Antioxidant,anticancer activities and mechanistic studies of the flavone glycoside diosmin and its oxidovanadium(IV) complex. Interactions with bovine serum albumin

The natural antioxidant flavonoid diosmin, found in citric fruits, showed low antioxidant properties among other flavonoids due to its structural characteristics and low cytotoxicity against lung (A549) and breast (T47D, SKBR3 and MDAMB231) cancer cell lines. The anticancer behavior has been improved by the metal complex generated with the flavonoid and the oxidovanadium(IV) ion. This new complex, [VO(dios)(OH)₃]Na₅·6H₂O (VOdios), has been synthesized and characterized both in solid and solution states. The interaction of the metal ion through the sugar moiety of diosmin precluded the improvement of the antioxidant effects. However, the cell-killing effects tested in human lung A549 and breast T47D, SKBR3 and MDAMB231 cancer cell lines, were enhanced by complexation. The anti-proliferative effects on the human lung cancer cell line were accompanied by cellular ROS generation and an increase in cytoplasm condensation. The breast cancer cell lines did not produce caspase3/7 activation, mitochondrial potential reduction and ROS generation. Therefore, a non-apoptotic form of cell death in a caspase- and oxidative stress-independent manner has been proposed. The protein binding ability has been monitored by the quenching of tryptophan emission in the presence of the compounds using bovine serum albumin (BSA) as a model protein. Both compounds could be distributed and transported in vivo and the complex displayed stronger binding affinity and higher contributions to the hydrogen bond and van der Waals forces.     

Diosmin exerts hepatoprotective and antihyperglycemic effects against sodium arsenite-induced toxicity through the modulation of oxidative stress and inflammation in mice

BackgroundChronic exposure to high concentrations of inorganic arsenic (NaAsO₂) in drinking water is related to an increase in the risk of liver toxicity and diabetes. Diosmin has various pharmacological properties, including antioxidant and anti-inflammatory properties. This study was designed to investigate the protective effects of diosmin on diabetes and hepatotoxicity caused by NaAsO₂.MethodsSixty male 8-week-old NMRI mice, weighing 25 ± 2 g, were randomly selected and put into six groups. The control (Group 1) was treated orally with distilled water, group 2 was treated with diosmin (100 mg/kg, p.o), group 3 received NaAsO₂ (10 mg/kg, p.o), and groups 4, 5, 6 received diosmin (25, 50, 100 mg/kg, p.o), respectively and NaAsO₂ (10 mg/kg, p.o). After 29 days, fasting blood sugar (FBS) measurement and glucose tolerance test were done. The mice were sacrificed on day 31, and blood and tissue (liver and pancreas) samples were taken. Then, serum and tissue samples were studied for biochemical and histological evaluations.ResultsThe results demonstrated that diosmin ameliorated glucose intolerance and decreased FBS compared to the NaAsO₂ group. Diosmin (50 and 100 mg/kg) improved the serum factors of liver function (alanine aminotransferase, aspartate transaminase, and alkaline phosphatase) in the groups receiving NaAsO₂. Moreover, increased levels of nitric oxide, tumor necrosis factor-alpha, and thiobarbituric acid reactive substances in liver tissue induced by NaAsO₂ were diminished by diosmin treatment. Administration of diosmin increased total thiol and enzymatic activities of catalase, superoxide dismutase, and glutathione peroxidase in liver tissue. Furthermore, treatment with diosmin reduced the increase in protein amount of Sirtuin 3 and nuclear factor kappa B in the groups receiving NaAsO₂. Also, the liver and pancreas histological lesions induced by NaAsO₂ were attenuated by diosmin treatment.ConclusionDiosmin has a preventive effect against hepatotoxicity and diabetes induced by NaAsO₂ in mice through its antioxidant and anti-inflammatory properties.     

自拟温阳利水汤联合地奥司明治疗乳腺癌术后上肢淋巴水肿的疗效观察

摘要 目的：探究自拟温阳利水汤联合地奥司明治疗乳腺癌术后上肢淋巴水肿的疗效。方法：选择2013年1月至2019年6月在我院经病理确诊为乳腺癌术后上肢淋巴水肿的住院患者80例,根据治疗方式不同分为两组,每组各40例,其中,对照组采用地奥司明进行治疗,研究组在对照组基础上联合自拟温阳利水汤进行治疗,两组均连续治疗15 d;对比两组的治疗总有效率,对比两组治疗前后的腕横纹、肘横纹、腕横纹上10 cm、肘横纹上10 cm处臂围;对比两组患者治疗前后的前屈、后伸、外展、内收等活动角度。结果：研究组治疗总有效率95.00 %（38/40）显著高于对照组75.00 %（30/40）,对比有显著差异（P＜0.05）;治疗前,两组的腕横纹、肘横纹、腕横纹上10 cm、肘横纹上10 cm处臂围对比无统计学差异（P＞0.05）;治疗后,两组的腕横纹、肘横纹、腕横纹上10 cm、肘横纹上10 cm处臂围均比治疗前有所减小,且研究组更小（P＜0.05）;治疗前,两组的前屈、后伸、外展、内收等活动角度对比无统计学差异（P＞0.05）;治疗后,两组患者的前屈、后伸、外展、内收等活动角度均比治疗前有所增大,且研究组更大（P＜0.05）。结论：自拟温阳利水汤联合地奥司明治疗乳腺癌术后上肢淋巴水肿的疗效显著,该方法可有效改善患者的肩关节活动度,临床应用价值较高。     

