scholarly journals ANTI-INFLAMMATORY AND ORAL TOXICITY ASSESSMENT OF R-38TM: A TRADITIONAL HERBAL SUPPLEMENT FOR ARTHRITIS

2021 ◽  
Vol 84 (1) ◽  
pp. 249-262
Author(s):  
Anis Amirah Mohamad ◽  
Fadzilah Adibah Abdul Majid ◽  
Suvik Assaw ◽  
Fadhilah Zainal Abidin ◽  
Anis Fadhlina ◽  
...  

R-38TM is a traditional herbal supplement for treating arthritis-related conditions. High-performance liquid chromatography (HPLC) analysis was performed for identification and quantification of rosmarinic acid in the R-38TM water extract. The anti-arthritic potential of the R-38TM water extract was investigated by measuring the production of IL-6 and TNF-α in inflamed cells. Xanthine oxidase (XO) and cyclooxygenase-2 (COX-2) inhibition assays were also conducted. The cytotoxic effect of R-38TM water extract was investigated on HSF1184 cell line. Acute and subacute oral toxicity studies were conducted on female Sprague-Dawley (SD) rats. The rosmarinic acid was identified at 1.208 min (3.61 %w/w). The inflamed cells showed a decrease in the production of IL-6 (55.9%) and TNF-α (52.13%). The COX-2 and XO enzymes were moderately inhibited by R-38TM water extract. The cytotoxicity analysis showed no cytotoxic effect on the cell. The acute and subacute oral toxicity studies revealed no mortality and normal body weight at all doses. There were no significant differences (p > 0.05) in organ weight, hematological and biochemical parameters, and histology of liver and kidneys with the control group. In conclusion, R-38TM water extract exhibited no toxic effect orally and may possess potential therapeutic properties against pro-inflammatory diseases including arthritis.

2018 ◽  
Vol 4 (1) ◽  
pp. 28
Author(s):  
Anas Omar Ashkurfu ◽  
Kis Djamiatun

Background: High fat diets are known to cause a positive fat balance and consequently to the accumulation of adipose mass, this diet does not seem to stimulate fat oxidation in the same way in obese and lean subjects. HFD was an inducing factor for ICAM-1 expression in the aorta of Wistar rats. HFD effect on ICAM-1 seems to be time dependent. ICAM-1 is one of the first events in the formation of atherosclerotic lesions. HFD up-regulated Cav-1, regulated expression other biomarker in HFD is eNOS. Recent studies showed that E. longifolia Jack protected HFD animal model from atherosclerosis based on the reduce atherosclerotic plaque size and formation HFD-rats treated with E. longifolia Jack.Objective: To prove that Eurycoma longifolia has anti inflammatory effect on endothelial cell blood vessels of Sprague Dawley rat with high fat diet.Method: Study design was experimental study, by used Randomized Post Test only Control Group Design with Kruskal-Wallis test was used to analyze the differences among groups and followed by a Mann Whitney test. Treatment is ethanolic or water extract of Eurycoma longifolia Jack, and out come are sICAM-1 and eNOS levels. Thirty Sprague Dawley (SD) Rat, were divided into 6 groups. C(-) was SD group, C(+) was group with HFD, X1 (SD treated with EL dosage 10 mg/kg), X2 (SD treated with EL dosage 15 mg/kg), X3 (HFD treated with EL dosage 10 mg/kg), X4 (HFD treated with EL dosage 15 mg/kg).


2019 ◽  
Author(s):  
Xiang Gao ◽  
Xian Ding ◽  
Huan Yi ◽  
Chuan-tao Lin ◽  
Yu-ping Wang ◽  
...  

