Rat Hind Paw Research Articles

Curcumin Niosomes Prepared from Proniosomal Gels: In Vitro Skin Permeability, Kinetic and In Vivo Studies.

Curcumin is a poorly water-soluble drug that is used for the treatment of inflammations, tumors, wound healing antioxidant and other diseases. In the current manuscript, it is successfully formulated into proniosome gels. The proniosomes are readily hydrated into niosomal formulations using warm water. Proniosomes were prepared using nonionic surfactants (tween 80, span 60) either solely or in combinations with cholesterol. The produced niosomal formulations were homogenous in size with vesicular sizes >343 and <1800 nm. The encapsulation efficiency percentage “EE%” of curcumin in niosomal formulations was different according to niosomal composition. It increased up to 99.74% in formulations of tween 80/Chol of 200 μmole/mL lipid concentration. Span 60/chol niosomes showed decreased curcumin EE%. Niosomal formulations showed increased SSTF and PC with enhancement ratios of more than 20-fold compared with curcumin suspension form. Kinetically, niosomes fitted to the Korsemeyer-Peppas model with non-Fickian transport according to their calculated n-values where curcumin suspension form showed Korsemeyer-Peppas kinetics with Fickian transport. Niosomal formulations deposited higher curcumin amounts in the skin compared with the suspension form. The best niosomal formulation (F9) was used for niosomal gel and emulgel fabrication. Finally, the anti-inflammatory activity of curcumin in various formulations was evaluated using a rat hind paw edema method and the % of swelling was 17.5% following 24 h in group treated with curcumin niosomal emulgel. In conclusion, this study suggests that the developed niosomal emulgel could significantly enhance the anti-inflammatory effect of curcumin and be an efficient carrier for the transdermal delivery of the drug.

Propofol-loaded nanomicelle with improved anesthetic, pharmacokinetic, hemocompatibility, safety, and permeation profiles

Propofol is known as one of the most potential anesthetics which suffer from limited duration of anesthesia water insolubility. Therefore, in the present study, a formulation of propofol- carboxylic acid-poly [ethylene glycol (COO-PEG)]-b-poly[ D,L lactide (PDLA)]-nanomicelle was developed and its characterization was done by transmission electron microscopy (TEM) and dynamic light scattering analysis (DLS) studies. Afterwards, drug release assay was carried out to determine the efficacy of COO-PEG-PLDA nanomicelle in drug delivery systems. Cytotoxic, hemolytic, pharmacokinetic, and permeation assays were also followed by anesthetic efficacy of propofol- COO-PEG-PLDA nanomicelle in the rat hind paw model. The results indicated that the diameter, hydrodynamic radius and zeta potential of fabricated drug-loaded nanomicelles were 30 nm, 73.24 nm and –23.59 mV, respectively and the nanomicelles were stable for a period of 50 min. Also, COO-PEG-PLDA nanomicelle showed a sustained propofol release at physiological pH. Moreover, it was indicated that COO-PEG-PLDA nanomicelle reduced the cytotoxic and hemolytic effects of propofol and increased the steady-state flux (Jss) by 6.64 times (***P < 0.001) and the cumulative amount of propofol permeated per cm2 of esophageal epithelium after 5 h (Q5h) by 6.01 times (***P < 0.001). Furthermore, pharmacokinetic data showed that COO-PEG-PLDA nanomicelles provided several fold increases in plasma concentration of propofol compared to free propofol at different time intervals. Finally, it was shown that COO-PEG-PLDA nanomicelles improved the induction time of anesthesia, anesthesia period and walking time induced by propofol. In conclusion, it may be suggested that encapsulation of propofol into diblock copolymer nanomicelles can be developed as a new novel therapeutic strategy, facilitating future research as a topical anesthetic.

Enhancement of Curcumin Anti-Inflammatory Effect via Formulation into Myrrh Oil-Based Nanoemulgel.

