Pelargonium SIDOIDES

n at u r a l c o l d s & f l u buster

MaDE wI th Organic certified our Vision

Our vision is to identify and develop new medicines from the vast botanical resources in Southern africa.

our Values

we honour the inherent value of african medicinal herbs. we respect nature and strive to employ the best practices in sustainable wild harvesting. we strive to uplift the communities we work with by developing profit sharing and skills development partnerships with indigenous people.

our mission

afrigetics wish to introduce the world to the immense healing power of african botanical resources. we are committed to developing commercially viable ingredients and developing strong supply chains to deliver our product to the international wellness market.

natural

africa science s u t.+27(0) 67 868 8488

ut ut [email protected] www.afrigetics.com O b 01 02 a 02 a b O ut Our ValuES u s 03

whY PElarGONIuM? 06

thE aFrIGEtICS StOrY t 07 he Pelarg

PrECIOuS PElarGONIuM O nium 09

s PErFECt PElarGONIuM t

O NaturES POwErhOuSE ry 11 CONTENTS aFrICaN OrIGINS 13

SuStaINablE SOurCING 15

PharMaCOlOGICal aCtION 18

thrEE-waY EFFECt the

s cience 19

ClINICal StuDIES 23

trEatablE CONDItIONS 25

INFOrMatION rESOurCES & KNOwlEDGE SharING 31

PrODuCt SPECIFICatIONS Pelargonium 32

FEaturED PrODuCt 34 P r O ducts raw MatErIal 36 s idoides lIquID ExtraCtS 39

PrODuCt DEVElOPMENt 41

rEquESt SaMPlE www. sales t. +27(0) 67 868 8488 @afrigetics.com 43 u afrigetics s t O

yO PaCKaGING .com u 45

lOGIStICS message Why should you be interested in #1 from Pelargonium sidoides? our Ceo Clinically Proven Pelargonium is proven to reduce the duration Over 20 clinical trials and many other studies have and severity of the been done on Pelargonium sidoides and the results are common cold. outstanding.

In this brochure I want to introduce you to our flagship product, Pelargonium sidoides, a plant that has significant commercial and healing potential in the world of natural cold and flu phytomedicines.

As the CEO of Afrigetics I look forward to developing partnerships that ensure our mutual success through doing business in a way that is ethical, innovative and dynamically responsive to the continually changing needs of our global natural products marketplace. Our goal is to be Commercial market the trusted experts in the supply of Pelargonium to success stories growth the global marketplace and to offer you a reliable The commercial success records Sales for the cough, cold, flu, and accredited supply chain with our range of ? of KalobaTM and Umcka ColdCareTM and allergy remedy market are innovative products. with reported sales of over EUR80 m constantly on the rise, especially nium #2 in 2006 alone. in the natural products category. #3 O steven Hurt Owner & Director elarg afrigetics botanicals P Business with GloBal Reach t.+27(0) 67 868 8488 [email protected] hy www.afrigetics.com

W 03 04 tHe afrigetiCs story

afrigetics is a leading exporter of southern african medicinal herbs. our award-winning team prides itself on providing superior african healing plants to the international market.

afrigetics is rooted in african ethnopharmacology. we are experts in traditional medicinal knowledge and our team maintain strong ties with local plant protecting and developing african botanical users. we are leaders in sustainable harvesting wisdom. we are poised to unlock the tremendous and diligent partners with rural harvesters. potential of african medicinal herbs and bring afrigetics is committed to combining twentieth these resources to a global platform. we wish to century innovation with ancient african indigenous share the success of the african pharmacopeia with knowledge. Our products are backed-by-science, the world and we believe the star of our medicine afrigetics has research partnerships with a chest is undoubtedly the african pelargonium. number of South african universities. we have a afrigetics seeks to empower our clients to reap proven track record as reliable exporters and are the benefits of these valued botanicals in their pioneering novel processing techniques to bring products, thus enabling others to share in the our clients tailor-made raw materials and extracts. healing power of nature.

afrigetics is driven by superior quality, we believe our standards of food safety set us apart. “We believe that the botanical afrigetics has invested in a state of the art quality resources of africa may hold the assurance system with FSSC 22000 accreditation. key to the treatment of major this Food Safety System Certification medical and health ailments and, demonstrates our company’s robust and effective we want to be at the forefront of these discoveries…” management system. Our reliable team are well positioned to meet the requirements of regulators, food business clients and consumers. In addition, MaDE wI th afrigetics are licenced distributors of indigenous Organic flora and FDa registered. certified

afrigetics are passionate about discovering, t.+27(0) 67 868 8488 [email protected] www.afrigetics.com 05 06 PreCious Pelargonium

africa’s natural relief for colds, fu and respiratory tract infections.

t.+27(0) 67 868 8488 [email protected] www.afrigetics.com 06 07 PerfeCt

harvested Pelargonium, in lesotho natures

Shipped from Cape town PoWerHouse

Pelargonium sidoides is a small and humble shrub that grows abundantly Processed in in the sun warmed, stony soil of Eden District the South african Eastern Cape and lesotho grasslands. Known locally by its common name, african geranium, it can be found nestled beneath tall grasses and aromatic floral neighbours on coastal slopes. the small indigenous herb has soft, velvety textured grey-green leaves and dark magenta coloured flowers.

