Optimization for ultrasonic-microwave synergetic extraction of total iridoid glycosides and screening of analgesic and anti-inflammatory active fractions from patrinia scabra Bunge (Valerianaceae)

Background Patrinia scabra Bunge is a well-known herbal medicine for its favorable treatment on inflammatory diseases owing to its effective ingredients, in which iridoid glycoside plays an extremely significant role. This article aimed to improve the content of total iridoid glycosides in crude extract through a series optimization of extraction procedure. Moreover, considering that both pain and inflammation are two correlated responses triggered in response to injury, irritants or pathogen, the article investigated the anti-inflammatory and analgesic activities of P. scabra to screen out the active fraction. Method P. scabra was extracted by ultrasonic-microwave synergistic extraction (UMSE) to obtain total iridoid glycosides (PSI), during which a series of conditions were investigated based on single-factor experiments. The extraction process was further optimized by a reliable statistical method of response surface methodology (RSM). The elution fractions of P. scabra extract were prepared by macroporous resin column chromatography. Through the various animal experiment including acetic acid-induced writhing test, formalin induced licking and flinching, carrageenan-induced mice paw oedema test and xylene-induced ear edema in mice, the active fractions with favorable analgesic and anti-inflammatory effect were reasonably screen out. Results The content of PSI could reach up to 81.42 ± 0.31 mg/g under the optimum conditions as follows: ethanol concentration of 52%, material-to-liquid ratio of 1:18 g/mL, microwave power at 610 W and extraction time of 45 min. After gradient elution by the macroporous resin, the content of PSI increased significantly. Compared with other concentrations of elution liquid, the content of PSI in 30 and 50% ethanol eluate was increased to reach 497.65 and 506.90 mg/g, respectively. Owing to the pharmacology experiment, it was reasonably revealed that 30 and 50% ethanol elution fractions of P. scabra could relieve pain centrally and peripherally, exhibiting good analgesic and anti-inflammatory activities. Conclusion Patrinia scabra possessed rich iridoids and exhibited significant analgesic and anti-inflammatory activities.

In vivo anti-inflammatory activity of rhizome of Drynaria quercifolia (L.) J. Sm.

Inflammation is found as a common pathogenic process in many of the chronic diseases. To manage them drugs having multiple active principles is needed. Here comes the importance of easily available, potent herbal medicines. Drynaria quercifolia (L.) J. Sm., is a medicinal fern and its rhizome is an ingredient of some Ayurvedic formulations with inflammation. Through present study in vivo analysis of powder (choorna) of the drug were done. Wistar Albino rats were used for the purpose. One group was control (no treatment) and the other three were treated groups given with the suspension of powdered drug in half the calculated effective dose (0.108 gm/200 gm b. Wt.), calculated effective dose (0.216gm/200 gm b. Wt.) and double the calculated effective dose (0.432 gm/200 gm b. Wt.). Repeated measures ANNOVA with Tukey’s post hoc analysis was used as statistical tool to analyse results within the group and one way ANNOVA with Tukey’s post hoc analysis was used for between group analysis. In all the three treated groups significant reduction in paw oedema noted at 2nd hour and maximum reduction at 4th hour after drug administration. But a highly significant reduction in paw oedema at shortest time after drug intake was produced by group administered with double the calculated effective dose of the drug. This showed dose dependent anti-inflammatory action of powder of rhizome of Drynaria quercifolia (L.) J. Sm. This activity can be due to the presence of anti-inflammatory phytoconstituents in the rhizome such as naringin, quercetin, friedelin, betasitosterol, etc.

A Multi-Pronged Approach to Assessing Inflammatory Inhibitory Activity of a New Cyclic Alkaloid Compound from Root Bark of Ziziphus Nummularia (Aubrev.)

