Maximal medical treatment of adenoid hypertrophy: a prospective study of preschool children.

PURPOSE: This study aimed to examine the effectiveness of the combined maximal medical treatment for adenoid hypertrophy in preschool children. METHODS: Sixty-four children underwent one-year combined therapy with intranasal mometasone furoate, oral desloratadine, nasal saline irrigation, and bacteriotherapy. Additionally, decongestion drops were applied during scheduled breaks. RESULTS: Of the 64 treated children, 72% showed clinical improvement in adenoid symptoms while 28% did not improve and underwent surgery. These groups differed significantly in terms of the overall reduction in ailments after treatment (p < 0.001), infection rate (p < 0.001), catarrh severity (p < 0.001) and nasal patency (p < 0.001). Endoscopic examination confirmed that responders experienced, on average, a decrease of 8.4% in the adenoid/choana ratio and an improvement in mucosal coverage of the adenoid. These effects were not observed in the group of children whose parents opted for surgery after nine months of conservative treatment. CONCLUSIONS: The proposed new schema of long-term maximal medical treatment with the use of combined intermittent treatment of intranasal mometasone furoate and decongestion drops, oral desloratadine, nasal saline irrigation, and bacteriotherapy can be attempted in patients with adenoid hypertrophy symptoms, and responders may avoid the need for surgery. The applied treatment breaks resulted in a low number of therapeutic side effects.

Individualized Homeopathic Medicines in the Management of Symptomatic Adenotonsillar Hypertrophy in Children: A Prospective Observational Study.

BACKGROUND: Globally, adenotonsillar hypertrophy (ATH) is one of the most prevalent upper respiratory tract disorders of children, with associated troublesome symptoms such as sleep apnea and cognitive disturbances. In this study, we evaluated the potential role of individualized homeopathic medicines in the management of symptomatic ATH in children. METHODS: A multicenter prospective observational study was conducted at five institutes under the Central Council for Research in Homoeopathy, India. Primary and secondary outcomes (symptom score for adenoids, other symptoms of ATH, Mallampati score, tonsillar size, Sleep-Related Breathing Disorder of the Paediatric Sleep Questionnaire [SRBD-PSQ]) were assessed through standardized questionnaires at baseline and at 3, 6, 9 and 12 months. Radiological investigations for assessing the adenoid/nasopharyngeal (A/N) ratio were carried out at baseline, 6 and 12 months. All analyses were carried out using an intention-to-treat approach. RESULTS: A total of 340 children were screened and 202 children suffering from ATH were enrolled and followed up monthly for 12 months. Each patient received individualized homeopathic treatment based on the totality of symptoms. Statistically significant reductions in adenoid symptom score, Mallampati score (including tonsillar size), SRBD-PSQ sleep quality assessment and A/N ratio were found over time up to 12 months (p < 0.001). Homeopathic medicines frequently indicated were Calcarea carbonicum, Phosphorus, Silicea, Sulphur, Calcarea phosphoricum, Pulsatilla, Lycopodium and Tuberculinum. No serious adverse events were recorded during the study period. CONCLUSION: This study suggests that homeopathic medicines may play a beneficial role in the management of symptomatic ATH in children. Well-designed comparative trials are warranted.

Integrated network pharmacology and molecular docking analyses of the mechanisms underlying the antihypertensive effects of lotusine.

Hypertension is a modifiable cardiovascular risk factor and cause of death worldwide. Lotusine, an alkaloid extracted from a plant used in traditional Chinese Medicine, has shown anti-hypertensive effects. However, its therapeutic efficacy requires further investigation. We adopted integrated network pharmacology and molecular docking approaches with the aim of investigating lotusine's antihypertensive effects and mechanisms of action in rat models. After identifying the optimal intravenous dosage, we observed the effects of lotusine administration on two-kidney, one-clip (2K1C) rats and spontaneously hypertensive rats (SHRs). Based on network pharmacology and molecular docking analyses, we measured renal sympathetic nerve activity (RSNA) to evaluate lotusine's effect. Finally, an abdominal aortic coarctation (AAC) model was established to evaluate lotusine's long-term effects. The network pharmacology analysis identified 21 intersection targets; of these, 17 were also implicated by the neuroactive live receiver interaction. Further integrated analysis showed high lotusine affinity for the cholinergic receptor nicotinic alpha 2 subunit, adrenoceptor beta 2, and adrenoceptor alpha 1B. Blood pressure of the 2K1C rats and SHRs decreased after treatment with 2.0 and 4.0 mg/kg of lotusine (P < 0.001 versus saline control). We also observed RSNA decreases consistent with the network pharmacology and molecular docking analysis results. Results from the AAC rat model indicated that myocardial hypertrophy was decreased with lotusine administration, demonstrated by echocardiography and hematoxylin and eosin and Masson staining. This study provides insights into the antihypertensive effects and underlying mechanisms of lotusine; lotusine may exert long-term protective effects against myocardial hypertrophy caused by elevated blood pressure.

