scholarly journals UP3005, a Botanical Composition Containing Two Standardized Extracts ofUncaria gambirandMorus alba, Improves Pain Sensitivity and Cartilage Degradations in Monosodium Iodoacetate-Induced Rat OA Disease Model

2015 ◽  
Vol 2015 ◽  
pp. 1-10 ◽  
Author(s):  
Mesfin Yimam ◽  
Young-Chul Lee ◽  
Tae-Woo Kim ◽  
Breanna Moore ◽  
Ping Jiao ◽  
...  

Osteoarthritis (OA) is a multifactorial disease primarily noted by cartilage degradation in association with inflammation that causes significant morbidity, joint pain, stiffness, and limited mobility. Present-day management of OA is inadequate due to the lack of principal therapies proven to be effective in hindering disease progression where symptomatic therapy focused approach masks the actual etiology leading to irreversible damage. Here, we describe the effect of UP3005, a composition containing a proprietary blend of two standardized extracts from the leaf ofUncaria gambirand the root bark ofMorus alba, in maintaining joint structural integrity and alleviating OA associated symptoms in monosodium-iodoacetate- (MIA-) induced rat OA disease model. Pain sensitivity, micro-CT, histopathology, and glycosaminoglycans (GAGs) level analysis were conducted. Diclofenac at 10 mg/kg was used as a reference compound. UP3005 resulted in almost a complete inhibition in proteoglycans degradation, reductions of 16.6% (week 4), 40.5% (week 5), and 22.0% (week 6) in pain sensitivity, statistically significant improvements in articular cartilage matrix integrity, minimal visual subchondral bone damage, and statistically significant increase in bone mineral density when compared to the vehicle control with MIA. Therefore, UP3005 could potentially be considered as an alternative therapy from natural sources for the treatment of OA and/or its associated symptoms.

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.


Biomedicines ◽  
2020 ◽  
Vol 8 (9) ◽  
pp. 369
Author(s):  
Kaori Iimura ◽  
Nobuhiro Watanabe ◽  
Philip Milliken ◽  
Yee-Hsee Hsieh ◽  
Stephen J. Lewis ◽  
...  

Electrical stimulation of myelinated afferent fibers of the superior laryngeal nerve (SLN) facilitates calcitonin secretion from the thyroid gland in anesthetized rats. In this study, we aimed to quantify the electrical SLN stimulation-induced systemic calcitonin release in conscious rats and to then clarify effects of chronic SLN stimulation on bone mineral density (BMD) in a rat ovariectomized disease model of osteoporosis. Cuff electrodes were implanted bilaterally on SLNs and after two weeks recovery were stimulated (0.5 ms, 90 microampere) repetitively at 40 Hz for 8 min. Immunoreactive calcitonin release was initially measured and quantified in systemic venous blood plasma samples from conscious healthy rats. For chronic SLN stimulation, stimuli were applied intermittently for 3–4 weeks, starting at five weeks after ovariectomy (OVX). After the end of the stimulation period, BMD of the femur and tibia was measured. SLN stimulation increased plasma immunoreactive calcitonin concentration by 13.3 ± 17.3 pg/mL (mean ± SD). BMD in proximal metaphysis of tibia (p = 0.0324) and in distal metaphysis of femur (p = 0.0510) in chronically SLN-stimulated rats was 4–5% higher than that in sham rats. Our findings demonstrate chronic electrical stimulation of the SLNs produced enhanced calcitonin release from the thyroid gland and partially improved bone loss in OVX rats.


Author(s):  
Huan Ma ◽  
Cong Nie ◽  
Ying Chen ◽  
Jinmiao Li ◽  
Yanjie Xie ◽  
...  

Cell cycle deregulation is involved in pathogenesis of many cancers, and often associated with protein kinase aberrations, including the polo-like kinase 1 (PLK1). Wehereby used retinoblastoma, an intraocular malignancy that lacks targeted therapy, as a disease model and set out to reveal targetability of PLK1 with a small molecularinhibitor ON-01910.Na. First, transcriptomic analysis on patient retinoblastoma tissues suggested that cell cycle progression was deregulated and confirmed that PLK1pathway was upregulated. Next, antitumor activity of ON-01910.Na was investigated inboth cellular and animal levels. Cytotoxicity induced by ON-01910.Na was tumor-specific and dose-dependent in retinoblastoma cells, whilst non-tumor cells wereminimally affected. In three-dimensional culture, ON-01910.Na demonstrated efficient drug-penetrability with multilayer cell death. Post-treatment transcriptomic findingsrevealed that cell cycle arrest and MAPK cascade activation were induced following PLK1 inhibition, and eventually result in apoptotic cell death. In Balb/c nude mice, a safe threshold of 0.8 nmol intravitreal dosage of ON-01910.Na was established for intraocular safety, which was demonstrated by structural integrity and functional preservation. Furthermore, intraocular and subcutaneous xenograft were significantlyreduced with ON-01910.Na treatments. For the first time, we demonstrated targetability of PLK1 in retinoblastoma by efficiently causing cell cycle arrest and apoptosis. Ourstudy is supportive that local treatment of ON-01910.Na may be a novel, effectivemodality benefiting patients with PLK1-aberrant tumors.


