Potential of Moringa oleifera root and Citrus sinensis fruit rind extracts in the treatment of ulcerative colitis in mice

Context: The plant Moringa oleifera Lam (Moringaceae), commonly known as the drumstick tree, is an indigenous species in India. This species has been of interest to researchers because traditionally its roots are reported in the treatment of ulcerative colitis (UC). Traditionally it is reported that Citrus sinensis Linn (Rutaceae) fruit rind when combined with M. oleifera will increase the efficacy of the plant in the treatment of UC.

Objective: The present work was undertaken to determine the effectiveness of M. oleifera root alone and in combination with C. sinensis fruit rind in the treatment of UC.

Materials and methods: Ethanol and aqueous extracts of M. oleifera roots (100 and 200?mg/kg, body weight) were screened alone and in equal combination with ethanol extract of C. sinensis fruit rind, i.e., 50?mg/kg each of C. sinensis and M. oleifera for their activity on acetic acid-induced UC in mice.

Results: Treatment with combination of extracts of M. oleifera root and C. sinensis fruit rind (50?mg/kg, each) showed less ulceration and hyperemia than individual extract (200?mg/kg) in histopathological observation. Acetic acid increased myeloperoxidase (MPO) level in blood and colon tissue to 342?U/mL and 384?U/mg, respectively. Combination of ethanol extract of M. oleifera root with C. sinensis fruit rind extract significantly (p?<?0.05) decreased MPO in blood and tissue to 278?U/mL and 291?U/mg, respectively. MPO in blood and tissue in control group was 85?±?1.2?U/mL and 96?±?1.3?U/mg, respectively. Similarly this combination significantly reduced malondialdehyde (MDA) level in blood and tissue to 7.11 nmol/mL and 8.19 nmol/mg, from 11.20 nmol/mL and 13.20 nmol/mg, respectively. MDA in blood and tissue in control group was 2.76?±?1.2 nmol/mL and 3.76?±?1.2 nmol/mg, respectively.

Discussion and conclusion: Results show that a combination of M. oleifera root extracts with C. sinensis fruit rind extract is effective in the treatment of UC and results are comparable with the standard drug prednisolone.     

Potential of the plant Thespesia populnea in the treatment of ulcerative colitis

Abstract

Context: Thespesia populnea Sol. ex Correa (Malvaceae), an indigenous tree species in India, is of interest to researchers because traditionally its heartwood is used in the treatment of ulcer and colic pain.

Objective: To validate its folk use in the treatment of ulcerative colitis (UC).

Materials and methods: Mice were administered intrarectal DNBS and then treated with different plant extracts (100 and 200?mg/kg), 30?min before and 24 and 48?h after DNBS infusion. Colonic mucosal injury was assessed by macroscopic and histological examination. Furthermore, malondialdehyde (MDA), myeloperoxidase (MPO), protease, and hemoglobin (Hb) contents were measured in tissue and blood samples.

Results: Administration of various extracts ameliorated macroscopic and microscopic scores which were altered due to DNBS treatment in mice. Hb concentration in blood was restored significantly by the aqueous extract to 17.20?±?0.5, which was reduced to 13.80?±?0.5 after treatment with DNBS. MDA level was increased to 10.82?nm/mg and 10.25?nm/ml in tissue and blood, respectively, due to DNBS treatment which was reduced to 2.69?nm/mg and 3.59?nm/ml in tissue and blood, respectively, by aqueous extract treatment. Similarly, MPO level was increased to 412?U/mg and 404?U/ml in tissue and blood, respectively, which was significantly reduced to 205?U/mg and 219?U/ml in tissue and blood, respectively, by aqueous extract treatment. Aqueous extract significantly reduced protease activity which was markedly increased in DNBS-treated animals.

Discussion and conclusion: Aqueous extract of heartwood of T. populnea is effective in the treatment of UC.     

