Evaluating the Effects of Chronic Administration of Natural Honey on the Development of Dependence on Morphine in the Male Rats

2019 ◽  
Vol 25 (4) ◽  
pp. 287-293
Author(s):  
Elham Fazli shojai ◽  
Moslem Najafi ◽  
Mohammad Charkhpour

Background: According to the previous studies, the exact mechanism of dependence on opioids and withdrawal syndrome has not been fully understood but one of the most important mechanisms is the increase of pro-inflammatory cytokines in CNS. On the other way, previous studies showed that natural honey (NHO) has anti-inflammatory properties. This study was aimed to evaluate the effects of chronic administration of natural honey on the development of morphine dependence in male rats. Methods: Honey was prepared from Tarom Oliya region in Zanjan province. Experiments were performed on male Wistar rats weighing 225-275 g, randomly divided into 6 groups (n=8). The study groups included morphine group, the three doses of morphine plus honey group (at doses of 200,400 and 800 mg/kg, i.p.), the morphine plus vehicle group, and the saline group. The subcutaneous injections of additive doses of morphine were used for 9 days to create morphine dependency. On the 9th day, one hour after the morning dose of morphine, naloxone (4 mg/kg, i.p.) was injected, and symptoms of withdrawal syndrome were assessed for 60 minutes. Then, blood samples were taken to measure TNF-α. One-way ANOVA and Tukey tests were used to compare the results. P- Value of <0.05 was considered as statistically significant. Results: The results of this study showed that intraperitoneal injection of honey at 3 doses (200, 400 and 800 mg/kg with p <0.001) could significantly decrease the total score of the symptoms compared to the morphine-vehicle control group. Natural honey (NHO) could significantly decrease TNF-α at dose of 400 mg/kg. Conclusion: The results indicated that chronic administration of NHO had beneficial effects in reducing symptoms of morphine withdrawal syndrome, and this effect is probably due to the anti-inflammatory effect caused by the polyphenolic compounds in honey.<br />

2019 ◽  
Vol 25 (1) ◽  
pp. 17-23
Author(s):  
Alireza Parvizpur ◽  
Kosar Parnian ◽  
Sama Samankan ◽  
Fatemeh Fathiazad ◽  
Mohammad Charkhpour

Background: Long-term exposure to opioids may lead to physical dependence and tolerance. The purpose of this study was to investigate the effects of Citrus aurantium essential oil (CEO) on the morphine-induced tolerance and dependence. Methods: To evaluate morphine tolerance, the experiments were carried out in 6 rat groups (n=8) in the weight range of 225-275 g. The control group received morphine (10 mg/kg/day) and the test groups received morphine with the different doses of essential oil (CEO 20, 40 and 80 mg/kg/day) or 4 mL/kg of essential oil vehicle (KolliphorÒ HS15 30% in normal saline that adjusted in pH=7.4 with phosphate buffer) intraperitoneally. The hot-plate test was carried out every other day, 90 minutes after the injections. To examine morphine withdrawal, male Wistar rats were divided into seven groups (n=8) randomly, including: morphine sulphate, CEO (20, 40 and 80 mg/kg) + morphine, vehicle of CEO + morphine. The rats were rendered morphine-dependent by injection of additive doses of morphine subcutaneously for 9 days. The procedure of the morphine administration was as following protocol: day1: 5 mg/kg/12h, day 2 and 3: 10 mg/kg/12h, day 4 and 5: 15 mg/kg/12h, day 6 and 7: 20 mg/kg/12h and day 8 and 9: 25 mg/kg/12h. In the 9th day, 2 hours after the last dose of morphine, naloxone (4 mg/kg) was injected intraperitoneally. Some withdrawal behaviors were counted for 60 minutes. Results: Morphine tolerance was completed after 5 days in the control group. The vehicle group showed tolerance on the 9th day (p-value=0.991), 20mg group in the 13th day (p-value to control=0.010, to vehicle=0.049), 40 mg group on the 15th day (p-value to control and vehicle<0.001) and 80 mg group on the 13th day (p-value to control= 0.001, to vehicle= 0.007). The results showed that CEO could reduce the morphine withdrawal syndrome and total withdrawal score (TWS). Intraperitoneally injection of CEO in two doses (40 mg/kg with p<0.001 and 80 mg/kg with p<0.01) significantly reduced the TWS in comparison to the morphine+vehicle treated group. Conclusion: The results indicated that chronic administration of C. aurantium essential oil extracted had beneficial effects in reducing morphine withdrawal syndrome and could significantly delay tolerance to morphine.


