Effects of Chaerophyllum macropodum Boiss. leaves essential oil in inflammatory and neuropathic pain: uncovering the possible mechanism of action.

BACKGROUND: Chaerophyllum macropodum Boiss. (popularly known as "Jafari farangi kohestani") is a predominant medicinal plant traditionally utilized in the treatments of peritoneal inflammation and headache in Persian folk medicine. Here, we have revealed the anti-neuropathic and anti-nociceptive activities of C. macropodum leaves essential oil (CMEO) in addition to uncovering the possible mechanisms of action. METHODS: Formalin-induced paw licking model was used to assess the anti-nociceptive activity of CMEO and its major constituent, terpinolene (TP). The anti-nociceptive activity of these compounds was determined by investigating the roles of various non-opioid and NO-cGMP-K+ channels. Additionally, the anti-neuropathic potential of CMEO and TP was determined using cervical spinal cord contusion/CCS technique. RESULTS: The CMEO exerted significant anti-nociceptive activity with a remarkable activity seen in the second phase of formalin-induced paw licking model and this activity were remarkably reversed by pre-treatment of naloxone (an opioid antagonist). Pretreatment with several types of NO-cGMP-potassium channel pathway meaningfully reversed the anti-nociceptive potential of CMEO in phase II of formalin model. Moreover, pre-treatment with several antagonists of non-opioid receptors revealed that only the antagonist of TRPV-1, serotonin type 3, 5-HT2, α2 adrenergic, and CB1 receptors (capsaicin, ondansetron, ketanserin, yohimbine, and SR141716A, respectively) reversed CMEO anti-nociception. CMEO and TP also remarkably reversed hyperalgesia and mechanical allodynia in the CCS technique. CONCLUSION: The CMEO exerts anti-nociceptive and anti-neuropathic activities via the modulation of NO-cGMP potassium channel pathway, opioid as well as several non-opioid receptor activity. TP might partly contribute to the observed activities of CMEO.

Insight into the possible mechanism(s) involved in the antinociceptive and antineuropathic activity of Descurainia sophia L. Webb ex Prantl essential oil.

ETHNOPHARMACOLOGICAL RELEVANCE: Descurainia sophia (L.)(Brassicaceae), popularly known as "Khaksheer", is a native species widely distributed in Iran. The seeds and essential oil has been used in local traditional medicine (Persian folk ethnomedicine) to treat fever, inflammation, back pain, and headache. AIM OF THE STUDY: To investigate in vitro anti-nociceptive and antineuropathic activities of Descurainia sophia seeds essential oil (DSEO) in rats and to determine the possible mechanism(s) involved. MATERIALS AND METHODS: The antinociceptive activity of DSEO or Linolenic acid (LA) was evaluated using the formalin induced paw licking test followed by determination on the role of NO-cGMP-K+ channel pathway as well as a number of non-opioid receptor systems (vanilloid, dopamine, cannabinoid, serotonin, peroxisome proliferator activated, and adrenergic receptors) in the modulation of DSEO-induced antinociceptive activity. Additionally, the cervical spinal cord contusion (CCS) model was used to study antineuropathic potential of DSEO or LA. RESULTS: DSEO exerted significant (p < 0.05) antinociceptive activity in formalin test (both phases) and altered mechanical allodynia and hyperalgesia observed in the CCS model. Pretreatment with glibenclamide, Nω-nitro-L-arginine methyl ester, tranilast, methylene blue, SCH23390, SR141716A and SR144528 restored DSEO-induced antinociceptive activity observed in the formalin test. Furthermore, LA also reduced nociceptive responses induced in the formalin and CCS models. CONCLUSION: DSEO inhibits inflammatory mediated nociceptive response partly via the modulation of NO-cGMP-K+ channels pathway well as the activation of vanilloid, dopamine, and cannabinoid receptors, and exerts antineuropathic activity possibly via the modulation of inflammatory mediated activity. Thus, these findings confirm the Persian ethno-medicine claim on the efficacy of D. Sophia.

Physospermum cornubienseL. alleviates nociceptive and neuropathic pain: Evidences and possible mechanisms.

