Inhibition of LPS‐Induced TNF‐α and NO Production in Mouse Macrophage and Inflammatory Response in Rat Animal Models by a Novel Ayurvedic Formulation,BV‐9238

Rheumatoid arthritis is a chronic crippling disease, where protein‐based tumor necrosis factor‐alpha (TNF‐α) inhibitors show significant relief, but with potentially fatal side effects. A need for a safe, oral, cost‐effective small molecule or phyto‐pharmaceutical is warranted. BV‐9238 is an Ayurvedic poly‐herbal formulation containing specialized standardized extracts of Withania somnifera, Boswellia serrata, Zingiber officinale and Curcuma longa. The anti‐inflammatory and anti‐arthritic effects of BV‐9238 were evaluated for inhibition of TNF‐α and nitric oxide (NO) production, in lipopolysaccharide‐stimulated, RAW 264.7, mouse macrophage cell line. BV‐9238 reduced TNF‐α and NO production, without any cytotoxic effects. Subsequently, the formulation was tested in adjuvant‐induced arthritis (AIA) and carrageenan‐induced paw edema (CPE) rat animal models. AIA was induced in rats by injecting Freund's complete adjuvant intra‐dermally in the paw, and BV‐9238 and controls were administered orally for 21 days. Arthritic scores in AIA study and inflamed paw volume in CPE study were significantly reduced upon treatment with BV‐9238. These results suggest that the anti‐inflammatory and anti‐arthritic effects of BV‐9238 are due to its inhibition of TNF‐α, and NO, and this formulation shows promise as an alternate therapy for inflammatory disorders where TNF‐α and NO play important roles. Copyright © 2014 John Wiley & Sons, Ltd.     

Houttuynia cordata Thunb. Volatile Oil Exhibited Anti‐inflammatory Effects In Vivo and Inhibited Nitric Oxide and Tumor Necrosis Factor‐α Production in LPS‐stimulated Mouse Peritoneal Macrophages In Vitro

Houttuynia cordata Thunb. (HC) is a medicinal herb that generally used in traditional Chinese medicine for treating allergic inflammation. The present study investigated the inhibitory effect of the volatile oil from HC Thunb. on animal models of inflammation and the production of inflammatory mediators in vivo and in vitro. In vivo, xylene‐induced mouse ear edema, formaldehyde‐induced paw edema and carrageenan‐induced mice paw edema were significantly decreased by HC volatile oil. HC volatile oil showed pronounced inhibition of prostaglandin (PG) E₂ and malondialdehyde production in the edematous exudates. In vitro exposure of mouse resident peritoneal macrophages to 1, 10, 100 and 1000 µg/mL of HC volatile oil significantly suppressed lipopolysaccharide (LPS)‐stimulated production of NO and tumor necrosis factor‐α (TNF‐α) in a dose‐dependent manner. Exposure to HC volatile oil had no effect on cell viability and systemic toxicity. Furthermore, HC volatile oil inhibited the production of NO and TNF‐α by down‐regulating LPS‐stimulated iNOS and TNF‐α mRNA expression. Western blot analysis showed that HC volatile oil attenuated LPS‐stimulated synthesis of iNOS and TNF‐α protein in the macrophages, in parallel. These findings add a novel aspect to the biological profile of HC and clarify its anti‐inflammatory mechanism. Copyright © 2012 John Wiley & Sons, Ltd.     

Anti‐Inflammatory Sesquiterpene Lactones from Lychnophora trichocarpha Spreng. (Brazilian Arnica)

