scholarly journals ACUTE TOXICITY OF CHITOSAN NANOPARTICLES CONTAINING MAHKOTA DEWA (PHALERIA MACROCARPA) LEAF EXTRACT AND ANTI-INFLAMMATORY EFFECTS IN A DEXTRAN SODIUM SULFATE-INDUCED MOUSE MODEL OF ULCERATIVE COLITIS

2018 ◽  
Vol 10 (1) ◽  
pp. 6
Author(s):  
Ari Estuningtyas ◽  
Santi Widiasari ◽  
Kusmardi Kusmardi

Objective: The plant mahkota dewa (Phaleria macrocarpa) is known to have anti-inflammatory effects. This study aimed to determine whetherchitosan nanoparticles containing mahkota dewa leaf extract would yield superior anti-inflammatory effects in the colon of a mouse model of dextransodium sulfate (DSS)-induced ulcerative colitis, compared with ethanol extract alone after testing the acute toxicities (lethal dose) of both preparations.Methods: For acute toxicity testing, 10 Sprague-Dawley rats were administered 6000 mg/kg body weight (BW) of leaf extract alone or with nanoparticles.Subsequently, mice were divided into the following six groups to determine the anti-inflammatory effects: Untreated, negative control (DSS 2% w/v), leafextract at 12.5 or 25 mg/kg BW, and leaf extract in chitosan nanoparticles at 6.25 or 12.5 mg/kg BW. To induce colitis, DSS (2% w/v) was administeredthrough drinking water for 6 weeks. The anti-inflammatory effect was observed histopathologically by imaging the inflammatory cells of the mice colonwith hematoxylin-eosin (HE) staining.Results: For acute toxicity testing, 10 Sprague-Dawley rats were administered 6000 mg/kg BW of leaf extract alone or with nanoparticles. Subsequently,mice were divided into the following six groups to determine the anti-inflammatory effects: Untreated, negative control (DSS 2% w/v), leaf extract at12.5 or 25 mg/kg BW, and leaf extract in chitosan nanoparticles at 6.25 or 12.5 mg/kg BW. To induce colitis, DSS (1% w/v) was administered throughdrinking water for 6 weeks. The anti-inflammatory effect was observed histopathologically by imaging the inflammatory cells of the mice colon withHE staining.Conclusion: Chitosan nanoparticles containing mahkota dewa leaf extract can be included in the practically non-toxic class of materials. However, anethanol extract of mahkota dewa leaf effectively inhibited DSS-induced inflammation in the mouse colon, regardless of delivery vehicle.

Author(s):  
Kusmardi Kusmardi ◽  
Arif Ramadhan Tamzir ◽  
Santi Widiasari ◽  
Ari Estuningtyas

Objective: The incidence of small intestine cancer (SIC) is rising despite available preventive measures. Kaempferol and quercetin are a potential chemopreventive agent for SIC, but in vivo findings are inconclusive. We aim to study the effects of kaempferol and quercetin on colitis-associated small intestine carcinogenesis in mice.Methods: Suppression effect was tested using mice divided into 6 groups of treatment, i.e.; normal (N) group, negative control (NC), leaf extract (medium dose [MD]) dose 12.5 and 25 mg/kg body weight (BW), leaf extract chitosan and nanoparticle of mahkota dewa (NPMD) dose 6.25 and 12.5 mg/kg BW. Dextran sulfate sodium induction of 1% w/v was administered through drinking water for 6 weeks of treatment. The suppression effect was observed histopathologically by counting the mitotic cells and hyperplasia cells of the crypt of small intestine with hematoxylin-eosin staining.Results: Mitosis cells mean of NC group was not significant difference either with MD 12.5 (p=0.394) or MD 6.5 (p=0.310). However, mitosis cell mean appears to be lower in the NPMD 12.5 (p=0.09) and NPMD 6.25 (p=0.05) groups than the NC group. There was a significant difference among the mean of hyperplasia NC group and MD and also NPMD group. Significant difference also can be showed between MD 12.5 and MD 25 (p=0.026), and between NPMD 6.25 and NPMD 12.5 (p=0.002), and between MD 12.5 and NPMD 12.5 (p=0.002).Conclusion: Our results demonstrate suppression of hyperplasia small intestine by either nanoparticle or extract of Phaleria macrocarpa extracts. The suppression of mitosis was showed by administration of nanoparticle.