[(16-methoxy-10-(3-methyl-butyl)-2-oxa-6, 9, 12-triaza-tricyclo [13.3.1.03, 7] nonadeca-1(18), 13, 15 (19), 16-tetraene-8, 11-Dione], a putative cyclic alkaloid compound (IC) isolated from the root bark of Ziziphus nummularia, showed potential anti-inflammatory potential. Nitric oxide (NO), prostaglandin-E2 (PGE2), and tumour necrosis factor-alpha (TNF- α) levels were measured in vitro to assess IC's potential. ADME simulations and molecular docking of IC by TNF- α receptor were also performed. The in vivo potentials of IC and ethanolic extract (EE) were investigated by assessing carrageenan-induced paw oedema and arachidonic acid/xylene-induced ear oedema. TNF-α inhibition was higher in IC than in others, with a maximal percent inhibition of 88.00 percent at 50.11 µM. IC generated hydrogen bonds with ASP 45 and GLN 47, according to in silico research. Carrageenan, xylene, and arachidonic acid-induced oedema were all significantly reduced by IC. As a result, IC may have clinical potential in the future treatment of inflammation.

ANTI-PYRETIC AND ANTI-INFLAMMATORY ACTIVITY OF AQUEOUS EXTRACT OFSOLANUM XANTHOCARPUM BERRIES IN SUITABLE ANIMAL MODELS

Background: Use of traditional medicines for treating various diseases have become a topic of global importance because of their safety, less side effects and cost-effectiveness. The present study was undertaken to evaluate the anti-pyretic and anti-inflammatory activity of aqueous extract of Solanum xanthocarpum berries (SXB) in suitable animal models. Methods: Anti-pyretic activity was assessed by dried yeast induced pyrexia in rats. Anti-inflammatory activity was evaluated using carrageenan induced paw oedema in rats. Three doses of the plant extract (500, 1000 and 1500 mg/kg) prepared by dissolving the drugs in 2% gum acacia were used. Paracetamol 33 mg/kg and aspirin 100 mg/kg were used as standard drugs for anti-pyretic and anti-inflammatory activity respectively. Vehicle served as a control drug. Results: Acute toxicity study results demonstrated no mortality of animals after 24 hours. The aqueous extract of the plant significantly decreased the rectal temperature of the rats and significantly prevented increase in volume of paw oedema. Conclusion: The aqueous extract of Solanum xanthocarpum berries exerts its anti-pyretic and anti-inflammatory activity activity. However, further studies with the plant are required to evaluate the dose dependent activity and also to determine the active principle responsible for exact mechanism for both antipyretic and anti-inflammatory activity.

Anti-inflammatory Activity of Sulphated Polysaccharide Isolated from Ulva fasciata

There are various components to an inflammatory reaction that can contribute to the associated symptoms and tissue injury and these include Oedema formation, leukocyte infiltration and granuloma formation. Anti-inflammatory activity of the polysaccharide isolated from Ulva fasciata was analysed by carrageenan induced acute paw Oedema and formalin induced chronic paw Oedema. The isolated polysaccharide showed anti-inflammatory activity. Keywords: Ulva fasciata, Sulphated Polysaccharide, Paw Oedema, Anti-inflammatory Activity

Investigating the analgesic properties of Kurkinorin, a novel mu-opioid receptor analogue of Salvinorin A

