Pharmacological Proprieties of the Ethanol Extract of Muehlenbeckia platyclada (F. Muell.) Meisn. Leaves

Antinociceptive and anti-inflammatory activities of the Muehlenbeckia platyclada leaves' ethanol extract were investigated in animal models. The extract (p.o.) reduced the number of abdominal contortions induced by acetic acid by 21.57% (400 mg/kg). After intraplantar injection of formalin, a dose of 400 mg/kg (p.o.) inhibited the time spent paw licking in the first phase (26.43%), while the second phase was inhibited by 10.90 and 36.65% at the doses of 200 and 400 mg/kg, respectively. The extract (p.o.) increased the reaction time on a hot plate at a dose of 400 mg/kg (32.68 and 40.30%) after 60 and 90 minutes of treatment, respectively. The paw edema was reduced by extract (p.o.) at doses of 100 (15.46 and 16.67%), 200 (22.68 and 25.64%) and 400 mg/kg (29.50 and 37.33%) after 3 to 4 h of carrageenan application, respectively. Doses of 100, 200 and 400 mg/kg (p.o.), administered 4 h after the carrageenan injection, reduced the exudate volume (11.28, 21.54 and 45.13%), while leukocyte migration was reduced by 21.21 and 29.70% at the doses of 200 and 400 mg/kg, respectively. These results indicate that the ethanol extract from M. platyclada may constitute a potential target for the discovery of new molecules with antinociceptive and anti-inflammatory activities that can be explored for their therapeutic use.     

Antinociceptive and Anti-Inflammatory Effects of Ethanol Extract from Vernonia polyanthes Leaves in Rodents

The ethanol extract from Vernonia polyanthes leaves (EEVP) was investigated for antinociceptive and anti-inflammatory effects at the doses (p.o.) of 100, 200 and 400 mg/kg in animal models. The extract reduced the number of abdominal contortions by 16.75% and 31.44% at a dose of 200 and 400 mg/kg, respectively. The results obtained showed that EEVP exerted a significant antinociceptive effect in the two phases of formalin. The EEVP increased the reaction time on a hot plate at the doses of 100, 200 and 400 mg/kg after 90 min of treatment. The paw edema was reduced by EEVP at the doses of 100, 200 and 400 mg/kg after 4 h of application of carrageenan. Doses of 200 and 400 mg/kg, administered 4 h before the carrageenan injection, significantly reduced the exudate volume (29.25 and 45.74%, respectively) and leukocyte migration (18.19 and 27.95%, respectively). These results suggest that V. polyanthes can be an active source of substances with antinociceptive and anti-inflammatory activities.     

New approaches to clarify antinociceptive and anti-inflammatory effects of the ethanol extract from Vernonia condensata leaves

The present study was aimed at evaluating the antinociceptive and anti-inflammatory effects of the ethanol extract from Vernonia condensata leaves in animal models, in order to afford a better understanding of these properties. The extract reduced the number of abdominal contortions at doses of 100 (51.00 ± 3.00), 200 (42.00 ± 2.98) and 400 mg/kg (39.00 ± 4.00). In formalin tests, a significant reduction in the licking time (p < 0.01) was observed in the first phase by 25.14 (200 mg/kg = 51.50 ± 4.44) and 31.15% (400 mg/kg = 48.00 ± 4.37). The doses of 100 (43.37 ± 5.15), 200 (34.62 ± 4.16) and 400 mg/kg (28.37 ± 3.98) inhibited (p < 0.001) the second phase. After 60 and 90 min of treatment, a dose of 400 mg/kg (10.13 ± 0.39 and 11.14 ± 1.33, respectively) increased the latency time. Doses of 200 and 400 mg/kg potentiated the sleeping time induced by diazepam, pentobarbital and meprobamate. The extracts (100, 200 and 400 mg/kg) showed anti-inflammatory effects by a decrease in paw edema. The extracts also reduced the exudate volume at the doses of 200 and 400 mg/kg. The leukocyte migration had significant effect (p < 0.001) at doses of 100, 200 and 400 mg/kg. The completion of additional experiments in the investigation of the antinociceptive and anti-inflammatory activities of V. condensata allowed a better understanding of the central and peripheral mechanisms involved.     

