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Editorial Special Issue Quality control In recent years consumers have taken greater interest and responsibility for their own health, both in terms of prevention and treatment, which has led to an escalation in the use and development of plant-based health products. The pharmaceutical industry produces products fortified with extracts of natural origin known to have beneficial active ingredients. Despite the common belief that natural products are safe they, just like synthetic compounds, all have inherent risks. In view of a suggested amendment to the general regulations of the Medicines and Related Substances Act, the Department of Health in South Africa has recommended that all herbal products are regulated in terms of safety, efficacy and quality. Safety and efficacy depend largely on the quality of the raw materials used. Considering the abovementioned amendment, quality assurance protocols are urgently required for indigenous medicinal plants to ensure high value products both for the local and export market. The South African government has acknowledged that an urgent need exists to ensure the quality of traditional medicines and the South African Bureau of Standards (SABS) has responded to this need and is in the process of developing standards for traditional medicines. On opening the new facilities at the SABS in October 2011 the president of South Africa, Mr Jacob Zuma, called for the acceleration of developing standards for traditional medicines and stated that it should be a national priority. Although some excellent work in the field of natural products has been carried out on South African plants, these studies mostly embrace classical natural product chemistry, bioprospecting and bioactivity testing (ethnopharmacology) while quality control aspects are being mostly neglected as a prominent research focus. This special issue has been compiled to achieve two objectives: 1. to collate a combination of review and original research papers which could be of value to both researchers and industry; and 2. to create an awareness around the importance of quality assessment and encourage local research on the quality, safety and efficacy of phytomedicines. Traditional medicines are extensively used in South Africa and a large informal industry has developed selling traditional medicines in various forms including semi- and full-processed mixtures. However, concerns have been raised about the quality of these products especially on manufacturing practices leading to possible adulteration, contamination with toxic substances (natural or synthetic), incorrect preparation practices as well as packaging and labelling issues as discussed by Ndhlala and Van Staden (2012-this issue). Ironically, a misconception still exists that due to the sessile nature of a plant its chemistry is equally stable. Ncube et al. (2012-this issue) discuss multitude of factors, specifically environmental conditions, impacting on the phytochemistry of a plant which inevitably will influence the medicinal properties and determine the efficacy of a plant and its derived extracts. Due to the chemical complexity of plants, analytical techniques are crucial to assess the quality of botanical extracts. Metabolomics which combines powerful analytical techniques with multivariate data modelling has revolutionised natural product research. Heyman and Meyer (2012-this issue) discuss nuclear magnetic resonance (NMR) metabolomics as a technique to achieve quick and reliable quality control and metabolite profiling of phytomedicines to ensure the quality and reproduc- ibility of herbal medicines. Although nuclear magnetic resonance is not as sensitive as other analytical techniques it is far more reproducible, non-destructive, covers a much wider dynamic range and sample preparation is simple. Another technique which is well suited for metabolomic studies is mass spectrometry. The application of this technology and research approach is illustrated by Albrecht et al. (2012-this issue) where terpenoid and flavonoid profiles are used to determine the provenance of Sutherlandia frutescens samples. Due to the importance of S. frutescens in traditional medicines and the continued commercial interest in Cancer bush a second paper by Mncwangi and Viljoen (2012-this issue) has been included which documents the amino acid profile in natural populations and cultivated material. This paper presents the first report on the variation of the claimed pharmacologically active phytoconstituents (amino acids and pinitol) and the information gathered during this study could be of value to select specific chemotypes for cultivation and for developing guidelines for quality control purposes. Centella asiatica is a well known medicinal plant, most notable for its wound healing properties. Pennywort has been commercialised and it is the subject of several patent applications particularly for its curative properties in dermatological formulations. Although this species has an expansive pan-tropical distribution little is known on the South African material. Asiaticoside is believed to be the major active principle and by using LCMS data Long et al. (2012-this issue) show the chemotaxonomic value of this saponin and report for the first time that South African material may be suitable for cultivation due to favourable levels of this bioactive molecule. www.elsevier.com/locate/sajb 0254-6299/$ -see front matter © 2012 SAAB. Published by Elsevier B.V. All rights reserved. http://dx.doi.org/10.1016/j.sajb.2012.08.006 Available online at www.sciencedirect.com South African Journal of Botany 82 (2012) 1 3

