The presence of substitutes or filler species in some cases reflects intentional, economically motivated and fraudulent practices by producers or vendors although the European Pharmacopoeia Ph. Counterfeiting by adding synthetic prescription drugs as chemical adulterants is another form of falsification, and Calahan et al.
Apart from the many cases of adulteration and general low quality of commercial herbal products, P. This latter case suggests either accidental contamination through poor manufacturing process or intentional adulteration for achieving an expected physiological or pharmacological effect Hoban et al. The presence of unlabeled species, plant extracts or synthetic chemical compounds might negatively interact with other medicinal plants, food supplements or prescription drugs and will pose significant risks for human health Jordan et al.
Adverse drug reactions ADRs due to herb—drug interactions HDI can appear in patients taking herbs and prescribed medications concomitantly Awortwe et al. Ginseng can interfere with various drugs, such as digoxin, insulin, anticoagulants, and monoamine oxidase inhibitors Sellami et al.
Pharmacovigilance relies heavily on ADR reporting, and despite initiatives to stimulate reporting of suspected ADRs associated with herbal medicines, numbers of herbal ADR reports are relatively low. ADRs Under-reporting is likely to be specific for herbal medicines, since their users usually do not look for medical advice about their use of such products, or report if they experience any adverse effects Barnes, The specific active constituents in Panax herbs, the ginsenosides, have been shown to improve immune function, reduce mental stress, and stabilize blood pressure while ginseng products are used as an endurance performance enhancer Sellami et al.
Nevertheless, authentic ginseng products does not represent a doping concern for athletes, as there were no positive tests for any International Olympic Committee IOC banned or restricted substances in any of the subjects after the ingestion of commercially available, proprietary ginseng root extract product Goel et al.
Adverse drug reactions to ginseng are associated with high doses and long-term usage Kiefer and Pantuso, ; Sellami et al. Long term use may cause blood clotting Mohammed Abdul et al.
Ginseng reduces the blood levels of warfarin and alcohol as well as induced mania if taken concomitantly with phenelzine, a non-selective and irreversible monoamine oxidase inhibitor used as an antidepressant and anxiolytic agent Chen et al. Moreover, women may experience additional side effects, such as vaginal bleeding and breast tenderness. Most of these side effects are serious enough to warrant stopping taking ginseng in breast cancer patients Sellami et al.
A rare adverse drug reaction to herbal and dietary supplementation, the drug-induced liver injury DILI , was reported as result from ingestion of ginseng for premenopausal symptoms Lin et al.
Recently, a website with a critically reviewed database presenting reported cases of ginseng-drug interactions was publicly launched Wu et al. The herbal medicines differ considerably from conventional medicines, and they pose a variety of challenges to their pharmacovigilance. For herbal pharmacovigilance, four main challenges: 1 Substitution and adulteration; 2 Nomenclature of herbals and ingredients of plant origin; 3 Lack of monitoring; and 4 Standardization, have been identified de Boer et al.
This review highlights that all four apply to ginseng commercial products, and support the challenge of detecting significant adverse drug reactions in a timely manner to protect consumers. Despite being the most valuable herbal product in terms of market value share, ginseng products are poorly regulated. Several authentication studies have shown that adulteration is not uncommon and not limited to any specific country of origin. The high market value of ginseng provides an incentive for fraudulent actors to generate profits at the expense of gullible consumers and honest producers, wholesalers and retailers.
Although authentication using traditional, pharmacopoeial, analytical methods such as TLC, HPLC and NMR can be used for advanced quality control, the standard authentication protocols are insufficient for efficiently detecting species adulteration, adulteration with synthetic pharmaceuticals and spiking of low quality products with marker compounds.
Cutting-edge approaches enable distinction of age-specific metabolite spectra, quantification of active ingredients and accurate identification of ginseng species, but these are not yet in widespread use.
