Obtusifolin, an Anthraquinone Extracted from Senna obtusifolia (L.) H.S.Irwin & Barneby, Reduces Inflammation in a Mouse Osteoarthritis Model

Osteoarthritis (OA) is an age-related degenerative disease that causes cartilage dysfunction and inflammation. Obtusifolin, an anthraquinone extracted from Senna obtusifolia (L.) H.S.Irwin & Barneby seeds, has anti-inflammatory functions; it could be used as a drug component to relieve OA symptoms. In this study, we investigated the effects of obtusifolin on OA inflammation. In vitro, interleukin (IL)-1β (1 ng/mL)-treated mouse chondrocytes were co-treated with obtusifolin at different concentrations. The expression of matrix metalloproteinase (Mmp) 3, Mmp13, cyclooxygenase 2 (Cox2), and signaling proteins was measured by polymerase chain reaction and Western blotting; collagenase activity and the PGE2 level were also determined. In vivo, OA-induced C57BL/6 mice were administered obtusifolin, and their cartilage was stained with Safranin O to observe damage. Obtusifolin inhibited Mmp3, Mmp13, and Cox2 expression to levels similar to or more than those after treatment with celecoxib. Additionally, obtusifolin decreased collagenase activity and the PGE2 level. Furthermore, obtusifolin regulated OA via the NF-κB signaling pathway. In surgically induced OA mouse models, the cartilage destruction decreased when obtusifolin was administered orally. Taken together, our results show that obtusifolin effectively reduces cartilage damage via the regulation of MMPs and Cox2 expression. Hence, we suggest that obtusifolin could be a component of another OA symptom reliever.

Possibilities for treating aspirin-i lesions of the stomach and duodenum in patients with chronic coronary heart disease

To evaluate possibilities of aspirin-induced gastroduodenopathy treatment in the patients with chronic ischemic heart disease by means of applying the internal endogenous prostaglandins stimulant. Material and methods. 340 patients suffering from chronic coronary heart disease and receiving a long-term acetylsalicylic acid (ASA) therapy were examined on the base of the cardiovascular care unit of The Nizhny Novgorod Regional Clinical Hospital named after N.A. Semaschko. There were evaluated frequency, nature and severity of the aspirin-induced gastroduodenopathy. The patients with coronary heart disease and aspirin-induced gastroduodenopathy were divided in two groups. In the first group of patients there was applied rebamipide therapy (in a single daily dose 300 mg) in combination with the proton pump inhibitor (PPI) — pantoprazole. In the second group there was applied only pantoprazole therapy. For the purpose of specification of AIG pathogenetic mechanisms development, all the examined chronic coronary heart disease cases were tested on the prostaglandin E2 (PGE2) level in blood serum before the therapy beginning and after the treatment. The control group was formed of chronic coronary heart disease patients showing no AIG evidence. Statistical processing of the received data was fulfilled with the program «Statistika 10.0». Results. AIG was registered in 15% out of 340 chronic coronary heart disease patients. According to the endoscopic examination erosive disease of the body and antrum prevailed among the patients. The PGE2 level in the blood serum was significantly lower (р = 0,00087) in these patients in comparison with the control group. In association with PPI and rebamipide mixed therapy, esophagogastroduodenoscopy results showed no pathological findings in gastrointestinal mucosa and statistically significant (р = 0,00067) blood serum PGE2 level growing in all the treated patients. As a result of exclusive PPI therapy there was marked positive dynamics in endoscopic view in 19 out of 25 patients and a tendency to normalization of PGE2 level in the blood serum. However, PGE2 level growing was insignificant. Conclusion. The presented research demonstrates the possibility of AIG treatment with the use of internal endogenous prostaglandins stimulant — rebamipide in complex with proton pump inhibitor PPI therapy.