ETHNOPHARMACOLOGICAL RELEVANCE: In Iranian/Persian folkloric medicine, Physospermum cornubiense (Shokaran Baghi in Persian) is used for the treatment of pain and inflammation. OBJECTIVE: This modern examination included Swiss mice to investigate the anti-neuropathic and anti-nociceptive effects of Physospermum cornubiense essential oil (PCEO). MATERIALS AND METHODS: To determine PCEO 's anti-nociceptive function in formalin-induced paw licking (FML) paradigm, researchers looked at the arginine-nitric oxide and potassium channels pathway in addition to involvements of more specific examples of receptors such as adrenergic, opioid, cannabinoid, peroxisome proliferator-activated (PPA), and transient receptor potential vanilloid. The CVC or cervical spinal cord contusion exemplar has also been used to induce neuropathic pain. RESULTS: PCEO (450mg/kg) relative to control mice in the phase_ II of FML exemplar provided strong antinociception (p < 0.001). Furthermore, pre-treatments with arginine, glibenclamide, methylene blue, L-NAME, SNP, GW6471, naloxonazine, and GW9662 (p < 0.05) returned the PCEO antinociceptive response in the FML (inflammatory phase) model. Orally limonene administration significantly diminished (p < 0.001) acute pain in inflammatory phase of FML test. Moreover, the von Frey test indicated that both PCEO and limonene could return neuropathic pain (mechanical allodynia) in CVC mice. CONCLUSION: The results obtained from this study, together with literature, give evidence of properties of PCEO for therapy of antinociceptive and neuropathic pain.

Thymus persicus (Ronniger ex Rech. f.) Jalas alleviates nociceptive and neuropathic pain behavior in mice: Multiple mechanisms of action.

ETHNOPHARMACOLOGICAL RELEVANCE: Thymus persicus (Roniger ex Reach F.) is an Iranian endemic medicinal plant of which essential oil and various products have numerous food and pharmaceutical applications (headache and fever treatments). OBJECTIVE: This modern research included Swiss mice to investigate the anti-nociceptive and anti-neuropathic effects of Thymus persicus aerial parts essential oil (TPEO). MATERIALS AND METHODS: To determine TPEO's anti-nociceptive function in the formalin-induced paw licking (FML), researchers looked at the L-arginine/NO/cGMP/KATP channel signaling pathway as well as multiple receptors as with serotonin, morphine, dopamine, and peroxisome proliferator-activated receptors. The CVC or cervical spinal cord contusion exemplar has also been used to induce neuropathic pain. RESULTS: TPEO (50, 100, and 150 mg/kg) relative to control mice in the phase-II of FML provided strong antinociception (p < 0.05, p < 0.01, p < 0.001, respectively). Furthermore, methylene blue, glibenclamide, Nω-nitro-L-arginine methyl ester, naloxonazine, nor-binaltorphimine, prazosin, yohimbine, and ondansetron pre-treating restored the TPEO anti-nociceptive activity in the FML (phase-II) exemplar (p < 0.05). In phase-II of the FML exemplar, carvacrol (one of the active components of TPEO) also greatly reduced pain (p < 0.001). Likewise, in CVC mice, TPEO altered mechanical allodynia and hyperalgesia. CONCLUSION: It was attained magnificently that TPEO could exerts antinociceptive effects through the involvement of L-arginine/NO/cGMP/KATP signaling pathway, adrenergic, opioid, and serotonin receptors. Moreover, it is demonstrate that anti-neuropathic activity of TPEO may be mediated by inflammatory function.

Bupleurum falcatum L. alleviates nociceptive and neuropathic pain: Potential mechanisms of action.

