Topical anti-inflammatory and analgesic activity of kirenol isolated from Siegesbeckia orientalis

Ethnopharmacological relevance

Siegesbeckia orientalis has been traditionally used as a topical anti-inflammatory and analgesic agent.

Aims of the study

Current study was designed to explore the topical anti-inflammatory and analgesic effects of a constituent isolated from Siegesbeckia orientalis (Compositae), in order to validate its folk use.

Materials and methods

Kirenol was isolated from ethanolic extract of Siegesbeckia orientalis. Several topical formulations containing kirenol were investigated for anti-inflammatory and analgesic activities in rat. The effects were studied using carrageenan-induced rat acute inflammation model, complete Freund's adjuvant (CFA)-induced chronic inflammation and formalin test in rats. Piroxicam gel and methyl salicylate ointment were studied as positive control for anti-inflammatory and analgesic activity, respectively.

Results

The anti-inflammatory effect of kirenol 0.4-0.5% (w/w) was similar to the effect of piroxicam gel 4 h after carrageenan injection. The analgesic activity of topical preparation with more than 0.4% (w/w) was observed in the late phase. These effects may be due, at least in part, to the pro-inflammatory cytokine production of IL-1β and TNF-α. The administration of kirenol cream at the dose of 0.3, 0.4 and 0.5% (w/w) significantly inhibited the development of joint swelling induced by CFA, which was auxiliary supported by histopathological studies.

Conclusion

Kirenol has demonstrated its significant potential to be further investigated for its discovery as a new lead compound for management of topical pain and inflammation, although further pharmacological research is necessary to fully understand its mechanism of action. It also supports the potential beneficial effect of topically administered Siegesbeckia orientalis in inflammatory diseases.     

Topical anti-inflammatory and analgesic activities of standardized pomegranate rind extract in comparison with its marker compound ellagic acid in vivo

Ethnopharmacological relevance

In Chinese traditional medicine, the peels of Punica granatum L. have been used to treat traumatic hemorrhage, burn, and ulcers.

Aims of the study

This study aimed to assess the topical anti-inflammatory and analgesic activities of a standardized pomegranate rind extract (SPRE) of which ellagic acid (EA) was the major antioxidant constituent and the marker compound.

Material and methods

The topical anti-inflammatory effects of SPRE were evaluated against acute models (croton oil-induced mouse ear edema and carrageenan-induced rat paw edema) and chronic model (complete Freund's adjuvant (CFA)-induced polyarthritis). The topical analgesic activities of SPRE were investigated in the rat punctuate mechanical hyperalgesia test and in the mouse formalin test. All studies of SPRE were carried out in parallel with its marker compound EA.

Results

SPRE (5%, 2.5%, and 1%, w/w) and the equivalent EA (0.65%, 0.325%, and 0.13%, w/w) dose-dependently reduced the croton oil-induced mouse ear edema with a maximal inhibition of 86.30% and 80.82%, respectively. SPRE dose-dependently attenuated the inflammatory responses in the carrageenan-induced rat paw edema and in the CFA-induced polyarthritis but the equivalent EA were effective only at the doses of 0.65% and 0.325%. Both SPRE (5%) and EA (0.65%) showed significant topical analgesic activities in the rat punctuate mechanical hyperalgesia test and in the mouse formalin test.

Conclusions

SPRE was more active as an anti-inflammatory agent than EA. The anti-inflammatory and analgesic effects of SPRE were achieved through inhibiting the leukocyte infiltration and modulating the pro-inflammatory cytokines IL-β and TNF-α. These results clearly demonstrated that SPRE is a promising phytomedicine that could find use in the treatment of inflammatory diseases.     

