Commiphora Extract Mixture Ameliorates Monosodium Iodoacetate-Induced Osteoarthritis

Osteoarthritis (OA) is a chronic inflammatory joint disease that affects millions of elderly people around the world. The conventional treatments for OA consisting of nonsteroidal anti-inflammatory drugs and steroid have negative health consequences, such as gastrointestinal, renal, and cardiac diseases. This study has evaluated the Commiphora extract mixture (HT083) on OA progression as an alternative treatment in animal models. The root of P. lactiflora and the gum resin of C. myrrha have been in use as traditional medicines against many health problems including bone disorders since ancient time. The extracts of P. lactiflora root and C. myrrha gum resin were mixed as 3:1 for their optimal effects. Male Sprague-Dawley rats were injected with monosodium iodoacetate (MIA) into the knee joints to induce the symptoms identical to human OA. HT083 substantially prevented the loss of weight-bearing inflicted with MIA in rats. The MIA-induced cartilage erosion as well as the subchondral bone damage in the rats was also reversed. In addition, the increase of serum IL-1β concentration, a crucial pro-inflammatory cytokine involved in OA progression was countered by HT083. Furthermore, HT083 significantly reduced the acetic acid-induced writhing response in mice. In vitro, HT083 has shown potent anti-inflammatory activities by inhibiting the production of NO and suppressing the interleukin -1β, interleukin -6, cyclooxygenase-2, and inducible nitric oxide synthase expression in lipopolysaccharide -stimulated RAW 264.7 cells. Given its potent analgesic and anti-inflammatory activities in MIA rats and acetic acid-induced writhing in mice, HT083 should be further studied in order to explain its mechanism of actions in alleviating OA pain and inflammation.

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Analgesic and Anti-Inflammatory Effects of Aucklandia lappa Root Extracts on Acetic Acid-Induced Writhing in Mice and Monosodium Iodoacetate-Induced Osteoarthritis in Rats

Plants ◽

10.3390/plants10010042 ◽

2020 ◽

Vol 10 (1) ◽

pp. 42

Author(s):

Hee-Geun Jo ◽

Geon-Yeong Lee ◽

Chae Yun Baek ◽

Ho Sueb Song ◽

Donghun Lee

Keyword(s):

Acetic Acid ◽

Weight Bearing ◽

Bone Diseases ◽

Joint Disease ◽

Root Extracts ◽

Raw264.7 Macrophages ◽

Age Related ◽

Monosodium Iodoacetate ◽

Anti Inflammatory

Osteoarthritis (OA) is an age-related joint disease and one of the most common degenerative bone diseases among elderly people. The currently used therapeutic strategies relying on nonsteroidal anti-inflammatory drugs (NSAIDs) and steroids for OA are often associated with gastrointestinal, cardiovascular, and kidney disorders, despite being proven effective. Aucklandia lappa is a well-known traditional medicine. The root of A. lappa root has several bioactive compounds and has been in use as a natural remedy for bone diseases and other health conditions. We evaluated the A. lappa root extracts on OA progression as a natural therapeutic agent. A. lappa substantially reduced writhing numbers in mice induced with acetic acid. Monosodium iodoacetate (MIA) was injected into the rats through their knee joints of rats to induce experimental OA, which shows similar pathological characteristics to OA in human. A. lappa substantially reduced the MIA-induced weight-bearing of hind limb and reversed the cartilage erosion in MIA rats. IL-1β, a representative inflammatory mediator in OA, was also markedly decreased by A. lappa in the serum of MIA rats. In vitro, A. lappa lowered the secretion of NO and suppressed the IL-1β, COX-2, IL-6, and iNOS production in RAW264.7 macrophages activated with LPS. Based on its analgesic and anti-inflammatory effects, A. lappa could be a potential remedial agent against OA.