The Anti-Inflammatory Effects of the Methanolic Extract and Fractions from Davilla elliptica St. Hil. (Dilleniaceae) on Bothrops jararaca Envenomation

Inflammation and haemorrhage are the main characteristics of tissue injury in botropic envenomation. Although some studies have shown that anti-venom prevents systemic reactions, it is not efficient in preventing tissue injury at the site of the bite. Therefore, this work was undertaken to investigate the anti-inflammatory effects of the methanolic extract and fractions from D. elliptica and to evaluate the role of matrix metalloproteinases (MMPs) in this process. Effects of the extract and fractions from D. elliptica were evaluated using a carrageenan-induced paw oedema model in rats, and leukocyte rolling was visualized by intravital. The quantification of MMPs activities (MMP-2 and MMP-9) extracted from the dermis of mice treated with extract and fractions alone or incubated with venom was determined by zymographic analyses. Our results show that intraperitoneal (i.p.) injection of fractions significantly reduced paw oedema after the carrageenan challenge. Treatment with the tannins fraction also resulted in considerable inhibition of the rolling of leukocytes and this fraction was able to decrease the activation of MMP-9. These results confirmed the anti-inflammatory activity of the methanolic extract and tannins fraction of D. elliptica and showed that the dermonecrosis properties of B. jararaca venom might be mediated through the inhibition of MMP-9 activity.     

Antioxidant,Analgesic, Anti-Inflammatory,and Hepatoprotective Effects of the Ethanol Extract of Mahonia oiwakensis Stem

The aim of this study was to evaluate pharmacological properties of ethanol extracted from Mahonia oiwakensis Hayata stems (MOS_EtOH). The pharmacological properties included antioxidant, analgesic, anti-inflammatory and hepatoprotective effects. The protoberberine alkaloid content of the MOS_EtOH was analyzed by high-performance liquid chromatography (HPLC). The results revealed that three alkaloids, berberine, palmatine and jatrorrhizine, could be identified. Moreover, the MOS_EtOH exhibited antioxidative activity using the DPPH assay (IC₅₀, 0.743 mg/mL). The DPPH radical scavenging activity of MOS_EtOH was five times higher that that of vitamin C. MOS_EtOH was also found to inhibit pain induced by acetic acid, formalin, and carrageenan inflammation. Treatment with MOS_EtOH (100 and 500 mg/kg) or silymarin (200 mg/kg) decreased the serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels compared with the CCl₄-treated group. Histological evaluation showed that MOS_EtOH reduced the degree of liver injury, including vacuolization, inflammation and necrosis of hepatocytes. The anti-inflammatory and hepatoprotective effect of MOS_EtOH were found to be related to the modulation of antioxidant enzyme activity in the liver and decreases in malondialdehyde (MDA) level and nitric oxide (NO) contents. Our findings suggest that MOS_EtOH has analgesic, anti-inflammatory and hepatoprotective effects. These effects support the use of MOS_EtOH for relieving pain and inflammation in folk medicine.     

Antinociceptive and Anti-Inflammatory Effects of Ethanolic Extracts of Glycine max (L.) Merr and Rhynchosia nulubilis Seeds

The aim of this study was to assess the in vivo potential of ethanolic extracts of Glycine max (L.) Merr. (SoRiTae) and Rhynchosia nulubilis (Yak-Kong) seeds as natural anti-nociceptive and anti-inflammatory agents. To assess the anti-nociceptive and anti-inflammatory potential, the ethanolic extracts of SoRiTae and Yak-Kong seeds were tested in arachidonic acid-induced ear edema, carrageenan induced paw edema, formalin-induced licking time, acetic acid induced writhing and hot plate-induced thermal stimulation in mice. The administration of ethanolic extracts of SoRiTae and Yak-Kong seeds evoked a significant effect of anti-nociceptive and anti-inflammatory activities as compared to standards aminopyrine and indomethacin. The ear edema, paw edema, paw licking time, pain and writhes in mice were significantly reduced (p < 0.05) as compared to the control. The results obtained in this study indicate that both SoRiTae and Yak-Kong soybeans possesses potential anti-nociceptive and anti-inflammatory activities.     