Abstract Background Perioperative neurocognitive disorder (PND) is the progressive deterioration of cognitive function after surgery. The purpose of this study was to observe the effect of preoperative pain on inflammatory factors and neuronal apoptosis in the hippocampus of rats. Methods 36 adult male Sprague-Dawley rats were randomly divided into 4 groups: the control group, the pain group, the pain+operation group, and the operation group. 6 days before the surgery, the rats received cognitive training, and the cognitive evaluation was carried out on the1, 3 and 7th days after the surgery. The rats were killed on the first, third and seventh days after the surgery (n = 3 rats/day). The cognitive function of rats was evaluated by the Morris Water Maze (MWM), and the expression levels of the pro-inflammatory cytokines interleukin 6(IL-6), Interleukin 1β(IL-1β)and Tumor Necrosis Factor-α(TNF-α), Acetylcholine(Ach)and Cyclic Adenosine monophosphate(cAMP), protein kinase A(PKA)and gamma-aminobutyric acid type A receptors(GABAA) in the hippocampus were measured on the 1st, 3rd and 7th days after the operation. Results Our results showed that the pain model rats exhibited impaired behavior on the first day (P< 0.001), and this lasted until the 7th day after the operation (P≤0.002 and P≤0. 001, respectively). Preoperative pain model rats showed a higher level of apoptosis than that shown by the simple operation rats. On the 1st, 3rd and 7th days after the operation, the protein content of IL-1β, IL-6 and TNF-α in the pain operation group was increased compared to that in the simple operation group (P<0.001). ACh, cAMP, PKA and GABAA expression in the hippocampus was decreased after operation in the preoperative pain model rats. Conclusion Preoperative pain is a key risk factor for the development of PND. The ACh-PKA-GABAA signaling pathway plays a key role in the acetylcholine pathway.


2019 ◽  
Vol 2019 ◽  
pp. 1-10
Author(s):  
Kyungjin Lee ◽  
Ho-Young Choi

Studies on the safety of herbal medicine are essential for the development of new drugs. The aim of this study was to evaluate the no-observed-adverse-effect-level (NOAEL) of HVC1 (Gamisamhwangsasim-tang, a 30% ethanol extract of a mixture of Pruni Cortex, Scutellariae Radix, Coptidis Rhizoma, and Rhei Rhizoma) and identify its target organs after oral administration to Sprague-Dawley (SD) rats repeatedly for 13 weeks. Three test groups were treated with HVC1 at a dose of either 500 (low-dose), 1,000 (middle-dose), or 2,000 (high-dose) mg/kg/day. Another group received high-dose HVC1 and was observed for 4 weeks following treatment to examine recovery from the effects of the extract. All treatment groups were compared to a vehicle control group. During the study, mortality, clinical signs, body weight changes, food consumption, abnormal lesions in the eye, urinary parameters, hematological parameters, blood coagulation time, blood biochemical parameters, changes in organ weight, gross findings, and histopathological changes were examined. No systemic toxicity related to HVC1 was observed in any group, and it was concluded that the NOAEL of HVC1 was 2,000 mg/kg/day. No target organ was identified.


2015 ◽  
Vol 93 (6) ◽  
pp. 465-473 ◽  
Author(s):  
Jaime H. Gómez-Zamudio ◽  
Rebeca García-Macedo ◽  
Martha Lázaro-Suárez ◽  
Maximiliano Ibarra-Barajas ◽  
Jesús Kumate ◽  
...  

Glycine has been used to reduce oxidative stress and proinflammatory mediators in some metabolic disorders; however, its effect on the vasculature has been poorly studied. The aim of this work was to explore the effect of glycine on endothelial dysfunction in aged rats. Aortic rings with intact or denuded endothelium were obtained from untreated or glycine-treated male Sprague–Dawley rats at 5 and 15 months of age. Concentration–response curves to phenylephrine (PHE) were obtained from aortic rings incubated with NG-nitro-l-arginine methyl ester (l-NAME), superoxide dismutase (SOD), indomethacin, SC-560, and NS-398. Aortic mRNA expression of endothelial nitric oxide synthase (eNOS), NADPH oxidase 4 (NOX-4), cyclooxygenase 1 (COX-1), cyclooxygenase 2 (COX-2), tumour necrosis factor (TNF)-α, and interleukin-1 β was measured by real time RT–PCR. The endothelial modulation of the contraction by PHE was decreased in aortic rings from aged rats. Glycine treatment improved this modulator effect and increased relaxation to acetylcholine. Glycine augmented the sensitivity for PHE in the presence of l-NAME and SOD. It also reduced the contraction by incubation with indomethacin, SC-560, and NS-398. Glycine increased the mRNA expression of eNOS and decreased the expression of COX-2 and TNF-α. Glycine improved the endothelium function in aged rats possibly by enhancing eNOS expression and reducing the role of superoxide anion and contractile prostanoids that increase the nitric oxide bioavailability.


