Ilze Vermaak

Eugenol--from the remote Maluku Islands to the international market place: a review of a remarkable and versatile molecule.

Eugenol is a major volatile constituent of clove essential oil obtained through hydrodistillation of mainly Eugenia caryophyllata (=Syzygium aromaticum) buds and leaves. It is a remarkably versatile molecule incorporated as a functional ingredient in numerous products and has found application in the pharmaceutical, agricultural, fragrance, flavour, cosmetic and various other industries. Its vast range of pharmacological activities has been well-researched and includes antimicrobial, anti-inflammatory, analgesic, anti-oxidant and anticancer activities, amongst others. In addition, it is widely used in agricultural applications to protect foods from micro-organisms during storage, which might have an effect on human health, and as a pesticide and fumigant. As a functional ingredient, it is included in many dental preparations and it has also been shown to enhance skin permeation of various drugs. Eugenol is considered safe as a food additive but due to the wide range of different applications, extensive use and availability of clove oil, it is pertinent to discuss the general toxicity with special reference to contact dermatitis. This review summarises the pharmacological, agricultural and other applications of eugenol with specific emphasis on mechanism of action as well as toxicity data.

Menthol: A simple monoterpene with remarkable biological properties

Menthol is a cyclic monoterpene alcohol which possesses well-known cooling characteristics and a residual minty smell of the oil remnants from which it was obtained. Because of these attributes it is one of the most important flavouring additives besides vanilla and citrus. Due to this reason it is used in a variety of consumer products ranging from confections such as chocolate and chewing gum to oral-care products such as toothpaste as well as in over-the-counter medicinal products for its cooling and biological effects. Its cooling effects are not exclusive to medicinal use. Approximately one quarter of the cigarettes on the market contain menthol and small amounts of menthol are even included in non-mentholated cigarettes. Natural menthol is isolated exclusively from Mentha canadensis, but can also be synthesised on industrial scale through various processes. Although menthol exists in eight stereoisomeric forms, (-)-menthol from the natural source and synthesised menthol with the same structure is the most preferred isomer. The demand for menthol is high and it was previously estimated that the worldwide use of menthol was 30-32,000 metric tonnes per annum. Menthol is not a predominant compound of the essential oils as it can only be found as a constituent of a limited number of aromatic plants. These plants are known to exhibit biological activity in vitro and in vivo such as antibacterial, antifungal, antipruritic, anticancer and analgesic effects, and are also an effective fumigant. In addition, menthol is one of the most effective terpenes used to enhance the dermal penetration of pharmaceuticals. This review summarises the chemical and biological properties of menthol and highlights its cooling effects and toxicity.

Camphor—A Fumigant during the Black Death and a Coveted Fragrant Wood in Ancient Egypt and Babylon—A Review

The fragrant camphor tree (Cinnamomum camphora) and its products, such as camphor oil, have been coveted since ancient times. Having a rich history of traditional use, it was particularly used as a fumigant during the era of the Black Death and considered as a valuable ingredient in both perfume and embalming fluid. Camphor has been widely used as a fragrance in cosmetics, as a food flavourant, as a common ingredient in household cleaners, as well as in topically applied analgesics and rubefacients for the treatment of minor muscle aches and pains. Camphor, traditionally obtained through the distillation of the wood of the camphor tree, is a major essential oil component of many aromatic plant species, as it is biosynthetically synthesised; it can also be chemically synthesised using mainly turpentine as a starting material. Camphor exhibits a number of biological properties such as insecticidal, antimicrobial, antiviral, anticoccidial, anti-nociceptive, anticancer and antitussive activities, in addition to its use as a skin penetration enhancer. However, camphor is a very toxic substance and numerous cases of camphor poisoning have been documented. This review briefly summarises the uses and synthesis of camphor and discusses the biological properties and toxicity of this valuable molecule.

Devil's Claw-a review of the ethnobotany, phytochemistry and biological activity of Harpagophytum procumbens.

