The Phytochemistry Unit aspires to develop and establish innovative methodologies for producing quality control standards and clinically proven traditional medicine products. Concomitantly, we are engaged in the discovery of new molecule entities from natural resources for the treatment or prevention of various diseases. Our research begins from the field to discovery and quality control schemes for safe and efficacious natural products.
1. Producing standardized herbal products and chemical markers
Here in Phytochemistry Unit, we produce premium extracts at the laboratory scale through selections of high-quality raw materials, authentication, and quantification of chemical or biomarkers for safety and efficacy studies. To ensure quality raw materials, authentications of the raw materials are often aided by botanical, DNA fingerprinting, and chemical fingerprint analysis.
A chemical fingerprint analysis provides a unique pattern of compounds present in the selected natural products. Before further research on the extract, chemical markers selected from this fingerprint are quantified to monitor the chemical consistency. Multiple analytical tools including semi-automated HPTLC, HPLC-PDA, LC-MS and NMR are available for chromatographic and quantitative analysis.
In addition, we are committed in developing efficient separation methods for the isolation and purification of chemical markers for further research. Whenever possible, we establish simple and cost-efficient methods to purify the chemical markers of interest. However, for complex chemical separations, new separation and isolation protocol are developed via cutting-edge technologies such as flash chromatography, recycling preparative HPLC, and CPC coupled to UV and ELSD detectors. Currently, we have established purification methods for several chemical markers from Carica papaya (betik), Hibiscus sabdariffa (Roselle), Ficus deltoidea (Mas cotek), Dioscorea hispida (Ubi gadung) and Schizophyllum commune (Kulat sisir).
|Figure 1: Raw material sourcing to produce premium standardized extracts|
2. Discovery of new chemical entities from natural products
Malaysia’s biodiversity remains a largely unexploited biological source of natural bioactive molecules. In Malaysia, the gap between exploration and exploitation is still huge and warrants continuous discovery efforts. By working together with internal and external research partners, the Phytochemistry Unit engages in the discovery of new chemical entities for anti-microbial, cancer chemoprevention, anti-inflammatory, anti-aging and other bioactivities from various medicinal plants and fungi sources.
Our role is to prioritize and characterize the bioactive secondary metabolites. We are interested in developing a combined strategy of bioassay-guided fractionation with LC-MS dereplication for rapid annotations of the secondary metabolites in the selected natural products extracts or enriched fractions. This effort requires in-depth chemical profiling and organization of the fragmentation patterns into molecular networks for studying the structural relatedness and the relationship with bioactivity. After a potential bioactive compound has been identified in an extract or fraction, the typical workflow includes the purification and structural elucidations by dedicated preparative chromatographic and spectroscopic systems.
Currently, one aspect that remains a massive challenge in this strategy is the automated metabolite annotations from publicly assessable compound/spectral databases, especially for Malaysian native plants. As part of our effort in conserving plants species threatened with extinction, these databases should include high-value medicinal plants and all endangered species. Collaborative initiatives especially among research establishments in Malaysia may partly resolve this challenge in the future.
Figure 2: Analytical instruments used for natural products drug discovery
3. Developing quality control standards for herbals
The Phytochemistry Unit contributes actively to Malaysian Herbal Monograph initiatives for the development of the specifications and authentication of various species. This includes monographs for Moringa oleifera (Merunggai), Clinacanthus nutans (Belalai gajah), Momordica charantia (Peria katak), Mitragyna speciosa (Ketum), Carica papaya (Daun Betik), Brucea javanica (Melada pahit), Curcuma zedoaria (Kunyit putih), Syzygium polyanthum (Daun Salam), Schizophyllum commune (Kulat sisir), Dioscorea hispida (Ubi gadong), and Smilax myosotiflora (Ubi jaga).
While simple and accessible analytical methodologies such as HPTLC and HPLC are more common for the national quality control standards, we are committed to explore more current and comprehensive quality control strategies of Malaysian native natural products towards drug discovery and delivery. For this, we use untargeted LC-MS and NMR-based metabolomics combined with multivariate analysis. These approaches may shift the conventional paradigm of drug screening of natural origin to more reliable and rigorous phytochemical analysis. The untargeted metabolomics approach includes the large-scale study of all secondary metabolites present in a living system. It can be extended in quality control of herbals via studying the relationship between the whole metabolome of selected natural products and their bioactivity, and other factors such as varieties, geographical origins, post-harvest processing. Implementing such methodology in our herbal research accelerates the development of quality control strategies for several Malaysian high-value medicinal plants; Ficus deltoidea, Hibiscus sabdariffa, and Carica papaya.