Project description:The Phytexponent is used to treat pain and inflammation in complementary and alternative medicine practices; however, empirical data supporting its pharmacological efficacy and safety is scanty, hence the present study. We used the carrageenan-induced paw oedema and the acetic acid-induced writhing techniques to determine the anti-inflammatory and analgesic efficacies, respectively, of the Phytexponent in Swiss albino mice models. The 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT) assay technique was used to investigate the in vitro cytotoxic effects of the Phytexponent in the Vero E6 cell line. The Phytexponent exerted significant (P < .05) anti-inflammatory effects in the carrageenan-induced paw oedema mouse model in a dose- and time-dependent manner, with significantly higher efficacy at 250 mg/Kg BW, than indomethacin (4 mg/Kg BW), in the first, second, and third hour (P < .05). Besides, the Phytexponent significantly reduced the acetic acid-induced writhing frequency in mice (P < .05), in a dose-dependent manner, depicting its analgesic efficacy. Notably, the Phytexponent (at doses: 125 mg/Kg BW and 250 mg/Kg BW) exhibited significantly higher analgesic efficacy than the Indomethacin (P<.05). Moreover, the Phytexponent was not cytotoxic to Vero E6 cells (CC50 >1000 µg/ml) compared to cyclophosphamide (CC50 = 2.48 µg/ml). Thus, the Phytexponent has significant in vivo anti-inflammatory and analgesic efficacy in mice models and is not cytotoxic to Vero E6 cell line, depicting its therapeutic potential upon further empirical investigation.
Project description:Recently, we found that the deletion of TRPC5 leads to increased inflammation and pain-related behaviour in two animal models of arthritis. (-)-Englerin A (EA), an extract from the East African plant Phyllanthus engleri has been identified as a TRPC4/5 agonist. Here, we studied whether or not EA has any anti-inflammatory and analgesic properties via TRPC4/5 in the carrageenan model of inflammation. We found that EA treatment in CD1 mice inhibited thermal hyperalgesia and mechanical allodynia in a dose-dependent manner. Furthermore, EA significantly reduced the volume of carrageenan-induced paw oedema and the mass of the treated paws. Additionally, in dorsal root ganglion (DRG) neurons cultured from WT 129S1/SvIm mice, EA induced a dose-dependent cobalt uptake that was surprisingly preserved in cultured DRG neurons from 129S1/SvIm TRPC5 KO mice. Likewise, EA-induced anti-inflammatory and analgesic effects were preserved in the carrageenan model in animals lacking TRPC5 expression or in mice treated with TRPC4/5 antagonist ML204.This study demonstrates that while EA activates a sub-population of DRG neurons, it induces a novel TRPC4/5-independent analgesic and anti-inflammatory effect in vivo. Future studies are needed to elucidate the molecular and cellular mechanisms underlying EA's anti-inflammatory and analgesic effects.
Project description:Inflammatory pain is caused by peripheral tissue injury and inflammation. Inflammation leads to peripheral sensitization, which may further cause central sensitization, resulting in chronic pain and progressive functional disability. Neuroimmune crosstalk plays an essential role in the development and maintenance of inflammatory pain. Studies in recent years have shown that acupuncture can exert anti-inflammatory and analgesic effects by regulating peripheral (i.e., involving local acupoints and inflamed regions) and central neuroimmune interactions. At the local acupoints, acupuncture can activate the TRPV1 and TRPV2 channels of mast cells, thereby promoting degranulation and the release of histamine, adenosine, and other immune mediators, which interact with receptors on nerve endings and initiate neuroimmune regulation. At sites of inflammation, acupuncture enables the recruitment of immune cells, causing the release of opioid peptides, while also exerting direct analgesic effects via nerve endings. Furthermore, acupuncture promotes the balance of immune cells and regulates the release of inflammatory factors, thereby reducing the stimulation of nociceptive receptors in peripheral organs. Acupuncture also alleviates peripheral neurogenic inflammation by inhibiting the release of substance P (SP) and calcitonin gene-related peptide from the dorsal root ganglia. At the central nervous system level, acupuncture inhibits the crosstalk between glial cells and neurons by inhibiting the p38 MAPK, ERK, and JNK signaling pathways and regulating the release of inflammatory mediators. It also reduces the excitability of the pain pathway by reducing the release of excitatory neurotransmitters and promoting the release of inhibitory neurotransmitters from neurons and glial cells. In conclusion, the regulation of neuroimmune crosstalk at the peripheral and central levels mediates the anti-inflammatory and analgesic effects of acupuncture on inflammatory pain in an integrated manner. These findings provide novel insights enabling the clinical application of acupuncture in the treatment of inflammatory diseases.
