scholarly journals UP1306: A Composition Containing Standardized Extracts of Acacia catechu and Morus alba for Arthritis Management

Nutrients ◽  
2019 ◽  
Vol 11 (2) ◽  
pp. 272 ◽  
Author(s):  
Mesfin Yimam ◽  
Teresa Horm ◽  
Laura Wright ◽  
Ping Jiao ◽  
Mei Hong ◽  
...  

Osteoarthritis (OA) is characterized by progressive articular cartilage degradation. Although there have been significant advances in OA management, to date, there are no effective treatment options to modify progression of the disease. We believe these unmet needs could be bridged by nutrients from natural products. Collagen induced arthritis in rats was developed and utilized to evaluate anti-inflammatory and cartilage protection activity of orally administered botanical composition, UP1306 (50 mg/kg) and Methotrexate (75 µg/kg) daily for three weeks. Objective arthritis severity markers, urine, synovial lavage, and serum were collected. At necropsy, the hock joint from each rat was collected for histopathology analysis. Urinary cartilage degradation marker (CTX-II), pro-inflammatory cytokines (tumor necrosis factor α (TNF-α), interleukin-1β (IL-1β), and IL-6), and proteases (Matrix Metallopeptidase 3 (MMP3) and 13) were measured. Rats treated with UP1306 showed statistically significant improvements in arthritis severity markers, including uCTX-II (91.4% vs. collagen-induced arthritis (CIA)), serum IL-1β, TNF-α, and IL-6 levels as well as synovial MMP-13. The histopathology data were also well aligned with the severity score of arthritis for both UP1306 and Methotrexate. UP1306, a botanical composition that contains a standardized blend of extracts from the heartwood of Acacia catechu and the root bark of Morus alba, could potentially be considered as a dietary supplement product for the management of arthritis.

2017 ◽  
Vol 2017 ◽  
pp. 1-10 ◽  
Author(s):  
Mesfin Yimam ◽  
Teresa Horm ◽  
Laura Wright ◽  
Ping Jiao ◽  
Mei Hong ◽  
...  

Although there have been augmented advances in drug discovery, current OA management is inadequate due to the lack of successful therapies proven to be effective in modifying disease progression. For some, the risk outweighs the benefit. As a result, there is a desperate need for safe and efficacious natural alternatives. Here we evaluated a composition fromMorus alba,Scutellaria baicalensis, andAcacia catechuin maintaining joint structural integrity and alleviating OA associated symptoms in monoiodoacetate- (MIA-) induced rat OA disease model. Study lasted for 6 weeks. 59.6%, 64.6%, 70.7%, 69.9%, and 70.3% reductions in pain sensitivity were observed for rats treated with the composition from week 1 to week 5, respectively. Statistically significant improvements in articular cartilage matrix integrity (maintained at 57.1% versus MIA + vehicle treated rats) were shown from the modified total Mankin score for animals treated with the composition. The composition showed a statistically significant reduction in uCTX-II level (54.1% reductions). The merit of combining these botanicals was also demonstrated in their synergistic analgesic activity. Therefore, the standardized blend ofMorus alba,Scutellaria baicalensis, andAcacia catechucould potentially be considered as an alternative remedy from natural sources for the management of OA and/or its associated symptoms.


2020 ◽  
Vol 7 (2) ◽  
pp. 57
Author(s):  
Eric Danilo Pauls Sotelo ◽  
Cynthia Prado Vendruscolo ◽  
Joice Fülber ◽  
Sarah Raphaela Torquato Seidel ◽  
Fernando Mosquera Jaramillo ◽  
...  

Several studies in human and equine medicine have produced controversial results regarding the role of dimethylsulfoxide (DMSO) as a therapeutic agent. This study aimed to evaluate the effect of joint lavage with different DMSO concentrations on biomarkers of synovial fluid inflammation and cartilage degradation in joints with lipopolysaccharide (LPS)-induced synovitis. Twenty-six tibiotarsal joints of 13 horses were randomly distributed into four groups (lactated Ringer’s solution; 5% DMSO in lactated Ringer’s; 10% DMSO in lactated Ringer’s; and sham). All animals were evaluated for the presence of lameness, and synovial fluid analyses were performed at 0 h, 1 h, 8 h, 24 h, and 48 h (T0, T1, T8, T24, and T48, respectively). The white blood cell counts (WBC), total protein (TP), urea, prostaglandin E2 (PGE2), interleukin (IL)-1β, IL-6, IL-10, tumor necrosis factor-α (TNF-α), hyaluronic acid (HA), and chondroitin sulfate (CS) concentrations were measured. The WBC counts and PGE2, IL-1β, IL-6, and TP concentrations increased in all groups at T8 compared to baseline values (p < 0.05). At T48, only the 5% DMSO and 10% DMSO groups showed a significant decrease in WBC counts (p < 0.05). Furthermore, the 10% DMSO group had lower concentrations of PGE2 and IL-1β at T48 than at T8 (p < 0.05) and presented lower IL-6 levels than the5% DMSO and lactated Ringer’s groups at T24. All groups showed an increase in CS concentration after LPS-induced synovitis. Joint lavage with 10% DMSO in lactated Ringer’s has anti-inflammatory but not chondroprotective effects.