2018 ◽  
Vol 96 (1) ◽  
pp. 32-37 ◽  
Author(s):  
Parisa Hasanein ◽  
Rosa Seifi

Alcohol is a severe hepatotoxicant that causes a variety of liver disorders. Rosmarinic acid (RA), a natural phenol, shows some biological activities, including antioxidant and anti-inflammatory effects. We investigated the effects of RA (10 mg/kg) against ethanol-induced oxidative damage and hepatotoxicity in rats. Animals received ethanol (4 g/kg, i.g.) and (or) RA (10 mg/kg, i.g.) daily for 4 weeks. At the end of the treatment period, rats were weighed and use for biochemical, molecular, and histopathological examinations. Ethanol increased hepatic lipid peroxidation (P < 0.001) and decreased hepatic levels of reduced glutathione (P < 0.01), catalase (P < 0.05), and superoxide dismutase (P < 0.001) compared with control group. RA prevented the prooxidant and antioxidant imbalance induced by ethanol in liver. Furthermore, RA ameliorated the increased liver mass, serum levels of ALT, AST, LDH, TNF-α, and IL-6 in ethanol group. Necrosis and infiltration of inflammatory cells in liver parenchyma were attenuated by RA treatment. Our findings showed that RA prevents ethanol-induced oxidant/antioxidant imbalance and liver injury in an experimental model of ethanol-induced hepatotoxicity. Therefore, RA may be a good candidate to protect against ethanol-induced hepatotoxicity; this deserves consideration and further examination.


2013 ◽  
Vol 2013 ◽  
pp. 1-14 ◽  
Author(s):  
Kwan Yuet Ping ◽  
Ibrahim Darah ◽  
Yeng Chen ◽  
Subramaniam Sreeramanan ◽  
Sreenivasan Sasidharan

DespiteEuphorbia hirtaL. ethnomedicinal benefits, very few studies have described the potential toxicity. The aim of the present study was to evaluate thein vivotoxicity of methanolic extracts ofE. hirta. The acute and subchronic oral toxicity ofE. hirtawas evaluated in Sprague Dawley rats. The extract at a single dose of 5000 mg/kg did not produce treatment related signs of toxicity or mortality in any of the animals tested during the 14-day observation period. Therefore, the LD 50 of this plant was estimated to be more than 5000 mg/kg. In the repeated dose 90-day oral toxicity study, the administration of 50 mg/kg, 250 mg/kg, and 1000 mg/kg/day ofE. hirtaextract per body weight revealed no significant difference (P>0.05) in food and water consumptions, body weight change, haematological and biochemical parameters, relative organ weights, and gross findings compared to the control group. Macropathology and histopathology examinations of all organs including the liver did not reveal morphological alteration. Analyses of these results with the information of signs, behaviour, and health monitoring could lead to the conclusion that the long-term oral administration ofE. hirtaextract for 90 days does not cause sub-chronic toxicity.


2004 ◽  
Vol 23 (2) ◽  
pp. 107-112 ◽  
Author(s):  
Shoji Tsubuku ◽  
Kazuhisa Hatayama ◽  
Kazunori Mawatari ◽  
Miro Smriga ◽  
Takeshi Kimura

l-Glutamine (Gln) is a semiessential amino acid used in enteral feeding in critically ill patients, and is contained in numerous dietary supplements available to the general public. This study evaluated toxicological effects of Gln in male and female Sprague-Dawley rats. Gln produced by Ajinomoto Co. (Tokyo, Japan) was incorporated into a standard diet at doses equal to 1.25%, 2.5%, and 5.0% ( w/ w), respectivelly. A control group of rats received only a standard diet. All diets were administered ad libitum for 13 consecutive weeks. To examine recoverability of any potential effects, the administration period was followed by a 5-week recovery period, during which only the standard diet was provided to all animals. Throughout the administration and recovery periods, no deaths were observed, and no changes in diet consumption, ophthalmologic findings, gross pathology, and histopathology were detected. Several changes in urine parameters (total protein, urine pH, and a positive incidence (±) of ketone bodies) were observed in the 2.5% and 5.0% groups at the end of the administration period. Minor increases were found in hematology parameters for the 5.0% group (platelet count, γ-globulin, lactate dehydrogenase [LDH]), but all changes were within physiological range. No effects of administration were observed in the 1.25% group. The no-observed-adverse-effect level (NOAEL) for Gln was estimated at 1.25% for both genders (males 0.83 ± 0.01 g/kg/day; females, 0.96 ± 0.06 g/kg/day).