Composition,anti-inflammatory,and antioxidant activities of avocado oil obtained from Duke and Fuerte cultivars

Avocado (Persea americana Mill.) fruit and oil are traditionally used for their antioxidant, anti-inflammatory and anti-aging properties. We investigated chemical variability between two avocado cultivars (Duke and Fuerte) in relation to their antioxidant and anti-inflammatory activities. Duke cultivar showed higher β-carotene and α-tocopherol content but significantly lower lipid content (36% dry weight) compared to Fuerte (52% dry weight). The ethanolic extract of Duke cultivar showed good antioxidant properties in 2,2-diphenyl-1-picrylhydrazyl radical scavenging assay with IC₅₀ at 27.21 μg/ml, while that of Fuerte showed weak activity. Meanwhile, in rat paw edema anti-inflammatory model, Duke oil (15 mg/kg) was slightly more effective in reducing inflammation by 41.12% after 1 h compared to Fuerte oil (15 mg/kg). However, after 4 h, both oils showed comparable inhibition of edema by 35.39% and 34.14% (15 mg/kg). The study underscores that variability in chemical composition of different avocado cultivars could affect biological activities attributed to the fruit and its oil.     

Hypoglycemic Effects of Crude Polysaccharide from Purslane

The effects of crude polysaccharide from Purslane (CPP) on body weight (bw), blood glucose, total cholesterol (TC), high-density lipoprotein cholesterol (HDL-c), triglyceride (TG) and serum insulin levels were studied in diabetes mellitus mice. CPP treatment (200, 400 mg/kg bw) for 28 days resulted in a significant decrease in the concentrations of fasting blood glucose (FBG), TC and TG. Furthermore, CPP significantly increased the concentration of HDL-c, body weight and serum insulin level in the mice. In addition, according to acute toxicity studies and single cell gel electrophoresis analysis, CPP did not produce any physical or behavioral signs of toxicity. More significantly, our data demonstrated CPP exhibited the best effects at the dose of 400 mg/kg bw. The above results suggest that CPP can control blood glucose and modulate the metabolism of glucose and blood lipids in diabetes mellitus mice, so we conclude that CPP should be evaluated as a candidate for future studies on diabetes mellitus.     

Anti-Inflammatory Effects of 4-Methylcyclopentadecanone on Edema Models in Mice

The present study evaluated the anti-inflammatory effects of 4-methylcyclopentadecanone (4-MCPC) on edema models in mice and aimed to determine the safety of 4-MCPC after acute exposure. The acute toxicity of 4-MCPC was evaluated by oral administration to rats of single doses of 0, 5, 50, 500 and 5000 mg/kg. Toxic symptoms were observed for 14 days. The anti-inflammatory activity was evaluated in xylene-induced mouse ear edema and carrageenan-induced mouse paw edema. The animals were treated with 4-MCPC once every day for seven consecutive days. Edema index, % inhibition, IL-1β, TNF-α, PGE₂ and MPO levels in paws were detected after the treatment with xylene or carrageenan. Our results indicated that the LD₅₀ value of 4-MCPC in rats is greater than 5000 mg/kg. The ED₅₀ of 4-MCPC in xylene-induced mouse ear edema model was 7.5 mg/kg. 4-MCPC (8 or 16 mg/kg) remarkably inhibited carrageenan-induced mouse paw edema. Further study revealed that 4-MCPC treatment also decreased IL-1β, TNF-α, PGE₂ and MPO levels in mice paws. Intragastric administration of 4-MCPC exhibited more significant anti-inflammatory activity than muscone at a dose of 16 mg/kg. Taken together, our results suggest that 4-MCPC has potent anti-inflammatory activity and the mechanisms might be related to the decreases of the levels of IL-1β, TNF-α, PGE₂ and MPO in inflamed paws.     

