Neuroprotective effect of Azadirachta indica standardized extract in partial sciatic nerve injury in rats

Chronic neuropathic pain is a common and widely recognized pain syndrome for patients and difficult to manage for physicians. Azadirachta indica (AI) possesses analgesic, anti-inflammatory, and antioxidant properties. To evaluate the neuroprotective effect of AI standardized extract in an animal model of peripheral neuropathy induced by partial sciatic nerve ligation (PSNL). PSNL was induced in male Wistar rats (180-200 g) with tight ligation of the nerve. Rats received treatment with either vehicle i.e. distilled water (PSNL control), Pyridoxine (100 mg/kg, p.o.) or AI (100, 200 and 400 mg/kg, p.o.) for 28 days. Various behavioral parameters, biochemical, molecular and histological parameters were evaluated. PSNL resulted in a significant decrease (p < 0.05) in allodynia, hy- peralgesia, motor coordination and motor nerve conduction velocity (MNCV) whereas chronic treatment with AI (200 and 400 mg/kg) significantly attenuated (p < 0.05) these behavioral changes. Enhanced activity of oxidative- nitrosative stress, inflammatory mediators (TNF-α, IL-1β, and NF-κB) as well as mRNA expression of Bax, Caspase-3, and iNOs were significantly attenuated (p < 0.05) by AI treatment. It also significantly increased (p < 0.05) peripheral blood oxygen content and Bcl-2 mRNA expression. The flow cytometric analysis revealed that AI (200 and 400 mg/kg) treatment significantly attenuated neural apoptosis and reactive oxygen species levels. PSNL induced histological aberrations were also decreased by AI treatment. Azadirachta indica exerts its neuro- protection against PSNL induced neuropathic pain via inhibition of oxidative-nitrosative stress, the release of pro-inflammatory cytokines and apoptosis to improve MNCV (graphical abstract, Figure 1)

Hesperidin ameliorates bleomycin-induced experimental pulmonary fibrosis via inhibition of TGF-β1/Smad3/AMPK and IκBα/NF-κB pathways

Bleomycin (BLM) is a chemotherapeutic agent which is associated with Idiopathic pulmonary fibrosis (IPF) due to its chronic administration. Hesperidin, a bioflavonoid has been reported to possess antioxidant, anti-inflammatory, wound healing, and antiapoptotic potential. To eval uate the therapeutic potential of hesperidin against BLM-induced pulmonary fibrosis and deciph er its possible mechanism of action. Intraperitoneal administration of BLM (6 IU/kg) caused induction of IPF in Sprague-Dawley rats. Rats were treated with hesperidin (25, 50, and 100 mg/kg, p.o.) for 28 days, followed by estimation of various parameters in ronchoalveolar lavage fluid (BALF) and lung. Hesperidin (50 and 100 mg/kg) administration significantly meliorated (p < 0.05) alterations induced by BLM in lung index, percent oxygen saturation, serum ALP and LDH levels, BALF differential cell count, and lung function test. Elevated levels of oxido-nitrosative stress, hydroxyproline, and myeloperoxidase levels in BALF and lung were significantly decreased by hesperid in on day 14. Hesperidin significantly inhibited BLM-induced down-regulated lung Nrf2 an d HO-1 as well as up-regulated TNF-α, IL-1β, IL-6, collagen-1, TGF-β, and Smad-3 mRNA expressions. Western blot analysis showed that alteration in lung NF-κ B, Iκ B α , AMPK, and PP2C-α protein expressions were ameliorated by hesperidin on day 28. Furthermore, BLM induced histological and ultrastructural aberrations in the lung which were attenuated by hesperidin treatment. Hesperidin alleviates BLM-induced IPF via inhibition of TGF-β1/Smad3/AMPK and IκBα/NF-κB pathways which in turn ameliorate the modulation of oxido-inflammatory markers (Nrf2 and HO-1) and pro-inflammatory markers (TNF-α, IL-1β, and IL-6) to reduce collagen deposition during pulmonary fibrosis

Add-on therapy of herbal formulation rich in standardized fenugreek seed extract in type 2 diabetes mellitus patients with insulin therapy: An efficacy and safety study

