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1.
BMC Pharmacol Toxicol ; 25(1): 15, 2024 Feb 05.
Artículo en Inglés | MEDLINE | ID: mdl-38317260

RESUMEN

BACKGROUND: Zinc Gluconate (ZG) is a safe and effective supplement for zinc. However, there is limited research on the optimal dosage for intravenous injection and the safety evaluation of animal models for ZG. This study aims to determine the safe dose range of ZG for intravenous injection in C57BL/6J mice. METHODS: A Dose titration experiment was conducted to determine the LD50 and 95% confidence interval (95%CI) of ZG in mice. Based on the LD50, four sub-lethal doses (SLD) of ZG were evaluated. Following three injections of each SLD and monitoring for seven days, serum zinc levels were measured, and pathological changes in the liver, kidney, and spleen tissues of mice were determined by histological staining. RESULTS: The dose titration experiment determined the LD50 of ZG in mice to be 39.6 mg/kg, with a 95%CI of 31.8-49.3 mg/kg. There was a statistically significant difference in the overall serum zinc levels (H = 36.912, P < 0.001) following SLD administration. Pairwise comparisons showed that the serum zinc levels of the 1/2 LD50 and 3/4 LD50 groups were significantly higher than those of the control group (P < 0.001); the serum zinc level of the 3/4 LD50 group was significantly higher than those of the 1/8 LD50 and 1/4 LD50 groups (P < 0.05). There was a positive correlation between the different SLDs of ZG and the serum zinc levels in mice (rs = 0.973, P < 0.001). H&E staining showed no significant histological abnormalities or lesions in the liver, kidney, and spleen tissues of mice in all experimental groups. CONCLUSION: The appropriate dose range of ZG for intravenous injection in C57BL/6J mice was clarified, providing a reference for future experimental research.


Asunto(s)
Gluconatos , Riñón , Zinc , Ratones , Animales , Ratones Endogámicos C57BL , Dosificación Letal Mediana , Zinc/toxicidad
4.
Brain Res Bull ; 199: 110667, 2023 07.
Artículo en Inglés | MEDLINE | ID: mdl-37192717

RESUMEN

The complement system is crucial to the innate immune system. It has the function of destroying pathogens by activating the classical, alternative, and lectin pathways. The complement system is important in nervous system diseases such as cerebrovascular and neurodegenerative diseases. Activation of the complement system involves a series of intercellular signaling and cascade reactions. However, research on the source and transport mechanisms of the complement system in neurological diseases is still in its infancy. Studies have increasingly found that extracellular vesicles (EVs), a classic intercellular communication paradigm, may play a role in complement signaling disorders. Here, we systematically review the EV-mediated activation of complement pathways in different neurological diseases. We also discuss the prospect of EVs as future immunotherapy targets.


Asunto(s)
Vesículas Extracelulares , Enfermedades Neurodegenerativas , Humanos , Vesículas Extracelulares/metabolismo , Proteínas del Sistema Complemento/metabolismo , Enfermedades Neurodegenerativas/metabolismo , Comunicación Celular , Transducción de Señal
5.
Fitoterapia ; 168: 105520, 2023 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-37121406

RESUMEN

Four new diastereoisomeric neolignan glycosides (1-4) along with nine known lignan glycosides (5-13) were isolated from the root bark of Lycium chinense Mill. Their structures with absolute configurations were elucidated on the basis of NMR spectroscopy, ECD, Mo2(OAc)4-induced ECD spectra, enzymatic hydrolysis and acid hydrolysis. The isolated compounds were evaluated for their α-glucosidase inhibitory activity. Compounds 8 and 13 exhibited moderate inhibitory activities against α-glucosidase with IC50 values of 26.82 ± 2.71 and 43.14 ± 2.81 µg/mL.