Annona muricata (Annonaceae): A Review of Its Traditional Uses,Isolated Acetogenins and Biological Activities

Annona muricata is a member of the Annonaceae family and is a fruit tree with a long history of traditional use. A. muricata, also known as soursop, graviola and guanabana, is an evergreen plant that is mostly distributed in tropical and subtropical regions of the world. The fruits of A. muricata are extensively used to prepare syrups, candies, beverages, ice creams and shakes. A wide array of ethnomedicinal activities is contributed to different parts of A. muricata, and indigenous communities in Africa and South America extensively use this plant in their folk medicine. Numerous investigations have substantiated these activities, including anticancer, anticonvulsant, anti-arthritic, antiparasitic, antimalarial, hepatoprotective and antidiabetic activities. Phytochemical studies reveal that annonaceous acetogenins are the major constituents of A. muricata. More than 100 annonaceous acetogenins have been isolated from leaves, barks, seeds, roots and fruits of A. muricata. In view of the immense studies on A. muricata, this review strives to unite available information regarding its phytochemistry, traditional uses and biological activities.     

Caffeine Inhibits NLRP3 Inflammasome Activation by Downregulating TLR4/MAPK/NF-κB Signaling Pathway in an Experimental NASH Model

Caffeine elicits protective effects against liver diseases, such as NASH; however, its mechanism of action involving the pyrin domain-containing-3 (NLRP3) inflammasome signaling pathway remains to be elucidated. This study aimed to evaluate the effect of caffeine on the NLRP3 inflammasome signaling pathway in a rat model of NASH. NASH was induced by feeding rats a high-fat, -sucrose, and -cholesterol diet (HFSCD) for 15 weeks along with a weekly low dose (400 mg/kg, i.p.) of CCl₄. Caffeine was administered at 50 mg/kg p.o. The effects of HFSCD+CCl₄ and caffeine on the liver were evaluated using biochemical, ultrastructural, histological, and molecular biological approaches. The HFSCD+CCl₄-treated rats showed fat accumulation in the liver, elevated levels of inflammatory mediators, NLRP3 inflammasome activation, antioxidant dysregulation, and liver fibrosis. Caffeine reduced necrosis, cholestasis, oxidative stress, and fibrosis. Caffeine exhibited anti-inflammatory effects by attenuating NLRP3 inflammasome activation. Moreover, caffeine prevented increases in toll-like receptor 4 (TLR4) and nuclear factor-κB (NF-κB) protein levels and mitigated the phosphorylation of mitogen-activated protein kinase (MAPK). Importantly, caffeine prevented the activation of hepatic stellate cells. This study is the first to report that caffeine ameliorates NASH by inhibiting NLRP3 inflammasome activation through the suppression of the TLR4/MAPK/NF-κB signaling pathway.     

Memantine Prevents the WIN 55,212-2 Evoked Cross-Priming of Ethanol-Induced Conditioned Place Preference (CPP)

The activation of the endocannabinoid system controls the release of many neurotransmitters involved in the brain reward pathways, including glutamate. Both endocannabinoid and glutamate systems are crucial for alcohol relapse. In the present study, we hypothesize that N-methyl-D-aspartate (NMDA) glutamate receptors regulate the ability of a priming dose of WIN 55,212-2 to cross-reinstate ethanol-induced conditioned place preference (CPP). To test this hypothesis, ethanol-induced (1.0 g/kg, 10% w/v, i.p.) CPP (unbiased method) was established using male adult Wistar rats. After CPP extinction, one group of animals received WIN 55,212-2 (1.0 and 2.0 mg/kg, i.p.), the cannabinoid receptor 1 (CB1) agonist, or ethanol, and the other group received memantine (3.0 or 10 mg/kg, i.p.), the NMDA antagonist and WIN 55,212-2 on the reinstatement day. Our results showed that a priming injection of WIN 55,212-2 (2.0 mg/kg, i.p.) reinstated (cross-reinstated) ethanol-induced CPP with similar efficacy to ethanol. Memantine (3.0 or 10 mg/kg, i.p.) pretreatment blocked this WIN 55,212-2 effect. Furthermore, our experiments indicated that ethanol withdrawal (7 days withdrawal after 10 days ethanol administration) down-regulated the CNR1 (encoding CB1), GRIN1/2A (encoding GluN1 and GluN2A subunit of the NMDA receptor) genes expression in the prefrontal cortex and dorsal striatum, but up-regulated these in the hippocampus, confirming the involvement of these receptors in ethanol rewarding effects. Thus, our results show that the endocannabinoid system is involved in the motivational properties of ethanol, and glutamate may control cannabinoid induced relapse into ethanol seeking behavior.     