MI performed the literature systematic search and analyzed the results. MI and HB wrote the manuscript together. The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. Ahmad, R. Extraction and UHPLC-DAD detection of undeclared substances in market-available dietary supplements and slimming products in Eastern region, Saudi Arabia: an application of principal component analysis.
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Kiefer, D. Panax ginseng. PubMed Abstract Google Scholar. Kim, N. Meyer, and Panax vietnamensis Ha et Grushv. Each Panax species may have slightly different uses 9 , 11 but all contain ginsenosides or panaxosides —steroidal saponins that contain the 4 trans -ring rigid steroid skeleton—and differ mainly by the number, type, and location of their sugar moieties 11 , Ginsenosides are unique to Panax species, are associated with the pharmacologic activity of Panax species, and are used as marker compounds for quality control 9 , 11 — The relative amounts of ginsenosides may also be used to differentiate between Panax species.
Siberian ginseng, prepared from the dried roots of Eleutherococcus or Acanthopanax senticosus Rupr. Constituents of E. Concentrations and ratios of the respective marker compounds were then compared with information stated on the product label. Twenty-five commercial products labeled as ginseng were purchased from a local health food store.
Eight of the products were identified as containing P. Each product tested was unique; multiple samples of the same product or different lots were not tested. Calibration standards, quality-control samples, and fortified samples were prepared fresh daily from the stock solutions.
Samples with concentrations above this range were diluted and reanalyzed. Both positive and negative quality-control samples were extracted and analyzed with each batch of commercial samples. For powdered samples, all the capsules in the bottle were opened and the contents mixed thoroughly before taking an aliquot for analysis to minimize any potential capsule-to-capsule variability.
Ginsenosides were extracted from samples, standards, and controls by a modification of the method reported by Li et al Recovery was determined by comparing the amount recovered from the fortified sample ie, the amount in fortified samples less the amount in nonfortified samples with unextracted solutions prepared at the fortified concentrations.
After centrifugation, the supernatant fluid was added to bonded-phase extraction columns BondElut C, HF; Varian Sample Preparation that had been preconditioned with 2 mL methanol followed by 2 mL water. Eleutherosides were liquid extracted by using a modification of the procedure reported by Yat et al Ginsenosides were separated and quantitated by using a flow rate of 1.
Quantitation was based on ultraviolet absorption at nm. Concentrations of ginsenosides and eleutherosides in commercial samples were determined by peak area with use of external standard analysis with a 5-point calibration curve extracted with each batch of samples.
Positive and negative quality-control samples were added to each batch of samples. Ginsenoside samples were extracted and analyzed in duplicate on 2 separate occasions and eleutheroside samples were extracted and analyzed in duplicate on one occasion.
All of the commercial ginseng products contained the appropriate marker compounds and were correctly labeled as to genus of the plant material. Products labeled as containing Panax species contained ginsenosides, products labeled as containing E.
Although it would be difficult to identify the species of Panax used in each preparation, the 4 products labeled as American ginseng had ginsenoside profiles typical of P. Concentrations of ginsenosides in commercial ginseng products labeled as containing Panax species 1. Values are the mean of quadruplicate determinations. The mean CV for each determination was 9. ND, not detected. Concentrations of eleutherosides in commercial ginseng products labeled as containing Eleutherococcus senticosus 1.
Values are the mean of duplicate determinations. The mean CV for each determination was 6. There was, however, significant product-to-product variability in the amount of ginsenosides or eleutherosides present. Total ginsenoside concentrations varied fold 0. Total eleutheroside concentrations varied fold 0. The mean CV for quadruplicate analysis of samples containing ginsenosides was 9.
The mean CV for the duplicate analysis of samples containing eleutherosides was 6. Of the 25 samples tested, 11 were labeled as containing a specific concentration of ginsenosides or eleutherosides. Of these, 5 contained more than the labeled concentration of ginsenosides or eleutherosides and 6 contained less than the specified concentration.
