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

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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Evaluation of anti-inflammatory activity of Justicia secunda Vahl leaf extract using in vitro and in vivo inflammation models

Clinical Phytoscience ◽

10.1186/s40816-019-0137-8 ◽

2019 ◽

Vol 5 (1) ◽

Cited By ~ 1

Author(s):

Godswill Nduka Anyasor ◽

Azeezat Adenike Okanlawon ◽

Babafemi Ogunbiyi

Keyword(s):

Erythrocyte Membrane ◽

Diclofenac Sodium ◽

Inflammatory Activity ◽

Dependent Manner ◽

Paw Edema ◽

In Vivo Models ◽

In Vivo Inflammation ◽

Anti Inflammatory

Abstract Background Justicia secunda Vahl. is a medicinal plant used in ethnomedical practice as therapy to manage inflammation. Therefore, this study was designed to evaluate the anti-inflammatory activity of methanol extract of J. secunda leaves (MEJSL) using in vitro and in vivo inflammation models. Methods Seventy-percent MEJSL was prepared following standard procedure. In vitro anti-inflammatory assays were performed using heat-induced bovine serum albumin (BSA) denaturation and erythrocyte membrane stabilization assays. Carrageenan and formaldehyde induced inflammation in rat models were used to evaluate the anti-inflammatory activity of MEJSL in vivo. Diclofenac sodium was used as a reference drug. In addition, liver and kidney function assays and hematological analysis were carried out. Results Data revealed that varying concentrations of MEJSL significantly (P < 0.05) inhibited heat-induced BSA denaturation and stabilized erythrocyte membrane against hypotonicity-induced hemolysis when compared with diclofenac sodium in a concentration-dependent manner. In vivo study showed that 10 mg/kg body weight (b.w.) diclofenac sodium, 100 and 300 mg/kg b.w. MEJSL suppressed carrageenan-induced paw edema at the sixth hour by 71.14%, 83.08%, and 89.05%, respectively. Furthermore, 10 mg/kg b.w. diclofenac sodium, 100 and 300 mg/kg b.w. MEJSL inhibited formaldehyde-induced paw edema by 72.53%, 74.73%, and 76.48%, respectively. Animals treated with varying doses of MEJSL had reduced plasma aspartate aminotransferase and alanine aminotransferase activities; urea and creatinine concentrations; and modulated hematological parameters when compared with the untreated control group. Conclusions Findings from this study showed that MEJSL exhibited substantial anti-inflammatory actions in the in vitro and in vivo models. It also indicated that MEJSL anti-inflammatory mechanisms of action could be through interference with phase 2 inflammatory stressors, upregulation of cytoprotective genes, stabilization of inflammatory cell membranes and immunomodulatory activity.

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Treatment of Non-Alcoholic Steatosis: Preclinical Study of a New Nutraceutical Multitarget Formulation

Nutrients ◽

10.3390/nu12061819 ◽

2020 ◽

Vol 12 (6) ◽

pp. 1819

Author(s):

Laura Micheli ◽

Alessandra Pacini ◽

Lorenzo Di Cesare Mannelli ◽

Elena Trallori ◽

Roberta D’Ambrosio ◽

...

Keyword(s):