Cyclodextrin-Complexed Ocimum basilicum Leaves Essential Oil Increases Fos Protein Expression in the Central Nervous System and Produce an Antihyperalgesic Effect in Animal Models for Fibromyalgia

O. basilicum leaves produce essential oils (LEO) rich in monoterpenes. The short half-life and water insolubility are limitations for LEO medical uses. β-Cyclodextrin (β-CD) has been employed to improve the pharmacological properties of LEO. We assessed the antihyperalgesic profile of LEO, isolated or complexed in β-CD (LEO/β-CD), on an animal model for fibromyalgia. Behavioral tests: mice were treated every day with either LEO/β-CD (25, 50 or 100 mg/kg, p.o.), LEO (25 mg/kg, p.o.), tramadol (TRM 4 mg/kg, i.p.) or vehicle (saline), and 60 min after treatment behavioral parameters were assessed. Therefore, mice were evaluated for mechanical hyperalgesia (von Frey), motor coordination (Rota-rod) and muscle strength (Grip Strength Metter) in a mice fibromyalgia model. After 27 days, we evaluated the central nervous system (CNS) pathways involved in the effect induced by experimental drugs through immunofluorescence protocol to Fos protein. The differential scanning analysis (DSC), thermogravimetry/derivate thermogravimetry (TG/DTG) and infrared absorption spectroscopy (FTIR) curves indicated that the products prepared were able to incorporate the LEO efficiently. Oral treatment with LEO or LEO-βCD, at all doses tested, produced a significant reduction of mechanical hyperalgesia and we were able to significantly increase Fos protein expression. Together, our results provide evidence that LEO, isolated or complexed with β-CD, produces analgesic effects on chronic non-inflammatory pain as fibromyalgia.     

Protective Effect of Tulbaghia violacea Harv. on Aortic Pathology, Tissue Antioxidant Enzymes and Liver Damage in Diet-Induced Atherosclerotic Rats

The protective effect Tulbaghia violacea rhizomes (TVR) against derangements in serum lipid profile, tissue antioxidant enzyme depletion, endothelium dysfunction and histopathological changes in the aorta and liver of rats fed with an atherosclerogenic (Ath) diet (4% cholesterol, 1% cholic acid and 0.5% thiouracil) was investigated in this study. Co-treatment with the TVR extracts (250 and 500 mg/kg body weight for two weeks significantly (p < 0.05) protected against elevated serum triglyceride (TG), total cholesterol (TC), LDL-cholesterol, VLDL-cholesterol and decreased HDL-cholesterol in a dosedependent manner when compared with the atherogenic control. The extracts also reduced (p < 0.05) elevated thiobabutric reacting substance (TBARS) and reversed endothelial dysfunction parameters (fibrinogen and total NO levels) and tissue antioxidant enzyme activities to near normal. The protective ability of the extract was confirmed by the significant (p < 0.05) reduction in the activities of serum markers of liver (LDH, AST, ALT, ALP, bilirubin) and kidney damage (creatinine and bilirubin) in extract-treated groups compared with the atherogenic control group. Also, histopathology evaluations of aorta sections revealed that the extracts protected against the development of fatty streak plaques (aorta) and fatty changes in hepatocytes. The observed activities of the extracts compared favorably with standard drug atorvastatin. Our study thus showed that the methanolic extract of TVR could protect against the early onset of atherosclerosis.     