Anti-inflammatory and antipyretic effects of Trigonella foenum-graecum leaves extract in the rat

Anti-inflammatory and antipyretic effects of the Trigonella foenum-graecum (TFG) leaves extract, an Iranian medicinal plant, were examined. For anti-inflammatory activity, the formalin-induced edema model was used. Hyperthermia was induced by intraperitoneal injection of 20% (w/v) aqueous suspension of brewer's yeast. Sodium salicylate (SS) was used as a positive control. Both TFG and SS significantly reduced formalin-induced edema in single dose (TFG 1000 and 2000 mg/kg, SS 300 mg/kg) and chronic administration (TFG 1000 mg/kg and SS 300 mg/kg). TFG and SS also significantly reduced hyperthermia induced by brewer's yeast in 1 and 2 h after their administration. The results indicate that the TFG leaves extract possess anti-inflammatory as well as antipyretic properties in both i.p. and p.o. administration. Phytochemical studies indicate that alkaloids, cardiac glycosides, and phenols are the major component in the extract. Although existence of three anti-inflammatory, analgesic and antipyretic effects in this extract suggest a NSAID-like mechanism for it, but the presence of alkaloids, the absence of other effective compounds such as flavonoids, saponins, steroids, etc., and also its analgesic effect on tail-flick test that usually is not produced by NSAIDs, suggest another mechanism for the extract. So the possibility of alkaloids as effective compounds, in this extract, increases.     

马鞭草化学成分及药理活性研究进展

马鞭草为中国传统中药,具有活血散瘀、解毒、利水、退黄等功效,临床上常用于水肿、疟疾、黄疸、肝炎、咳嗽、流行性感冒等症的治疗。马鞭草所含化学成分众多,其中黄酮类、环烯醚萜类、苯乙醇苷类、三萜类、挥发油类等成分为其主要活性成分。现代药理研究表明,马鞭草具有抗炎、抗病毒、抗菌、镇咳、抗肿瘤及调节免疫等作用。文章总结了近20年来国内外有关马鞭草化学成分、药理及毒性相关文献,对其研究进展进行综述,为马鞭草的药物开发及临床应用提供依据。     

Ocimum sanctum: an experimental study evaluating its anti-inflammatory, analgesic and antipyretic activity in animals

A methanol extract and an aqueous suspension of Ocimum sanctum inhibited acute as well as chronic inflammation in rats as tested by carrageenan-induced pedal edema and croton oil-induced granuloma and exudate, respectively. In both test procedures, the anti-inflammatory response of 500 mg/kg of methanol extract and aqueous suspension was comparable to the response observed with 300 mg/kg of sodium salicylate. Both the extract and suspension showed analgesic activity in the mouse hotplate procedure and the methanol extract caused an increase in the tail-withdrawal reaction time of a subanalgesic dose of morphine. Both preparations reduced typhoid-paratyphoid A/B vaccine-induced pyrexia. The antipyretic action of the methanol extract and aqueous suspension was weaker and of shorter duration than that of 300 mg/kg sodium salicylate. Oral premedication with the methanol extract and the aqueous suspension delayed castor oil-induced diarrhoea in rats.     

Anti-inflammatory,wound healing and in-vivo antioxidant properties of the leaves of Ficus amplissima Smith

Ethno pharmacological relevance

Ficus amplissima, commonly known as kal-itchchi, being used in folklore medicine, leaves juice is applied externally on old chronic wounds and the latex is applied on the wound.

Aim

There was no scientific evidence justifying the medicinal use of Ficus amplissima, therefore the present study was aimed at evaluation of anti-inflammatory, wound healing and in-vivo antioxidant activity of the plant.

Materials and methods

In the present study the acetone extract of Ficus amplissima leaves were studied for enzymatic antioxidant activity through different assays, anti-inflammatory by using carrageenan and histamine induced rat paw edema models (50 mg, 100 mg acetone extract) and wound healing activity by incorporating the two doses (1% (w/w) and 2% (w/w)) of acetone extract and simple ointment base B.P. in concentration of 0.5% (w/w) using excision and incision wound models in rats. In case of the excision wound model wound contraction and period of epithelization was studied while incision wound model was evaluated by determining tensile strength.

Results

Ficus amplissima leaves expressed the potent anti-inflammatory and in-vivo antioxidant activity where 100 mg acetone extract showed high activity. Treatment of wound with ointment containing 2% (w/w) acetone extract exhibited significant (P<0.001) wound healing activity.

Conclusion

The acetone extract of Ficus amplissima leaves exhibited better anti-inflammatory, wound healing and in-vivo antioxidant activity probably due to phenols constituents.     