Asunto(s)
Lignanos , Lycium , Lignanos/farmacología , Glicósidos/química , Lycium/química , alfa-Glucosidasas , Estructura Molecular , Corteza de la Planta/química
6.
Medicine (Baltimore) ; 101(47): e31804, 2022 Nov 25.
Artículo en Inglés | MEDLINE | ID: mdl-36451468

RESUMEN

BACKGROUND: Parkinson disease (PD) is a worldwide spread neurodegenerative disorder. Dopamine replacement therapy is currently the mainstream treatment, which can alleviate the symptoms but induces motor complications. Acupuncture therapy is effective for PD. As a form of acupuncture, the abdominal acupuncture has been used to relieve symptoms in patients with PD, but its effectiveness and safety have not yet reached a definitive conclusion. Therefore, this systematic review and meta-analysis protocol is planned to evaluate the efficacy and safety of abdominal acupuncture for PD patients. METHODS: Six English databases (PubMed, Web of Science, MEDLINE, EMBASE, Springer Cochrane Library, and WHO International Clinical Trials Registry Platform) and 4 Chinese databases (Wan Fang Database, Chinese Scientific Journal Database, China National Knowledge Infrastructure Database, and Chinese Biomedical Literature Database) will be searched normatively according to the rule of each database from the inception to August 20, 2022. Two reviewers will independently conduct article selection, data collection, and risk of bias evaluation. Any disagreement will be resolved by discussion with the third reviewer. Either the fixed-effects or random-effects model will be used for data synthesis based on the heterogeneity test. Either the fixed-effects or random-effects model will be used for data synthesis based on the heterogeneity test. The analysis will be conducted by RevMan 5.3 software according to Cochrane Handbook. RESULTS: The aim of this systematic review is to provide high-quality evidence to assess the efficacy and safety of abdominal acupuncture for patients in Parkinson's disease. The efficacy and safety of abdominal acupuncture for PD will be comprehensively assessed from the outcomes, including the effectiveness rate. The Unified Parkinson Disease Rating Scale (UPDRS) and Webster scale, Motor symptom scores utilizing UPDRS III scale, Dopamine (DA) content, and Nonmotor symptom scores employing UPDRS I scale, Activities of daily living using UDPRS II; Complications of treatment applying UPDRS IV, antioxidant ability: super oxide dismutase activity and Lipide Peroxide (LPO) content, Content of inflammatory cytokines, tumor necrosis factor-α and interleukin-1ß, and adverse events as the secondary outcome. CONCLUSION: This systematic review will explore whether abdominal acupuncture is an effective and safe intervention for patients in Parkinson's disease.


Asunto(s)
Terapia por Acupuntura , Enfermedad de Parkinson , Humanos , Enfermedad de Parkinson/terapia , Dopamina , Actividades Cotidianas , Revisiones Sistemáticas como Asunto , Metaanálisis como Asunto , Terapia por Acupuntura/efectos adversos
7.
Phytomedicine ; 107: 154460, 2022 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-36182798

RESUMEN

BACKGROUND: Qingchang Wenzhong Decoction (QCWZD), a chinese herbal prescription, is widely used for ulcerative colitis (UC). Nevertheless, the active ingredients and mechanism of QCWZD in UC have not yet been explained clearly. PURPOSE: This research focuses on the identification of the effective ingredients of QCWZD and the prediction and verification of their potential targets. METHODS: The UC mice were established by adding 3.0% dextran sulfate sodium (DSS) to sterile water for one week. Concurrently, mice in the treatment group were gavage QCWZD or mesalazine. LC-MS analyzed the main components absorbed after QCWZD treatment, and network pharmacology predicted their possible targets. ELISA, qPCR, immunohistochemistry and immunofluorescence experiments were used to evaluate the colonic inflammation level and the intestinal barrier completeness. The percentage of Th17 and Treg lymphocytes was detected by flow cytometry. RESULTS: After QCWZD treatment, twenty-seven compounds were identified from the serum. In addition, QCWZD treatment significantly reduced the increased myeloperoxidase (MPO) and inflammatory cell infiltration caused by DSS in the colonic. In addition, QCWZD can reduce the secretion of inflammatory factors in serum and promote the expression of mRNAs and proteins of occludin and ZO-1. Network pharmacology analysis indicated that inhibiting IL-6-STAT3 pathway may be necessary for QCWZD to treat UC. Flow cytometry analysis showed that QCWZD can restore the normal proportion of Th17 lymphocytes in UC mice. Mechanistically, QCWZD inhibited the phosphorylation of JAK2-STAT3 pathway, reducing the transcriptional activation of RORγT and IL-17A. CONCLUSIONS: Overall, for the first time, our work revealed the components of QCWZD absorbed into blood, indicated that the effective ingredients of QCWZD may inhibit IL-6-STAT3 pathway and inhibit the differentiation of Th17 lymphocytes to reduce colon inflammation.