The aerial parts of Lychnophora trichocarpha Spreng. (Asteraceae) are used macerated in water or ethanol to treat inflammation, pain, rheumatism, contusions, bruises and insect bites in Brazilian traditional medicine. In this study, anti‐inflammatory activity of ethanol extract from aerial parts of L. trichocarpha and its ethyl acetate fraction was investigated. Sesquiterpene lactones, lychnopholide (Lyc) and eremantholide C (EreC), isolated of ethyl acetate fraction, were also assayed for in vitro and in vivo anti‐inflammatory activity. Topical treatment with ointments containing ethanol extract, its ethyl acetate fraction and sesquiterpene lactones significantly reduced carrageenan‐induced mice paw oedema. In vitro assays demonstrated that Lyc inhibited interferon ‐γ/lipopolysaccharide ‐stimulated nitric oxide (NO) production in J774A.1 macrophages and increased production of IL‐10 anti‐inflammatory cytokine. The reduction of tumor necrosis factor‐α (TNF‐α) production by EreC was accompanied by an increased production of IL‐10 in a concentration‐dependent manner in J774A.1 macrophages. The anti‐inflammatory effect of Lyc seems to involve the inhibition of production of NO and increased production of IL‐10. The mechanism of the effect of EreC on the reduction of carrageenan‐induced paw oedema may be attributed to inhibition of production of TNF‐α and stimulation of IL‐10 production. The results corroborate the use of ethanol extract from Lychnophora trichocarpha in folk medicine for anti‐inflammatory action and indicate that the topical route is suitable for use. Copyright © 2012 John Wiley & Sons, Ltd.     

Antihyperalgesic and Antiedematous Activities of Bisabolol‐Oxides‐Rich Matricaria Oil in a Rat Model of Inflammation

From the dried flower heads of Matricaria recutita L., essential oil was isolated by hydrodistillation, and in the obtained blue oil, α‐bisabolol oxide A (21.5%), α‐bisabolol oxide B (25.5%) and (Z)‐spiroether (cis‐en‐yn‐spiroether) (10.3%) were identified as the main compounds, by gas chromatography (GC) and GC–mass spectrometry analyses. The antihyperalgesic effects of this oil were examined in a rat model of inflammation induced by carrageenan, through a modified ‘paw‐pressure’ test. Antiedematous effects were examined in a rat model of inflammation induced by carrageenan, dextran and histamine, through plethysmometry. Matricaria oil (25, 50 and 100 mg/kg, p.o.) exhibited a significant dose‐dependent reduction of hyperalgesia and edema induced by carrageenan in both prophylactic and therapeutic treatment schemes. It was more efficacious in the prophylactic treatment scheme, and the corresponding median effective dose (ED₅₀) ± standard error of the mean (SEM) values were 49.8 ± 6.0 and 42.4 ± 0.2 mg/kg for antihyperalgesic and antiedematous effects, respectively. Prophylactic treatments with matricaria oil (25, 50 and 100 mg/kg, p.o.) caused a significant dose‐dependent antiedematous effect in dextran‐induced edema with lower efficacy than in the carrageenan model. In a dose of 100 mg/kg, p.o., matricaria oil caused a slight reduction of histamine‐induced edema. These results suggest that bisabolol‐oxide‐rich matricaria oil may be effective against pain and edema present in various inflammatory conditions, which supports matricaria traditional uses. Copyright © 2013 John Wiley & Sons, Ltd.     

Anti‐Inflammatory and Antinociceptive Activity of Urera aurantiaca

Urera aurantiaca Wedd. (Urticaceae) is a medicinal plant commonly used in traditional medicine to relieve pain in inflammatory processes. In the present study, the in vivo anti‐inflammatory and antinociceptive effects of U. aurantiaca methanolic extract and its possible mechanisms of action were investigated. The extract showed anti‐inflammatory activity in the ear edema in mice test (34.3% inhibition), myeloperoxidase (MPO) activity was markedly reduced in animals administered with the extract: within 49.6% and 68.5%. In the histological analysis, intense dermal edema and intense cellular infiltration of inflammatory cells were markedly reduced in the ear tissue of the animals treated with the extract. In the carrageenan‐induced hind paw edema in rats assay the extract provoked a significant inhibition of the inflammation (45.5%, 5 h after the treatment) and the MPO activity was markedly reduced (maximum inhibition 71.7%), The extract also exhibited significant and dose‐dependent inhibitory effect on the increased vascular permeability induced by acetic acid. The extract presented antioxidant activity in both 2,2‐diphenyl‐1‐picrylhydrazyl and 2,2′‐azinobis 3‐ethylbenzothiazoline 6‐sulfonic acid tests and its total phenol content was 35.4 ± 0.06 mg GAE/g of extract. Also, the extract produced significant inhibition on nociception induced by acetic acid (ED₅₀: 8.7 mg/kg, i.p.) administered intraperitoneally and orally. Naloxone significantly prevented this activity. Copyright © 2014 John Wiley & Sons, Ltd.     

