No abstract

The urgent need for new anti-HIV/AIDS drugs is a global concern. In addition to obvious economical and commercial hurdles, HIV/AIDS patients are faced with multifarious difficulties associated with the currently approved anti-HIV drugs. Adverse effects, the emergence of drug resistance and the narrow spectrum of activity have limited the therapeutic usefulness of the various reverse transcriptase and protease inhibitors that are currently available on the market. This has driven many scientists to look for new anti-retrovirals with better efficacy, safety and affordability. As has always been the case in the search for cures, natural sources offer great promise. Several natural products, mostly of plant origin have been shown to possess promising activities that could assist in the prevention and/or amelioration of the disease. Many of these anti-HIV agents have other medicinal values as well, which afford them further prospective as novel leads for the development of new drugs that can deal with both the virus and the various disorders that characterize HIV/AIDS. The aim of this review is to report new discoveries and updates pertaining to anti-HIV natural products. In the review anti-HIV agents have been classified according to their chemical classes rather than their target in the HIV replicative cycle, which is the most frequently encountered approach. Perusal of the literature revealed that most of these promising naturally derived anti-HIV compounds are flavonoids, coumarins, terpenoids, alkaloids, polyphenols, polysaccharides or proteins. It is our strong conviction that the results and experiences with many of the anti-HIV natural products will inspire and motivate even more researchers to look for new leads from plants and other natural sources.

Diabetic complications are attributed to hyperglycaemic condition which is in turn associated with the polyol pathway and advanced glycation end products. Aldose reductase (AR) is the principal enzyme of polyol pathway which plays a vital role in the development of diabetic complications. AR inhibitory activity can be screened by both in vitro and in vivo methods. In vitro assays for AR enzyme are further classified on the basis of the source of enzyme such as rat lens, rat kidney, cataracted human eye lens, bovine eyes and human recombinant AR enzymes, whereas the in vivo model is based on the determination of lens galactitol levels. A number of synthetic AR inhibitors (ARIs) including tolrestat and sorbinil have been developed, but all of these suffer from drawbacks such as poor permeation and safety issues. Therefore, pharmaceutical companies and many researchers have been carrying out research to find new, potent and safe ARIs from natural sources. Thus, many naturally occurring compounds have been reported to have AR inhibitory activity. The present review attempts to highlight phytochemicals and plant extracts with potential AR inhibitory activity. It also summarizes the classes of compounds which have proven AR inhibitory activity. Phytochemicals such as quercetin, kaempferol and ellagic acid are found to be the most promising ARIs. The exhaustive literature presented in this article clearly indicates the role of plant extracts and phytochemicals as potential ARIs.

Inhibition of biosynthetic enzymes and translation and translocation processes, elicitation, and precursor feeding were used to probe biosynthetic pathway compartmentation, substrate-product relationships, and yield limitation of the diterpenoid taxanes in cell cultures of Taxus chinensis (PRO1-95). The results suggest the following: (i) the source of isopentenyl pyrophosphate in taxane production is likely plastidic rather than cytoplasmic; (ii) baccatin III may not be a direct precusor of Taxol (Taxol is a registered trademark of Bristol-Myers Squibb for paclitaxel); (iii) baccatin III appears to have cytoplasmic and plastidic biosynthetic components, while Taxol production is essentially plastidic; and (iv) arachidonic acid specifically stimulates Taxol production but does not have a significant effect on baccatin III yield. Semiempirical mathematical models were used to describe these results and predict potential yield-limiting steps. Model simulations suggest that, under current operating conditions, Taxol production in Taxus chinensis (PRO1-95) cultures is limited by the ability of the cells to convert phenylalanine to phenylisoserine rather than by the branch-point acyl transferase. This result is supported by the lack of improvement of Taxol yield by feeding phenylalanine or benzoylglycine. The methods described in this article, while specifically expanding our knowledge of taxane production in PRO1-95 cultures, could be generally useful in investigating complex aspects of secondary metabolic pathways in plant cell cultures, especially when details of the pathway and compartmentation are sparse.

The addition of cell extracts and cultures filtrate of Pencillium minioluteum, Botrytis cinerea, Verticillium dahliae, and Gilocladium deliqucescens on the tenth day after transferring Taxus sp. (RO1-M28) cell suspensions into an induction medium, further improved the production of Taxol ® and total taxanes. Arachidonic acid (lmg/L) addition at the time of inoculation increased Taxol production by 150%. Oxidative stress induction and copper sulphate or sodium orthovanadate addition had no effect on Taxol production. Three categories of elicitors; those specifically stimulating Taxol production, those specifically stimulating the producion of other taxanes, and those stimulating taxane production uniformly, could be identified. The biosynthetic site of action of these elicitors is currently not known.~I'axol is a registered trademark of Bristol Myers Squibb for paclitaxel.