists of household products as common and diverse as cosmetics, sunscreens, toothpaste, and medicine. Previous studies of zinc oxide and titanium dioxide in non-nanoparticle format using animals have found few adverse effects. This has led the FDA to classify zinc oxide as GRAS (generally recognized as safe) for use as a food additive. However, there is no regulation specific for the use of these chemicals in nanoparticle format. Recent studies, however, have begun to raise concerns over the pervasive use of these compounds in nanoparticle forms. Unfortunately, there is a lack of easily-adaptable screening methods that would allow for the detection of their biological effects.
We adapted two image-based assays, a fluorescence resonance energy transfer-based caspase activation assay and a green fluorescent protein coupled-LC3 assay, to test for the biological effects of different nanoparticles in a high-throughput format. We show that zinc oxide nanoparticles are cytotoxic. We also show that titanium dioxide nanoparticles are highly effective in inducing autophagy, a cellular disposal mechanism that is often activated when the cell is under stress.
We suggest that these image-based assays provide a method of screening for the biological effects of similar compounds that is both efficient and sensitive as well as do not involve the use of animals.
Ayurveda is a traditional form of medicine used by majority of the Indians. Here we report three cases of lead toxicity, following intake of Ayurvedic medicines. Three patients presented with blood lead levels (BLLs) of 122.4, 115 and 42.8 μg/dl respectively at the time of hospitalization. The first case was chelated with D- penicillamine, the second with calcium disodium ethylene diamino tetra acetate (EDTA) and the third with environmental intervention and education. Associated Ayurvedic products were collected from patients and analyzed for metallic concentration. Cessation of Ayurvedic medication along with chelation, nutritional intervention and education, reduced the BLL to 27.4 μg/dl in the first case after 1 year, 21.1 μg/dl after 9 months in the second and 18.2 μg/dl after 6 months in the third case.
Lead toxicity; Ayurvedic medicine; Abdominal pain; Chelation; Blood lead level
Arsenic and lead have been found in a number of traditional Ayurvedic medicines, and the practice of Rasa Shastra (combining herbs with metals, minerals and gems), or plant ingredients that contain these elements, may be possible sources. To obtain an estimate of arsenic and lead solubility in the human gastrointestinal tract, bioaccessibility of the two elements was measured in 42 medicines, using a physiologically-based extraction test. The test consisted of a gastric phase at pH 1.8 containing organic acids, pepsin and salt, followed by an intestinal phase, at pH 7 and containing bile and pancreatin. Arsenic speciation was measured in a subset of samples that had sufficiently high arsenic concentrations for the X-ray absorption near edge structure analysis used. Bioaccessible lead was found in 76% of samples, with a large range of bioaccessibility results, but only 29% of samples had bioaccessible arsenic. Lead bioaccessibility was high (close to 100%) in a medicine (Mahayograj Guggulu) that had been compounded with bhasmas (calcined minerals), including naga (lead) bhasma. For the samples in which arsenic speciation was measured, bioaccessible arsenic was correlated with the sum of As(V)–O and As(III)–O and negatively correlated with As–S. These results suggest that the bioaccessible species in the samples had been oxidized from assumed As–S raw medicinal ingredients (realgar, As4S4, added to naga (lead) bhasma and As(III)–S species in plants). Consumption at recommended doses of all medicines with bioaccessibile lead or arsenic would lead to the exceedance of at least one standard for acceptable daily intake of toxic elements.
Arsenic; Lead; Bioaccessibility; Ayurvedic; Speciation; Risk
The lysophospholipase D enzyme, autotaxin (ATX), has been linked to numerous human diseases including cancer, neurophatic pain, obesity, and Alzheimer’s disease. Although the ATX protein was initially purified and characterized in 1992, a link to bioactive lipid metabolism was not made until 2002. In the past decade, metal chelators, lysophospholipid product analogs, and more recently small non-lipid inhibitors of the enzyme were successfully identified. The majority of these inhibitors have been characterized using recombinant purified ATX in vitro, with very few examples studied in more complex systems. Translation of ATX inhibitors from the hands of medicinal chemists to clinical use will require substantially expanded characterization of ATX inhibitors in vivo.