Anti‐Arthritic and Antiinflammatory Effects of the Traditional Uighur Formula Kursi Caper In Vivo

Kursi Caper (KC) is a Uighur medicine based on caper which is widely used to treat arthritis and rheumatism, and preliminary studies in our laboratory showed that this traditional formula may possess potent antiinflammatory effects. This study confirms the antiinflammatory effect of KC in the adjuvant induced arthritis (AIA) model, the carrageenan and cotton‐pellet induced granuloma rat models, and further investigates in vivo the mechanism of action by measuring relevant indicators of anti‐arthritic activity. KC showed significant and dose‐dependent anti‐arthritic and antiinflammatory effects, demonstrated by reduced paw edema and arthritic scores in all animal models. Histopathological examination showed that KC reduced levels of synovial inflammatory factors in AIA rats. The overproduction of TNF‐α and IL‐1β was attenuated, and CAT, MDA and SOD levels were restored to normal in KC‐treated rats. KC also significantly reduced LPS‐induced proliferation of B lymphocytes and ConA induced proliferation of T lymphocytes in a dose‐dependent manner. Flow cytometry showed that the high dose KC‐treated group had a significantly decreased frequency of Th17 cells. This study indicates that KC can significantly attenuate arthritis and inflammation in rats by decreasing the levels of inflammatory cytokines, regulating oxidative stress, reducing lymphocyte proliferation and decreasing Th17. This supports the traditional use of KC as a potential modern therapeutic agent for the treatment of arthritis and related conditions. Copyright © 2015 John Wiley & Sons, Ltd.     

Effects of Ginkgo Biloba Extract EGb‐761 on Neuropathic Pain in Mice: Involvement of Opioid System

Neuropathic pain is considered as one of the most difficult types of pain to manage with conventional analgesics. EGb‐761 is extracted from leaves of Ginkgo biloba and has analgesia and anti‐inflammatory properties. This study aimed to examine the effect of EGb‐761 on chronic constriction injury (CCI)‐induced neuropathic pain behaviors, including thermal hyperalgesia and mechanical allodynia, and to explore the possible mechanisms underlying this action. To this end, CCI mice were intraperitoneally injected with EGb‐761 (10, 20, 40, and 80 mg/kg), and thermal hyperalgesia, mechanical allodynia, cytokines, and mu‐opioid receptor expression were measured. Results showed that EGb‐761 attenuated thermal hyperalgesia and mechanical allodynia dose‐dependently and the best delivery time window was from day 7 to day 14 after CCI. Additionally, EGb‐761 treatment significantly decreased pro‐inflammatory cytokines and enhanced mu opioid receptor (MOR) expression in the sciatic nerve. Moreover, the opioid antagonist naloxone prevented the effect of EGb‐761 on thermal hyperalgesia and mechanical allodynia but did not influence the effect of EGb‐761 on inflammatory cytokines. In conclusion, this study suggests that the potential of EGb‐761 as a new analgesic for neuropathic pain treatment, and opioid system may be involved in the EGb‐761‐induced attenuation of thermal hyperalgesia and mechanical allodynia. Copyright © 2016 John Wiley & Sons, Ltd.     