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Page 1: Special Issue — Quality control

www.elsevier.com/locate/sajb

Available online at www.sciencedirect.com

South African Journal of Botany 82 (2012) 1–3

Editorial

Special Issue — Quality control

In recent years consumers have taken greater interest andresponsibility for their own health, both in terms of preventionand treatment, which has led to an escalation in the use anddevelopment of plant-based health products. The pharmaceuticalindustry produces products fortified with extracts of naturalorigin known to have beneficial active ingredients. Despite thecommon belief that natural products are safe they, just likesynthetic compounds, all have inherent risks.

In view of a suggested amendment to the general regulationsof the Medicines and Related Substances Act, the Department ofHealth in South Africa has recommended that all herbal productsare regulated in terms of safety, efficacy and quality. Safety andefficacy depend largely on the quality of the raw materials used.Considering the abovementioned amendment, quality assuranceprotocols are urgently required for indigenous medicinal plants toensure high value products both for the local and export market.The South African government has acknowledged that an urgentneed exists to ensure the quality of traditional medicines and theSouth African Bureau of Standards (SABS) has responded to thisneed and is in the process of developing standards for traditionalmedicines. On opening the new facilities at the SABS in October2011 the president of South Africa, Mr Jacob Zuma, called for theacceleration of developing standards for traditional medicinesand stated that it should be a national priority. Although someexcellent work in the field of natural products has been carried outon South African plants, these studies mostly embrace classicalnatural product chemistry, bioprospecting and bioactivity testing(ethnopharmacology) while quality control aspects are beingmostly neglected as a prominent research focus. This specialissue has been compiled to achieve two objectives: 1. to collate acombination of review and original research papers which couldbe of value to both researchers and industry; and 2. to create anawareness around the importance of quality assessment andencourage local research on the quality, safety and efficacy ofphytomedicines.

Traditional medicines are extensively used in South Africa anda large informal industry has developed selling traditionalmedicines in various forms including semi- and full-processedmixtures. However, concerns have been raised about the quality ofthese products especially on manufacturing practices leading topossible adulteration, contamination with toxic substances (naturalor synthetic), incorrect preparation practices as well as packagingand labelling issues as discussed by Ndhlala and Van Staden

0254-6299/$ -see front matter © 2012 SAAB. Published by Elsevier B.V. All rightshttp://dx.doi.org/10.1016/j.sajb.2012.08.006

(2012-this issue). Ironically, a misconception still exists that due tothe sessile nature of a plant its chemistry is equally stable. Ncubeet al. (2012-this issue) discuss multitude of factors, specificallyenvironmental conditions, impacting on the phytochemistry of aplant which inevitably will influence the medicinal properties anddetermine the efficacy of a plant and its derived extracts.