Potential of Moringa oleifera root and Citrus sinensis fruit rind extracts in the treatment of ulcerative colitis in mice

Context: The plant Moringa oleifera Lam (Moringaceae), commonly known as the drumstick tree, is an indigenous species in India. This species has been of interest to researchers because traditionally its roots are reported in the treatment of ulcerative colitis (UC). Traditionally it is reported that Citrus sinensis Linn (Rutaceae) fruit rind when combined with M. oleifera will increase the efficacy of the plant in the treatment of UC. Objective: The present work was undertaken to determine the effectiveness of M. oleifera root alone and in combination with C. sinensis fruit rind in the treatment of UC. Materials and methods: Ethanol and aqueous extracts of M. oleifera roots (100 and 200?mg/kg, body weight) were screened alone and in equal combination with ethanol extract of C. sinensis fruit rind, i.e., 50?mg/kg each of C. sinensis and M. oleifera for their activity on acetic acid-induced UC in mice. Results: Treatment with combination of extracts of M. oleifera root and C. sinensis fruit rind (50?mg/kg, each) showed less ulceration and hyperemia than individual extract (200?mg/kg) in histopathological observation. Acetic acid increased myeloperoxidase (MPO) level in blood and colon tissue to 342?U/mL and 384?U/mg, respectively. Combination of ethanol extract of M. oleifera root with C. sinensis fruit rind extract significantly (p?相似文献   

Beneficial effect of Amorphophallus paeoniifolius tuber on experimental ulcerative colitis in rats

Context: The tuber of Amorphophallus paeoniifolius (Dennst.) Nicolson (Araceae), commonly called Suran or Jimmikand, has high medicinal value and is used ethnomedicinally for the treatment of different gastrointestinal and inflammatory disorders.

Objective: The present study evaluated the effects of extracts of Amorphophallus paeoniifolius tubers on acetic acid-induced ulcerative colitis (UC) in rats.

Materials and methods: Wistar rats were orally administered methanol extract (APME) or aqueous extract (APAE) (250 and 500?mg/kg) or standard drug, prednisolone (PRDS) (4?mg/kg) for 7 days. On 6th day of treatment, UC was induced by transrectal instillation of 4% acetic acid (AA) and after 48?h colitis was assessed by measuring colitis parameters, biochemical estimations and histology of colon.

Results: APME or APAE pretreatment significantly (p?p?p?Discussion and conclusion: APME and APAE showed a preventive effect on UC, and ameliorated inflammation and oxidative damage in colon. The effects may be attributed to presence of phytochemicals, betulinic acid, β-sitosterol, and glucomannan. In conclusion, the tuber of Amorphophallus paeoniifolius exhibited an anticolitic effect through anti-inflammatory and antioxidant action.     

Effects of triptolide on pharmacokinetics of fenofibrate in rats and its potential mechanism

1. Triptolide and fenofibrate are often used together for the treatment of nephrotic syndrome in Chinese clinics.

2. This study investigates the effects of triptolide on the pharmacokinetics of fenofibrate in rats and it potential mechanism.

3. The pharmacokinetics of fenofibrate (20?mg/kg) with or without triptolide pretreatment (2?mg/kg/day for seven days) were investigated. Additionally, the inhibitory effects of triptolide on the metabolic stability of fenofibrate were investigated using rat liver microsome incubation systems.

4. The results indicated that the C_max (35.34?±?7.52 vs. 30.43?±?6.45?μg/mL), t_1/2 (6.17?±?1.15 vs. 4.90?±?0.82?h) and AUC_(0–t) (468.12?±?35.84 vs. 416.35?±?32.68?mg?h?L^?1) of fenofibric acid decreased significantly (p?<?.05). The T_max of fenofibric acid increased significantly (p?<?.05) from 5.12?±?0.36 to 6.07?±?0.68?h. Additionally, the metabolic stability of fenofibrate was prolonged from 35.8?±?6.2 to 48.6?±?7.5?min (p?<?.05) with the pretreatment of triptolide.

5. In conclusion, these results indicated that triptolide could affect the pharmacokinetics of fenofibric acid, possibly by inhibiting the metabolism of fenofibrate in rat liver when they were co-administered.

     

Selenium and rutin alone or in combination do not have stronger protective effects than their separate effects against cadmium-induced renal damage

Context: Selenium (Se) and rutin (RUT) are antioxidants that protect against tissue damage.

Objective: In this study, the separate and combine protective effects of RUT and Se against cadmium (Cd)-induced renal damage were evaluated in rats.

Materials and methods: Wistar rats were treated by gavage to RUT (30?mg/kg) or Se (0.15?ppm) or Cd (200?ppm) in drinking water alone or in combination (30?mg/kg RUT?+0.15?ppm Se?+?200?ppm Cd). Corn oil was used as vehicle (2?mL/kg). After a 5-week treatment period, rat kidneys were removed for biochemical assays and histopathological examination. Se and Cd levels were evaluated by flame atomic absorption spectrophotometry.

