Therapeutic Values of Human Urinary Kallidinogenase on Cerebrovascular Diseases

Abstract

The term “tissue kallikrein” is used to describe a group of serine proteases shared considerable sequence homology and colocalize in the same chromosomal locus 19q13. 2–q13.4. It has been widely discovered in various tissues and has been proved to be involved in kinds of pathophysiological processes, such as inhibiting oxidative stress, inflammation, apoptosis, fibrosis and promoting angiogenesis, and neurogenesis. Human Urinary Kallidinogenase (HUK) extracted from human urine is a member of tissue kallikrein which could convert kininogen to kinin and hence improve the plasma kinin level. Medical value of HUK has been widely investigated in China, especially on acute ischemic stroke. In this review, we will summarize the therapeutic values of Human Urinary Kallidinogenase on acute ischemic stroke and its potential mechanisms.

Human urinary kallidinogenase in acute ischemic stroke: A single‐arm, multicenter, phase IV study (RESK study)

“…In fact, the safety profile observed here was consistent with that expected from patients receiving HUK, as reported in other studies. 18 , 20 Similar to those studies, BP reduction and fever were the most common AEs after HUK infusion. Thus, these events, especially BP reduction, should be alert and focused on in clinical practice.…”

“…Similar to our results, several meta‐analyses also demonstrated the effects of HUK, including decreasing stroke recurrence risk and marked neurological improvement. 20 Regrettably, we cannot exclude the influence of the combined drugs or other factors on HUK efficacy because of the single‐arm study design. Therefore, we analyzed the effects of the usage of combined drugs on HUK efficacy using the subgroup analysis and logistic regression (Tables S1–S3 ).…”

Increase in Blood–Brain Barrier Permeability is Modulated by Tissue Kallikrein via Activation of Bradykinin B1 and B2 Receptor-Mediated Signaling

“…To investigate the effect of TK on BBB, 48 C57BL/6 male mice were divided equally into four groups: control (intravenous injection of 0.9% saline solution), standard-dose TK treatment, medium-dose TK treatment, and high-dose TK treatment. We took the TK concentration which is employed in clinical and basic studies 17 as standard-dose TK treatment (intravenous injection of HUK with 25×10 −3 PNA U/kg), and then increased TK concentration on multiple. Finally, the TK concentration which can increase the permeability of BBB to EB was regarded as high-dose TK treatment (intravenous injection of HUK with 400×10 −3 PNA U/kg), and the intermediate concentration was used as the medium-dose TK treatment (intravenous injection of HUK with 100×10 −3 PNA U/kg).…”

Human Urinary Kallidinogenase Reduces Lipopolysaccharide-Induced Neuroinflammation and Oxidative Stress in BV-2 Cells

“…In contrast, kallikrein has much more amount in plasma. Accumulated studies have reported the function of tissue kallikrein on antiapoptotic, antioxidant, and antiexcitotoxic properties, suggesting that tissue kallikrein could be an effective therapy for neurological disorders [10]. Human urinary kallidinogenase (UK) is a tissue kallikrein derived from human urine, cleaving kininogen to release bradykinin [11].…”