Diosmin Research Articles

Ovicidal and larvicidal activity of extracts from medicinal-plants against Haemonchus contortus

The use of medicinal plants (MP) containing bioactive compounds is an alternative strategy to control of parasitic nematode of small ruminants Haemonchus contortus at various stages of their life cycle. The aims of this study were to determine the in vitro anthelmintic activity of both aqueous and methanolic extracts from 13 medicinal plants typical for Central Europe, and to determine quantity of selected plant secondary metabolites (PSMs) in the methanolic extracts. In vitro egg hatch test and larval development tests were conducted to determine the possible anthelmintic effects of methanolic and aqueous extracts of the roots of Althaea officinalis L., Petasites hybridus L. and Inula helenium L.; flowers of Malva sylvestris L. and Chamomilla recutita L.; leaves of Plantago lanceolata L. and Rosmarinus officinalis L.; seeds of Foeniculum vulgare Mill. and stems of Solidago virgaurea L., Fumaria officinalis L., Hyssopus officinalis L., Melisa officinalis L. and Artemisia absinthium L. on eggs and larvae of H. contortus. Ultra-performance liquid chromatography and tandem mass spectroscopy was used for quantifying six PSMs: gallic acid (GA), rutin (RU), diosmin (DI), hesperidin (HE), quercetin (QU) and kaempferol (KA). RU content of the most effective methanolic extracts was in the order: M. sylvestris (9.33 mg/g DM) > A. absinthium (6.10 mg/g DM) > C. recutita (0.42 mg/g DM). The highest concentration of QU (44.8 mg/g DM) and KA (6.59 mg/g DM) were detected in stems of F. officinalis comparing to the other evaluated plants. The most significant (p < 0.05) anthelmintic effects exhibited methanolic extracts of A. absinthium in both in vitro tests (i.e., egg hatch test and larval development test). Additionally, only two methanolic extracts of C. recutita and M. sylvestris were comparable to activity of A. absinthium using the larval development test. Wider spectrum of aqueous extracts exhibited stronger ovicidal activity in comparison to methanolic extracts. The similar trend was observed in evaluating of larvicidal activity of aqueous and methanolic plant extracts.

Dual-targeted casein micelles as green nanomedicine for synergistic phytotherapy of hepatocellular carcinoma

In recent years, green nanomedicines have made transformative difference in cancer therapy researches. Herein, we propose dual-functionalized spray-dried casein micelles (CAS-MCs) for combined delivery of two phytochemicals; berberine (BRB) and diosmin (DSN) as targeted therapy of hepatocellular carcinoma (HCC). The nanomicelles enabled parenteral delivery of the poorly soluble DSN via its encapsulation within their hydrophobic core. Moreover, sustained release of the water soluble BRB was attained by hydrophobic ion pairing with sodium deoxycholate followed by genipin crosslinking of CAS-MCs. Dual-active targeting of MCs, via conjugating both lactobionic acid (LA) and folic acid (FA), resulted in superior cytotoxicity and higher cellular uptake against HepG2 cells compared to single-targeted and non-targeted CAS-MCs. The dual-targeted DSN/BRB-loaded CAS-MCs demonstrated superior in vivo anti-tumor efficacy in HCC bearing mice as revealed by down regulation of cell necrosis markers (NF-κB and TNF-α), inflammatory marker COX2, inhibition of angiogenesis and induction of apoptosis. Histopathological analysis and immunohistochemical Ki67 staining confirmed the superiority of the dual-targeted micelles. Ex-vivo imaging showed preferential liver-specific accumulation of dual-targeted CAS-MCs. Overall, this approach combined the benefits of traditional herbal medicine with nanotechnology via LA/FA-CAS-MCs loaded with BRB and DSN as a promising nanoplatform for targeted HCC therapy.