The concentrations found ranged from As shown in Table 3 , several studies reported significant variability in the concentrations of ginsenosides and eleutherosides in commercial products. Because different analytic methods were used in the various studies, the values can be compared only generally.
The amounts of ginsenosides determined in the present study were within the same ranges shown in Table 3 , but were somewhat lower than those reported for products in the United States 8 and Europe 22 , 23 and for dried, intact ginseng roots sold for use in traditional Chinese medicines These differences in ginsenoside concentrations are not surprising considering the variability in species used, the lack of standardized analytic methods, and the practice in Europe of fortifying herbal products with plant extracts to increase the concentration of marker compounds.
The eleutheroside concentrations found in this study were also within the same range reported by others 17 , Reported concentrations of ginsenosides and eleutherosides in commercial products 1. Different analytic methods were used in the various studies; therefore, the values shown are only generally comparable.
NA, not available. Our analyses showed that the commercial ginseng products tested were appropriately labeled as to plant genus, but that variability among the products was considerable. In contrast with the results of some studies 7 , 8 , all of the products we tested contained at least some amount of the appropriate marker compounds, either ginsenosides or eleutherosides.
Furthermore, the marker compound profile for products labeled as American ginseng ie, no ginsenoside Rf and a low ratio of Rg 1 to Rb 1 indicated that the correct Panax species P. However, like other investigators, we found significant variability in concentrations of the marker compound, ie, measured concentrations were markedly different from the labeled concentrations. In general, Siberian ginseng products varied more than did Asian ginseng products and liquid extracts varied more than did powdered products.
This may not be surprising because it has been suggested that the increased demand for medicinal plants will lead to the harvesting of immature plants and thus a gradual lowering of ginsenoside concentrations, which may affect the overall quality of the commercial products There are relatively few published data on eleutheroside concentrations in either herbal products or intact E. Although the E. The variability in concentration of the marker compound observed by all investigators suggests a need for standardization.
European manufacturers have offered standardized herbal extracts for some time, at least to the extent that the extraction procedure is adjusted to ensure that a predetermined amount of a known constituent is present in each product.
Similarly, many US manufacturers of herbal products now include marker compound concentrations on labels even though this is not currently required. However, the presence of specific concentrations of marker compounds ie, chemically based standardization may not guarantee pharmacologic activity. First, for most herbal products, data are insufficient to assign activity to a particular marker compound; therefore, there is no evidence on which to establish a threshold concentration.
To suggest that ginseng's biological activity is determined by only a few of its components may be too simplistic. In Asia, the quality of ginseng is not determined by the ginsenoside content but rather by the origin and age of the plant and the physical characteristics of the root.
In all Panax species, ginsenoside concentrations are considerably higher in the flowers and leaves than in the root 9 , 11 , 16 , but these portions are infrequently used. Similarly, ginsenoside concentrations are typically higher in the species P. This suggests that commercial value is not necessarily related to ginsenoside concentration. When standardization is achieved by fortifying with concentrated extracts, the desired activity of the final product may be altered or chemical residues from the extraction process may be present.
In Germany, for example, P. Activity-based standardization, as is done now for pharmaceuticals of biological origin, may be more appropriate than is chemically based standardization for herbal products because many components may contribute to activity.
Ginseng: a miracle sources of herbal and pharmacological uses. Complementary and Alternative Medicine in Gastroenterology. Pain on the Plane. This case discusses a pharmacokinetic interaction between warfarin and ginseng resulting in the decreased anticoagulant effect of warfarin. Warfarin is a cytochrome P 2C9 substrate and ginseng is … Expand. Analysis of ginsenosides by chromatography and mass spectrometry: release of 20 S-protopanaxadiol and 20 S-protopanaxatriol for quantitation.
Changes in bone density with lactation. Bone density in women receiving depot medroxyprogesterone acetate for contraception. International Patterns of Osteoporosis.
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