this insignificant looking plant however contains a treasure trove of medicinal compounds and has been part of local healing practices for millennia. Pelargonium is an example of nature’s immune boosting and pathogen fighting power. It is celebrated as afrigetics botanicals’ flagship commercial herb.

t.+27(0) 67 868 8488 [email protected] www.afrigetics.com 08 09 the drug is listed in the european and african afriCan Pharmacopoeia and has european approval as a herbal etHnobotaniCal medicine and food supplement. origins

the original hunter gatherer inhabitants of Southern In the 1990’s, a German drug manufacturer, Schwabe africa, the Koi-San, knew of this herb and used Pharmaceuticals, developed a highly popular herbal it for the treatment of diarrhoea and dysentery. cough syrup called “umckaloabo” containing Knowledge of the small bush later fell into the liquid extract Eps7630. In 2006, this company hands of the Cape Dutch colonists, who christened sold more than Eur80 million of this pelargonium it rooirabas, perhaps for its red tinted tuberous based product. the drug is listed in the European roots. herdsmen dubbed the plant “Kalverbossie”, and african Pharmacopoeia and has European meaning ‘calf bush’ and used the woody twisted approval as a herbal medicine and food supplement. underground rhizomes to treat stomach complaints Schwabe’s withdrawal of the patents for this in their animals. It served in Cape herbal medicine as medicine in 2010 has allowed other pharmaceutical a tonic for weakness, fatigue and in the treatment of companies to follow suit and explore the potential of gonorrhoea. this natural remedy.

the ethnobotanical potential of african Geranium was brought to Europe in the early 1900’s after a young explorer called Charles henry Stevens was treated in South africa for his pulmonary tuberculosis by a local healer. a bitter tea made of the roots of the plant drove his illness into remission. he then used the umckaloabo herb to develop “Stevens’ Consumption Cure” and marketed it in England. It wasn’t until the 1970’s, well after Steven’s death that the plant ingredient of his remedy was identified as Pelargonium. t.+27(0) 67 868 8488 [email protected] www.afrigetics.com 10 11 Afrigetics Botanicals sustainable recognises the immense value in South Africa’s sourCing indigenous medicinal plants benefit ly and works in partnership replanting the cuttings. they leave the deeper, more PP with KP Botanicals to mature roots in the soil, to allow for rapid regrowth su provide a sustainable after harvesting. In addition to supplementing long-term supply of wild their income, and under the stipulations of the harvested Pelargonium. biodiversity act, local collectors and land owners profit from a benefit sharing agreement where a rand value of their harvest is paid into a government controlled ‘bioprospecting trust Fund’ for

Currently P. sidoides is listed on the red Data list distribution within the community. of South africa’s species as of ‘least concern’, they state that less than 5% of the local population afrigetics botanicals recognises that despite its best is being impacted by harvesting (red Data list, efforts, currently well managed wild stocks may be 2017). Even so, strict controls by the South african subject to depletion in the future and are actively Department of Environmental affairs require working with the university of Stellenbosch towards collectors to obtain a bioprospecting licence. within refining a cultivation system for P. sidoides. Plant the constraints of the biodiversity act, our primary breeding practices will be used to identify cultivars processors identifies areas of wild cultivation and with the highest levels of active ingredients and trains harvesters in rural areas to identify and grow these on specialized farms in the Eden District collect the Pelargonium. Care is taken to prevent using ecological cultivation methods. overharvesting of the underground tuberous roots and so to provide a supply for posterity, protect with this aim in mind, our primary processing the herb from extinction and to provide an ongoing partners have entered into a benefit sharing livelihood for local collectors. agreement with the indigenous communities of Southern africa who harvest our herbs through a

Many of the collectors subcontracted by our primary network of 350 families. Furthermore, as licensed processors are elderly members in their communities collaborators of a bio-prospectors permit, we are with rich traditional knowledge of indigenous plants. poised to continue unlocking the potential of africa’s harvesters actively propagate the plant material Green Gold, for many years to come.

as it is collected, by breaking off aerial shoots and t.+27(0) 67 868 8488 [email protected] www.afrigetics.com 12 13 PHarmaCologiCal Traditional herbal medicinal product for the symptomatic Pelargonium s idoides aCtion treatment of the common cold Pelargonium acts by preventing bacteria from both the duration and severity of these illnesses. sticking to the cells lining the respiratory system One such preparation, Eps7630, prepared by and by stimulating white blood cells to attack and Schwabe Pharmaceuticals has been the subject of destroy these invading bacteria. the chemicals over 20 clinical studies, involving 9000 people. contained in this medicine also help to support the immune system by producing specific proteins, Pelargonium’s success as a cold and flu buster is called defensins, to protect cells from invasion. the unsurprising as over half of general practitioner’s antiviral properties of P. sidoides lies in its ability to visits involve patients complaining of upper stimulate the body’s cells to produce interferon, a respiratory tract infections. adults can suffer from chemical that ‘interferes’ with virus replication. Its as many as four colds annually and young children antibacterial effect is attributed to chemicals in the get up to 12 times per year. It is considered to be extract causing the tiny hair-like projections which the single largest cause of work and school related line our respiratory tract, called cilia, to beat faster absenteeism. antibiotics are generally considered and to expel mucous. In addition, chemicals found in to be ineffective for most cases of colds and flu, yet the plant have a mucolytic effect, helping to dissolve treatment is clearly needed. thick mucus in the airways. the dried rhizomes of P. sidoides contain a host of there is no cure for the common cold, since it is chemical compounds. among these are polyphenols spread by a virus, but Pelargonium has been proven including gallic acids. Polyphenols are a group of to aid healing. this herbal medicine has been shown plant chemicals which give foods a bitter taste, to be safe and effective and may form an important represent potent plant defence chemicals and often alternative to antibiotics. act as powerful antioxidants. root extracts are rich in coumarins, including a unique phytochemical called Many pharmaceutical companies use ethanol to ‘umckalin’. In addition, the remedy contains powerful extract the active ingredients from the pelargonium flavonoids including quercetin, catechin and root. these extracts have proven effective for the gallocatechin. these plant nutrients are responsible treatment of respiratory tract infections including for vivid colour in fruit and vegetables and have anti-