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Andrographis paniculata Extract Relieves Pain and Inflammation in Monosodium Iodoacetate-Induced Osteoarthritis and Acetic Acid-Induced Writhing in Animal Models

Processes ◽

10.3390/pr8070873 ◽

2020 ◽

Vol 8 (7) ◽

pp. 873

Author(s):

Donghun Lee ◽

Chae Yun Baek ◽

Ji Hong Hwang ◽

Mi-Yeon Kim

Keyword(s):

Acetic Acid ◽

Weight Bearing ◽

Cartilage Damage ◽

Degenerative Joint Disease ◽

Andrographis Paniculata ◽

Joint Disease ◽

Tnf Α ◽

Monosodium Iodoacetate ◽

History Of

Osteoarthritis (OA), being the most prominent degenerative joint disease is affecting millions of elderly people worldwide. Although Andrographis paniculata is an ethnic medicine with a long history of being used as analgesic agent, no study using a monosodium iodoacetate (MIA) model has investigated its potential activities against OA. In this study, experimental OA was induced in rats with a knee injection of MIA, which represents the pathological characteristics of OA in humans. A. paniculata extract (APE) substantially reversed the loss of hind limb weight-bearing and the cartilage damage resulted from the OA induction in rats. Additionally, the levels of serum pro-inflammatory cytokines, such as IL-1β, IL-6, and TNF-α as well as the concentration of matrix metalloproteinases, including MMP-1, MMP-3, MMP-8, and MMP-13 were decreased by APE administration. Acetic acid-induced writhing responses in mice which quantitatively measure pain were significantly reduced by APE. In vitro, APE inhibited the generation of NO and downregulated the expression of IL-1β, IL-6, COX-2, and iNOS in lipopolysaccharide (LPS)-stimulated RAW264.7 cells. The above results suggest the potential use APE as a therapeutic agent against OA.

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Balanophora spicataand Lupeol Acetate Possess Antinociceptive and Anti-Inflammatory ActivitiesIn VivoandIn Vitro

Evidence-based Complementary and Alternative Medicine ◽

10.1155/2012/371273 ◽

2012 ◽

Vol 2012 ◽

pp. 1-10 ◽

Cited By ~ 16

Author(s):

Yuh-Fung Chen ◽

Chien Ching ◽

Tian-Shung Wu ◽

Chi-Rei Wu ◽

Wen-Tsong Hsieh ◽

...

Keyword(s):

Acetic Acid ◽

Vascular Permeability ◽

Crude Extract ◽

Late Phase ◽

Raw 264.7 Cells ◽

No Production ◽

Hexane Layer ◽

Lupeol Acetate ◽

Anti Inflammatory

Aims of the present study were to investigate effects ofBalanophora spicata(BS) on antinociception and anti-inflammation bothin vivoandin vitro. Crude extract of BS inhibited vascular permeability induced by histamine, serotonin, bradykinin, and PGE2, but not by PAF. Furthermore, BS crude extract, different layers (n-hexane, ethyl acetate,n-butanol, and water layer), and lupeol acetate had significant antinociceptive and anti-inflammatory effects on acetic acid-induced abdominal writhing response, formalin-induced licking behavior, carrageenan-, and serotonin-induced paw edema. Then-hexane layer had the most effective potency among all layers (IC50: 67.33 mg/kg on writhing response; IC50s: 34.2 mg/kg and 21.29 mg/kg on the early phase and late phase of formalin test, resp.). Additionally, lupeol acetate which was isolated from then-hexane layer of BS effectively inhibited the acetic acid-induced writhing response (IC50: 28.32 mg/kg), formalin-induced licking behavior (IC50: 20.95 mg/kg), NO production (IC50: 4.102 μM), iNOS expression (IC50: 5.35 μM), and COX2 expression (IC50: 5.13 μM) in LPS-stimulated RAW 264.7 cells. In conclusion, BS has antinociceptive and anti-inflammatory effects which may be partially due to the inhibition of changes in vascular permeability induced by histamine, serotonin, bradykinin, and PGE2and the attenuation of iNOS and COX-2 expression.

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Anti-Inflammatory and Antiosteoarthritis Effects ofSaposhnikovia divaricata ethanolExtract:In VitroandIn VivoStudies

Evidence-based Complementary and Alternative Medicine ◽

10.1155/2016/1984238 ◽

2016 ◽

Vol 2016 ◽

pp. 1-8 ◽

Cited By ~ 19

Author(s):

Jin Mi Chun ◽

Hyo Seon Kim ◽

A Yeong Lee ◽

Seung-Hyung Kim ◽

Ho Kyoung Kim

Keyword(s):

