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

Central Research Institute, WhanIn Pharm. Co., Ltd, Yeongtong-Gu, Suwon-si, Republic of Korea.
Journal of ethnopharmacology (Impact Factor: 3). 09/2010; 131(2):485-96. DOI: 10.1016/j.jep.2010.07.025
Source: PubMed

ABSTRACT 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.

Download full-text


Available from: Kyoung Soo Kim, Sep 22, 2014
1 Follower
22 Reads
  • Source
    • "It is a widely used herb in China for the treatment of infection by exopathogenic wind-heat or epidemic febrile diseases.[11142728] The dried flower and buds of Flos Lonicerae have shown various pharmacological effects including anti-nociceptive, anti-diabetic, anti-tumor, antioxidant, anti-angiogenic, antipyretic, antiviral, and hepatoprotective activities.[6293031]Flos Lonicerae demonstrated anti-inflammatory properties through suppression of mediator release from the mast cells activated by secretagogues.[32] "
    [Show abstract] [Hide abstract]
    ABSTRACT: Inflammation is a normal immune response; but if the body's regulation of inflammation is dysfunctional, then it will have an adverse effect on the body. Although use of modern drugs for inflammation has a relieving effect, it is still unsatisfactory. Moreover, the emergence of drug-resistant strains and even new kinds of microorganisms is causing significant morbidity and mortality. Recently, more attention has been focused on herbal medicine to treat various diseases because of the ability of the herbs to affect multiple target signaling pathways and their multiple mechanisms of action. Thus, a large number of studies have reported on the anti-inflammatory and antimicrobial effects of the traditional Chinese herbs. Literature survey was performed by conducting systematic electronic search in PubMed, Science Direct, Google Scholar, and in books. This review has listed 11 heat-clearing Chinese herbs (HCCHs) including Scutellaria baicalensis ( Huáng Qín), Coptis chinensis ( Huáng Lián), Flos Lonicerae ( Jīn Yín Hūa), Forsythia suspensa ( Lián Qiào), Isatidis Folium ( Dà Qīn Yè), Radix Isatidis ( Bǎn Lán Gēn), Viola yedoensis ( Zǐ Huā Dì Dīn), Pulsatilla Radix ( Bái Tóu Wēn), Andrographis paniculata ( Chuān Xīn Lián), Houttuynia cordata ( Yú Xīng Cǎo), and Patrinia Herba ( Bài Jiàn Cǎo), which have anti-inflammatory and antimicrobial effects, and has described their effects through different mechanisms of action and multiple targets. Their ability to affect multiple target signaling pathways and their potential mechanisms of action contributing to their anti-inflammatory and antimicrobial activity may be related to their action of removing heat and counteracting toxicity. Further studies are needed on the collection of HCCHs to know the detailed mechanism of action of herbs in this group for the assessment of effective drug.
    Journal of Traditional and Complementary Medicine 03/2014; 4(2):93-98. DOI:10.4103/2225-4110.126635
  • Source
    • "We standardized WIN-34B for quality control according to a previous report [13] and analyzed the major compounds of WIN-34B with the aim of standardizing its practical use and aiding in medicinal development. Data from several previous studies indicate that WIN-34B exhibits excellent analgesic and anti-inflammatory properties in the experimental models [13] and did not cause toxicity or gastric injury when orally administered to rats [14]. Also, WIN-34B showed that anti-inflammatory effect is mediate by reducing inflammatory mediators and regulating MMPs, ADAMTSs, and TIMPs via IκB-α and MAP kinases signal pathways in IL-1β-stimulated human OA fibroblast-like synoviocytes [15]. "
    [Show abstract] [Hide abstract]