prevents bacteria causes cilia to stimulates white immune system produces mucolytic effect bronchitis, tonsillitis, sinusitis and the common cold. inflammatory and immune boosting properties. from sticking to beat faster and blood cells support by interferon that helps to dissolve Clinical trials have shown the medicine to reduce the cells lining to expel mucous to attack and producing ‘interferes’ with thick mucus in t.+27(0) 67 868 8488 the respiratory & bacteria destroy bacteria defensins to virus replication airways [email protected] system protect cells www.afrigetics.com 14 15 tHree-Way effeCt Pelargonium has been shown to have a three-way effect

antibaCterial antiviral eXPeCtorant

the Pelargonium sidoides Similarly, Pelargonium the extract acts as an extract prevents bacteria from sidoides prevents viruses expectorant, allowing the attaching to cells in mucous from attaching to the body to expel contaminated membranes.1 mucous membrane cells and mucous, making conditions stimulates the body’s immune less suitable for the Pelargonium sidoides system in such a way that multiplication of the bacteria extracts inhibit the both bacteria and viruses are and viruses – can only find adherence of bacteria such prevented from multiplying.1 animal data. as Streptococcus pyogenes and helicobacter pylori to In vitro, the extracts show the three-way effect attacks epithelial cells in vitro. efficacy against cellular the acute infection at its infections with influenza root, the stabilisation of the Furthermore, ciliated cells virus, hSV, EMCV, rSV, immune system prevents a re- isolated from the nasal coronavirus, parainfluenza infection and the vicious circle epithelium enhanced their virus, and coxsackie virus, of infection, a short recovery ciliary beat frequency in the and this appears to be phase and new infection is presence of these extracts, mainly mediated indirectly by broken. which should allow a better inhibition of virus attachment removal of excess mucous and spreading. and bacteria.

1. witte K, Koch E, Volk h-D, wolk K, Sabat r. the Pelargonium sidoides Extract EPs 7630 Drives the t.+27(0) 67 868 8488 Innate Immune Defense by activating Selected MaP Kinase Pathways in human Monocytes. PlOS ONE [email protected] 2015;1-13. | DOI:10.1371/journal.pone.0138075 www.afrigetics.com 16 16 CliniCal studies

Summary of Clinical Studies into Effcacy of Pelargonium sidoides extract EPs 7630

the efficacy of the Pelargonium sidoides extract bereznoy (2003) points out that more than half of against a number of bacterial and viral infections the Pelargonium sidoides extract group were able has been well researched. this extract has been the to get out of bad after two days of treatment. In the subject of over 20 clinical studies involving more placebo group, however, more than half the patients than 9,000 patients, including children as young as were either still in bed on day 4 or had abandoned one year (brown, 2009). It has been shown to safely the study because of a lack of efficacy. this and effectively treat acute upper respiratory tract reduction in bed rest of 48 hours under Pelargonium infections such as bronchitis, tonsillopharyngitis, sidoides extract, compared with the placebo, shows sinusitis and the common cold. the following is a the benefit of this treatment. Indeed, it is more than summary of some of the clinical data available: double the reported benefit of antibiotic treatment at 16 hours (Del Mar, 2001). Six days after beginning treatment, 80% of the Pelargonium sidoides extract tonsillitis group were back at school, whereas only 20% of the placebo group were able to resume school (bereznoy Professor V.V. bereznoy MD, treated over 140 et al, 2003). children with bacterial tonsillitis in a placebo- controlled trial in Kiev in 2003. his treated approximately half the children with Eps 7630 bronchitis (manufactured by Schwabe Pharmaceuticals) and the remainder with a placebo. the children took Matthys et al, (2003) studied the efficacy of 3ml of the extract per day for 6 days. researchers Pelargonium sidoides extract in adults with acute in this study monitored pain, difficulty swallowing, bronchitis. the group of researchers conducted salivation, redness, fever and headache, using a a randomized, double-blind, placebo-controlled ‘tonsillitis severity score’. bereznoy’s study confirmed trial on over 450 patients. this study found that the superiority of Pelargonium sidoides extract Pelargonium sidoides extract was superior in efficacy compared to the placebo. the study demonstrated compared to placebo in the treatment of adults the ability of Pelargonium sidoides extract to reduce with acute bronchitis. treatment with Pelargonium the severity of all five symptoms, shortened the sidoides extract clearly reduced the severity of duration of the illness and protected patients from symptoms, duration of illness and shortened the time complications. taken off work by nearly 2 days (Matthys et al, 2003). rapid recovery was observed in three quarters of the patients treated with Pelargonium sidoides Further observational studies by haidvogl and heger extract and a third of those treated with the placebo. (2007) examined the effect of Pelargonium sidoides

