Evaluation of the in vitro Cytotoxicity of some Sesquiterpene Lactones on a Human Lung Carcinoma Cell Line Using the Fast Green Dye Exclusion Assay.

Amongst the properties associated with the sesquiterpene lactones, their cytotoxicity is probably the most valuable. In this IN VITRO study cytotoxicity of some sesquiterpene lactones from EUPATORIUM CANNABINUM L. and related compounds have been tested on a human small cell lung carcinoma cell line, using the Fast Green dye exclusion assay (FGA). From the results certain conclusions could be drawn about structure activity relationship. Eupatoriopicrin, eupatoriopicrin acetonide, "substance 1" and hiyodorilactone E showed highest cytotoxicity (ID50 1-2 microg/ml) following 1 h incubation. Moieties of the sesquiterpene lactones (alpha-methylene gamma-butyrolactone, eupatolide, angelic and tiglic acid) and related compounds (alantolactone and isoalantolactone) were less or not active at these concentrations. From the results of the experiments it can be concluded that the entire molecule (germacranolide ester) is necessary for optimal cytotoxicity IN VITRO and that cytotoxicity increases with decreasing hydrophilicity.     

Orodispersible films as a personalized dosage form for nursing home residents,an exploratory study

International Journal of Clinical Pharmacy - Background A frequent problem in ageing patients, and thus in nursing home residents, is dysphagia, affecting the ability to swallow solid dosage forms....     

Cytotoxicity of Artemisinin,a Dimer of Dihydroartemisinin,Artemisitene and Eupatoriopicrin as Evaluated by the MTT and Clonogenic Assay

Artemisinin and its derivatives possess an endoperoxide bridge, which is thought to lead to the production of free-radical species. The cytotoxicity of some of these agents to a murine Ehrlich ascites (EN19) and a human HeLa S3 cancer cell line was determined using the MTT and the clonogenic assay. The MTT assay cannot distinguish between growth inhibition and cell killing, while the clonogenic assay detects actual cell death. The use of both assays to test a certain drug may give information on the mode of its cytotoxicity (i.e. growth inhibition versus cell killing). The endoperoxides artemisinin and the dimer of dihydroartemisinin showed much higher cytotoxicity in the MTT assay compared with the clonogenic assay. Thus these drugs mainly induced growth inhibition. For artemisitene and eupatoriopicrin, which possess an exocyclic methylene with alkylating properties, both tests yielded comparable results. For these compounds the MTT assay merely determined cell killing. For the reference drugs cisplatin and doxorubicin the MTT assay showed lower cytotoxicity than the clonogenic assay. This may be explained by the metabolic activity of cells that were clonogenically dead. Moreover, our experiments have shown that the MTT assay may lead to misinterpretations concerning the mode of action of certain drugs, when it is used as a substitute for the clonogenic assay.     

Isolation, purification, and cytotoxicity of 5-methoxypodophyllotoxin, a lignan from a root culture of Linum flavum.

A method has been developed for the large scale isolation of 5-methoxypodophyllotoxin [1] from a high-producing root culture derived from Linum flavum. A closely related lignan, 5'-demethoxy-5-methoxypodophyllotoxin [2], was also present in the root culture and was the cause of the main isolation difficulties. Essential steps in the isolation procedure are CH2Cl2 and XAD-4 extraction and XAD-8 cc followed by Si gel chromatography, using two different mobile phases. The isolated 5-methoxypodophyllotoxin [1] was very pure (greater than 99%) and possessed the desired stereochemical configuration, namely (-)-5-methoxypodophyllotoxin [1]. The in vitro cytotoxicity of 5-methoxypodophyllotoxin [1] against EAT and HeLa cells was determined and compared with those of podophyllotoxin [3], etoposide (VP-16-213) [4], teniposide (VM-26) [5], and 5-methoxypodophyllotoxin-4-beta-D-glucoside [6]. It appeared that 5-methoxypodophyllotoxin [1] has about the same cytotoxic potency as podophyllotoxin [3].     

Eupatorium cannabinum L.

A review onEupatorium cannabinum L. is given, including botany, history and constituents. The sesquiterpene lactones are discussed in more detail, covering their biosynthesis, isolation, analysis and biological activity. Special attention is paid to the cytotoxic and antitumour activities of the sesquiterpene lactones.     

Mucuna pruriens: Improvement of the biotechnological production of the anti-Parkinson drug L-dopa by plant cell selection

Routinely grown cell suspension cultures ofMucuna pruriens L. (Fabaceae) were able to endogenously accumulate the anti-Parkinson drug L-dihydroxyphenylalanine (L-dopa) in the range between 0.2 and 2% on a dry weight (DW) basis. The green colour that developed in light-exposed cultures, appeared to be a suitable marker to select cells with an increased L-dopa biosynthesis and/or phenoloxidase activity. For this purpose, saccharose concentrations from 0 to 4% (w/v), and light intensities of 1,000 and 2,000 lux, were involved in the selection procedure. After 6 months, photomixotrophic callus cultures with a rapid growth and a high L-dopa content of 0.9% (DW) were obtained on 2% saccharose and under 1,000 lux. The cell suspensions, derived from these calli, accumulated up to 6% (DW) L-dopa, which was the highest stable content ever measured in cultures ofM. pruriens. An L-dopa yield of approximately 1.2 g/l was calculated after 6 days of growth. In contrast, compared with the standard-grown parent cell line, the phenoloxidase activity, and consequently the bioconversion capacity as measured after entrapment in calcium alginate, of these high-producing cultures was approximately threefold lower.     

Traditional Chinese herbal medicine

Herbal medicine, acupuncture and moxibustion, and massage are the three major constituent parts of traditional Chinese medicine. Although acupuncture is well known in many Western countries, Chinese herbal medicine, the most important part of traditional Chinese medicine, is less well known in the West. This article gives a brief introduction to the written history, theory, and teaching of Chinese herbal medicine in China. It also describes modern scientific research into and the quality control of Chinese herbal medicines in China. Some examples of how new drugs derived from Chinese herbs have been developed on the basis of traditional therapeutic experience are presented. Finally, the situation of Chinese herbal medicine in the West is discussed.     

In vitro cytotoxicity of sesquiterpene lactones from Eupatorium cannabinum L. and semi-synthetic derivatives from eupatoriopicrin

In this study 13 semi-synthetic derivatives were prepared from the sesquiterpene lactone eupatoriopicrin, with the aim of obtaining compounds that are more active than eupatoriopicrin, and to give more insight into structure–activity relationships. The compounds were screened for cytotoxicity in vitro against the tumour cell lines EAT, P388, FIO 26, L5178Y(s) (murine) and HeLa (human). Cytotoxicity was compared with the germacranolides eupatoriopicrin, 5′-dehydroxy eupatoriopicrin (‘compound 1’), hiyodorilactone E, eupatolide and eucannabinolide from Eupatorium cannabinum L. and with the eudesmanolides alantolactone and isoalantolactone from Inula helenium L. Acetalization of both hydroxyl groups in the ester side chain of eupatoriopicrin with acetone enhanced cytotoxicity 2–7-fold. Introduction of bulky groups, such as alkyl groups with a longer carbon chain and (halogenated) acetophenone derivatives, via acetalization, reversed the enhancement. Oxidation at the germacrane ring structure of eupatoriopicrin acetonide, yielding an alcohol or an epoxy derivative, affected cytotoxicity adversely.