Background: Curcumin (Cur) possesses a variety of beneficial pharmacological properties including antioxidant, antimicrobial, anti-cancer and anti-inflammatory activities. Nevertheless, the low aqueous solubility and subsequent poor bioavailability greatly limits its effectiveness. Besides, the role of myrrh oil as an essential oil in treating inflammatory disorders has been recently demonstrated. The objective of the current investigation is to enhance Cur efficacy via developing Cur nanoemulgel, which helps to improve its solubility and permeability, for transdermal delivery. Methods: The formulated preparations (Cur gel, emulgel and nanoemulgel) were evaluated for their physical appearance, spreadability, viscosity, particle size, in vitro release and ex vivo drug permeation studies. The in vivo anti-inflammatory activity was estimated using the carrageenan-induced rat hind paw edema method. Results: The formulated Cur-loaded preparations exhibited good physical characteristics that were in the acceptable range of transdermal preparations. The release of Cur from gel, emulgel and nanoemulgel after 12 h was 72.17 ± 3.76, 51.93 ± 3.81 and 62.0 ± 3.9%, respectively. Skin permeation of Cur was significantly (p < 0.05) improved when formulated into nanoemulgel since it showed the best steady state transdermal flux (SSTF) value (108.6 ± 3.8 µg/cm2·h) with the highest enhancement ratio (ER) (7.1 ± 0.2). In vivo anti-inflammatory studies proved that Cur-loaded nanoemulgel displayed the lowest percent of swelling (26.6% after 12 h). Conclusions: The obtained data confirmed the potential of the nanoemulgel dosage form and established the synergism of myrrh oil and Cur as an advanced anti-inflammatory drug.

ANTI-INFLAMMATORY POTENTIAL OF FLEMINGIA STROBILIFERA R.BR . ROOTS: AN EXPERIMENTAL STUDY IN RAT MODELS

Flemingia strobilifera R.Br. (Fabaceae), is a perennial plant traditionally used as an indigenous medicine for its pharmacological characteristics. The goal of our experimentation was to study the chloroform extract of F. strobilifera roots for its anti-inflammatory potential through anti-inflammatory models like carrageenan - elicited rat hind paw edema , cotton pellet - elicited granuloma formation, and carrageenan - elicited leucocyte to justify ethno-medicinal use of the plant. Indomethacin, a reference drug, was used to compare anti-inflammatory potential. The extract, administered respectively with a lower dose of 30 mg and 60 mg per kg body weight as higher dose, three hour post treatment, produced a significant reduction (p &lt; 0.01) in the edema of paw and substantial decrease in implanted cotton pellets dry weight. We conclude that the chloroform extract of roots of F. strobilifera possess osedependent, anti-inflammatory activity.

RETRACTED: Dobera glabra (Forssk.) Poir. (Salvadoraceae); phenolic constituents of the aqueous leaves extract and evaluation of its anti-inflammatory, analgesic activities

BackgroundThe plant kingdom is considered one of the most common sources for structural and biological diversity. In particular, the wild category acquires our attention to investigate the phytochemical and the biological evaluations. MethodsDobera glabra was exposed to phytochemical examination using HPLC-ESI-MS analysis. Furthermore, the anti-inflammatory activity was evaluated using carrageenan-induced rat paw edema model, whereas both the central and peripheral analgesic activities were tested via hot plate test in rats and acetic acid-induced writhing in mice, respectively. ResultsTwenty phenolic compounds of D. glabra aqueous leaves extract were emphasized by liquid chromatography coupled with mass spectrometry. Moreover, D. glabra exhibited both anti-inflammatory and peripheral analgesic activities. Furthermore, D. glabra significantly decreased the immune expression of MMP-9, TNF-α and TGF-β1 in the hind paw of rats. ConclusionD. glabra possess peripheral anti-nociceptive and anti-inflammatory effects in rats mediated through its anti-oxidant and anti-inflammatory activities. The activity of D. glabra leaves extract might be attributed to the presence of hydroxy and keto structures.

