Weiyang Chen

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.

Intestinal drug transport enhancement by Aloe vera.

The effect of Aloe vera (L.) Burm. f. (Aloe barbadensis Miller) gel and whole leaf extract on the permeability of Caco-2 cell monolayers was determined. Solutions of gel and the whole leaf extract were applied to the cell monolayers, and the transepithelial electrical resistance was monitored for 2 hours, which was then continued for another 2 hours after removal of the test solutions to measure reversibility of the effect. The transport of insulin in the presence and absence of the A. vera gel and whole leaf extract solutions was also investigated. Both the A. vera gel and whole leaf extract were able to significantly reduce the transepithelial electrical resistance of the Caco-2 cell monolayers at concentrations above 0.5 % w/v and thereby showed the ability to open tight junctions between adjacent cells. This effect was fully reversible, as the electrical resistance of the cell monolayers returned to the original value upon removal of the test solutions. The A. vera gel and whole leaf extract solutions significantly enhanced the transport of insulin across the Caco-2 cell monolayers compared with the control. The results suggest that these plant products have a high potential to be used as absorption enhancers in novel dosage forms for drugs with poor bioavailabilities when administered orally. On the other hand, an uncontrolled increase in the bioavailability of drugs that are taken simultaneously with A. vera gel and whole leaf extract products may result in adverse effects, and the potential exists that toxic blood plasma levels may be reached.

Effect of Sinomenine on the In Vitro Intestinal Epithelial Transport of Selected Compounds

Herbal products can interfere with allopathic medicinal treatment through pharmacokinetic and pharmacodynamic interactions. Although pharmacokinetic interactions that alter drug absorption may cause variable and unsatisfactory drug bioavailability, a drug absorption enhancement effect of a herb may be used to ensure sufficient absorption of poorly absorbable drugs. The effect of the hydrochloride salt of sinomenine, an alkaloid obtained from the plant Sinomenium acutum, on the transepithelial electrical resistance and transport of different compounds (including cimetidine, vitamin C, rutin, luteolin and insulin) across Caco‐2 epithelial cell monolayers was investigated in this study. Sinomenine HCl induced a concentration dependent lowering effect on the transepithelial electrical resistance of Caco‐2 cell monolayers, which was completely reversible. Sinomenine HCl significantly increased the transport of all the test compounds in the apical‐to‐basolateral direction compared with the control group and decreased the transport of cimetidine, a P‐glycoprotein substrate, in the basolateral‐to‐apical direction. From these results it can be concluded that sinomenine HCl increases drug absorption across the intestinal epithelium by means of one or more mechanisms including a transient opening of the tight junctions (as indicated by a reduction in transepithelial electrical resistance) to allow for paracellular transport and/or inhibition of active drug efflux transport (as indicated by inhibition of basolateral‐to‐apical transport of cimetidine). Copyright

Hyperspectral Imaging and Chemometric Modeling of Echinacea — A Novel Approach in the Quality Control of Herbal Medicines

Echinacea species are popularly included in various formulations to treat upper respiratory tract infections. These products are of commercial importance, with a collective sales figure of

Chitosan–polycarbophil interpolyelectrolyte complex as a matrix former for controlled release of poorly water-soluble drugs I: in vitro evaluation

132 million in 2009. Due to their close taxonomic alliance it is difficult to distinguish between the three Echinacea species and incidences of incorrectly labeled commercial products have been reported. The potential of hyperspectral imaging as a rapid quality control method for raw material and products containing Echinacea species was investigated. Hyperspectral images of root and leaf material of authentic Echinacea species (E. angustifolia, E. pallida and E. purpurea) were acquired using a sisuChema shortwave infrared (SWIR) hyperspectral pushbroom imaging system with a spectral range of 920–2514 nm. Principal component analysis (PCA) plots showed a clear distinction between the root and leaf samples of the three Echinacea species and further differentiated the roots of different species. A classification model with a high coefficient of determination was constructed to predict the identity of the species included in commercial products. The majority of products (12 out of 20) were convincingly predicted as containing E. purpurea, E. angustifolia or both. The use of ultra performance liquid chromatography-mass spectrometry (UPLC-MS) in the differentiation of the species presented a challenge due to chemical similarities between the solvent extracts. The results show that hyperspectral imaging is an objective and non-destructive quality control method for authenticating raw material.

In vitro permeation of Mesembrine alkaloids from Sceletium tortuosum across porcine buccal, sublingual, and intestinal mucosa

Purpose: It was previously shown in our laboratories that the interpolyelectrolyte complex between chitosan and polycarbophil has promise as a matrix former to control the release of water-soluble drugs. This study further investigates the applications of this polymeric complex to produce controlled release matrices for poorly water-soluble drugs. Methods: The swelling, erosion, and drug release performance of matrix-type tablets containing the chitosan–polycarbophil complex as matrix former was compared to those consisting of hydroxypropylmethylcellulose and a simple mixture of chitosan and polycarbophil powders. Results: The chitosan–polycarbophil complex matrices showed good swelling with relatively low erosion and slower drug release compared to those prepared from other polymeric materials. They also exhibited release exponent (n) values closer to unity and therefore to zero-order release compared to the other matrices. Conclusions: The chitosan–polycarbophil complex formed matrix-type tablets that controlled the release of poorly water-soluble drugs approaching zero-order kinetics. The mechanism of drug release was mainly diffusion from swollen systems.