Author(s):  
Ronaldo Panggabean ◽  
Nofita ◽  
Ade Maria Ulfa

Basil leaf have antioxidants such as flavonoids, so it is thought to have a hepatoprotective effect. This study aims to investigate the effect of basil leaf extract on SGOT and SGPT levels in male rats induced by paracetamol. Basil leaf extract was carried out by the percolation method using ethyl acetate solvent, Some 20 male sprague dawley rats were randomly divided into 5 groups. Basil leaf extract (400 mg/kgBB and 600 mg/kgBB) and sylimarin (100 mg/kgBB) were carried out every day for 28 days, paracetamol was induced 24 hours after giving the last day of basil leaf extract. The parameters measured were SGOT and SGPT level to assess the effect of basil leaf extract on liver damage caused by paracetamol. The results showed that basil leaf extract (400 mg/kgBB dan 600 mg/kgBB) showed that the activities of SGOT and SGPT levels were statistically significant (p<0,05) to negative control. Basil leaf extract shows the effect of hepatoprotector on liver induced by paracetamol, however the effect given was not able to equate with positive control.


Author(s):  
KUSMARDI KUSMARDI ◽  
NUR AFIAHUDDIN TUMPU ◽  
ARI ESTUNINGTYAS

Objective: Although an anti-inflammatory effect of Phaleria macrocarpa (Mahkota Dewa in Indonesian) leaf extract has been reported, the extract shows toxicity as the dose increases. Chitosan nanoparticles are known to have transport properties that can enhance the targeting of active compounds to tissues at a lower dose. The present study sought to determine whether the extract in chitosan nanoparticles can suppress angiogenesis in the colon tissue of mice. Methods: We determined the antiangiogenic effect in 6 groups Swiss Webster mice: normal (N) group, negative control (NC) administered drinking water containing DSS 2% w/v (7 d) and followed by water without DSS (7 d) in 3 cycles, 12.5 and 25 mg leaf extract of P. macrocarpa/mouse (EPM 12.5 and EPM 25) groups, and 6.25 and 12.5 mg leaf extract of P. macrocarpa in chitosan nanoparticles/mouse (NPPM 6.25 and NPPM 12.5) groups. Hematoxylin and eosin-stained samples was performed to determine the amount of angiogenesis in the colon tissue. Results: The angiogenesis in the NPPM 12.5 (p = 0.105) and EPM 25 (p = 0.07) groups was not significantly different to that in the negative control group (administered DSS alone). By contrast, angiogenesis in the EPM 12.5 (p = 0.03) and NPPM 6.25 (p = 0.02) groups was significantly less than that in the DSS group. Conclusion: Angiogenesis in the colon tissue of mice was reduced by the extract with or without chitosan nanoparticles. The greatest reduction was found for the 12.5 mg/mouse dose of P. macrocarpa leaf extract in chitosan nanoparticles.


2019 ◽  
Vol 2019 ◽  
pp. 1-13 ◽  
Author(s):  
Zeyu Li ◽  
Dongdong Chen ◽  
Yifan Jia ◽  
Yang Feng ◽  
Cong Wang ◽  
...  

Cholestatic liver injury, due to obstruction of the biliary tract or genetic defects, is often accompanied by progressive inflammation and liver fibrosis. Methane-rich saline (MRS) has anti-inflammatory properties. However, whether MRS can provide protective effect in cholestatic liver injury is still unclear. In this study, Sprague-Dawley rats received bile duct ligation (BDL) to generate a cholestatic model followed by MRS treatment (10 mL/kg, ip treatment) every 12 h after the operation to explore the potential protective mechanism of MRS in cholestatic liver injury. We found that MRS effectively improved liver function, alleviated liver pathological damage, and localized infiltration of inflammatory cells. MRS treatment decreased the expression of hepatic fibrosis-associated proteins to alleviate liver fibrosis. Furthermore, MRS treatment suppressed the TLR4/NF-κB pathway and further reduced the levels of proinflammatory factors. Downregulation of NF-κB subsequently reduced the NLRP3 expression to inhibit pyroptosis. Our data indicated that methane treatment prevented cholestatic liver injury via anti-inflammatory properties that involved the TLR4/NF-κB/NLRP3 signaling pathway.