Anti‐inflammatory properties of cryptolepine

Cryptolepine is the major alkaloid of the West African shrub, Cryptolepis sanguinolenta. Cryptolepine has been shown to inhibit nitric oxide production, and DNA binding of Nuclear Factor‐kappa B following inflammatory stimuli in vitro. In order to validate the anti‐inflammatory property of this compound in vivo, we investigated its effects on a number of animal models of inflammation. Cryptolepine (10–40 mg/kg i.p.) produced significant dose‐dependent inhibition of the carrageenan‐induced rat paw oedema, and carrageenan‐induced pleurisy in rats. These effects were compared with those of the non‐steroidal anti‐inflammatory drug indomethacin (10 mg/kg). At doses of 10–40 mg/kg i.p., cryptolepine inhibited lipopolysaccharide (LPS)‐induced microvascular permeability in mice in a dose‐related fashion. Oral administration of up to 40 mg/kg of the compound for four consecutive days did not induce gastric lesion formation in rats. Analgesic activity was also exhibited by cryptolepine through a dose‐related (10–40 mg/kg i.p.) inhibition of writhing induced by i.p. administration of acetic acid in mice. The results of this study reveal that cryptolepine possesses in vivo anti‐inflammatory activity. Copyright © 2009 John Wiley & Sons, Ltd.     

Anti‐Nociceptive Effect of Resveratrol During Inflammatory Hyperalgesia via Differential Regulation of pro‐Inflammatory Mediators

Sensitization of nociceptive neurons by inflammatory mediators leads to hypersensitivity for normal painful stimuli which is termed hyperalgesia. Oxidative stress is an essential factor in pathological pain; therefore, antioxidants qualify as potential anti‐hyperalgesic agents. The present study examines the efficacy of the natural antioxidant resveratrol in complete Freund's adjuvant (CFA) induced hyperalgesic rats. Thermal hyperalgesia was measured at different time points by paw withdrawal latency test and confirmed by c‐Fos expression in spinal dorsal horn. The impact of resveratrol treatment on inflammatory mediators at peripheral (paw skin) and central (spinal cord) sites was determined during early (6 h) as well as late phase (48 h) of hyperalgesia. Intraplanter injection of CFA increased the level of cytokines IL‐1β, TNF‐α and IL‐6 as well as inflammatory enzymes COX‐2 and iNOS in paw skin in both phases. In case of spinal cord, the level of COX‐2 was found to be elevated in both phases, whereas iNOS could not be detected. The cytokines were found to be elevated only in late phase in spinal cord. Administration of resveratrol (20 mg/kg) shifted the level of all inflammatory mediators towards normal, except cytokines in paw skin. The present study suggests that the anti‐nociceptive effect of resveratrol is implicated at both peripheral and central sites in a tissue specific manner. Copyright © 2016 John Wiley & Sons, Ltd.     

Aqueous Extract of Rosmarinus officinalis L. Inhibits Neutrophil Influx and Cytokine Secretion

Rosmarinus officinalis L. phenolic compounds have attracted considerable attention because of their antioxidant and antimicrobial properties, including its ability to treat inflammatory disorders. In this work, we investigated the in vivo and in vitro effects of R. officinalis aqueous extract on neutrophil trafficking from the blood into an inflamed tissue, on cell‐derived secretion of chemical mediators, and on oxidative stress. Anti‐inflammatory activity was investigated using carrageenan‐induced inflammation in the subcutaneous tissue of male Wistar rats orally treated with the R. officinalis extract (100, 200, or 400 mg/kg). The leukocyte influx (optical microscopy), secretion of chemical mediators (prostaglandin E2 (PGE2), TNF‐α, interleukin 6 (IL‐6), leukotriene B4 (LTB4), and cytokine‐induced neutrophil chemoattractant 1 by enzyme‐linked immunosorbent assay), and the anti‐oxidative profile (super oxide dismutase (SOD), glutathione peroxidase, and thiobarbituric acid reactive substance (TBARS) spectrophotometry) were quantified in the inflamed exudate. N‐Formyl‐methionine‐leucine‐phenylalanine‐induced chemotaxis, lipopolysaccharide‐induced NO₂^? production (Greiss reaction), and adhesion molecule expression (flow cytometry) were in vitro quantified using oyster glycogen recruited peritoneal neutrophils previous treated with the extract (1, 10, or 100 µg/mL). Animals orally treated with phosphate‐buffered saline and neutrophils incubated with Hank's balanced salt solution were used as control. R. officinalis extract oral treatment caused a dose‐dependent reduction in the neutrophil migration as well as decreased SOD, TBARS, LTB4, PGE2, IL‐6, and TNF‐α levels in the inflamed exudate. In vitro treatment with R. officinalis decreased neutrophil chemotaxis, NO₂^? production, and shedding of L‐selectin and β2 integrin expressions. Results here presented show that R. officinalis aqueous extract displays important in vivo and in vitro anti‐inflammatory actions by blocking pathways of neutrophil migration and secretion, suggesting its therapeutic application to acute inflammatory reactions. Copyright © 2014 John Wiley & Sons, Ltd.     

