The analgesic and anti-inflammatory effect of WIN-34B, a new herbal formula for osteoarthritis composed of Lonicera japonica Thunb and Anemarrhena asphodeloides BUNGE in vivo.

Lonicera japonica Thunb and Anemarrhena asphodeloides BUNGE have been used for the treatment of a variety of inflammatory diseases, cold and infective diseases in many countries, including Korea and China. This study aimed to assess the anti-nociceptive and anti-inflammatory activities of n-butanol fraction (WIN-34B) prepared from dried flowers of Lonicera japonica and dried roots of Anemarrhena asphodeloides as potential novel treatment of osteoarthritis. Anti-nociceptive activities of WIN-34B (100, 200 and 400 mg/kg, p.o.) were measured using acetic acid-induced writhing response, formalin-induced paw licking, hot plate, radiant heat tail-flick, carrageenan-induced paw pressure, and Hargreaves tests, respectively. Anti-inflammatory activities of WIN-34B (100, 200 and 400 mg/kg, p.o.) were assessed using acetic acid-induced vascular permeability, carrageenan-induced paw edema, and croton oil-induced ear edema. Anti-osteoarthritis effect of WIN-34B was analyzed using monosodium iodoacetate (MIA)-induced osteoarthritis animal model. WIN-34B exhibited better anti-inflammatory activity than that of celecoxib in carrageenan at the dose of 200 mg/kg and croton oil-induced paw edema and ear edema at the doses of 200 and 400 mg/kg. WIN-34B exhibited significant anti-inflammatory effects on vascular permeability. WIN-34B also exhibited significant anti-nociceptive activities in the late phase of formalin-induced paw licking and writhing response model in mice. In radiant heat tail-flick and carrageenan-induced paw pressure tests, WIN-34B at the dose of 400 mg/kg and at the doses of 200 and 400 mg/kg presented similar activities to indomethacin and celecoxib. Compared to indomethacin WIN-34B at 400mg/kg showed similar or better anti-nociceptive activities after 1 and 2h of theraphy in the hot plate test and better anti-nociceptive activity than that of celecoxib in Hargreves test. In the MIA-induced osteoarthritis animal models, WIN-34B at 400 mg/kg exhibited similar or better anti-nociceptive property than that of celecoxib throughout the pain measurement periods. When compared to celecoxib, WIN-34B exhibited similar or better anti-nociceptive and anti-inflammatory activities in osteoarthritic animal models, which may become a potential novel treatment for osteoarthritis.

Kang M ，Jung I ，Hur J ，Kim SH ，Lee JH ，Kang JY ，Jung KC ，Kim KS ，Yoo MC ，Park DS ，Lee JD ，Cho YB ... -  《-》

Anti-nociceptive and anti-inflammatory effects of Croton crassifolius ethanol extract.

Croton crassifolius has been used to treat snake bites, stomach ache, sternalgia, joint pain, as well as pharyngitis, jaundice, and rheumatoid arthritis in traditional Chinese medicine. However, there is no scientific evidence which supports the use in the literature. To investigate the anti-nociceptive and anti-inflammatory effects of ethanol extract of C. crassifolius. Anti-nociceptive actions of C. crassifolius were assessed in mice using the hot-plate test, acetic acid-induced writhing test, and formalin test. Anti-inflammatory effects of C. crassifolius were determined in three animal models: acetic acid-induced capillary permeability accentuation in mice, carrageenan-induced edema of the hind paw in rats, and cotton pellet-induced granuloma formation in rats. Ethanol extract of C. crassifolius showed no significant anti-nociceptive activity in the hot-plate test. However, extract at dosages of 45, 90 and 180 mg/kg significantly reduced acetic acid-induced writhing by 28.89% (P<0.05), 38.37% (P<0.05), and 56.53% (P<0.001), respectively. The extract also caused marked dose-related inhibition of formalin-induced pain in the second phase (P<0.05 for 45 mg/kg, P<0.001 for 90 and 180 mg/kg extract). C. crassifolius extract at dosages of 45, 90 and 180 mg/kg significantly reduced acetic acid-induced capillary permeability accentuation in mice by 26.18% (P<0.05), 65.70% (P<0.001), and 79.19% (P<0.001), and suppressed carrageenan-induced paw edema by 21.28% (P<0.05), 30.69% (P<0.01), and 49.17% (P<0.001) at 6 h after carrageenan injection, respectively. 180 mg/kg of the extract also showed significant activity against carrageenan-induced paw edema at 4 h. At 90 and 180 mg/kg, the extract inhibited cotton pellet-induced granuloma formation in rats. These results collectively demonstrate that the ethanol extract of C. crassifolius possesses peripheral anti-nociceptive and anti-inflammatory effects, providing evidence to rationalize the traditional use of C. crassifolius for the treatment of pain and inflammation.

Zhao J ，Fang F ，Yu L ，Wang G ，Yang L ... -  《-》

Gastroprotective and safety effects of WIN-34B, a novel treatment for osteoarthritis, compared to NSAIDs.