ETHNOPHARMACOLOGICAL RELEVANCE: In Iranian folkloric medicine, Bupleurum falcatum L. (Chinese Thoroughwax) has been used as a selective analgesic remedy for several centuries. OBJECTIVE: The current research was conducted to explore the anti-nociceptive and anti-allodynic action of Bupleurum falcatum L. roots essential oil (BFEO) in Swiss mice. MATERIALS AND METHODS: Formalin-induced paw licking (FIPL) model was applied for exploring of BFEO antinociceptive effects (neurogenic or inflammatory pain). The involvements of L-arginine-NO-cGMP-KATP channel pathway and several receptors such as opioid, peroxisome proliferator-activated (PPA), cannabinoid, transient receptor potential vanilloid, and adrenergic receptors were assesses to detect the anti-nociceptive activity of BFEO. Cervical spinal cord contusion (CSC) paradigm was employed for induction of neuropathic pain. RESULTS: BFEO (100 mg/kg), in the FIPL model, produced significant antinociception compared to the control mice (p < 0.01). Furthermore, L-arginine, methylene blue, glibenclamide, naloxonazine, GW9662, and SR141716A pre-treatments restored the BFEO anti-nociceptive effects (p < 0.05) in the FIPL (second phase) test (p < 0.05). Intraperitoneal administration of saikosaponin A (one of the main constituents of BFEO) partially alleviated (p < 0.05) pain in FIPL test. Likewise, in CSC mice, the von Frey assay exhibited that BFEO could alter mechanical allodynia. CONCLUSION: Finally, it seems that, in male mice, BFEO has both anti-allodynic and anti-nociceptive effects. The present data also suggest activating the L-arginine-NO-cGMP-KATP channel pathway as well as interaction of opioid, PPA, and cannabinoid receptors in the BFEO anti-nociceptive activities. These results also propose that BFEO could effectively attenuate allodynia in CSC mice.

Artemisia biennis Willd.: Anti-Nociceptive effects and possible mechanisms of action.

ETHNOPHARMACOLOGICAL RELEVANCE: Artemisia biennis Willd. (Dermane in Persian) has been used as an antinociceptive remedy in Iranian folkloric medicine. OBJECTIVE: The aim of the present study was to evaluate the anti-nociceptive effects of Artemisia biennis Willd. aerial part essential oil (ABAEO) on male Swiss mice. MATERIALS AND METHODS: Nociceptive pain techniques including acetic acid-induced writhing (AAIW), formalin-induced paw licking (FPL), glutamate-induced paw licking (GPL), and tail-flick (TF) models were applied. We assessed opioid and L-arginine-NO-cGMP-KATP pathways to detect the possible anti-nociceptive properties of ABAEO. In addition, neuropathic pain was induced by the cervical spinal cord contusion model. RESULTS: ABAEO (120 mg/kg) had a significant anti-nociceptive activities in comparison to the control animals (p < 0.05) in the AAIW, TF, GPL, and FPL assays. The selective opioid antagonist (naloxonazine) administration in the AAIW test alleviated the anti-nociceptive effect of ABAEO (p < 0.05). L-arginine, methylene blue, and glibenclamide treatment prevented the ABAEO anti-nociceptive effects (p < 0.05); however, sodium nitroprusside could profoundly potentiate the ABAEO-associated antinociception in the FPL (phase II) test (p < 0.05). In nociceptive pain models, Cr (one of the main constituents of ABAEO) showed significant anti-nociceptive effects (p < 0.05). Moreover, the von Frey results indicated that ABAEO could attenuate mechanical allodynia in mice. CONCLUSION: Our observation revealed the anti-nociceptive effects of ABAEO in male mice. These effects could include, at least in part, modulating glutamatergic mechanisms via opioid systems. Our data output also indicates activating the L-arginine-NO-cGMP-KATP system in ABAEO anti-nociceptive activities.

Effect of Transcutaneous Electrical Nerve Stimulation on the Pain Intensity During Insertion of Needle in Patients Undergoing Spinal Anesthesia: A Randomized Controlled Study.