Adjunctive Treatment of Pediatric Adenoidal Hypertrophy: A Review.

Context: Adenoids play an important role in the protection of the upper respiratory tract against pathogens. Nonphysiological enlargement of adenoids is defined as adenoid hypertrophy (AH). In treating AH, physicians prefer medical therapy and often disregard adjunctive methods. Studies on the effects of adjunctive methods on adenoid tissue are quite scarce. Objective: The current review aims to examine the clinical studies that have investigated adjunctive methods-nasal irrigation, herbal therapy, bacteriotherapy, and halotherapy-used to treat AH and its associated symptoms and to evaluate their effectiveness in pediatric patients. Design: The research team performed a narrative review by searching seven electronic databases (Pubmed, Cochrane Library, Google Scholar, Web of Science, EMBASE, Science Citation Index and Elsevier) were used for the literature search. The search used the keywords adenoid hypertrophy, adjunctive treatment, nasal irrigation, herbal medications, bacteriotherapy and halotherapy. Setting: This study was took place in Department of Anatomy, Medicine Faculty, Istanbul Medeniyet University. Results: The nasal irrigation with hypertonic solution decreased to size of enlarged adenoid tissue. The bacteriotherapy used with nasal spray and tablet form decreased to surgery rate and adenoid size.The adenoid and/or tonsillar hypertrophy were decreased by halotherapy used with micronized, iodized-salt aerosol. Conclusions: A review of studies on this matter indicates that the studied adjunctive methods can be used safely in the treatment of AH, either separately or in combination with conventional medical treatment. However further clinical studies are needed on this topic.

Photodynamic therapy of adenoid hypertrophy in acute rhinosinusitis.

A first step for microorganisms to reach the respiratory system and cause infectious disease is colonization in the nasopharynx. Humans inhale a bacterial load of up to 106 per cubic meter of air per day [1], including transient microorganisms between the upper and lower airways. This can lead to lung infections, amounting to billions of dollars in annual direct treatment costs in the United States, depending on the etiologic agent [2,3]. Curcumin has been described as a photosensitizer (PS) that, activated at 450 nm, is efficient against planktonic bacteria [4] and biofilms [5]. At the same time, effects on microbial interactions are commonly detected in the upper respiratory tract and should be considered for the treatment of adenoids [6]. We, therefore, propose in this study to optimize photodynamic therapy (PDT) conditions in vitro by simulating bacterial coinfection conditions in nasal cavities evaluated by the response surface method, where we can evaluate interactions of treatment variables. From this, the clinical case of the treatment of rhinosinusitis was carried out using PDT with nasal lighting. The absence of symptoms that characterize the disease was monitored and evaluated by the Kepler Meyer method. The study points out considerations that can be evaluated for the treatment to be a possibility of clinical indication in the control of rhinosinusitis.

6-gingerol ameliorates metabolic disorders by inhibiting hypertrophy and hyperplasia of adipocytes in high-fat-diet induced obese mice.