Cross-linked chitosan matrix-based multiple-unit drug delivery systems

Sceletium tortuosum is an indigenous South African plant that has traditionally been used for its mood-enhancing properties. Recently, products containing S. tortuosum have become increasingly popular and are commonly administered as tablets, capsules, teas, decoctions, or tinctures, while traditionally the dried plant material has been masticated. This study evaluated the in vitro permeability of the four major S. tortuosum alkaloids (i.e., mesembrine, mesembrenone, mesembrenol, and mesembranol) across porcine intestinal, sublingual, and buccal tissues in their pure form and in the form of three different crude plant extracts, namely water, methanol, and an acid-base alkaloid-enriched extract. The permeability of mesembrine across intestinal tissue was higher than that of the highly permeable reference compound caffeine (which served as a positive control for membrane permeability) both in its pure form, as well as in the form of crude extracts. The intestinal permeability of mesembranol was similar to that of caffeine, while those of mesembrenol and mesembrenone were lower than that of caffeine, but much higher than that of the poorly permeable reference compound atenolol (which served as a negative control for membrane permeability). In general, the permeabilities of the alkaloids were lower across the sublingual and the buccal tissues than across the intestinal tissue. However, comparing the transport of the alkaloids with that of the reference compounds, there are indications that transport across the membranes of the oral cavity may contribute considerably to the overall bioavailability of the alkaloids, depending on pre-systemic metabolism, when the plant material is chewed and kept in the mouth for prolonged periods. The results from this study confirmed the ability of the alkaloids of S. tortuosum in purified or crude extract form to permeate across intestinal, buccal, and sublingual mucosal tissues.

Quantification of Rosmarinic Acid in Salvia Species Indigenous to South Africa by HPTLC

Matrix-based multiple-unit drug delivery systems were manufactured by the compression of conventional and cross-linked chitosan into mini-matrices, which were then loaded into hard gelatin capsules. Three different types of mini-matrices were manufactured by direct compression of chitosan powder (not cross-linked), cross-linked chitosan microparticles or cross-linked chitosan granules and were characterized in terms of their physical properties such as hardness, friability, dimensions as well as their swelling and dissolution characteristics. The mini-matrices were film coated with Eudragit polymers (i.e. Eudragit L100, S100 and L100-55) to allow for drug release to start at different pH values. Several combinations of the coated mini-matrices were loaded into hard gelatin capsules to provide for rapid release as well as for delayed-onset sustained release from each multiple-unit drug delivery system. Release kinetics of the matrices consisting of cross-linked chitosan microparticles are presented as well as the in vitro release profiles of the multiple-unit drug delivery systems.

Skullcap and germander: preventing potential toxicity through the application of hyperspectral imaging and multivariate image analysis as a novel quality control method.

The genus Salvia (Lamiaceae) encompasses about 900 species worldwide of which 26 are found in southern Africa. Salvia spp have several medicinal uses in South Africa such as antimicrobial, anticancer, antimalarial, and antituberculosis properties. Rosmarinic acid (RA) has been identified as one of the major molecules responsible for these various medicinal properties. Eleven Salvia species (18 samples) collected at different localities in South Africa were extracted with methanol in order to determine the level of RA present in the extracts. High-performance thin-layer chromatography (HPTLC) analysis was performed on glass silica gel 60 F254 plates developed with ethyl acetate, toluene, and formic acid (6:3:1, v/v), while a gradient of acetic acid and methanol was used for high-performance liquid chromatography-ultra violet (HPLC-UV) analysis. Densitometric quantification was performed at λ = 328 nm (the wavelength of maximum absorption of RA) by fluorescence scanning using a CAMAG TLC Scanner 3. Polynomial (HPTLC) and linear (HPLC-UV) regression analyses were used to determine the amount of RA in the extracts. The mobile phase used for HPTLC produced good separation for RA (RF = 0.42). A good polynomial regression model was obtained in the range of 200–1000 ng and peak areas with the correlation coefficient (R2) of 0.9995. The coefficient of variation (%) of intra-day and inter-day precision of RA at 400 ng per band were 1.44 and 4.48, respectively. Salvia runcinata contained the highest (145.71 mg g−1) RA content. The paired sample t-test showed no statistical significant difference in the estimation of the amount of RA in the solvent extracts using the two chromatographic techniques. The prescribed method is simple, fast, reliable, sensitive and here proposed for the routine assay of Salvia extracts containing RA.