Brazilian Ginseng extraction via LPSE and SFE: Global yields, extraction kinetics, chemical composition and antioxidant activity

Brazilian Ginseng extracts of two species, Pfaffia paniculata and Pfaffia glomerata, were obtained by supercritical fluid extraction (SFE) with CO₂ and by low-pressure solvent extraction (LPSE) with methanol, hexane and ethanol. The SFE assays were conducted at pressures of 100, 200 and 300 bar, and temperatures of 30 and 50 °C. The qualitative chemical compositions of the extracts were determined by thin layer chromatography (TLC). One of the active principles of interest from P. glomerata extract, β-ecdysone, was identified and quantified by HPLC. The antioxidant activities of Brazilian Ginseng extracts were determined by the coupled reaction of linolenic acid and β-carotene. For P. paniculata, the highest SFE yield was obtained at 200 bar/50 °C (0.22%, dry basis—d.b.), while the best extraction condition for P. glomerata was obtained at 200 bar/30 °C (0.18%, d.b.). The higher extract yields obtained by LPSE were 2.0% and 5.8% (w/w, d.b.) for P. paniculata and P. glomerata, respectively, both obtained with methanol as extraction solvent. From the overall extraction curve of P. glomerata, it was possible to obtain the kinetic parameters of extraction; the duration of the CER (constant extraction rate) period was determined as 134 min. The TLC plates showed the possible presence of flavonoids in the ethanolic extract for both Pfaffia species. The antioxidant activity analysis detected that LPSE extracts had higher activity than SFE extracts.     

Boesenbergia pandurata Attenuates Diet-Induced Obesity by Activating AMP-Activated Protein Kinase and Regulating Lipid Metabolism

Obesity, a chronic metabolic disorder, is characterized by enlarged fat mass and dysregulation of lipid metabolism. The medicinal plant, Boesenbergia pandurata (Roxb.) Schltr., has been reported to possess anti-oxidative and anti-inflammatory properties; however, its anti-obesity activity is unexplored. The present study was conducted to determine whether B. pandurata extract (BPE), prepared from its rhizome parts, attenuated high-fat diet (HFD)-induced obesity in C57BL/6J mice. The molecular mechanism was investigated in 3T3-L1 adipocytes and HepG2 human hepatoma cells. BPE treatment decreased triglyceride accumulation in both 3T3-L1 adipocytes and HepG2 hepatocytes by activating AMP-activated protein kinase (AMPK) signaling and regulating the expression of lipid metabolism-related proteins. In the animal model, oral administration of BPE (200 mg/kg/day for 8 weeks) significantly reduced HFD-induced body weight gain without altering the amount of food intake. In addition, elevated serum levels of total cholesterol, low-density lipoprotein cholesterol, and triglycerides were suppressed by BPE administration. Fat pad masses were reduced in BPE-treated mice, as evidenced by reduced adipocyte size. Furthermore, BPE protected against the development of nonalcoholic fatty liver by decreasing hepatic triglyceride accumulation. BPE also activated AMPK signaling and altered the expression of lipid metabolism-related proteins in white adipose tissue and liver. Taken together, these findings indicate that BPE attenuates HFD-induced obesity by activating AMPK and regulating lipid metabolism, suggesting a potent anti-obesity agent.     

Pereskia aculeata Muller (Cactaceae) Leaves: Chemical Composition and Biological Activities

The aims of this work were to study the chemical composition of the essential oil from the leaves of Pereskia aculeata and to evaluate some biological activities of three leaf extracts. The phenolic content, antioxidant activity, and in vitro antimicrobial and antifungal activities were determined. The methanol extract showed antioxidant activity (EC₅₀ 7.09 mg/mL) and high polyphenols content (15.04 ± 0.31 mg gallic acid equivalents (GAE)/g). The petroleum ether extract exhibited potent antibacterial activity against Escherichia coli, whereas the chloroform extract showed inhibitory activity against Bacillus cereus and Staphylococcus aureus. The petroleum ether and methanol extracts were more effective in inhibiting the growth of Aspergillus versicolor. The possible cytotoxicity of extracts on neuroblastoma SH-SY5Y cancer cell line and the influence on adenylate cyclase (ADCY) expression was also studied. P. aculeata chloroform extract showed antiproliferative activity with an IC₅₀ value of 262.83 µg/mL. Treatments of SH-SY5Y neuroblastoma cells with 100 µg/mL of methanol extract significantly reduced ADCY1 expression.     