Protective effect of diosmin against doxorubicin-induced nephrotoxicity

Doxorubicin (Dox) is an anthracycline antibiotic that is primarily used for treating various solid tumors including that of pulmonary, ovary, breast, uterine, cervix, and several blood cancers. However, nephrotoxicity associated with Dox treatment limits its clinical use. Administration of Dox in combination with compounds exhibiting antioxidant properties are being used to minimize the side effects of Dox. Diosmin is a flavonoid glycoside with numerous beneficial properties that is found in the pericarp of many citrus fruits. Diosmin has demonstrated antioxidant, anti-inflammatory, and anti-apoptotic effects in response to various insults, although the exact mechanism remains unknown. Therefore, this study was designed to evaluate the effect of diosmin in preventing kidney damage in response to Dox treatment. Male Wistar rats were randomly divided into four groups: control group, Dox group (20 mg/kg, i.p.), Dox plus low-dose diosmin group (100 mg/kg orally), and Dox plus high-dose diosmin group (200 mg/kg orally). A single intraperitoneal injection of Dox resulted in kidney damage as evidenced by significant alterations in kidney markers, histological abnormalities, and the attenuation of antioxidant defense mechanisms (GSH, SOD, and CAT). Moreover, Dox treatment significantly altered the expression of oxidative stress, inflammatory, and anti-apoptotic protein markers. Diosmin pretreatment alleviated Dox-induced nephrotoxicity by ameliorating the antioxidant mechanism, decreasing inflammation and apoptosis, and restoring kidney architecture. In conclusion, our results indicate that diosmin is a promising therapeutic agent for the prevention of nephrotoxicity associated with DOX.     

吻合器痔上黏膜环切术联合地奥司明对混合痔患者肛肠动力学及血清炎症因子的影响

摘要 目的：探讨吻合器痔上黏膜环切术（PPH）联合地奥司明对混合痔患者肛肠动力学及血清炎症因子的影响。方法：选择2018年5月~2021年5月期间我院收治的混合痔患者115例,随机分为2组：对照组（57例）、观察组（58例）,对照组给予PPH治疗,观察组给予PPH联合地奥司明治疗,比较两组疗效、症状评分、肛肠动力学指标及血清炎症因子水平,记录随访期间复发情况。结果：观察组的临床总有效率较对照组高（P<0.05）。观察组术后3个月的直肠感觉阈、直肠耐受量高于对照组,直肠-肛管压力差低于对照组（P<0.05）。观察组术后7 d的血清C反应蛋白（CRP）、肿瘤坏死因子-α（TNF-α）和白介素-6（IL-6）水平均低于对照组（P<0.05）。观察组术后3个月的肛周出血评分、 肛缘水肿评分、肛周瘙痒评分均低于对照组（P<0.05）。观察组的复发率较对照组更低（P<0.05）。结论：混合痔患者在PPH术后给予地奥司明治疗,可明显改善术后症状和机体肛肠动力学,并降低血清炎症因子水平,同时还可减少复发率,临床疗效值得肯定。     

Antihyperlipidemic potential of diosmin in Swiss Albino mice with high-fat diet induced hyperlipidemia

The aim of this study was to investigate the antihyperlipidemic potential of Diosmin (DS) in mice fed with a high-fat diet (HFD). Animals were divided in five groups (n = 6). The total duration of the study was 90 days split into two intervals. During the first 45-day interval, mice were administered with HFD, whereas during the second 45-day interval they were co-administered HFD plus DS or the standard drug atorvastatin. DS was administered at the dose of 100 and 200 mg/kg;p.o. DS treatment to HFD-induced hyperlipidemic mice caused significant decrements in the levels of total cholesterol, triglycerides, LDL-C and VLDL-C. Moreover, DS resulted in significant increase in the levels of HDL-C and improvements in total protein levels, whereas it caused remarkable decreases in SGOT, SGPT and ALP enzymatic activities in hyperlipidemic mice. Histopathological examination of hyperlipidemic mice revealed a disorganized hepatic tissue, fatty changes, and mononuclear cell infiltration, which were all ameliorated by DS administration. The results revealed that DS possesses potential ameliorating benefits again.st hyperlipidemia induced by HFD on lipid profile, liver function enzymes and hepatic histoarchitecture. Further investigations are highly recommended and clinical trials are warranted in order to assess the efficacy and to fully dissect the mode-of-action underpinning the observed antihyperlipidemic effect of DS.     

Diosmin binding to human serum albumin and its preventive action against degradation due to oxidative injuries

Diosmin is a glycosylated polyphenolic compound, commonly found in fruits and vegetables, which is utilized for the pharmacological formulation of some drugs. The interactions of diosmin to human serum albumin have been investigated by fluorescence, UV–visible, FTIR spectroscopy, native electrophoresis and protein–ligand docking studies. The fluorescence studies indicate that the binding site of the additive involves modifications of environment around Trp214 at the level of subdomain IIA. Combining the curve-fitting results of infrared Amide I′ band, the modifications of protein secondary structure have been estimated, indicating a decrease in α-helix structure following flavonoid binding. Data obtained by fluorescence and UV–visible spectroscopy, FTIR experiments and molecular modeling afforded a clear picture of the association mode of diosmin to HSA, suggesting that the primary binding site of diosmin is located in Sudlow's site I. Computational mapping confirms this observation suggesting that the possible binding site of diosmin is located in the hydrophobic cavity of subdomain IIA, whose microenvironment is able to help and stabilize the binding of the ligand in non-planar conformation. Moreover the binding of diosmin to HSA significantly contributes to protect the protein against degradation due to HCLO and Fenton reaction.