Hepatoprotective effects of diosmin and/or sildenafil against cholestatic liver cirrhosis: The role of Keap-1/Nrf-2 and P38-MAPK/NF-κB/iNOS signaling pathway

The present study was designed to investigate the potential protective effects of diosmin (DS) and/or sildenafil against bile duct ligation (BDL). In order to achieve this goal, BDL was performed to induce liver cirrhosis, DS (100 mg/kg/day, p.o.) and sildenafil (10 mg/kg, twice daily, p.o.) were administrated alone or in combination 24 h after the surgical operation and lasted for 4 weeks. Liver function biomarkers, fibrotic markers, oxidative stress markers, mRNA expression of NF-κB-p65, P38-MAPK, Nrf-2, and Keap-1, as well as protein expression of cytoglobin, NF-κB-p65, Nrf-2, iNOS and eNOS were investigated concomitantly with histopathological study. The results revealed that, 4 weeks of BDL induced a significant alteration in liver functions, fibrotic and oxidative stress markers. Furthermore, up-regulation of NF-κB-p65, P38-MAPK, Keap-1 and iNOS concomitantly with down-regulation of Nrf-2, cytoglobin and eNOS expressions were observed after BDL. DS and/or sildenafil treatment significantly alleviated the disturbance induced by BDL. These findings were further supported by the improvement in histopathological features. Additionally, co-administration of DS and sildenafil were found to significantly improved liver defects due to BDL as compared to the individual drugs. It can be concluded that, DS and sildenafil exhibit hepatoprotective effects through modulation of Keap-1/Nrf-2 and P38-MAPK/NF-κB/iNOS pathway.

Targeting Keap-1/Nrf-2 pathway and cytoglobin as a potential protective mechanism of diosmin and pentoxifylline against cholestatic liver cirrhosis

AimThe effects of diosmin (DS), pentoxifylline (PTX) and their combination on inflammatory response, oxidant/antioxidant balance, cytoglobin and cirrhotic reaction during bile duct ligation (BDL) were investigated and explored. Main methodsFifty adult male Wistar albino rats were randomly allocated to five groups as following, sham: received vehicle only, BDL: subjected to common BDL without treatment, BDL plus DS: received 100 mg/kg/day orally, BDL plus PTX: received 50 mg/kg/day orally, BDL plus DS plus PTX: received DS and PTX in the same manner. The test period lasted 28 days, liver tissues and blood samples were collected to investigate biochemical markers (liver function biomarkers, oxidative stress markers, and antifibrotic markers), mRNA expression of Nrf-2, Keap-1, NF-κB-p65 and p38-MAPK by real-time PCR, protein expression of cytoglobin and NF-κB-p65 by western blot and iNOS and eNOS by immunohistochemistry. Histopathological study was performed to confirm our results. Key findingsChronic BDL induced a significant alteration in liver functions, oxidative stress and fibrotic markers. Furthermore, unfavorable effects on gene and protein expression were observed after BDL. Histopathological findings of this group showed parallel effects. DS, PTX and their combination treatment significantly ameliorated the disturbance that occurred due to BDL. Similar findings were observed in liver histopathology. SignificanceDS and PTX could mitigate liver cirrhosis through modulation of Keap-1/Nrf-2/GSH and NF-κB-p65/p38-MAPK signaling pathways. In addition, we demonstrated that the hepatoprotective effect of DS and PTX is mediated by up-regulation of cytoglobin with inhibition of fibrotic reaction.

Comparative periodontoprotective effectiveness of diosmin or qvercetin in rats which received hormonal contraceptive

Aim: Determine periodontoprotective effectiveness of bioflavonoides diosmin and quercetin after introducing hormonal contraceptive. Methods: The rats received contraceptive (estradiol+drospirenon) during 30 days. Preparation of diosmin (“Normoven”) introduced per os in dose 84 mg/kg. Preparation of quercetin (“Quertulin”) introduced per os in dose 8 mg/kg. The activities of elastase and lysozyme were determined in gum and serum, the activities of alkaline (AlPh) and acid (AcPh) phosphatases, the contents of calcium and protein were determined in periodontal bone. The degree of bone atrophy of alveolar outgrowth was determined. Results: Was established that the introduction of the contraceptive decreased the mineralizing activity of the bone and increased the degree of atrophy of alveolar outgrowth. Simultaneous introduction of the bioflavonoides stimulated mineralizing activity and reduced the degree of atrophy of alveolar bone. Quercetin was more effective. Conclusion: Bioflavonoides have periodontoprotective activity after using hormonal contraceptive.

