Natural products to target inflammation

Chapter 1 Most Western lifestyle diseases such as type 2 diabetes mellitus, cardiovascular disease and cancer have a chronic inflammatory process at its base. Therefore, inflammation is an important therapeutic target. Due to their potency, steroidal drugs dominate the current treatment of inflammatory disorders. However, steroidal drugs can also exert a broad range of side effects. This thesis looks at the field of ‘natural products‘ to find alternatives. A natural product is a molecule produced by a living organism. Chapter 2 We performed a systematic literature review in which we ranked the anti-inflammatory performance and bioavailability of 102 natural products. Although many of these products do appear to show promise, bioavaibility is often poor. Furthermore, many studies focus on single inflammatory pathways and single molecules, making meaningful comparison difficult. Chapter 2 Therefore, we compared the response of multiple inflammatory mediators to eight well-known natural products. The steroidal drug prednisolone was included as golden standard. We identified curcumin and berberine as promising alternatives to steroidal drugs. Chapter 4 One strategy to improve the low aqueous solubility of natural products is by loading them into nanoparticles. Low-density lipoprotein (LDL) has many attractive properties with regard to inflammation and bioavailability. For that reason, we developed an effective new method to use LDL as a nanoparticle for drug delivery. Chapter 5 Curcumin, with its favorable anti-inflammatory profile but poor bioavailability, is a prime candidate for encapsulation in nanoparticles. In an in vitro comparison of LDL and three other nanoparticles, the former achieved the highest relative curcumin loading capacity. Chapter 6 Berberine has been described to have cardioprotective in addition to anti-inflammatory properties. To enhance the aqueous solibility, we prepared a liposomal formulation and showed that berberine, when properly delivered, protects cardiac function after myocardial infarction in mice. Chapter 7 Human safety and toxicity is an important concern in the development of pharmaceuticals. However, there is still little attention for their (aquatic) environmental safety and the indirect impact on human health after exposure. To emphasize this, we compared the environmental impact of berberine and prednisolone. Chapter 8 To conclude, we have shown that natural products, especially when encapsulated in nanoparticles, can indeed serve as potential alternatives for steroidal drugs in inflammatory diseases.