Investigation into the Authenticity of Commercial Rhodiola rosea Products by ¹H NMR, HPLC-MS/MS, and HPTLC

Reviewed: Booker A, Jalil B, Frommenwiler D, et al. The authenticity and quality of Rhodiola rosea products. Phytomedicine. October 31, 2015; [epub ahead of print]. doi: 10.1016/j.phymed.2015.10.006.

The root and rhizome of Rhodiola rosea (Crassulaceae) is widely used as an ingredient in dietary supplements. The European Medicines Agency’s Community Herbal Monograph lists the temporary relief of symptoms of stress, such as fatigue and sensation of weakness, as health benefits.¹ Most of the evidence in support of improving mental fatigue has been from clinical studies with the proprietary product SHR-5 (drug extract ratio 4:1; extraction solvent 70% ethanol; manufactured by the Swedish Herbal Institute; Göteborg, Sweden). Rhodiola crenulata (hong jing tian) is the only official Rhodiola species listed in the Chinese Pharmacopoeia, but other species, such as R. heterodonta, R. quadrifida, R. semenovii, and R. kirilowii, are used in traditional Chinese medicine (TCM) as well.² A survey of R. crenulata raw materials from drugstores and hospitals in China showed that a variety of Rhodiola species are sold labeled as hong jing tian.³

The present work investigated 39 samples altogether, including R. rosea crude drug material (2), bulk powders (3), hard capsule extracts (21), soft gel capsules (1), tablets (9) claiming to be R. rosea, and aqueous extracts of R. crenulata (3). The crude drug material was used as reference material. Two of the products analyzed were combined with vitamins and other herbal extracts. Most products (37) were not registered and were readily available over the Internet and from retail outlets as food supplements.

The researchers used proton nuclear magnetic resonance (¹H NMR), high-performance liquid chromatography–mass spectrometry (HPLC-MS), and high-performance thin-layer chromatography (HPTLC) to analyze the samples. Data from the ¹H NMR analysis were subjected to statistical evaluation by principal component analysis (PCA), but the model appeared to poorly discriminate among products containing R. rosea extracts and those extracts containing R. crenulata or other Rhodiola species. This may be due to the presence of large amounts of glycosides and excipients, which may have been similar enough to prevent grouping the various species into distinct clusters, or the fact that the species are chemically similar.

The HPTLC analysis showed incorrect labelling in seven products, based on the absence of rosavin, a marker compound that is characteristic for R. rosea, and the overall fingerprint, which was different from the R. rosea reference material. In five of these products, the data showed the presence of salidroside, indicating that the ingredient was made from a different Rhodiola species, e.g., R. crenulata or R. quadrifida. One product contained the amino acid 5-hydroxytryptophan (5-HTP) besides the excipients, and one did not contain any identifiable substances. The identity of 5-HTP was confirmed by NMR and HPLC-MS/MS data.

Comment: This paper raises some questions about the authenticity of dietary supplements labeled to contain R. rosea. Approximately 20% of the products analyzed were mislabeled; a case of economic adulteration is the sale of 5-HTP, a naturally occurring (e.g., in Griffonia simplicifolia, Fabaceae) amino acid that is sold as a mood-enhancing dietary supplement. The sale of R. crenulata, which is less expensive than R. rosea according to the authors of the paper, could be a case of economically motivated adulteration, but could also be due to the interchangeable use of some of the Rhodiola species in TCM. In China, different species (e.g., R. algida, R. crenulata, R. kirilowii, R. quadrifida, R. sachalinensis, R. yunnanensis) can be used for the same conditions depending on local traditions and availability.^2-4 The chemical composition of some of these species was found to differ according to Liu et al.,⁵ but the pharmacological effects are considered similar. To our knowledge, there are no data that indicate that the use of R. crenulata is unsafe; therefore, the presence of R. crenulata in dietary supplements labeled to contain R. rosea is not a safety concern. However, most of the available human clinical studies have been carried out using R. rosea;⁶ therefore, the scientific data in support of the benefits of R. rosea for mental and physical fatigue are more compelling.

The paper also demonstrates one of the shortcomings of using a chemometric approach to detect adulteration of finished products containing botanical ingredients. While multivariate statistics work well with crude raw materials, where processing can be standardized, differences in the manufacturing process, and the addition of various excipients, may modify the chemical fingerprint of the finished product to an extent where chemometric models no longer provide useful results. Interestingly enough, the use of a relatively simple HPTLC analysis was more successful in the detection of adulteration than the ¹H NMR approach. While the experimental part is well done, the paper would have benefitted if one or several botanically authenticated materials was included in the work.

References

1.     European Medicines Agency Committee on Herbal Medicinal Products (HMPC). Community herbal monograph on Rhodiola rosea L., rhizoma et radix. London: European Medicines Agency; 2012. Available at: http://www.ema.europa.eu/docs/en_GB/document_library/Herbal_-_Community_herbal_monograph/2012/05/WC500127863.pdf. Accessed January 6, 2016.

2.     Qi Y-J, Cui S, Lu D-X, et al. Effects of the aqueous extract of a Tibetan herb, Rhodiola algida var. tangutica on proliferation and HIF-1α, HIF-2α expression in MCF-7 cells under hypoxic condition in vitro. Cancer Cell Int. 2015;15:81. Doi: 10.1186/s12935-015-0225-x.

3.     Xin T, Li X, Yao H, et al. Survey of commercial Rhodiola products revealed species diversity and potential safety issues. Sci Rep. 2015;5:8337. doi: 10.1038/srep08337.

4.     Rhodiola. Shen-Nong Limited website. Available at: http://www.shen-nong.com/eng/herbal/hongjingtian.html. Accessed January 6, 2016.

5.     Liu Z, Liu Y, Liu C, et al. The chemotaxonomic classification of Rhodiola plants and its correlation with morphological characteristics and genetic taxonomy. Chem Cent J. 2013;7(1):118. Doi: 10.1186/1752-153X-7-118.

6.     Brown RP, Gerbarg PL, Ramazanov Z. Rhodiola rosea: a phytomedicinal overview. HerbalGram. 2002;(56):40-52.