Control Group ◽

High Dose ◽

Standard Diet ◽

Dependent Manner ◽

Post Injury ◽

In Vivo Models ◽

Pathologic Features ◽

Anti Inflammatory

Multifactorial pathogenesis of non-alcoholic steatohepatitis (NASH) disease, a wide-spread liver pathology associated with metabolic alterations triggered by hepatic steatosis, should be hit by multitarget therapeutics. We tested a multicomponent food supplement mixture (AP-NHm), whose components have anti-dislipidemic, antioxidant and anti-inflammatory effects, on in vitro and in vivo models of NASH. In vitro, hepatic cells cultures were treated for 24 h with 0.5 mM oleic acid (OA): in the co-treatment set cells were co-treated with AP-NH mixtures (AP-NHm, 1:3:10 ratio) and in the post-injury set AP-NHm was added for 48 h after OA damage. In vivo, C57BL/6 mice were fed with high-fat diet (HFD) for 12 weeks, inducing NASH at 7th week, and treated with AP-NHm at two dosages (1:3 ratio) in co-treatment or post-injury protocols, while a control group was fed with a standard diet. In in vitro co-treatment protocol, alterations of redox balance, proinflammatory cytokines release and glucose uptake were restored in a dose-dependent manner, at highest dosages also in post-injury regimen. In both regimens, pathologic dyslipidemias were also ameliorated by AP-NHm. In vivo, high-dose-AP-NHm-co-treated-HFD mice dose-dependently gained less body weight, were protected from dyslipidemia, and showed a lower liver weight. Dose-dependently, AP-NHm treatment lowered hepatic LDL, HDL, triglycerides levels and oxidative damage; co-treatment regimen was anti-inflammatory, reducing TNF-α and IL-8 levels. Hepatic lipidic infiltration significantly decreased in co-treated and post-injury-AP-NHm-HFD animals. The multitarget approach with AP-NHm was effective in preventing and reducing NASH-related pathologic features, warranting for the clinical development of this compound.

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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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Molecular Insight into the Anti-Inflammatory Effects of the Curcumin Ester Prodrug Curcumin Diglutaric Acid In Vitro and In Vivo

International Journal of Molecular Sciences ◽

10.3390/ijms21165700 ◽

2020 ◽

Vol 21 (16) ◽

pp. 5700 ◽

Cited By ~ 1

Author(s):

Rianthong Phumsuay ◽

Chawanphat Muangnoi ◽

Peththa Wadu Dasuni Wasana ◽

Hasriadi Hasriadi ◽

Opa Vajragupta ◽

...

Keyword(s):

Time Course ◽

Area Under The Curve ◽

Dependent Manner ◽

Paw Edema ◽

Inflammatory Agent ◽

Potent Inhibition ◽

Anti Inflammatory ◽

Ester Prodrug

Curcumin diglutaric acid (CurDG), an ester prodrug of curcumin, has the potential to be developed as an anti-inflammatory agent due to its improved solubility and stability. In this study, the anti-inflammatory effects of CurDG were evaluated. The effects of CurDG on inflammatory mediators were evaluated in LPS-stimulated RAW 264.7 macrophage cells. CurDG reduced the increased levels of NO, IL-6, and TNF- α, as well as iNOS and COX-2 expression in cells to a greater extent than those of curcumin, along with the potent inhibition of MAPK (ERK1/2, JNK, and p38) activity. The anti-inflammatory effects were assessed in vivo by employing a carrageenan-induced mouse paw edema model. Oral administration of CurDG demonstrated significant anti-inflammatory effects in a dose-dependent manner in mice. The effects were significantly higher compared to those of curcumin at the corresponding doses (p < 0.05). Moreover, 25 mg/kg curcumin did not exert a significant anti-inflammatory effect for the overall time course as indicated by the area under the curve data, while the equimolar dose of CurDG produced significant anti-inflammatory effects comparable with 50, 100, and 200 mg/kg curcumin (p < 0.05). Similarly, CurDG significantly reduced the proinflammatory cytokine expression in paw edema tissues compared to curcumin (p < 0.05). These results provide the first experimental evidence for CurDG as a promising anti-inflammatory agent.

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IN VITRO ANTIOXIDANT AND IN VIVO ANTI-INFLAMMATORY ACTIVITY OF THE AERIAL PART OF BLUMEA ERIANTHA DC

International Journal of Pharmacy and Pharmaceutical Sciences ◽

10.22159/ijpps.2018v10i7.25588 ◽

2018 ◽

Vol 10 (7) ◽

pp. 75 ◽

Cited By ~ 1

Author(s):

Urmila U. Tambewagh ◽

Supada Rambhau Rojatkar

Keyword(s):

