Abstract：
BACKGROUND: Uncaria tomentosa Willd. DC., is used in the Amazonian region of South America, wherein ethnic groups use the plant to treat diseases, including gastric disorders. However, despite its widespread popular use, this species has yet to be assessed for its anti-ulcer effects.
OBJECTIVE: In this study, we aimed to evaluate the in vivo gastroprotective and gastric healing activities of an aqueous extract of the bark of Uncaria tomentosa (AEUt) and sought to gain an understanding of the pharmacological mechanisms underlying these biological effects.
METHODS: To verify the gastroprotective properties rats were treated with AEUt (30, 60, or 120 mg/kg) prior to inducing gastric ulceration with ethanol or piroxicam. Additionally, the involvement of nitric oxide, non-protein sulfhydryl compounds (NP-SH), α-2 adrenergic receptors, and prostaglandins was investigated. Furthermore, a pylorus ligature model was employed to investigate the antisecretory activity of AEUt. The gastric healing effects of AEUt (60 mg/kg) were examined in rats in which ulceration had been induced with 80% acetic acid, whereas the quality of healing was evaluated in mice with interleukin-induced recurrent ulcers. We also evaluated the in vivo thickness of the gastric wall using ultrasonography. Moreover, the levels of reduced glutathione (GSH) and malondialdehyde (MDA) were evaluated in ulcerated mucosa, and we determined the activities of the enzymes myeloperoxidase (MPO), N-acetyl-β-D-glycosaminidase, superoxide dismutase, catalase, and glutathione S-transferase. In addition, we assessed the effects of AEUt on cell viability and subjected the AEUt to phytochemical analyses.
RESULTS: Administration of the AEUt (60 or 120 mg/kg) prevented ethanol- and piroxicam-induced ulceration, which was also confirmed histologically. Moreover, we observed that pre-treatment with NEM and indomethacin abolished the gastroprotective effects of AEUt, thereby indicating the involvement of NP-SH and prostaglandins in these protective effects. In addition, we found that the administration of AEUt had no appreciable effects on the volume, acidity, or peptic activity of gastric juice. Furthermore, the AEUt (60 mg/kg) accelerated the gastric healing of acetic acid-induced ulcers by 46.2% and ultrasonographic findings revealed a reduction in the gastric wall thickness in this group. The gastric healing effect of AEUt was also accompanied by a reduction in MPO activity. The AEUt (60 mg/kg) also minimized ulcer recurrence in mice exposed to IL-1β and was associated with the maintenance of GSH levels and a reduction in MDA contents. We deduce that the biological effects of AEUt could be associated with the activities of polyphenols and the alkaloids isomitraphylline and mitraphylline, identified as predominant constituents of the AEUt. Furthermore, we found no evidence to indicate that AEUt would have any cytotoxic effects.
CONCLUSIONS: Collectively, our findings provide compelling evidence indicating the therapeutic efficacy of U. tomentosa. Our data indicate that compounds in AEUt confer gastroprotection and that this preventive effect of AEUt was accompanied by gastric healing and a reduction in gastric ulcer recurrence. Moreover, we provide evidence to indicate that the gastroprotective and gastric healing effects involve the antioxidant system and anti-inflammatory responses that contribute to preserving the gastric mucosa.
OBJECTIVE: In this study, we aimed to evaluate the in vivo gastroprotective and gastric healing activities of an aqueous extract of the bark of Uncaria tomentosa (AEUt) and sought to gain an understanding of the pharmacological mechanisms underlying these biological effects.
METHODS: To verify the gastroprotective properties rats were treated with AEUt (30, 60, or 120 mg/kg) prior to inducing gastric ulceration with ethanol or piroxicam. Additionally, the involvement of nitric oxide, non-protein sulfhydryl compounds (NP-SH), α-2 adrenergic receptors, and prostaglandins was investigated. Furthermore, a pylorus ligature model was employed to investigate the antisecretory activity of AEUt. The gastric healing effects of AEUt (60 mg/kg) were examined in rats in which ulceration had been induced with 80% acetic acid, whereas the quality of healing was evaluated in mice with interleukin-induced recurrent ulcers. We also evaluated the in vivo thickness of the gastric wall using ultrasonography. Moreover, the levels of reduced glutathione (GSH) and malondialdehyde (MDA) were evaluated in ulcerated mucosa, and we determined the activities of the enzymes myeloperoxidase (MPO), N-acetyl-β-D-glycosaminidase, superoxide dismutase, catalase, and glutathione S-transferase. In addition, we assessed the effects of AEUt on cell viability and subjected the AEUt to phytochemical analyses.
RESULTS: Administration of the AEUt (60 or 120 mg/kg) prevented ethanol- and piroxicam-induced ulceration, which was also confirmed histologically. Moreover, we observed that pre-treatment with NEM and indomethacin abolished the gastroprotective effects of AEUt, thereby indicating the involvement of NP-SH and prostaglandins in these protective effects. In addition, we found that the administration of AEUt had no appreciable effects on the volume, acidity, or peptic activity of gastric juice. Furthermore, the AEUt (60 mg/kg) accelerated the gastric healing of acetic acid-induced ulcers by 46.2% and ultrasonographic findings revealed a reduction in the gastric wall thickness in this group. The gastric healing effect of AEUt was also accompanied by a reduction in MPO activity. The AEUt (60 mg/kg) also minimized ulcer recurrence in mice exposed to IL-1β and was associated with the maintenance of GSH levels and a reduction in MDA contents. We deduce that the biological effects of AEUt could be associated with the activities of polyphenols and the alkaloids isomitraphylline and mitraphylline, identified as predominant constituents of the AEUt. Furthermore, we found no evidence to indicate that AEUt would have any cytotoxic effects.
