Current Bioactive Compounds - Volume 4, Issue 1, 2008

Bidens pilosa L. (Asteraceae) is routinely used in African pharmacopoeia for the management of inflammations, diarrhoea and cardiovascular disorders including hypertension. The implication of β-adrenomimetic agonist substances in the hypotension and vasodilatation induced by a chromatographic active fraction F2 of the leaves aqueous extract (BpF2) were investigated. BpF2 induced a dose-dependent hypotension (1 mg/kg b.w.- 25 mg/kg b.w.) in the rabbit. It caused a concentration dependent (10-12 mg/ml- 10-1 mg/ml) decrease in the force of contraction of the isolated guinea-pig aorta. The hypotension and vasodilatation elicited by BpF2 were attenuated in the presence of propranolol (a β-adrenoceptor antagonist). The results suggest that BpF2 could contain β-adrenomimetic agonist substances that may be partly responsible for the hypotension and the vasodilatation. This would therefore justify the use of the plant to treat hypertension.

The need of using chemically modified siRNA agents for gene silencing continuously increasing as appropriate chemical modification improves their specificity, nuclease stability, potency, and in vivo cellular delivery. The future success of RNAi technology also depends on identifying drug carriers that are non-toxic and tissue-specific in directing the RNAi agents to the desired locations in a cost effective fashion. This review will cover recently reported chemically modified siRNA agents for improving specificity and potency of mRNA knockdown, their nuclease stability, cellular uptake and improved biodistribution. In addition to the chemical modifications and their biological impact, this review also focuses on the in vivo RNAi delivery techniques.

About 20 species from Callicarpa have reported ethnobotanical and ethnomedical uses, and several members of this genus are well known in the traditional medical systems of China and South Asia. Ethnomedical reports indicate their use in the treatment of hepatitis, rheumatism, fever, headache, indigestion, and other ailments. Several species of Callicarpa have been reported to be used against cancer (e.g., Callicarpa americana root to treat skin cancer and Callicarpa rubella bark to treat tumors of the large intestine). Extracts from about 14 species in this genus have been evaluated for biological activity, including antibacterial, antifungal, anti-insect growth, cytotoxic, and phytotoxic activities. In addition to amino acids, benzenoids, simple carbohydrates, and lipids, numerous diterpenes, flavonoids, phenylpropanoids, phytosterols, sesquiterpenes, and triterpenes have been detected in or isolated from the genus Callicarpa. The essential oils of Callicarpa americana have recently been reported to have antialgal and phytotoxic activities, and several isolates from this species (and C. japonica) were identified as contributing to the mosquito bitedeterrent activity that was first indicated by folkloric usage. Recent bioassay-guided investigations of C. americana extracts have resulted in the isolation of several active compounds, mainly of the clerodane diterpene structural type.

The larvicidal activity of Pimpinella anisum (anise) and Apium graveolens (celery) seed extracts was evaluated against 4th instar Aedes aegypti larvae under laboratory conditions as per WHO methodology. Preliminary screening showed anise seed extracts to be more active than celery seed extracts and hexane produced the best extract of anise seeds giving a mildly potent lethal concentration of 403.84 mg/L. Other researchers have reported higher efficacies which cannot be explained by differences in extraction method or choice of solvent. Other probable causes of efficacy variability in phytochemical potency studies are discussed and bioinsecticide screening standards are recommended.

Increasing drug resistance among bacteria, fungi and other pathogenic microbes and the remarkable increase in the incidence of fungal infections like dermatomycoses in the world population underscore our inadequacy to deal with them. Thus there is an urgent need to search chemically novel, natural, renewable and safe anti-microbial substances that can offer opportunity for innovation of new drugs to combat the widespread dermatomycoses. Six fungal endophytic strains (Scytalidium sp. MCPL AzF 023, Pestalotiopsis sp. MCPL AzB 153, Colletotrichum sp. MCPL AzR 249, Alternaria sp. MCPL AzL 198, Nigrospora sp. MCPL AzS 076, and Chloridium sp. MCPL AzR 142) from Azadirachta indica A Juss were screened and evaluated their efficacy against dermatophytes Trichophyton and Microsporum. The susceptibility test was performed by whole plate diffusion method. The EtOAc extracted Scytalidium, Chloroform extracted Nigrospora, Colletotrichum, and Alternaria, ethyl ether extracted Nigrospora in particular significantly reduced the growth of dermatophytes. The MIC ranged from 125-400 μg ml-1 for Trichophyton and 200-350 μg ml-1 for Microsporum while the MFC ranged from 230 to 425 μg ml-1. The chloroform, EtOAc, and ethyl ether were the solvents that might dissolve major active fractions of Pestalotiopsis, Scytalidium and Chloridium. The growth patterns of dermatophytes were also significantly distorted at concentration of 100 μg ml-1 (below MIC), which is statistically significant with reference to untreated fungi. In this study, we recovered bioactive fractions that might be chemically novel and effective against dermatophytes particularly and on other human and plant pathogens in general. Thus we might anticipate some new bioactive compounds to design new effective drugs against dermatomycoses initially.

Glutathione S-transferases (GSTs) are phase II detoxification enzymes that function in the conjugation of glutathione (GSH) to cytotoxic substances rendering them water soluble and easily excreted from the body. Many tumor cells tend to strongly increase the expression of GST, and this is thought to be associated with a poor prognosis for response to anticancer treatment of patients. Such in vitro over-expression of GST may indeed be the basis of the reduced sensitivity of cancer cells to cytostatics. Alkylating anticancer drugs have been found to be effectively conjugated to GSH, catalyzed by GST, thereby decreasing the potency of such drugs. GSTs are also believed to detoxify endogenous substances that are formed as a consequence of oxidative stress, protecting cancer cells against cytostatic-induced oxidative stress and, subsequently, apoptosis. In addition, GSTs inhibit the mitogen-activated protein kinase signal transduction pathway by binding proteins that play major roles in transmission of cellular survival and death signals. These result in a reduced activity of apoptosis-dependent anticancer drugs due to high GST activity in cancer cells. GST has also been proposed to be the major detoxification tool that protects parasites against the host immune response and antiparasitic drugs. In order to ameliorate these resistances, a rationale has been established to utilize agents that specifically inhibit the various classes of GST as adjuvant in chemotherapy. In the past two decades, several compounds have been reported to selectively inhibit GST isoenzymes. In this review, synthetic and naturally occurring organic compounds exhibiting GST inhibition will be described.

Paclitaxil is a non-water soluble anti-cancer drug with problems of solvent related toxicities due to use of ethanol and polyethylated castor-oil for administration. Several formulations have been prepared to overcome the solubility problem and the present work describes one of such possibility of the preparation of water-soluble paclitaxil nanoparticles by Emulsion-solvent evaporation technique. The paclitaxil nanoparticles were prepared by nanoemulsification using human serum albumin as polymer. The prepared nanoparticles were evaluated by stability studies, encapsulating efficiency, in-vitro toxicity studies. It aims to verify the in vivo capacity of the formed nanoparticles to reduce the toxicity, which would have been caused by the conventional Cremophor EL. The prepared nanoparticles were soluble in 0.9%NaCl, showed better encapsulating efficiency and the reconstituted solution was stable for more than 24 hrs. In-vivo abnormal toxicity studies were carried out on albino mice and guinea pig and showed that the paclitaxilnanoparticles formed had no toxicity as compared to Cremophor EL.