t.+27(0) 67 868 8488 [email protected] www.afrigetics.com 18 19 extract on over 740 children with acute bronchitis. their cold symptoms including; nasal discharge, the researchers monitored treatment with the herbal sore throat, nasal congestion, sneezing, hoarseness, extract for up to 14 days. Five ‘bronchitis specific cough, headache, muscle aches, and fever. lizogub, symptoms’ were summed up to give an overall riley and herger (2009) report that Pelargonium measure of disease severity. haidvogl and heger sidoides extract represents an effective treatment concluded that Pelargonium sidoides extract is a of the common cold. after 10 days, 78.8% of the safe and effective treatment for acute bronchitis. Pelargonium sidoides extract group was clinically In addition, they note that in 88.3% of cases, cured compared with 31.4% in the placebo group. the responsible physician rated the treatment as the Pelargonium sidoides extract group returned to successful. adverse events were minor and transitory work on average of 2 days earlier than the placebo group.

sinusitis In conclusion, clinical trials have shown that P. sidoides extract is an effective treatment for a a randomized, double-blind, placebo-controlled number of upper respiratory tract infections. study of 103 adult patients with acute sinusitis was Kolodziej (2011) points to the reasons for its conducted by bachert et al at 11 clinics, in Kiev, therapeutic effects; antibacterial activity, antiviral in 2009. the patients were studied for 21 days activity, immune stimulation and an increase in and assessed on 6 symptoms of sinusitis including ciliary beat frequency. headache, nasal obstruction and discharge. bachert et al (2009) report that by day 7, 63% of the Pelargonium sidoides extract group were back to BiBliography work compared with 37% in the placebo group. by bachert, C. et al. 2009, ‘treatment of acute rhinosinusitis with the preparation day 21, sinus x-rays were normal in more than 90% from Pelargonium sidoides EPs 7630: a randomized, double-blind, placebo- controlled trial’, rhinology, Vol. 47, no. 1, pp 51-58 of the Pelargonium sidoides extract group compared with 10% for the placebo group. the researchers bereznoy, V. et al. 2003, ‘Efficacy of extract of Pelargonium sidoides in children with acute non-group a beta-hemolytic Streptococcal highlighted “improvements shown in the patients’ tonsillopharyngitis; a randomised, double-blinded, placebo-controlled trial’, alternative therapies, Vol. 9, no. 5, pp 68-79 health-related quality of life, activity level and general well-being”, they further observed a quicker brown, D. 2009, ‘Pelargonium sidoides Extract (EPs 7630) alternative treatment of acute upper respiratory tract Infections’, Natural Medicine return to work. bachert et al (2009) conclude that Journal, Vol. 1, issue 12,

“Pelargonium sidoides extract should be considered Del Mar, C. Glasziou, P. Spinks, a. 2001, ‘antibiotics for Sore throat’, the as a possible first line treatment even in patients Cochrane library, Issue 1 suffering from an acute rhinosinusitis of presumably haidvogl, M. and heger, M. 2007, ‘treatment effect and safety of EPs 7630 solution in acute bronchitis in childhood: report of a multicentre bacterial origin”. observational study’, Phytomedicine, Vol. 14, supp. 1, pp 60-64

Kolodziej, h. 2011, ‘antimicrobial, antiviral and Immunomodulatory activity Studies of Pelargonium sidoides (Eps 7630) in the context of health Common Cold Promotion’, Pharmaceuticals, Vol. 4, no. 10, pp 1295-1314 lizogub, V. riley, D. heger, M. 2007, ‘Efficacy of a Pelargonium sidoides preparation in patients with the common cold: a randomized, double-blind, lizogub, riley and herger (2009) examined the placebo-controlled clinical trial’, Explore, Vol. 3, Issue. 6, pp 573-584.

efficacy of Pelargonium sidoides extract on Matthys, h. et al, 2003, ‘Efficacy and safety of an extract of Pelargonium patients with the common cold, one of the most sidoides (EPs 7630) in adults with acute bronchitis: a randomised, double- blind, placebo-controlled trial’, Phytomedicine, Vol. 10, supp. 4, pp 7-17 prevalent illness in the world. the study compared Pelargonium sidoides extract to a placebo over 10 days. Over 100 patients were tracked according to t.+27(0) 67 868 8488 [email protected] www.afrigetics.com 20 21 treatable Conditions

Colds

acute, self-limited viral infection causing upper respiratory symptoms (ie allergiC cough, sore throat, CougHs etc.) astHma Sudden, forceful expulsion of air from the type I reactions lungs to clear material underlie atopic from the airways and to disorders protect the lungs from develop < 1 h particles that after exposure have been to antigen inhaled

sinusitis bronCHitis

Inflammation of Inflammation of the the sinuses, most tracheobronchial tree, commonly caused by commonly following a viral or bacterial a urI, the cause is infection or by an almost always a viral allergy infection

rHinitis Inflammation of PHaryngitis the nasal mucous membrane Sore throat is pain in the laryngitis posterior pharynx that occurs with or without Inflammation of swallowing the voice box (larynx) Pneumonia

acute inflammation of the lungs caused by infection

antibacterial antiviral expectorant

t.+27(0) 67 868 8488 [email protected] www.afrigetics.com 22 23 information resourCes

this is a summary of the scientific conclusions this summary is not intended to provide practical reached by the Committee on herbal Medicinal advice on how to use medicines containing Products (hMPC) on the medicinal uses of pelargonium root. For practical information about pelargonium root. the hMPC conclusions are taken using pelargonium root medicines, patients into account by Eu Member States when evaluating should read the package leaflet that comes applications for the licensing of herbal medicines with the medicine or contact their doctor or containing pelargonium root. pharmacist.

go to : WWW.ema.euroPa.eu/en/ mediCines/Herbal/Pelargonii-radiX

t.+27(0) 67 868 8488 [email protected] www.afrigetics.com 24 25 WHat is Pelargonium root? WHat evidenCe suPPorts tHe use of Pelargonium root mediCines?