<p>Background: The mu-opioid receptor (MOPr) activating drugs such as morphine, fentanyl, etorphine and methadone are used to treat moderate to severe pain. However, their long-term use produces serious adverse effects such as respiratory depression, sedation, tolerance, nausea, dependence, and constipation and this signifies the search for an alternate pain therapeutic agent. Here we report the investigation of antinociceptive and side effect profiles of a structurally unique MOPr-activating drug, kurkinorin from Salvinorin A (Sal A) that was compared with morphine and herkinorin. Methods: Adult male B6-SJL mice (22-29 g) were used to investigate the antinociceptive effects of kurkinorin, herkinorin and morphine utilising the 50° C warm-water tail-withdrawal assay. The 2% intra-dermal formalin assay was used to evaluate acute nociceptive and inflammatory pain and paw oedema. The side effect profiles were evaluated by measuring core-body temperature and utilising behavioural tests of motor co-ordination (accelerating rotarod test). Kurkinorin’s rewarding properties were assessed using the conditioned place preference (CPP) assay in male Sprague-Dawley rats (240-350 g). Results: Kurkinorin produced significant antinociceptive effects in the tail-withdrawal assay at both 5 (p<0.01, 10 min, p<0.001, 15-60 min) and 10 mg/kg (p<0.001, 5-90 min, p<0.01, 120 min) and attenuated both nociceptive and inflammatory pain in the 2% intra-dermal formalin model in mice. The analgesic effects of kurkinorin at 10 mg/kg were similar to the analgesic effects of morphine at the same dose. The decrease in pain score in the intra-dermal formalin assay with kurkinorin and morphine produced a corresponding reduction of paw oedema. In comparison, herkinorin had reduced analgesic effects in the tail-withdrawal assay (10 mg/kg, p<0.05, 30 min) and attenuated inflammatory pain in the intra-dermal formalin assay (10 mg/kg, p<0.001) with reduced paw oedema (10 mg/kg, p<0.05). Morphine produced significant motor incoordination effects from 15-60 min post injection whereas kurkinorin produced no significant motor impairment. Kurkinorin and herkinorin (5 mg/kg, i.p) did not produce rewarding effects, whereas morphine produced a significant, rewarding effect in the CPP assay. Kurkinorin produced no change in the core body temperature while morphine significantly reduced the body temperature. Conclusions: Kurkinorin is central acting and is as potent as morphine in attenuating acute nociceptive and inflammatory pain. It produced no significant sedative and rewarding effects. Therefore, kurkinorin has been identified as a structurally new class of mu-opioid analgesic, displaying improvements compared to morphine.</p>

Investigating the analgesic properties of Kurkinorin, a novel mu-opioid receptor analogue of Salvinorin A

<p>Background: The mu-opioid receptor (MOPr) activating drugs such as morphine, fentanyl, etorphine and methadone are used to treat moderate to severe pain. However, their long-term use produces serious adverse effects such as respiratory depression, sedation, tolerance, nausea, dependence, and constipation and this signifies the search for an alternate pain therapeutic agent. Here we report the investigation of antinociceptive and side effect profiles of a structurally unique MOPr-activating drug, kurkinorin from Salvinorin A (Sal A) that was compared with morphine and herkinorin. Methods: Adult male B6-SJL mice (22-29 g) were used to investigate the antinociceptive effects of kurkinorin, herkinorin and morphine utilising the 50° C warm-water tail-withdrawal assay. The 2% intra-dermal formalin assay was used to evaluate acute nociceptive and inflammatory pain and paw oedema. The side effect profiles were evaluated by measuring core-body temperature and utilising behavioural tests of motor co-ordination (accelerating rotarod test). Kurkinorin’s rewarding properties were assessed using the conditioned place preference (CPP) assay in male Sprague-Dawley rats (240-350 g). Results: Kurkinorin produced significant antinociceptive effects in the tail-withdrawal assay at both 5 (p<0.01, 10 min, p<0.001, 15-60 min) and 10 mg/kg (p<0.001, 5-90 min, p<0.01, 120 min) and attenuated both nociceptive and inflammatory pain in the 2% intra-dermal formalin model in mice. The analgesic effects of kurkinorin at 10 mg/kg were similar to the analgesic effects of morphine at the same dose. The decrease in pain score in the intra-dermal formalin assay with kurkinorin and morphine produced a corresponding reduction of paw oedema. In comparison, herkinorin had reduced analgesic effects in the tail-withdrawal assay (10 mg/kg, p<0.05, 30 min) and attenuated inflammatory pain in the intra-dermal formalin assay (10 mg/kg, p<0.001) with reduced paw oedema (10 mg/kg, p<0.05). Morphine produced significant motor incoordination effects from 15-60 min post injection whereas kurkinorin produced no significant motor impairment. Kurkinorin and herkinorin (5 mg/kg, i.p) did not produce rewarding effects, whereas morphine produced a significant, rewarding effect in the CPP assay. Kurkinorin produced no change in the core body temperature while morphine significantly reduced the body temperature. Conclusions: Kurkinorin is central acting and is as potent as morphine in attenuating acute nociceptive and inflammatory pain. It produced no significant sedative and rewarding effects. Therefore, kurkinorin has been identified as a structurally new class of mu-opioid analgesic, displaying improvements compared to morphine.</p>

Analgesic, Anti-inflammatory and Antipyretic Activity of Rotula aquatica Lour Leave