Autotaxin; lysophosphatidic acid; lysophospholipase D; NPP2; cancer
Although the majority of published cases of lead poisoning come from occupational exposures, some traditional remedies may also contain toxic amounts of lead. Ayurveda is a system of traditional medicine that is native to India and is used in many parts of world as an alternative to standard treatment regimens. Here, we report the case of a 58-year-old woman who presented with abdominal pain, anemia, liver function abnormalities, and an elevated blood lead level. The patient was found to have been taking the Ayurvedic medicine Jambrulin prior to presentation. Chemical analysis of the medication showed high levels of lead. Following treatment with an oral chelating agent, the patient's symptoms resolved and laboratory abnormalities normalized. This case highlights the need for increased awareness that some Ayurvedic medicines may contain potentially harmful levels of heavy metals and people who use them are at risk of developing associated toxicities.
Lead poisoning; basophilic stippling; anemia; Ayurveda
Traditional Chinese medicine (TCM) has been practiced for thousands of years, but only within the last few decades has its use become more widespread outside of Asia. Concerns continue to be raised about the efficacy, legality, and safety of many popular complementary alternative medicines, including TCMs. Ingredients of some TCMs are known to include derivatives of endangered, trade-restricted species of plants and animals, and therefore contravene the Convention on International Trade in Endangered Species (CITES) legislation. Chromatographic studies have detected the presence of heavy metals and plant toxins within some TCMs, and there are numerous cases of adverse reactions. It is in the interests of both biodiversity conservation and public safety that techniques are developed to screen medicinals like TCMs. Targeting both the p-loop region of the plastid trnL gene and the mitochondrial 16S ribosomal RNA gene, over 49,000 amplicon sequence reads were generated from 15 TCM samples presented in the form of powders, tablets, capsules, bile flakes, and herbal teas. Here we show that second-generation, high-throughput sequencing (HTS) of DNA represents an effective means to genetically audit organic ingredients within complex TCMs. Comparison of DNA sequence data to reference databases revealed the presence of 68 different plant families and included genera, such as Ephedra and Asarum, that are potentially toxic. Similarly, animal families were identified that include genera that are classified as vulnerable, endangered, or critically endangered, including Asiatic black bear (Ursus thibetanus) and Saiga antelope (Saiga tatarica). Bovidae, Cervidae, and Bufonidae DNA were also detected in many of the TCM samples and were rarely declared on the product packaging. This study demonstrates that deep sequencing via HTS is an efficient and cost-effective way to audit highly processed TCM products and will assist in monitoring their legality and safety especially when plant reference databases become better established.
Chemicals derived from plants and animals are widely used in traditional Chinese medicine (TCM), and it is commonplace for remedies to contain a complex list of ingredients. Due to their heterogeneous origins, and subsequent processing into pills and powders, it can be difficult for the biological origin of ingredients within each remedy to be reliably determined. In this study, we have, for the first time, used a second-generation DNA sequencing method to analyse TCM remedies and determine their animal and plant composition. Using this deep-sequencing approach we identified plant species that are known to contain toxic chemicals and identified animal DNA from species that are currently endangered and protected by international laws. Consumers need to be made aware of legal and health safety issues that surround TCMs before adopting them as a treatment option. More widespread testing of complementary medicines using the DNA methods developed herein represents an efficient and cost-effective way to audit their composition.
Ayurveda is a unique system of medicine which uses metals and minerals in the form of bhasma (fine powder obtained through calcinations). Mandura is one of such mineral having various therapeutic uses. An effort has been made in the present study to characterize raw and processed Mandura using sophisticated analytical tools as a step forward to standardization. Mandura bhasma was prepared following references of Ayurvedic classics. To assure the quality of the prepared bhasma, Rasa Shastra quality control tests like rekhapurnatvam (particles enter into furrows of human hand), varitara (floating of product particles on water), irreversible etc., were used. Bhasma fulfilling these tests was analyzed using X-ray Diffraction (XRD) analysis. This revealed that raw Mandura contained Fe2Si04, and Mandura bhasma contained Fe2O3 and SiO2. Scanning Electron Microscopy (SEM) studies showed that the grains in Mandura bhasma were uniformly arranged in agglomerates of sizes 200-300 nm as compared to the raw Mandura, which showed a scattered arrangement of grains of sizes 10-2 microns. It may be concluded that this conversion of raw Mandura, a complex compound, into a mixture of simple compounds having nano-sized particles is due to the particular process of calcination employed.
Mandura bhasma; X-ray diffraction; Scanning electron microscopy