How natural are 'natural herbal remedies'? A Saudi perspective

OBJECTIVE: There is a rapidly growing trend in the consumption of herbal remedies in industrialised and developing countries. Users of herbal remedies are at risk of toxicity and adverse interactions of herbal preparations due to their frequent contamination with metals and adulteration with synthetic drugs. The purpose of this study was to assess the quality of herbal remedies present on the market in Saudi Arabia in recent years. METHODOLOGY: 247 herbal remedies and related preparations were examined from 2000-2001 at the Toxicology Laboratory, King Faisal Specialist Hospital and Research Centre, Riyadh, Saudi Arabia. Herbal powder samples were the most common sample type examined (n = 80), followed by complete, packed preparations (n = 59), single undescribed capsules or pills (n = 46), loose plant leaves or seeds (n = 28), creams (n = 18) and liquid or jelly samples (n = 16). All samples were subjected to toxicological screening for organic substances using gas chromatographic-mass spectrometric analysis, screening for heavy metals (arsenic, mercury, and lead) using inductive coupled plasma-mass spectrometry and microbiological examination. RESULTS: The preparations analysed were used to treat the following indications: leukaemia and other forms of cancer (n = 22); obesity (n = 18); diabetes mellitus (n = 14); rheumatic disorders (n = 14); skin pigmentation problems (n = 11); or to enhance male sexual activity (n = 9). In 123 cases, the indication of use was not known. 39 samples contained high concentrations of heavy metals. This was particularly striking in remedies used to treat leukaemia (arsenic content of 522-161,600 ppm) and in creams for whitening skin (mercury content of 5,700-126,000 ppm). Eight preparations contained synthetic drugs (e.g. benzodiazepines and tricyclic antidepressants in sedative preparations, cyproheptadine in a remedy to gain bodyweight, ibuprofen and dipyrone in herbal capsules used to treat rheumatism). 18 samples were contaminated with micro-organisms. 14 samples contained toxic substances of natural origin. Of the 247 examined preparations, 77 (i.e. over 30%) were disqualified due to high heavy metals content, bacterial contamination or presence of toxic organic substances. CONCLUSION: The study shows an urgent need to control the production, importing and selling of herbal preparations.     

HPLC and GC-MS screening of Chinese proprietary medicine for undeclared therapeutic substances

Traditional Chinese medicine includes raw medicinal materials and Chinese proprietary medicine (CPM). Despite being of natural origin, toxic effects, adulteration with synthetic therapeutic substances and even deaths had been associated with CPM. There is thus a need to develop analytical technique to rapidly screen for undeclared toxic and therapeutic substances in CPM. In this study, a high performance liquid chromatography-diode-array detection method was developed and used to screen for undeclared therapeutic substances in CPM. An ultraviolet (UV) library of 266 drugs had been compiled. Solute identification was performed by comparing the analytical data (UV spectra, retention time and relative retention time) with those of the 266 standards. Gas chromatography-mass spectrometry was used as a confirmation method. These chromatographic methods had been shown to be selective and reproducible in screening for undeclared drugs in CPM. Using the method developed, 41 CPM samples in seven categories were screened for undeclared therapeutic substances. One anti-asthmatic CPM was found to contain codeine.     

Consumers’ attitude towards the use and safety of herbal medicines and herbal dietary supplements in Serbia

Background The use of herbal medicines and herbal dietary supplements in Serbia is very common and many patients consume herbal preparations with conventional drug therapy. Objective The aim of this survey was to evaluate the consumers’ awareness of herbal remedies and the safety of herbal dietary supplements, their attitude towards combining herbals and drugs, and the source of recommendations for their use. Setting The study included all consumers who bought herbal remedies and herbal dietary supplements in 15 pharmacies on the territory of Novi Sad during 2011 and who accepted to be interviewed. Methods Structured interviews using questionnaire, conducted by pharmacists. The questionnaire included 4 parts: socio-demographic characteristics of consumers, source of recommendations for the use of herbal products, attitude towards safety of herbal remedies and herbal dietary supplements use and their combination with regular drugs, as well as the question of purchased herbal products. Main outcome measure Consumers’ attitude towards the safety and use of herbal medicines and herbal dietary supplements measured by 9 items. Results The majority of interviewed participants were highly educated, aged 41–60 and they consumed herbal remedies on their own initiative or on recommendation of nonmedically educated person, without previous consultation with medical doctor or pharmacist. Out of all participants: 88.9 % did not consider it important to inform their physician or pharmacist about use of herbal remedies and herbal dietary supplements; 73.3 % found the use of herbal remedies harmless (where 9.4 % did not have any attitude towards that issue), while 40.3 % of participants regarded the combining of herbal and regular drugs unsafe. Conclusion There is a need for consumers’ education on reliable use of herbal medicines and herbal dietary supplements, in order to improve their awareness of the limits of herbal remedies safety and potential risks of their combination with drugs.     