CONCLUSIONS: Collectively, our findings provide compelling evidence indicating the therapeutic efficacy of U. tomentosa. Our data indicate that compounds in AEUt confer gastroprotection and that this preventive effect of AEUt was accompanied by gastric healing and a reduction in gastric ulcer recurrence. Moreover, we provide evidence to indicate that the gastroprotective and gastric healing effects involve the antioxidant system and anti-inflammatory responses that contribute to preserving the gastric mucosa.
摘要：
背景：钩藤。DC.,用于南美洲的亚马逊地区，其中种族群体使用植物来治疗疾病，包括胃部疾病.然而,尽管它广泛使用，该物种的抗溃疡作用尚待评估。
目的：在本研究中，我们旨在评估钩藤树皮水提物(AEUt)的体内胃保护和胃愈合活性,并试图了解这些生物学效应的药理机制.
方法:为了验证胃保护特性,在用乙醇或吡罗昔康诱导胃溃疡之前,用AEUT(30、60或120mg/kg)处理大鼠。此外,一氧化氮的参与，非蛋白质巯基化合物（NP-SH），α-2肾上腺素能受体，和前列腺素进行了调查。此外，采用幽门结扎模型研究AEUt的抗分泌活性。在用80％乙酸诱导溃疡的大鼠中检查了AEUT（60mg/kg）的胃愈合作用，而在白细胞介素诱导的复发性溃疡小鼠中评估愈合质量。我们还使用超声检查评估了体内胃壁的厚度。此外，在溃疡粘膜中评估还原型谷胱甘肽（GSH）和丙二醛（MDA）的水平，我们测定了髓过氧化物酶（MPO）的活性，N-乙酰-β-D-糖胺酶,超氧化物歧化酶,过氧化氢酶,和谷胱甘肽S-转移酶。此外,我们评估了AEUt对细胞活力的影响，并对AEUt进行了植物化学分析。
结果：服用AEUt（60或120mg/kg）可预防乙醇和吡罗昔康引起的溃疡，这在组织学上也得到了证实。此外，我们观察到，用NEM和吲哚美辛预处理消除了AEUt的胃保护作用，从而表明NP-SH和前列腺素参与这些保护作用。此外,我们发现AEUt的管理对体积没有明显的影响，酸度,或胃液的消化性活动。此外，AEUT（60mg/kg）使乙酸引起的溃疡的胃愈合加速了46.2％，超声检查发现该组胃壁厚度减少。AEUt的胃愈合效果也伴随着MPO活性的降低。AEUt（60mg/kg）还可最大程度地减少暴露于IL-1β的小鼠的溃疡复发，并与维持GSH水平和降低MDA含量有关。我们推断AEUt的生物学效应可能与多酚和生物碱的活性有关。被确定为AEUt的主要成分。此外，我们没有发现证据表明AEUt会产生任何细胞毒性作用.
结论：总的来说，我们的研究结果提供了令人信服的证据,表明了绒毛膜下的治疗效果.我们的数据表明，AEUt中的化合物具有胃保护作用，并且AEUt的这种预防作用伴随着胃愈合和胃溃疡复发的减少。此外，我们提供的证据表明，胃保护和胃愈合作用涉及抗氧化系统和抗炎反应，有助于保护胃粘膜。
目的：在本研究中，我们旨在评估钩藤树皮水提物(AEUt)的体内胃保护和胃愈合活性,并试图了解这些生物学效应的药理机制.
方法:为了验证胃保护特性,在用乙醇或吡罗昔康诱导胃溃疡之前,用AEUT(30、60或120mg/kg)处理大鼠。此外,一氧化氮的参与，非蛋白质巯基化合物（NP-SH），α-2肾上腺素能受体，和前列腺素进行了调查。此外，采用幽门结扎模型研究AEUt的抗分泌活性。在用80％乙酸诱导溃疡的大鼠中检查了AEUT（60mg/kg）的胃愈合作用，而在白细胞介素诱导的复发性溃疡小鼠中评估愈合质量。我们还使用超声检查评估了体内胃壁的厚度。此外，在溃疡粘膜中评估还原型谷胱甘肽（GSH）和丙二醛（MDA）的水平，我们测定了髓过氧化物酶（MPO）的活性，N-乙酰-β-D-糖胺酶,超氧化物歧化酶,过氧化氢酶,和谷胱甘肽S-转移酶。此外,我们评估了AEUt对细胞活力的影响，并对AEUt进行了植物化学分析。
结果：服用AEUt（60或120mg/kg）可预防乙醇和吡罗昔康引起的溃疡，这在组织学上也得到了证实。此外，我们观察到，用NEM和吲哚美辛预处理消除了AEUt的胃保护作用，从而表明NP-SH和前列腺素参与这些保护作用。此外,我们发现AEUt的管理对体积没有明显的影响，酸度,或胃液的消化性活动。此外，AEUT（60mg/kg）使乙酸引起的溃疡的胃愈合加速了46.2％，超声检查发现该组胃壁厚度减少。AEUt的胃愈合效果也伴随着MPO活性的降低。AEUt（60mg/kg）还可最大程度地减少暴露于IL-1β的小鼠的溃疡复发，并与维持GSH水平和降低MDA含量有关。我们推断AEUt的生物学效应可能与多酚和生物碱的活性有关。被确定为AEUt的主要成分。此外，我们没有发现证据表明AEUt会产生任何细胞毒性作用.
结论：总的来说，我们的研究结果提供了令人信服的证据,表明了绒毛膜下的治疗效果.我们的数据表明，AEUt中的化合物具有胃保护作用，并且AEUt的这种预防作用伴随着胃愈合和胃溃疡复发的减少。此外，我们提供的证据表明，胃保护和胃愈合作用涉及抗氧化系统和抗炎反应，有助于保护胃粘膜。