The Association between Functional Polymorphisms of COX-2 and Serum PGE2 Level in ESCC Patients in North of Iran

Background: Esophageal cancer is recognized as one of the most fatal diseases around the world. Many factors are involved in the development of esophageal cancer, including genetic factors and inflammation. Cyclooxygenase-2 (COX-2) and its downstream signaling are the most important proinflammatory factors contributing to cancer. The present study aimed to evaluate the relationship between the polymorphisms and expression of COX-2 and prostaglandin-E2 (PGE2) level in patients with esophageal squamous cell carcinoma (ESCC) in Golestan Province (Iran), situated on the “esophageal cancer belt”. Methods: In this case-control study, blood and biopsy samples were obtained from ESCC patients and healthy controls. The COX-2 polymorphisms for -1195, -1290, -765, and +8473 SNPs were assayed using PCR-RFLP assay, while the level of PGE2 was measured using an ELISA kit. In addition, real-time PCR assay and immunohistochemistry (IHC) were performed to assay mRNA and protein expression of COX-2, respectively. Results: An association was found between 8473TC genotype and risk of ESCC (OR= 5.417, P= 0.036). In addition, mRNA and protein expression of COX-2 in ESCC patients was higher than the controls (P=0.001 and P=0.048, respectively). Based on the findings, the level of PGE-2 was significantly higher in ESCC patients, compared to the controls (P= 0.045). However, ROC curve analysis revealed PGE2 is a weak biomarker for diagnosis of ESCC. There was a significant relationship between the level of PGE2 and 8473CC, 8473TC, -765CC, and -1290AA genotypes (P= 0.028, P= 0.022, P= 0.024, and P= 0.011, respectively). Conclusion: Based on our results, functional polymorphisms of COX-2 (8473CC, 8473TC, - 765CC, and -1290AA) increase PGE2 level and carriers of these polymorphisms might be more susceptible to ESCC.

Perbandingan Intensitas Nyeri dan Kadar Prostaglandin Kombinasi Tramadol dan Deksketoprofen dengan Tramadol dan Parasetamol Intravena pada Pasien Bedah Ortopedi Ekstremitas Bawah

Analgesia multimodal adalah prinsip manajemen nyeri pascaoperasi. Penelitian ini merupakan uji klinis rancangan acak tersamar ganda. Tujuan penelitian ini membandingkan efek kombinasi analgesik tramadol dan deksketoprofen dengan tramadol dan parasetamol terhadap intensitas nyeri dan kadar prostaglandin (PGE2) di RSUP Dr. Wahidin Sudirohusodo serta Rumah Sakit Jejaring di Makassar pada bulan Juli–September 2018. Empat puluh enam pasien ASA PS I dan II yang menjalani operasi ortopedi ekstremitas bawah dibagi menjadi dua kelompok. Kelompok D adalah pasien yang menerima 50 mg tramadol dengan 50 mg deksketoprofen dan kelompok P adalah pasien yang menerima 50 mg tramadol dengan 1.000 mg parasetamol intravena. PGE2 dan intensitas nyeri dicatat selama penutupan kulit sebelum pemberian obat 8 dan 16 jam sesudahnya. Data dianalisis menggunakan Uji Mann-Whitney U dan paired t-test yang sesuai. Numeric rating scale (NRS) kelompok tramadol dan deksketoprofen lebih rendah dibanding dengan kelompok tramadol dan parasetamol dengan perbedaan bermakna (p<0,05). Kadar PGE2 menurun pada kelompok tramadol dan deksketoprofen (T1–T2 p=0,009 dan T0–T2 p=0,01), sedangkan kadar PGE2 pada kelompok tramadol dan parasetamol meningkat (T2–T1 p=0,227 dan T0–T2 p=0,706). Simpulan, kombinasi tramadol dan deksketoprofen mengurangi tingkat PGE2 dan intensitas nyeri dibanding dengan kombinasi tramadol dan parasetamol. Dexketoprofen Combination and Tramadol Paracetamol Combination in Lower Limb Orthopedic SurgeryMultimodal analgesia is one of the principles of postoperative pain management. This study aimed to compare the effect of analgesic combination of tramadol dexketoprofen and tramadol paracetamol on pain intensity and prostaglandin (PGE2) level. Forty-six ASA PS I and II patients undergoing lower limb orthopedic surgery were allocated into two groups. Group D received 50 mg tramadol with 50 mg dexketoprofen and group P received 50 mg tramadol with 1,000 mg paracetamol intravenously. The PGE2 and pain intensity were recorded during skin closure prior to drug administration, 8 and 16 hours afterwards. Data were analyzed as appropriate using Mann-Whitney U and paired t-test. The NRS of two groups were significantly different where the NRS of the Tramadol Dexketoprofen group was lower than that of the tramadol and paracetamol group (NRS T1 p=0.049, NRS T2 p=0.035). The PGE2 levels decreased in the tramadol dexketoprofen groups (T1–T2 p=0.009 and T0–T2 p=0.01), whereas PGE2 levels in tramadol paracetamol group increased (T2–T1 p=0.227 and T0–T2 p=0.706). In conclusion, tramadol dexketoprofen combination reduces the PGE2 level and pain intensity as opposed to tramadol paracetamol combination.