Use of multiresponse statistical techniques to optimize the separation of diosmin, hesperidin, diosmetin and hesperitin in different pharmaceutical preparations by high performance liquid chromatography with UV-DAD

A new method for the separation and determination of four flavonoids: hesperidin (HES), diosmin (DIO), hesperitin (HTIN), and diosmetin (DTIN) in pure form and pharmaceutical formulations has been developed by using high performance liquid chromatography (HPLC) with UV-DAD detection. Multivariate statistics (2k full factorial and Box Behnken Designs) has been used for the multiresponse optimization of the chromatographic separation, which was completed in 22min, and carried out on a symmetry® C18 column (250×3mm; 5µm) as stationary phase. Separation was conducted by gradient elution mode using a mixture of methanol, acetonitrile and water pH: 2.5 (CH3COOH), as mobile phase. Analytes were separated setting the column at 22°C, with a flow rate of 0.58mLmin−1 and detected at 285nm. Under the optimized conditions, the flavonoids showed retention times of: 8.62, 11.53, 18.55 and 19.94min for HES, DIO, HTIN and DTIN, respectively. Limits of detection and quantification were <0.0156µgmL−1 and <0.100µgmL−1, respectively. Linearity was achieved with good correlation coefficients values (r2=0.999; n=5). Intra-day and inter-day precision were found to be less than 3.44% (n=7). Finally, the proposed method was successfully applied to determine the target flavonoids in pharmaceutical preparations with satisfactory recoveries (between 95.2% and 107.9%), demonstrating that should also find application in the quality control, as well as in the pharmacokinetic studies of these drugs.

Anti-inflammatory, antioxidant and anti-apoptotic activity of diosmin in acetic acid-induced ulcerative colitis.

This study aimed to evaluate the effects of diosmin (DIO) on UC. UC was induced in rats by rectal administration of acetic acid (AA). The degree of mucosal ulceration and damage was determined by evaluating the disease activity index (DAI) and colon damage index scores. Inflammation, oxidative stress and apoptotic responses were determined by measuring the levels of tumour necrosis factor-α (TNF-α), cyclooxygenase-2 (COX-II), malondialdehyde (MDA) and reduced glutathione (GSH) in addition to myeloperoxidase (MPO) activity and caspase-3 expression. The results of this study indicate that AA caused increase in DAI and colon damage index scores. Also, markers of inflammation (TNF-α, COX-II and MPO) and oxidative stress (MDA and reduced GSH) were significantly elevated. These changes were associated with increases in colon caspase-3 expression. Treatment of rats with two doses of DIO produced a dose-dependent decline in DAI and colon damage index scores. Also, DIO resulted in significant reduction of inflammatory and oxidative stress markers as well as reduced the expression of caspase-3. DIO therapy decreased UC development depending on its ability to decreases inflammation, oxidative stress and apoptosis in rat colon.

Influence of diosmin on the metabolism and disposition of carbamazepine in healthy subjects

1. Carbamazepine (CBZ) is an antiepileptic drug with narrow therapeutic window and administration in humans receiving long-term therapy with diosmin (DSN) may occur, which leads to CYP3A4-mediated drug interactions. The purpose of the present study was to assess the influence of DSN on the metabolism and pharmacokinetics of CBZ in healthy volunteers.2. An open-label, sequential, two-period study was conducted in 12 healthy male volunteers. A single dose of DSN 500 mg was administered once daily for 10 days during treatment phase. A single dose of CBZ 200 mg was administered during control and after treatment phases under fasting conditions. The blood samples were collected after CBZ dosing at predetermined time intervals and analyzed by LC-MS/MS.3. Treatment with DSN significantly enhanced the maximum plasma concentration (Cmax), area under the curve (AUC), half-life (t1/2) and significantly decreased the apparent oral clearance (CL/F) and elimination rate constant (Kel) of CBZ. On the other hand, treatment with DSN significantly decreased the Cmax and AUC of carbamazepine 10, 11-epoxide (CBZE). Furthermore, treatment with DSN significantly decreased the metabolite to parent ratios of Cmax and AUC, indicating the reduced metabolism of CBZ to CBZE.4. The results suggest that the altered CYP3A4 enzyme activity and pharmacokinetics of CBZ might be attributed to DSN-mediated inhibition of CYP3A4 enzyme, which indicates pharmacokinetic interaction present between DSN and CBZ. Therefore, we conclude that DSN has an inhibiting effect on the metabolism and disposition of CBZ.