Results: The malondialdehyde and glutathione levels as well as superoxide dismutase and catalase activities in the Cd-treated animals were increased compared with control values (0.056?±?0.0003 versus 0.011?±?0.0005?μmol/mg; 0.005?±?0.0006 versus 0.00085?±?0.0002?μg/mg; 1.62?±?0.09 versus 0.48?±?0.12 units/mg; 650?±?25 versus 361.89?±?31?μmol H₂O₂/mg, respectively). Cd treatment was also associated with decreased renal Se concentration (4.19?±?0.92 versus 7.73?±?0.7?μg/g dry weight), increased alkaline phosphatase (0.07?±?0.0015 versus 0.033?±?0.0019 unit/mg), acid phosphatase (0.029?±?0.0021 versus 0.015?±?0.0016 unit/mg), and lactate dehydrogenase (0.032?±?0.004 versus 0.014?±?0.0027 unit/mg) activities, respectively, and with evidence of severe renal damage. The combination of RUT and Se or their separate effects prevented the Cd-induced oxidative renal damage. However, their combine effects do not have stronger effects than their separate effect against Cd-induced renal damage.

Discussion and conclusion: RUT and Se function as potent antioxidant in the protection of renal damage induced by Cd.     

Prevention of arsenic-mediated reproductive toxicity in adult female rats by high protein diet

Abstract

Context: The detrimental effects of arsenic on female reproductive functions may involve overt oxidative stress. Casein and pea [Pisum sativum Linn. (Fabaceae)] proteins have antioxidant properties.

Objective: To investigate the role of casein- and pea-supplemented high-protein diet (HPD) in utero-ovarian protection from arsenic toxicity.

Materials and methods: Adult female Wistar rats were orally gavaged with vehicle (Gr-I) or arsenic at 3?ppm/rat/d (Gr-II and Gr-III) for 30 consecutive days, when they were maintained on either regular diet containing 18% protein (Gr-I and Gr-II), or HPD containing 27% protein in the form of casein (20%) and pea (7%) (Gr-III). Reproductive functions were evaluated using a battery of biochemical and histological techniques.

Results: As compared to Gr-I, the Gr-II rats suffered from loss of estrous cyclicity, reduction in weight (mg/100?g body weight) of ovary (Gr-I: 54.3?±?4.2 versus Gr-II: 35.8?±?1.6; p?<?0.001) and uterus (Gr-I: 161.7?±?24.6 versus Gr-II: 94.44?±?13.2; p?<?0.05), utero-ovarian degeneration, attenuated ovarian activities (unit/mg tissue/h) of Δ⁵, 3β-hydroxysteroid dehydrogenase (Gr-I: 3.41?±?0.12 versus Gr-II: 2.31?±?0.09; p?<?0.01) and 17β-hydroxysteroid dehydrogenase (Gr-I: 3.82?±?0.57 versus Gr-II: 1.24?±?0.19; p?<?0.001), and decreased serum estradiol level (pg/ml) (Gr-I: 61.5?±?2.06 versus 34.1?±?2.34; p?<?0.001). Ovarian DNA damage was preponderant with blatant generation of malondialdehyde (nM/mg tissue; Gr-I: 15.10?±?2.45 versus Gr-II: 29.51?±?3.44; p?<?0.01) and attenuated superoxide dismutase activity (unit/mg tissue) (Gr-I: 2.18?±?0.19 versus Gr-II: 1.33?±?0.18; p?<?0.05). The Gr-III rats were significantly protected from these ill effects of arsenic.

Discussion and conclusion: HPD, by way of antioxidant properties, may find prospective role in the protection of reproductive damage caused by arsenic.     

Effects of berberine on the pharmacokinetics of losartan and its metabolite EXP3174 in rats and its mechanism

Context: Losartan and berberine (BBR) are often simultaneously used for the treatment of senile diabetic nephropathy in clinics. However, the potential herb–drug interaction between losartan and BBR is unknown.

Objective: This study investigates the influence of BBR on the pharmacokinetics of losartan and EXP3174, and investigates the effects of BBR on the metabolic stability of losartan.

Materials and methods: The pharmacokinetic profiles losartan and EXP3174 of orally administered losartan (10?mg/kg) with and without pretreatment with BBR (20?mg/kg) within 24?h were determined in Sprague-Dawley rats. The inhibitory effects of BBR on the metabolic stability of losartan were investigated using rat liver microsomes.