Due to the chemical complexity of plants, analyticaltechniques are crucial to assess the quality of botanical extracts.Metabolomics which combines powerful analytical techniqueswith multivariate data modelling has revolutionised naturalproduct research. Heyman and Meyer (2012-this issue) discussnuclear magnetic resonance (NMR) metabolomics as a techniqueto achieve quick and reliable quality control and metaboliteprofiling of phytomedicines to ensure the quality and reproduc-ibility of herbal medicines. Although nuclear magnetic resonanceis not as sensitive as other analytical techniques it is far morereproducible, non-destructive, covers a much wider dynamicrange and sample preparation is simple. Another technique whichis well suited for metabolomic studies is mass spectrometry. Theapplication of this technology and research approach is illustratedbyAlbrecht et al. (2012-this issue) where terpenoid and flavonoidprofiles are used to determine the provenance of Sutherlandiafrutescens samples. Due to the importance of S. frutescens intraditional medicines and the continued commercial interest inCancer bush a second paper byMncwangi and Viljoen (2012-thisissue) has been included which documents the amino acid profilein natural populations and cultivatedmaterial. This paper presentsthe first report on the variation of the claimed pharmacologicallyactive phytoconstituents (amino acids and pinitol) and theinformation gathered during this study could be of value toselect specific chemotypes for cultivation and for developingguidelines for quality control purposes.Centella asiatica is a wellknown medicinal plant, most notable for its wound healingproperties. Pennywort has been commercialised and it is thesubject of several patent applications particularly for its curativeproperties in dermatological formulations. Although thisspecies has an expansive pan-tropical distribution little isknown on the South African material. Asiaticoside is believedto be the major active principle and by using LC–MS dataLong et al. (2012-this issue) show the chemotaxonomic valueof this saponin and report for the first time that South Africanmaterial may be suitable for cultivation due to favourablelevels of this bioactive molecule.

reserved.

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The quality of natural products is in part determined throughauthentication of plant material and/or the quantification ofbiomarkers. Pelargonium sidoides, indigenous to Lesotho andSouth Africa, is perhaps one of the most well-known plantremedies used for the treatment of respiratory tract infections.However, it is commonly adulterated or substituted withPelargonium reniforme highlighting the need for rapid andsimple authentication methods. Maree and Viljoen (2012-thisissue) performed a thorough investigation of various methodsable to authenticate these two species including mid infraredspectroscopy (MIR), near infrared (NIR) hyperspectral imaging(HSI), high performance thin layer chromatography (HPTLC),liquid chromatography coupled to mass spectrometry (LC–MS)and 1H NMR spectroscopy. They discuss the usefulness of thesemethods to distinguish between the two species and suggest thebest methods to be used. Another export product of significantimportance is Sceletium tortuosum which contains the psycho-active alkaloids mesembrenol, mesembranol, mesembrenone andmesembrine. The quantification of these compounds is animportant step in the quality control of products manufacturedfrom Sceletium as the pharmacological activity is ascribed to thepresence and quantities of these compounds. Shikanga et al.(2012-this issue) describe two elegant methods for the quantifi-cation of mesembrine-type alkaloids: reverse phase ultra highperformance liquid chromatography with a photodiode arraydetector (RP-UHPLC PDA) and gas chromatography coupled tomass spectroscopy (GC–MS). Both methods were validated forlinearity, repeatability and recovery and were found to berepeatable and precise and therefore suitable for routine qualitymonitoring.

Although not as yet commercialised, Tulbaghia species arewidely used in traditional medicines. Focussing on thesulphur-containing compounds (which are believed to beresponsible for the anti-candida properties), Jäger and Stafford(2012-this issue) investigated 8 species and developed a simplequantitative TLC dilution method to establish the sulphur contentof the extracts. Stability during storage is of paramountimportance, yet it is often neglected for herbal products. Usingthe developed method, the authors demonstrate the reduction ofsulphur levels in Tulbaghia rhizomes and show the application ofthe method to detect adulteration.

Although cycads are mostly known for their horticulturalsplendour, many species are traded as traditional medicines. Theplants have been shown to contain carcinogenic, mutagenic,teratogenic and neurotoxic properties emphasising the need forquality control of its toxic principles. The study by Nair and VanStaden (2012-this issue) deals with the isolation of macrozaminfrom seed kernels of Encephalartos transvenosus and thequantification of this toxic methylazoxymethanol (MAM)glycoside via HPLC in selected indigenous cycads.

It is most appropriate that the special issue carries threepapers on indigenous teas (Rooibos and Honeybush) whichboast an illustrious history of traditional use and have becomepopular export products. As in the case of phytomedicine, anherbal tea needs to be assayed for quality especially if marketedand sold for health promoting properties. Joubert et al.(2012-this issue) illustrate the potential of vibrational

spectroscopy (NIR) to determine the content of mangiferinand xanthones in Cyclopia genistoides and Cyclopia subternataand apply chemometric modelling (OPLS-DA) to successfullydistinguish between these two commercially important speciesused in the production of Honeybush tea.