Author(s):  
Dejidmaa B ◽  
Uuganbayar B ◽  
Erdenechimeg Ch ◽  
Chimedragchaa Ch ◽  
Munkhzul G

Gardi -5 has been used in traditional Mongolian medicine as an analgesic and antibacterial medicine. The drug has been studied in chemical-pharmacological research. We have a new natural patch from the prepared Gardi-5. The present work was undertaken to evaluate the traditional drug Gardi patch for its anti-inflammatory activity.The method of Miho Sekiquichi was used to study acute inflammation. Rats in groups of five each were treated with vehicle, Gardi patch and Ketoprofen patch one hour prior to Carrageenan injection. 0.1 ml of 1% Carrageenan was injected into the sub plantar tissue of left hind paw of each rat. Swelling of carrageenan injected foot was measured at 0, 30, 60, 120, 180, 240, 300 mins using Plethysmometer (UGO Basile, Italy). The right hind paw was injected with 0.1 ml of vehicle.The Gardi patch significantly (p=0.000) inhibited carrageenan induced rat paw edema as compared to control group. In assay data, the TNF-α, PGE2 secretion in serum were highly elevated by carrageenan induction but administration of Gardi patch significantly reduced serum secretion of inflammatory mediators as compared to vehicle group. Gardi patch has an anti-inflammatory properties.


2016 ◽  
Vol 27 (4) ◽  
pp. 387-391
Author(s):  
Mohammad Reza Shahraki ◽  
Zahra Samadi Noshahr ◽  
Hassan Ahmadvand ◽  
Alireza Nakhaie

Abstract Background: Insulin resistance is a metabolic disorder which affects the diabetes mellitus pathophysiology and alters the cell excitability. This study has been designed to evaluate the anti-nociceptive and anti-inflammatory effects of chronic administration of Withania somnifera root (WSR) in fructose drinking water rats. Methods: An experiment was carried out on 48 Wistar-Albino male rats, weighting 200±30 g, which were divided into six groups (n=8): control group (C), control morphine (CM), W. somnifera group (WS) which received WSR (62.5 mg/g diet), W. somnifera naloxone group (WSN) which received WSR and naloxone, fructose (F) group which received fructose drinking water and FWS group which received fructose-enriched drinking water and WSR during the trial period. A biphasic pain response was induced after intraplantar injection of formalin (50 μL, 1%). Pain behavior was measured using Dubuisson methods. The obtained data were analyzed by SPSS software V. 18, using ANOVA and Tukey test. Results were expressed as mean±SD. Statistical differences were considered significant at p<0.05. Results: The results showed that the insulin resistance index, blood sugar, insulin, IL-6, TNF-α, and acute and chronic pain score in the F group were significantly increased in comparison with the control group, but these parameters in the FWS group were significantly decreased compared with the F group (p<0.001). Conclusions: Our findings indicated that chronic oral administration of WSR has analgesic and anti-inflammatory effects in fructose drinking water rats and causes improved insulin resistance index.