Results: The C_max (1.26?±?0.37 versus 1.96?±?0.45?mg/L) and the AUC_(0–t) (8.25?±?0.89 versus 12.70?±?1.42?mg h/L) of losartan were significantly (p?<?0.05) increased by BBR compared to the control, while the C_max (0.97?±?0.15 versus 0.77?±?0.06?mg/L) of EXP3174 was significantly decreased compared to the control (p?<?0.05). The T_max of losartan was prolonged from 0.41?±?0.12 to 0.52?±?0.18?h, but the difference was not significant. However, the T_max of EXP3174 was decreased significantly (p?<?0.05) from 8.14?±?0.36 to 3.33?±?0.28?h. The metabolic stability of losartan was increased from 37.4 to 59.6?min.

Discussion and conclusion: We infer that BBR might increase the plasma concentration of losartan and decrease the concentration of EXP3174 through inhibiting the activity of CYP3A4 or CYP2C9.     

Nephroprotective activity of Macrothelypteris oligophlebia rhizomes ethanol extract

Context: Macrothelypteris oligophlebia (Bak.) Ching (Thelypteridaceae) is a Chinese herbal medicine used traditionally for the treatment of diseases such as edema, boils, burns, and roundworms. However, research about the nephroprotective potential of this plant is not available.

Objective: Present study was designed to evaluate the protective effect of ethanol extract of M. oligophlebia rhizomes (EMO) on gentamicin (GM)-induced nephrotoxicity.

Materials and methods: Rats were intraperitoneal (i.p.) injected with GM (100?mg/kg) to induce nephrotoxicity and simultaneously EMO (250 and 500?mg/kg) was orally given to GM-treated rats for 8 days. Blood urea nitrogen (BUN), serum creatinine (Cr), malondialdehyde (MDA), nitric oxide (NO), superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GSH-Px) were evaluated in renal tissues. Histopathological analysis was used for evaluation of the renal damage.

Results: Administration with GM-induced renal dysfunction in rats. Pre-treatment with EMO (500?mg/kg) significantly decreased the levels of BUN, Cr, MDA and NO (decreased BUN from 12.71?±?1.28 to 7.19?±?0.23 mmol/l, Cr from 39.77?±?5.34 to 19.17?±?0.90 μmol/l, MDA from 5.60?±?0.37 to 2.63?±?0.24 nmol/ml, and NO from 868.17?±?22.67 to 589.51?±?8.83 μmol/ml), and also restored the activities of renal antioxidant enzymes (SOD, CAT, and GSH-Px) (restored SOD from 1.59?±?0.17 to 2.94?±?0.13?U/mg protein, CAT from 3.22?±?0.34 to 10.57?±?0.27?U/mg protein, and GSH-Px from 9.11?±?1.29 to 20.72?±?1.83?U/mg protein).

Discussion and conclusion: Our results suggest that the rhizomes of M. oligophlebia potentially have a protective role in renal tissue against oxidative stress in acute renal failure.     

Phytochemical screening and analgesic profile of the lyophilized aqueous extract obtained from Chrysobalanus icaco leaves in experimental protocols

Context: Chrysobalanus icaco L. (Chrysobalanaceae) has been used for the treatment of abdominal pain and cramps.

Objective: Assess the chemical and pharmacological profile of the lyophilized aqueous extract from C. icaco leaves (AEC).

Materials and methods: Chromatographic methods were used to assess compounds from AEC. Mice were treated with vehicle (control group) or AEC (100, 200 or 400?mg/kg, p.o.) (group with 7–8 mice) and the analgesic profile was assessed employing the acetic acid-induced writhing, formalin, hot plate tests and hyperalgesia induced by carrageenan (CG) or tumour necrosis factor-alpha. The animal motor performance was assessed using rota-rod and grip strength tests.

Results: The chromatographic profile of AEC demonstrated the presence of terpenoid compounds. The acute pretreatment with AEC, at all doses, produced a significant (p?<?0.01) inhibition of painful bahaviour (11.4?±?3.6; 10.3?±?2.8; 11.3?±?2.2) when compared to the control group (24.7?±?4.7) in acetic acid-induced writhing test. In the formalin test, AEC were effective in the second phase (p?<?0.01) (57.2?±?10.3; 56.3?±?9.2; 54.7?±?8.9) when compared to control group (121.9?±?18.5). No response was observed in the hot plate test. The higher dose of AEC produced a significant (p?<?0.01 or p?<?0.05) inhibitory effect on the mechanical hyperalgesia test. AEC did not affect the motor performance of the mice.