Author(s):  
Mohamed Ketta ◽  
Eva Tůmová ◽  
Roman Stupka ◽  
Jaroslav Čítek ◽  
Darina Chodová

Cadmium (Cd) is a toxic heavy metal, discharged into environments naturally or anthropogenically, where industrial and agricultural revolutions have led to serious Cd pollution into the environment. Poultry feed may be contaminated by Cd due to its presence in concentrates and supplements, and also in the machinery and equipment used in feed production and processing. After absorption in the digestive system, Cd largely accumulates in kidneys, liver, bones and other organs and causes irreversible damage to these organs. Higher doses of Cd in the poultry diet reduced feed intake, body weight, bone mineral density, egg production and eggshell quality. Selenium (Se) is an essential micronutrient and important component of a variety of antioxidant enzymes, with the ability to antagonize metal toxicity including Cd. Hence, in the current review, we try to summarize recent information about the toxicological effects of Cd and provide updated information about the role of Se as an effective strategy in reducing Cd toxicity in poultry.


2021 ◽  
Author(s):  
Yung-Chang Lu ◽  
Ting-Kuo Chang ◽  
Tzu-Chiao Lin ◽  
Shu-Ting Yeh ◽  
Hsu-Wei Fang ◽  
...  

Abstract Background: Osteolysis is one of the most prevalent clinical complications of total joint replacement (TJR). Wedelolactone (WDL) is a coumestan compound derived from the Wedelia chinensis plant and has been demonstrated to exhibit anti-inflammatory properties. This study aimed to investigate the use of WDL as a potential treatment for reducing the risk of particle-induced osteolysis using a well-established particle-induced mice calvarial disease model. Methods: Thirty-two C57BL/6J mice were randomized into four groups: sham, polystyrene particles (PS), PS particles with WDL treatment for 4 weeks (WDL 4w) and PS particles with WDL treatment for 8 weeks (WDL 8w). Micro-CT was used to quantitatively analyze the bone mass. Osteoclast numbers were also measured from histological analysis. Results: The results showed that bone mineral density was significantly higher in the WDL 8w group than in the PS group (p < 0.05), and both the WDL 4 and WDL 8w groups had lower osteoclast numbers (p < 0.05). No significant difference in osteoclast number was found between the WDL 4w and WDL 8w groups. Conclusions: These results support the use of WDL as a herbal medicine for reducing the severity of particle-induced osteolysis after TJR.


2021 ◽  
Vol 5 (Supplement_1) ◽  
pp. 188-189
Author(s):  
Lina Ma ◽  
Yaxin Zhang ◽  
Pan Liu ◽  
Yun Li

Abstract Background The disease concept is increasingly being replaced by a functional approach to address the healthcare needs of the older people. WHO proposed the Integrated Care for Older People (ICOPE) screening tool to identify older people with priority conditions associated with declines in intrinsic capacity (IC). Very few evidence on the clinical utility of the ICOPE tool is available. Objectives: To determine if the tool can identify adults with poor physical and mental function. Method: 376 participants aged 50–97 years were included. IC was assessed with the WHO ICOPE screening tool, covering the following five domains: cognitive decline, limited mobility, malnutrition, sensory loss, and depressive symptoms. We assessed the activities of daily living, the Fried frailty phenotype, FRAIL scale, SARC-F scale, MMSE, GDS, social frailty, and quality of life. Peak expiratory flow, bones mineral density, body composition were obtained. Results 69.1% of the participants showed declines in IC. Participants with declines in IC were older, had more chronic diseases, worse general health, worse physical function as indicated by lower Barthel index, walk speed, grip strength, and physical fatigue, worse mental function indicated by lower MMSE scores, higher GDS scores, more mental fatigue, and worse social function. After adjusting for age, IC was positively correlated with walking speed, resilience score, and MMSE score and negatively correlated with frailty, SARC-F score, IADL score, GDS score, and physical and mental fatigue. Conclusion The WHO ICOPE screening tool is useful to identify adults with poor physical and mental function in Chinese older adults.