The dried flowers of Lonicera japonica, also known as Japanese honeysuckle, and the dried root of Anemarrhena asphodeloides, the component herbs of WIN-34B, are traditionally used in Eastern medicine to treat various inflammatory conditions including arthritis. To study the acute and chronic toxicities of WIN-34B and to compare its effects on gastric mucosa with those of diclofenac, a widely used NSAID, and celecoxib, a selective COX-2 inhibitor. To investigate acute toxicity, we orally administered a single dose of 5,000 mg/kg WIN-34B to rats. To investigate chronic toxicity, we orally administered 500, 1000 or 2,000 mg/kg WIN-34B to rats daily for 13 weeks. To assess its effects on gastric mucosa, rats received either a single dose or repeated doses of WIN-34B (400, 1000, or 2,000 mg/kg), diclofenac (10, 40, or 80 mg/kg), celecoxib (100 or 1,000 mg/kg), or vehicle, after which samples of gastric mucosa were assessed grossly and histologically. We also measured tissue activity of myeloperoxidase and synthesis of eicosanoids, including prostaglandin E(2) (PGE(2)) and leukotriene B(4) (LTB(4)). To further assess its effects, we administered WIN-34B to rats either intraperitoneally or orally, measured gastric injury scores using a rat model of diclofenac-induced gastric injury, and measured eicosanoid synthesis. WIN-34B showed no signs of acute or chronic toxicity in terms of general behavior, gross appearance of the internal organs, blood chemistry, or mortality. WIN-34B did not cause significant gastric mucosal damage after single or repeated doses. In contrast, diclofenac and celecoxib both caused gastric damage. In terms of eicosanoid synthesis, WIN-34B significantly suppressed LTB(4) synthesis while both diclofenac and celecoxib increased LTB(4) synthesis. WIN-34B slightly reduced PGE(2) production, while both diclofenac and celecoxib significantly reduced PGE(2) production. In a rat model of diclofenac-induced gastric injury, WIN-34B significantly suppressed LTB(4) synthesis and restored PGE(2) release. These results demonstrate that WIN-34B did not cause acute or chronic toxicity in male or female rats. In addition, WIN-34B did not cause significant gastric mucosal damage, instead appearing to protect the mucosa from diclofenac-induced gastric damage through the regulation of PGE(2) and LTB(4).

Huh JE ，Lee WI ，Seo BK ，Baek YH ，Lee JD ，Choi DY ，Park DS ... -  《-》

Anti-inflammatory and analgesic activity of different extracts of Commiphora myrrha.

This present study was carried out to evaluate the anti-inflammatory and analgesic effects of 85% ethanol extract (EE) of Commiphora myrrha and its different fractions partitioned with petroleum ether extract (EPE), ethyl acetate extract (EEA), n-butanol extract (EBu), and the water extract (ECY). Moreover, the chemical constituents in EPE were analyzed and identified by UPLC-QTOF/MS/MS. The anti-inflammatory activities were investigated by utilizing the paw edema mice induced by formalin. In addition, we determined the levels of PGE(2) in the edema paw. While the analgesic activity was examined against thermally and chemically induced nociceptive pain in mice, using the acetic acid and hot-plate test methods. The effects of the administration of dolantin or indomethacin were also studied for references. The components in EPE were analyzed by the ultra-performance liquid chromatography coupled with mass spectrum. In the anti-inflammatory test, EE inhibited the development of paw swelling induced by formalin significantly. The pharmacological activities of the petroleum ether fraction (EPE) were stronger than the EE extract and other fractions at the dose of 100mg/kg, and furthermore significantly decreased the levels of inflammatory factor PGE(2) in the edema paw tissue at the fourth hour after formalin injection. It has been also shown that the ethanol extract (EE) significantly reduced acetic acid-induced writhing response in mice at the dose of 200mg/kg, and 100mg/kg. The petroleum ether fraction (EPE) showed significant analgesic activity in the model at the dose of 100mg/kg (p<0.01), and the ethyl acetate fraction (EEA) exhibited less analgesic activity (p<0.05). All test samples showed no significant analgesic activity on the hot plate pain threshold in mice. The UPLC-MS/MS chromatogram analysis of EPE stated that EPE contains the ingredients of sesquiterpenes, diterpenes, and diterpenic acids. Moreover, seven main compounds were identified. These data demonstrated that the EE and EPE posses analgesic and anti-inflammatory activities and may support the fact the traditional application of this herb in treating various diseases associated with inflammatory pain.

Su S ，Wang T ，Duan JA ，Zhou W ，Hua YQ ，Tang YP ，Yu L ，Qian DW ... -  《-》

Anti-inflammatory, analgesic and antipyretic effects of friedelin isolated from Azima tetracantha Lam. in mouse and rat models.

Friedelin was isolated from Azima tetracantha Lam. leaves collected from Kallakurichi, Villuppuram district, Tamil Nadu, India. The anti-inflammatory, analgesic and antipyretic activities of friedelin have been investigated in Wistar rats and mice. Friedelin was isolated from the hexane extract of leaves of A. tetracantha using column chromatography. The effects of friedelin on inflammation were studied by using carrageenan-induced hind paw oedema, croton oil-induced ear oedema, acetic acid-induced vascular permeability, cotton pellet-induced granuloma and adjuvant-induced arthritis. The analgesic effect of friedelin was evaluated using the acetic acid-induced abdominal constriction response, formalin-induced paw licking response and the hot-plate test. The antipyretic effect of friedelin was evaluated using the yeast-induced hyperthermia test in rats. In the acute phase of inflammation, maximum inhibitions of 52.5 and 68.7% (P<0.05) were noted with 40 mg/kg friedelin in carrageenan-induced paw oedema and croton oil-induced ear oedema, respectively. Administration of friedelin (40 mg/kg) significantly (P<0.05) decreased the formation of granuloma tissue induced by cotton pellet at a rate of 36.3%. In the adjuvant-induced arthritis test friedelin inhibited 54.5% of paw thickness. Friedelin inhibited acetic acid-induced vascular permeability in mice. Friedelin also produced significant (P<0.05) analgesic activity in the acetic acid-induced abdominal constriction response and formalin-induced paw licking response. In the hot-plate test, friedelin did not show any significant results when compared with control. Treatment with friedelin showed a significant (P<0.05) dose-dependent reduction in pyrexia in rats. The results suggested that friedelin possessed potent anti-inflammatory, analgesic and antipyretic activities.

Antonisamy P ，Duraipandiyan V ，Ignacimuthu S 《-》