Discussion: The terpenoids from AEC are known for its analgesic and anti-inflammatory properties. So, these results corroborate the experiments using the AEC in inflammatory pain protocols.

Conclusion: Our results suggest that AEC act against inflammatory pain.     

Standardized myrtol attenuates lipopolysaccharide induced acute lung injury in mice

Context: Standardized myrtol, an essential oil containing primarily cineole, limonene and α-pinene, has been used for treating nasosinusitis, bronchitis and chronic obstructive pulmonary disease (COPD).

Objective: To investigate the effects of standardized myrtol in a model of acute lung injury (ALI) induced by lipopolysaccharides (LPS).

Materials and methods: Male BALB/c mice were treated with standardized myrtol for 1.5?h prior to exposure of atomized LPS. Six hours after LPS challenge, lung injury was determined by the neutrophil recruitment, cytokine levels and total protein concentration in the bronchoalveolar lavage fluid (BALF) and myeloperoxidase (MPO) activity in the lung tissue. Additionally, pathological changes and NF-κB activation in the lung were examined by haematoxylin and eosin staining and western blot, respectively.

Results: In LPS-challenged mice, standardized myrtol at a dose of 1200?mg/kg significantly inhibited the neutrophile counts (from 820.97?±?142.44 to 280.42?±?65.45, 10³/mL), protein concentration (from 0.331?±?0.02 to 0.183?±?0.01, mg/mL) and inflammatory cytokines level (TNF-α: from 6072.70?±?748.40 to 2317.70?±?500.14, ng/mL; IL-6: from 1184.85?±?143.58 to 509.57?±?133.03, ng/mL) in BALF. Standardized myrtol also attenuated LPS-induced MPO activity (from 0.82?±?0.04 to 0.48?±?0.06, U/g) and pathological changes (lung injury score: from 11.67?±?0.33 to 7.83?±?0.79) in the lung. Further study demonstrated that standardized myrtol prevented LPS-induced NF-κB activation in lung tissues.

Discussion and conclusion: Together, these data suggest that standardized myrtol has the potential to protect against LPS-induced airway inflammation in a model of ALI.     

Lipid-lowering property of Clausena anisum-olens in hypercholesterolemic rats

Context: Clausena anisum-olens (Blanco) Merr. (Rutaceae) is a medicinal shrub which has been reported to have various pharmacological uses. No study regarding the effects of C. anisum-olens on cholesterol-lowering has been reported.

Objective: The effects of the ethanol extract of C. anisum-olens leaves on the cholesterol level of hypercholesterolemic rats were evaluated.

Materials and methods: Acute oral toxicity of the extract (175, 550 and 2000?mg/kg) was determined using female Sprague-Dawley rats, as described in OECD 425 Main test guidelines. The lipid-lowering assay utilized 30 male Sprague-Dawley rats divided into five groups (A–E). Triton X-100 was administered to induce hypercholesterolemia. After hypercholesterolemia induction, oral treatment of Atorvastatin and crude ethanol extract was given daily to the treatment groups for 14 days. The total cholesterol, triglycerides, HDL and LDL were determined before induction, after induction, after first week of treatment and after second week of treatment.

Results: Acute oral toxicity showed the crude extract is nontoxic up to 2000?mg/kg. The lipid-lowering assay indicated reduction of serum cholesterol (87.21?±?5.10?mg/dL), triglycerides (58.09?±?4.10?mg/dL) and LDL (27.82?±?4.11?mg/dL) for 200?mg/kw extract. Reduction in serum cholesterol (74.72?±?3.64?mg/dL), triglycerides (52.79?±?2.98?mg/dL) and LDL (12.06?±?5.51?mg/dL) were observed for 400?mg/kg group. The result is comparable to Atorvastatin, which showed serum cholesterol (80.90?±?9.72?mg/dL), triglycerides (55.94?±?7.19?mg/dL) and LDL (22.09?±?7.60?mg/dL) reduction.

Discussion and conclusion: The crude extract of C. anisum-olens proved to be useful in lowering of cholesterol.     

Effects of calcitriol on bone mineral density in patients treated with esomeprazole

Context: Proton pump inhibitor (PPI) increases the risk of decrease in bone mineral density (BMD). However, whether calcitrol improves this situation is unknown.

Objective: The current study investigates the effects of calcitriol on BMD in patients with esomeprazole therapy.