Role of calcitonin gene-related peptide in pain regulation in the parabrachial nucleus of naive rats and rats with neuropathic pain

Researches have shown that calcitonin gene-related peptide (CGRP) plays a pivotal role in pain modulation. Nociceptive information from the periphery is relayed from parabrachial nucleus (PBN) to brain regions implicated involved in pain. This study investigated the effects and mechanisms of CGRP and CGRP receptors in pain regulation in the PBN of naive and neuropathic pain rats. Chronic sciatic nerve ligation was used to model neuropathic pain, CGRP and CGRP 8–37 were injected into the PBN of the rats, and calcitonin receptor-like receptor (CLR), a main structure of CGRP receptor, was knocked down by lentivirus-coated CLR siRNA. The hot plate test (HPT) and the Randall Selitto Test (RST) was used to determine the latency of the rat hindpaw response. The expression of CLR was detected with RT-PCR and western blotting. We found that intra-PBN injecting of CGRP induced an obvious anti-nociceptive effect in naive and neuropathic pain rats in a dose-dependent manner, the CGRP-induced antinociception was significantly reduced after injection of CGRP 8–37, Moreover, the mRNA and protein levels of CLR, in PBN decreased significantly and the antinociception CGRP-induced was also significantly lower in neuropathic pain rats than that in naive rats. Knockdown CLR in PBN decreased the expression of CLR and the antinociception induced by CGRP was observably decreased. Our results demonstrate that CGRP induced antinociception in PBN of naive or neuropathic pain rats, CGRP receptor mediates this effect. Neuropathic pain induced decreases in the expression of CGRP receptor, as well as in CGRP-induced antinociception in PBN.

AKTIVITAS ANTIINFLAMASI FRAKSI ETANOL DAUN GEDI (Abelmoschus manihot L. Medik) PADA TIKUS PUTIH GALUR WISTAR

Gedi leaves (Abelmoschus manihot L. Medik) has been used empirically by the people of North Sulawesi to cure the disease. Flavonoids and steroids in Gedi leaves suspected to have anti-inflammatory effects. This Study aims to examine the anti-inflammatory effects of ethanol fraction from Gedi leaves (Abelmoschus manihot L. Medik) on edema of white males wistar foot induced with 1 % caragen, and to determine an effective dose of fraction to decrease the edema volume of Rat foot. The test was done using Rat Hind Paw Edeme or esthablished an artificial inflammation in left foot of white male rats. The treatments were carried out on five groups, the positive control group was administered with diclofenac sodium, the negative control group was administered with CMC Na 0,5 % solution, and the fraction groups were administered with 12 mg/Kg BB, 27 mg/Kg BB, 54 mg/Kg BB. Edema volume were measured every hour for 5 hours using a pletismometer. The average of edema volume (mL) and time (hour) were used to calculate the percentage of anti-inflammatory on each group compared to the negative control group. Obtained data were analyzed by one-way ANOVA followed by LSD test with confident level was 0,05. The result of this study indicate that gedi leaves can reduce edema volume of rat foot that induced with 1 % caragen and anti-inflammatory activity showed in ethanol fraction from Gedi leaves 12 mg/Kg BB by 55,2 %, 27 mg/Kg BB by 64,4% and 54 mg/Kg BB by 62,2%.Keywords : Daun Gedi (Abelmoschus manihot L. Medik), anti-inflammatory, edema

Neuronal delivery of nanoparticles via nerve fibres in the skin

Accessing the peripheral nervous system (PNS) by topically applied nanoparticles is a simple and novel approach with clinical applications in several PNS disorders. Skin is richly innervated by long peripheral axons that arise from cell bodies located distally within ganglia. In this study we attempt to target dorsal root ganglia (DRG) neurons, via their axons by topical application of lectin-functionalized gold nanoparticles (IB4-AuNP). In vitro, 140.2 ± 1.9 nm IB4-AuNP were found to bind both axons and cell bodies of DRG neurons, and AuNP applied at the axonal terminals were found to translocate to the cell bodies. Topical application of IB4-AuNP on rat hind-paw resulted in accumulation of three to fourfold higher AuNP in lumbar DRG than in contralateral control DRGs. Results from this study clearly suggest that topically applied nanoparticles with neurotropic targeting ligands can be utilized for delivering nanoparticles to neuronal cell bodies via axonal transport mechanisms.