The present study was aimed to evaluate analgesic, anti-inflammatory and anti pyretic activity of methanolic extract and aqueous extract of leave of Rotula aquatica L. in mice and rats. The methanolic extract of R. aquatica L. leave at a dose of 200mg/kg body weight has shown significant analgesic, antipyretic and anti-inflammatory activity as compared to aqueous extract. The result of hot plate method indicated that the total methanolic extract showed significant increase (P<0.01) in reaction time at a 3,4and 6 hours comparable to the reference drug Pentazocin but lesser (P<0.05) after 2hr. The tail immersion and hot plate tests revealed that plant has high analgesic activity. Both tests showed highest degree of analgesia in methanolic extract compared to aqueous extract. The total methanolic extract of R.aquatica L. leave at the a dose of 200mg/kg body weight has shown significant (p<0.01) antipyretic activity as compared to aqueous extract, methanolic extract also found to have significant result in Carrageenin-induced paw oedema; suspect edmodeo faction may be due to possible inhibition of lipooxygenase pathway.

Protective Effect of Methyl gallate on Murine Antigen-Induced Arthritis by Inhibiting Inflammatory Process and Bone Erosion

Methyl gallate (MG) is a plant-derived phenolic compound known to present remarkable anti-inflammatory effect in different experimental models such as paw oedema, pleurisy, zymosan-induced arthritis and colitis. Herein we investigated the effect of MG in the mice model of antigen-induced arthritis (AIA), a model with complex inflammatory response, driven primally by immune process and that cause bone and cartilage erosion similarly found in rheumatoid arthritis. Arthritis was induced by i.a injection of albumin methylated from bovine serum (mBSA) in C57BL/6 male mice previously immunized. The dose-response analysis of MG (0.7-70 mg/kg; p.o) showed that maximum inhibition was reached with the dose of 7 mg/kg on paw oedema and cell infiltration induced by AIA at 7 h. Treatment with MG (7mg/kg; p.o) or with the reference drug, dexamethasone (Dexa,10 mg/kg, ip) reduced AIA oedema formation, leukocyte infiltration, release of extracellular DNA and cytokine production 7 and 24 h (acute response). Mice treated daily with MG for seven days showed no significant weight loss or liver and kidney toxicity contrary to Dexa that induced some degree of toxicity. Prolonged treatment with MG inhibited the late inflammatory response (28 days) reducing oedema formation, cell infiltration, synovial hyperplasia, pannus formation and cartilage degradation as observed in histopathological analyses. Ultimately, MG reduced bone resorption as evidenced by a decrease in tartrate-resistant acid phosphate (TRAP)-positive cells number in femur histology. Altogether, we demonstrate that MG ameliorates the inflammatory reaction driven primarily by the immune process, suggesting a potential therapeutic application in arthritis treatment.

In Vivo Anti-Inflammatory and Antioxidant Potentials of Ethanolic Flower Extract and Isolated Compound, Rutin from Bauhinia tomentosa L.

Bauhinia tomentosa L. belonging to the family Caesalpiniaceae is a traditional medicinal plant species used by the local healers for the treatment of inflammation and other ailments. The present study was addressed to isolate and characterize bioactive entities exists in the ethanolic extract of B. tomentosa flower. Moreover, the anti-inflammatory effects of crude and isolated compounds were assessed using carrageenan induced paw oedema model. Indomethacin, a renowned reference drug was used for comparison. In vivo antioxidant activities were achieved using standard procedures. In anti-inflammatory studies, the isolated compound, rutin (10mg/kgb.w.) manifested potent activity by inhibiting paw oedema (92.6%) than the crude extracts (88.7%). With reference to these findings, rutin also registered eminent therapeutic property in terms of in vivo antioxidant activity. Therefore, the current study exposed that the anti-inflammatory effects of isolated compound, rutin is more expected to depend on their ability to inhibit the production of proinflammatory mediators and proposes that the studied plant species can be deliberated as one of the finest, versatile and most frequently used household remedies for varied manifestations. Furthermore, the compound isolated may serve as a lead molecule for the formulation of active novel drugs without any adverse side effects.