Antioxidant Activity ◽

Aerial Part ◽

Methanol Extract ◽

Reducing Power ◽

Dependent Manner ◽

Paw Edema ◽

Anti Inflammatory ◽

In Vitro Antioxidant Activity

Objective: Objective of the present study was to carry out in vivo anti-inflammatory and in vitro antioxidant activity of methanol extract of aerial part of the Blumea eriantha DC belonging to family Asteraceae.Methods: The shade dried aerial part of B. eriantha (0.5 kg) was powdered and extracted with methanol (1.5 x 3L) at room temperature (24h x 3). After filtration combined all the three extracts and were concentrated on rotary evaporator under reduced pressure at 40 °C, thereby providing crude methanol extract which was subsequently employed for further studies. Anti-inflammatory effect was studied by carrageenan-induced paw edema model in rats at dose level 100, 200, and 400 mg/kg. Acute oral toxicity study and in vitro antioxidant potential of the extract was also studied. The in vitro antioxidant activity of methanol extract of aerial part of Blumea eriantha DC was evaluated against 1,1-diphenyl-2-picrylhydrazyl (DPPH), hydrogen peroxide (H2O2) and hydroxyl (OH) radicalscavenging and reducing power assays.Results: The results indicate that methanol extract of Blumea eriantha (BEME, 400 mg/kg) exhibited significant inhibition (p<0.001) of increase in paw edema at 5th h. IC50 value of BEME showed significant antioxidant activity. The extract exhibits promising free radical scavenging effect of DPPH, H2O2, OH and reducing power in a dose-dependent manner up to 100µg/ml concentration while the reference standard Ascorbic acid demonstrated more scavenging potential than the methanol extract of Blumea eriantha The methanol extract was found to be safe at the dose of 2000 mg/kg.Conclusion: The results of the experimental study confirmed that methanol extract of Blumea eriantha DC possesses significant anti-inflammatory and antioxidant activity.

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The Anti-Inflammatory and Antioxidant Effects of Sodium Propionate

International Journal of Molecular Sciences ◽

10.3390/ijms21083026 ◽

2020 ◽

Vol 21 (8) ◽

pp. 3026 ◽

Cited By ~ 1

Author(s):

Alessia Filippone ◽

Marika Lanza ◽

Michela Campolo ◽

Giovanna Casili ◽

Irene Paterniti ◽

...

Keyword(s):

Heme Oxygenase 1 ◽

Dependent Manner ◽

Sodium Propionate ◽

Intraplantar Injection ◽

Concentration Dependent Manner ◽

In Vivo Models ◽

Anti Oxidant ◽

Anti Inflammatory

The major end-products of dietary fiber fermentation by gut microbiota are the short-chain fatty acids (SCFAs) acetate, propionate, and butyrate, which have been shown to modulate host metabolism via effects on metabolic pathways at different tissue sites. Several studies showed the inhibitory effects of sodium propionate (SP) on nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) pathway. We carried out an in vitro model of inflammation on the J774-A1 cell line, by stimulation with lipopolysaccharide (LPS) and H2O2, followed by the pre-treatment with SP at 0.1, 1 mM and 10 mM. To evaluate the effect on acute inflammation and superoxide anion-induced pain, we performed a model of carrageenan (CAR)-induced rat paw inflammation and intraplantar injection of KO2 where rats received SP orally (10, 30, and 100 mg/kg). SP decreased in concentration-dependent-manner the expression of cicloxigenase-2 (COX-2) and inducible nitric oxide synthase (iNOS) following LPS stimulation. SP was able to enhance anti-oxidant enzyme production such as manganese superoxide dismutase (MnSOD) and heme oxygenase-1 (HO-1) following H2O2 stimulation. In in vivo models, SP (30 and 100 mg/kg) reduced paw inflammation and tissue damage after CAR and KO2 injection. Our results demonstrated the anti-inflammatory and anti-oxidant properties of SP; therefore, we propose that SP may be an effective strategy for the treatment of inflammatory diseases.

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Aspartame induces angiogenesis in vitro and in vivo models

Human & Experimental Toxicology ◽

10.1177/0960327114537535 ◽

2014 ◽

Vol 34 (3) ◽

pp. 260-265 ◽

Cited By ~ 5

Author(s):

F Yesildal ◽

FN Aydin ◽

S Deveci ◽

S Tekin ◽

I Aydin ◽

...