Prostaglandin E2 and patent ductus arteriosus in premature infants

Background Patent ductus arteriosus (PDA) is a congenital heart disease most commonly occurring in premature infants. Spontaneous ductus arteriosus (DA) closure in premature infants has been suggested to be associated with duct lumen maturity and the DA sensitivity to prostaglandin E2 (PGE2).Objective To assess for a possible correlation between serum PGE2 levels and PDA size in premature infants.Methods This observational study using repeated measurements on premature infants with PDA detected at days 2-3 of life was undertaken in Cipto Mangunkusumo Hospital and Fatmawati Hospital, Jakarta, from April to May 2014. The PDA was diagnosed using 2-D echocardiography and PGE2 levels were measured by immunoassay. Pearson’s correlation test was used to evaluate a possible correlation between PGE2 level and DA diameter.Results Thirty-three premature infants of median gestational age 31 (range 28-32) weeks and median birth weight 1,360 (range 1,000-1,500) grams were enrolled. Almost two-thirds of the subjects were male. Almost all (30/33) subjects had spontaneous DA closure before the age of 10 days. Subjects’ mean DA diameter was 2.9 (SD 0.5) mm with maximum flow velocity of 0.2 (SD 0.06) cm/sec, and left atrial-to-aortic root ratio (LA/Ao) of 1.5 (SD 0.2). Their mean PGE2 levels at the ages of 2-3, 5-7, and after 10 days were 5,238.6 (SD 1,225.2), 4,178.2 (SD 1,534.5), and 915.2 (SD 151.6) pg/mL, respectively. The PGE2 level at days 2-3 was significantly correlated with DA diameter (r = 0.667; P < 0.001), but not at days 5-7 (r = 0.292; P = 0.105) or at day 10 (r = 0.041; P = 0.941).Conclusion There is a strong, positive correlation between the PGE2 level and DA diameter in preterm infants at 2-3 days of age. However, there is no significant correlation between PGE2 level and persistence of PDA.

Soy Saponins Meditate the Progression of Colon Cancer in Rats by Inhibiting the Activity of β-Glucuronidase and the Number of Aberrant Crypt Foci but Not Cyclooxygenase-2 Activity

Objective. The effect of extracted crude soybean saponins on preneoplastic lesions, aberrant crypt foci (ACF), and the related mechanism were investigated. Research Methods and Procedures. Rats were assigned into five groups according to different doses of extracted crude soybean saponins and received 1,2-dimethylhydrazine (DMH) injection in week 5. In week 15, all rats were sacrificed. The number of ACFs, the cyclooxygenase-2 (COX-2) protein expression, the level of prostaglandins E2 (PGE2), and the activity of β-glucuronidase were examined. Results. Results revealed that the consumption of extracted crude soybean saponins decreased the number of ACFs and the activity of β-glucuronidase in rats, while the expression of COX-2 protein and PGE2 level were not affected. Conclusions. Soybean saponins were effective in inhibiting colon cancer by downregulating the activity of β-glucuronidase in colonic mucosa but not the COX-2 protein expression and PGE2 level.