Anatomy remains one of the most classical techniques usedin pharmacognosy. Anatomy allows one to discover convinc-ing diagnostic characters for a specific botanical species (ofcrucial importance in quality control), and it also allows one toobserve the distribution of compounds in the plant matrix. Asseveral Cyclopia species are considered for commercialisation,Stepanova et al. (2012-this issue) developed a simple yetvaluable key to differentiate between several species based onmorphological and anatomical characteristics. Furthermore,the distribution of phenolics is reported for the first time whichmay impact on harvesting and production methods. Rooibostea produced from Aspalathus linearis is undoubtedly the mostimportant indigenous resource which has been commercialisedin South Africa and is now widely exported to various parts ofthe world. Due to the polymorphic nature of A. linearis Kotinaet al. (2012-this issue) compared the anatomy of various wild-growing forms to one another and also that of the wild-grownsamples to cultivated material. In addition, anatomical featureswhich could distinguish between rooibos tea and other herbalteas are discussed.

Once formulated, herbal products need to be packaged in asuitable form for distribution to the consumers. Ndhlala et al.(2012-this issue) describe some effects of toxic phthalates, suchas bis(2-ethylhexyl) phthalates (a common plasticiser) used incheap soft plastics, and its metabolites and emphasise the needwhich exists for the quality assessment of herbal formulations intheir finished form. An assessment of the possible risks ofphthalate contaminants in herbal products and the detection,quantification and monitoring of plasticisers in herbal remediesare also highlighted.

Contamination may also occur in the form of heavy metalcontamination and despite the dire effects on health, includingliver and kidney failures as well as fatalities, it is often notconsidered when discussing the quality of herbal products.Street (2012-this issue) reviewed heavy metal contaminationincluding the points at which contamination may occur, andsuggested that regulations are necessary to control the heavymetal content in herbal products. The presence of heavy metalsin herbal concoctions available on the market in South Africa wasconfirmed by Okem et al. (2012-this issue) who used inductivelycoupled plasma-optical emission spectrophotometry (ICP-OES)to screen various products. They report high levels of heavymetals such as cadmium, mercury and lead in some of theproducts. The levels of heavy metals detected as compared to theWorld Health Organisation standards emphasises the urgent needto routinely screen herbal products as part of a quality controlregimen.

It is necessary from time to time to review the methods weuse to screen plants for different biological activities and toreflect on where we are going with the traditional knowledgewe possess. Aremu et al. (2012-this issue) note that severalSouth African plants have promising anthelmintic properties

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3Editorial

but that research in this area has been neglected despite the highincidence of helminth infection in poorer communities in SouthAfrica. This may be due to the lack of robust, rapid and reliablescreening techniques and they therefore critically reviewedthese methods and suggested improvements to ensure thateffective products may be produced in the future.

Ensuring quality remains a fundamental step in the plant‐to‐product pipeline. Herbal medicines are sold extensively on theinformal market and phytomedicines are available to con-sumers without prescription. Quality determines the efficacyand safety of any herbal medicine and hence a pre-requisite toensure consumer trust and confidence in any product. Thisspecial issue has aimed to collate a selection of papershighlighting the importance of quality control, to illustrate thevarious methods which are used to assess quality and to applythese techniques to several indigenous resources which couldbe of value in the production of consumer products.

We wish to thank all the authors who have contributed to thisspecial issue and we want to especially thank the 45 Nationaland International reviewers who reviewed the 19 papers whichwere submitted for possible inclusion in this issue.

References

Albrecht, C.J., Stander, M.A., Grobbelaar, M.C., Colling, J., Kossmann, J.,Hills, P.N., Makunga, N.P., 2012. LC–MS-based metabolomics assist withquality assessment and traceability of wild and cultivated plants ofSutherlandia frutescens (Fabaceae). South African Journal of Botany 82,33–45 (this issue).