OBJECTIVES: Accumulating studies revealed that 6-gingerol, a compound extracted mainly from ginger, treats obesity by preventing hyperlipidemia in vivo induced by high-fat-diet (HFD). The present study intends to further evaluate the efficacy of 6-gingerol in the treatment of obesity and investigate its potential mechanism. METHODS: Obese mice were established by HFD induction. Bioinformatic analysis was used to predict the possible pathways enrolled by the application of 6-gingerol. Body weight and the levels of blood glucose and lipids were examined and analyzed for the evaluation of the therapeutic effect of 6-gingerol. The size and amounts as well as the status of adipocytes were determined by histological staining. The expression levels of related proteins in adipose tissue were assessed by immunohistochemical staining, immunofluorescent staining, and Western blot analysis. In addition, the expression levels of related mRNA were assessed by RT-qPCR. RESULTS: HFD induced obesity was significantly curbed by 6-gingerol treatment. Here inhibition mechanism of 6-gingerol is demonstrated on excessive hypertrophy and hyperplasia of adipocytes in white adipose tissue (WAT), which may be related to the regulation of adipocytokines, such as PPARγ, C/EBPα, FABP4 and adiponectin, and the TLR3/IL-6/JAK1/STAT3 axis. Moreover, 6-gingerol treatment suppressed the expressions of IL-1ß and CD68 in the liver and AKT/INSR/IRS-1 in epididymal WAT. CONCLUSION: The results suggested that 6-gingerol could alleviate metabolic inflammation in the liver and insulin resistance to treat obesity. The mechanism is mainly involved in the inhibition of excessive hypertrophy and hyperplasia of adipocytes.

Yacon-based product improves intestinal hypertrophy and modulates the production of glucagon-like peptide-1 in postmenopausal experimental model.

AIMS: The progressive decline in estrogen level puts postmenopausal women at a higher risk of developing cardiometabolic diseases. Thus, we evaluated the potential beneficial effects of yacon-based product (YBP) on glycemic profile and intestinal health of postmenopausal rats. METHODS: Eighty Wistar rats were randomized into 4 ovariectomized (OVX) groups or 4 celiotomized groups treated with a standard diet (SD) or diet supplemented with YBP at 6% of fructooligosaccharide (FOS)/inulin. KEY FINDINGS: The continued consumption of YBP at 6% of FOS/inulin did not generate liver damage and gastrointestinal disorders. Rats fed with YBP displayed higher food consumption, but this did not increase the body weight gain, abdominal circumference and body fat percentual of OVX rats. Furthermore, we also found that the FOS/inulin fermentation present in the YBP resulted in cecum, ileum and colon crypts hypertrophy and increased the lactic acid levels in the cecal content. We observed an increase of glucagon-like peptide-1 (GLP-1) immunoreactive cells and there was no change in the glucose and insulin plasma levels of YBP-fed OVX rats. SIGNIFICANCE: Our findings indicated that YBP when consumed previously and after the menopausal period has important effects on the morphology and function of intestinal mucous of rats and has potential to modulate indirectly the glycemic and insulinemic profiles, weight gain and body fat percentual in the hypoestrogenic period through metabolites produced in the fermentation process.

Ginsenoside Rg3 attenuates angiotensin II-induced myocardial hypertrophy through repressing NLRP3 inflammasome and oxidative stress via modulating SIRT1/NF-κB pathway.

BACKGROUND: Ginsenoside Rg3 (Rg3), one of the most potent components extracted from the roots of the traditional Chinese herb Panax ginseng, has prominent roles in anti-tumor and anti-inflammation. However, the applications of Rg3 against myocardial hypertrophy are not fully revealed. METHODS: Transverse aortic constriction (TAC) was adopted to build the myocardial hypertrophy model in rats. The in vitro model of myocardial hypertrophy was induced by angiotensin II (Ang II) in the human cardiomyocyte cell line AC16 and HCM, which were then treated with different doses of Rg3. The levels of myocardial hypertrophy markers (ANP, BNP, and ß-MHC) were detected by quantitative real-time polymerase chain reaction (qRT-PCR). Western blot (WB) was conducted to verify the expressions of myocardial fibrosis-associated proteins (MyHc, Collagen Ⅰ, and TGF-ß1) and oxidative stress (OS) proteins (HO-1 and Nrf2). The markers of fibrosis, hypertrophy, NLRP3 inflammasome and OS in cardiomyocytes were evaluated by qRT-PCR, western blot (WB), enzyme-linked immunosorbent assay (ELISA), and cellular immunofluorescence, respectively. Furthermore, pharmacological intervention on sirtuin-1 (SIRT1) was performed to clarify the function of SIRT1 in Rg3-mediated effects. RESULTS: Rg3 dose-dependently attenuated the Ang II-induced myocardial hypertrophy and fibrosis. What's more, Rg3 markedly inhibited NLRP3-ASC-Caspase1 inflammasome and OS (reflected by SOD, MDA, HO-1, and Nrf2) in cardiomyocytes treated with Ang II. Mechanistically, Rg3 attenuated NF-κB activation and promoted SIRT1 expression. Inhibiting SIRT1 (by AGK2) mostly reversed Rg3-mediated effects against Ang II-induced myocardial hypertrophy and fibrosis. In the TAC rat model, administration of Rg3 mitigated myocardial hypertrophy and fibrosis through pressing overproduced inflammation and OS. CONCLUSION: Rg3 prevents Ang II-induced myocardial hypertrophy via inactivating NLRP3 inflammasome and oxidative stress by modulating the SIRT1/NF-κB pathway.

