Guggulu, the resinous gum exudate from a small tree with short, thorny branches known as Commiphora mukul (Hook ex Stocks) Engl. It is also correctly known as Commiphora wightii (Arnott.) Bhanol.), guggul, and false myrrh Guggulu is one of the components of various formulations of traditional Ayurvedic medicine used to treat inflammation, obesity, and lipid disorders.
Guggulu belongs to the genus Commiphora, the genus of the myrrhs. Commiphora belongs the Burseraceae family which includes frankincense and myrrh. The genus Commiphora actually contains approximately 190 species of shrubs and trees, which are distributed throughout the (sub-) tropical regions of Africa, the western Indian Ocean islands, the Arabian Peninsula, India, and Vietnam. The genus is drought-tolerant and common throughout the dry scrub areas, seasonally dry tropical forests, and woodlands of these regions.
A growing body of basic and clinical evidence indicates that inflammation is at the root in genesis of many disease afflicting humankind. The list is almost endless and includes: coronary artery disease, autoimmune diseases, obesity, asthma, peptic ulcer, tuberculosis, rheumatoid arthritis (and other arthitidies), ulcerative colitis, Crohn’s disease, chronic sinusitis, chronic active hepatitis, chronic periodontitis, and many more as yet uncharacterized conditions.
The medicinal properties of herbs used in traditional medicine systems such as Ayurvedic medicine (AM) and traditional Chinese medicine (TCM) are attributed to the presence of different types of biologically active compounds. However, the pharmacological effects of herbal medicines usually depend not only on the major constituents, but also on minor ones. Hence quality control, discovery of active constituents, and proof of efficacy have long been considered critical and challenging research tasks for modernizing traditional herbal medicines. In the reductionist approach, sometimes identifying low-abundance active phytocompounds in medicinal plants is barely achievable. Similarly, deciphering a synergistic action of multiple ingredients in a single plant or multiple medicinal plant formulations has been very difficult. In metabolomics studies, establishing a chromatographic fingerprint with GC–MS, LC–MS, or LC–NMR online analysis as the characteristic representation of the chemical or pharmacologically active components in herbal medicines is attracting immense interest.
The proof of efficacy of phytomedicines and the determination of their mechanism of action are major challenges for an evidence-based phytotherapy. The main obstacle preventing herbal medicines from meeting the stringent requirements of the conventional medicine industrial complex is efficacy and economic utilization of modern pharmacological tools to investigate their mechanism of action. The inherent chemical diversity of the plant metabolome creates significant analytical challenges and there is no single experimental approach that can detect all metabolites. Additionally, the biological variation in each individual metabolism and the dependence of metabolism on environmental factors necessitates large sample numbers to achieve the appropriate statistical power required for meaningful biological interpretation. To address these challenges, we turn to systems biology for the solution.
Systems biology, which consists of genomics, epigenomics, proteomics, and metabolomics,seeks to describe the complex interactions between biological system components and to predict biological system behavior. Genomics is a discipline in genetics that applies recombinant DNA, DNA sequencing, and bioinformatics to sequence, assemble, and analyze the function and structure of genomes. Epigenetic regulation involves heritable alteration of gene expression by modifying chromatin structure without changing primary DNA sequences. Proteomics allows us to obtain a more holistic and integrated view of biology by studying all the proteins of a cell rather than each one individually.
Metabolomics is one of the key approaches of systems biology that consists of studying biochemical networks having a set of metabolites, enzymes, reactions and their interactions Metabolomics measures the metabolic profiling (e.g. low molecular weight metabolites) of the systems (plant cells and/or human subjects) and provides a holistic picture of the effects of an herbal preparation. It is relatively non-invasive and utilizes urine or plasma samples which simplifies large scale research. Since metabolomics and proteomics analyze different types of molecules, they complement each other when apply to study the mechanisms of herbal medicine. Metabolomics-proteomics has emerged as a powerful tool to investigate physiological conditions, mutations, changes in response to external factors, and adaptation.
The technology platform of genomics, proteomics and metabolomics ("-omic-" technologies) are high-throughput technologies. This means that they increase exponentially the number of proteins/genes that can be detected simultaneously and therefore can relate complex mixtures to complex effects using gene/protein expression profiles. Provided that phytomedicine-specific gene/protein expression profiles can be developed, these technologies are extremely useful for the determination of the mode of action of phytomedicines and allow us to investigate herbal extracts without prominent active principle(s). High speed and high throughput techniques also allow herbal medicine effects to be studied for the whole body and not just at the molecular and cellular level. It may also facilitate scientific dialog between holistic and conventional Western medicine. Post-translational modifications (PTMs) are the key regulators of protein activity and involve the modifications of proteins by small compounds, lipids, or even a group of chemicals, detectable today through metabolomic analysis. It would be interesting to apply metabolomics-proteomics to detect PTMs after herbal treatment.
The application of metabolomics has already revealed that gene/protein expression profiles induced by single drugs and the ones induced by the combination of the same drugs can be entirely different. These results make the old mode of action concept of isolated "active principles" of an herbal medicine extremely questionable. Although this old paradigm is still universally accepted, the new findings must and will lead to a change in understanding towards the systems biology paradigm of utilizing complex mixtures in clinical medicine. There is also yet another very realistic application for this research. In the future, the use of metabolome-refined herbal extracts in combination with other conventional biochemical medicines, rather than as isolated single compound(s), may prove to be very useful as broader and more holistic therapeutic agents for a variety of human health care applications.
There have been many published laboratory and clinical studies which confirm the anti-inflammatory and hypolipidemic activities of Guggulu. Our proposed research focuses on the mechanisms of action of the anti-inflammatory effects. A review of the literature  reveals that Guggulu anti-inflammatory action has been verified and that a vast number of its different components have been isolated and identified as possessing anti-inflammatory.
Our proposed research will use a systems biology approach described above to elucidate the specific mechanism(s) of action of Guggulu’s anti-inflammatory actions. This research is expected to provide solid evidence-based scientific rationale for the use of Guggulu in a variety of clinical settings and break new ground for the development of other modern phytomedicines.
 The first mention of guggulu (bdellium) is found in an ancient text known as the Atharvaveda (c. 1200 BC) where it is praised as a boon to mankind:
"Diseases (consumptions) flee apart from it as from a wild beast flee the deer. If thou, O Bdellium (guggulu), art produced from Sindhu or hast come from sea, the quality of both have I taken to keep this man unscathed." (AVŚ 19.38.2)
The intermediate link between pure molecular biology at the bench and clinical studies using humans are studies utilizing fruit flies, yeast, and worms. Whether cells be from yeast, flies, worms, or humans, all cells stay alive and healthy through identical mechanisms. This is why organisms like Drosophila melanogaster (fruit flies), C. elegans (worms), and S. cerevisiae (yeast), which can be rapidly and inexpensively studied, have led to so many important recent discoveries that have translated into clinical treatments for people. The FHMR “simple organism” approach is efficient and cost effective, and will result in proven and practical therapies for specific diseases in the shortest possible time. This approach isn’t exactly innovative; its been used for decades in association with earlier technologies. At FHMR, we are using state-of-the-art reliable genetic, epigenetic and metabolomic methods to create worms, flies, and yeast that carry genetic, epigenomic, and metabolomic anomalies corresponding to those of patients with a specific disease condition. When we find an herbal, pharmacological, or lifestyle therapy that will cure, for example, a fruit fly’s and a worm’s disease and know its molecular mechanism, we have a very strong candidate to treat the human version of that disease. Many research groups have conducted studies using simpler organism models in the past, but not at the scale we will execute and not with the advanced technologies we will incorporate.