Angiotensin-(1-7) attenuates collagen-induced arthritis via inhibiting oxidative stress in rats.

The present study was designed to investigate the anti-rheumatic effects and the mechanism of angiotensin (Ang)-(1-7) in rat models with collagen-induced arthritis (CIA). The CIA model was established using male Wistar rats by intradermal injection of bovine collagen-II in complete Freund's adjuvant at the base of the tail. The levels of angiotensin converting enzyme 2 (ACE2)/Ang-(1-7)/Mas receptor (MasR) were reduced in CIA rats. The attenuation of paw swelling and arthritis scores and improvement of indexes of spleen and thymus were done by Ang-(1-7) injection in CIA rats. The increased levels of inflammatory cytokines, such as interleukin (IL)-1β, IL-6, tumor necrosis factor (TNF)-α, and interferon (IFN)-γ in the serum and hind paw were blocked by Ang-(1-7) administration. In addition, enhanced NADPH oxidase (Nox) activity, increased levels of superoxide anions and malondialdehyde (MDA), and weakened superoxide dismutase (SOD) activity, were all reversed by treatment with Ang-(1-7). Nox1 overexpression reversed the suppressing effects of Ang-(1-7) on paw swelling and arthritis scores in CIA rats. The Ang-(1-7)-induced improvement in spleen and thymus indexes in CIA rats was abolished by Nox1 overexpression. Nox1 overexpression reversed the inhibitory effects of Ang-(1-7) by increasing IL-1β, IL-6, TNF-α, and IFN-γ levels in the serum and hind paw of CIA rats. These results demonstrated that Nox1 increased the oxidative stress in arthritis, and Ang-(1-7) improved rheumatism in arthritis via inhibiting oxidative stress.

Wutou decoction attenuates rheumatoid arthritis by modulating the Ahr/LOC101928120/SHC1 pathway

Context Wutou decoction (WTD) is a Chinese herbal formula alleviating rheumatoid arthritis (RA). SHC adaptor protein 1 (SHC1) regulates apoptosis, inflammation, and the production of reactive oxygen species (ROS). The LOC101928120 gene is located near the SHC1 gene. Bioinformatics analysis showed that the long non-coding RNA LOC101928120 binds to histone deacetylase HDAC1 that might regulate SHC1 expression. The LOC101928120 gene might be targeted by the transcriptional factor Aryl hydrocarbon receptor (Ahr). Objective This study determines the involvement of the Ahr/LOC101928120/SHC1 pathway in WTD alleviation of RA. Materials and methods Wistar rats were injected with complete Freund’s adjuvant in the hind footpad to construe the RA model. WTD (9.8 g/kg/day) was administered intragastrically for 15 days. The CHON-001 chondrocyte cells were treated with IL-1β (10 ng/mL) alone or in combination with WTD (1 μg/mL). A RNA pull-down assay was performed to determine the interaction between LOC101928120 and HDAC1. Ahr targeting the LOC101928120 gene was detected using luciferase reporter and chromatin immunoprecipitation assays. Results WTD alleviated the swelling of the hind paw in rats with RA and suppressed the chondrocyte apoptosis and ROS production caused by IL-1β. WTD decreased SHC1 but increased LOC101928120 in IL-1β-treated chondrocytes. SHC1 knockdown and LOC101928120 overexpression also showed the protection. However, LOC101928120 knockdown attenuated the protective effects of WTD. WTD stimulated Ahr, which promoted LOC101928120 transcription. LOC101928120 recruited HDAC1 to the promoter region of the SHC1 gene, thereby decreasing SHC1. Discussion and conclusion This study revealed a new mechanism by which WTD alleviates RA by modulating the Ahr/LOC101928120/SHC1 pathway.