2018 ◽  
Vol 32 (04) ◽  
pp. 352-360 ◽  
Author(s):  
Chunli Wang ◽  
Qingjia Chi ◽  
Chunming Xu ◽  
Kang Xu ◽  
Yanjun Zhang ◽  
...  

AbstractThis study aims to confirm the effects of synoviocytes (SCs) on regulating lysyl oxidases (LOXs) and matrix metalloproteinase (MMP)-1, 2, 3 in the normal and injured anterior cruciate ligament (ACL) fibroblasts response to tumor necrosis factor-α(TNF-α). The gene and protein expression levels of LOXs and MMP-1, 2, 3 in SCs cocultured ACL fibroblasts (ACLfs) induced by TNF-α and mechanical injury were analyzed by real-time polymerase chain reaction (PCR) and western bolting; the MMP-2 activity were analyzed by zymography. The results exhibited that TNF-α alone slightly downregulated the expressions of LOXs and upregulated the expression of MMP-1, 2, 3 in both normal and injured ACL fibroblasts. The decrease of LOXs and increase of MMP-1, 2, 3 in ACLfs response to TNF-α were further promoted by coculture. Taken together, these results show for the first time that the crosstalk between ACLfs and SCs could modulate the LOXs and MMP-1, 2, 3 synthesis in ACLfs in the presence of TNF-α. Accumulation of MMPs in the isolated fluid-containing space not only disrupts the balance of ACL healing, but also increases cartilage degradation and accelerates osteoarthritis (OA) in injured joint. Based on this mechanism, targeting inhibition of MMPs could provide a promising therapeutic strategy for acute ligament injury.


1998 ◽  
Vol 187 (4) ◽  
pp. 461-468 ◽  
Author(s):  
Tonino Alonzi ◽  
Elena Fattori ◽  
Domenico Lazzaro ◽  
Patrizia Costa ◽  
Lesley Probert ◽  
...  

Interleukin-6 (IL-6) is overproduced in the joints of patients with rheumatoid arthritis (RA) and, based on its multiple stimulatory effects on cells of the immune system and on vascular endothelia, osteoclasts, and synovial fibroblasts, is believed to participate in the development and clinical manifestations of this disease. In this study we have analysed the effect of ablating cytokine production in two mouse models of arthritis: collagen-induced arthritis (CIA) in DBA/1J mice and the inflammatory polyarthritis of tumor necrosis factor α (TNF-α) transgenic mice. IL-6 was ablated by intercrossing an IL-6 null mutation into both arthritis-susceptible genetic backgrounds and disease development was monitored by measuring clinical, histological, and biochemical parameters. Two opposite responses were observed; while arthritis in TNF-α transgenic mice was not affected by inactivation of the IL-6 gene, DBA/1J, IL-6−/− mice were completely protected from CIA, accompanied by a reduced antibody response to type II collagen and the absence of inflammatory cells and tissue damage in knee joints. These results are discussed in the light of the present knowledge of cytokine networks in chronic inflammatory disorders and suggest that IL-6 receptor antagonists might be beneficial for the treatment of RA.


2021 ◽  
Author(s):  
Harumi Jyonouchi ◽  
Lee Geng

Autism spectrum disorder (ASD) is a behaviorally defined syndrome with frequent co-morbidities. Evidence indicate a role of innate immunity in ASD pathogenesis. This study addressed whether innate immune abnormalities are associated with ASD co-morbid conditions and/or other clinical co-variables when assessed as changes in monocyte cytokine profiles. This study included 109 ASD (median 11.5 year) and 26 non-ASD subjects (median 11.4 year). Monocyte cytokine profiles were evaluated in association with age/ethnicity, ASD severity, medications, and co-morbidities present in >15% of ASD subjects [gastrointestinal (GI) symptoms, epilepsy, allergic rhinitis, specific antibody deficiency (SAD), and fluctuating behavioral symptoms resembling pediatric acute-onset neuropsychiatric syndrome (PANS)]. ASD severity did not affect frequency of co-morbid conditions. GI symptoms, epilepsy, SAD, and PANS like symptoms revealed associations with changes in production of tumor necrosis factor-α (TNF-α)/soluble TNF-receptor II (sTNFRII), interleukin-1ß (IL-1ß)/IL-6/IL-10, and IL-6, respectively, mostly independent of other co-variables. ASD severity was associated with changes in multiple cytokines but frequently affected by other clinical co-variables. Our findings revealed associations between specific monocyte cytokine profiles and certain co-morbid conditions in ASD subjects, independent of other clinical co-variables. Our findings will aid in assessing treatment options for ASD co-morbidities and their effects on ASD behavioral symptoms.