Project description:Dehydroepiandrosterone (DHEA), an adrenal and neurosteroid hormone with strong neuroprotective and immunomodulatory properties, and ligand for all high-affinity neurotrophin tyrosine kinase receptors (Trk), also exerts important effects on hyperalgesia. Its synthetic, 17-spiro-epoxy analogue, BNN27, cannot be converted to estrogen or androgen as DHEA; it is a specific agonist of TrkA, the receptor of pain regulator Nerve Growth Factor (NGF), and it conserves the immunomodulatory properties of DHEA. Our study aimed to evaluate the anti-nociceptive and anti-inflammatory properties of BNN27 during Complete Freund's Adjuvant (CFA)-induced inflammatory hyperalgesia in mice. Hyperalgesia was evaluated using the Hargreaves test. Inflammatory markers such as cytokines, NGF and opioids were measured, additionally to corticosterone and the protein kinase B (AKT) signaling pathway. We showed for the first time that treatment with BNN27 reversed hyperalgesia produced by CFA. The effect of BNN27 involved the inhibition of NGF in the dorsal root ganglia (DRG) and the increased synthesis of opioid peptides and their receptors in the inflamed paw. We also found alterations in the cytokine levels as well as in the phosphorylation of AKT2. Our findings strongly support that BNN27 represents a lead molecule for the development of analgesic and anti-inflammatory compounds with potential therapeutic applications in inflammatory hyperalgesia.
Project description:BackgroundThe medicinal plant Siegesbeckia orientalis L. has been commonly used for the treatment of acute arthritis, rheumatism, and gout in Vietnam. However, pharmacological research of this plant associated with gout has not been reported. Anti-hyperuricemic and anti-inflammatory effects were evaluated and observed for the crude ethanol extract (CEE) of S. orientalis. Retention of these biological properties was found in a n-butanol-soluble fraction (BuOH fr.) of the extract, and therefore further biological and chemical investigations were undertaken on the BuOH fr. to support the medical relevance of this plant.MethodsThe aerial part of S. orientalis was obtained in the mountainous region of Vietnam. The crude ethanol extract (CEE) and its BuOH fr. were prepared from the plant materials. Anti-hyperuricemic activities of the CEE and BuOH fr. were tested in vivo using the model oxonate-induced hyperuricemia rats through determination of serum uric acid levels and inhibitory effects on xanthine oxidase (XO) in the rat liver. Anti-inflammatory activities of the BuOH fr. were also evaluated in vivo using carrageenan-induced paw edema and urate-induced synovitis in rats. Active components of the BuOH fr. were characterized by comparison of HPLC retention time (t R) and spectroscopic data (UV, 1H-NMR) with those of reference compounds.ResultsThe CEE of S. orientalis displayed anti-hyperuricemic activity, and the BuOH fr. was found to be the most active portion of the extract. Further in vivo studies on this fraction showed 31.4% decrease of serum uric acid levels, 32.7% inhibition of xanthine oxidase (XO), 30.4% reduction of paw edema volume, symptomatic relief in urate-induced synovitis and significant analgesic effect at the dose of 120 mg/kg, as compared to the corresponding values of the control groups. Chemical analysis of the BuOH fr. revealed high phenolic content, identified as caffeic acid analogues and flavonones.ConclusionsThis study suggested that anti-hyperuricemic and anti-inflammatory mechanism of S. orientalis is related to XO inhibitory effect of the phenolic components. Our findings support the use of this plant as the treatment of gout and other inflammatory diseases.