Antiinflammatory effect of topically applied propolis extract in carrageenan-induced rat hind paw edema

The antiinflammatory effect of an ointment containing propolis extract (3%-7%) was examined using carrageenan-induced hind paw edema in rats. Treatment with the ointment inhibited the edema moderately, and the inhibition was significant at 5% and 7%. Additionally, the effect of the ointment on chemotaxis of human polymorphonuclear leukocytes (PMNs) was investigated using the agarose plate method. Migration of PMNs toward zymosan-treated serum was inhibited in the presence of 5% propolis ointment. These results demonstrate that topical application of propolis extract is effective in inhibiting carrageenan-induced rat hind paw edema, and its inhibitory effect on the chemotaxis of PMNs may also contribute to the antiinflammatory effect.     

Anti-inflammatory and analgesic activity of Biebersteinia multifida DC. root extract

The root of Biebersteinia multifida DC (Geraniaceae), a native plant of Iran, has been used topically for the treatment of musculoskeletal disorders as a folk medicine. The anti-inflammatory and analgesic effects of the root extract were studied using carrageenan induced edema and formalin tests. A similar activity was seen between Biebersteinia multifida root extract (10 mg/kg; i.p.) and indomethacin (4 mg/kg; i.p.) in carrageenan test. The results of formalin test showed the analgesic activity of the root extract (50 mg/kg; i.p.) was comparable with morphine (10 mg/kg; i.p.) at the first phase of formalin test. Furthermore, the probable ulcerogenic activity of the root extract was also studied. The extract did not show any ulcerogenic effect at anti-inflammatory doses (10 mg/kg; p.o.).     

Anti-inflammatory and antipyretic properties of Clerodendrum petasites S. Moore

The methanol extract from Clerodendrum petasites S. Moore (CP extract) was assessed for anti-inflammatory and antipyretic activities on the experimental animal models. It was found that CP extract possessed moderate inhibitory activity on acute phase of inflammation in a dose-related manner as seen in ethyl phenylpropiolate-induced ear edema (ED(50)=2.34 mg/ear) as well as carrageenin-induced hind paw edema (ED(30)=420.41 mg/kg) in rats. However, CP extract did not elicit any inhibitory effect on arachidonic acid-induced hind paw edema in rats. In subchronic inflammatory model, CP extract provoked a significant reduction of transudation but had no effect on proliferative phase when tested in cotton pellet-induced granuloma model. CP extract also reduced the alkaline phosphatase activity in serum of rats in this animal model. Moreover, CP extract possessed an excellent antipyretic effect when tested in yeast-induced hyperthermic rats. It is postulated that the anti-inflammatory and antipyretic effects of CP extract are caused by the inhibition of the prostaglandin synthesis. Anyhow, CP extract did not possess any analgesic activity in acetic acid-induced writhing response in mice. The results obtained show that C. petasites has beneficial properties since it possesses potent antipyretic and moderate anti-inflammatory activities without ulcerogenic effect.     

Anti-inflammatory and analgesic activities of Mallotus spodocarpus Airy shaw

The chloroform extract from the roots of Mallotus spodocarpus was investigated for anti-inflammatory and analgesic activities in animal models. In acute inflammatory models, the extract significantly inhibited ethyl phenylpropiolate-induced ear edema and carrageenin- and arachidonic acid-induced hind paw edema in rats. In the chronic inflammatory model using the cotton pellet-induced granuloma in rats, the extract exhibited inhibitory activity on the formation of granuloma. The extract also elicited pronounced inhibitory effect on acetic acid-induced writhing response in mice in the analgesic test. The results obtained suggest marked anti-inflammatory and analgesic activity of the extract.     

