Genistein Ameliorated Vascular Endothelial Growth Factor-A (VEGF-A) and Estrogen Receptor-Alpha (ER-α) in Endometriosis Mice Model, In Vivo and In Silico.

Endometriosis (EM) is a gynecological disorder that causes morbidity in women and is characterized by endometrial tissue in the uterus cavity. This study investigated the mechanism of genistein in the VEGF-A and ER-α expression through in vivo and in silico approaches. An in vivo study was conducted by thirty-six mice that were divided into six groups including control, EM, and EM treatment with genistein with the doses of 1.3, 1.95, 2.6, and 3.25 mg/day for 14 days. Peritoneal tissues with lesions were collected and analyzed by immunohistochemistry to measure the VEGF-A and ER-α expression. The data were analyzed using a statistical approach using one-way ANOVA followed by Tukey HSD test with a significant value p < 0.05. In silico study was conducted for investigating the inhibition mechanism of genistein in VEGF-A and ER-α protein. Genistein significantly reduced the VEGF-A and ER-α expression with the optimum dose of 3.25 mg/day. Molecular docking showed that genistein inhibited VEGF-A in several active site residues of VEGF-A, also blocked the ER-α protein in estradiol binding sites. This study concluded that genistein prevented endometriosis by performing the antiangiogenic activity and showed a similar function to estradiol.

Venom composition of Trimeresurus albolabris, T. insularis, T. puniceus and T. purpureomaculatus from Indonesia

Background: Several studies have been published on the characterization of Trimeresurus venoms. However, there is still limited information concerning the venom composition of Trimeresurus species distributed throughout Indonesia, which contributes to significant snakebite envenomation cases. The present study describes a comparative on the composition of T. albolabris, T. insularis, T. puniceus, and T. purpureomaculatus venoms originated from Indonesia. Methods: Protein content in the venom of four Trimeresurus species was determined using Bradford assay, and the venom proteome was elucidated using one-dimension SDS PAGE nano-ESI- LCMS/MS shotgun proteomics. Results: The venom of T. albolabris contained the highest protein content of 11.1 mg/mL, followed by T. puniceus, T. insularis and T. purpureomaculatus venom with 10.7 mg/mL, 8.9 mg/mL and 5.54 mg/mL protein, respectively. In total, our venomic analysis identified 65 proteins belonging to 16 protein families in T. purpureomaculatus; 64 proteins belonging to 18 protein families in T. albolabris; 58 different proteins belonging to 14 protein families in T. puniceus; and 48 different proteins belonging to 14 protein familiesin T. insularis. Four major proteins identified in all venoms belonged to snake venom metalloproteinase, C-type lectin, snake venom serine protease, and phospholipase A2. There were 11 common proteins in all venoms, and T. puniceus venom has the highest number of unique proteins compared to the other three venoms. Cluster analysis of the proteins and venoms showed that T. puniceus venom has the most distinct venom composition. Conclusions: Overall, the results highlighted venom compositional variation of four Trimeresurus spp. from Indonesia. The venoms appear to be highly similar, comprising at least four protein families that correlate with venom's toxin properties and function. This study adds more information on venom variability among Trimeresurus species within the close geographic origin and may contribute to the development of optimum heterologous antivenom.(AU)

Phytochemical characteristics from Phaleria macrocarpa and its inhibitory activity on the peritoneal damage of endometriosis.

BACKGROUND: Endometriois represents a gynecological disease that still becomes an issue in community. Phaleria macrocarpa is a plant native to Indonesia that contains an antioxidant substance, which may serve as apoptotic modulator and useful for angiogenesis. OBJECTIVE: This study aims to evaluate the effects of flavonoid isolates from P. macrocarpa (PM) on the development of granulomas, apoptosis, proliferation, and angiogenesis of the disease. MATERIAL AND METHODS: Total thirty mice (Mus musculus) were categorized into six groups, including the normal group (without any treatment), EMT (endometriosis) group, and EMT group treated with PM flavonoid isolates. Identification of the active compounds of P. macrocarpa was done using LC-HRMS. Measurement of granuloma scores and vascular density was done histologically. Apoptosis and proliferation analysis was performed by immunohistochemical techniques. RESULTS: There was an increase in granulomas, proliferation, and apoptosis in the peritoneal tissues of the endometriosis model. This change can be normalized by extract of P. macrocarpa. CONCLUSION: We concluded that the flavonoid isolates from P. macrocarpa can suppress the growth of endometriosis lesions through normalization of proliferation and apoptosis. Thus, the P. macrocarpa flavonoid can be used as an alternative to inhibit the development of endometriosis.

Molecular Docking for Active Compounds of Scurrula Atropurpurea as Anti-inflammatory Candidate in Endometriosis.

INTRODUCTION: Endometriosis is still a problem for women all over the world. There are no studies that apply herbs, especially Scurrula atropurpurea to inhibit the development of inflammation in endometriosis. AIM: The purpose of this study was to analyze the docking of active ingredient of Scurrula atropurpurea on NFkB-IkB complex with IKK in silico way. MATERIAL AND METHODS: The nine active ingredients of Scurrula atropurpurea analyzed here were including aviculin (CID 10391477), caffeine (CID 2519), catechin (CID: 9064), epicatechin (CID: 72276), kaempferol (CID 5280863), quercetin (CID 5280343), quercitrin (CID 5280459)), rutin (CID 5280805), and theobromine (CID 5429). The sequence of study procedures included searching for amino acid sequences and active plant component structures, protein 3D structure modeling, docking and analysis of protein-ligand interaction. RESULTS: Regarding the NFkB-IkB complex, it was found that all active ingredients can interact where the strongest interaction sequence was rutin (-314.35 kJ/mol). Regarding the interaction between IKK and NFkB-IkB, the nine active ingredients can reduce bond energy, except rutin. CONCLUSIONS: the active ingredients of Scurrula atropurpurea having the potential effect as anti-inflammatory is rutin so that it can be isolated and used as an alternative ingredient in inhibiting inflammation in endometriosis.