The effect of diosmin on the pharmacokinetics of fexofenadine in healthy human volunteers

1. Diosmin (DSN) has been found to possess P-glycoprotein (P-gp) inhibition activity in vitro and in vivo in rats, which may have potential to cause P-gp-mediated interactions in humans. The purpose of the present study was to investigate the effect of DSN on pharmacokinetics of fexofenadine (FEX) in healthy human volunteers.2. An open-label, two-period, sequential study was conducted in 12 healthy male volunteers. A single dose of FEX 120 mg was administered to volunteers during control and treatment phases. A single dose of DSN 500 mg was administered to volunteers daily for period of 10 days. The blood and urine samples were collected at predetermined time intervals after FEX dosing and analyzed by LC-MS/MS.3. Treatment with DSN significantly increased the peak maximum plasma concentration (Cmax) and area under the plasma concentration–time curve (AUC) of FEX by 49.2% (523.28 versus 780.63 ng/mL) and 64.4% (3459.48 versus 5687.74 ng h/mL), respectively as compared to control phase. On the other hand, apparent oral clearance (CL/F) of FEX was significantly decreased by 41.3% (37.03 versus 21.75 L/h) and there was no significant change was observed in Tmax, T1/2, and CLr (renal clearance) upon treatment with DSN when compared to control.4. The results suggest that altered pharmacokinetics of FEX might be attributed to DSN-mediated inhibition of P-gp-mediated efflux in humans. Therefore, we conclude that intake of DSN or dietary supplements containing DSN may potentially increase the absorption or bioavailability of FEX, a P-gp substrate in humans.

Simultaneous determination of four vasoactive phytochemicals in different pharmaceutical preparations by a simple HPLC-DAD method

A new, simple isocratic HPLC method was developed and validated for the simultaneous estimation of four vasoactive phytochemicals: ascorbic acid (ASC), rutin (RUT), hesperidin (HSP), and diosmin (DSM) in different pharmaceutical preparations.

Diosmin protects against ethanol-induced gastric injury in rats: novel anti-ulcer actions.

Alcohol consumption has been commonly associated with gastric mucosal lesions including gastric ulcer. Diosmin (DIO) is a natural citrus flavone with remarkable antioxidant and anti-inflammatory features that underlay its protection against cardiac, hepatic and renal injuries. However, its impact on gastric ulcer has not yet been elucidated. Thus, the current study aimed to investigate the potential protective effects of DIO against ethanol-induced gastric injury in rats. Pretreatment with DIO (100 mg/kg p.o.) attenuated the severity of ethanol gastric mucosal damage as evidenced by lowering of ulcer index (UI) scores, area of gastric lesions, histopathologic aberrations and leukocyte invasion. These actions were analogous to those exerted by the reference antiulcer sucralfate. DIO suppressed gastric inflammation by curbing of myeloperoxidase (MPO) and tumor necrosis factor-α (TNF-α) levels along with nuclear factor kappa B (NF-κB) p65 expression. It also augmented the anti-inflammatory interleukin-10 (IL-10) levels. Meanwhile, DIO halted gastric oxidative stress via inhibition of lipid peroxides with concomitant enhancement of glutathione (GSH), glutathione peroxidase (GPx) and the total antioxidant capacity (TAC). With respect to gastric mucosal apoptosis, DIO suppressed caspase-3 activity and cytochrome C (Cyt C) with enhancement of the anti-apoptotic B cell lymphoma-2 (Bcl-2) in favor of cell survival. These favorable actions were associated with upregulation of the gastric cytoprotective prostaglandin E2 (PGE2) and nitric oxide (NO). Together, these findings accentuate the gastroprotective actions of DIO in ethanol gastric injury which were mediated via concerted multi-pronged actions, including suppression of gastric inflammation, oxidative stress and apoptosis besides boosting of the antioxidant and the cytoprotective defenses.

