Proteases play a pivotal role in many signaling pathways; inhibitors of well-established proteases have shown a substantial therapeutic success. This study aimed to examine the in vivo effects of 3 protease inhibitors isolated from Bauhinia species: i) Bauhinia mollis elastase inhibitor, which blocks human neutrophil elastase (Kiapp 2.8 nM) and cathepsin G (Kiapp 1.0 nM) activities; ii) Bauhinia mollis trypsin inhibitor, a trypsin inhibitor (Kiapp 5.0 nM); and iii) Bauhinia bauhinioides cruzipain inhibitor, which inhibits elastase (Kiapp 2.6 nM), cathepsin G (Kiapp 160.0 nM), and the cysteine proteases cathepsin L (Kiapp 0.2 nM). Bauhinia bauhinioides cruzipain inhibitor, Bauhinia mollis elastase inhibitor, and Bauhinia mollis trypsin inhibitor were isolated using acetone and ammonium sulfate fractionations, DEAE-Sephadex, trypsin-Sepharose, and Resource-Q chromatographies. Mice and rats were treated intraperitoneally with 1 dose of inhibitor; gastric mucosal lesions were induced by cold-restraint stress. Oral pretreatment of mice with Bauhinia mollis elastase inhibitor or Bauhinia mollis trypsin inhibitor (1 - 10 mg/kg) did not show anti-ulcer effect, while Bauhinia bauhinioides cruzipain inhibitor (0.1 - 1.0 mg/kg) produced a similar reduction of the index of mucosal damage at all effective doses (30 to 33% < control). In rats at doses lower than those used in mice, Bauhinia mollis elastase inhibitor and Bauhinia bauhinioides cruzipain inhibitor reduced the index of mucosal damage by 66% and 54% of controls, respectively. The results indicate a protective effect against gastric mucosal lesions associated with elastase inhibition but not inhibition of trypsin activities. Moreover, the lack of Bauhinia mollis elastase inhibitor efficacy observed in mice may possibly be related to the reported structural differences of elastase in mice and rats.

中文翻译：

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紫荆蛋白酶抑制剂通过阻断中性粒细胞酶来减轻胃溃疡

蛋白酶在许多信号通路中发挥着关键作用。公认的蛋白酶抑制剂已显示出巨大的治疗成功。本研究旨在检查从紫荆属物种中分离的 3 种蛋白酶抑制剂的体内作用：i) 紫荆弹性蛋白酶抑制剂，可阻断人类中性粒细胞弹性蛋白酶 (Kiapp 2.8 nM) 和组织蛋白酶 G (Kiapp 1.0 nM) 的活性；ii) Bauhinia mollis 胰蛋白酶抑制剂，一种胰蛋白酶抑制剂 (Kiapp 5.0 nM)；iii) Bauhinia bauhinioides cruzipain 抑制剂，可抑制弹性蛋白酶 (Kiapp 2.6 nM)、组织蛋白酶 G (Kiapp 160.0 nM) 和半胱氨酸蛋白酶组织蛋白酶 L (Kiapp 0.2 nM)。Bauhinia bauhinioides cruzipain 抑制剂、Bauhinia mollis 弹性蛋白酶抑制剂和 Bauhinia mollis 胰蛋白酶抑制剂使用丙酮和硫酸铵分级分离、DEAE-Sephadex、胰蛋白酶-Sepharose、和 Resource-Q 色谱法。小鼠和大鼠腹腔注射 1 剂抑制剂；冷胁迫诱发胃黏膜病变。用紫荆弹性蛋白酶抑制剂或紫荆胰蛋白酶抑制剂 (1 - 10 毫克/公斤) 对小鼠进行口服预处理未显示抗溃疡作用，而紫荆花抑制剂 (0.1 - 1.0 毫克/公斤) 产生类似的指数降低所有有效剂量下的粘膜损伤（30% 至 33% < 对照）。在剂量低于小鼠剂量的大鼠中，紫荆弹性蛋白酶抑制剂和紫荆花紫荆抑制剂使粘膜损伤指数分别降低了对照组的 66% 和 54%。结果表明对与弹性蛋白酶抑制相关的胃粘膜损伤的保护作用，而不是胰蛋白酶活性的抑制。而且，