Keyword(s):

Wound Healing ◽

Umbilical Vein ◽

Tube Formation ◽

Control Group ◽

Dependent Manner ◽

Xtt Assay ◽

Skin Wound Healing ◽

In Vivo Models

Angiogenesis is the process of generating new blood vessels from preexisting vessels and is considered essential in many pathological conditions. The purpose of the present study is to evaluate the effect of aspartame on angiogenesis in vivo chick chorioallantoic membrane (CAM) and wound-healing models as well as in vitro 2,3-bis-2 H-tetrazolium-5-carboxanilide (XTT) and tube formation assays. In CAM assay, aspartame increased angiogenesis in a concentration-dependent manner. Compared with the control group, aspartame has significantly increased vessel proliferation ( p < 0.001). In addition, in vivo rat model of skin wound-healing study showed that aspartame group had better healing than control group, and this was statistically significant at p < 0.05. There was a slight proliferative effect of aspartame on human umbilical vein endothelial cells on XTT assay in vitro, but it was not statistically significant; and there was no antiangiogenic effect of aspartame on tube formation assay in vitro. These results provide evidence that aspartame induces angiogenesis in vitro and in vivo; so regular use may have undesirable effect on susceptible cases.

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Anti-Inflammatory Comparison of Melatonin and Its Bromobenzoylamide Derivatives in Lipopolysaccharide (LPS)-Induced RAW 264.7 Cells and Croton Oil-Induced Mice Ear Edema

Molecules ◽

10.3390/molecules26144285 ◽

2021 ◽

Vol 26 (14) ◽

pp. 4285

Author(s):

Pimpichaya Sangchart ◽

Panyada Panyatip ◽

Teerasak Damrongrungruang ◽

Aroonsri Priprem ◽

Pramote Mahakunakorn ◽

...

Keyword(s):

Raw 264.7 Cells ◽

Raw 264.7 ◽

Dependent Manner ◽

In Vivo Models ◽

Raw 264.7 Macrophages ◽

Ear Edema ◽

Croton Oil ◽

Anti Inflammatory

The pineal gland is a neuroendocrine organ that plays an important role in anti-inflammation through the hormone melatonin. The anti-inflammatory effects of melatonin and its derivatives have been reported in both in vitro and in vivo models. Our previous study reported the potent antioxidant and neuroprotective activities of bromobenzoylamide substituted melatonin. In silico analysis successfully predicted that melatonin bromobenzoylamid derivatives were protected from metabolism by CYP2A1, which is a key enzyme of the melatonin metabolism process. Therefore, the anti-inflammatory activities of melatonin and its bromobenzoylamide derivatives BBM and EBM were investigated in LPS-induced RAW 264.7 macrophages and croton oil-induced ear edema in mice. The experiments showed that BBM and EBM significantly reduced production of the inflammatory mediators interleukin-6 (IL-6), prostaglandin E2 (PGE2), and nitric oxide (NO) in a dose-dependent manner, but only slightly affected TNF-α in LPS-induced RAW 264.7 macrophages. This suggests that modifying melatonin at either the N1-position or the N-acetyl side chain affected production of NO, PGE2 and IL-6 in in vitro model. In the croton oil-induced mouse ear edema model, BBM, significantly decreased ear edema thickness at 2–4 h. It leads to conclude that bromobenzoylamide derivatives of melatonin may be one of the potential candidates for a new type of anti-inflammatory agent.

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Evaluation of Analgesic and Anti-Inflammatory Activities of Water Extract of Galla Chinensis In Vivo Models

Evidence-based Complementary and Alternative Medicine ◽

10.1155/2018/6784032 ◽

2018 ◽

Vol 2018 ◽

pp. 1-7 ◽

Cited By ~ 3

Author(s):

Kai Sun ◽

Xu Song ◽

RenYong Jia ◽

Zhongqiong Yin ◽

Yuanfeng Zou ◽

...