Rat Model ◽

Weight Bearing ◽

Raw 264.7 Cells ◽

Prostaglandin E ◽

Histopathological Analysis ◽

Raw 264.7 ◽

Anti Inflammatory ◽

Saposhnikovia Divaricata

Saposhnikovia divaricataSchischkin has been used in traditional medicine to treat pain, inflammation, and arthritis. The aim of this study was to investigate the anti-inflammatory and antiosteoarthritis activities ofSaposhnikovia divaricataextract (SDE). The anti-inflammatory effect of SDE was evaluatedin vitroin lipopolysaccharide- (LPS-) treated RAW 264.7 cells. The antiosteoarthritic effect of SDE was investigated in anin vivorat model of monosodium iodoacetate- (MIA-) induced osteoarthritis (OA) in which rats were treated orally with SDE (200 mg/kg) for 28 days. The effects of SDE were assessedin vivoby histopathological analysis and by measuring weight-bearing distribution, cytokine serum levels, and joint tissue inflammation-related gene expression. SDE showed anti-inflammatory activity by inhibiting the production of nitric oxide (NO), prostaglandin E2(PGE2), tumor necrosis factor-α(TNF-α), and interleukin-6 (IL-6) in LPS-induced RAW 264.7 cells. In addition, SDE promoted recovery of hind limb weight-bearing, inhibited the production of proinflammatory cytokines and mediators, and protected cartilage and subchondral bone tissue in the OA rat model. Therefore, SDE is a potential therapeutic agent for OA and/or associated symptoms.

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The Anti-Inflammatory Activity of Palmitoylethanolamide Ameliorates Osteoarthritis Induced by Monosodium Iodoacetate in Sprague Dawley Rats

10.21203/rs.3.rs-629822/v1 ◽

2021 ◽

Author(s):

Jae In Jung ◽

Hyun Sook Lee ◽

Young Eun Jeon ◽

So Mi Kim ◽

Su Hee Hong ◽

...

Keyword(s):

Mrna Expression ◽

Acid Amide ◽

Leukotriene B4 ◽

Joint Disease ◽

Control Group ◽

Sprague Dawley ◽

Sprague Dawley Rats ◽

Tnf Α ◽

Monosodium Iodoacetate ◽

Anti Inflammatory

Abstract Novel treatment strategies are urgently required for osteoarthritis (OA), a degenerative joint disease. Palmitoylethanolamide (PEA) is a naturally occurring fatty acid amide with analgesic and anti-inflammatory effects. We aimed to examine its effect on OA and molecular mechanism of actions in monosodium iodoacetate (MIA)-induced OA Sprague Dawley rats. The experimental animals were divided into five groups: normal control group (injected with saline + treated with phosphate-buffered saline (PBS), NOR), control group (injected with MIA + treated with PBS, CON), 50 or 100 mg/kg body weight (BW)/day PEA-treated group (injected with MIA + treated with 50 or 100 mg of PEA/kg BW/day, PEA50 or PEA 100), and positive control group (injected with MIA + treated with 6 mg of diclofenac/kg BW/day, DiC). Changes in blood and body parameters, gene expression of inflammatory mediators and cytokines, knee thickness, and joint tissue were observed. We found no adverse effects of oral administration of PEA on BW, liver, or kidneys. PEA reduced knee joint swelling and cartilage degradation in MIA-induced OA rats. The serum levels of leukotriene B4, nitric oxide, tumor necrosis factor (TNF)-α, interleukin (IL)-1β, and prostaglandin E2 considerably reduced in the PEA100 group compared to those in the CON group. In the synovia of knee joints, mRNA expression of iNOS, 5-Lox, Cox-2, Il-1β, Tnf-α, Mmp-2, -3, -9, and − 13 noticeably reduced with MIA administration. Meanwhile, Timp-1 mRNA expression noticeably decreased in the CON group but increased to the normal level with PEA treatment. Thus, we demonstrated that PEA can be used as an effective therapeutic agent for OA.

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Anti-Inflammatory and Chondroprotective Effects of Platelet-Derived Growth Factor-BB on Osteoarthritis Rat Models

10.21203/rs.3.rs-786857/v1 ◽

2021 ◽

Author(s):

Yu Cai ◽

Zhengchao Wang ◽

Bokai Liao ◽

Zhenxing Sun ◽

Pengfei Zhu

Keyword(s):