Effect of a Selection of Skin Penetration Enhancers on Topical Anti-Inflammatory Effect of Boswellic Acids in Carrageenan-Induced Paw Edema in Rats.

Background:Boswellia species have been used for treatment of chronic inflammatory disease. Several studies have documented the anti-inflammatory effect of Boswellic acids (BAs) after systemic administration. This study was aimed to evaluate the effect of some skin penetration enhancers on topical anti-inflammatory effect of BAs in rats.Materials and Methods:Male Wistar rats weighting 180–220 were used. Anti-inflammatory activity was assessed using carrageenan test. BAs dissolved in ethanol, propylene glycol 2%, 5%, olive oil and applied topically. Menthol, D-limonene, or eucalyptus oil 0.5%, 1% were also tested as other skin penetration enhancers and applied topically 30 min prior to subplantar injection of carrageenan into the right hind paw of rats. The volume of the paw was measured at 0 and 4 h after carrageenan with a digital plethysmometer and the difference was used as an index of inflammation. Piroxicam gel was used as a standard drug.Results:A 4% ethanolic solution of BAs showed significant anti-inflammatory effect. Propylene glycol (2% and 5%) in alcohol did not change the effect. Olive oil also enhanced penetration of BAs. Menthol 0.5%, 1% and D-limonene 0.5%, 1% did not show any significant change compared to olive oil alone. In the present study, eucalyptus oil 1% in olive oil was known as the best carrier for transdermal delivery of BAs.Conclusion:BAs have considerable topical anti-inflammatory effects and olive oil alone or especially in combination with eucalyptus oil can be promising vehicles for skin penetration of topical BAs.

Egg white-induced inflammation models: A study of edema profile and histological change of rat's paw.

ABSTRACTThe egg white was used to induce rat paw inflammation, with inadequate references to explain its mechanism. It's contained protein was identified as an allergen was suspected to trigger an inflammatory reaction. This research was aimed to evaluate the use of egg white as an inflammatory inductor in inflammation animal models through edema profile and histological change. Male Wistar rats were divided into three groups, which were given λ-carrageenan, fresh takes of the hen's egg white, and sterile saline solution. Edema was induced by subcutaneous injection of 0.1 ml of λ-carrageenan (1%), egg white, and sterile saline solution as the control in the hind paw of rats. Paw volume was measured before and then at 1, 2, 3, 4, 5, 6, and 24 h after the inductor injection. Paw tissue was taken for evaluation of rats’ paw histological change. The data were analyzed by one-way ANOVA followed by LSD test. The results of the study showed that the egg white could induce rat paw inflammation. Edema formation began in the 1st h and reached the peaks in the 2nd h after the subcutaneous injection of egg white. A number of leukocyte cells were also found in the inflamed paw tissues. Egg white was potential as an edema inductor for animal models of inflammation for the evaluation of new drugs or natural product with anti-inflammation activity.

Evaluation of efficacy of Ocimum sanctum, Azadirachta indica, and their combination in comparison with aspirin on acute inflammatory pain