Juzentaihoto extract suppresses adipocyte hypertrophy and improves hyperglycemia in KKAy mice.

Juzentaihoto is a herbal medicine with reported anti-inflammatory effects, and it is predicted to improve inflammation and insulin sensitivity within obesity. In the present study, juzentaihoto hot water extract (JTT) was administered to obese type 2 diabetic model mice (KKAy) for 56 days. In addition, the effects of JTT on the adipose tissue, glucose metabolism, and blood lipids were evaluated for examining its impact on insulin sensitivity and obesity. As a result of JTT administration, KKAy mice exhibited suppressed adipocyte hypertrophy, decreased the mRNA levels of tumor necrosis factor α, and increased the mRNA levels of adiponectin in epididymal fat tissue. In addition, fasting blood glucose levels, blood triglyceride, and total cholesterol decreased. In summary, these data indicated that JTT administration suppressed the production of inflammatory cytokines and increased adiponectin levels in the adipose tissue. Therefore, with improved insulin sensitivity, blood glucose, and lipid decreased.

Development of a simple osteoarthritis model useful to predict in vitro the anti-hypertrophic action of drugs.

Osteoarthritis (OA) is characterized by cartilage degradation, inflammation, and hypertrophy. Therapies are mainly symptomatic and aim to manage pain. Consequently, medical community is waiting for new treatments able to reduce OA process. This study aims to develop an in vitro simple OA model useful to predict drug ability to reduce cartilage hypertrophy. Human primary OA chondrocytes were incubated with transforming growth factor beta 1 (TGF-ß1). Hypertrophy was evaluated by Runx2, type X collagen, MMP13, and VEGF expression. Cartilage anabolism was investigated by Sox9, aggrecan, type II collagen, and glycosaminoglycan expression. In chondrocytes, TGF-ß1 increased expression of hypertrophic genes and activated canonical WNT pathway, while it decreased dramatically cartilage anabolism, suggesting that this treatment could mimic some OA features in vitro. Additionally, EZH2 inhibition, that has been previously reported to decrease cartilage hypertrophy and reduce OA development in vivo, attenuated COL10A1 and MMP13 upregulation and SOX9 downregulation induced by TGF-ß1 treatment. Similarly, pterosin B (an inhibitor of Sik3), and DMOG (a hypoxia-inducible factor prolyl hydroxylase which mimicks hypoxia), repressed the expression of hypertrophy markers in TGF-ß stimulated chondrocytes. In conclusion, we established an innovative OA model in vitro. This cheap and simple model will be useful to quickly screen new drugs with potential anti-arthritic effects, in complementary to current inflammatory models, and should permit to accelerate development of efficient treatments against OA able to reduce cartilage hypertrophy.

Pyrogallol-Phloroglucinol-6,6-Bieckol Alleviates Obesity and Systemic Inflammation in a Mouse Model by Reducing Expression of RAGE and RAGE Ligands.

Ecklonia cava (E. cava) can alleviate diet-induced obesity in animal models, and phlorotannins contained in E. cava help prevent hypertrophy-induced adipocyte differentiation. Receptor for advanced glycation end-products (RAGE) is well known to induce hypertrophy of visceral fat and to trigger inflammation substantially. While the relationship between RAGE and obesity and inflammation has been well-characterized, few studies describe the effects of phlorotannin on RAGE. In this study, we investigated the anti-obesity effects of pyrogallol-phloroglucinol-6,6-bieckol (PPB)-a single compound from the ethanoic extract of E. cava-mediated by a reduction in the inflammation caused by RAGE and RAGE ligands. In visceral fat, PPB (i) significantly inhibited RAGE ligands, (ii) reduced the expression of RAGE, and (iii) reduced the binding ratio between RAGE and RAGE ligands. Under lower expression of RAGE, RAGE ligands and their cognate binding, the differentiation of macrophages found in visceral fat into M1-type-the pro-inflammatory form of this immune cell-was reduced. As the M1-type macrophage decreased, pro-inflammatory cytokines, which cause obesity, decreased in visceral fat. The results of this study highlight the anti-obesity effects of PPB, with the effects mediated by reductions in RAGE, RAGE ligands, and inflammation.