Pelargonium root is the common name for the root of the plants Pelargonium sidoides DC and Pelargonium re- the hMPC conclusions on the use of these weaknesses in the design and outcome of the niforme Curt. The HMPC conclusions only cover pelargonium root preparations that are obtained by putting the pelargonium root medicines for treating common studies. therefore, the hMPC conclusions on plant material in a solvent (such as ethanol) to dissolve compounds and form a liquid extract. The solvent may colds are based on their ‘traditional use’. this the use of these pelargonium root medicines are then be evaporated to obtain a dry extract. Herbal medicines containing these pelargonium root preparations means that, although there is insufficient evidence based on their long-standing use. For detailed are usually available in liquid or solid forms to be taken by mouth. Pelargonium root preparations may also be from clinical trials, the effectiveness of these herbal information on the studies assessed by the found in combination with other herbal substances in some herbal medicines. These combinations are not cov- medicines is plausible and there is evidence that hMPC, see the hMPC assessment report. ered in this summary. they have been used safely in this way for at least 30 years (including at least 15 years within the Eu). Moreover, the intended use does not require medical WHat are tHe HmPC ConClusions on its mediCinal uses? supervision.

In its assessment, the hMPC also considered 3 studies The HMPC concluded that, on the basis of their long-standing involving patients with acute bronchitis (inflammation use, these pelargonium root preparations can be used to treat of the airways in the lungs), where pelargonium root the symptoms of the common cold. Pelargonium root medicines was compared with placebo (a dummy treatment). should only be used in patients from the age of 6 years. If although a possible effect in improving symptoms symptoms last longer than 1 week or worsen while taking the of bronchitis such as cough was observed, firm medicine, a doctor or qualified healthcare practitioner should be conclusions could not be drawn as there were consulted. Detailed instructions on how to take pelargonium root medicines and who can use them can be found in the package WHat are tHe risks assoCiated WitH leaflet that comes with the medicine. Pelargonium root mediCines?

HoW are Pelargonium root mediCines aPProved in tHe eu? Very rare side effects (seen in less than 1 patient in 10,000) have been reported with pelargonium root medicines. These include mild gut complaints such as diarrhoea, discomfort around the stomach area, nausea or vomiting, difficulty swallowing, mild nasal and gum bleeding and allergic reactions. Liver problems have also been

Any applications for the licensing of medicines containing pelargonium root have to be submitted to the national reported but the frequency is not known. authorities responsible for medicinal products, which will assess the application for the herbal medicine and take into account the scientific conclusions of the HMPC. Information on the use and licensing of pelargonium root go to : WWW.ema.euroPa.eu/en/ medicines in EU Member States should be obtained from the relevant national authorities. mediCines/Herbal/Pelargonii-radiX

t.+27(0) 67 868 8488 [email protected] www.afrigetics.com 26 27 Available online at www.sciencedirect.com knoWledge-sHaring South African Journal of Botany 74 (2008) 260–267 www.elsevier.com/locate/sajb

Join our knowledge-sharing folder. We have several papers and readings available on our Measuring and optimising umckalin concentration in wild-harvested and cultivated Pelargonium sidoides (Geraniaceae) knowledge platform. Please use the QR code or follow the link to access these resources.