Objective: To assess the safety and efficacy of herbal formulation rich in standardized fenugreek seed extract (IND-2) add-on therapy in type 2 diabetes mellitus (T2DM) patients who were on insulin treatment in prospective, single arm, open-label, uncontrolled, multicentre trial. Methods: T2DM patients (n=30) with aged 18-80 years who were stabilized on insulin treatment with fasting blood sugar (FBS) level between 100-140 mg/dL received IND-2 capsules (700 mg, thrice a day) for 16 weeks. The primary endpoints were an assessment of FBS at week 2, 4, 6, 8, 12 and 16. Secondary end-points include post-prandial blood sugar level, glycosylated Hb (HbA1c), reduction in the dose of insulin and number of hypoglycemic attacks, and improvement in lipid profile at various weeks. Safety and adverse events (AEs) were also assessed during the study. Results: Study was completed in twenty T2DM patients, and there was no significant reduction in FBS and post-prandial blood sugar level after addon therapy of IND-2. However, add-on therapy of IND-2 significantly reduced (P<0.01) the HbA1c values, requirements of insulin and hypoglycemic events as compared with baseline. Total cholesterol, high-density lipoproteins-cholesterol, and low-density lipoprotein-cholesterol levels were significantly increased (P<0.01) after IND-2 add-on therapy. Body weight and safety outcomes did not differ significantly in IND-2 add-on therapy group at week 16. Additionally, add-on therapy of IND-2 did not produce any serious adverse events. Conclusions: The results of present investigation suggest that add-on therapy of IND-2 with insulin in T2DM patients improves glycaemic control through a decrease in levels of HbA1c and number of insulin doses needed per day without an increase in body weight and risk of hypoglycemia. Thus, IND-2 may provide a safe and well-tolerated add-on therapy option for the management of T2DM

Effect of naringin on hemodynamic changes and left ventricular function in renal artery occluded renovascular hypertension in rats

Background: Renal artery occlusion (RAO) induced hypertension is a major health problem associated with structural and functional variations of the renal and cardiac vasculature. Naringin a flavanone glycoside derived possesses metal-chelating, antioxidant and free radical scavenging properties. Objective: The objective of this study was to investigate the antihypertensive activity of naringin in RAO induced hypertension in rats.Material and Methods: Male Wistar rats (180-200 g) were divided into five groups Sham, RAO, naringin (20, 40 and 80 mg/kg). Animals were pretreated with naringin (20, 40 and 80 mg/kg p.o) for 4 weeks. On the last day of the experiment, left renal artery was occluded with renal bulldog clamp for 4 h. After assessment of hemodynamic and left ventricular function various biochemical (superoxide dismutase [SOD], glutathione [GSH] and malondialdehyde [MDA]) and histological parameters were determined in the kidney. Results: RAO group significantly (P < 0.001) increased hemodynamic parameters at 15, 30 and 45 min of clamp removal. Naringin (40 and 80 mg/kg) treated groups showed a significant decrease in hemodynamic parameters at 15 min. after clamp removal that remained sustained for 60 min. Naringin (40 and 80 mg/kg) treated groups showed significant improvement in left ventricular function at 15, 30 and 45 min after clamp removal. Alteration in level of SOD, GSH and MDA was significantly restored by naringin (40 and 80 mg/kg) treatment. It also reduced histological aberration induced in kidney by RAO. Conclusion: It is concluded that the antihypertensive activity of naringin may result through inhibition of oxidative stress

Glycosides based standardized fenugreek seed extract ameliorates bleomycin-induced liver fibrosis in rats via modulation of endogenous enzymes

Background: Liver fibrosis a complex process of excess collagen deposition resulted in disturbance of hepatic cellar function. Glycosides based standardized fenugreek seed extract (SFSE-G) has potent anti-inflammatory, antioxidant, and anti-fibrotic properties. Objective: The aim of this study is to evaluate the hepatoprotective potential of SFSE-G against bleomycin (BLM)-induced liver fibrosis in laboratory animals. Materials and Methods: Sprague-Dawley rats (180–220 g) were assigned to various groups, namely, normal, sham, BLM control, SFSE-G (5, 10, 20, and 40 mg/kg, p.o.), methylprednisolone (10 mg/kg, p.o.), and sildenafil (25 mg/kg, p.o.). Liver fibrosis was induced in various groups (except normal and sham) by single intratracheal BLM (6 IU/kg) injection. Various biochemical, molecular (reverse transcription polymerase chain reaction) and histological parameters were evaluated. Results: Intratracheal BLM administration caused significant induction (P < 0.001) of hepatotoxicity and liver fibrosis reflected by elevated levels of serum aspartate transaminase (AST), alanine transaminase (ALT), total as well as direct bilirubin, and gamma-glutamyl transferase (GGT). Administration of SFSE-G (20 and 40 mg/kg, p.o.) significantly reduced (P < 0.001) levels of AST, ALT, and GGT and significantly increased (P < 0.001) the level of serum albumin. BLM-induced elevated liver oxidative stress and decreased total antioxidant capacity was significantly restored (P < 0.001) by SFSE-G (20 and 40 mg/kg) treatment. It also significantly inhibited BLM-induced alteration in liver Farnesoid X receptor (FXR) mRNA expression. SFSE-G treatment reduced histopathological alteration induced by BLM in liver. Conclusion: SFSE-G exerts its hepatoprotective potential via inhibition of oxido-nitrosative stress and modulation of FXR mRNA expression thus ameliorates BLM-induced liver fibrosis