中、西药药代动力学相互作用研究进展

中药治疗各种疾病历史悠久,一般认为天然药物比合成药物安全导致中药在世界范围内的应用急剧增长,但中药同样具有潜在的不良反应和药物相互作用。本文综述并讨论了近几年来关于中、西药药代动力学相互作用研究,以促进中药的合理、安全使用。     

Suspected-target and non-targeted screenings of phosphodiesterase 5 inhibitors in herbal remedies using liquid chromatography–quadrupole time-of-flight–mass spectrometry

The lucrative market of herbal remedies spurs rampant adulteration, particularly with pharmaceutical drugs and their unapproved analogues. A comprehensive screening strategy is, therefore, warranted to detect these adulterants and, accordingly, to safeguard public health. This study uses the data-dependent acquisition of liquid chromatography-quadrupole time-of-flight–mass spectrometry (LC–QTOF–MS) to screen phosphodiesterase 5 (PDE5) inhibitors in herbal remedies using suspected-target and non-targeted strategies. For the suspected-target screening, we used a library comprising 95 PDE5 inhibitors. For the non-targeted screening, we adopted top-down and bottom-up approaches to flag novel PDE5 inhibitor analogues based on common fragmentation patterns. LC–QTOF–MS was optimised and validated for capsule and tablet dosage forms using 23 target analytes, selected to represent different groups of PDE5 inhibitors. The method exhibited excellent specificity and linearity with limit of detection and limit of quantification of <40 and 80 ng/mL, respectively. The accuracy ranged from 79.0% to 124.7% with a precision of <14.9% relative standard deviation. The modified, quick, easy, cheap, effective, rugged, and safe extraction provided insignificant matrix effect within −9.1%–8.0% and satisfactory extraction recovery of 71.5%–105.8%. These strategies were used to screen 52 herbal remedy samples that claimed to enhance male sexual performance. The suspected-target screening resulted in 33 positive samples, revealing 10 target analytes and 2 suspected analytes. Systematic MS and tandem MS interrogations using the non-targeted screening returned insignificant signals, indicating the absence of potentially novel analogues. The target analytes were quantified from 0.03 to 121.31 mg per dose of each sample. The proposed strategies ensure that all PDE5 inhibitors are comprehensively screened, providing a useful tool to curb the widespread adulteration of herbal remedies.     

X-ray powder diffractometry and liquid chromatography studies of sibutramine and its analogues content in herbal dietary supplements

The contemporary societies of the developed countries are prone to use traditional far-east medicines as remedies for all diseases. Some of them, such as obesity, might be classified as civilization diseases. Combating the problem, people try not only several miraculous diets but also herbal infusions (teas) and variety of “herbal” preparations. All these believing that such treatment is healthy and harmless as far as it is “natural”. Leaving out of the way the question if herbal medicines can be taken safely without doctors’ control the query arises if the common preparations are strictly natural and herbal.Here we report examples of quality studies of such medicines using both X-ray powder diffraction (XRPD) and liquid chromatography (LC) with various types of detection: ultraviolet (UV), coulometric electrode array (CEAD) and time-of-flight mass spectrometry (TOF-MS). Especially the XRPD assisted with an optical microscopy seems to be useful as a fast screening method of general sample composition of such preparations. First of all it can discriminate between capsules containing pure herbal materials and those with some chemical.     

Herbal drugs for diabetic treatment: an updated review of patents

Diabetes mellitus is the most common endocrine disorder, affecting 16 million individuals in the United States and 200 million worldwide. Despite the use of advanced synthetic drugs for the treatment, use of herbal remedies is gaining higher importance because of synthetic drugs have drawbacks and limitations. The herbal drugs with antidiabetic activity are extensively formulated commercially because of easy availability, affordability and less side effects as compared to the synthetic antidiabetic drugs. Antidiabetic herbal formulations (AHF) are considered to be more effective for the management of diabetes. There are around 600 herbal drug manufacturers in India of which almost all manufacturers are developing AHF in addition to others. Till date, no article is published to give detailed information of the patents on AHF. Thus, this review article undertake the attempt for providing updated information on the type of diabetes and patented AHF which will enhance the existing knowledge of the researchers.     

Chinese proprietary medicine in Singapore: regulatory control of toxic heavy metals and undeclared drugs.