ETHNOPHARMACOLOGICAL RELEVANCE Harpagophytum procumbens subps. procumbens (Burch.) DC. ex Meisn. (Pedaliaceae) is an important traditional medicine growing in the Kalahari region of southern Africa where it is consumed as a general health tonic and for treating diverse ailments including arthritis, pain, fever, ulcers and boils. AIM OF THE REVIEW To provide a comprehensive overview of the ethnobotany, phytochemistry and biological activity of H. procumbens and possibly make recommendations for further research. MATERIALS AND METHODS Peer-reviewed articles on H. procumbens were acquired on Scopus, ScienceDirect and SciFinder, there was no specific timeline set for the search. A focus group discussion was held with different communities in Botswana to further understand ethnobotanical uses of the plant. RESULTS Harpogophytum procumbens is used for a wide variety of health conditions in the form of infusions, decoctions, tinctures, powders and extracts. In addition to the common local use for arthritis and pain, other ethnomedicinal uses include dyspepsia, fever, blood diseases, urinary tract infections, postpartum pain, sprains, sores, ulcers and boils. Scientific studies revealed that H. procumbens exhibits analgesic, anti-oxidant, anti-diabetic, anti-epileptic, antimicrobial and antimalarial activities amongst others. Iridoid glycosides and phenylpropanoid glycosides have been the focus of phytochemical investigations as the biological activity has been ascribed to the iridoid glycosides (such as harpagoside and harpagide), which are common in nature and are known to possess anti-inflammatory activity. In addition, it has been shown that the hydrolysed products of harpagoside and harpagide have more pronounced anti-inflammatory activity when compared to the unhydrolysed compounds. Harpagophytum zeyheri is a close taxonomic ally of H. procumbens but H. procumbens is the favoured species of commerce, and contains higher levels of the pharmacologically active constituents. The two are used interchangeably and H. procumbens raw material is often intentionally adulterated with H. zeyheri and this may impact on the efficacy of inadequately controlled health products. The main exporter of this highly commercialised plant is Namibia. In 2009 alone, Harpagophytum exports were worth approximately €1.06 million. The high demand for health products based on this plant has led to over-harvesting, raising concerns about sustainability. Although only the secondary tubers are utilised commercially, the whole plant is often destroyed during harvesting. CONCLUSIONS Harpagophytum procumbens is used to treat a wide range of ailments. Some of the ethnobotanical claims have been confirmed through in vitro studies, however, when the constituents deemed to be the biologically active compounds were isolated the efficacy was lower than that of the whole extract. This necessitates the use of a different approach where all the metabolites are considered using a robust method such as spectroscopy; the phytochemical data can then be superimposed on the biological activity. Furthermore, there is a need to develop rapid and efficient quality control methods for both raw materials and products because the orthodox methods in current use are time-consuming and labour intensive.

A comprehensive scientific overview of Garcinia cambogia

The fruit rind of Garcinia gummi-gutta, commonly known as Garcinia cambogia (syn.), is extensively used traditionally as a flavourant in fish curries due to its sharp sour taste. Additional ethnobotanical uses include its use as a digestive and a traditional remedy to treat bowel complaints, intestinal parasites and rheumatism. This small fruit, reminiscent of a pumpkin in appearance, is currently most popularly used and widely advertised as a weight-loss supplement. Studies have shown that the extracts as well as (-)-hydroxycitric acid (HCA), a main organic acid component of the fruit rind, exhibited anti-obesity activity including reduced food intake and body fat gain by regulating the serotonin levels related to satiety, increased fat oxidation and decreased de novo lipogenesis. HCA is a potent inhibitor of adenosine triphosphate-citrate lyase, a catalyst for the conversion process of citrate to acetyl-coenzyme A, which plays a key role in fatty acid, cholesterol and triglycerides syntheses. The crude extract or constituents from the plant also exerted hypolipidaemic, antidiabetic, anti-inflammatory, anticancer, anthelmintic, anticholinesterase and hepatoprotective activities in in vitro and in vivo models. Phytochemical studies of various plant parts revealed the presence of mainly xanthones (e.g. carbogiol) and benzophenones (e.g. garcinol) together with organic acids (e.g. HCA) and amino acids (e.g. gamma aminobutyric acid). Currently, a large number of G. cambogia/HCA dietary supplements for weight management are being sold although the possible toxicity associated with the regular use of these supplements has raised concerns. In most cases, complaints have been related to multicomponent formulations and at this stage G. cambogia has not been confirmed as the potentially toxic culprit. This review presents a scientific overview of G. cambogia with reference to relevant botanical aspects, ethnobotanical uses, phytochemistry and biological activity as well as toxicity.