Asunto(s)
Colitis Ulcerosa , Animales , Colitis Ulcerosa/inducido químicamente , Colitis Ulcerosa/tratamiento farmacológico , Colitis Ulcerosa/metabolismo , Colon , Sulfato de Dextran , Modelos Animales de Enfermedad , Inflamación/metabolismo , Interleucina-17/metabolismo , Interleucina-6/metabolismo , Mesalamina/metabolismo , Mesalamina/farmacología , Mesalamina/uso terapéutico , Ratones , Ratones Endogámicos C57BL , Miembro 3 del Grupo F de la Subfamilia 1 de Receptores Nucleares/metabolismo , Ocludina/metabolismo , Peroxidasa/metabolismo , Células Th17 , Agua
8.
Materials (Basel) ; 15(15)2022 Aug 05.
Artículo en Inglés | MEDLINE | ID: mdl-35955329

RESUMEN

Phosphorus slag (PS), an industrial waste slag, has been used in geopolymers because it is rich in silicon and calcium. The poor performance of phosphorus slag-based geopolymer is due to its aluminum deficiency. In this work, low-calcium fly ash, treated by a wet-grinding process, named wet-grinding ultrafine fly ash (WUFA) was used as an Al supplement to replace some of the phosphorus slag, and the wet-grinding, ultrafine fly ash-phosphorus slag (WUFA-PS)-based geopolymer was prepared. The effects of the substitution amount of WUFA and the activator dosage on the hydration properties, mechanical properties, pore structure and SEM of the WUFA-PS geopolymer were discussed in detail. The results indicate that WUFA and more activators contribute to the Al and high alkalinity environment, which positively induces the production of more geopolymer gels, thus releasing more heat and optimizing the pore structure of the matrix. The compressive strength increased by up to 28.1%. The enhanced performance of the WUFA-PS-based geopolymer may also arise from the filling effect and activity improvement of WUFA. This study has proved the feasibility of preparing a geopolymer by blending wet-grinding ultrafine fly ash and phosphorus slag and has provided references for the ratio and performance evaluation of WUFA-PS-based geopolymer concrete.

9.
J Patient Exp ; 9: 23743735221113160, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35860789

RESUMEN

The COVID-19 pandemic caused healthcare systems and patients to cancel or postpone healthcare services, particularly preventive care. Many patients still have not received these services raising concerns about the potential for preventable morbidity and mortality. At Sutter Health, a large integrated healthcare system in Northern California, we conducted a population-based email survey in August 2020 to evaluate perceptions and preferences about where, when, and how healthcare is delivered during the COVID-19 pandemic. In total, 3351 patients completed surveys, and 42.6% reported that they would "wait until they felt safe" before receiving a colonoscopy as compared to 22.4% for a mammogram. The doctor's office was the most common preferred location for receiving vaccines/shots (79.9%), though many also reported preferring an outdoor setting or in a car (63.7%). With over 40% of patients reporting that they would "wait until they feel safe" for a colonoscopy, healthcare systems could focus on promoting other evidence-based options such a fecal-occult blood test to ensure timely colon cancer screening.

10.
Heliyon ; 8(7): e09940, 2022 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-35865979

RESUMEN

Elucidating the pharmaceutical mechanisms behind traditional Chinese medicine (TCM) is the key to promote its modernization process. In China, soaking TCM in liquor has a history of thousands of years, and many TCMs have to be processed into liquor before they can be used to treat diseases. Chinese liquor (Baijiu) contains more than 2,000 trace components, the interaction mechanism between TCM and Baijiu still remains unclear, making TCM a "mystery". The TCM industry commonly employs chromatographic and spectrographic technology to investigate the redox activity of TCM substances. However, only investigating the redox differences in specific active substances cannot provide a complete understanding of the redox activity of TCM substances. Thus, we employed the electrochemical approach to study the overall redox activity of substances in TCM in situ. The key result is that the redox substances in Baijiu function as a mediator for the redox reaction of Polygonum multiflorum extract. The redox efficiency of the extract is enhanced because of the faster electron transferability of the redox mediator in Baijiu.

