B. H. Kroes

Curcacycline A — a novel cyclic octapeptide isolated from the latex of Jatropha curcas L.

From the latex of Jatropha curcas L. (Euphorbiaceae) a novel cyclic octapeptide was isolated, which we named curcacycline A. The compound was found to contain one threonine, one valine, two glycine, and four leucine residues. By two‐dimensional 1H‐NMR spectroscopy (HOHAHA and ROESY), its sequence was determined to be Gly1‐Leu2‐Leu3‐Gly4‐Thr5‐Val6‐Leu7Leu8‐Gly1. Curcacycline A displays a moderate inhibition of (i) classical pathway activity of human complement and (ii) proliferation of human T‐cells.

Inhibition of human complement by beta-glycyrrhetinic acid.

Licorice, the root extract of Glycyrrhiza glabra L., is used as a medicine for various diseases. Anti‐inflammatory as well as anti‐allergic activities have been attributed to one of its main constituents, glycyrrhizin. These activities are mainly ascribed to the action of the aglycone, β‐glycyrrhetinic acid. β‐Glycyrrhetinic acid has a steroid‐like structure and is believed to have immunomodulatory properties. To determine whether interference with complement functions may contribute to the immunomodulatory activity of β‐glycyrrhetinic acid, its effects on the classical and alternative activation pathways of human complement were investigated. We found that β‐glycyrrhetinic acid is a potent inhibitor of the classical complement pathway (IC50=35 μm), whereas no inhibitory activity was observed towards the alternative pathway (IC50>2500 μm). The anticomplementary activity of β‐glycyrrhetinic acid was dependent on its conformation, since the α‐form was not active. It was also established that naturally occurring steroids, e.g. hydrocortisone and cortisone, did not inhibit human complement activity under similar conditions. Detailed mechanistic studies revealed that β‐glycyrrhetinic acid acts at the level of complement component C2.

Immunomodulatory and anti-inflammatory activity of Picrorhiza scrophulariiflora.

Extracts of the rhizomes of Picrorhiza scrophulariiflora Pennell (Scrophulariaceae) were investigated for their in vitro and in vivo immunomodulatory properties. Diethyl ether extracts showed potent inhibitory activity towards the classical pathway of the complement system, the respiratory burst of activated polymorphonuclear leukocytes, and mitogen-induced proliferation of T-lymphocytes. Furthermore, such extracts showed anti-inflammatory activity towards carrageenan-induced paw edema. No effects were observed in experimentally induced arthritis in mice.

Fermentation in traditional medicine: the impact of Woodfordia fruticosa flowers on the immunomodulatory activity, and the alcohol and sugar contents of Nimba arishta

Abstract The impact of Woodfordia fruticosa flowers on the immunomodulatory activity, and alcohol and sugar contents of the ayurvedic drug ‘Nimba arishta’ was investigated by means of model preparations. The use of Woodfordia flowers in model preparations resulted in a substantial increase of the inhibition of both human complement activity and chemiluminescence generated by zymosan-stimulated human polymorphonuclear leukocytes. It was established that the increased biological activity was not due to microbial interference, but to immuno-active constituents released from the Woodfordia flowers. It was also found that the flowers themselves are not the source of alcohol-producing microorganisms. Experiments performed with yeasts isolated from commercial Nimba arishtas showed, in agreement with empirical findings, significantly raised alcohol content upon addition of Woodfordia. An invertase activity exhibited by Woodfordia flowers may be causative of this effect.

Multifidin—A cyanoglucoside in the latex of Jatropha multifida

Abstract A novel non-cyanogenic cyanoglucoside, 1-cyano-3-β- d -glucopyranosyloxy-(Z)-1-methyl-1-propene, was isolated from the latex of Jatropha multifida . The compound was named multifidin.

Podacycline A and B, two cyclic peptides in the latex of Jatropha podagrica

Two novel cyclic peptides were isolated from the latex of Jatropha podagrica, which we named podacycline A and B. Podacycline A is a cyclic nonapeptide with the sequence Gly1-Leu2-Leu3-Gly4-Ala5-Val6-Trp7-Ala8-Gly9+ ++-Gly1. The sequence of podacycline B, a cyclic heptapeptide, was determined to be Phe1-Ala2-Gly3-Thr4-Ile5-Phe6-Gly7-Phe1. The amino acid residues of both compounds were found to have the L-configuration.

