From the lipophilic extract of Verbesina turbacensis (-)-bornyl caffeate (1), (-)-bornyl ferulate (2), (-)-bornyl p-coumarate (3), and (-)-bornyl cis-4-hydroxycinnamate (4) were isolated. The structures were established from spectral (UV, MS, 1H and 13C NMR) and polarimetric data. Compounds 1-3 were studied for their antiinflammatory activity using the 5-lipoxygenase assay. It could be shown that the strong influence on the 5-lipoxygenase pathway is due to their antioxidative properties which was proven in an in-vitro (TLC analysis with DPPH reagent) and an ex-vivo (inhibition of chemiluminescence in human polymorphonuclear granulocytes (PMNs)) test system. Thus, the inhibitory activity on 5-lipoxygenase and on the production of reactive oxygen species in human PMNs contributes to the reported anti-inflammatory activity for V. turbacensis.
Skeletal muscle regeneration after myonecrosis involves the activation, proliferation and fusion of myogenic cells, and a coordinated inflammatory response encompassing phagocytosis of necrotic cell debris, and the concerted synthesis of cytokines and growth factors. Myonecrosis often occurs in snakebite envenomings. In the case of venoms that cause myotoxicity without affecting the vasculature, such as those of many elapid snakes, regeneration proceeds successfully. In contrast, in envenomings by most viperid snakes, which affect the vasculature and extracellular matrix in addition to muscle fibers, regeneration is largely impaired and, therefore, the muscle mass is reduced and replaced by fibro-adipose tissue. This review discusses possible causes for such poor regenerative outcome including: (a) damage to muscle microvasculature, which causes tissue hypoxia and affects the inflammatory response and the timely removal of necrotic tissue; (b) damage to intramuscular nerves, which results in atrophy of regenerating fibers; (c) degradation of muscle cell basement membrane, compromising the spatial niche for proliferating myoblasts; (d) widespread degradation of the extracellular matrix; and (e) persistence of venom components in the damaged tissue, which may affect myogenic cells at critical points in the regenerative process. Understanding the causes of poor muscle regeneration may pave the way for the development of novel therapeutic interventions aimed at fostering the regenerative process in envenomed patients.