Materials and methods: Three hundred and eighty-six participants with gastrointestinal ulcerations were enrolled and randomly assigned into controlled and supplemented groups. Participants in the controlled group were prescribed esomeprazole (20?mg/qd), while the supplemented group was prescribed esomeprazole (20?mg/qd) and calcitriol (2.5?μg/qd). BMD, serum levels of calcium, carboxy-terminal collagen crosslinks (CTX), and alkaline-phosphatase (ALP) were assessed.

Results: (1) No significant between-group difference of age, gender, smoking, previous glucocorticoid use and hemoglobin level was found; (2) after 10.6?±?0.8?d of PPI therapy, BMD T score in the controlled group was slightly increased compared with initial (?1.25?±?0.08 versus ?1.28?±?0.06, p?=?0.084), while there was no change in the supplemented group (?1.25?±?0.05 versus ?1.26?±?0.03, p?=?0.308); (3) during study termination, calcium level in the supplemented group was slightly higher than the controlled group (2.05?±?0.03?mmol/L versus 2.01?±?0.05?mmol/L, p?=?0.073), while no significant differences of CTX (366.57?±?43.71?pg/mL versus 373.15?±?50.23?pg/mL, p?=?0.036) and ALP were found among these two groups (50.47?±?9.32?U/L versus 52.23?±?10.45?U/L, p?=?0.075).

Conclusion: Patients with gastrointestinal ulcerations with esomeprazole therapy, calcitriol supplement showed no efficacy on BMD changes.     

The application of 1,8-cineole,a terpenoid oxide present in medicinal plants,inhibits castor oil-induced diarrhea in rats

Abstract

Context: 1,8-Cineole, a terpene, characterized as a major constituent occurring in the essential oils of several aromatic plants. It is widely used in pharmaceutical industry, as a food additive and for culinary purposes.

Objective: This study investigates the inhibitory effect of 1,8-cineole on transit time and diarrhea in animal models.

Materials and methods: Acute toxicity and lethality of 1-8-cineole was determined by Lork’s guidelines. The antidiarrheal effect of 1,8-cineole was investigated by determining the intestinal transit and enterpooling in rats. In all experiments, different doses of 1,8-cineole (20–120?mg/kg), atropine, and loperamide were administered orally.

Results: The LD₅₀ of 1,8-cineole for oral administration was estimated to be 1280?mg/kg. 1,8-Cineole (20–120?mg/kg) did not show a significant decrease in small intestine transit (p?>?0.05); however, the highest dose displayed a significant decrease in comparison with atropine (p?<?0.05). This substance decreased the peristaltic index value to 68?±?0.36% at a dose of 120?mg/kg compared with the control group (85.22?±?4.31%) in the castor oil transit test. 1,8-Cineole significantly delayed the onset of diarrhea to ?142.33?±?6.08?min at 120?mg/kg, while the time was 103.66?±?20.73?min for the control and >240?min for the loperamide. Moreover, 1,8-cineole significantly decreased intestinal fluid accumulation (p?<?0.05).

Conclusions: This study demonstrated antispasmodic and antisecretory activities of 1,8-cineole and rationalized the traditional use of the plant containing various levels of this terpene in the treatment of gastrointestinal complains such as diarrhea.     

Protective potential of Tamarindus indica against gentamicin-induced nephrotoxicity

Context: Gentamicin is an antibiotic that is effective against Gram-negative microorganisms. However, its clinical applications are often limited due to nephrotoxic effects.

Objective: This study investigated the protective effects of aqueous-ethanol extract of Tamarindus indica L. (Leguminosae) fruits against gentamicin-induced renal toxicity.

Materials and methods: A daily dose of 200?mg/kg of 70% aqueous-ethanol extract derived from T. indica was employed in male rabbits as a co-therapy with gentamicin (80?mg/kg) for a period of three weeks. Serum and urinary renal function parameters and histological assessments were carried out and compared with one way analysis of variance (Graphpad prism version 5.00, Graphpad Software, San Diego, CA).

Results: The results showed that gentamicin-treated animals had significantly elevated blood urea nitrogen (54.1?±?2.6?mg/dl), serum creatinine (4.0?±?0.1?mg/dl), serum uric acid (2.3?±?0.1?mg/dl) and urinary protein excretion (3.8?±?0.3?mg/dl) with a fall in body weight (10?±?1%), creatinine clearance (0.7?±?0.09?ml/min), serum potassium (3.4?±?0.1?mEq/l), serum calcium (7.6?±?0.2?mg/dl), urinary volume (126?±?9?ml/24?h) and urinary lactate dehydrogenase secretion (103.1?±?4.2?U/l). However, animals treated by co-therapy with gentamicin and T. indica had significantly improved renal structure and function.