2015 ◽  
Vol 26 (1) ◽  
pp. 114-117

Garidi-5, a traditional medicine composed of 5 herbs including Terminalia chebula Retz., Aconitum Kusnezoffii Reichb., Acorus calamus L., Saussurea lappa L., and musk of Moschus moschiferus, has been used in traditional Mongolian medicine as an analgesic and antibacterial medicine. The present work was undertaken to evaluate the traditional drug Garidi-5 for its anti-inflammatory activity. Methods. The method of Winter et al. was used to study acute inflammation. Rats in groups of five each were treated with vehicle, Garidi-5 (20, 80 and 200 mg/kg, p.o.) and Indometacin (10 mg/kg) one hour prior to Carrageenan injection. 0.1 ml of 1% Carrageenan was injected into the subplantar tissue of left hind paw of each rat. Swelling of carrageenan injected foot was measured at 0, 0.5, 2, 4 h using Plethysmometer (UGO Basile, Italy)). The right hind paw was injected with 0.1 ml of vehicle. Results. The Garidi-5 (20, 80 and 200 mg/kg) significantly (P<0.01) inhibited carrageenan induced rat paw edema as compared to control group. Maximum inhibition of paw edema was observed with Garidi-5 (80 and 200 mg/kg) at 4 h when compared to the control group. In assay data, the TNF-α secretion in serum were highly elevated by carrageenan induction but administration of Garidi-5 significantly reduced serum secretion of inflammatory mediators as compared to vehicle group. Conclusion. In conclusion, these results suggested that Mongolian traditional drug Garidi-5 analgesic and anti-inflammatory effects.


2021 ◽  
pp. 074823372110226
Author(s):  
Gholamali Jelodar ◽  
Mansour Azimzadeh ◽  
Fatemeh Radmard ◽  
Narges Darvishhoo

Exposure to mobile phone radiation causes deleterious health effects on biological systems. The objects of this study were to investigate the effect of 900-MHz radiofrequency waves (RFW) emitted from base transceiver station antenna on intrapancreatic homocysteine (Hcy), tumor necrosis factor-α (TNF-α), and nerve growth factor (NGF) as predisposing factors involved in pancreatic beta cell damage. Thirty male rats (Sprague-Dawley, 200 ± 10 g) were randomly divided into the control (without any exposure) and exposed groups: short time (2 h/day), long time (4 h/day), and exposed to 900-MHz RFW for 30 consecutive days. On the last days of the experiment, animals were killed and pancreas tissue was dissected out for evaluation of serotonin, Hcy, TNF-α, and NGF. There was a significant decrease in the serotonin and NGF levels in the pancreatic tissue of exposed groups compared to the control group ( p < 0.05). Also, the levels of serotonin and NGF in the long-time exposure were significantly lower than the short-time exposure ( p < 0.05). However, levels of Hcy and TNF-α were significantly increased in the pancreas of exposed groups compared to the control groups ( p < 0.05). Exposure to 900-MHz RFW decreased pancreatic NGF and serotonin levels and increased the proinflammatory markers (Hcy and TNF-α), which can be a predisposing factor for type 2 diabetes.


Biomedicines ◽  
2021 ◽  
Vol 9 (7) ◽  
pp. 716
Author(s):  
Oksana Sintsova ◽  
Irina Gladkikh ◽  
Anna Klimovich ◽  
Yulia Palikova ◽  
Viktor Palikov ◽  
...  

Currently the TRPV1 (transient receptor potential vanilloid type 1) channel is considered to be one of the main targets for pro-inflammatory mediators including TNF-α. Similarly, the inhibition of TRPV1 activity in the peripheral nervous system affects pro-inflammatory mediator production and enhances analgesia in total. In this study, the analgesic and anti-inflammatory effects of HCRG21, the first peptide blocker of TRPV1, were demonstrated in a mice model of carrageenan-induced paw edema. HCRG21 in doses of 0.1 and 1 mg/kg inhibited edema formation compared to the control, demonstrated complete edema disappearance in 24 h in a dose of 1 mg/kg, and effectively reduced the productionof TNF-α in both doses examined. ELISA analysis of blood taken 24 h after carrageenan administration showed a dramatic cytokine value decrease to 25 pg/mL by HCRG21 versus 100 pg/mL in the negative control group, which was less than the TNF-α level in the intact group (40 pg/mL). The HCRG21 demonstrated potent analgesic effects on the models of mechanical and thermal hyperalgesia in carrageenan-induced paw edema. The HCRG21 relief effect was comparable to that of indomethacin taken orally in a dose of 5 mg/kg, but was superior to this nonsteroidal anti-inflammatory drug (NSAID) in duration (which lasted 24 h) in the mechanical sensitivity experiment. The results confirm the existence of a close relationship between TRPV1 activity and TNF-α production once again, and prove the superior pharmacological potential of TRPV1 blockers and the HCRG21 peptide in particular.