Background: Aspirin, a potent drug used for acute inflammatory pain, is also associated with various adverse effects, whereas some Indian herbs such as Ocimum sanctum and Azadirachta indica are known to have efficacy against such pain with less serious adverse effects. Aims and Objectives: This study aims to evaluate efficacy of Ocimum sanctum, Azadirachta indica, and their combination in acute inflammatory pain in comparison with aspirin. Materials and Methods: Wistar albino rats of either sex (150–250 g) were divided into five groups with six rats in each group. To induce inflammation, formalin (2.5%, 0.1 ml) was injected into subplantar region of the left hind paw of rats. The study groups were administered orally with distilled water (3 ml), aspirin (200 mg/kg), O. sanctum (400 mg/kg), A. indica (500 mg/kg), and their combination (combination of O. sanctum and A. indica having 400 mg/kg O. sanctum + 500 mg/kg A. indica) half an hour before administration of formalin. Effect of test drugs was assessed by the formalin test, where rats were observed for a period of 40 min to record any response after formalin injection. Two responses were observed ~ time spent in paw licking and number of paw lifting in early/neurogenic and late/inflammatory phases. Results (mean ± SD) were analyzed using one-way ANOVA test followed by Tukey’s HSD test. Results: A. indica had produced a comparable effect to aspirin on inflammatory phase of pain. Conclusion: A. indica could be used as an add-on therapy to conventional drugs for acute inflammatory pain. However, clinical studies on humans would be required to test its accurate efficacy.

Synthesis, Characterization and Biological Evaluation of Novel Acridine Derivatives for Anti-Inflammatory and Analgesic Activities

Synthesis and investigation of anti-inflammatory and analgesic studies of novel N-(5-substituted phenyl-1,3,4-thiadiazol-2-yl) acridin-9-amine derivatives are presented in this article. The title compounds were synthesized by the condensation reaction of 9-chloroacridine and 5-phenyl-1,3,4-thiadiazol-2-amine analogues in presence of N-methyl-2-pyrrolidine and ethyl acetate. All the compounds were screened for their anti-inflammatory and analgesic activities by carrageenan induced rat hind paw edema method and acetic acid induced writhing method respectively. Among the tested compounds, the compound N-(5-(4-chlorophenyl)-1,3,4-thiadiazol-2-yl) acridin-9-amine and N-(5-(4-flourophenyl)-1,3,4-thiadiazol-2-yl) acridin-9-amine with chloro and flouro substituents respectively displayed potent activity when compared to the standard drugs. We also investigated the drug likeness score of the synthesized compounds, the drug likeness score was in correlation with the results obtained in biological activity. The semi planar heterocyclic structure of the acridine nucleus may be the reason for its appreciable reactivity with varied biological receptors. In addition, the drug likeness data of synthesized compounds made them promising leads for the future development of anti-inflammatory and analgesic agents.

Changes in peripheral HCN2 channels during persistent inflammation

ABSTRACT Nociceptor sensitization following nerve injury or inflammation leads to chronic pain. An increase in the nociceptor hyperpolarization-activated current, Ih, is observed in many models of pathological pain. Pharmacological blockade of Ih prevents the mechanical and thermal hypersensitivity that occurs during pathological pain. Alterations in the Hyperpolarization-activated Cyclic Nucleotide-gated ion channel 2 (HCN2) mediate Ih-dependent thermal and mechanical hyperalgesia. Limited knowledge exists regarding the nature of these changes during chronic inflammatory pain. Modifications in HCN2 expression and post-translational SUMOylation have been observed in the Complete Freund’s Adjuvant (CFA) model of chronic inflammatory pain. Intra-plantar injection of CFA into the rat hindpaw induces unilateral hyperalgesia that is sustained for up to 14 days following injection. The hindpaw is innervated by primary afferents in lumbar DRG, L4-6. Adjustments in HCN2 expression and SUMOylation have been well-documented for L5 DRG during the first 7 days of CFA-induced inflammation. Here, we examine bilateral L4 and L6 DRG at day 1 and day 3 post-CFA. Using L4 and L6 DRG cryosections, HCN2 expression and SUMOylation were measured with immunohistochemistry and proximity ligation assays, respectively. Our findings indicate that intra-plantar injection of CFA elicited a bilateral increase in HCN2 expression in L4 and L6 DRG at day 1, but not day 3, and enhanced HCN2 SUMOylation in ipsilateral L6 DRG at day 1 and day 3. Changes in HCN2 expression and SUMOylation were transient over this time course. Our study suggests that HCN2 is regulated by multiple mechanisms during CFA-induced inflammation.