Growth Factor ◽

Signaling Pathways ◽

Proinflammatory Cytokines ◽

Platelet Derived Growth Factor ◽

Sprague Dawley ◽

Sprague Dawley Rats ◽

Mechanistic Analysis ◽

Monosodium Iodoacetate ◽

Anti Inflammatory

Abstract Background: It has been proved that PDGF-BB could protect the chondrocytes via multiple mechanisms. The present study aims to further investigating the anti-inflammatory and chondroprotective effects of platelet-derived growth factor (PDGF)-BB on osteoarthritis (OA).Methods: We established an osteoarthritis model in Sprague-Dawley rats through intraarticular injection of 3 mg/50 µL monosodium iodoacetate (MIA). The effects of PDGF-BB on MIA-induced OA were assessed by histopathological staining, real-time PCR, and western blotting. Chondrocytes were transfected with or without SOX-9 siRNA, induced by MIA and treated with PDGF-BB, and cell viability, proinflammatory cytokines, and specific markers were analyzed. For mechanistic analysis, the expression of p-SOX-9/SOX-9, p-RunX-2/RunX-2, and p-PKA/PKA and activation of the JAK2/STAT3, PI3K/AKT, and p38 pathways were analyzed.Results: PDGF-BB significantly inhibited the degeneration of cartilage in MIA-induced OA with reductions in proinflammatory cytokines (IL-1, IL-6, collagen Ⅹ, MMPs and ADATMS) and increases in collagen II, aggrecan, and integrin α5β1, and these effects could be reversed by a PDGFR-β antagonist. Consistently, the in vitro results showed similar effects. PDGF-BB treatment suppressed the activation of the JAK2/STAT3, PI3K/AKT, and p38 signaling pathways after MIA induction in both cartilage and chondrocytes. In addition, activation of PKA by PDGF-BB enhanced SOX-9 phosphorylation, which increased anabolic activity, and attenuated RunX-2 phosphorylation, which decreased catabolic activity. The PKA inhibitor and SOX-9 siRNA suppressed PDGF-BB-mediated chondroprotection.Conclusions: PDGF-BB could attenuate OA development by regulating the JAK2/STAT3 PI3K/AKT and p38 signaling pathways by inhibiting inflammation and enhancing cell proliferation via PKA-mediated regulation of SOX-9/RunX-2.

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Cartilage protective and anti-analgesic effects of ALM16 on monosodium iodoacetate induced osteoarthritis in rats

BMC Complementary and Alternative Medicine ◽

10.1186/s12906-019-2746-7 ◽

2019 ◽

Vol 19 (1) ◽

Cited By ~ 4

Author(s):

Doo Jin Choi ◽

Soo-Im Choi ◽

Bo-Ram Choi ◽

Young-Seob Lee ◽

Dae Young Lee ◽

...

Keyword(s):

Joint Disease ◽

Control Group ◽

Dependent Manner ◽

Paw Edema ◽

In Vivo Models ◽

Age Related ◽

Monosodium Iodoacetate ◽

Anti Inflammatory

Abstract Background Osteoarthritis (OA) is an age-related joint disease with characteristics that involve the progressive degradation of articular cartilage and resulting chronic pain. Previously, we reported that Astragalus membranaceus and Lithospermum erythrorhizon showed significant anti-inflammatory and anti-osteoarthritis activities. The objective of this study was to examine the protective effects of ALM16, a new herbal mixture (7:3) of ethanol extracts of A. membranaceus and L. erythrorhizon, against OA in in vitro and in vivo models. Methods The levels of matrix metalloproteinase (MMP)-1, −3 and − 13 and glycosaminoglycan (GAG) in interleukin (IL)-1β or ALM16 treated SW1353 cells were determined using an enzyme-linked immunosorbent and quantitative kit, respectively. In vivo, the anti-analgesic and anti-inflammatory activities of ALM16 were assessed via the acetic acid-induced writhing response and in a carrageenan-induced paw edema model in ICR mice, respectively. In addition, the chondroprotective effects of ALM16 were analyzed using a single-intra-articular injection of monosodium iodoacetate (MIA) in the right knee joint of Wister/ST rat. All samples were orally administered daily for 2 weeks starting 1 week after the MIA injection. The paw withdrawal threshold (PWT) in MIA-injected rats was measured by the von Frey test using the up-down method. Histopathological changes of the cartilage in OA rats were analyzed by hematoxylin and eosin (H&E) staining. Results ALM16 remarkably reduced the GAG degradation and MMP levels in IL-1β treated SW1353 cells. ALM16 markedly decreased the thickness of the paw edema and writhing response in a dose-dependent manner in mice. In the MIA-induced OA rat model, ALM16 significantly reduced the PWT compared to the control group. In particular, from histological observations, ALM16 showed clear improvement of OA lesions, such as the loss of necrotic chondrocytes and cartilage erosion of more than 200 mg/kg b.w., comparable to or better than a positive drug control (JOINS™, 200 mg/kg) in the cartilage of MIA-OA rats. Conclusions Our results demonstrate that ALM16 has a strong chondroprotective effect against the OA model in vitro and in vivo, likely attributed to its anti-inflammatory activity and inhibition of MMP production.