2016 ◽  
Vol 1 (3) ◽  
pp. 1-10
Author(s):  
Elemo Olajumoke ◽  
Oreagba Ibrahim ◽  
Akinyede Akinwunmi ◽  
Nicholas Viola

2021 ◽  
pp. neurintsurg-2021-017504
Author(s):  
Stefan Wanderer ◽  
Lukas Andereggen ◽  
Jan Mrosek ◽  
Sepide Kashefiolasl ◽  
Gerrit Alexander Schubert ◽  
...  

BackgroundPoor patient outcomes after aneurysmal subarachnoid hemorrhage (SAH) occur due to a multifactorial process, mainly involving cerebral inflammation (CI), delayed cerebral vasospasm (DCVS), and delayed cerebral ischemia, followed by neurodegeneration. CI is mainly triggered by enhanced synthesis of serotonin (5-HT), prostaglandin F2alpha (PGF2a), and cytokines such as interleukins. Levosimendan (LV), a calcium-channel sensitizer, has already displayed anti-inflammatory effects in patients with severe heart failure. Therefore, we wanted to elucidate its potential anti-inflammatory role on the cerebral vasculature after SAH.MethodsExperimental SAH was induced by using an experimental double-hemorrhage model. Sprague Dawley rats were harvested on day 3 and day 5 after the ictus. The basilar artery was used for isometric investigations of the muscular media tone. Vessel segments were either preincubated with LV or without, with precontraction performed with 5-HT or PGF2a followed by application of acetylcholine (ACh) or LV.ResultsAfter preincubation with LV 10−4 M and 5-HT precontraction, ACh triggered a strong vasorelaxation in sham segments (LV 10−4 M, Emax 65%; LV 10−5 M, Emax 48%; no LV, Emax 53%). Interestingly, SAH D3 (LV 10−4, Emax 76%) and D5 (LV 10−4, Emax 79%) segments showed greater vasorelaxation compared with sham. An LV series after PGF2a precontraction showed significantly enhanced relaxation in the sham (P=0.004) and SAH groups (P=0.0008) compared with solvent control vessels.ConclusionsLV application after SAH seems to beneficially influence DCVS by antagonizing 5-HT- and PGF2a-triggered vasoconstriction. Considering this spasmolytic effect, LV might have a role in the treatment of SAH, additionally in selected patients suffering takotsubo cardiomyopathy.


2009 ◽  
Vol 29 (2) ◽  
pp. 93-101 ◽  
Author(s):  
Amal A El-Bakary ◽  
Sahar A El-Dakrory ◽  
Sohayla M Attalla ◽  
Nawal A Hasanein ◽  
Hala A Malek

Methanol poisoning is a hazardous intoxication characterized by visual impairment and formic acidemia. The therapy for methanol poisoning is alcohol dehydrogenase (ADH) inhibitors to prevent formate accumulation. Ranitidine has been considered to be an inhibitor of both gastric alcohol and hepatic aldehyde dehydrogenase enzymes. This study aimed at testing ranitidine as an antidote for methanol acute toxicity and comparing it with ethanol and 4-methyl pyrazole (4-MP). This study was conducted on 48 Sprague-Dawley rats, divided into 6 groups, with 8 rats in each group (one negative control group [C1], two positive control groups [C2, C3] and three test groups [1, 2 and 3]). C2, C3 and all test groups were exposed to nitrous oxide by inhalation, then, C3 group was given methanol (3 g/kg orally). The three test groups 1, 2 and 3 were given ethanol (0.5 g/kg orally), 4-MP (15 mg/kg intraperitoneally) and ranitidine (30 mg/kg intraperitoneally), respectively, 4 hours after giving methanol. Rats were sacrificed and heparinized, cardiac blood samples were collected for blood pH and bicarbonate. Non-heparinized blood samples were collected for formate levels by high performance liquid chromatography. Eye balls were enucleated for histological examination of the retina. Ranitidine corrected metabolic acidosis (p = .025), decreased formate levels (p = .014) and improved the histological findings in the retina induced by acute methanol toxicity.


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