Hypertrophic muscle growth and metabolic efficiency were impaired by chronic heat stress, improved by zilpaterol supplementation, and not affected by ractopamine supplementation in feedlot lambs1.

Feedlot performance is reduced by heat stress and improved by ß adrenergic agonists (ßAA). However, the physiological mechanisms underlying these outcomes are not well characterized, and anecdotal reports suggest that ßAA may confound the effects of heat stress on wellbeing. Thus, we sought to determine how heat stress and ßAA affect growth, metabolic efficiency, and health indicators in lambs on a feedlot diet. Wethers (38.6 ± 1.9 kg) were housed under thermoneutral (controls; n = 25) or heat stress (n = 24) conditions for 21 d. In a 2 × 3 factorial, their diets contained no supplement (unsupplemented), ractopamine (ß1AA), or zilpaterol (ß2AA). Blood was collected on days -3, 3, 9, and 21. On day 22, lambs were harvested and ex vivo skeletal muscle glucose oxidation was determined to gauge metabolic efficiency. Feet and organ tissue damage was assessed by veterinary pathologists. Heat stress reduced (P < 0.05) feed intake by 21%, final bodyweight (BW) by 2.6 kg, and flexor digitorum superficialis (FDS) muscle mass by 5%. ß2AA increased (P < 0.05) FDS mass/BW by 9% and average muscle fiber area by 13% compared with unsupplemented lambs. Blood lymphocytes and monocytes were greater (P < 0.05) in heat-stressed lambs, consistent with systemic inflammation. Plasma insulin was 22% greater (P < 0.05) and glucose/insulin was 16% less (P < 0.05) in heat-stressed lambs than controls. Blood plasma urea nitrogen was increased (P < 0.05) by heat stress on day 3 but reduced (P < 0.05) on days 9 and 21. Plasma lipase and lactate dehydrogenase were reduced (P < 0.05) by heat stress. Glucose oxidation was 17% less (P < 0.05) in muscle from heat-stressed lambs compared with controls and 15% greater (P < 0.05) for ß2AA-supplemented compared with unsupplemented lambs. Environment and supplement interacted (P < 0.05) for rectal temperature, which was increased (P < 0.05) by heat stress on all days but more so (P < 0.05) in ß2AA-supplemented lambs on days 4, 9, and 16. Heat stress increased (P < 0.05) the frequency of hoof wall overgrowth, but ßAA did not produce any pathologies. We conclude that reduced performance in heat-stressed lambs was mediated by reduced feed intake, muscle growth, and metabolic efficiency. ß2AA increased muscle growth and improved metabolic efficiency by increasing muscle glucose oxidation, but no such effects were observed with ractopamine. Finally, ßAA supplementation was not detrimental to health indicators in this study, nor did it worsen the effects of heat stress.

Effectiveness and safety of Chinese herbal medicine for pediatric adenoid hypertrophy: A meta-analysis.

OBJECTIVE: Chinese herbal medicine has been gradually used to treat pediatric adenoid hypertrophy. This meta-analysis were conducted to evaluate the clinical efficacy and safety of Chinese herbal medicine in the treatment of pediatric adenoid hypertrophy. METHODS: Randomized controlled trials involving Chinese herbal medicine in the treatment of pediatric adenoid hypertrophy were identified from Cochrane Central Register of Controlled Trials, PubMed, EMBASE, Chinese National Knowledge Infrastructure, Chinese Biomedical Database, Wanfang Database and VIP Information Database. The methodological quality of trials was evaluated with Cochrane Handbook criteria, and the Cochrane Collaboration's Review Manager 5.3 software was used for Meta-analysis. RESULTS: A total of 13 valid articles involving 1038 patients were included. The meta-analysis showed that: Compared with western medicine treatment, Chinese herbal medicine significantly improved clinical efficacy (RR = 1.33, 95% CI [1.24,1.43]), and significantly decreased A/N ratio (MD = -0.04,95%CI [-0.05,-0.03]). Chinese herbal medicine also prominently improved the quality of life (MD = -4.77,95%CI [-8.35,-1.20]). Meanwhile, it dramatically improved snoring (MD = -0.46,95%CI [-0.62,-0.30]); mouth breathing (MD = -0.52,95%CI [-0.66,-0.39]); nasal obstruction (MD = -0.56,95%CI [-0.68,-0.45]). CONCLUSION: Chinese herbal medicine has good clinical efficacy and safety on pediatric adenoid hypertrophy, which need to be confirmed by high quality, multiple-centre, large sample randomized controlled trials.