Discussion and conclusion: Co-therapy of 200?mg/kg/d of T. indica for a period of three weeks successfully prevented functional and morphological derangements caused by gentamicin as assessed by different renal function parameters and histological examinations.     

Prostatic protective nature of the flavonoid-rich fraction from Cyclosorus acuminatus on carrageenan-induced non-bacterial prostatitis in rat

Context: Cyclosorus acuminatus (Houtt.) Nakai (Thelypteridaceae) is used in Chinese traditional medicine for inflammation and pyretic stranguria.

Objective: This study investigates the prostatic protective potential of the flavonoid-rich [(2S)-5,7,5′-trihydroxyflavanone glycosides] fraction from C. acuminatus (FCA).

Materials and methods: Chronic non-bacterial prostatitis (CNBP) was induced by injecting 20?μl of 1% carrageenan into the rat prostate. Subsequently, FCA (150 or 300?mg/kg/d) was orally given once a day for 4 weeks. Finally, the levels of proinflammatory cytokines and the prostatic expression of peroxisome proliferator activated receptor-γ (PPAR-γ) were evaluated.

Results: Treatment with 300?mg/kg/d FCA ameliorated the carrageenan-induced higher prostatic index (PI) state and proinflammatory cytokines levels (NFκB from 2602?±?588 to 1348?±?300?pg/ml, TNF-α from 151.6?±?10.4 to 126.0?±?3.52?pg/ml, IL-1β from 153.7?±?14.8 to 63.9?±?6.7?pg/ml, COX-2 from 313.3?±?16.5 to 263.1?±?15.1?pg/ml, PGE from 1532?±?130 to 864?±?126?pg/ml, NOS from 33.7?±?3.0 to 23.6?±?1.6?U/mg protein, and NO from 40.3?±?2.9 to 27.1?±?2.9?μmol/g protein) as well as regulated the prostatic expression of PPAR-γ (increased about 3.50-fold) when compared to the rat model of prostatitis.

Discussion and conclusion: FCA could exert a prostatic protective response via modulating the prostatic expression of PPAR-γ and eventually alleviating the NFκB dependent inflammatory response.     

Effects of rosmarinic acid on acetaminophen-induced hepatotoxicity in male Wistar rats

Context: Drug-induced liver injury is a significant worldwide clinical problem. Rosmarinic acid (RA), a natural phenol, has antioxidant effects.

Objective: The effects of RA against acetaminophen (N-acetyl-p-amino-phenol (APAP))-induced oxidative damage and hepatotoxicity in rats were investigated.

Materials and methods: Male Wistar rats were pretreated with RA (10, 50 and 100?mg/kg, i.g.) for one week. On day 7, rats received APAP (500?mg/kg, i.p.). Then aspartate aminotransferase (AST), alanine aminotransferase (ALT), albumin, total protein, malondialdehyde (MDA), glutathione (GSH), total antioxidant capacity (TAC), glutathione S-transferase (GST), cytochrome CYP450 and histopathological changes were determined.

Results: APAP-induced oxidative stress in liver by a significant increase in the level of MDA (7.6?±?0.21?nmol/mg) as well as a decrease in the contents of TAC (1.75?±?0.14?μmol/g), GSH (1.9?±?0.22?μmol/g) and GST) 3.2?±?0.28?U/mg). RA treatment decreased MDA (4.32?±?0.35?nmol/mg) but increased the contents of TAC (3.51?±?0.34?μmol/g), GSH (3.42?±?0.16?μmol/g) and GST (5.71?±?0.71?μmol/g) in APAP group. RA 100?mg/kg decreased ALT (91.5?±?1.5?U/L), AST (169?±?8.8?U/L) and CYP450 (3?±?0.2?nmol/min/mg) in APAP group. Histologically RA attenuated hepatic damage by decreasing necrosis, inflammation, and haemorrhage in liver sections of APAP group.

Discussion and conclusions: This is the first report that oral administration of RA dose-dependently elicited significant hepatoprotective effects in rats through inhibition of hepatic CYP2E1 activity and lipid peroxidation. RA-protected hepatic GSH and GST reserves and total tissue antioxidant capacity.     