Keyword(s):

Capillary Permeability ◽

Water Extract ◽

Control Group ◽

Paw Edema ◽

Hot Plate ◽

Hot Plate Test ◽

In Vivo Models ◽

Ear Edema ◽

Anti Inflammatory

Aim. Pain and inflammation are associated with many diseases in humans and animals. Galla Chinensis, a traditional Chinese medicine, has a variety of pharmacological properties. The purpose of this study was to evaluate analgesic and anti-inflammatory activities of Galla Chinensis through different animal models. Method. The analgesic activities were evaluated by hot-plate and writhing tests. The anti-inflammatory effects were assessed by ear edema, capillary permeability, and paw edema tests. The contents of cytokines (NO, iNOS, PGE2, and IL-10) in serum of rats in paw edema test were inspected by ELISA assays. Results. In the hot-plate test, Galla Chinensis could significantly extend pain threshold when compared to control group. The inhibitory rates of writhes ranged from 36.62% to 68.57% in Galla Chinensis-treated mice. Treatment with Galla Chinensis (1 and 0.5 g/kg) could significantly inhibit ear edema (47.45 and 36.91%, resp.; P < 0.01). Galla Chinensis (1 g/kg) had significant (P < 0.05) anti-inflammatory activity in capillary permeability test (29.04%). In carrageenan-induced edema test, the inhibitory rates were 43.71% and 44.07% (P < 0.01) at 1 h and 2 h after administration of Galla Chinensis (1 g/kg), respectively, and the levels of proinflammatory cytokines were significantly reduced. Conclusion. These results suggest that Galla Chinensis has analgesic and anti-inflammatory effects, which may be a candidate drug for the treatment of inflammation and pain.

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Evaluation of Anti-Inflammatory Activities of a Triterpene β-Elemonic Acid in Frankincense In Vivo and In Vitro

Molecules ◽

10.3390/molecules24061187 ◽

2019 ◽

Vol 24 (6) ◽

pp. 1187 ◽

Cited By ~ 2

Author(s):

Yue Zhang ◽

Ying-li Yu ◽

Hua Tian ◽

Ru-yu Bai ◽

Ya-nan Bi ◽

...

Keyword(s):

Inflammatory Diseases ◽

Interleukin 10 ◽

The Body ◽

Raw264.7 Cells ◽

Control Group ◽

Intragastric Administration ◽

Dependent Manner ◽

Anti Inflammatory

The purpose of this research was to extract and separate the compounds from frankincense, and then evaluate their anti-inflammatory effects. The isolated compound was a representative tetracyclic triterpenes of glycine structure according to 1H-NMR and 13C-NMR spectra, which is β-elemonic acid (β-EA). We determined the content of six different localities of frankincense; the average content of β-EA was 41.96 mg/g. The toxic effects of β-EA administration (400, 200, 100 mg/kg) for four weeks in Kunming (KM) mice were observed. Compared with the control group, the body weight of mice, the visceral coefficients and serum indicators in the β-EA groups showed no systematic variations. The anti-inflammatory effects of β-EA were evaluated in LPS-induced RAW264.7 cells, xylene-induced induced ear inflammation in mice, carrageenin-induced paw edema in mice, and cotton pellet induced granuloma formation in rats. β-EA inhibited overproduction of tumor necrosis factor-α(TNF-α), interleukin-6 (IL-6), monocyte chemotactic protein 1 (MCP-1), soluble TNF receptor 1 (sTNF R1), Eotaxin-2, Interleukin 10 (IL-10) and granulocyte colony-stimulating factor (GCSF) in the RAW264.7 cells. Intragastric administration with β-EA (300, 200, and 100 mg/kg in mice, and 210, 140, and 70 mg/kg in rats) all produced distinct anti-inflammatory effects in vivo in a dose-dependent manner. Following treatment with β-EA (300 mg/kg, i.g.), the NO level in mice ears and PGE2 in mice paws both decreased (p < 0.01). In conclusion, our study indicates that β-EA could be a potential anti-inflammatory agent for the treatment of inflammatory diseases.

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