In vitro immunomodulatory activity of Filipendula ulmaria

Extracts of the roots, herb and flowers of Filipendula ulmaria (L.) Maxim. were investigated for in vitro immunomodulatory properties. Strong inhibitory activity was found towards the classical pathway of complement in the ethyl acetate extracts of roots and flowers, in all methanol extracts and in the aqueous root extract. Except for the light‐petroleum extracts, all fractions tested inhibited the production of reactive oxygen species by human polymorphonuclear leukocytes. The diethyl ether root extract was found to be most potent in inhibiting lymphocyte proliferation. The role of tannins and other constituents in these processes are discussed.

The legal framework governing the quality of (traditional) herbal medicinal products in the European Union

In the European Union a complex regulatory framework is in place for the regulation of (traditional) herbal medicinal products. It is based on the principle that a marketing authorisation granted by the competent authorities is required for placing medicinal products on the market. The requirements and procedures for acquiring such a marketing authorisation are laid down in regulations, directives and scientific guidelines. This paper gives an overview of the quality requirements for (traditional) herbal medicinal products that are contained in European pharmaceutical legislation. Pharmaceutical quality of medicinal product is the basis for ensuring safe and effective medicines. The basic principles governing the assurance of the quality of medicinal products in the European Union are primarily defined in the amended Directive 2001/83/EC and Directive 2003/63/EC. Quality requirements of herbal medicinal products are also laid down in scientific guidelines. Scientific guidelines provide a basis for practical harmonisation of how the competent authorities of EU Member States interpret and apply the detailed requirements for the demonstration of quality laid down in regulations and directives. Detailed quality requirements for herbal medicinal products on the European market are contained in European Union (EU) pharmaceutical legislation. They include a system of manufacturing authorisations which ensures that all herbal medicinal products on the European market are manufactured/imported only by authorised manufacturers, whose activities are regularly inspected by the competent authorities. Additionally, as starting materials only active substances are allowed which have been manufactured in accordance with the GMP for starting materials as adopted by the Community. The European regulatory framework encompasses specific requirements for herbal medicinal products. These requirements are independent from the legal status. Thus, the same quality standards equally apply to herbal products based on clinical evidence and traditional herbal medicinal products. The basic principle is that the quality of herbal medicinal products is intrinsically associated with the quality standard of the herbal substances and/or herbal preparations. Furthermore, the herbal substance or herbal preparation in its entirety is regarded as the active substance. Consequently, a mere determination of the content of marker(s) or constituents with known therapeutic activity is not sufficient for the quality control of herbal medicinal products. Specific quality requirements include thorough product characterisation, adherence to the Good Agricultural and Collection Practices, good manufacturing practices and validated manufacturing process, e.g., raw material testing, in-process testing, fingerprint characterisation etc. Quality control of herbal medicinal products is primarily intended to define the quality of the herbal substance/preparation and herbal medicinal product rather than to establish full characterisation.

In-Vitro Assays for Activity-Guided Enrichment of Immunomodulatory Plant Constituents

It has been known for ages or even millennia that certain plants or plant preparations may be used successfully to selectively treat immunological disorders. In the course of the last centuries, it has become clear that the active ?rinciple(s) of such ‘immunomodulatory’ plants/plant preparations may be single chemical entities or more complex mixtures of related substances that can either enhance or suppress deranged immunological reactions. Depending on their mode of action, plant-derived ‘immunomodulators’ can be used to stimulate the immune system of immunocompromised individuals (patients with congenital or acquired immunodeficiencies, young children, or elderly people) or, alternatively, to suppress the immune system of hyperreactive subjects (patients with allergic, autoimmune, and/or rheumatic diseases) or transplantation patients. There are even examples of plant derived substances with more or less selective anti-lymphoproliferative effects.

European Perspective on Garlic and Its Regulation

Garlic products are marketed in the European Union (EU) as foodstuffs and as herbal medicinal products. All EU countries have garlic foodstuffs on their markets. In contrast, garlic medicinal products are available only in a limited number of EU member states. This difference is due to discrepancies among the national laws of EU member states. This article gives an overview of the status of garlic products in EU countries and their approved medical claims and discusses legislative options for the authorization of garlic products as medicinal products. Developments in the food area that could affect the status of and health claims on garlic foodstuffs are also presented.