    ABSTRACT: We sought to determine the cartilage repair capacity of WIN-34B in the collagenase-induced osteoarthritis rabbit model and in progenitor cells from subchondral bone. The cartilage protective effect of WIN-34B was measured by clinical and histological scores, cartilage area, and proteoglycan and collagen contents in the collagenase-induced osteoarthritis rabbit model. The efficacy of chondrogenic differentiation of WIN-34B was assessed by expression of CD105, CD73, type II collagen, and aggrecan in vivo and was analyzed by the surface markers of progenitor cells, the mRNA levels of chondrogenic marker genes, and the level of proteoglycan, GAG, and type II collagen in vitro. Oral administration of WIN-34B significantly increased cartilage area, and this was associated with the recovery of proteoglycan and collagen content. Moreover, WIN-34B at 200 mg/kg significantly increased the expression of CD105, CD73, type II collagen, and aggrecan compared to the vehicle group. WIN-34B markedly enhanced the chondrogenic differentiation of CD105 and type II collagen in the progenitor cells from subchondral bone. Also, we confirmed that treatment with WIN-34B strongly increased the number of SH-2(CD105) cells and expression type II collagen in subchondral progenitor cells. Moreover, WIN-34B significantly increased proteoglycan, as measured by alcian blue staining; the mRNA level of type II α 1 collagen, cartilage link protein, and aggrecan; and the inhibition of cartilage matrix molecules, such as GAG and type II collagen, in IL-1 β -treated progenitor cells. These findings suggest that WIN-34B could be a potential candidate for effective anti-osteoarthritic therapy with cartilage repair as well as cartilage protection via enhancement of chondrogenic differentiation in the collagenase-induced osteoarthritis rabbit model and progenitor cells from subchondral bone.
    Evidence-based Complementary and Alternative Medicine 08/2013; 2013:527561. DOI:10.1155/2013/527561 · 1.88 Impact Factor
  • Source
    • "WIN-34B was standardized for quality control according to a previous report [19], and used high pressure liquid chromatography (HPLC) analysis to identify the standard compounds, mangiferin and chlorogenic acid. Chromatographic analysis of WIN-34B was performed with a reverse-phase HPLC system (Waters, Milford, MA) equipped with the Waters Breeze System (2695 Separations Module, 996 Photodiode Array Detector, Empower 2 Software Build 2154). "
    [Show abstract] [Hide abstract]
    ABSTRACT: Background WIN-34B is a novel Oriental medicine, which represents the n-butanol fraction prepared from dried flowers of Lonicera japonica Thunb and dried roots of Anemarrhena asphodeloides BUNGE. The component herb of WIN-34B is used for arthritis treatment in East Asian countries. The aim of this study was to determine the cartilage-protective effects and mechanisms of WIN-34B and its major phenolic compounds, chlorogenic acid and mangiferin, in osteoarthritis (OA) human cartilage explants culture and chondrocytes. Methods The investigation focused on whether WIN-34B and its standard compounds protected cartilage in interleukin (IL)-1β-stimulated cartilage explants culture and chondrocytes derived from OA patients. Also, the mechanisms of WIN-34B on matrix metalloproteinases (MMPs), tissue inhibitor of matrix metalloproteinases (TIMPs), inflammatory mediators, and mitogen-activated protein kinases (MAPKs) pathways were assessed. Results WIN-34B was not cytotoxic to cultured cartilage explants or chondrocytes. WIN-34B dose-dependently inhibited the release of glycosaminoglycan and type II collagen, increased the mRNA expression of aggrecan and type II collagen, and recovered the intensity of proteoglycan and collagen by histological analysis in IL-1β-stimulated human cartilage explants culture. The cartilage protective effect of WIN-34B was similar to or better than that of chlorogenic acid and mangiferin. Compared to chlorogenic acid and mangiferin, WIN-34B displayed equal or greater decreases in the levels of MMP-1, MMP-3, MMP-13, ADAMTS-4, and ADAMTS-5, and markedly up-regulated TIMP-1 and TIMP-3. WIN-34B inhibited inflammatory mediators involved in cartilage destruction, such as prostaglandin E2, nitric oxide, tumor necrosis factor-alpha, and IL-1β. The phosphorylation of extracellular signal-regulated kinase, c-Jun N-terminal kinase (JNK), and p38 was significantly reduced by WIN-34B treatment, while phosphorylation of JNK was only inhibited by chlorogenic acid or mangiferin in IL-1β-stimulated chondrocytes. Conclusions WIN-34B is potentially valuable as a treatment for OA by virtue of its suppression of MMPs, ADAMTSs, and inflammatory mediators, and it’s up-regulation of TIMP-1 and TIMP-3 involved in the MAPK pathway.
    BMC Complementary and Alternative Medicine 12/2012; 12(1):256. DOI:10.1186/1472-6882-12-256 · 2.02 Impact Factor
Show more