Effect of osthole on advanced glycation end products-induced renal tubular hypertrophy and role of klotho in its mechanism of action.

BACKGROUND: Osthole has been widely reported to have pharmacological activities such as anti-cancer, anti-inflammation and anti-hyperlipidemic effects. Klotho was identified as an anti-senescence protein in a variety of tissues. Loss of klotho has been associated with chronic kidney disease. However, potential roles and molecular events for osthole and klotho in diabetic nephropathy remain unclear. PURPOSE: In the current study, we undertook to study the effect of osthole on klotho expression in advanced glycation end products (AGE)-cultured human renal proximal tubular cells, and to investigate the molecular mechanisms of osthole and exogenous klotho against AGE-induced renal tubular hypertrophy. METHODS: Cell viability was elucidated by MTT assay. Protein expression was measured by Western blotting. mRNA level was analyzed by real-time PCR. Cellular hypertrophy growth was evaluated by hypertrophy index. Relative cell size was detected by flow cytometry. RESULTS: We found that raising the ambient AGE concentration causes a dose-dependent decrease in klotho synthesis. Osthole significantly increased AGE-inhibited klotho mRNA and protein expression. Osthole and exogenous klotho treatments significantly attenuated AGE-induced Janus kinase 2 (JAK2)-signal transducers and activators of transcription 1 (STAT1) and STAT3 activation. Moreover, protein levels of suppressor of cytokine signaling 1 (SOCS1) and SOCS3 were augmented by osthole and exogenous klotho. The abilities of osthole and exogenous klotho to reverse AGE-induced cellular hypertrophy were verified by the observation that osthole and exogenous klotho inhibited p21Waf1/Cip1/collagen IV/RAGE expression, total protein content, and cell size. CONCLUSION: Consequently, we found that osthole attenuated AGE-induced renal tubular hypertrophy via induction of klotho expression and suppression of the JAK2-STAT1/STAT3 signaling. These results also showed that klotho might be used as a unique molecular target for the treatment of diabetic nephropathy.

Meta-analysis of Chinese medicine in the treatment of adenoidal hypertrophy in children.

OBJECTIVE: To evaluate the efficacy and safety of Chinese medicine in the treatment of adenoid hypertrophy in children. METHOD: Screening standard articles, extracting relevant data from meta-analysis, were analyzed by Revman5.1 software, by searching PubMed, Medline, VIP, Wan Fang and Chinese HowNet database 2006-2016 in traditional Chinese medicine treatment of children with adenoid literature. RESULTS: 206 articles met the inclusion criteria, of which ten were selected and included in the meta-analysis, and there were 803 patients. The results showed that the remission rate of the Chinese medicine treatment group was better than that of the Western medicine group. The combined effect of the amount of OR 2.06, 95% Cl (1.45, 2.96) and the combined effect of the amount of the test Z = 4.12, P < 0.00001 showed the recurrence of the disease was lower in traditional Chinese medicine treatment group than the Western medicine group. The combined effect of the amount of OR 3.05, 95% Cl (2.11, 4.56) and the combined effect of the amount of the test Z = 5.86, P < 0.00001 showed the total effective rate is high in the traditional Chinese medicine treatment group than the Western medicine group. The difference between the combined effect of the amount of OR 2.79, 95% Cl (1.78, 5.03) and the combined effect of the amount of the test of Z = 4.54, P < 0.00001 was statistically significant, which showed the treatment effect of Chinese medicine group is obviously better than the Western medicine group. CONCLUSION: The use of Chinese medicine for the treatment of children with adenoid hypertrophy has good clinical efficacy.

Fucosylated chondroitin sulfate from Isostichopus badionotus alleviates metabolic syndromes and gut microbiota dysbiosis induced by high-fat and high-fructose diet.