Hyperspectral imaging in the quality control of herbal medicines - the case of neurotoxic Japanese star anise.

Illicium verum (Chinese star anise) dried fruit is popularly used as a remedy to treat infant colic. However, instances of life-threatening adverse events in infants have been recorded after use, in some cases due to substitution and/or adulteration of I. verum with Illicium anisatum (Japanese star anise), which is toxic. It is evident that rapid and efficient quality control methods are of utmost importance to prevent re-occurrence of such dire consequences. The potential of short wave infrared (SWIR) hyperspectral imaging and image analysis as a rapid quality control method to distinguish between I. anisatum and I. verum whole dried fruit was investigated. Images were acquired using a sisuChema SWIR hyperspectral pushbroom imaging system with a spectral range of 920-2514 nm. Principal component analysis (PCA) was applied to the images to reduce the high dimensionality of the data, remove unwanted background and to visualise the data. A classification model with 4 principal components and an R²X_cum of 0.84 and R²Y_cum of 0.81 was developed for the 2 species using partial least squares discriminant analysis (PLS-DA). The model was subsequently used to accurately predict the identity of I. anisatum (98.42%) and I. verum (97.85%) introduced into the model as an external dataset. The results show that SWIR hyperspectral imaging is an objective and non-destructive quality control method that can be successfully used to identify whole dried fruit of I. anisatum and I. verum. In addition, this method has the potential to detect I. anisatum whole dried fruits within large batches of I. verum through upscaling to a conveyor belt system.

Hoodia gordonii: An Up-to-Date Review of a Commercially Important Anti-Obesity Plant

Hoodia gordonii is a spiny succulent plant popularly consumed for its purported anti-obesity effect. Traditionally used by the Khoi-San of South Africa and Namibia as a hunger and thirst suppressant while on long hunting trips, the commercialisation of this plant has been highly controversial due to intellectual property rights and benefit sharing issues, as well as the fact that several prominent pharmaceutical companies involved in its development have withdrawn their interest. Quality control has been the main focus of scientific studies as the supply of H. gordonii plant material is limited due to its sparse geographical distribution, slow maturation rate, need for a permit to cultivate or export material as well as high public demand, contributing to adulteration of a large amount of products. Despite the isolation of numerous steroidal glycosides from H. gordonii, the main focus has been on the pregnane glycoside P57, considered to be the active ingredient and marker molecule to determine quality of raw material and products. Publications based on scientific studies of key aspects such as in vivo biopharmaceutics, the biological activity of all chemical constituents, clinical efficacy, and especially safety are insufficient or completely absent causing great concern as H. gordonii is one of the most widely consumed anti-obesity products of natural origin. This review offers an up-to-date overview of all the current available knowledge pertaining to H. gordonii achieved by systematic analysis of the available literature.

From arrow poison to herbal medicine – The ethnobotanical, phytochemical and pharmacological significance of Cissampelos (Menispermaceae)

ETHNOPHARMACOLOGICAL RELEVANCE Cissampelos species have a rich history of traditional use, being used for both therapeutic and toxic properties. It is traditionally applied therapeutically in a diverse range of conditions and diseases including asthma, cough, fever, arthritis, obesity, dysentery, snakebite, jaundice and heart, blood pressure and skin-related problems. Conversely, it was traditionally included in preparations of curare applied as arrow poison during hunting to cause death of animals by asphyxiation. This review unites the ethnobotanical knowledge on Cissampelos with the phytochemistry and pharmacological activity which has been explored thus far. In addition, it identifies knowledge gaps and suggests further research opportunities. METHODS The available electronic literature on the genus Cissampelos was collected using database searches including Scopus, Google Scholar, Pubmed, Web of Science, etc. The searches were limited to peer-reviewed English journals with the exception of books and a few articles in foreign languages which were included. RESULTS The literature revealed that pharmacological activity including analgesic and antipyretic, anti-inflammatory, anti-allergic, bronchodilator, immunomodulatory, memory-enhancing, antidepressant, neuroprotective, antimicrobial, antimalarial, antiparasitic, anti-ulcer, anticancer, anti-oxidant, cardiovascular, muscle-relaxant, hepatoprotective, antidiabetic, antidiarrhoeal, antifertility, and antivenom activity have been confirmed in vitro and/or in vivo for various Cissampelos species. Cissampelos pareira L. and Cissampelos sympodialis Eichl. are the most explored species of this genus and the smallest number of studies have been conducted on Cissampelos laxiflora Moldenke and Cissampelos tenuipes Engl. Many alkaloids isolated from Cissampelos such as warifteine, methylwarifteine, berberine, hayatin and hayatidin showed promising anti-allergic, immunosuppressive, antidepressant, anticancer, vasodilatory and muscle-relaxant activities. CONCLUSION The plants of this genus are used in traditional medicine for the treatment of various ailments. These plants are a rich source of bioactive bisbenzylisoquinoline and aporphine alkaloids together with other minor constituents. Although these plants are reputable and revered in various traditional medicine systems, many have not yet been screened chemically or pharmacologically and so there is a vast amount of research still to be conducted to validate their traditional use.