11.
Signal Transduct Target Ther ; 7(1): 192, 2022 06 22.
Artículo en Inglés | MEDLINE | ID: mdl-35729157

RESUMEN

Folic acid, served as dietary supplement, is closely linked to one-carbon metabolism and methionine metabolism. Previous clinical evidence indicated that folic acid supplementation displays dual effect on cancer development, promoting or suppressing tumor formation and progression. However, the underlying mechanism remains to be uncovered. Here, we report that high-folate diet significantly promotes cancer development in mice with hepatocellular carcinoma (HCC) induced by DEN/high-fat diet (HFD), simultaneously with increased expression of methionine adenosyltransferase 2A (gene name, MAT2A; protein name, MATIIα), the key enzyme in methionine metabolism, and acceleration of methionine cycle in cancer tissues. In contrast, folate-free diet reduces MATIIα expression and impedes HFD-induced HCC development. Notably, methionine metabolism is dynamically reprogrammed with valosin-containing protein p97/p47 complex-interacting protein (VCIP135) which functions as a deubiquitylating enzyme to bind and stabilize MATIIα in response to folic acid signal. Consistently, upregulation of MATIIα expression is positively correlated with increased VCIP135 protein level in human HCC tissues compared to adjacent tissues. Furthermore, liver-specific knockout of Mat2a remarkably abolishes the advocating effect of folic acid on HFD-induced HCC, demonstrating that the effect of high or free folate-diet on HFD-induced HCC relies on Mat2a. Moreover, folate and multiple intermediate metabolites in one-carbon metabolism are significantly decreased in vivo and in vitro upon Mat2a deletion. Together, folate promotes the integration of methionine and one-carbon metabolism, contributing to HCC development via hijacking MATIIα metabolic pathway. This study provides insight into folate-promoted cancer development, strongly recommending the tailor-made folate supplement guideline for both sub-healthy populations and patients with cancer expressing high level of MATIIα expression.


Asunto(s)
Ácido Fólico , Metionina Adenosiltransferasa , Animales , Dieta , Ácido Fólico/farmacología , Neoplasias Hepáticas Experimentales/genética , Neoplasias Hepáticas Experimentales/metabolismo , Neoplasias Hepáticas Experimentales/patología , Metionina/metabolismo , Metionina Adenosiltransferasa/genética , Metionina Adenosiltransferasa/metabolismo , Ratones
12.
Phytother Res ; 36(6): 2660-2676, 2022 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-35545249

RESUMEN

The excessive deposition of extracellular matrix (ECM) is the main characteristic of liver fibrosis, and hepatic stellate cells (HSCs) are the main source of ECM. The removal of activated HSCs has a reversal effect on liver fibrosis. Western blot and MTT analysis indicated that curcumol could relieve hepatic fibrosis by promoting HSCs receptor-interacting protein kinase 1/3 (RIP1/RIP3)-dependent necroptosis. Importantly, autophagy flow was monitored by constructing the mRFP-GFP-LC3 plasmid, and it was found that curcumol cleared activated HSCs in a necroptosis manner that was dependent on autophagy. Our study suggested that the activation of necrosome formed by RIP1 and RIP3 depended on Atg5, and that autophagosomes were also necessary for curcumol-induced necroptosis. Furthermore, microscale thermophoresis and co-immunoprecipitation assay results proved that curcumol could target Sirt1 to regulate autophagy by reducing the acetylation level of Atg5. The HSCs-specific silencing of Sirt1 exacerbated CCl4 -induced liver fibrosis in mice. The deacetylation of Atg5 not only accelerated the accumulation of autophagosomes but also enhanced the interaction between Atg5 and RIP1/RIP3 to induce necroptosis. Overall, our study indicated that curcumol could activate Sirt1 to promote Atg5 deacetylation and enhanced its protein-protein interaction function, thereby inducing autophagy and promoting the necroptosis of HSCs to reduce liver fibrosis.