Fucosylated chondroitin sulfate from Isostichopus badionotus (fCS-Ib) is a kind of sulfated polysaccharides with well-repeated structure. In our former publications, fCS-Ib has been reported to be a functional food ingredient with hypoglycemic and antilipemic activities. However, there is no systematic study to investigate the effects of fCS-Ib on metabolic syndromes. In the present study, C57BL/6 mice fed on a high-fat and high sucrose diet (HFSD) for 6 weeks was used to cause metabolic syndromes. The final results showed that fCS-Ib alleviated obesity, hyperlipidemia, hyperglycemia, inflammation, liver steatosis, and adipocyte hypertrophy caused by HFSD. Meanwhile, fCS-Ib showed powerful effects on moderating gut microbiota dysbiosis in the HFSD-fed mice. Supplement of fCS-Ib could reduce ratio of Firmicutes to Bacteroidetes by decreasing abundance of Lachnospiraceae and Allobaculum while increasing abundance of Porphyromonadaceae, Barnesiella, and Bacteroides. Our results showed that fCS-Ib could be further developed as a potential pharmaceutical agent to prevent metabolic syndromes and gut microbiota dysbiosis.

Agkistrodon ameliorates pain response and prevents cartilage degradation in monosodium iodoacetate-induced osteoarthritic rats by inhibiting chondrocyte hypertrophy and apoptosis.

ETHNOPHARMACOLOGICAL RELEVANCE: Osteoarthritis (OA), characterized by joint pain and cartilage degradation, is the most common form of joint disease worldwide but with no satisfactory therapy available. The ethanol extract of Agkistrodon acutus (EAA) has been widely used as a traditional Chinese medicine (TCM) for the treatment of arthralgia and inflammatory diseases, but there is no report regarding its efficacy on OA to date. Here, we determined the effects of EAA on the pain behavior and cartilage degradation in vivo and clarified its target genes and proteins associated with chondrocyte hypertrophy and apoptosis in vitro. MATERIALS AND METHODS: In vivo OA model was established by intra-articular injection (1.5 mg) of monosodium iodoacetate (MIA) into rats and weekly treated by intra-articular administration of EAA at a dose range from 0.3 to 0.9 g/kg for four weeks. The pain behavior parameters, thermal withdrawal latency (TWL) and mechanical withdrawal threshold (MWT) were tested before and after the treatment. Then histopathologic, immunohistochemical and TUNEL analyses of the articular cartilage were conducted, followed by Mankin's scoring. In vitro, the effects of EAA on chondrocytes were evaluated via assays of cell viability, immunofluorescence, real time PCR, and Western blot. UPLC-MS was applied to determine the chemical composition of EAA. RESULTS: The animal data showed that EEA not only attenuated the pain hypersensitivity but also blocked the cartilage degeneration by improving chondrocyte survival and suppressing chondrocyte apoptosis at a dose-dependent manner in OA rats. Furthermore, EAA remarkably restored the abnormal expression of collagen type II (Col2) and matrix metalloproteinase-13 (MMP13) in cartilage of OA rats. The cellular data showed that EAA significantly increased the cell viability of chondrocytes against OA-like damage and restored the abnormal expressions of Col2 and MMP13 in damaged chondrocytes. The molecular data showed that EAA significantly restored the abnormal mRNA expressions of Col2, Col10, MMP2 and MMP13 as well as the abnormal protein expressions of MMP13, PARP (total and cleaved) in chondrocytes under pathological condition. UPLC-MS analysis showed the known main components of EAA, including amino acides (glycine, L-aspartic acid, L-glutamic acid, and L-hydroxyproline), nucleoside (uridine), purines (xanthine and hypoxanthine), and pyrimidine (uracil). CONCLUSIONS: Our data demonstrate that EAA exerts antinociceptive and chondroprotective effects on OA through suppressing chondrocyte hypertrophy and apoptosis with restoration of the molecular expressions of anabolism and catabolism in chondrocytes. It provides a promising TCM candidate of novel agent for OA therapy.

Secretoneurin suppresses cardiac hypertrophy through suppression of oxidant stress.