NF-κB-Targeted Anti-Inflammatory Activity of Prunella vulgaris var. lilacina in Macrophages RAW 264.7

Prunella vulgaris var. lilacina, a herbal medicine, has long been used in Korea for the treatment of sore throat, and to alleviate fever and accelerate wound healing. Although the therapeutic effect of P. vulgaris var. lilacina is likely associated with anti-inflammatory activity, the precise underlying mechanisms are largely unknown. Here, we sought to elucidate the possible mechanisms of the anti-inflammatory activity. We have investigated the anti-inflammatory activity of the various solvent fractions (hexane, butanol, chloroform and water) from the ethanol extract of P. vulgaris var. lilacina in activated macrophages. The hexane fraction exhibited higher anti-inflammatory activities, inducing inhibition of nitric oxide and prostaglandin E2 production as well as inducible nitric oxide synthase, cyclooxygenase-2, and tumor necrosis factor-α mRNA expression in response to lipopolysaccharide stimulation. Moreover, the hexane fraction from P. vulgaris var. lilacina significantly inhibited the activation of the nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) and the nuclear translocation of the NF-κB p50 and p65 subunits. These results indicate that P. vulgaris var. lilacina has an anti-inflammatory capacity in vitro, suggesting that it could be a potential source of natural anti-inflammatory agents.     

Celastrol Attenuates Inflammatory and Neuropathic Pain Mediated by Cannabinoid Receptor Type 2

Celastrol, a major active ingredient of Chinese herb Tripterygium wilfordii Hook. f. (thunder god vine), has exhibited a broad spectrum of pharmacological activities, including anti-inflammation, anti-cancer and immunosuppression. In the present study, we used animal models of inflammatory pain and neuropathic pain, generated by carrageenan injection and spared nerve injury (SNI), respectively, to evaluate the effect of celastrol and to address the mechanisms underlying pain processing. Intraperitoneal (i.p.) injection of celastrol produced a dose-dependent inhibition of carrageenan-induced edema and allodynia. Real-time PCR analysis showed that celastrol (0.3 mg/kg, i.p.) significantly reduced mRNA expressions of inflammatory cytokines, TNF-α, IL-6, IL-1β, in carrageenan-injected mice. In SNI mice, pain behavior studies showed that celastrol (1 mg/kg, i.p.) effectively prevented the hypersensitivity of mechanical nociceptive response on the third day post-surgery and the seventh day post-surgery. Furthermore, the anti-hyperalgesic effects of celastrol in carrageenan-injected mice and SNI mice were reversed by SR144528 (1 mg/kg, i.p.), a specific cannabinoid receptor-2 (CB₂) receptor antagonist, but not by SR141716 (1 mg/kg, i.p.), a specific cannabinoid receptor-1 (CB₁) receptor antagonist. Taken together, our results demonstrate the analgesia effects of celastrol through CB₂ signaling and propose the potential of exploiting celastrol as a novel candidate for pain relief.     

In Vivo Anti-Tumor Activity and Toxicological Evaluations of Perillaldehyde 8,9-Epoxide,a Derivative of Perillyl Alcohol

Recent studies have revealed the high cytotoxicity of p-menthane derivatives against human tumor cells. In this study, the substance perillaldehyde 8,9-epoxide, a p-menthane class derivative obtained from (S)-(−)-perillyl alcohol, was selected in order to assess antitumor activity against experimental sarcoma 180 tumors. Toxicological effects related to the liver, spleen, kidneys and hematology were evaluated in mice submitted to treatment. The tumor growth inhibition rate was 38.4%, 58.7%, 35.3%, 45.4% and 68.1% at doses of 100 and 200 mg/kg/day for perillaldehyde 8,9-epoxide, perillyl alcohol and 25 mg/kg/day for 5-FU intraperitoneal treatments, respectively. No toxicologically significant effect was found in liver and kidney parameters analyzed in Sarcoma 180-inoculated mice treated with perillaldehyde 8,9-epoxide. Histopathological analyses of the liver, spleen, and kidneys were free from any morphological changes in the organs of the animals treated with perillaldehyde 8,9-epoxide. In conclusion, the data suggest that perillaldehyde 8,9-epoxide possesses significant antitumor activity without systemic toxicity for the tested parameters. By comparison, there was no statistical difference for the antitumor activity between perillaldehyde 8,9-epoxide and perillyl alcohol.