Project description:Graphical abstract Erica arborea L. is a medicinal plant vastly used in therapeutic purposes in several parts of the world for antimicrobial, anti-inflammatory, and diuretic purposes, and in treating urinary infections and kidney stones. The current investigation aimed to evaluate the medicinal use of E. arborea in Algeria's Bejaia region, and to examine the anti-urolithiatic, antibacterial, anti-inflammatory (in vivo), analgesic, and toxicity effects of E. arborea hydromethanolic extracts from leaves (EALE) and flowers (EALE) to give a justification for its use in the traditional medicine. The in vitro anti-urolithiathic activity of E. arborea leaf and flower hydromethanolic extracts nucleation and aggregation of crystals were measured using spectrophotometric methods. The agar disk diffusion assay and minimum inhibitory concentration (MIC) determination were employed to estimate the antibacterial effect of EAME against three Gram-positive and three Gram-negative bacterial strains in vitro. In addition, the xylene and croton oil-induced ear edema methods in mice were used to examine the topical and oral anti-inflammatory potential of the extracts. Similarly, the analgesic effect of the extract was assessed via the acetic acid-induced abdominal constriction in mice, whereas the acute toxicity of EAME was conducted following OECD guidelines. An ethnobotanical survey was conducted among 171 informants with 212 questionnaire cards. Results indicated that 28.04 % of people in the studied region used E. arborea in traditional folk medicine. Additionally, results revealed the presence of epicatechin, palmitic acid, and kaempferol-3-O-glucoside in the plant extracts. Results also showed that EAME exhibits significant and dose-dependent anti-urolithiatic activity in nucleation and aggregation assays. Furthermore, results revealed that the extracts exhibit significant antibacterial activity. The E. arborea flower extract (EAFE) showed maximum antibacterial activity, especially against P. aeruginosa, E. coli, S. gallinarum, and B. cereus. In addition, a greater minimum inhibitory concentration (MIC) in this extract was found at 1.60 mg/mL against M. luteus strain compared to the positive control. Moreover, the EAME caused a significant inhibition influence in the xylene and croton oil-induced edematous in mice. In contrast, the topical anti-inflammatory potential showed that extracts exhibit a considerable anti-edematogenic effect in both animal models. In the writhing reaction induced by the acetic acid model, the two extracts significantly reduced abdominal contractions. Finally, results of the toxicity assay showed that EAME is safe and no deaths or changes in mice behavior were observed even when doses as high as 5 g/kg DW were used. From the ethnopharmacological studies, our consequences endorse the benefit of E. arborea in folk medicine. Results of this investigation suggest that the leaf and flower extracts of E. arborea exhibit notable anti-urolithiatic, anti-inflammatory, analgesic, and antibacterial activities and are safe as a natural source of drugs with the above effects.
Project description:The present study evaluated the anti-inflammatory and analgesic effects of conventional curcumin (cC) and curcumin nanoparticles (nC) associated with diclofenac sodium (D) in experimental acute inflammation (AI) induced by carrageenan administration. Seven groups of eight randomly selected Wistar-Bratislava white rats were evaluated. One group was the control (C), and AI was induced in the other six groups. The AI group was treated with saline solution, the AID group was treated with D, the AIcC200 and AInC200 groups were treated with cC and nC, respectively, while AIcC200D and AInC200D were treated with cC and nC, respectively, both associated with D. Conventional curcumin, nC, and D were administered in a single dose of 200 mg/kg b.w. for cC and nC and 5 mg/kg b.w. for D. Association of cC or nC to D resulted in significant antinociceptive activity, and improved mechanical pressure stimulation and heat thresholds at 3, 5, 7 and 24 h (p < 0.03). The association of cC and nC with D (AIcC200D and AInC200D groups) showed significantly lower plasma and tissue levels of tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and interleukin-1β (IL-1β) up to 2.5 times, with the best results in the group who received nC. Moreover, AInC200D presented the least severe histopathological changes with a reduced level of inflammation in the dermis and hypodermis. The combination of nC to D showed efficiency in reducing pain, inflammatory cytokines, and histological changes in acute inflammation.