Traditional Chinese medicine (TCM) is gaining popularity as a form of complementary and alternative medicine. Reports of efficacy of TCM are increasing in numbers. TCM includes both crude Chinese medicinal materials (plants, animal parts and minerals) and Chinese proprietary medicine (CPM) [final dosage forms]. Despite the belief that CPM and herbal remedies are of natural origin, unlike Western medicine, and are hence safe and without many adverse effects, there have been numerous reports of adverse effects associated with herbal remedies. Factors affecting the safety of herbal medicines include intrinsic toxicity, adulteration, substitution, contamination, misidentification, lack of standardisation, incorrect preparation and/or dosage and inappropriate labelling and/or advertising. Hence, new regulations on the control of CPM were enforced in Singapore with effect from 1 September 1999. These include licensing and labelling requirements, as well as control of microbial contamination. This article also reviews reports of excessive toxic heavy metals and undeclared drugs in CPM in Singapore between 1990 and 1997. The names, uses, toxic heavy metal or drug detected and the year of detection are tabulated. Information on the brand or manufacturer's name are provided whenever available. The public and healthcare professionals should be better informed of the basic concept of TCM and its usefulness, as well as the potential adverse effects associated with its use. Greater control over the safety and quality of CPM could be achieved through good manufacturing practice, regulatory control, research, education, reporting usage of Chinese medicine (as in drug history) as well as reporting of adverse events.     

Adulteration of herbal antidiabetic products with undeclared pharmaceuticals: a case series in Hong Kong

AIMS

The current study aims to examine the problem of adulteration of herbal antidiabetic products with undeclared pharmaceuticals, including both registered and banned drugs.

METHODS

All cases involving use of adulterated herbal antidiabetic products referred to a tertiary centre for clinical toxicology analysis from 2005 to 2010 inclusive were retrospectively reviewed. The patients'' demographic characteristics, clinical presentations, medical history, drug history and the analytical findings of the herbal antidiabetic products were studied.

RESULTS

A total of 27 cases involving use of 29 adulterated herbal antidiabetic products were identified. Seventeen of the patients (63%) had clinical toxicities associated with the illicit products. Hypoglycaemia was the most common adverse effect, followed by lactic acidosis. Analysis of the 29 illicit herbal antidiabetic products revealed eight undeclared registered or banned oral antidiabetic agents, namely glibenclamide (n = 22), phenformin (n = 18), metformin (n = 6), rosiglitazone (n = 6), gliclazide (n = 2), glimepiride (n = 2), nateglinide (n = 1) and repaglinide (n = 1). Non-antidiabetic drugs were also detected in some products. Up to four adulterants were detected within the same product.

CONCLUSIONS

Adulteration of herbal antidiabetic products with undeclared pharmaceuticals is a significant yet under-recognized problem. Patients taking these illicit products could be at risk of potentially fatal adverse effects. It is important to educate the public to avoid taking pCMs of dubious source. Effective regulatory measures should be put in place to address the problem.     

Analysis of undeclared synthetic phosphodiesterase-5 inhibitors in dietary supplements and herbal matrices by LC-ESI-MS and LC-UV

A liquid chromatography-electrospray ionisation-mass spectrometry (LC-ESI-MS) method was developed to screen for the presence of synthetic phosphodiesterase type 5 (PDE-5) inhibitors including sildenafil, tadalafil and vardenafil. The method was applied to the analysis of dietary supplements and bulk herbal materials. Bulk powders or composites of tablets, capsules or liquids were prepared and an extraction of PDE-5 inhibitors was performed using a mixture of acetonitrile and water with sonication. Identification of sildenafil, vardenafil or tadalafil was accomplished using a single quadrupole mass spectrometer coupled to a liquid chromatograph with an electrospray interface. Positive ion detection in the full scan mode was used while in-source collision induced dissociation (CID) provided several structurally significant fragment ions to aid in the mass spectral identification. Approximately half of the 40 botanical products analyzed were found to contain undeclared synthetic PDE-5 inhibitors. For products found to contain one of these three compounds by LC-MS, HPLC with UV detection was used for quantitation.     

Herb-drug interactions: Focus on metabolic enzymes and transporters

As the uses of herbal medicines from traditional natural products are increased, the need for pharmacokinetic studies and relevant data are also increased for safe pharmacotherapy. The market entry for the traditional herbal medicine is easier compared with that for synthetic drugs because of a lower regulatory barrier. Thus, the exact mechanisms for the absorption, distribution, metabolism and excretion of active components in herbal medicines and the potential herb-drug interactions are not always fully understood. Recently, there has been an increasing interest in pharmacokinetic studies of herbal remedies and relevant data of commonly used herbal remedies are accumulating in this field. In this review, the effects of nine botanicals (ginkgo, green tea, grapes, licorice, saw palmetto, garlic milk thistle, ginseng and St. John’s wort) on metabolic enzymes and transporters affecting absorption and disposition of herbal products are summarized. The source of samples (extracts and individual components), the species (human and animal) and in vivo and in vitro systems were separately reviewed for a better understanding of herb-drug interactions.     