2016 ◽  
Author(s):  
Joshua N. Goldstein

Dizziness is a relatively common condition in the emergency setting. Patient descriptions of their symptoms can be vague and inconsistent. This review highlights the most important aspects of the history and physical examination that can help differentiate among different causes of dizziness. In addition, it covers the pathophysiology of inner ear disease, including diagrams of vestibular anatomy. For the history, it is critical to capture dizziness, duration, triggers for dizziness, and associated symptoms. For the physical examination, a focused neurologic assessment is important, including balance, coordination, as well as an oculomotor assessment. For treatment of benign positional vertigo, various canalith repositioning maneuvers are described and diagrams shown. For vestibular neuritis, treatment options including vestibular rehabilitation and steroids are discussed. Finally, medical options for symptomatic therapy are listed.  Key words: Dizziness, benign positional vertigo, canalith repositioning maneuver, vestibular disorders. This review contains 7 highly rendered figures, 7 tables, and 40 references.


2019 ◽  
Vol 3 (Supplement_1) ◽  
Author(s):  
Yun Tai Kim ◽  
Eun Yeong Lim ◽  
Young-Do Nam ◽  
Hee Soon Shin

Abstract Objectives Menopause is a natural process, where ovaries produce less reproductive hormones, which degrades the quality of life. Hormone replacement therapy was used primarily to reduce menopausal symptoms but new therapies are needed because they have a risk in long-term use. Probiotics are well known for their beneficial effects on bowel health, obesity, and immunity, and they have been reported to have useful effects on menopause in recent years. This study examined the effects of Lactobacillus acidophilus YT1 on menopausal symptoms in ovariectomized (OVX) rats. Methods Twelve weeks-old female SD rats were divided into five groups: (1) sham + DW, (2) OVX + DW, (3) OVX + estradiol, (4) OVX + L. acidophilus YT1, and (5) OVX + Lactobacillus reuteri that were treated once daily for 12 weeks after OVX. Results Pain sensitivity, depression-related behavior, and fat mass were significantly increased at 12 weeks after OVX and the bone mineral density was decreased. These menopause symptoms were significantly recovered by a daily oral treatment of L. acidophilus YT1 for 12 weeks. In addition, L. acidophilus YT1 enhanced intestinal barrier function by up-regulation tight junction expression in Caco-2 cell monolayers. Conclusions The treatment of L. acidophilus YT1 could alleviate menopausal symptoms, such as increased pain sensitivity, depression, body fat, and bone loss in menopausal women, which suggests it could be developed as a functional food and probiotics for elderly women health. Funding Sources This research was supported by the main research Program (E0164502-03) of the Korea Food Research Institute funded by the Minstry of Science and ICT.


2017 ◽  
Vol 20 (6) ◽  
pp. 568-576 ◽  
Author(s):  
Mesfin Yimam ◽  
Young-Chul Lee ◽  
Laura Wright ◽  
Ping Jiao ◽  
Teresa Horm ◽  
...  

Pharmaceutics ◽  
2020 ◽  
Vol 12 (12) ◽  
pp. 1245
Author(s):  
Sunmin Park ◽  
Bo Reum Moon ◽  
Ji Eun Kim ◽  
Hyun Joo Kim ◽  
Ting Zhang

Water extracts of both Morus alba L. root bark (MBW) and Cornus officinalis Siebold and Zucc fruit (CFW) have traditionally been used to promote men’s health in the elderly in Asia. We determined that the 12-week consumption of MBW and CFW could alleviate testosterone-deficiency syndrome and osteoarthritis (OA) symptoms in testosterone-deficient rats, and the action mechanisms were explored. Rats with bilateral orchiectomy (ORX) were fed a 45% fat diet containing either 0.5% MBW (ORX-MBW), 0.5% CFW(ORX-CFW), or 0.5% dextrin (ORX-CON). Sham-operated rats also received 0.5% dextrin (Non-ORX-CON). After 8 weeks of treatment, all rats had an injection of monoiodoacetate (MIA) into the left knee, and they continued the same diet for the additional 4 weeks. ORX-CFW and ORX-MBW partially prevented the reduction of serum testosterone concentrations and decreased insulin resistance, compared to the ORX-CON. ORX-CFW and ORX-MBW protected against the reduction of bone mineral density (BMD) and lean body mass (LBM) compared to the ORX-CON. The limping and edema scores were lower in the order of the ORX-CON, ORX-CRF = ORX-MBW, and Non-ORX-CON (p < 0.05). The scores for pain behaviors, measured by weight-distribution on the OA leg and maximum running velocity on a treadmill, significantly decreased in the same order as limping scores. ORX-MBW protected against the increased expression of matrix metalloproteinase (MMP)-3 and MMP-13 and reduced the production of inflammatory markers such as TNF-α and IL-1β, by MIA in the articular cartilage, compared to the ORX-CON (p < 0.05). The cartilage damage near the tidemark of the knee and proteoglycan loss was significantly less in ORX-MBW than ORX-CON. In conclusion, MBW, possibly CFW, could be effective alternative therapeutic agents for preventing osteoarthritis in testosterone-deficient elderly men.


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