Author(s):  
Maciej Kwiatek ◽  
Tomasz Gęca ◽  
Anna Kwaśniewska

The advantage in response of Th2 over Th1 is observed in normal pregnancy in peripheral blood. A disturbance of this balance can lead to symptoms of miscarriage and pregnancy loss. The aim of this study was to evaluate the pro- and anti-inflammatory cytokines in sera of women who were diagnosed with missed miscarriage in the first trimester and to compare this systemic immune response to the response in women with normal pregnancy. The study group consisted of 61 patients diagnosed with missed miscarriage. In total, 19 healthy women with uncomplicated first trimester created the control group. Cytokines were determined in the maternal serum by ELISA. The analysis included INF-γ, TNF-α, Il-1β, Il-4, Il-5, Il-6, Il-9, Il-10, Il-13 and TGF-β1. Th1 cytokine levels in the study group reached slightly higher values for INF-γ, Il-1β and slightly lower for IL-6 and TNF-α. In turn, Th2 cytokine levels in the study group were slightly higher (Il-9, Il-13), significantly higher (Il4, p = 0.015; Il-5, p = 0.0003) or showed no differences with the control group (Il-10). Slightly lower concentration involved only TGF-β1. Analysis of the correlation between levels of pro- and anti-inflammatory cytokines resulted in some discrepancies, without showing predominance of a specific immune response. The results did not confirm that women with missed miscarriage had an advantage in any type of immune response in comparison to women with normal pregnancy.


2021 ◽  
Vol 2021 ◽  
pp. 1-13
Author(s):  
Reza Shirazinia ◽  
Ali Akbar Golabchifar ◽  
Vafa Baradaran Rahimi ◽  
Abbas Jamshidian ◽  
Alireza Samzadeh-Kermani ◽  
...  

Lead is one of the most common environmental contaminants in the Earth’s crust, which induces a wide range of humans biochemical changes. Previous studies showed that Opuntia dillenii (OD) fruit possesses several antioxidant and anti-inflammatory properties. The present study evaluates OD fruit hydroalcoholic extract (OHAE) hepatoprotective effects against lead acetate- (Pb-) induced toxicity in both animal and cellular models. Male rats were grouped as follows: control, Pb (25 mg/kg/d i.p.), and groups 3 and 4 received OHAE at 100 and 200 mg/kg/d + Pb (25 mg/kg/d i.p.), for ten days of the experiment. Thereafter, we evaluated the levels of alkaline phosphatase (ALP), alanine aminotransferase (ALT), and aspartate aminotransferase (AST), catalase (CAT) activity and malondialdehyde (MDA) in serum, and liver histopathology. Additionally, the cell study was also done using the HepG2 cell line for measuring the direct effects of the extract on cell viability, oxidative stress MDA, and glutathione (GSH) and inflammation tumor necrosis factor-α (TNF-α) following the Pb-induced cytotoxicity. Pb significantly increased the serum levels of ALT, AST, ALP, and MDA and liver histopathological scores but notably decreased CAT activity compared to the control group ( p < 0.001 for all cases). OHAE (100 and 200 mg/kg) significantly reduced the levels of serum liver enzyme activities and MDA as well as histopathological scores while it significantly increased CAT activity compared to the Pb group ( p < 0.001 –0.05 for all cases). OHAE (20, 40, and 80 μg/ml) concentration dependently and significantly reduced the levels of MDA and TNF-α, while it increased the levels of GSH and cell viability in comparison to the Pb group ( p < 0.001 –0.05 for all cases). These data suggest that OHAE may have hepatoprotective effects against Pb-induced liver toxicity both in vitro and in vivo by its antioxidant and anti-inflammatory activities.


2020 ◽  
Author(s):  
Wenjun Shi ◽  
Fei Yang ◽  
Liting Wang ◽  
Nankun Qin ◽  
Chengxiang Wang ◽  
...  