Diosmin protects against cerebral ischemia/reperfusion injury through activating JAK2/STAT3 signal pathway in mice

Background and objectApoptosis is a major form of cell death in cerebral ischemia/reperfusion (I/R) pathogenesis and may represent a target for treatment. Diosmin (DM), a micronized purified flavonoid drug, possesses an anti-apoptotic effect in the treatment of varicose veins and renal injury. However, the effect of DM in the acute phase of cerebral I/R is not clear. This study investigated DM’s role in cerebral I/R and its potential mechanism. MethodsMale CD-1 mice were subjected to transient middle cerebral artery occlusion (tMCAO). Experiment 1 was used to evaluate the time course expression of Janus tyrosine kinase-2 (JAK2), signal transducer and activator of transcription-3 (STAT3), phosphorylated JAK2 (pJAK2) and phosphorylated STAT3 (pSTAT3) after cerebral I/R, and six time points were included. In experiment 2, DM was given orally at doses of 50mg/kg or 100mg/kg for 6 consecutive days before receiving tMCAO. At 24h after reperfusion, neurological deficit, Nissl staining, brain water content and infarct volume were examined. Bcl-2, Bax, pJAK2, and pSTAT3 were detected by immunohistochemistry, qRT-PCR and Western blot. Confocal microscope was used to observe the location of pSTAT3 in the cerebral cortex. ResultsCompared with Vehicle group, the high dose of DM significantly alleviated neurological deficit, brain water content, infarct volume, increased the Nissl-positive cells, upregulated the expression of pJAK2, pSTAT3 and Bcl-2 and downregulated Bax (P<0.05). ConclusionThese results showed that DM protected against cerebral I/R injury through activating JAK2/STAT3 signal pathway.

Diosmin protects against TCE (trichloroethylene) induced renal injury in Wistar rats: Plausible role of p53, Bax and caspases

Diosmin (DM) is a naturally occurring flavone and has been found to possess numerous therapeutic properties. In this study, we used DM as a protective agent against the nephrotoxic effects of the environmental toxicant trichloroethylene (TCE). Male Wistar rats were divided into five groups (I–V, n 6). Groups II, III and IV received an oral administration of TCE at a dose of 1000 mg/kg body weight for twenty consecutive days. The animals in groups II and III received an oral treatment of DM at doses of 20 and 40 mg/kg body weight, respectively, for twenty consecutive days, while groups I and V were given maize oil (5 ml/kg body weight and DM 40 mg/kg body weight, respectively) for 20 d. The protective effects of DM on TCE-induced oxidative stress and caspase-dependent apoptosis were investigated by assaying oxidative stress biomarkers, lipid peroxidation (LPO), serum toxicity markers, alkaline unwinding assay, caspase-3, -7 and -9, Bax and p53 expression. Oral administration of TCE in rats enhanced renal LPO, depleted glutathione content and antioxidant enzymes, induced DNA strand breaks (P,0·001), modulated the expression of Bax and p53 protein and induced the expression of caspase-3, -7 and -9. Co-treatment with DM prevented oxidative stress by restoring the levels of antioxidant enzymes; furthermore, a significant dose-dependent decrease in DNA disintegration and kidney toxicity markers such as blood urea N, creatinine, lactate dehydrogenase and kidney injury molecule-1 was observed. DM also effectively decreased the TCE-induced up-regulation of Bax and p53. Data from the present study establish the protective role of DM against TCE-induced renal damage.

Development of novel polymer-stabilized diosmin nanosuspensions: In vitro appraisal and ex vivo permeation

