Design and semisynthesis of oleanolic acid derivatives as VEGF inhibitors: Inhibition of VEGF-induced proliferation, angiogenesis, and VEGFR2 activation in HUVECs / 中国天然药物

Angiogenesis inhibitors targeting the VEGF signaling pathway are developed into drugs for the treatment of vaious diseases, such as cancer, rheumatoid arthritis, and age-related macular degeneration. Recent studies have revealed that oleanolic acid (OA), a natural pentacyclic triterpenoid, inhibited the VEGF/VEGFR2 signaling pathway and angiogenesis in HUVECs, which may represent an attractive VEGF inhibitor. In this paper, rational structural modification towards OA was performed in order to improve its inhibitory effects aganist VEGF and anti-angiogenesis potential. As a result, a series of novel OA derivatives, possessing α,β-unsaturated ketone system in ring A and amide functional group at C-28, were prepared and evaluated for cytotoxicity and their ability to inhibit VEGF-induced abnormal proliferation of HUVECs. The results showed that two promising derivatives, OA-1 and OA-16, exhibited no in vitro cytotoxicity against HUVECs but showed more potent inhibitory activity against VEGF-induced proliferation and angiogenesis in HUVECs, compared with OA. The results of Western blot indicated that OA-1 and OA-16 inhibited VEGF-induced VEGFR2 activation. Furthermore, small interfering RNA experiments were performed to confirm that both compounds inhibited VEGF-induced angiogenesis via VEGFR2. Thus, the present study resulted in the discovery of new promising OA-inspired VEGF inhibitors, which can serve as potential lead compounds for the treatment of angiogenesis-related diseases.

Cambios en la presión arterial sistémica por uso de Bevacizumab intravítreo / Changes in systemic blood pressure by intravitreal bevacizumab

Introducción: El estudio busca evaluar si existe diferencia en la presión arterial sistémica previa y 24 horas posterior de la aplicación de Bevacizumab intravítreo en pacientes con diversas retinopatías. Metodología: Se examinaron a 68 pacientes, con el objetivo de determinar la presión arterial previa y posterior a la aplicación de Bevacizumab intravítreo. Para el análisis se utilizó un estudio observacional prospectivo tipo cohorte. Se comprobó a través del método de t-student para muestras apareadas con un alfa de 0.05, si existen cambios significativos a nivel de presión sistémica arterial previa de la administración intravítreo y 24 horas posteriores a ella. Resultados: Se estudiaron 68 pacientes con diversas retinopatías, excluyéndose 4 por no cumplir con los criterios de inclusión para el estudio. Se obtuvo cambios de la presión arterial sistémica que resultaron en un aumento aproximado de 7.44 mmHg en la presión sistólica y de 2.41 mmHg en la presión diastólica. Conclusiones: El Bevacizumab intravítreo causa un aumento en la presión arterial sistémica 24 horas posterior al su uso. Como ya se había observado en otros estudios siendo esta una causa adversa de uso en pacientes de riesgo.

Introduction: The study aimed to evaluate possible differences in previous systemic arterial blood pressure and 24 hours after the application of intravitreal Bevacizumab in patients with various retinopathies. Method: A total of 68 patients were studied with the objective of determining arterial blood pressure before and after the application of intravitreal Bevacizumab. This is a prospective observational cohort study and possible differences were calculated by t-student test for paired samples with an alpha of 0.05. Significant changes of arterial blood pressure were evaluated previous to intravitreal administration and 24 hours after. Results: A total of 68 patients with various retinopathies were studied. Four were excluded because did not meet the inclusion criteria. Changes in systemic blood pressure showed in an increase of approximately 7.44 mmHg in systolic pressure and an increase of 2.41 mmHg in the diastolic one. Conclusions: Intravitreal Bevacizumab mildly increase systemic blood pressure 24 hours after its use. As already observed in other studies, this is an adverse cause for its use in risk patients.

Advances of vascular endothelial growth factor inhibitors in the treatment of psoriasis / 天津医药

Psoriasis is a common inflammatory autoimmune disease. Angiogenesis is known to be a key pathogenic fea?ture of psoriasis. The elevation of vascular endothelial growth factor (VEGF) has been demonstrated in the skin and plasma of patients with psoriasis. A number of case reports have indicated that VEGF inhibitor is effective in patients with psoriasis. VEGF inhibitors are consisted of three categories:anti-VEGF monoclonal antibodies, VEGF receptor antagonists and tyro?sine kinase inhibitors. This article reviewed the current clinical application and therapeutic potential of VEGF inhibitors in psoriasis .