Herbal remedies affecting coagulation: A review

Context: Herbal remedies are used to treat a large variety of diseases, including blood-related disorders. However, a number of herbal preparations have been reported to cause variations in clotting time, this is mainly by disruption of the coagulation cascade.

Objective: The compiling of plants investigated for effects on the coagulation cascade.

Methods: Information was withdrawn from Google Scholar and the journal databases Scopus and PubMed.

Results: Sixty-five herbal remedies were identified with antiplatelet, anticoagulant, or coagulating ability. Bioactive compounds included polyphenols, taxanes, coumarins, saponins, fucoidans, and polysaccharides.

Conclusion: Although research has been conducted on the effect of herbal remedies on coagulation, most information relies on in vitro assays. Contradictory evidence is present on bleeding risks with herbal uses, though herb–drug interactions pose a threat. As the safety of many herbals has not been proven, nor their effect on blood parameters determined, the use of herbal preparations before undergoing any surgical procedure should discontinued.     

Unregulated alternative medicine

Unconventional (i.e. alternative, traditional, or complementary) treatments are used by many individuals for a variety of symptoms and disorders. Reports on fraudulent products used for unconventional treatments are not uncommon. These include herbal remedies offered as "natural" while containing non-labeled synthetic pharmacological ingredients or even toxic agents, patients not being informed of active ingredients, products containing no active substances, or unqualified individuals or "clinics" delivering dangerous advice or treatment. Reports on tainted topical products remain rare due to the high analytical demands necessary to detect minimal traces of unknown ingredients, the fact that patients often use medications from different sources, and patient over-reliance on the effectiveness of folk remedies or advertised claims. The patients' assumption of receiving a safe and effective therapy by "natural" products has shown to be unreliable. The authors urge that quality standards for "natural" and pharmaceutical products should be the same and that only qualified professionals should deliver treatment and medical advice.     

Adulteration of South African traditional herbal remedies

Traditional herbal remedies are used as alternative medicine by a large proportion of people worldwide. Herbals are generally perceived as safe, harmless, and free from side effects, but there have been reports of adulteration of Asian herbal remedies with Western pharmaceuticals, a practice that has not hitherto been observed in Africa. The authors present 2 cases from South Africa in which herbal remedies, consumed by patients admitted to hospital, were found to be adulterated with commercially available Western medicines. The adulterants were identified using high-performance liquid chromatography with a photodiode array detector and gas chromatography-mass spectrometry. The authors alert clinicians to the fact that adulteration of herbal remedies may become more common and should be considered, especially in cases where the symptoms are confusing in light of the history.     

液质联用快速测定中药样品中的化学药物

蛴螬在祖国传统医学中有着悠久的使用历史.有破血、行瘀、散结、通乳等功效,用于治疗折损瘀痛、破伤风、喉痹、目翳等病症.目前蛴螬的具体化学成分不明确.现代药理研究表明该动物药具有抗肿瘤、保肝、治疗口疮等多种生物活性,是一种极具研究和开发价值的动物药.     

Over the counter (OTC) oral remedies for arthritis and rheumatism: how effective are they?

Background: Increasingly patients resort to alternative remedies for arthritis and rheumatism, perhaps partly impelled by reports of toxicities from prescribed non-steroid anti-inflammatory drugs (NSAID). There is uncertainty about whether the most common alternative treatments provide relief or may cause adverse reactions. Aim: To ascertain the validity of manufacturers' claims permitted by the Therapeutic Goods Administration (TGA) in Australia for a range of self-medication products to treat the pain and inflammation of arthritis, available in local pharmacies, supermarkets or by mail order and in other countries. Methods: OTC products were administered orally to rats in standard assays for suppressing experimental arthritis and fever and for determining potential gastrotoxicity. Results: The three NSAIDs available OTC were efficacious but gastrotoxic. Of the 37 herbal formulations examined, seven were as effective as ibuprofen in the anti-arthritic assay without causing gastric bleeding. Five of the 10 animal-sourced products tested were also effective without evident toxicity. Within a certain class of product, e.g. celery seed extracts or dried mussel preparations, efficacies ranged from almost zero to highly effective. Conclusions: Consumers currently have no guide to the likely efficacy of TGA-approved remedies. Quality control is urgently needed to justify the veracity of TGA-permitted and other claims on product labels.