Bromelain kallikrein

Its mechanism of action, however, is not completely elucidated. Kamakura et aL [94] studied the effects of stem bromelain on tlw plasma kallikrein system, bradykinin levels and plasma exudation at the inflammatory site in rats with a kaolin-induced inflammation of an air couch. Bromelain caused a dose-... 

The anti-inflaminatory action of bromelain preparations is the result of dif-fjrjnt mechanisms thatnft simultaneous 11. First there is, as described sbevr, the depletion of the plasma kallikrein system, inhibiting the generation of bndykinin, a known chemical mediator of inflammation. Second, there is a negative action... 

Its mechanism of action, however, is not completely elucidated. Kamakura et al. [94] studied the effects of stem bromelain on the plasma kallikrein system, bradykinin levels and plasma exudation at the inflammatory site in rats with a kaolin-induced inflammation of an air pouch. Bromelain caused a dose-dependent decrease of bradykinin levels (measured with the method of Minami et al. [95]) at the inflammatory site and a parallel decrease of the prekallikrein levels in sera [88]. Plasma exudation was also reduced dose-dependently. Bradykinin-degrading activity in sera was elevated after bromelain treatment, but not in the pouch fluid. The authors conclude that bromelain inhibits plasma exudation through inhibition of the bradykinin generation at the inflammatory site via depletion of the plasma kallikrein system. Bromelain also shows a dose-dependent analgesic effect in concanavalin A-injected paws of 5.6 mg/kg i.v.), considered to be due to decrease of high molecular weight kininogen [96]. 

Even when mechanisms and pathways are unknown, it is sometimes possible to use Arrhenius or empirical equations to determine apparent rate constants at other temperatures. Apparent first-order rate constants for a-chymotrypsin and bromelain inactivation exhibited linear Arrhenius plots (Fig. 21 1).879 Apparent rate constants for kallikrein inactivation calculated according to the reaction scheme in Eq. (5.1) resulted in the temperature dependence seen in Fig. 212.850 For inactivation of various peptide and protein pharmaceuticals... 

Figure 214. Arrhenius plots for the inactivation of marketed solid digestive enzyme formulations. A, a-Chy-motrypsin troche A, a-chymotrypsin tablet , [i-galactosidase powder, v, bromelain tablets O, kallikrein capsule. (Reproduced from Ref. 888 with permission.)...

Apparent activation energy values have also been reported for solid-state degradation of peptide and protein pharmaceuticals. The reported values include 1-2 kcal/mol for human interferon-P formulated with human serum albumin887 15 kcal/mol for freeze-dried urokinase (Fig. 213)838 and 11-18 kcal/mol for a-chymotrypsin and bromelain tablets, kallikrein capsules, and P-galactosidase powder (Fig. 214).888... 

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