Anti-inflammatory and antinociceptive effects of the selective cannabinoid CB2 receptor agonist ABK5

Cannabinoid receptors are a potential target for anti-inflammatory and pain therapeutics. There are two subtypes, CB1 and CB2, and Δ9-tetrahydrocannabinol activates both of them, providing an analgesic effect but also psychoactive side effects. The psychoactive side effects are considered to be caused by activation of CB1, but not CB2. ABK5 is a CB2 subtype selective agonist that has a very different structure from known cannabinoid receptor agonists. Here, we report anti-inflammatory effects of ABK5 using the T-cell line Jurkat cells, and antinociceptive effect in an inflammatory pain model in rats. Production of the cytokines IL-2 and TNF-α was measured in stimulated Jurkat cells and MOLT-4 cells, and CXCL12-mediated chemotaxis of Jurkat cells was evaluated by a transwell migration assay. Anti-inflammatory and antinociceptive effects of ABK5 were also evaluated in a hindpaw CFA model in rats. ABK5 significantly decreased production of IL-2 and TNF-α measured as both mRNA and protein levels, and reduced chemotaxis towards CXCL12. It also attenuated edema and increased mechanical threshold in the hindpaw of CFA-treated rats. These results suggest that ABK5 is a good lead compound for the development of potential anti-inflammatory and analgesic agents.

UJI AKTIVITAS ANTI INFLAMASI EKSTRAK ETANOL DAUN BUNI (Antidesma bunius L. Spreng) TERHADAP TIKUS PUTIH (Rattus norvegicus)

One of medicinal plant empirically used for traditional is buni leaves (Antidesma bunius L. Spreng) This plant is potential to be developed as medicine for anti-inflammatory. A research on anti-inflammatory activity test of ethanol extract buni leaves (Antidesma bunius L. Spreng) to mice with Rat hind paw edema method. The purpose of study was to investigate the anti-inflammatory activity of the ethanol extract buni leaves (Antidesma bunius L. Spreng) to mice induced with carrageen. The research has done by giving orally suspension of ethanol extract buni leaves (Antidesma bunius L. Spreng) in the dose 5 mg/kg BB, 50 mg/kg BB, and 500 mg/kg BB, Sodium CMC 1% w/v as control negatove and Sodium Diclofenac as control positive. Measurements were made every hour for six hours used plethysmometer. The result after statistically analyzed using Complete Randomized Design showed that dose of 5 mg/kg BB, 50 mg/kg BB and 500 mg/kg BB have anti- inflammatory activity. The result of Duncan’s Real Distance Different test (BNJD) dose 50 mg/kg BB showed that anti-inflammatory activity did not significantly different with Sodium Diclofenac ((α = 0,05).

Antioxidant, Anti-Inflammatory, and Analgesic Activities of Aqueous Extract of Diploknema butyracea (Roxb.) H.J. Lam Bark.

Diploknema butyracea (Roxb.) H.J. Lam is a multipurpose tree used by the Nepalese indigenous people for medicinal purposes such as rheumatism, asthma, and ulcer and other purposes such as cooking and lighting. However, there is no scientific evidence for the medicinal uses of this plant. The present study aimed to explore the phytochemical constituents, estimate the total phenolic content, evaluate antioxidant activity, and investigate the in vivo anti-inflammatory and analgesic activities of aqueous extract of Diploknema butyracea (Roxb.) H.J. Lam bark (ADBB). Phytochemical screening was performed using standard methods. The total phenolic content was determined using the Folin–Ciocalteu method. The in vitro antioxidant activity was determined using 2, 2-diphenyl-1-picrylhydrazyl radical scavenging assay and nitric oxide radical scavenging assay. For the in vivo studies, the plant extract was given in three different doses (50, 100, and 200 mg/kg body weight) to male albino Wistar rats. Anti-inflammatory and analgesic studies were carried out using the carrageenan-induced rat paw edema and the hot plate method, respectively. Results revealed the presence of different phytoconstituents such as flavonoids, tannins, glycosides, terpenoids, and carbohydrates together with a considerable amount of phenolic compounds. Antioxidant assays indicated the potent antioxidant activity of the plant extracts. The higher dose of D. butyracea (200 mg/kg) exhibited a maximum and significant inhibition (53.20%) of rat hind paw edema volume at 4 h and showed a greater increment in latency time (12.15 ± 1.81 sec) in the hot plate test at 120 min. The present study demonstrated the antioxidant, anti-inflammatory, and analgesic potential of ADBB, which supports its traditional medicinal use.