Effect of pramlintide as an adjunct to basal insulin on markers of cardiovascular risk in patients with type 2 diabetes

ABSTRACT

Objective: Intensification of insulin therapy in patients with type 2 diabetes, while improving glycemic control, often leads to an increase in body weight and other markers of cardiovascular risk. The effects of pramlintide as an adjunct to basal insulin titration (without mealtime insulin) on glycemia and cardiovascular risk markers were examined.

Research design and methods: This was a post hoc analysis of a 16-week, double-blind, placebo-controlled study in patients with type 2 diabetes (N?=?211) using insulin glargine (without mealtime insulin)?±?oral agents. Patients were randomized to treatment with placebo or pramlintide (60 or 120?µg with major meals), and insulin glargine was titrated to target a fasting plasma glucose concentration of ≥70 to <100?mg/dL.

Main outcome measures: Endpoints included the change from baseline to Week 16 in body weight, high sensitivity C-reactive protein (hsCRP), triglycerides, HDL, LDL, and blood pressure.

Results: Pramlintide-treated patients lost weight and placebo-treated patients gained weight during 16 weeks of treatment (?1.6?±?0.3?kg vs. +0.7?±?0.3?kg, p?<?0.001; mean?±?SE). hsCRP was reduced in pramlintide-treated versus placebo-treated patients (?0.8?±?0.2?mg/L vs. 0.1?±?0.2?mg/L, p?<?0.01; mean?±?SE). Patients with baseline hsCRP?>?3?mg/L (high cardiovascular risk) demonstrated greater hsCRP reductions with pramlintide versus placebo treatment at Week 16 (p?<?0.05). Patients with baseline triglycerides ≥150?mg/dL or ≥200?mg/dL (high cardiovascular risk) showed significant reductions from baseline in triglyceride concentrations with pramlintide (?43?±?14?mg/dL or ?59?±?19?mg/dL; p?<?0.05; mean?±?SE) but not with placebo (1?±?29?mg/dLor ?3?±?54?mg/dL; mean?±?SE). No significant differences between pramlintide and placebo were observed for changes in HDL, LDL, or blood pressure. Pramlintide treatment was generally well tolerated. The most frequent adverse event related to pramlintide was mild-to-moderate nausea (31% pramlintide vs. 10% placebo). Pramlintide added to basal insulin did not increase the incidence of hypoglycemia. A limitation of the study was its relatively short duration.

Conclusions: Pramlintide, as an adjunct to basal insulin, was associated with improvements in several cardiovascular risk markers, warranting long-term clinical studies to determine its potential effects on cardiovascular risk.     

Effects of rosmarinic acid on an experimental model of painful diabetic neuropathy in rats

Context: Diabetic neuropathic (DN) pain is one of the diabetes complications. Rosmarinic acid (RA), a natural phenol antioxidant, shows some biological activities, including anti-inflammatory, analgesic, and anti-diabetic effects.

Objectives: We investigated the efficacy of RA administration (10 and 30?mg/kg) on streptozotocin (STZ)-induced neuropathy in rats.

Material and methods: The animals received saline or RA (10 and 30?mg/kg, p.o.; once daily) for 8 weeks. DN was evaluated by the tail flick (TF) method, formalin test, and tactile allodynia. At the end, all rats were weighed and underwent plasma glucose measurement.

Results: There was an increase in licking time during both formalin test phases in diabetic animals (138.5?±?10.7 and 448.7?±?2.6?s) that was decreased by RA10?mg/kg (103.5?±?7.5 and 284.4?±?19?s) and RA 30?mg/kg (81.8?±?11 and 192.7?±?14?s). RA 30?mg/kg caused anti-nociception during the early phase in treated controls (52.1?±?6?s) than untreated controls (99.4?±?5.9?s). The TF latency in diabetics (2.9?±?0.1?s) was increased in RA10 and 30?mg/kg treated diabetics (5.3?±?0.4 and 6?±?0.86?s). The paw withdrawal threshold (PWT) of the diabetics (3.6?±?0.7?g) was increased after RA 10 and 30?mg/kg (13.8?±?0.3 and 14?±?0.4?g) treatment. RA did not induce a significant change in body weight and plasma glucose of rats.

Conclusion: RA showed efficacy in amelioration of some aspects of DN. Therefore, RA makes a good candidate for DN treatment in clinical studies.