The neuropeptide secretoneurin (SN) plays protective roles in myocardial ischemia. In the present study, the effect of SN in cardiac hypertrophy was investigated. We observed that, in isoproterenol (ISO) treatment induced cardiac or cardiomyocytes hypertrophy, a marked increase in the expression of endogenous SN in mouse plasma, myocardium and primary-cultured cardiomyocytes occurs. In hypertrophic mice, the heart size, heart weight/body weight (HW/BW) ratio, cardiomyocyte size, and atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) expression were significantly higher than those in controls but were effectively suppressed by SN gene therapy. Similarly, the protective effects of SN were also observed in cultured cardiomyocytes following ISO treatment. SN significantly increased the activity of catalase and superoxide dismutase (SOD) in parallel with the decrease in reactive oxygen species levels in cardiomyocytes. We observed that SN evoked the activation of all of the AMPK, P38/MAPK and ERK/MAPK pathways in cardiomyocytes, but pretreatment with only AMPK inhibitor (compound C) and ERK1/2/MAPK inhibitor (PD98059) counteracted the protective effects of SN against cardiomyocyte hypertrophy and the suppressive effects of SN on oxidant stress in cardiomyocytes. These results indicated that endogenous SN is induced in hypertrophic cardiomyocytes, and may play a protective role in the pathogenesis of cardiac hypertrophy. These results suggest that exogenous SN supplementation protects the cardiac hypertrophy induced by ISO treatment through the activation of AMPK and ERK/MAPK pathways, thus upregulating antioxidants and suppressing oxidative stress.

EFFECT OF ASTRAGALOSIDE ON VITAMIN D-RECEPTOR EXPRESSION AFTER ENDOTHELIN-1-INDUCED CARDIOMYOCYTE INJURY.

BACKGROUND: Astragaloside, which is one of the main components of Astragalus membranaceus, has been widely used in the treatment of congestive heart failure in China, and it can protect cardiomyocytes. Its mechanism of action remains unclear. Therefore, the present study was carried out to investigate the influence of astragaloside on rat cardiomyocytes stimulated with endothelin-1 (ET-1), and explored the underlying mechanism. MATERIALS AND METHODS: ET-1 was used to stimulate primary rat cardiomyocytes and establish a cardiomyocyte hypertrophy model. Different astragaloside doses were administered in combination with ET-1. Cardiomyocyte hypertrophy and apoptosis were examined using transmission electron microscopy (TEM) and flow cytometry, respectively. The molecular mechanism was explored by analyzing the mRNA of the vitamin D receptor (VDR), cytochrome P450 family 27 subfamily B member 1(CYP27B), cytochrome P450 family 24 subfamily A member 1(CYP24A) and renin mRNA levels by quantificational real-time polymerase chain reaction(qRT-PCR). RESULTS: Rat cardiomyocyte hypertrophy model was established successfully. Astragaloside administration significantly affected cell apoptosis and significantly inhibited ET-1-induced cardiomyocyte hypertrophy in a dose-dependent manner. Astragaloside treatment affected the expression of signaling molecules in the vitamin D axis. CONCLUSION: Astragaloside inhibits ET-1-induced cardiomyocyte hypertrophy. This effect can be reversed by regulating the levels of the relevant factors in the vitamin D axis.

Traditional Chinese Medication Qiliqiangxin Protects Against Cardiac Remodeling and Dysfunction in Spontaneously Hypertensive Rats.

Qiliqiangxin (QLQX), a traditional Chinese herbs medication, exerted protective effect in chronic heart failure patients in a multicenter randomized double-blind study. QLQX has also been found to improve cardiac function and reduce cardiac fibrosis in spontaneously hypertension animal model. However, the effect of longterm treatment with QLQX in such a condition and the related molecular mechanisms remain largely unknown. In the present study, thirteen-week-old spontaneously hypertensive rats (SHRs) were treated by daily intragastric administration of QLQX or saline for one year. Echocardiography, electron microscopy, and Masson's trichrome staining were used to determine cardiac function, mitochondria ultrastructure, and cardiac fibrosis, respectively. Quantitative reverse transcription polymerase chain reactions (qRT-PCRs) and Western blotting were used to determine gene expressions. We found that QLQX significantly improved cardiac function and reduced gene markers of pathological hypertrophy including ANP, BNP, and Myh7. QLQX also attenuated cardiac fibrosis and apoptosis in SHRs as evidenced by downregulation of α-SMA, collagen I, collagen III, and TGF-ß expressions and reduction of Bax to Bcl-2 ratio. Moreover, the damage of mitochondrial ultrastructure was greatly improved and the reduction of PPAR-α, PPAR-γ, and PGC-1α expression levels was significantly restored in SHRs by treatment with QLQX. In conclusion, longterm treatment with QLQX protects against cardiac remodeling and dysfunction in hypertension by increasing PPARs and PGC-1α.