Asunto(s)
Células Estrelladas Hepáticas , Lisina , Animales , Autofagia , Cirrosis Hepática/inducido químicamente , Cirrosis Hepática/tratamiento farmacológico , Lisina/metabolismo , Ratones , Necroptosis , Sesquiterpenos , Sirtuina 1/metabolismo
13.
Artículo en Inglés | MEDLINE | ID: mdl-35586687

RESUMEN

Objective: This study aims to evaluate the clinical effects of Ling Gui Zhu Gan formula (LGZG), a famous TCM formula, for the management of serum lipids and obesity and preliminarily elucidates the bioactive components and the potential mechanism. Methods: Cluster analysis was adopted to investigate the TCM herbs and their frequency of occurrence for treating hyperlipidemia and obesity in an academic experience database of Chinese famous TCM doctors (http://www.gjmlzy.com:83). Then, relevant randomized controlled trials (RCTs) about LGZG supplementation in improving lipid levels and obesity were retrieved and analyzed. Lastly, the integration of network pharmacology, as well as greedy algorithms, which are theoretically well founded for the set cover in computer science, was exploited to identify the bioactive components of LGZG and to reveal potential mechanisms for attenuation or reversal of hyperlipidemia and obesity. Results: Based on the cluster analysis of 104 cases in TCM academic experience database, four TCM herbs in LGZG showed high-use frequency for treating hyperlipidemia and obesity. Meta-analysis on 19 randomized controlled trials (RCTs) with 1716 participants indicated that LGZG supplementation significantly decreased the serum levels of total triglycerides, total cholesterol, low-density lipoprotein cholesterol, BMI, and body weight and increased high-density lipoprotein cholesterol, compared with clinical control groups. No serious adverse effect was detected in all studies. Twenty-one bioactive components of LGZG, mainly flavonoids (i.e., naringenin, kaempferol, and kumatakenin), saponins (i.e., hederagenin), and fatty acids (i.e., eicosenoic acid), had the potential benefits possibly by regulating multiple targets such as PTPN1, CYP19A1, and ESR2, as well as a few complex pathways including the TNF signaling pathway, PPAR signaling pathway, arachidonic acid metabolism, fat digestion, and absorption. Conclusion: The present study has proved the clinical value of LGZG as a complementary treatment for attenuation or reversal of hyperlipidemia and obesity. More high-quality clinical and experimental studies in the future are demanded to verify its effects and the precise mechanism of action.

14.
JMIR Hum Factors ; 9(1): e34090, 2022 03 30.
Artículo en Inglés | MEDLINE | ID: mdl-35353051

RESUMEN

BACKGROUND: Behavioral economics-based techniques have been an increasingly utilized method in health care to influence behavior change by modifying language in patient communication (through choice architecture and the framing of words). Patient portals are a key tool for facilitating patient engagement in their health, and interventions deployed via patient portals have been effective in improving utilization of preventive health services. OBJECTIVE: We examined the impacts of behavioral economics-based nudge health maintenance reminders on appointment scheduling through a patient portal and appointment completion for 2 preventive services: Medicare wellness visits and Pap smear. METHODS: We conducted a retrospective observational study using electronic health record data from an integrated health care system in Northern California. Nudge health maintenance reminders with behavioral economics-based language were implemented for all sites in November 2017 for Medicare wellness visits and for selected sites in February 2018 for Pap smears. We analyzed 125,369 health maintenance reminders for Medicare wellness visits, and 585,358 health maintenance reminders for Pap smear sent between January 2017 and February 2020. The primary outcomes were rate of appointments scheduled through the patient portal and appointment completion rate. We compared the outcomes between those who received the new, behavioral economics-based health maintenance reminders (the nudge group) and those who received the original, standard health maintenance reminders (the control group). We used segmented regression with interrupted time series to assess the immediate and gradual effect of the nudge for Medicare wellness visits, and we used logistic regression to assess the association of nudge health maintenance reminders, adjusting for the propensity to receive a nudge health maintenance reminder, for Pap smear. RESULTS: The rates of appointments scheduled through the patient portal were higher for nudge health maintenance reminder recipients than those for control health maintenance reminder recipients (Medicare wellness visits-nudge: 12,537/96,839, 13.0%; control: 2,769/28,530, 9.7%, P<.001; Pap smear-nudge: 8,239/287,149, 2.9%; control: 1,868/120,047, 1.6%; P<.001). Rates of appointment completion were higher for nudge health maintenance reminders for Pap smear (nudge: 67,399/287,149, 23.5% control: 20,393/120,047, 17.0%; P<.001) but were comparable for Medicare wellness visits (nudge: 49,835/96,839, 51.5% control: 14,781/28,530, 51.8%; P=.30). There was a marginally gradual effect of nudge on number of appointments scheduled through the patient portal for the overall Medicare wellness visits sample (at a monthly rate of 0.26%, P=.09), and a significant gradual effect among scheduled appointments (at a monthly rate of 0.46%, P=.04). For Pap smear, nudge health maintenance reminders were positively associated with number of appointments scheduled through the patient portal (overall sample: propensity adjusted odds ratio [OR] 1.62; 95% CI 1.50-1.74; among scheduled appointments: propensity adjusted OR 1.61, 95% CI 1.47-1.76) and with appointment completion (propensity adjusted OR 1.07; 1.04-1.10). CONCLUSIONS: Nudges, a behavioral economics-based approach to providing health maintenance reminders, increased the number of appointments scheduled through the patient portal for Medicare wellness visits and Pap smear. Our study demonstrates that a simple approach-framing and modifying language in an electronic message-can have a significant and long-term impact on patient engagement and access to care.

