The potential of tropane alkaloids and other phytochemical compounds of the South African Erythroxylum species to target pathogenic factors in rheumatoid arthritis

Abstract

Rheumatoid arthritis is the third most common type of arthritis worldwide; and it is also one of the most common autoimmune diseases found today. Studies have shown that the life expectancy of a patient can be reduced by as much as 10 to 15 years due to the co-morbidities associated with chronic inflammation, a hallmark of the disease. Inflammation is characterized by pain, swelling and oxidative stress leading to tissue damage. Extract of three of the southern African erythroxylums were investigated as a potential modifying drug for chronic inflammation. All three extracts exhibited very good antioxidant activity, especially E. emarginatum with an EC50 of 3μg/ml. This is a very good indication that the extract will prevent further tissue damage and inhibit inflammatory proliferation. E. emarginatum also showed very good COX inhibitory results with selectivity to the COX-2 enzyme. An EC20 of 1.38μg/ml was obtained for COX-2 inhibition. This is a key step in preventing inflammatory pain and stopping the inflammatory process early on. Moderate antibacterial activity was also observed indicating elimination of the initiating factor of the disease. Furthermore these extracts proved to be non-toxic in cell culture studies, and were found to be chemically rich and diverse, containing compounds from all classes including 1.35 ± 0.063 (SD) mg of methylecgonine per gram of leaf material in E. emarginatum and trace amounts of atropine, hyoscyamine, tropacocaine, transcinnamoylcocaine and anhydrous methylecgonine. Interestingly, E. emarginatum contained high levels of methylecgonine, the precursors to cocaine, compared to E. coca. This could indicate a blockage in the cocaine synthesis pathway. Gene sequencing results showed that a version of the cocaine synthase gene is present in E. emarginatum. Point mutations observed in the gene sequence could explain the inability of the E. emarginatum to produce cocaine. Overall the results indicate very good potential for these plants to be used medicinally as chronic inflammation modifying drugs.