马鞭草环烯醚萜苷类成分的研究

目的：探索马鞭草抗早孕有效成分。方法：甲醇渗漉提取,反复硅胶柱层析分离,理化常数和光谱分析鉴定化合物结构。结果：从马鞭草甲醇提取物中分离并鉴定了３个环烯醚萜苷,分别为马鞭草苷（Ⅰ）、３,４二氢马鞭草苷（Ⅱ）和５－羟基马鞭草甘（Ⅲ）。结论：其中Ⅱ为新的天然化合物。     

Anti-inflammatory, analgesic and antipyretic activities of the extract of gamboge from Garcinia hanburyi Hook f

In Thai folklore medicine, gamboge, the yellow gum-resin secreted from Garcinia hanburyi, is used for infected wound, pain and edema The ethyl acetate extract from Garcinia hanburyi (GH5763) was assessed for anti-inflammatory, analgesic and antipyretic activities using experimental animal models. It was found that GH5763 possessed inhibitory activity on acute phase of inflammation as seen in ethyl phenylpropiolate-induced ear edema and carrageenin-induced hind paw edema in rats. However, GH5763 did not elicit any inhibitory effect on arachidonic acid-induced hind paw edema. In subchronic inflammatory model, GH5763 provoked a significant reduction of both transudative and proliferative phase when tested on cotton pellet-induced granuloma model. GH5763 also reduced the alkaline phosphatase activity in serum of rats in this animal model. In the analgesic test, GH5763 elicited inhibitory activity on acetic acid-induced writhing response and on both the early and the late phase of formalin test. Moreover, GH5763 also possessed an excellent antipyretic effect when tested in yeast-induced hyperthermic rats. It is postulated that the anti-inflammatory, analgesic and antipyretic activities of GH5763 are caused by the inhibition of the prostaglandin biosynthesis.     

Anti-inflammatory, analgesic and antipyretic effects of methanol extract from Bauhinia racemosa stem bark in animal models

In this study, the anti-inflammatory, analgesic, and antipyretic effects of 50, 100 and 200 mg/kg body weight of methanol extract obtained from Bauhinia racemosa stem bark, the so-called MEBR, were investigated. The effects of MEBR on the acute and chronic phases of inflammation were studied in carrageenan, dextran and mediators (histamine and serotonin)-induced paw oedema and cotton pellet-induced granuloma, respectively. Analgesic effect of MEBR was evaluated in acetic acid-induced writhing and hotplate tests. Antipyretic activity of MEBR was evaluated by yeast-induced hyperpyrexia in rats. The anti-oedema effect of MEBR was compared with 10 mg/kg of indomethacin orally. In acute phase of inflammation, a maximum inhibition of 44.9, 43.2, 44.8 and 45.9% (P<0.001) was noted at the dose of 200 mg/kg b.w. after 3h of treatment with MEBR in carrageenan, dextran, histamine and serotonin-induced paw oedema, respectively. Administration of MEBR (200 mg/kg b.w.) and indomethacin (10 mg/kg b.w.) significantly (P<0.05) decreased the formation of granuloma tissue induced by cotton pellet method at a rate of 50.4 and 56.2%, respectively. The extract also inhibited peritoneal leukocyte migration in mice. The MEBR also produced significant (P<0.01) analgesic activity in both models. Further, the MEBR potentiated the morphine- and aspirin-induced analgesic in mice. Treatment with MEBR showed a significant (P<0.01) dose-dependent reduction in pyrexia in rats. The results suggest that MEBR possess potent anti-inflammatory, analgesic and antipyretic activity.     

高载药量萘普生凝胶的制备及抗炎镇痛作用研究

目的:制备载药量高、渗透效果好的萘普生凝胶并考查其抗炎、镇痛作用。方法:以卡波姆980为凝胶基质、丙二醇为保湿剂、卡必醇为促渗剂和增溶剂制备不同载药量的萘普生凝胶。用二甲苯诱导小鼠耳廓肿胀,卡拉胶诱发大鼠足跖肿胀,考查萘普生凝胶的抗炎作用;用热板法和扭体法观察萘普生凝胶对小鼠的镇痛作用。以1%的双氯芬酸钠凝胶剂作为阳性对照药,1%、2%和4%的萘普生凝胶分组给药。结果:加入25%的卡必醇后,所制凝胶的载药量可达4%,其稳态渗透速率可达324.1μg.cm-2.h-1。2%和4%萘普生凝胶对二甲苯引起的小鼠耳肿胀、卡拉胶所致大鼠足跖肿胀和醋酸引起的小鼠疼痛扭体反应均有较好的抑制作用,并能明显提高热板法小鼠的痛阈,改善痛阈提高百分率。与阳性药物组相比,2%、4%的萘普生凝胶剂组均显示相近或更好的抗炎镇痛作用。结论:以卡必醇为促渗剂和增溶剂所制的萘普生凝胶经皮给药制剂,对大鼠及小鼠的炎症及痛反应模型均有抑制作用,有望成为萘普生的新型给药制剂。     