15.
Phytomedicine ; 99: 153977, 2022 May.
Artículo en Inglés | MEDLINE | ID: mdl-35305353

RESUMEN

BACKGROUND: Human enterovirus 68 (EV68) is a primary etiological agent for respiratory illnesses, while no effective drug has yet used in clinics largely because the pathogenesis of EV68 is not clear. DNA damage response (DDR) responds to cellular DNA breaks and is also involved in viral replication. Three DDR pathways includes ataxia telangiectasia mutated (ATM), ATM and Rad3-related (ATR), and DNA-dependent protein kinase (DNA-PK). Natural products proved to be an excellent source for the discovery and isolation of novel antivirals. Among them, tanshinone IIA, resveratrol, silibinin, rutin and quercetin are reported to target DDR, therefore their roles in anti-EV68 are investigated in this study. PURPOSE: This study investigated the anti-EV68 ability of various natural compounds related to DDR. STUDY DESIGN AND METHODS: The methods include cell counting, flow cytometry, western blot, Immunofluorescence staining, comet assays, quantitative real-time RT PCR and short interfering RNAs (siRNAs) for analysis of cell number, cell cycle, protein expression, protein location, DNA damage, mRNA level and knock down target gene, respectively. RESULTS: EV68 infection induced DDR. Down-regulation or inhibition of ATM or DNA-PK lowered DDR in EV68-infected cells and mitigated viral protein expression, however, down-regulation or inhibition of ATR unexpectedly up-regulated DDR, and promoted viral protein expression. Meanwhile tanshinone IIA, resveratrol, and silibinin inhibited ATM and/or DNA-PK activation and decreased viral proliferation, while rutin and quercetin inhibited ATR activation and promoted viral production. The role of them in ATM, DNA-PK and ATR activation was consistent with previous reports. CONCLUSION: Tanshinone IIA, resveratrol and silibinin inhibited EV68 proliferation through inhibiting ATM and/or DNA-PK activation, and they were effective anti-EV68 candidates.

16.
Sheng Li Xue Bao ; 74(6): 949-958, 2022 Dec 25.
Artículo en Chino | MEDLINE | ID: mdl-36594383

RESUMEN

Tanshinone IIa is a key ingredient extracted from the traditional Chinese medicine Salvia miltiorrhiza (Danshen), and is widely used to treat various cardiovascular diseases. Vascular calcification is a common pathological change of cardiovascular tissues in patients with chronic kidney disease, diabetes, hypertension and atherosclerosis. However, whether Tanshinone IIa inhibits vascular calcification and the underlying mechanisms remain largely unknown. This study aims to investigate whether Tanshinone IIa can inhibit vascular calcification using high phosphate-induced vascular smooth muscle cell and aortic ring calcification model, and high dose vitamin D3 (vD3)-induced mouse models of vascular calcification. Alizarin red staining and calcium quantitative assay showed that Tanshinone IIa significantly inhibited high phosphate-induced vascular smooth muscle cell and aortic ring calcification. qPCR and Western blot showed that Tanshinone IIa attenuated the osteogenic transition of vascular smooth muscle cells. In addition, Tanshinone IIa also significantly inhibited high dose vD3-induced mouse aortic calcification and aortic osteogenic transition. Mechanistically, Tanshinone IIa inhibited the activation of NF-κB and ß-catenin signaling in normal vascular smooth muscle cells. Similar to Tanshinone IIa, inhibition of NF-κB and ß-catenin signaling using the chemical inhibitors SC75741 and LF3 attenuated high phosphate-induced vascular smooth muscle cell calcification. These results suggest that Tanshinone IIa attenuates vascular calcification at least in part through inhibition of NF-κB and ß-catenin signaling, and Tanshinone IIa may be a potential drug for the treatment of vascular calcification.