2017 ◽  
Vol 2017 ◽  
pp. 1-9 ◽  
Author(s):  
Douglas S. Kalman ◽  
Susan J. Hewlings

The purpose of this study was to determine the effects of UP1306 on discomfort and function in adults with osteoarthritis of the knee. In a randomized, double-blinded, placebo-controlled, parallel design, 135 subjects received UP1306, a standardized, proprietary extract of Morus alba and Acacia catechu, glucosamine chondroitin, or placebo for 12 weeks. Discomfort, stiffness, and activities of daily living measured by the WOMAC questionnaire and VAS (pain/discomfort) were improved within all groups. Range of motion and distance walked were improved. There were no changes in TNFα levels for any of the products. There was a significant difference in urinary C-telopeptides of type II collagen (CTX-II), a marker of cartilage degradation between UP1306, and placebo after 12 weeks (p=0.029). All efficacy measurements were improved from baseline to most time-points for UP1306, the comparator, and placebo without a significant association between the products. There was a significant difference between the changes of uCTX-II for UP1306 and placebo after 12 weeks. Early intervention with UP1306 aimed at reducing bone and cartilage degradation through reported inhibition of catabolic proinflammatory pathways may help to prevent joint cartilage damage. This study is registered with Clinical Trial ID ISRCTN15418623.


2018 ◽  
Vol 94 ◽  
pp. 115-123 ◽  
Author(s):  
Mesfin Yimam ◽  
Ping Jiao ◽  
Mei Hong ◽  
Lidia Brownell ◽  
Hyun-Jin Kim ◽  
...  

2009 ◽  
Vol 6 (1) ◽  
pp. 57-63 ◽  
Author(s):  
Mengjie Wu ◽  
Zhiyuan Gu

Moutan Cortex, a widely used traditional Chinese medicine for the treatment of various diseases, is the root bark ofPaeonia suffruticosa Andrews(Paeoniaceae). Most of the pharmacological investigations of Moutan Cortex have been addressed to its central nervous system activities, anti-oxidative and sedative actions. Otherwise, there are few reports about the active compounds with anti-inflammatory activity of Moutan Cortex. The aim of the present study was to screen and identify bioactive compounds with anti-inflammatory effect from Moutan Cortex. With the aid of preparative high performance liquid chromatography (HPLC) technique, ethyl acetate and ethanol extract of Moutan Cortex were isolated into twenty-two fractions. Bioactivities of these fractions were evaluated by measuring expression of tumor necrosis factor-α (TNF-α) in rat synoviocytes subjected to interleukin-1β (IL-1β). Eight compounds were isolated from six active fractions and identified by HPLC/MSn. Purified compounds, paeoniflorin, paeonol and pentagalloylglucose resulted in dose-dependent inhibition of TNF-α synthesis and IL-6 production in synoviocytes treated with proinflammatory mediator. These results suggested that paeonol, paeoniflorin, glycosides and pentagalloylglucose contribute to the anti-inflammatory effect of Moutan Cortex.


2020 ◽  
Vol 2 (2) ◽  
Author(s):  
Khadiga Ahmed Ismail

Background: Tumor necrosis Factor-α (TNF-α) is encoded and controlled by TNF-α gene, which is involved in rheumatoid arthritis (RA) susceptibility. This research aimed to identify genetic variations of TNF-α (G308A) and to establish its association with inflammatory markers in Rheumatoid Arthritis predisposition. Methods: In the present study, fifty RA patients and fifty volunteers were involved and evaluated for the C-reactive protein, rheumatoid factor, and TNF-α were estimated by ELISA, Erythrocyte Sedimentation Rate (ESR) by Wintergreen method and for TNF-α-308 G>A polymorphism by polymerase chain reaction with amplification refractory mutation system (PCR-ARMS). Results: The CRP, RF, ESR and TNF-α were significantly elevated in RA patients relative to controls. The serum level TNF-α was also significantly elevated in female patients and in patients ≥50 years. Analysis of TNF-308 gene polymorphism revealed that GG genotypes were more prevalent in RA patients than in the healthy individuals and that GG genotype may be a potential factor to RA. The G allele was more common in RA than in the control. Elevated TNF-α serum levels were significantly associated the GG genotype and functional disability in RA patients. Conclusion: TNF-α promoter 308polymorphism GG genotype may be considered as a risk factor for RA and the TNF-α serum level was significantly related to the functional disability in the disease.


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