BACKGROUND AND OBJECTIVES: Needle insertion pain during spinal anesthesia is an unpleasant experience for patients. This study aimed to investigate the effects of Transcutaneous Electrical Nerve Stimulation (TENS) on the pain intensity during the insertion of spinal needles in patients undergoing spinal anesthesia. MATERIALS AND METHODS: In a double-blind clinical trial, 60 candidates for elective Trans Ureteral Lithotripsy surgery under spinal anesthesia were randomly divided into intervention and control groups. The electrodes of the TENS device were placed in the space between L3-L4 and L5-S1 vertebrae. The intensity of pain during insertion of the spinal needle by Visual Analog Scale and the frequency of attempts were recorded. RESULTS: The mean age of the study samples was 34.26 ± 5.07 and 32.8 ± 5.28 in the control and intervention group, respectively. The pain intensity during insertion of spinal needles was less significant in the intervention group compared to the control group (p = 0.001). The number of attempts to insert the spinal needle between the two groups was not statistically significant (p = 0.51). The duration of spinal anesthesia implementation procedure by physician in the intervention group was significantly shorter than that of the control group (p = 0.001). CONCLUSION: The use of TENS effectively reduced the pain of spinal needle insertion. Considering these beneficial effects, it is suggested that this procedure be used to relive pain in patients with spinal anesthesia.

Effect of Nebulized Eucalyptus for Preventing Ventilator-associated Pneumonia in Patients Under Mechanical Ventilation: A Randomized Double Blind Clinical Trial.

BACKGROUND: Pneumonia caused by the ventilator is the most common acquired infection in the intensive care unit (ICU), which increases the morbidity and mortality of the patients. Eucalyptus plant has antiseptic properties that may mollify such morbidity and mortality. OBJECTIVE: To assess the effect of Eucalyptus incense on prevention of pneumonia in patients with endotracheal tube in the ICU. RESEARCH DESIGN: A randomized controlled clinical trial with parallel groups of 100 patients undergoing mechanical ventilation. SETTING: An ICU in a teaching hospital. INTERVENTIONS: Randomization to received Eucalyptus solution 5% (intervention group = 50) and received 10 cc distilled water as an inhaler 3 times/d (every 8 h/d for 20 min) (control group = 50). PRIMARY OUTCOME MEASURES: The incidence of early and delay pneumonia and pulmonary infections based on clinical pulmonary infection criteria were assessed. RESULTS: The incidence of late pneumonia was significantly lower in the intervention group compared with control groups (P < .01). The prevalence of Klebsiella, Candida albicans, and Staphylococcus aureus was significantly decreased in the intervention group (P < .01). CONCLUSION: The results present study showed that Eucalyptus inhalation is effective in reducing the incidence of pulmonary infection in patients under ventilation.

Antinociceptive activity of Cnicus benedictus L. leaf extract: a mechanistic evaluation.

BACKGROUND AND PURPOSE: Cnicus benedictus, a medicinal herb, traditionally had been used for the treatment of stomachache pain. In this study, the possible efficacy of Cnicus benedictus leaf methanolic extract (CBHE) and also cnicin, one of its major constituents, was measured on pain. EXPERIMENTAL APPROACH: In this study, pain assessment tests include writhing, tail-flick (TF), and formalin- induced paw licking test (FIPLT) were used. To understand the possible mediated anti-nociceptive mechanism of CBHE, the opioid mechanism(s), and involvement of the L-arginine/ nitric oxide/cGMP/ATP-sensitive potassium channel pathway (LNCaP) were scrutinized. FINDINGS/RESULTS: In TF and writhing tests, CBHE (150 and 300 mg/kg, i.p) remarkably exhibited an anti-nociceptive effect compared to that of the control. Furthermore, CBHE (150 and 300 mg/kg, i.p) in comparison with the control showed a noteworthy anti-nociceptive effect (P < 0.01) in the tonic phase of FIPLT. In the writhing test, administration of selective opioid antagonist (naltrindole, nor-binaltorphimine, and naloxonazine) attenuated the anti-nociceptive effect of CBHE (300 mg/kg) in comparison with control. Moreover, pre-treatment with Nω-nitro-L-arginine methyl ester hydrochloride, L-arginine hydrochloride, and glibenclamide significantly blocked the CBHE (300 mg/kg) anti-nociception (P < 0.05) while administration of sodium nitroprusside remarkably potentiated (P < 0.05) the antinociception induced by CBHE in the tonic phase of the FIPLT. Besides, cnicin (30 mg/kg) showed noteworthy anti-nociceptive effects in writhing, TF, and FIPLT paradigms. CONCLUSION AND IMPLICATIONS: Taken together, we elucidate that both CBHE and cnicin demonstrated antinociceptive effects in behavioral tests. The possible mechanisms of CBHE antinociception may involve in various neural signaling and modulatory pathways including LNCaP and opioidergic mechanisms.