Evaluation of health-related quality of life in hemolytic uraemic syndrome patients treated with eculizumab: a systematic evaluation on basis of EMPRO

<p><b>Background:</b> Hemolytic uraemic syndrome (HUS) is progressive renal failure disease and determination of their quality of life (QoL) on the basis of patient-reported outcomes (PROs) are becoming increasingly important in the economic evaluations for its treatment with eculizumab (ECU).</p> <p><b>Aim:</b> To perform the systematic evaluation of QoL in HUS patients treated with ECU on the basis of Evaluating Measures of Patient Reported Outcomes (EMPRO) tool.</p> <p><b>Materials and methods:</b> A systematic review was conducted in PubMed, EMBASE, the Cochrane Library, CINAHL and Google Scholar till September 2016 by two independent researchers. Each identified instrument was evaluated for its quality of performance by using the EMPRO tool for its overall score and seven attribute specific scores (range 0–100, worst to best).</p> <p><b>Results:</b> Five different PROs instruments were identified from 10 articles (<i>n</i> = 112) which showed eculizumab significantly improves health-related quality of life (HRQOL) in atypical HUS (aHUS) patients. Amongst five instruments viz. EuroQol five dimensions questionnaire (EQ-5 D), Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F), Headache Impact Test-6 (HIT-6), 36-Item Short Form Health Survey (SF-36) and Visual Analogue Scale (VAS), the overall EMPRO score was higher for VAS (73.83) and EQ-5 D (73.81). Whereas, FACIT-F and HIT- 6 were just able to meet the minimal threshold of EMPRO scoring (50.24 and 59.09, respectively).</p> <p><b>Conclusions:</b> Evidence from present investigation support that eculizumab significantly improves HRQoL in patients with aHUS furthermore, EQ-5 D and VAS instrument should be recommended for assessing HRQoL in them. However, selection of PRO instrument for determination of QoL in HUS entirely depend upon the study requirements.</p

Hesperidin, a plant flavonoid accelerated the cutaneous wound healing in streptozotocin-induced diabetic rats

Background: Delayed wound healing is a diverse, multifactorial, complex and inter-related complication of diabetes resulting in significant clinical morbidity. Hesperidin possesses potent antidiabetic and wound healing activity. Aim: To evaluate the potential of hesperidin against experimentally induced diabetes foot ulcers. Methods: Diabetes was induced experimentally by streptozotocin (STZ, 55 mg/kg, i.p.) in Sprague Dawley rats (180-220 g) and wounds were created on the dorsal surface of the hind paw of rats. Hesperidin (25, 50 and 100 mg/kg, p.o.) was administered for 21 days after wound stabilization. Various biochemical, molecular and histopathological parameters were evaluated in wound tissue. Results: STZ-induced decrease in body weight and increase in blood glucose, food, and water intake was significantly (p < 0.05) inhibited by hesperidin (50 and 100 mg/kg) treatment. It showed a significant increase (p < 0.05) in percent wound closure and serum insulin level. The STZ-induced decrease in SOD and GSH level, as well as elevated MDA and NO levels, were significantly (p < 0.05) attenuated by hesperidin (50 and 100 mg/kg) treatment. Intraperitoneal administration of STZ caused significant down-regulation in VEGF-c, Ang-1, Tie-2, TGF-β and Smad 2/3 mRNA expression in wound tissues whereas hesperidin (50 and 100 mg/kg) treatment showed significant up-regulation in these mRNA expressions. STZ-induced alteration in would architecture was also attenuated by hesperidin (50 and 100 mg/kg) treatment. Conclusion: Together, treatment with hesperidin accelerate angiogenesis and vasculogenesis via up-regulation of VEGF-c, Ang-1/Tie-2, TGF-β and Smad-2/3 mRNA expression to enhance wound healing in chronic diabetic foot ulcers