Scanty solubility and permeability of diosmin (DSN) are perpetrators for its poor oral absorption and high inter-subject variation. This article investigated the potential of novel DSN nanosuspensions to improve drug delivery characteristics. Bottom-up nanoprecipitation technique has been employed for nanosuspension development. Variables optimized encompassed polymeric stabilizer type, DSN: stabilizer ratio, excess stabilizer removal, spray drying, and mannitol incorporation. In vitro characterization included particle size (PS), infrared spectroscopy (IR), differential scanning calorimetry (DSC), X-ray powder diffraction (XRD), transmission electron microscope (TEM), scanning electron microscopy (SEM), and dissolution profile. Ex vivo permeation was assessed in rats using non-everted sac technique and HPLC. Optimal DSN nanosuspension (DSN:hydroxypropylmethyl cellulose HPMC 2:1) was prepared with acid base neutralization technique. The formula exhibited the lowest PS (336 nm) with 99.9% drug loading and enhanced reconstitution properties after mannitol incorporation. SEM and TEM revealed discrete, oval drug nanocrystals with higher surface coverage with HPMC compared to MC. DSN nanosuspension demonstrated a significant enhancement in DSN dissolution (100% dissolved) compared to crude drug (51%). Permeation studies revealed 89% DSN permeated from the nanosuspension after 120 min compared to non-detected amounts from drug suspension. Conclusively, novel DSN nanosuspension could successful improve its dissolution and permeation characteristics with promising consequences of better drug delivery.

Egypt withdrawals Diosmin 150mg

Egypt withdrawals Diosmin 150mg

Binding of an anticancer Rutaceae plant flavonoid glycoside with calf thymus DNA: Biophysical and electrochemical studies

In the present work, we report the interaction of a bioactive Rutaceae plant flavonoid glycoside, diosmin (DIO) with calf thymus DNA employing ethidium bromide as a fluorescence probe. The mode of binding between DIO and DNA was investigated by UV absorption, fluorescence, 3D-fluorescence, fluorescence polarization, FT-IR, circular dichroism, melting temperature (Tm) measurements and differential pulse voltammogram studies. The results revealed the intercalative mode of binding between DIO and DNA. Further, the values of thermodynamic parameters, ∆H° (−388.32kJmol−1) and ∆S° (−1.22kJmol−1K−1) indicated that the van der Waals forces and hydrogen bond played a major role in the binding of DIO to DNA. The observed negative ∆G° values revealed the spontaneity of interaction process. The binding of DIO to DNA–EB was found to be stronger in the presence of coexisting substances.

Diosmin protects against trichloroethylene-induced renal injury in Wistar rats: plausible role of p53, Bax and caspases

Diosmin (DM) is a naturally occurring flavone and has been found to possess numerous therapeutic properties. In this study, we used DM as a protective agent against the nephrotoxic effects of the environmental toxicant trichloroethylene (TCE). Male Wistar rats were divided into five groups (I-V, n 6). Groups II, III and IV received an oral administration of TCE at a dose of 1000 mg/kg body weight for twenty consecutive days. The animals in groups II and III received an oral treatment of DM at doses of 20 and 40 mg/kg body weight, respectively, for twenty consecutive days, while groups I and V were given maize oil (5 ml/kg body weight and DM 40 mg/kg body weight, respectively) for 20 d. The protective effects of DM on TCE-induced oxidative stress and caspase-dependent apoptosis were investigated by assaying oxidative stress biomarkers, lipid peroxidation (LPO), serum toxicity markers, alkaline unwinding assay, caspase-3, -7 and -9, Bax and p53 expression. Oral administration of TCE in rats enhanced renal LPO, depleted glutathione content and antioxidant enzymes, induced DNA strand breaks (P<0·001), modulated the expression of Bax and p53 protein and induced the expression of caspase-3, -7 and -9. Co-treatment with DM prevented oxidative stress by restoring the levels of antioxidant enzymes; furthermore, a significant dose-dependent decrease in DNA disintegration and kidney toxicity markers such as blood urea N, creatinine, lactate dehydrogenase and kidney injury molecule-1 was observed. DM also effectively decreased the TCE-induced up-regulation of Bax and p53. Data from the present study establish the protective role of DM against TCE-induced renal damage.