Intracerebroventricular microinjection of kaempferol on memory retention of passive avoidance learning in rats: involvement of cholinergic mechanism(s).

Purpose of the study: Kaempferol (KM) is a flavonoid found in plant-derived foods and medicinal plants. Recently, it is well established that KM plays a protective role to develop Alzheimer's disease. The current study aimed at evaluating the effect of intracerebroventricular micro-injection of KM on memory retention of passive avoidance learning (MRPAM) and identifying the potentially related cholinergic mechanisms (ChMs) in rats. Materials and methods: In the current study, male Wistar rats randomly divided into control, vehicle and KM (10, 20 and 40 µg/rat) groups. Moreover, MRPAM was evaluated by shuttle box test. The role of ChM was studied using non-selective and selective acetylcholine antagonists (scopolamine [SCN], 4-DAMP and methoctramine [MN], respectively) as well as pirenzepine (PZ) in combination with KM. Results: The employment of KM (40 µg/rat) improved the SCN-induced memory impairment in MRPAM. Co-treatment with KM (40 µg/rat) plus 4-DAMP significantly increased the step-through latency (STL, P < 0.05; 167 ± 28 s) and decreased the total dark chamber (TDC, P < 0.05; 121 ± 31 s) compared with those of the 4-DAMP group (STL: 75 ± 13 s; TDC: 178 ± 46 s). Co-treatment with KM (40 µg/rat) plus PZ attenuated STL, and also increased TDC (P < 0.01; 220 ± 28 s) compared with those of the PZ group. Co-treatment with KM (10 and 20 µg/rat) and MN increased STL (P < 0.05), and deceased TDC compared with those of the MN group (P < 0.01). Conclusions: Totally, the results of the present study showed that cholinergic system may be involved in improving effect of KM on SCN-induced memory impairment.

Autologous Platelet-Released Growth Factor and Sexual Dysfunction Amendment: A Pilot Clinical Trial of Successful Improvement Sexual Dysfunction after Pelvic Irradiation

Sexual dysfunction (SDF) is a common sequel to cancer treatment which affects the quality of life in women treated with pelvic radiotherapy. The aim of this study was to evaluate the safety, symptom resolution and objective improvement the injection of autologous platelet released growth factor (APRGF) for treatment of SDF in cited patients. This prospective pilot study enrolled 10 cancer-free patients with SDF who underwent pelvic radiotherapy at least 5 years ago, randomly. Each patient was received 1-2 cc APRGF within four weeks and all patients were re-evaluated at eight weeks and six months. CD34 immuno histochemistry and Masson's trichrome staining were performed on vaginal biopsy section for angiogenesis and fibrosis assay respectively. Sexual satisfaction after the injection of APRFG was clinically difference and the entire patient had sexual satisfaction. In the patient's follow-up, none of them needs to repeat the treatment. Our results declared that APRGF injection was effective and symptoms were disappeared in the entire patients. Significant objective improvements in vaginal diameter (mean before injection, 6.5 cm vs 7.1 cm after injection) (p-value = 0.001) and vaginal flexibility (mean before treatment, 0.72 cm vs 1.85 cm after injection) (P-value = 0.026) were observed. Characteristics of discharge before the injection in 60% of patients were included dry vagina and 40% had mild discharge but after injection 40% of patients had moderate and also 60% had mild and sufficient discharge (P-value= 0.190). Overally, our patients reported better sexual function and showed better vaginal function indexes, after APRFG injection.

Transcutaneous Electrical Nerve Stimulation at the Acupuncture Points to Relieve Pain of Patients Under Mechanical Ventilation: A Randomized Controlled Study.