A.G. White a,⁎, M.T. Davies-Coleman b, B.S. Ripley a

a Department of Botany, Rhodes University, PO Box 94, Grahamstown, 6140, South Africa b Department of Chemistry, Rhodes University, PO Box 94, Grahamstown, 6140, South Africa Journal of Ethnopharmacology 119 (2008) 420–433 Received 24 July 2007; received in revised form 18 November 2007; accepted 29 November 2007 Measuring and optimising umckalin Contents lists available at ScienceDirect concentration in wild-harvested and Journal of Ethnopharmacology Abstract cultivated“ Pelargonium sidoides (Geraniaceae) Pelargonium sidoides DC. (Geraniaceae) root extracts are used locally and globally as herbal medicines. Subsequently, high levels of wildjournal root homepage: www.elsevier.com/locate/jethpharm harvest in the years preceding this study, to supply international demand for raw materials, prompted this investigation of the prospects for sustainable root harvest through wild collection and greenhouse cultivation. A novel method was developed for the purification of umckalin, a bioactive constituent in root extracts, such that the root umckalin concentrations of wild and cultivated plants couldReview be quantified by HPLC. A geographical survey of wild plants revealed that root umckalin concentrations were inversely related to the average annual rainfall of the collection site (r2 =0.43, 2 “ pb0.0001) and directly related to soil pH (r =0.46, pb0.0001). Thus, the possibility of inducing highAhistorical, umckalin concentrations scientific in greenhouse- and commercial perspective on the cultivated plants was investigated by subjecting plants to water stress. This treatment, and those usingmedicinal leaf applied hormonesuse of (cytokininPelargonium and sidoides (Geraniaceae) gibberellin) and root competition with a fast growing annual (Conyza albida), did not significantly affect root umckalin concentrations compared to A detailed review of the ethnobotany and well-watered controls. However, greenhouse-cultivated control plants showed wild equivalent umckalinT. concentrationsBrendler a,and B.-E. circa van six Wyktimes greateb, r growth rates than plants in a wild harvest experiment. These results support the ex situ cultivation of roots to supply future market demand. ∗ a commercial history of Pelargonium © 2007 SAAB. Published by Elsevier B.V. All rights reserved. Plantaphile, Immanuelkirchstrasse 32, 10405 Berlin, Germany b Department of Botany and Plant Biotechnology, University of Johannesburg, P.O. Box 524, Auckland Park 2006, South Africa Keywords: Conservation; Coumarin; Cultivation; EPs 7630; Pelargonium sidoides; Umckalin; Umckaloabo; Wild harvest “ sidoides is presented, together with a brief article info abstract summary of pre-clinical and clinical scientific Article history: Ethnopharmacological context: A detailed review of the ethnobotany and commercial history of Pelargo- Received 19 May 2008 nium sidoides is presented, together with a brief summary of pre-clinical and clinical scientific results that results that support the use of the plant in Received in revised form 16 July 2008 support the use of the plant in modern, evidence-based phytomedicines. The aim is to identify the main 1. Introduction uses, commercial P. sidoidesAcceptedroot 21 July extracts 2008 have become popular factors responsible for the success in product development. (e.g. Pelargonium, MedicherbAvailable UK; onlinePelargonium 3 August 2008 Syrup, Biohar- Materials and methods: The literature studied includes all modern scientific papers and also old documents modern, evidence-based phytomedicines. The Many South African medicinal plants, including Pelargonium mony Africa and Umckaloabo®, Spitzner) for the treatment of and books that are no longer readily accessible. Keywords: sidoides, Harpagophytum procumbens and H. zerheri (devil's upper-respiratory tract infections. These are available interna- Results: Available ethnobotanical information shows that several tuberous Pelargonium species (including Commercialisation aim is to identify the main factors responsible claw), Aloe ferox (Cape aloe) and Agathosma betulina (buchu), tionally in countries includingEthnobotany Germany, Mexico, Turkey, Brazil Pelargonium sidoides) are important traditional medicines with a rich ethnobotanical history. A summary are used in the production of internationally marketed herbal (e.g. Matthys et al., 2003;Medicinal Chuchalin plants et al., 2005) and South of the interesting history of the commercial development of Stevens’ Cure or Umckaloabo in Europe is Pelargonium sidoides DC. presented. Scientific evidence for the efficacy of the product, mainly as a treatment for acute bronchitis, for the success in product development. remedies for the treatment of various ailments (Van Wyk et al., Africa (White, 2007). ThePharmacology bioactive constituents isolated from is reviewed. These include numerous in vitro studies as well as 18 clinical studies. The botanical identity 2000). As a result, the wild stocks of these plants are susceptible to P.sidoides root extracts include:Umckaloabo the coumarins umckalin and 6,8- of the plant and its complex mixture of coumarins and other chemical constituents are summarised. over-exploitation. dihydroxy-5,7-dimethoxycoumarin (Kayser and Kolodziej, Conclusions: The use of Pelargonium stems or tubers for a variety of ailments (including the complications Traditionally, infusions made from the tuberous, woody roots 1997), gallic acid and its methyl ester (Kayser and Kolodziej, of dysentery) is an important but hitherto under-estimated part of traditional medicine in southern Africa. Key elements in the successful development of Pelargonium sidoides from a profound traditional remedy to of P. reniforme and P. sidoides are used for the treatment of 1997), (+)-catechin (Kolodziej et al., 2003), and certain fatty acids a highly successful phytomedicine include the choice of species, a favourable cost–benefit ratio, innovative diarrhoea, dysentery, colds and lung infections, including tuber- (Seidel and Taylor, 2004) and tannins (Kolodziej et al., 2005). marketing over many years, good scientific evidence of the botanical and chemical identity of the product and convincing proof of concept. “ culosis (Bladt, 1977; Van Wyk and Gericke, 2000). This usage is This combined traditional and commercial use has led to the particularly prevalent amongst the Xhosa people of the Eastern extensive harvest of wild plants in the Eastern Cape. Harvest is not © 2008 Elsevier Ireland Ltd. All rights reserved. Cape Province of South Africa. In addition to these traditional restricted to P. sidoides, the species preferred by the international market, as P. reniforme plants are mistakenly harvested due to Contents ⁎ Corresponding author. their very similar appearance to those of P. sidoides, except when E-mail address: [email protected] (A.G. White). in flower. Despite the demand for harvested roots, speculation still 1. Introduction ...... 421 0254-6299/$ - see front matter © 2007 SAAB. Published by Elsevier B.V. All rights reserved. 2. Historical and commercial perspectives ...... 421 doi:10.1016/j.sajb.2007.11.015 2.1. Ethnobotany ...... 421 2.2. Etymology of “Umckaloabo” ...... 423 2.3. History of commercialisation ...... 423 2.4. Production and raw material identification ...... 424 2.5. Standardisation and dosage ...... 427 2.6. Products, patents and regulatory aspects ...... 427 3. Scientific perspectives ...... 427 3.1. Botanical identity and relationships ...... 427 3.2. Chemistry ...... 427 3.3. Pharmacology ...... 428 3.3.1. Antibacterial and antifungal properties ...... 428 3.3.2. Antimycobacterial properties ...... 428 3.3.3. Immunomodulatory properties ...... 429