Aremu, A.O., Finnie, J.F., Van Staden, J., 2012. Potential of South Africanmedicinal plants used as anthelmintics— their efficacy, safety concerns andre-appraisal of current screening methods. South African Journal of Botany82, 134–150 (this issue).

Heyman, H.M., Meyer, J.J.M., 2012. NMR-based metabolomics as a qualitycontrol tool for herbal products. South African Journal of Botany 82, 21–32.

Jäger, A.K., Stafford, G.I., 2012. Quality assessment of Tulbaghia rhizomes.South African Journal of Botany 82, 92–98 (this issue).

Joubert, E., Botha, M., Maicu, C., De Beer, D., Manley, M., 2012. Rapidscreening methods for estimation of mangiferin and xanthone contents ofCyclopia subternata plant material. South African Journal of Botany 82,113–122 (this issue).

Edited by J Van Staden

Kotina, E.L., Stepanova, A.V., Tilney, P.M., Van Wyk, B.-E., 2012. Thepharmacognostic value of leaf and stem anatomy in rooibos tea (Aspalathuslinearis). South African Journal of Botany 82, 129–133 (this issue).

Long, H.S., Stander, M.A., Van Wyk, B.-E., 2012. Notes on the occurrence andsignificance of triterpenoids (asiaticoside and related compounds) andcaffeoylquinic acids in Centella species. South African Journal of Botany82, 53–59 (this issue).

Maree, J.E., Viljoen, A.M., 2012. Phytochemical distinction betweenPelargonium sidoides and Pelargonium reniforme — a quality controlperspective. South African Journal of Botany 82, 83–91 (this issue).

Mncwangi, N., Viljoen, A.M.., 2012. Quantitative variation of amino acids inSutherlandia frutescens (Cancer bush) — towards setting parameters forquality control. South African Journal of Botany 82, 46–52 (this issue).

Nair, J.J., Van Staden, J., 2012. Isolation and quantification of the toxicmethylazoxymethanol glycoside macrozamin in selected South Africancycad species. South African Journal of Botany 82, 108–112 (this issue).

Ncube, B., Finnie, J.F., Van Staden, J., 2012. Quality from the field: the impactof environmental factors as quality determinants in medicinal plants. SouthAfrican Journal of Botany 82, 11–20 (this issue).

Ndhlala, A.R., Ncube, B., Van Staden, J., 2012. Ensuring quality in herbalmedicines: toxic phthalates in plastic-packaged commercial herbal products.South African Journal of Botany 82, 60–66 (this issue).

Ndhlala, A.R., Van Staden, J., 2012. Smokescreens and mirrors in safety andquality of herbal medicines: a case of commercialized herbal preparations.South African Journal of Botany 82, 4–10 (this issue).

Okem, A., Southway, C., Ndhlala, A.R., Van Staden, J., 2012. Determination oftotal and bioavailable heavy and trace metals in South African commercialherbal concoctions using ICP-OES. South African Journal of Botany 82,75–82 (this issue).

Shikanga, E.A., Kamatou, G.P.P., Chen, S., Vijoen, A.M., 2012. Validated RP-UPLC and GC–MS methods for the analysis of psychoactive alkaloids inSceletium tortuosum. South African Journal of Botany 82, 99–107 (this issue).

Stepanova, A.V., Kotina, E.L., Tilney, P.M., Van Wyk, B.-E., 2012. Leaf andstem anatomy of honeybush tea (Cyclopia species, Fabaceae). SouthAfrican Journal of Botany 82, 123–128 (this issue).

Street, R.A., 2012. Heavy metals in medicinal plant products — an Africanperspective. South African Journal of Botany 82, 67–74 (this issue).

Alvaro Viljoen*Ilze VermaakGuest Editor

Department of Pharmaceutical Sciences, Tshwane University of Technology,Private Bag X680, Pretoria 0001, South Africa

*Corresponding author.E-mail address: [email protected].(A. Viljoen),

[email protected].(I. Vermaak).