电针镇痛时炎症痛大鼠PAG部位I型白细胞介素-1受体mRNA表达的变化

目的 :本实验观察炎症痛和针刺镇痛时 ,大鼠中脑导水管周围灰质 (PAG)部位I型白细胞介素 1受体基因 (IL 1RImRNA)表达的变化。方法 :实验分正常组、炎症痛组、假电针组、电针组。正常对照组大鼠脚掌注射生理盐水 ,炎症痛各组大鼠脚掌注射 2 %角叉菜胶 ( 1 0 0 μL)造成炎症痛模型。在角叉菜胶注射 3hr后大鼠处于一种稳定的痛敏状态。电针组大鼠于造模前电针将致炎侧“足三里”和“昆仑”穴 3 0min ,假电针组大鼠给予同样处理但不通电。实验采用原位杂交技术 ,观察脚掌注射角叉菜胶 3hr后大鼠中脑导水管周围灰质 (PAG)部位IL 1RImRNA表达的变化及针刺对其的影响。结果 :致炎后 3hr大鼠痛阈显著降低 ,大鼠PAG部位的IL 1RImRNA表达显著增加 ,假电针组大鼠该部位的IL 1RImRNA表达与炎症痛组相比无显著变化 ,而电针组大鼠该部位的IL 1RImRNA阳性细胞数与假电针组相比显著减少。结论 :炎症痛可引起大鼠PAG部位的IL 1RImRNA表达增加 ,而电针镇痛则抑制炎症痛引起的大鼠PAG部位IL 1RImRNA表达     

Electroacupuncture inhibits inflammatory edema and hyperalgesia through regulation of cyclooxygenase synthesis in both peripheral and central nociceptive sites

We investigated the anti-inflammatory effects of electroacupuncture (EA) on carrageenan-induced inflammatory model in association with peripheral and spinal COX-2 expression. EA with 2, 15 and 120 Hz, especially 2 Hz, had significant inhibitory effects on the developing of edema and hyperalgesia, which was measured in 30-min intervals after carrageenan injection. Therefore, we investigated whether the effect of 2 Hz EA on carrageenan-induced edema and hyperalgesia is associated with peripheral and spinal expression of inflammatory proteins. The expression of cyclooxygenase (COX)-1, COX-2, and inducible nitric oxide synthase (iNOS) was inhibited by 2 Hz EA in carrageenan-injected rat paws. Interestingly, we found that the mRNA of COX-1 and COX-2 expression in the spine was not induced by 2 Hz EA treatment after carrageenan-induced peripheral inflammation. In addition, synthesis of prostaglandin E(2) (PGE(2)) was partially inhibited by 2 Hz EA treatment in both peripheral and spinal nociceptive regions. In conclusion, EA treatment might be a useful therapy for mitigation of inflammatory edema and hyperalgesia through regulation of COX-2 expression in both peripheral and central nociceptive sites.     