∗ Corresponding author. Tel.: +27 11 5592412; fax: +27 11 5592411. E-mail address: [email protected] (B.-E. van Wyk). go to our Website for knoWledge

0378-8741/$ – see front matter © 2008 Elsevier Ireland Ltd. All rights reserved. doi:10.1016/j.jep.2008.07.037 https://afrigetics.com/pelargonium-research/ t.+27(0) 67 868 8488 [email protected] www.afrigetics.com 28 29 Product comPosition umckalin uses Pelargonium s idoides

Pela PoWertm Standardized to not less 70% native extract ProduCts ema11-70 than 550ppm umckalin. used as a standardized active ingredient in pelargonium sidoides formulations for featured batch specific Pela PoWertm umckalin determination, liquid drops, cough syrups, 1100 100% native extract minimum 1100ppm. effervescents, sprays, tablets or capsules.

PieCes Shredded whole Nlt 100ppm For further processing pelargonium root

milled Dark brown to reddish granular For further processing PoWder powder milled from dried Nlt 100ppm pelargonium root

tinCture Ethanolic tincture made Single ingredient for etHanol according to Pharmacopoeaia batch Specific the formulation of liquid monograph method. phytomedicines.

Concentrated botanical glycerine syrup made with For the formulation of cough tinCture pelargonium sidoides, with batch specific syrups or liquid herbal glyCerol rich, dark colour and distinctive medicines. taste profile. Sugar and alcohol-free.

umckalin can be Dark brown to reddish opaque- ready to use sugar-free cough CougH syruP standardized to liquid with syrupy viscosity and syrup with mint. mint flavor customer specification

MaDE wI th Organic certified t.+27(0) 67 868 8488 [email protected] *OptiOnal www.afrigetics.com 30 31 Pelargonium s idoides 1 2

PelaPowerTM PelaPowerTM featured EMA11-70 1100 ProduCt For pharmaceutical application For nutraceutical application

A Natural Phytocare Solution for Colds and Flu

with over 16 years experience of supplying Pelargonium PelaPower™ is a pelargonium sidoides standardised dry sidoides to our customers around the world we have powder extract which has been made according to the come to understand this powerful plant medicine better principles of the EMA monograph. By making an equivalent than almost anyone. Our expertise has led us to the extract that complies with the EMA guidelines our customers development of a standardized extract of pelargonium can create products that enable them to make health which is poised to unlock the significant healing potential claims of pelargonium medicines recognised in the

of this plant for the world of natural, plant-based pharmacopoeia. medicines. o ur P roC ess With DMF and GMP certificate. With GMP certificate. t e CHniC al features The pelargonium raw material is first tested as per the European Pharmacopoeia specification. We then produce a Dry extract, (Der 4-25:1) liquid extract as per EMA monograph DER 4-25:1 extraction using 11% or 60% ethanol. This liquid extract is then dried Product descriPtion Product descriPtion Dark brown to reddish fine powder extract with excipient. Dark brown to reddish fine powder extract. to produce our PelaPower™ EMA11-70 powder extract for extraction solvent ethanol 11% or 60% (m/m) pharmaceutical applications (DMF and GMP) Active ingredient Active ingredient umckalin: Nlt 500ppm umckalin: Nlt 1100ppm (FSSC22000, no DMF). umckalin and umckalin-7-Sulphate as scopoletin: umckalin and umckalin-7-Sulphate as scopoletin: batch specific (range:500-3600) batch specific Gallic acid: batch Specific Gallic acid: batch Specific

PAckAging descriPtion PAck size PAckAging descriPtion PAck size Afrigetics is a vertically integrated Pelargonium supplier and thus controls harvesting, drying, Polyfoil ziplock bag. 1kg Polyfoil ziplock bag. 1kg processing and extraction from start to finish. This means we have the ability to control starting Umckalin content of the raw material and thus determine an accurate outcome of active content in our extract as well as control raw material cost. MaDE wI th t.+27(0) 67 868 8488 Organic [email protected] certified www.afrigetics.com 32 *OptiOnal 33 Pelargonium s idoides sustainably Wild Harvested, organic Certified raW material (Optional).

afrigetics specializes in the supply of wild-harvested Pelargonium sidoides and offers a range product from raw materials to extracts and finished products. Our products are handled within an FSSC22000 environment and adhere to the requirements of the international marketplace.

Pelargonium sidoides Whole, Dried Pieces Pelargonium sidoides Milled Powder

Product descriPtion Product descriPtion Dark brown to reddish powder made from dried Dark brown to reddish pieces of shredded whole whole pelargonium root with a particle size Pelargonium root, cut and sifted according to <10% retained on a 425 micron sieve customer specification.