Lyophilized phytosomal nanocarriers as platforms for enhanced diosmin delivery: optimization and ex vivo permeation

Diosmin (DSN) is an outstanding phlebotonic flavonoid with a tolerable potential for the treatment of colon and hepatocellular carcinoma. Being highly insoluble, DSN bioavailability suffers from high inter-subject variation due to variable degrees of permeation. This work endeavored to develop novel DSN loaded phytosomes in order to improve drug dissolution and intestinal permeability. Three preparation methods (solvent evaporation, salting out, and lyophilization) were compared. Nanocarrier optimization encompassed different soybean phospholipid (SPC) types, different solvents, and different DSN:SPC molar ratios (1:1, 1:2, and 1:4). In vitro appraisal encompassed differential scanning calorimetry, infrared spectroscopy, particle size, zeta potential, polydispersity index, transmission electron microscopy, drug content, and in vitro stability. Comparative dissolution studies were performed under sink versus non-sink conditions. Ex vivo intestinal permeation studies were performed on rats utilizing noneverted sac technique and high-performance liquid chromatography analysis. The results revealed lyophilization as the optimum preparation technique using SPC and solvent mixture (Dimethyl sulphoxide:t-butylalchol) in a 1:2 ratio. Complex formation was contended by differential scanning calorimetry and infrared data. Optimal lyophilized phytosomal nanocarriers (LPNs) exhibited the lowest particle size (316 nm), adequate zeta-potential (−27 mV), and good in vitro stability. Well formed, discrete vesicles were revealed by transmission electron microscopy, drug content, and in vitro stability. Comparative dissolution studies were performed. LPNs demonstrated significant enhancement in DSN dissolution compared to crude drug, physical mixture, and generic and brand DSN products. Permeation studies revealed 80% DSN permeated from LPNs via oxygenated rat intestine compared to non-detectable amounts from suspension. In this study, LPNs (99% drug loading) could be successfully tailored for DSN with improved dissolution and permeation characteristics, which is promising for lowering the influence of exogenous factors and increasing drug delivery.

Antihyperlipidemic effect of diosmin: A citrus flavonoid on lipid metabolism in experimental diabetic rats

The present study was hypothesized to evaluated the antihyperlipidemic effect of diosmin (DS) on lipid metabolism in experimental diabetic rats. Diabetes was induced male albino Wistar rats by intraperitoneal administration of streptozotocin (STZ) (45mg/kg b.w.) 15min after the ip administration of nicotinamide (NA) (110mg/kg b.w.). DS were administered to diabetic rats intragastrically at 100mg/kg b.w. for 45days. The levels of plasma and tissue lipids (cholesterol, triglycerides) (TGs), free fatty acids (FFAs) and phospholipids (PLs), low density, very low-density lipoproteins (LDL and VLDL), and high-density-cholesterol (HDL-C) were measured. The activities of 3-hydroxy 3-methylglutaryl coenzyme A (HMG-CoA) reductase, lipoprotein lipase (LPL) and lecithin cholesterol acyl transferase (LCAT) were assayed. The levels of plasma and tissue lipids decreased with significant increase in HDL-C levels. The altered activities of lipid metabolic enzymes were restored to near normal. The present findings suggest that DS can potentially ameliorate lipid abnormalities in experimental diabetes.

Ameliorative effect of diosmin, a citrus flavonoid against streptozotocin-nicotinamide generated oxidative stress induced diabetic rats

Oxidative stress has been suggested as a contributory factor in development and complication of diabetes. The aim of the study was to evaluate the effect of diosmin (DS) in oxidative stress in streptozotocin-nicotinamide (STZ-NA)-induced diabetic rats by measuring the lipid peroxidation (LPO) as well as the ameliorative properties. Experimental diabetes was induced by a single intraperitoneal (i.p) injection of STZ (45mg/kg body weight (b.w.)) dissolved in 0.1mol/L citrate buffer (pH 4.5), 15min after the i.p administration of NA (110mg/kg b.w.). Diabetic rats exhibited increased plasma glucose with significant decrease in plasma insulin levels. The activities of antioxidant enzymes superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), glutathione-S-transferase (GST) and the levels of low-molecular weight antioxidants vitamin C, vitamin E and reduced glutathione (GSH) were decreased while increases in the levels of LPO markers were observed in liver and kidney tissues of diabetic control rats as compared to normal control rats. Oral treatment with DS (100mg/kg/day) for a period of 45days showed significant ameliorative effects on all the biochemical parameters studied. Biochemical findings were supported by histological studies. These results indicated that DS has potential ameliorative effects in addition to its antidiabetic effect in type 2 diabetic rats.