What the devil is in your phytomedicine? Exploring species substitution in Harpagophytum through chemometric modeling of 1H-NMR and UHPLC-MS datasets.

Harpagophytum procumbens (Pedaliaceae) and its close taxonomical ally Harpagophytum zeyheri, indigenous to southern Africa, are being harvested for exportation to Europe where phytomedicines are developed to treat inflammation-related disorders. The phytochemical variation within and between natural populations of H. procumbens (n=241) and H. zeyheri (n=107) was explored using proton nuclear magnetic resonance ((1)H-NMR) and ultra-high performance liquid chromatography coupled to mass spectrometry (UHPLC-MS) in combination with multivariate data analysis methods. The UHPLC-MS results revealed significant variation in the harpagoside content: H. procumbens (0.17-4.37%); H. zeyheri (0.00-3.07%). Only 41% of the H. procumbens samples and 17% of the H. zeyheri samples met the pharmacopoeial specification of ⩾1.2%. Both principal component analysis (PCA) and orthogonal projections to latent structures discriminant analysis (OPLS-DA) indicated separation based on species (UHPLC-MS data OPLS-DA model statistics: R(2)X=0.258, R(2)Y (cum)=0.957 and Q(2)(cum)=0.934; (1)H-NMR data OPLS-DA model statistics: R(2)X=0.830, R(2)Y=0.865 (cum) and Q(2)(cum)=0.829). It was concluded that two species are not chemically equivalent and should not be used interchangeably.

Vibrational Spectroscopy as a Rapid Quality Control Method for Melaleuca alternifolia Cheel (Tea Tree Oil)

INTRODUCTION Tea tree oil (TTO) is an important commercial oil which has found application in the flavour, fragrance and cosmetic industries. The quality is determined by the relative concentration of its major constituents: 1,8-cineole, terpinen-4-ol, α-terpineol, α-terpinene, terpinolene, γ-terpinene and limonene. Gas chromatography coupled to mass spectrometry (GC-MS) is traditionally used for qualitative and quantitative analyses but is expensive and time consuming. OBJECTIVE To evaluate the use of vibrational spectroscopy in tandem with chemometric data analysis as a fast and low-cost alternative method for the quality control of TTO. METHODS Spectral data were acquired in both the mid-infrared (MIR) and near infrared (NIR) wavelength regions and reference data obtained using GC-MS with flame ionisation detection (FID). Principal component analysis (PCA) was used to investigate the data by observing clustering and identifying outliers. Partial least squares (PLS) multivariate calibration models were constructed for the quantification of the seven major constituents. RESULTS High correlation coefficients (R(2) ) of ≥ 0.75 were obtained for the seven major compounds and 1,8-cineole showed the best correlation coefficients for both MIR and NIR data (R(2)  = 0.97 and 0.95, respectively). Low values were obtained for the root mean square error of estimation (RMSEE) and root mean square error of prediction (RMSEP) values thereby confirming accuracy. CONCLUSION The accurate prediction of the external dataset after introduction into the models confirmed that both MIR and NIR spectroscopy are valuable methods for quantification of the major compounds of TTO when compared with the reference data obtained using GC-MS. Copyright