2020 ◽  
Vol 7 (1) ◽  
pp. 27-38
Author(s):  
M. K. Nik Hasan ◽  
I. Abdul Wahab ◽  
H. H. Mizaton ◽  
M. A. Rasadah

Myrmecodia plant or ant-nest plant is from Rubiaceae family. Rubiaceae are mainly tropical woody plants, consist mostly of trees and shrubs and can be found in temperate regions. Myrmecodia platytyrea (MyP) are believed to have medicinal value.  This study was designed in order to investigate the effect of MyP extract as anti hypercholesterolemic agent. The results showed that treatment of MyP can significantly reduce (p<0.05) low density lipoprotein (LDL) compared to negative control group. The extract was significantly increase (p<0.05) high density lipoprotein (HDL) concentration compared to negative control group. Besides that, MyP increased fecal cholesterol and fecal bile compared to normal control group. It was also found that lipid profile was significantly decreased (p<0.05) in MyP treatment group. All biochemistry data showed that MyP water extract was not toxic at all.


2020 ◽  
Vol 7 (2) ◽  
pp. 69-80
Author(s):  
M. K. Nik Hasan ◽  
I. Abdul Wahab ◽  
H. H. Mizaton ◽  
M. A. Rasadah

Myrmecodia plant or ant-nest plant is from Rubiaceae family. Rubiaceae are mainly tropical woody plants, consist mostly of trees and shrubs and can be found in temperate regions. Myrmecodia platytyrea (MyP) are believed to have medicinal value.  This study was designed in order to investigate the effect of MyP extract as anti hypercholesterolemic agent. The results showed that treatment of MyP can significantly reduce (p<0.05) low density lipoprotein (LDL) compared to negative control group. The extract was significantly increase (p<0.05) high density lipoprotein (HDL) concentration compared to negative control group. Besides that, MyP increased fecal cholesterol and fecal bile compared to normal control group. It was also found that lipid profile was significantly decreased (p<0.05) in MyP treatment group. All biochemistry data showed that MyP water extract was not toxic at all.


2021 ◽  
Vol 20 (11) ◽  
pp. 2305-2310
Author(s):  
Jinan Zheng ◽  
Qing Huang ◽  
Jingjing Fang

Purpose: To determine the protective effect of puerarin against acute liver injury in septic rats, and the mechanism involved.Methods: Eighty-seven Sprague-Dawley (SD) rats were assigned to control, sepsis and puerarin groups (each having 29 rats). Serum levels of NF-kB, TNF-α, IL-1 β, IL-6, ALT and AST were assayed. Liver lesions and levels of NO, SOD, iNOS and malondialdehyde (MDA) were measured using standard procedures.Results: Compared with the control group, the levels of NF-kB, TNF-α, IL-1β, IL-6, AST, ALT, NO, MDA and iNOS significantly increased in the sepsis group, while SOD level decreased significantly. In contrast, there were marked decreases in NF-kB, TNF-α, IL-1β, AST, ALT, NO, MDA and iNOS in puerarin group, relative to the sepsis group, while SOD expression level was significantly increased (p <0.05). The level of p-p38 in liver of septic rats was up-regulated, relative to control rats, while Nrf2 significantly decreased (p < 0.05). The expression level of p-p38 in the puerarin group was significantly decreased, relative to the sepsis group, while the expression level of Nrf2 significantly increased (p < 0.05).Conclusion: Puerarin mitigates acute liver injury in septic rats by inhibiting NF-kB and p38 signaling pathway, down-regulating proinflammatory factors, and suppressing oxidative stress. Thus, puerarin may be developed for use in the treatment liver injury.


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