Longitudinal Transcriptomic Profiling in Carrageenan-Induced Rat Hind Paw Peripheral Inflammation and Hyperalgesia Reveals Progressive Recruitment of Innate Immune System Components

Pain is a common but potentially debilitating symptom, often requiring complex management strategies. To understand the molecular dynamics of peripheral inflammation and nociceptive pain, we investigated longitudinal changes in behavior, tissue structure, and transcriptomic profiles in the rat carrageenan-induced peripheral inflammation model. Sequential changes in the number of differentially expressed genes are consistent with temporal recruitment of key leukocyte populations, mainly neutrophils and macrophages with each wave being preceded by upregulation of the cell-specific chemoattractants, Cxcl1 and Cxcl2, and Ccl2 and Ccl7, respectively. We defined 12 temporal gene clusters based on expression pattern. Within the patterns we extracted genes comprising the inflammatory secretome and others related to nociceptive tissue remodeling and to sensory perception of pain. Structural tissue changes, involving upregulation of multiple collagens occurred as soon as 1-hour postinjection, consistent with inflammatory tissue remodeling. Inflammatory expression profiling revealed a broad-spectrum, temporally orchestrated molecular and cellular recruitment process. The results provide numerous potential targets for modulation of pain and inflammation. PerspectiveThis study investigates the highly orchestrated biological response during tissue inflammation with precise assessment of molecular dynamics at the transcriptional level. The results identify transcriptional changes that define an evolving inflammatory state in rats. This study provides foundational data for identifying markers of, and potential treatments for, inflammation and pain in patients.

UVB irradiation induces contralateral changes in galanin, substance P and c-fos immunoreactivity in rat dorsal root ganglia, dorsal horn and lateral spinal nucleus

The selection of control group is crucial, as the use of an inadequate group may strongly affect the results. In this study we examine the effect on contralateral tissue protein levels, in a model of unilateral UVB irradiation, as the contralateral side is commonly used as a control. Previous studies have shown that UVB irradiation increases immunoreactivity for inflammatory regulated neuropeptides.Unilateral UVB irradiation of rat hind paw was performed and corresponding contralateral spinal cord and dorsal root ganglia (DRG) were collected 2–96 h after and investigated for changes in galanin, substance P and c-fos immunoreactivity. Control tissue was collected from naïve rats. Measurement of skin blood flow from contralateral heel hind paws (Doppler), revealed no change compared to naïve rats. However, UVB irradiation caused a significant reduction in the contralateral proportion of galanin immunopositive DRG neurons, at all-time points, as well as an increase in the contralateral spinal cord dorsal horn, around the central canal and in the lateral spinal nucleus (2–48 h). The contralateral proportion of SP positive DRG neurons and dorsal horn immunoreactivity was unchanged, whereas the lateral spinal nucleus area showed increased immunoreactivity (48 h). UVB irradiation also induced a slight contralateral upregulation of c-fos in the dorsal horn/central canal area (24 and 48 h). In summary, unilateral UVB irradiation induced contralateral changes in inflammatory/nociceptive neuropeptides in spinal cord and afferent pathways involved in pain signaling already within 24 h, a time point when also ipsilateral neurochemical/physiological changes have been reported for rats and humans.