Antinociceptive Effect of Lupeol: Evidence for a Role of Cytokines Inhibition

The present study investigates the antinociceptive properties of lupeol in models of inflammatory and post‐operative pain, as well as its mechanisms of action. The effects of lupeol were tested against acetic acid‐induced writhing, formalin test, carrageenan‐induced hyperalgesia, and post‐operative pain model. Cytokine levels were determined by ELISA. Mice motor performance was evaluated in the rota rod and open‐field tests. Pre‐treatment of mice with lupeol (5–100 mg/kg IP) produced a dose‐related inhibition of writhing in mice. The maximal antinociception produced by lupeol (60 mg/kg) was unaffected in mice pre‐treated with yohimbine (α2 adrenoceptor antagonist; 2 mg/kg IP), L‐arginine (substrate for nitric oxide synthase; 600 mg/kg IP), glibenclamide (the K_ATP‐channel blocker; 2 mg/kg IP), and methysergide maleate (serotoninergic receptors antagonist; 5 mg/kg IP). Furthermore, lupeol (25–100 mg/kg) inhibited the late phase of formalin test. Pre‐treatment with lupeol (50 and 100 mg/kg) inhibited the hyperalgesia and the local increase in tumor necrosis factor‐α (TNF‐α) and interleukin‐1β (IL‐1β) levels induced by carrageenan. In contrast, lupeol did not inhibit the post‐operative pain. Lupeol‐treated mice did not show any motor performance alterations or apparent systemic toxicity. Our results demonstrate that lupeol has consistent antinociceptive properties during inflammatory pain, but not post‐operative pain, acting through the inhibition of IL‐1β and TNF‐α production. Copyright © 2012 John Wiley & Sons, Ltd.     

Effect of pine pollen extract on experimental chronic arthritis

The effects of pine pollen extract (PE) on Freund's complete adjuvant (FCA)‐induced arthritis and collagen‐induced arthritis (CIA) were investigated. The oral administration of PE (100 and 200 mg/kg per day) for 21 days after subcutaneous immunization with FCA, significantly reduced hindpaw swelling and the production of inflammatory cytokines (TNF‐α, IL‐1β and IL‐6) compared with the FCA‐induced arthritis group. Treatment with the PE (100 mg/kg) also decreased the serum levels of LDL‐cholesterol and increased HDL‐cholesterol contents compared with those of the arthritis group. Since CIA is a model of some types of human autoimmune rheumatoid arthritis (RA), the study examined whether PE is efficacious against CIA in mice and investigated the possible antioxidant potential of PE on CIA. Arthritis in DBA/1J mice was induced by subcutaneous immunization with bovine type II collagen. PE (100 and 200 mg/kg) was orally administered once daily for 49 days after initial immunization with type II collagen. The arthritis score and paw edema were markedly suppressed in the groups treated with PE. Moreover, administration of PE (100 mg/kg) for 49 days reduced the serum levels of rheumatoid factor, anti‐type II collagen antibody, TNF‐α, IL‐1β, IL‐6, protein carbonyl, advanced glycation endproducts, malondialdehyde and LDL‐cholesterol compared with that of CIA mice. These results suggest that the pine pollen might be beneficial in the treatment of chronic inflammatory disorders. Copyright © 2009 John Wiley & Sons, Ltd.     

蒙药风痛灵胶囊抗炎、镇痛作用的实验研究

目的:观察风痛灵胶囊的抗炎、镇痛作用。方法:采用二甲苯致小鼠耳廓肿胀、角叉菜致大鼠足肿胀、棉球致大鼠肉芽肿实验,观察风痛灵胶囊的抗炎效果;通过小鼠热板实验、小鼠扭体实验观察该药对疼痛的影响。结果:风痛灵胶囊可明显降低二甲苯致小鼠耳廓肿胀、角叉菜胶致大鼠足肿胀及大鼠棉球肉芽肿(P0.05);对小鼠热板致痛和醋酸致痛有显著的减轻作用(P0.05)。结论:风痛灵胶囊具有明显的抗炎、镇痛作用。     

Anti‐inflammatory activity of Rhodiola rosea – “a second‐generation adaptogen”

Rhodiola rosea (golden root), a unique phytoadaptogen grown in high‐altitude regions has gained attention for its various therapeutic properties. In India, this plant is found in the Himalayan belt and has not been completely explored for its beneficial health effects. The present study was undertaken to evaluate the anti‐inflammatory efficacy of the tincture extract of Rhodiola rosea roots (RTE). The anti‐inflammatory activity was determined through carrageenan‐induced paw oedema, formaldehyde‐induced arthritis and nystatin‐induced paw oedema in rat model. The tincture extract exhibited inhibitory effect against acute and subacute inflammation at a dose of 250 mg/kg body weight. Inhibition of nystatin‐induced oedema was also observed in a dose‐dependent manner. The in vitro inhibitory effects of the tincture extract from R. rosea roots was evaluated against the enzymes relating to inflammation. The enzymes include cyclooxygenase‐1 (COX‐1), cyclooxygenase‐2 (COX‐2) and Phospholipase A₂ (PLA₂). The extract showed varying inhibitory activities against these enzymes depending on the concentrations. A potent inhibition was observed against Cox‐2 and PLA₂. Inhibition of nystatin induced oedema and phospholipase A₂ suggested that membrane stabilization could be the most probable mechanism of action of RTE in anti‐inflammation. The findings in this study may provide the use of R. rosea root extract in the treatment of inflammatory conditions. Copyright © 2009 John Wiley & Sons, Ltd.     

