Cell biology in Herbal drug discovery

Plants have been the basis of many traditional herbal medicine systems throughout the world and continue to provide mankind with new remedies. There is a great deal of interest and support for the search of new and useful drugs from plants in countries such as India, China, Japan and Germany. The process of drug discovery from plants is multi and inter disciplinary.  Among the core disciplines related to pharmaceutical research, in vitro cell culture technology has evolved as an indispensable part of drug discovery from plants.

 In vitro methods are widely used to study activities of plant extracts at the cellular and molecular level. These readily reproducible assay systems measure critical parameters such as physicochemical properties, metabolism, drug interactions, and toxicity. By uncovering early in the discovery stage the defects that can eliminate candidate drugs from preclinical and clinical development, these techniques can save significant cost, time and effort. Furthermore, in vitro methods are powerful tools to refine, replace and reduce animal experiments, either -alone, or as part of a testing strategy. This will have a great effect on the ability of science to make real step towards the complete replacement of animals.

Specific in vitro cell models can be employed to study cell interactions, cell environment interactions, intracellular activity, cell products, site and mechanism of action and genetic studies with herbal formulations.  Apart from the convenience, the lack of ethical dilemmas (unlike in human or animal studies), a control of the experimental environment, the ability to characterize the sample and maintenance of homogeneity in the procedure are the major advantages of employing in vitro cell culture technology. Up-scaling and mechanization are also major advantages of in vitro cell culture technology, allowing high-throughput screens.

In herbal drug discovery process, several in vitro models are optimized for high throughput screening efficiencies, allowing the entire libraries of potential pharmacologically relevant molecules to be screened for different types of cell signals relevant to tissue damage or therapeutic goals. Creative approaches to multiplexed cell-based assay designs that select specific cell types, signaling pathways and reporters are also carried out.

 In the last two decades mammalian cell culture has matured from being merely a research tool into one of the foundations of the biopharmaceutical industry, and its use is continuing to expand rapidly. New approaches using cell biology, molecular biology and genetic manipulation will help to provide in vitro models that may be much more closely correlated with in vivo tissue responses. In vitro cell models have tremendous potential in the field of stem cell and regenerative medicine. There is an increasing need for larger scale generation of stem cell derived therapeutics for clinical applications. With the advances in genetics and biomedical engineering, transfected cell culture and 3D tissue models have been developed.

Stably transfected cell lines are valuable tools for studying the pharmacological properties and functional characteristics of putative drug candidates.

The universal recognition of the need for better in vitro model systems for predicting drug response in humans has lead to several important developments in cell biology. Most notably, primary cell lines derived from a wide range of normal human tissues are now being used as more relevant models for drug evaluation. New genetic technologies such as siRNA and gene knock-out animals are now proving useful in validating new drug targets. The system biology approach is gaining importance in drug discovery and numerous cell-based technology platforms are available that can simultaneously evaluate multiple assay parameters.

The future development for drug discovery will clearly involve the in vitro cell culture technology with the advancement in stem cell technology, transgenics, 3D tissue models or biological- and silicon-integrated chip systems and other sophisticated systems yet to be envisioned.