Project description:Cancer, pain and inflammation have long been a cause for concern amongst patients, clinicians and research scientists. There is an alarming increase in the demand for medicines suppressing these disease conditions. The present study investigates the role of Syzygium mundagam bark methanol (SMBM) extract against MCF-7 breast cancer cells, pain and inflammation. The MCF-7 cells treated with SMBM were analyzed for adenosine triphosphate (ATP), lactate dehydrogenase (LDH) levels, changes in cell morphology and nuclear damage. Hot plate, acetic acid and formalin-induced pain models were followed to determine the analgesic activity. Anti-inflammatory activity was studied using carrageenan, egg albumin and cotton pellet induced rat models. Microscopic images of cells in SMBM treated groups showed prominent cell shrinkage and nuclear damage. Hoechst stain results supported the cell death morphology. The decline in ATP (47.96%) and increased LDH (40.96%) content indicated SMBM induced toxicity in MCF-7 cells. In the in vivo study, a higher dose (200 mg/kg) of the extract was found to be effective in reducing pain and inflammation. The results are promising and the action of the extract on MCF-7 cells, pain and inflammation models indicate the potential of drugs of natural origin to improve current therapies.
Project description:Arthritis is a widespread inflammatory disease associated with progressive articular surface degradation, ongoing pain, and hyperalgesia causing the development of functional limitations and disability. TRPV1 channel is one of the high-potential targets for the treatment of inflammatory diseases. Polypeptide APHC3 from sea anemone Heteractis crispa is a mode-selective TRPV1 antagonist that causes mild hypothermia and shows significant anti-inflammatory and analgesic activity in different models of pain. We evaluated the anti-inflammatory properties of APHC3 in models of monosodium iodoacetate (MIA)-induced osteoarthritis and complete Freund's adjuvant (CFA)-induced rheumatoid monoarthritis in comparison with commonly used non-steroidal anti-inflammatory drugs (NSAIDs) such as diclofenac, ibuprofen, and meloxicam. Subcutaneous administration of APHC3 (0.1 mg/kg) significantly reversed joint swelling, disability, grip strength impairment, and thermal and mechanical hypersensitivity. The effect of APHC3 was equal to or better than that of reference NSAIDs. Protracted treatment with APHC3 decreased IL-1b concentration in synovial fluid, reduced inflammatory changes in joints, and prevented the progression of cartilage degradation. Therefore, polypeptide APHC3 has the potential to be an analgesic and anti-inflammatory substance for the alleviation of arthritis symptoms.
Project description:To date, no study has been conducted to explore the bioactivity of the crinoid Comanthus bennetti. Here we report the anti-inflammatory properties of comaparvin (5,8-dihydroxy-10-methoxy-2-propylbenzo[h]chromen-4-one) based on in vivo experiments. Our preliminary screening for anti-inflammatory activity revealed that the crude extract of Comanthus bennetti significantly inhibited the expression of pro-inflammatory proteins in lipopolysaccharide (LPS)-stimulated murine RAW 264.7 macrophage cells. Comaparvin isolated from crinoids significantly decreased the expression of inducible nitric oxide synthase (iNOS) protein and mRNA in LPS-stimulated macrophage cells. Moreover, our results showed that post-treatment with comaparvin significantly inhibited mechanical allodynia, thermal hyperalgesia and weight-bearing deficits in rats with carrageenan-induced inflammation. Comaparvin also attenuated leukocyte infiltration and iNOS protein expression in carrageenan-induced inflamed paws. These results suggest that comaparvin is a potential anti-inflammatory therapeutic agent against inflammatory pain.