Topical anti-inflammatory activity of Serjania erecta Radlk (Sapindaceae) extracts

Serjania erecta Radlk (Sapindaceae), commonly called cinco-folhas or cipó-cinco-folhas in Brazil, is thought to be effective for treating several inflammatory diseases. In order to verify the topical anti-inflammatory effect of Serjania erecta, hydroalcoholic extract and fractions were obtained by extraction in solvents of increasing polarity and were tested in mouse models using croton-oil-induced inflammation. Our findings showed that topical application of Serjania erecta hydroalcoholic extract (0.01-3.0 mg/ear), and the dichloromethane (0.03-1.0 mg/ear), ethyl acetate (0.03-1.0 mg/ear), and hexane (0.003-1.0 mg/ear) fractions revealed significant activity, causing a dose-dependent reduction of croton-oil ear edema (ID(50)=0.14 mg/ear, 0.23 mg/ear, 0.14 mg/ear, 0.04 mg/ear, respectively). The extract and all tested fractions also decreased tissue myeloperoxidase activity (indicative of polymorphonuclear leukocytes influx) in mouse-ears treated with croton oil with a maximum inhibition of 72% at 3.0 mg/ear for the hydroalcoholic extract and 81%, 78%, and 83% at 1.0mg/ear for dichloromethane, ethyl acetate and hexane fractions, respectively. As expected, dexamethasone (0.05 mg/ear) was effective in inhibiting both edema and myeloperoxidase activity (99% and 82%, respectively). In conclusion, our results indicate a topical anti-inflammatory effect for the species of Serjania studied.     

狭叶荨麻根、茎、叶的抗炎镇痛作用

目的研究狭叶荨麻Urticaangustifolia根、茎、叶70%乙醇提取物及狭叶荨麻根水提取物的抗炎、镇痛作用。方法二甲苯致小鼠耳廓肿胀实验;冰醋酸致小鼠扭体反应实验。结果狭叶荨麻根、茎、叶70%乙醇提取物及狭叶荨麻根水提取物能明显对抗二甲苯致小鼠耳廓肿胀,并显著抑制0.5%醋酸致小鼠扭体反应。结论狭叶荨麻根、茎、叶70%乙醇提取物及狭叶荨麻根水提取物具有显著的抗炎、镇痛活性。     

Topical anti-inflammatory activity of Salvia officinalis L. leaves: the relevance of ursolic acid

Salvia officinalis L. leaves, obtained from four plant populations of different origin, were investigated for their topical anti-inflammatory properties. The n-hexane and the chloroform extracts dose-dependently inhibited the Croton oil-induced ear oedema in mice, the chloroform extracts being the most active. By contrast, the methanol extracts showed a very low effect and the essential oil was inactive. Chemical and pharmacological investigation of the most potent chloroform extract, issued from an autochthonous sage population grown in the submediterranean climatic region of Slovenia, revealed ursolic acid as the main component involved in its anti-inflammatory activity. The anti-inflammatory effect of ursolic acid (ID50 = 0.14 microMoles/cm2) was two fold more potent than that of indomethacin (ID50 = 0.26 microMoles/cm2), which was used as a reference non-steroidal anti-inflammatory drug (NSAID). The content of ursolic acid in sage and sage-based remedies for the topical treatment of inflammatory diseases is proposed as a parameter for quality control purposes.     