Asunto(s)
FN-kappa B , Calcificación Vascular , Animales , Ratones , FN-kappa B/genética , FN-kappa B/metabolismo , beta Catenina/genética , beta Catenina/metabolismo , Transducción de Señal , Miocitos del Músculo Liso/metabolismo , Calcificación Vascular/tratamiento farmacológico , Calcificación Vascular/metabolismo , Fosfatos/metabolismo
17.
Medicine (Baltimore) ; 101(52): e31773, 2022 Dec 30.
Artículo en Inglés | MEDLINE | ID: mdl-36596052

RESUMEN

Yixue Qiyuan is a representative work of Yuansu Zhang, a famous medical scientist during the Jin Dynasty. The contents of Five Yun and Six Qi are quite rich, especially the discussion on the treatment prescription and medication of Six Qi, which has a significant impact on the development of traditional Chinese medicine. Therefore, analyzing his drug rules and summarizing his medical thoughts can provide a reference for the clinical application of the theory of Five Yun and Six Qi. Based on the TCM inheritance auxiliary platform (V2.5), the data analyzed 63 first prescriptions and 134 drugs contained in the six Qi prescription sections of Yixue Qiyuan. Based on the frequency analysis, correlation rule analysis, four qi and five flavors, and meridian analysis, the formula rules for wind, summer heat, wet soil, fire, dryness, and cold water were obtained, and medical thought was summarized. Drug rules of prescription and medical thought can provide a useful reference for the classical study of traditional Chinese medicine and the application of the Six Qi theory in clinical practice.


Asunto(s)
Prescripciones de Medicamentos , Qi , Humanos , Medicina Tradicional China , Meridianos
18.
Chin J Integr Med ; 28(12): 1072-1080, 2022 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-34241801

RESUMEN

OBJECTIVE: To compare the clinical efficacy and safety of oral administration of Buxue Yimu Pills (BYP, ), ferrous sulfate (FS), and the combination of BYP and FS on gynecological anemia, and investigate the mechanisms using network pharmacology. METHODS: A randomized, controlled, multi-center clinical trial was conducted. Totally 150 patients with hemoglobin of 70-110 g/L due to gynecological conditions were recruited and randomized (using the block randomization method) into Buxue Yimu Pills group (24 g/d), oral iron group (FS Tablets, 0.9 g/d), and combined treatment group (BYP, 24 g/d plus FS Tablets, 0.9 g/d), 50 patients in each group. At the enrollment and 4-week treatment, complete blood count, serum iron indexes were evaluated. Adverse events, liver and renal functions, as well as blood coagulation were observed. Network pharmacology was conducted to identify the active ingredients and explore the potential mechanisms of BYP. RESULTS: Ten (20%) and 7 (14%) participants discontinued the therapy due to gastrointestinal symptoms in oral iron and combination treatment groups. All 3 groups showed elevated hemoglobin. The patients in the iron group exhibited typically elevated in serum iron and ferritin and decreased in total iron-binding capacity. No change in iron indexes was observed in BYP group. The patients in the combination treatment group neither showed significant changes in serum ferritin nor total iron-binding capacity. No significant adverse reactions were observed in the BYP group. The network pharmacology identified 27 bioactive compounds and 145 targets of BYP on gynecological anemia. Biological processes and pathways including regulation of inflammation, hormone, angiogenesis and hemostasis, response to decreased oxygen levels, effects on myeloma cell, and response to metal ions were identified. CONCLUSION: BYP contributes to the practical improvement on gynecological anemia potentially through multi-target mechanisms and optimized iron re-distribution. (Trial registration: No. NCT03232554).