BACKGROUND AND OBJECTIVE: Electrical stimulation and acupuncture points as nonpharmacological methods have been the focus of pain reduction in different patients. This study is aimed at determining the effects of transcutaneous electrical nerve stimulation (TENS) on the acupuncture points of pain in patients under mechanical ventilators. MATERIALS AND METHODS: This randomized double-blind clinical trial study was conducted on 50 patients undergoing mechanical ventilation in intensive care units of Imam Reza hospital in Kermanshah, Iran, in 2017. The patients were randomly allocated into intervention and placebo groups. In the intervention group, TENS electrodes were placed on points Hegu and Zusanli. Pain severity was measured using the Care Pain Observation Tool scale, and the dosages of narcotics and sedation intake were recorded. Data were analyzed using the Statistical Package for the Social Sciences (SPSS) software, version 19. RESULTS: The level of pain in patients decreased in the intervention group in comparison with the sham group, and this decline was significant during certain hours (p < 0.05). The amount of analgesic and sedation drugs used was less significant in the intervention group than in the sham group (p = 0.01; p = 0.04). CONCLUSION: The results showed that the use of TENS on acupuncture points can decrease the level of pain and opioid consumption in intubated patients under a mechanical ventilator.

Antinociceptive activity of Inula britannica L. and patuletin: In vivo and possible mechanisms studies.

ETHNOPHARMACOLOGICAL RELEVANCE: Inula britannica L. is a predominant medicinal plant traditionally utilized in the treatments of arthritis and back pain in Iranian folk medicine. AIM OF THE STUDY: The purpose of this research was to evaluate the antinociceptive effects of Inula britannica L. flower essential oil (IBLEO) and one of its major constituents, Patuletin (Pn), in male mice. MATERIALS AND METHODS: In this study, we used pain assessment tests including acetic acid-induced writhing, tail-flick (TF), formalin induced paw licking (FIPL) model, and glutamate-induced paw licking (GPL). For understanding the supposed antinociceptive mechanisms of IBLEO, opioid and L-arginine/NO/cGMP/ KATP pathways were examined. RESULTS: In the TF, writhing, GPL, and FIPL tests, a dosage of 100 mg/kg of IBLEO showed noteworthy antinociceptive effects in comparison with control (p < 0.05). In writhing test, administration of selective opioid antagonists (naltrindole, nor-binaltorphimine, and naloxonazine) attenuated the antinociceptive effect of IBLEO in comparison with control (p < 0.001). Both methylene blue and glibenclamide blocked the antinociceptive effect of IBLEO (p < 0.05), but the administration of L-arginine or sodium nitroprusside fundamentally potentiated the antinociception induced by IBLEO in phase II of the FIPL (p < 0.05). Additionally, patuletin showed significant antinociceptive effects in writhing, FIPL, and GPL tests (p < 0.01). CONCLUSION: The results of this examination showed that IBLEO and Pn have antinociceptive effects. The modulation of glutamatergic systems by opioid receptors could be involved, at least in part, in these effects. Our data also suggest the activation of the L-arginine/NO/cGMP/KATP pathway in IBLEO antinociceptive effects.

Effect of Hydroalcoholic Leaves Extract of Rhus Coriaria on Pain in Male Rats.

