Plumeria rubra L.- A review on its ethnopharmacological, morphological, phytochemical, pharmacological and toxicological studies.

ETHNOPHARMACOLOGICAL RELEVANCE: Plumeria rubra L. (Apocynaceae) is a deciduous, commonly ornamental, tropical plant grown in home premises, parks, gardens, graveyards, because of its beautiful and attractive flowers of various colours and size. The different parts of the plant are used traditionally to treat various diseases and conditions like leprosy, inflammation, diabetic mellitus, ulcers, wounds, itching, acne, toothache, earache, tongue cleaning, pain, asthma, constipation and antifertility. AIM OF THE REVIEW: The main aim of this review is to provide an overview and critically analyze the reported ethnomedical uses, phytochemistry, pharmacological activities and toxicological studies of P. rubra and to identify the remaining gaps and thus supply a basis for further investigations. The review also focuses towards drawing attention of people and researchers about the wide spread pharmaceutical properties of the plant for its better utilization in the coming future. MATERIAL AND METHODS: All the relevant data and information on P. rubra was gathered using various databases such as PubMed, Springer, Taylor and Francis imprints, NCBI (National Center for Biotechnology Information), Science direct, Google scholar, Chemspider, SciFinder, research and review articles from peer-reviewed journals and unpublished data such as Phd thesis, etc. Some other 'grey literature' sources such as webpages, ethnobotanical books, chapters, wikipedia were also studied. RESULTS: More than 110 chemical constituents have been isolated from P. rubra including iridoids, terpenoids, flavonoids and flavonoid glycosides, alkaloids, glycosides, fatty acid esters, carbohydrates, animo acids, lignan, coumarin, volatile oils, etc. The important chemical constituents responsible for pharmacological activities of the plant are fulvoplumierin, plumieride, rubrinol, lupeol, oleanolic acid, stigmasterol, taraxasteryl acetate, plumieride-p-E-coumarate, rubranonoside, rubrajalellol, plumericin, isoplumericin, etc. The plant possess a wide range of pharmacological activities present namely antibacterial, antiviral, anti-inflammatory, antipyretic, antidiabetic, hepatoprotective, anticancer, anthelmintic, antifertility and many other activities. CONCLUSION: P. rubra is a valuable medicinal source and further study in this topic can validate the traditional and ethnobotanical use of the plant. However, many aspects of the plant have not been studied yet. The pharmacological activity of active chemical constituent isolated from the plant is proven only for a couple of activities hence, lack of bio-guided isolation strategies is observed. Further studies on bioavailability, pharmacokinetics, mechanism of action and structural activity relationship studies of isolated pure compounds will contribute more in understanding their pharmacological effects. Higher doses of plant extracts are administered to experimental animals, therefore their toxicity and side effects in humans are needed to be thoroughly studied, although no side effect or toxicity is seen or observed in experimental animals. Studies are also essential to investigate the long term in vivo toxicity and clinical efficacy of the plant.

Efficacy of clofazimine - modified cyclodextrin against Mycobacterium avium complex in human macrophages

Clofazimine, a water insoluble substituted iminophenazine derivative with anti-mycobacterial and anti-inflammatory activity, is recommended by the WHO for the treatment of leprosy. It is also active against disseminated Mycobacterium avium complex (MAC) disease in HIV-infected patients. Recently, we achieved a 4000-fold increase of clofazimine water solubility using a novel modified clofazimine-cyclodextrin complex synthesized and patented by our group [Wasserlösliche, Iminiophenazinderivate enthaltende pharmazeutische Zusammensetzungen, deren Herstellung und Verwendung, German Patent, DE19814814C2]. In this paper we examine the activity of this complex against MAC in human macrophages, and evaluate its cytotoxicity. MAC-infected macrophages were treated for 24h with free or complexed clofazimine. The in vitro minimum inhibitory concentrations of both free and complexed clofazimine were 0.1 microg/ml. Free and complexed clofazimine inhibited the growth of MAC inside macrophages to a similar extent, while modified cyclodextrin alone had no observable effects on MAC or macrophages. Complexed clofazimine was not toxic to cells at concentrations effective against MAC. The TD(50) of the modified cyclodextrin in THP-1 cell line was 297 microg/ml.