Abstract BackgroundPlantaginis semen has been widely used as folk medicine and health care food against hyperuricemia (HUA) and gout, but little was known about its pharmacological mechanism. MethodsThe model was established by potassium oxonate intragastric administration. 42 Sprague-Dawley (SD) male rats were randomly divided into the control group, model group, benzbromarone group (10 mg/kg) and three Plantaginis semen groups (n = 7). The Plantaginis semen groups were treated orally with Plantaginis semen at 0.9375, 1.875 and 3.75 g/kg for 28 days. The levels of serum uric acid (UA), creatinine (Cr), triacylglycerol (TG) and tumor necrosis factor-α (TNF-α) were detected using enzyme-linked immunosorbent assay kits. Ultra performance liquid chromatography quadrupole time of flight mass spectrometry (UPLC-Q-TOF/MS) was used as the basis for serum lipidomics analysis, and orthogonal partial least squares discriminant analysis (OPLS-DA) was carried out for the pattern recognition and characteristic metabolites identification. The relative levels of critical regulatory factors of urate anion transporter 1(URAT1) and phosphatidylinositol 3-kinase/ protein kinases B (PI3K/Akt) were determined by quantitative real-time polymerase chain reaction (RT-qPCR). ResultsCompared with the model group, the levels of serum UA, Cr, and TG were significantly (p<0.01) decreased in benzbromarone and three Plantaginis semen groups and the level of serum TNF-α was significantly (p<0.05) decreased in benzbromarone and low dose of Plantaginis semen group. With lipidomics analysis, significant lipid metabolic perturbations were observed in HUA rats, 13 metabolites were identified as potential biomarkers and glycerophospholipid metabolism pathway was mostly affected. These perturbations can be partially restored via treatment of benzbromarone and Plantaginis semen. Additionally, the URAT1 and PI3K/Akt mRNA expression levels were significantly decreased (p<0.05) after treatment with benzbromarone and high dose of Plantaginis semen. ConclusionsPlantaginis semen had significant anti-HUA, anti-inflammatory and renal protection effects and could attenuate potassium oxonate-induced HUA through regulation of lipid metabolism disorder. Trial registrationNot applicable


Molecules ◽  
2020 ◽  
Vol 25 (16) ◽  
pp. 3697
Author(s):  
Tae-Kyeong Lee ◽  
Bora Kim ◽  
Dae Won Kim ◽  
Ji Hyeon Ahn ◽  
Hyejin Sim ◽  
...  

This current study investigates the facilitative effects and mechanisms of decursin, a major component of Angelica gigas Nakai (AGN), and AGN root extract on hair growth in mice. We perform high-performance liquid chromatography on AGN extract to show it contains 7.3% decursin. Hairs in mouse dorsal skin are shaved distilled in water, 0.15% decursin, and 2% AGN root extract (0.15% decursin in the diluted extract) and topically applied twice a day for 17 days. Hematoxylin and eosin staining are done to examine the morphological changes in the hair follicles. To compare the effects of decursin and AGN extract on inflammatory cytokines in the dorsal skin, Western blot analysis and immunohistochemistry for tumor necrosis factor α (TNF-α) and interleukin (IL)-1β as pro-inflammatory cytokines, and IL-4 and IL-13 as anti-inflammatory cytokines are conducted. The results show that the application of decursin and AGN extract confer effects on hair growth. Hair growth is significantly facilitated from seven days after the treatments compared to that in the control group, and completely grown hair was found 17 days after the treatments. The protein levels and immunoreactivity of TNF-α and IL-1β in this case are significantly decreased, whereas the IL-4 and IL-13 levels and immunoreactivity are significantly increased compared to those in the control group. Additionally, high-mobility group box 1, an inflammatory mediator, is elevated by the topical application of decursin and AGN extract. Taken together, the treatment of mouse dorsal skin with AGE root extract containing decursin promotes hair growth by regulating pro- and/or anti-inflammatory cytokines. We, therefore, suggest that AGN root extract as well as decursin can be utilized as materials for developing hair growth-facilitating treatments.


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