Pain Modulation by Lignans (Phyllanthin and Hypophyllanthin) and Tannin (Corilagin) Rich Extracts of Phyllanthus amarus in Carrageenan‐induced Thermal and Mechanical Chronic Muscle Hyperalgesia

The current study was aimed at evaluating the antihyperalgesic effects of lignans (phyllanthin and hypophyllanthin) and tannin (corilagin) rich three standardized extracts of Phyllanthus amarus in a model of chronic musculoskeletal inflammatory pain. Three percent carrageenan injected in the gastrocnemius muscle produced hyperalgesia to mechanical and heat stimuli ipsilaterally, which spreads to the contralateral side within 7 to 9 days. To investigate the effects on chronic thermal and mechanical hypersensitivity, three extracts of P. amarus in three doses (100, 200, and 400 mg/kg) were administered to animals intraperitoneally from 14th day to 22nd day after intramuscular injection of carrageenan. It was observed that intraperitoneal administrations of Phyllanthus extracts showed antihyperalgesic activity, as they elevated thermal and mechanical threshold, which was supported by histopathological observations along with reduction in prostaglandin E2 (PGE2) concentration. In conclusion, we strongly suggest that the observed antihyperalgesic and antiinflammatory effects of P. amarus in current pain model are mediated via spinal or supraspinal neuronal mechanisms, mainly by inhibition of PGE2. Modulation of chronic muscular inflammation may be due to presence of phytoconstituents like phyllanthin, hypophyllanthin, and corilagin, which offers a promising means for treatment of chronic muscle pain. Copyright © 2015 John Wiley & Sons, Ltd.     

八正合剂抗感染作用的实验研究

目的　探讨八正合剂治疗泌尿系统感染性疾病的药理学作用基础。方法　将大肠杆菌注入小鼠膀胱后观察药物对细菌上行感染肾脏的抑制作用 ;家兔 iv大肠杆菌内毒素后观察药物对细菌内毒素引起机体发热的影响 ;采用大鼠足跖 sc角叉菜胶所致炎性肿胀模型观察药物对炎性肿胀及机械压迫足跖疼痛的抑制作用。结果　八正合剂 ig给药可显著降低大肠杆菌上行感染肾脏的带菌剖面百分率 [ED50 为 (11.0 1± 1.6 3) g/ kg,95 %可信限为9.5 0～ 12 .76 g/ kg],抑制大肠杆菌内毒素诱发家兔体温升高 ,减轻角叉菜胶所致大鼠足跖炎性肿胀及致炎后肿胀部位机械压迫痛阈降低程度。结论　八正合剂治疗泌尿系统感染性疾病的作用机制主要与其清除尿路细菌和减轻发热、肿胀、疼痛等炎症反应症状有关。     

胡桃青皮抗炎及镇痛作用的研究

目的：观察胡桃青皮的抗炎及镇痛作用。方法：采用醋酸所致小鼠腹腔毛细血管通透性增高模型及巴豆油引起小鼠耳壳炎症、角叉菜胶所致大鼠足肿胀模型,观察胡桃青皮的抗炎作用;用热板法及化学刺激法观察该药的镇痛作用。结果：胡桃青皮对巴豆油所致的小鼠耳壳肿胀、大鼠角叉菜胶性足肿胀、醋酸引起的小鼠腹腔毛细血管通透性增高均有明显的抑制作用;对热传导及化学刺激引起的拟痛反应有明显镇痛作用。结论：胡桃青皮具有明显的抗炎及镇痛作用