BACKGROUND: The drive toward the use of medicinal plants has been increasing in recent years. They have few side effects and a large variety of efficient components. OBJECTIVES: This study was designed to investigate the analgesic effects of hydroalcoholic Rhus coriaria leaf extract (HRCLE) in a rat model. MATERIALS AND METHODS: A total of 42 adult male rats were divided into seven groups: a control group (the animals did not receive any drug), three HRCLE groups, (receiving 80, 100, and 300 mg/kg, intraperitoneally [ip]), a morphine group (1 mg/kg, ip) an aspirin group (1 mg/kg, ip), and a group that received 300 mg/kg of HRCLE plus naloxone (1 mg/kg, ip). The analgesic effects of HRCLE were assessed via writhing, tail flick, and formalin tests, and the data obtained were compared with the control group using one-way analysis of variance and Tukey post hoc tests. RESULTS: HRCLE significantly inhibited the number of contractions induced by acetic acid in the writhing test at all doses, while anti-nociceptive activity was only shown at the 100 mg/kg dose (in the chronic phase) and at the 300 mg/kg dose (in the chronic-acute phase) in the formalin test. Interestingly, the greatest effect was observed at the 300 mg/kg HRCLE dose in the tail flick test. Simultaneous utilization of naloxone and HRCLE inhibited the anti-nociceptive effect of the extract in all tests. It is worth mentioning that aspirin and morphine revealed anti-nociceptive effects in all tests. CONCLUSIONS: Our findings suggest that the analgesic effect of HRCLE may be mediated via both peripheral and central mechanisms. The presence of flavonoids might be responsible for the anti-nociceptive activity of this plant.

Antinociceptive effects of Rhus coriaria L. extract in male rats.

It is well known that the tendency toward the medicinal plants is increasing in recent years. They have low side-effects and high varieties of efficient components. This study was designed to investigate the analgesic effect of hydro alcoholic leaf extract of Rhus coriaria (HRCLE) in a rat model. For this purpose, 42 adult male rats were divided into 7 groups: control, HRCLE (80, 100 and 300 mg/kg, i.p.), morphine (1 mg/kg, i.p.), aspirin (1 mg/kg, i.p.), and HRCLE 300 mg/kg plus naloxone (1 mg/kg, i.p.). The analgesic effects of HRCLE were assessed with writhing, tail flick and formalin tests. The data were compared with control by one-way ANOVA and Tukey post hoc test. All dose levels of HRCLE inhibited the number of contractions induced by acetic acid in the writhing test signfiicantly. None of the dose levels of HRCE have been showed antinociceptive activity in the formalin test except the dose of 100 mg/kg (at chronic phase) and the dose of 300 mg/kg (at chronic- acute phase). In the tail flick model, the highest effect was at the dose of 300 mg/kg of HRCLE (P < 0.01). Utilization of naloxone plus extract inhibited the antinociceptive effect of HRCLE. In this study, our findings suggest that analgesic effect for the HRCLE may be mediated via both peripheral and central mechanisms. The presence of flavonoids might be responsible for the antinociceptive activity of this plant.

Vaccinium arctostaphylos, a common herbal medicine in Iran: molecular and biochemical study of its antidiabetic effects on alloxan-diabetic Wistar rats.

AIM OF THE STUDY: The purpose of this study was to define antidiabetic effects of fruit of Vaccinium arctostaphylos L. (Ericaceae) which is traditionally used in Iran for improving of health status of diabetic patients. MATERIALS AND METHODS: Firstly, we examined the effect of ethanolic extract of Vaccinium arctostaphylos fruit on postprandial blood glucose (PBG) after 1, 3, 5, 8, and 24h following a single dose administration of the extract to alloxan-diabetic male Wistar rats. Also oral glucose tolerance test was carried out. Secondly, PBG was measured at the end of 1, 2 and 3 weeks following 3 weeks daily administration of the extract. At the end of treatment period the pancreatic INS and cardiac GLUT-4 mRNA expression and also the changes in the plasma lipid profiles and antioxidant enzymes activities were assessed. Finally, we examined the inhibitory activity of the extract against rat intestinal α-glucosidase. RESULTS: The obtained results showed mild acute (18%) and also significant chronic (35%) decrease in the PBG, significant reduction in triglyceride (47%) and notable rising of the erythrocyte superoxide dismutase (57%), glutathione peroxidase (35%) and catalase (19%) activities due to treatment with the extract. Also we observed increased expression of GLUT-4 and INS genes in plant extract treated Wistar rats. Furthermore, in vitro studies displayed 47% and 56% inhibitory effects of the extract on activity of intestinal maltase and sucrase enzymes, respectively. CONCLUSIONS: Findings of this study allow us to establish scientifically Vaccinium arctostaphylos fruit as a potent antidiabetic agent with antihyperglycemic, antioxidant and triglyceride lowering effects.