Active ingredient Active ingredient Not less than 100ppm umckalin Not less than 100ppm umckalin

sterilizAtion sterilizAtion Steam sterilization (*optional) Steam sterilization (Optional)

PAckAging descriPtion PAckAging descriPtion inner Packaging - 2 PVC plastic liner (Food grade) inner Packaging - 2 PVC plastic liner (food grade) Outer Packaging - white polypropylene Outer Packaging - white polypropylene agricultural agricultural weaved bag weaved bag

PAck size PAck size MaDE wI th MaDE wI th Organic Organic certified 15kg raw material certified 20kg raw material *OptiOnal *OptiOnal t.+27(0) 67 868 8488 [email protected] www.afrigetics.com 34 35 Glycerine Extract

Pelargonium s idoides Product descriPtion Concentrated botanical glycerine syrup made with pelargonium sidoides, with rich, dark liquid colour and distinctive taste profile. Sugar and alcohol-free

FeAtures eXtraCts For the formulation of cough syrups or liquid herbal medicines. adds pelargonium sidoides rich colour and flavour to your liquid afrigetics offers liquid extracts of Pelargonium formulations. sidoides as partially processed products Active ingredient that can be used for further processing. all batch specific extracts are manufactured for us by certified

facilities, audited under our FSSC 22000 PAckAging descriPtion PAck size program. GMP certification available. MaDE wI th PVC bucket with tamper-proof closure. Organic 5l or 25l certified *OptiOnal

Ethanolic Liquid Extract 1:8-10 Cough Syrup Formulation with Mint

Product descriPtion

Pelargonium sidoides ethanolic extract 1:8-10 Product descriPtion (alcohol 16-19%) alcohol-free and sugar-free Pelargonium sidoides vegetable glycerine tincture formulated FeAtures with mint oil. an ethanolic extract made according to the

pharmacopoeia monograph on Pelargonium FeAtures sidoides. this tincture can be used as an ingredient a non-alcoholic, sugar-free glycerine extract of in formulations for liquid drops, cough syrups or Pelargonium sidoides that is ready to use. sprays or as a ready-to-use product. Active ingredient

Active ingredient batch specific batch specific PAckAging descriPtion PAck size

PAckAging descriPtion PAck size PVC bucket with tamper-proof closure. 5l or 25l

MaDE wI th PVC bucket with tamper-proof closure. 5l or 25l MaDE wI th Organic Organic certified certified t.+27(0) 67 868 8488 [email protected] *OptiOnal *OptiOnal www.afrigetics.com 36 37 ProduCt develoPment

R & A A L G C O U

S H O

• L

F R E E •

we work closely with customers to help perfect their formulations into finished products and have developed White lAbel oPPortunity a variety of product concepts. we can manufcture cough syrup, tincture, tablets syruPs, cAPsules, eFFervescents, tinctures and effervescents with our standardized pelargonium extracts, according to the gMP licensed MAnuFActuring pharmacopoeia monograph methods under GMP license.

t.+27(0) 67 868 8488 [email protected] www.afrigetics.com 38 39 request samPle

Visit our website to request a sample and brochure.

sCan tHis qr Code to request a samPle on our Website

Go to afrigetics.com/request-a-sample u yO

t.+27(0) 67 868 8488

O [email protected] www.afrigetics.com s t s 40 41 u Our company offers packaging PaCkaging solutions that will withstand the toughest journeys by road, air or sea.

In striving to continually improve our services we have now gone the extra mile to ensure that our palletization is truly world class. Our company offers packaging solutions that will withstand the toughest journeys by road, air or sea. better packaging of your goods means fewer troubles further down the line by reducing the exposure to moisture (especially on sea cargo), damage by poor third party handling and general accidents that can occur during transit. Speak to us about your packaging requirements and we will listen to your every need.

Palletization

Shrink wrapped & strapped

t.+27(0) 67 868 8488 [email protected] www.afrigetics.com 42 43 logistiCs

afrigetics botanicals is export ready. Since June 2008 we have successfully delivered over 1000 consignments by air, sea and courier to North america (uSa, Canada), South america (brazil, argentina), west Europe (Germany, France, Italy, uK), Eastern Europe (ukraine, russia), asia (China, Korea) and the Middle East.

Our logistics training is compliant with INCOtErMS 2010 and we have substantial experience in all aspects pertaining to the export process - which is faithfully carried out by VDM Cargo Solutions.

• International Sea and Air Freight Forwarding • Customs Clearing • Warehousing (Bonded and Duty Paid) • Cartage (Deliveries) • Marine and Airfreight Insurance

world class

Over 900 exports award winning Incoterms consignments export business 2010 experts worldwide t.+27(0) 67 868 8488 [email protected] www.afrigetics.com 44 45 Through his vast experience and impressive network of dynamic industry partners, he has a clear understanding of client expectations and therefore forms an integral part in the logistics supply chain of our clients.

Franco van der Merwe, owner of VDM Cargo Solutions started his career at Customs in 1991 as auditor in the Excise department followed by a stint as a Customs import inspector before entering the private sector.

Over the past 27 years he has gained valuable experience in all aspects of imports and exports, from framing entries to heading up operations for a major clearing and forwarding house in South africa.

his passion for the industry and his clients ultimately led him to start VDM Cargo Solutions.

t.+27(0) 67 868 8488 [email protected] www.afrigetics.com 46 47 enquire Here www.afrigetics.com

sample requests: [email protected]

Contact tel: +27(0) 67 868 8488

factory and Warehouse: 22 Waenhout ave, knysna industrial, WC, rsa

Please get in touch, I am your personal contact

steVen Hurt CEO & Sales Director : [email protected] : +27(0) 67 868 8488 : +27(0) 81 365 5784 : stevenlindsayhurt