Asunto(s)
Anemia Ferropénica , Anemia , Medicamentos Herbarios Chinos , Humanos , Anemia/tratamiento farmacológico , Anemia Ferropénica/tratamiento farmacológico , Ferritinas/uso terapéutico , Hemoglobinas , Hierro/uso terapéutico , Farmacología en Red
19.
Acta Physiologica Sinica ; (6): 949-958, 2022.
Artículo en Chino | WPRIM | ID: wpr-970090

RESUMEN

Tanshinone IIa is a key ingredient extracted from the traditional Chinese medicine Salvia miltiorrhiza (Danshen), and is widely used to treat various cardiovascular diseases. Vascular calcification is a common pathological change of cardiovascular tissues in patients with chronic kidney disease, diabetes, hypertension and atherosclerosis. However, whether Tanshinone IIa inhibits vascular calcification and the underlying mechanisms remain largely unknown. This study aims to investigate whether Tanshinone IIa can inhibit vascular calcification using high phosphate-induced vascular smooth muscle cell and aortic ring calcification model, and high dose vitamin D3 (vD3)-induced mouse models of vascular calcification. Alizarin red staining and calcium quantitative assay showed that Tanshinone IIa significantly inhibited high phosphate-induced vascular smooth muscle cell and aortic ring calcification. qPCR and Western blot showed that Tanshinone IIa attenuated the osteogenic transition of vascular smooth muscle cells. In addition, Tanshinone IIa also significantly inhibited high dose vD3-induced mouse aortic calcification and aortic osteogenic transition. Mechanistically, Tanshinone IIa inhibited the activation of NF-κB and β-catenin signaling in normal vascular smooth muscle cells. Similar to Tanshinone IIa, inhibition of NF-κB and β-catenin signaling using the chemical inhibitors SC75741 and LF3 attenuated high phosphate-induced vascular smooth muscle cell calcification. These results suggest that Tanshinone IIa attenuates vascular calcification at least in part through inhibition of NF-κB and β-catenin signaling, and Tanshinone IIa may be a potential drug for the treatment of vascular calcification.


Asunto(s)
Animales , Ratones , FN-kappa B/metabolismo , beta Catenina/metabolismo , Transducción de Señal , Miocitos del Músculo Liso/metabolismo , Calcificación Vascular/metabolismo , Fosfatos/metabolismo
20.
Br J Pharmacol ; 178(18): 3696-3707, 2021 09.
Artículo en Inglés | MEDLINE | ID: mdl-33908038

RESUMEN

BACKGROUND AND PURPOSE: Mineralocorticoid receptors (MRs), glucocorticoid receptors (GRs) and corticotropin-releasing factor (CRF) in the paraventricular nucleus of hypothalamus (PVN) are involved in the response to stress. The present study investigated the role of GRs and MRs in the PVN in regulating depressive and anxiety-like behaviours. EXPERIMENTAL APPROACH: To model chronic stress, rats were exposed to corticosterone treatment via drinking water for 21 days, and GR antagonist RU486 and MR antagonist spironolactone, alone and combined, were directly injected in the PVN daily for the last 7 days of corticosterone treatment. Behavioural tests were run on days 22 and 23. Depressive- and anxiety-like behaviours were evaluated in forced swim test, sucrose preference test, novelty-suppressed feeding test and social interaction test. The expression of GRs, MRs and CRF were detected by western blot. KEY RESULTS: Rats exposed to corticosterone exhibited depressive- and anxiety-like behaviours. The expression of GRs and MRs decreased, and CRF levels increased in the PVN. The intra-PVN administration of RU486 increased the levels of GRs and CRF without influencing depressive- or anxiety-like behaviours. The spironolactone-treated group exhibited an increase in MRs without influencing GRs and CRF in the PVN and improved anxiety-like behaviours. Interestingly, the intra-PVN administration of RU486 and spironolactone combined restored expression of GRs, MRs and CRF and improved depressive- and anxiety-like behaviours. CONCLUSION AND IMPLICATIONS: In this rat model of stress, the simultaneous restoration of GRs, MRs and CRF in the PVN might play an important role in the treatment of depression and anxiety.


Asunto(s)
Núcleo Hipotalámico Paraventricular , Receptores de Mineralocorticoides , Animales , Corticosterona , Hormona Liberadora de Corticotropina/metabolismo , Glucocorticoides/farmacología , Hipotálamo/metabolismo , Ratas , Receptores de Glucocorticoides/metabolismo , Receptores de Mineralocorticoides/metabolismo
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