Analgesic, anti-inflammatory and antioxidant properties of Buddleja globosa, Buddlejaceae

ETHNOPHARMACOLOGICAL RELEVANCE: Buddleja globosa, known as "matico", is employed in Chile for wound healing. AIM OF THE STUDY: To validate the traditional use of the crude drug through in vivo and in vitro evaluation of the anti-inflammatory, analgesic and antioxidant properties of its extracts. MATERIALS AND METHODS: Sequential hexane, dichloromethane, methanol and total methanol extracts were studied using bioguided fractionation. The following activities were investigated: analgesic (writhing test), oral and topic anti-inflammatory (paw- and ear-induced edema), free radical scavenging and antioxidant activities (1,1-diphenyl-2-picrylhydrazyl, DPPH, superoxide anion, lipid peroxidation and xanthine oxidase inhibition). Sodium naproxen, nimesulide, indomethacin were used as reference drugs for in vivo, quercetin and allopurinol for in vitro assays. RESULTS: A mixture of alpha- and beta-amyrins was isolated from the hexane extract that showed 41.2% of analgesic effect at 600 mg/kg, inhibited by 47.7 and 79.0% the arachidonic acid (AA) and 12-deoxyphorbol-13-decanoate (TPA)-induced inflammation at 3mg/20 microL/ear, respectively. A mixture of beta-sitosterol, stigmasterol, stigmastenol, stigmastanol and campesterol was isolated from the fraction CD4-N and beta-sitosterol-glycoside from the fraction CD5-N, reducing TPA-induced inflammation by 78.2 and 83.7% at 1mg/20 microL/ear, respectively. The fraction CD4-N at 300 mg/kg also showed analgesic activity (38.7%). The methanol extract at 600mg/kg per os showed anti-inflammatory effect (61.4%), topic anti-inflammatory (56.7% on TPA) and analgesic activity (38.5%). Verbascoside and luteolin-7-O-glucoside were the major components of the methanol extract; apigenin 7-O-glucoside was also detected. Inhibition of superoxide anion, lipoperoxidation, and DPPH bleaching effect was found in the methanol serial and global extracts. CONCLUSIONS: The present report demonstrate the analgesic and anti-inflammatory properties of Buddleja globosa and validate its use in Chilean traditional medicine.     

Anti-inflammatory effect of Lithrea molleoides extracts and isolated active compounds

Aim of the study

In this study the anti-inflammatory activity of aqueous, dichloromethane (CH₂Cl₂) and methanolic (MeOH) extracts and two major compounds isolated from Lithrea molleoides (Vell.) Engl. (Anacardiaceae) were evaluated.

Materials and methods

Two classical experimental models were used, carrageenan-induced rat paw edema and 12-O-tetradecanoylphorbol-13 acetate (TPA) induced mouse ear edema.

Results

MeOH extracts exhibited a significant systemical anti-inflammatory effect in the carrageenan (inhibition of 46% at 3 h) and in the TPA-ear edema test (inhibition of 21%). The presence of methyl gallate (inhibition of 63% in TPA ear edema), as one of the main compounds in the active fraction from MeOH extract may be explained the effect observed. Also, 1,3-dihydroxy-(Z,Z)-5-(tridec-4′,7?dienyl) benzene obtained from CH₂Cl₂ extract showed a significant topical anti-inflammatory activity (inhibition of 68%). Furthermore, no signs of toxicity were observed with doses up to 3 g/kg in an acute toxicity assay.

Conclusions

The results of this study present evidence that Lithrea molleoides given either systemically or topically has anti-inflammatory properties.     

Anti-inflammatory and analgesic activity of Peperomia pellucida (L.) HBK (Piperaceae)

An aqueous extract of the aerial part of Peperomia pellucida (L.) HBK (Piperaceae) was tested for anti-inflammatory (paw edema induced by carrageenin and arachidonic acid) and analgesic activity (abdominal writhes and hot plate) in rats and mice, respectively. Oral administration of 200 and 400 mg/kg of the aqueous extract exhibited an anti-inflammatory activity in the carrageenin test, which was based on interference with prostaglandin synthesis, as confirmed by the arachidonic acid test. In the abdominal writhing test induced by acetic acid, 400 mg/kg of the plant extract had the highest analgesic activity, whereas in the hot-plate test the best dose was 100 mg/kg. The LD(50) showed that Peperomia pellucida (5000 mg/kg) presented low toxicity.