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A New Flavonol From Saussurea involucrata With Anti-Inflammatory Activity

Natural Product Communications ◽

10.1177/1934578x211007638 ◽

2021 ◽

Vol 16 (5) ◽

pp. 1934578X2110076

Author(s):

Sheng Pan ◽

Zi-Guan Zhu

Keyword(s):

Nitric Oxide ◽

Aerial Part ◽

Raw 264.7 Cells ◽

Raw 264.7 ◽

Spectroscopic Methods ◽

Soluble Extract ◽

Saussurea Involucrata ◽

Tnf Α ◽

Anti Inflammatory

A new flavonol named 6-(2'',3''-epoxy-3''-methylbutyl)-resokaempferol (1), together with five known compounds (2-6) were isolated from the EtOAc-soluble extract of the aerial part of Saussurea involucrata. Their structures were elucidated on the basis of spectroscopic methods. All compounds were evaluated for their anti-inflammatory effects by measuring the production of nitric oxide (NO) and TNF-α in vitro. Among them, compound 1 showed potential inhibitory activity on the production of NO and TNF-α in LPS-induced RAW 264.7 cells with IC50 values of 48.0 ± 1.5 and 41.4 ± 1.7 µM, respectively.

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Synthesis and anti-inflammatory activity of novel steroidal chalcones with 3β-pregnenolone ester derivatives in RAW 264.7 cells in vitro

Steroids ◽

10.1016/j.steroids.2021.108830 ◽

2021 ◽

pp. 108830

Author(s):

Xiaorui Cai ◽

Fei Sha ◽

Chuanyi Zhao ◽

Zhiwei Zheng ◽

Shulin Zhao ◽

...

Keyword(s):

Inflammatory Activity ◽

Raw 264.7 Cells ◽

Raw 264.7 ◽

Anti Inflammatory

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ANTI-INFLAMMATORY ACTIVITY OF CURCUMIN AND CAPSAICIN AUGMENTED IN COMBINATION

International Journal of Pharmacy and Pharmaceutical Sciences ◽

10.22159/ijpps.2017v9i6.18635 ◽

2017 ◽

Vol 9 (6) ◽

pp. 145

Author(s):

Thriveni Vasanth Kumar ◽

Manjunatha H. ◽

Rajesh Kp

Keyword(s):

Acetic Acid ◽

Protective Effect ◽

Vascular Permeability ◽

Diclofenac Sodium ◽

Significant Inhibition ◽

Inflammatory Activity ◽

Anti Inflammatory ◽

The Individual

Objective: Dietary curcumin and capsaicin are well known for their health beneficial potencies. The current study was done to assess the anti-inflammatory activity of curcumin, capsaicin and their combination by employing in vitro and in vivo models.Methods: We investigated the protective effect of curcumin, capsaicin and their combination using in vitro heat induced human red blood cell (HRBC) membrane stabilisation, in vivo 3% agar induced leukocyte mobilisation and acetic acid induced vascular permeability assay.Results: Curcumin, capsaicin and their combination exhibited concentration dependent protective effect against heat-induced HRBC membrane destabilisation, while combined curcumin and capsaicin restored 87.0±0.64 % membrane stability and it is found to be better than curcumin, capsaicin and diclofenac sodium (75.0±0.25. 72±0.9 and 80.0±0.31 %) protective effect. In agar suspension induced leukocyte mobilization assay, the combined curcumin and capsaicin had shown 39.5±1.58 % of inhibition compared to individual curcumin and capsaicin, which showed moderate inhibition of 16.0±3.14 and 21.6±2.17 % respectively. Besides, the combined curcumin and capsaicin had shown highly significant inhibition of acetic acid-induced vascular permeability in rats (62.0±3.14 %), whereas individual curcumin and capsaicin showed moderate inhibition of vascular permeability with 36.0±2.41 and 43.0±1.92 % respectively.Conclusion: This study demonstrates the significant anti-inflammatory property of combined curcumin and capsaicin at half of the individual concentration of curcumin and capsaicin.

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